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SDA-RF-CH-3.1
Bulletin ofthe World Health Organization, 61 (6): 967-979(1983)
© World Health Organization 1983
Interventions for the control of diarrhoeal diseases
among young children: supplementary feeding
programmes
R.G. Feachem*1
The effect of supplementary feeding programmes on diarrhoeal disease morbidity and
mortality among preschool children is reviewed using data from field studies in developing
countries. The supplementary feeding programmes considered are those that provide food
to preschool children on a continuing and community-wide basis. Nutritional rehabilitation
of sick children and feeding programmes in disasters and emergencies are not considered.
The evidence that poor nutritional status predisposes to increased diarrhoeal disease
incidence, or that supplementary feeding programmes can reduce diarrhoeal disease
incidence, is not strong. There is evidence that poor nutritional status predisposes to more
severe diarrhoea and to higher case fatality, and that supplementary feeding programmes
can reduce the severity of the diarrhoea and the mortality. However, supplementaryfeeding
programmes entail high costs and considerable logistic and managerial complexity and it is
unlikely that they are a cost-effective intervention for national diarrhoeal diseases control
programmes. Prospective studies into the effect of nutritional status on the severity of
etiology-specific diarrhoeas and the resulting deaths are warranted.
A synergism between diarrhoeal diseases and nu
tritional status has been accepted for many years (35)
and substantial research efforts have been directed
towards unravelling the nature of this synergism.
Some authorities (41) have suggested that the
enhancement of nutritional status by supplementary
feeding programmes may be an effective intervention
to reduce the rates of diarrhoeal diseases in preschool
children. Supplementary, feeding programmes refer
here to the planned distribution of foodstuffs to
improve the dietary intake of preschool children (6
months to 5-6 years is the usual age range of target
children). The food distribution may be on a ‘takehome’ basis or it may involve supervised feeding at
Teeding centres. Supplementary feeding programmes
may aim to reach the whole of a stated age-sex group,
or they may be targeted at children with particular
levels of nutritional deprivation. Several recent
reviews of supplementary feeding programmes pro
vide a useful background to this more focused
analysis (/, 8, 20, 23). The therapeutic feeding, over
short periods, of children suffering from severe mal
nutrition and diarrhoea is undoubtedly an essential
part of case management and can reduce the case
fatality rate among such children. In this review,
however, such nutritional rehabilitation of sick chil
dren is not considered and only data on the preventive
effect of more broadly targeted supplementary feed
ing programmes are considered. This review of the
role of supplementary feeding programmes in diar
rhoeal disease control is the second in a series of
reviews of potential anti-diarrhoea interventions
being published in the Bulletin of the World Health
Organization (15, 16).
EFFECTIVENESS
For supplementary feeding programmes to be an
effective diarrhoea control intervention, it must be
true that:
1 Reader in Tropical Public Health Engineering and Head of
Department of Tropical Hygiene, London School of Hygiene and
Tropical Medicine, Keppel Street, London WCIE 7HT, England.
Requests for reprints should be addressed to the Programme
Manager, Diarrhoeal Diseases Control Programme, World Health
Organization. 1211 Geneva 27, Switzerland.
4362
—967—
either
supplementary feeding
programmes can
improve the
nutritional status
of young children
hypothesis
I
968
R. G. FEACHEM
and
young children with
improved nutritional
status have reduced
diarrhoea morbidity
rales and/or mortality
rates and/or severity
hypothesis
2
supplementary feeding
programmes can reduce
diarrhoea morbidity
rates and/or mortality
rales and/or severity
in young children
hypothesis
3
Most of the literature on this topic has been addressed
to one or more of these specific hypotheses. The
potential effectiveness of supplementary feeding pro
grammes would be suggested by a demonstration
either of the correctness of hypotheses 1 and 2 or of
the correctness of hypothesis 3. The evidence for and
against the three hypotheses is now examined.
Hypothesis 1. Supplementary feeding programmes
can improve the nutritional status ofyoung children
Beaton & Ghassemi (<8) reviewed the impact on nu
tritional status of 43 supplementary feeding pro
grammes. Major differences in the nature and goals
of the feeding programmes, and in the methods for
evaluating their impact, make it difficult to draw
generalized conclusions from these programmes (7).
There is no doubt that supplementary feeding pro
grammes dan have a major impact on the nutritional
status of individual participating children, and that
the worse the initial nutritional state of the child, the
greater is the improvement in anthropometric indices
that may be attributed to the feeding programme.
Impact on the nutritional status of the target group as
a whole, however, is typically low or non-existent.
This lack of impact may be due to the following
factors:
structure. Coverage in programmes reviewed by
Beaton & Ghassemi was typically less than 10%.
(ii) Low levels ofsupplementation: in programmes
reviewed by Beaton & Ghassemi, the supplementation
was designed to meet 40-70% of the estimated energy
gap, but in practice only 10-25% of the gap was
closed. Energy intakes from supplementary food
ranged from 19 to 431 kcal (79.5 to 1803 kJ) per child
per day.
(iii) Food sharing: in take-home feeding pro
grammes, only 40-60% of the food distributed
appeared to reach the targeted children, the re
mainder being consumed by other family members or
being sold (8).
(iv) Food substitution: there is often a compen
satory decrease in the intake of other foods. In 5 out
of 7 programmes reviewed by Beaton & Ghassemi in
this regard, the net increase in energy intake among
the participating children, as a percentage of the
energy in the supplementary food ingested, was less
than 100% and in one programme it was as low as
16%.
Many of the feeding programmes reviewed by
Beaton & Ghassemi (<S) were research or pilot inter
ventions rather than routine feeding programmes,
and the former tend to have greater impact than the
latter. Some of the research interventions, for
instance in Colombia, Guatemala and India, pro
duced mean weight gains in project children that were
0.5-1.0 kg/year greater than in the control children.
These marked impacts in research interventions may
serve to define maximum impacts, but they do not
reflect the generally more modest achievements of
routine supplementary feeding programmes.
The programmes reviewed were, in general, not
effective in reaching children aged 6-23 months. This
is probably due to traditional practices of late wean
ing and to maternal attitudes towards appropriate
feeding regimens for children of this age. Since diar
rhoea rates are at their highest in this 6-23-month
period (56), this finding is important in the context of
diarrhoea control and suggests that attention may be
better directed towards improved weaning practices
than supplementary feeding programmes.
Hypothesis 2. Young children with improved nu
tritional status have reduced diarrhoeal morbidity
rates and/or mortality rates and/or severity.
Associations have been frequently reported be
tween poor nutritional status and increased diarrhoea
(i) Low coverage: a considerable proportion morbidity, mortality, and severity. This literature is
(20-75%) of children enrolled in supplementary comprehensively reviewed by Leslie." These associ* LESLIE, J. Child malnutrition and diarrhea: a longitudinal
feeding programmes fail to participate, while many
from north-east Brazil. Doctor of Science thesis, School of
more children in the region or country are denied study
Hygiene and Public Health, Johns Hopkins University, Baltimore
access because of limitations in the programme infra MD, USA, 1982.
969
SUPPLEMENTARY FEEDING FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
ations could be due to one or more of the
following:
— diarrhoea causes poor nutritional status (propo
sition 1);
— poor nutritional status predisposes to diarrhoea
(proposition 2);
— both poor nutritional status and diarrhoea are
associated with other factors such as a recent measles
attack or poverty (proposition 3).
The evidence for the first proposition (diarrhoea
causes poor nutritional status) is considerable (14,28,
29, 32).b This implies that diarrhoea control may be
an effective anti-malnutrition intervention. The third
proposition is also true, it being well established that
both diarrhoea and poor nutritional status are found
disproportionately among the deprived and under
privileged sections of the community (40). The pre
cise cause-and-effect relationships are not understood
See footnote a, page 968.
Table 1. Association between nutritional status and
diarrhoea incidence in rural Bangladesh"
Type of data collected
Finding
1.
Discharge weight-for-age
of 811 children (0-4 years)
treated for diarrhoea at
rural hospital compared
with weight-for-age of 882
children of the same age
range in the community.
For both males and females
the prevalence of severely
malnourished children
(< 60% weight-for-age)
was significantly higher
among diarrhoea cases
than among village
children.
2.
Diarrhoea treatment rate
over 2 years for 2019
children (12-23 months)
according to nutritional
status (weight-for-age,
weight-for-height, heightfor-age) at the start of
the 2-year period.
No association was found
between nutritional status
and diarrhoea treatment
rate, either for individual
anthropometric measures
or combined measures.
Diarrhoea incidence by
community surveillance
over 1 year among 207
children (0-4 years)
according to nutritional
status (weight-for-age)
at the start of 1 year's
surveillance.
No association was found
between nutritional status
and diarrhoea incidence
rate.
Probability of experiencing
diarrhoea in a given
4-week period among 207
children (0-4 years)
according to weight gain
(weight-for-age % increase,
body weight % increase,
body weight kg increase) in
previous 4-week period.
No association was found
between weight gain and
probability of diarrhoea.
3.
4.
' Summary of Chen et al. (13}.
but the general conclusion is that overall socio
economic development may gradually reduce both
diarrhoea and malnutrition. For the second propo
sition (poor nutritional status predisposes to diar
rhoea) there is uncertainty and controversy. It is only
if this proposition is correct that nutritional supple
mentation could be an effective anti-diarrhoea inter
vention.
Most studies into the association between diar
rhoea and nutrition have failed to separate propo
sition 1 from proposition 2, and have also failed to
allow for the confounding variables of proposition 3.
Only a few prospective studies have adequately
explored proposition 2. The study by Chen et al. (13)
in rural Bangladesh is summarized in Table 1, in
which the first finding is typical of many previous
studies and fails to disentangle propositions 1 and 2 or
to control for confounding variables; the remaining
findings are of greater interest and fail to show that
poor nutritional status predisposes to increased inci
dence of diarrhoeal illness.
Another prospective study was that of 343 children
aged 6-32 months in rural northern Nigeria (38). The
heights and weights of each child were recorded in
April and the incidence and duration of diarrhoea
were recorded during May-July by weekly home
visits. The period May-July coincides with the end of
the dry season and the start of the rains and is the
period of peak diarrhoea incidence. The results of this
study are shown in Table 2. Being underweight or
Table 2. Association between nutritional status and
diarrhoea incidence and duration among children aged
6-32 months in rural northern Nigeria"
Nutritional
status
No. of
children
Diarrhoea
attack rate
per child
over 3
months6
Time with
diarrhoea
*
(%)
Weight/age:
> 75%
220
1.25
8.5|
<75%
(underweight)
123
1.52
11.3 J
>90%
245
1.37
< 90% (stunting)
98
1.45
> 80%
302
1.29)
7.el „
< 80% (wasting)
41
1.90)
i3.ej
Height/age:
7,9l ..
10.8/
Weight/height:
Data from Tomkins (38).
Significance values of comparisons within anthropometric
groups: •P<0.02; •"PcO.OI; •••P<0.001.
970
R. G. FEACHEM
stunted did not predispose to increased diarrhoea inci
dence but being wasted was associated with a signifi
cantly higher attack rate. Being underweight, or
stunted or wasted were all associated with a signifi
cantly increased duration of diarrhoea, and this effect
was most marked for children who were wasted. The
major defect of this study is that socioeconomic and
environmental variables were not controlled. It could
be that children who were undernourished in April
tended to come from more crowded, less educated,
poorer and dirtier homes than other children (40).
Such disadvantaged children might experience in
creased exposure to diarrhoea-causing organisms
(and thus higher attack rates) and receive less
adequate care when sick (and thus have a longer
duration of illness) than other children. The Nigerian
report (38) provides no data on the degree of familial
clustering of the children with poor nutritional status.
Since the confounding variables mentioned above are
all family attributes, future studies of this type should
control for familial variation, perhaps by comparing
poorly nourished children with well nourished chil
dren in the same families. Trowbridge et al. (39)
found a strong association between poor nutritional
status and diarrhoea incidence in the subsequent 12
months in El Salvador, but recognized that this
association could be confounded by socioeconomic
status.
Other studies have recorded a relationship between
poor nutritional status and increased duration of diar
rhoea. Palmer et al. (30) found increased cholera
duration among hospitalized male Bangladeshis of
low weight-for-height, although, since anthropo
metric measures were made at discharge, it was not
clear whether the low weight caused prolonged
cholera or vice versa. In a prospective study in San
Jose, Costa Rica, the average duration of diarrhoea
episodes in children aged 12-59 months was signifi
cantly longer among those with low weight-for-age
than among others (22).
Two studies of children admitted to hospital with
acute diarrhoea of known etiology in Bangladesh
failed to find an association of poor nutritional status
with diarrhoea duration, but did find an association
with diarrhoea severity as measured by the rate of
stool output and degree of dehydration. In the first
study (70), which was of children with rotavirus
diarrhoea, those with low (<60%) weight-for-age
had a higher frequency of severe dehydration, but a
similar duration of diarrhoea, than others. In the
second study/ no difference was found in the rate of
stool output, total stool volume, or diarrhoea dur
ation between children of poor (< 80% weight-forheight) and better (> 80% weight-for-height) nuc BLACK, R. E. ET AL. Nutritional status, body size and severity
of diarrhoea associated with rotavirus or enterotoxigenic Escherichia
coli. (Unpublished).
tritional status who had been admitted to hospital
with acute rotavirus or enterotoxigenic Escherichia
coli diarrhoea. However, the rate of stool output (per
kg of body weight) was significantly higher among
children with small body size (low weight- and heightfor-age).
If poor nutritional status predisposes to more
severe diarrhoea, particularly in the form of more
dehydrating diarrhoea or diarrhoea of longer
duration, then it would be expected that poor nu
tritional status would predispose to diarrhoea mor
tality. Chen et al. (11) measured the heights and
weights of 2019 children aged 12-23 months in rural
Bangladesh and then recorded mortality among these
children over the following 2 years. A striking associ
ation between nutritional status (weight-for-age) and
subsequent diarrhoea mortality was recorded (Table
3), with children < 65% weight-for-age having a
diarrhoea mortality rate 3.8 times higher than
children > 65% weight-for-age. In this and another
report (12) a marked association between mortality
rate and socioeconomic status (measured by housing
floor area) in the same children was noted. Unfor
tunately the data on diarrhoea mortality by nu
tritional status are not controlled for socioeconomic
status and the possible importance of this confound
ing variable is not elucidated.
Other prospective studies have also reported an
association between poor nutrition and diarrhoea
mortality. In rural Punjab, India, 71% of under-3year-old children dying from diarrhoea were < 70%
weight-for-age in the two months preceding death
(27). The mean prevalence of < 70% weight-for-age
in children from the same community at the same time
was significantly lower (25%). In rural Bangladesh,
children aged 0-9 years who died of diarrhoea had a
pre-morbid mean weight-for-height of 74% of the
standard, compared with 83-86% of standard for
children who died of other causes and 88% of
standard for living controls (26).
In summary, the evidence that poor nutritional
status predisposes to increased diarrhoea incidence is
Table 3. Association between nutritional status and
diarrhoea mortality among children aged 12-23 months
(at start of study) in rural Bangladesh"
Nutritional
status (weightfor-age)
No. of
children
Diarrhoea
mortality
per 1000
over 2 years
All children
2019
20
Children < 65%
742
38
Children > 65%
1277
10
' Oata from Chen et al. (11).
971
SUPPLEMENTARY FEEDING FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
not strong. There is good evidence, however, that
children with poor nutritional status are more likely
to have dehydrating or prolonged diarrhoea, and are
more likely to die from diarrhoea, than well
nourished children. Data from Bangladesh suggest
that children < 65% weight-for-age have a diarrhoea
mortality rate 3.8 times higher than other children
(//). There is a need for more studies to clarify
further the association between poor nutritonal status
and risk of severe diarrhoea and diarrhoea death.
Such studies should be etiology-specific and pro
spective, and control for family socioeconomic
status. No studies so far reported meet these three cri
teria and very little is known of the possible differing
effects of nutritional status on diarrhoeas of differing
etiology.
Hypothesis 3. Supplementary feeding programmes
can reduce diarrhoea morbidity rates and/or mor
tality rates and/or severity in young children
Only a small minority of supplementary feeding
programmes collect data on their impacts, and only a
minority of these evaluate impact by measuring the
changes in mortality or morbidity. Annex 1 sum
marizes the results of evaluations of 9 supplementary
feeding programmes, which included measurement of
mortality and/or morbidity changes. Of the 9 pro
grammes, 6 investigated mortality changes and, of
these, 5 found that mortality was reduced while 1
found that it was not. Of the 5 programmes with a
mortality reduction, 2 included both nutritional
supplementation and curative health care and it is not
possible to separate out the impact of the nutritional
intervention alone. Three studies (in Guatemala in
1959-64; in Punjab, India; and in Peru) documented
a significant reduction in mortality that was
attributed to supplementary feeding alone, but no
data are presented on the impact on diarrhoea mor
tality specifically. It is reasonable to assume that the
percentage reduction in diarrhoea mortality is at least
as great as the reduction in mortality from all causes.
•With this assumption, the reduction in diarrhoea
mortality due to the supplementary feeding pro
grammes in Guatemala and the Punjab may have
been 19-31% among children under 1 year of age and
around 50% among children aged 1-4 years. In Peru
there was a striking (> 50%) reduction in diarrhoea
mortality among infants under 1 year of age.
Theoretical reductions in diarrhoea mortality
achieved by a supplementary feeding programme may
be computed (Table 4). Six different initial preva
lences of severe malnutrition are considered and
supplementary feeding programmes are assumed to
either eliminate severe malnutrition or to cut its preva
lence by half. Reductions in diarrhoea mortality are
then computed by assuming that severely mal-
Table 4. Estimated reductions in diarrhoea mortality
among children under 5 years of age due to supple
mentary feeding programmes of differing effectiveness
in communities with differing levels of severe malnu
trition
% of children <: 65% weight-for-age
before nutritional
intervention
after nutritional
intervention
% reduction
in diarrhoea
mortality rate
caused by
nutritional
intervention0
12
5
0
5
2.5
6
10
0
22
10
5
11
15
0
30
15
7.5
15
20
0
36
20
10
18
25
0
41
25
12.5
21
30
0
46
30
15
23
“ Assuming that children < 65% weight-for-age have a 3.8
times higher diarrhoea mortality rate than other children (see
Table 31.
nourished children have a diarrhoea mortality rate 3.8
times higher than other children and that only
severely malnourished children are predisposed to
diarrhoea mortality (//). The reductions in diarrhoea
mortality thus estimated are in the range 6-46% and
are greater in communities with a higher prevalence of
severe malnutrition. These calculations are greatly
simplified and take no account of age-related effects.
Children aged under 2 years have the highest diar
rhoea mortality rate (36) but are least affected by
supplementary feeding programmes. The relative risk
of diarrhoea mortality for severely malnourished chil
dren (3.8) was taken from a single study in Bangla
desh of children between 12 and 47 months of age.
Table 4 can be recomputed with respect to a particular
community in which the prevalence of severe malnu
trition and the differential diarrhoea mortality rates
of severely malnourished children are known.
Six of the 9 programmes were evaluated for their
impact on diarrhoea incidence: 1 showed an impact, 3
showed no impact, and 2 could not be interpreted
owing to deficient study methods. The one study that
showed an impact on diarrhoea morbidity (in
Madhya Pradesh, India) evaluated the combined
972
R. G. FEACHEM
impact of supplementary feeding of 6-35-month-old
children plus a comprehensive package of curative
and preventive health care. The effect of the nu
tritional intervention alone cannot be determined.
One study (in Guatemala, 1959-64) documented a
reduced case-fatality ratio for diarrhoea (1.7% vs
0.8%) and a reduced proportion of severe diarrhoeas
(20% vs 10%) that were attributed to the supple
mentary feeding intervention.
In summary, there is evidence from three studies
and from theoretical calculations that supplementary
feeding programmes can reduce diarrhoea mortality
in children under 5 years of age. The magnitude of
this reduction may be as high as 50% in some age
groups and in communities where severe malnutrition
is common. There is no evidence that supplementary
feeding can reduce diarrhoea incidence, and some evi
dence that it can reduce the case-fatality ratio and the
severity of diarrhoea episodes. These findings corre
spond closely to the conclusions on hypothesis 2.
reported costs of USS 21-147 (1982 dollars) per
participating child. Food accounted for between 54%
and 92% of these costs. When costs are jomputed not
per participating child, but per malnourished child
Gudged nutritionally or anthropometrically), the
figures increase considerably (Table 5).
If the annual cost per participating child is USS 100
(Table 5), and if a 20% reduction in diarrhoea mor
tality is achieved among participating children (Table
4) having a pre-intervention annual diarrhoea mor
tality rate of 1.4 per 100 children (36), the cost per
diarrhoea death averted is USS 36 000. Under the
most favourable conditions, with an annual cost per
participating child of USS 20 and a 50% diarrhoea
mortality reduction achieved, the cost per diarrhoea
death averted is USS 2900. These calculations under
estimate the cost-effectiveness of supplementary feed
ing programmes by assuming that they achieve no
benefits other than prevention of diarrhoea mor
tality.
FEASIBILITY
CONCLUSIONS
Supplementary feeding programmes have been
implemented in many developed and developing
countries. There is considerable accumulated oper
ational experience of such programmes and this has
been reviewed (7, 8). The major operational diffi
culties are to attain and sustain a high coverage of
targeted children and to ensure that the participating
children regularly ingest a sufficient amount of
supplementary energy. These and other difficulties
are discussed above in the section dealing with
hypothesis 1.
The evidence that poor nutritional status pre
disposes to increased diarrhoeal disease incidence, or
that supplementary feeding programmes can reduce
diarrhoeal disease incidence, is not strong. There is
evidence that poor nutritional status predisposes to
more severe diarrhoea and to higher case fatality, and
Table 5. Annual feeding programme costs in four
countries*
Annual cost (in 1982 US$)
per
participating
child
per child
with energy
deficit
per child
with anthro
pometric
deficiency
39
45
406
dry, take-home
21
23
103
wet, take-home
24
26
116
37
45
71
147
175
452
COSTS
Country
The costs of operational supplementary feeding
programmes reviewed by Beaton & Ghassemi (8) were
USS 23-39 (1982 dollars) per child enrolled per year.
These costs were for the provision of 300-400 kcal
(1255-1674 kJ) per child per day and include food
plus delivery and administration. Total costs in super
vised feeding programmes were somewhat higher
than in take-home programmes. The cost of food
accounted for about 70% of the total cost of takehome programmes. Since non-participation is com
mon (20-75% of children enrolled fail to participate),
the costs per participating child are increased by
1.25-4 times, thus giving a maximum cost range of
USS 29-156 (1982 dollars) per participating child per
year.
In a review of CARE preschool feeding pro
grammes in five countries, Anderson et al. (1)
Colombia
take-home
Dominican
Republic
Pakistan
take-home
Costa Rica
on-site
* Data from Anderson et al. If). Costs converted to 1982
USS using GNP deflators computed from data In Internationa!
financial statistics.
SUPPLEMENTARY FEEDING FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
that supplementary feeding programmes can reduce
diarrhoea severity and mortality.
Supplementary feeding programmes, however,
entail high costs and considerable logistic and
managerial complexity and have typically failed to
achieve a significant improvement in the nutritional
status of children aged 6-23 months, who have the
highest rates of sickness and death from diarrhoea. It
is unlikely that supplementary feeding programmes
are a cost-effective intervention for national diar
rhoeal diseases control programmes. Prospective
studies into the effect of nutritional status on the
severity of etiology-specific diarrhoeas and the result
ing deaths (using the methods recommended above)
973
are warranted.
Therapeutic feeding has not been included in this
review. Such feeding can be life-javing for the
severely malnourished child. Also not included are
feeding programmes implemented in emergency or
disaster situations where inadequate food availability
may be the cause of malnutrition for a majority of
children. Reviewed here are supplementary feeding
programmes designed to enhance food intake of pre
school children over several years and on a com
munity-wide basis. Such programmes are shown to be
costly, to be ineffective in reducing diarrhoea mor
bidity rates, and to be of uncertain effectiveness in
reducing diarrhoea mortality rates.
ACKNOWLEDGEMENTS
The author is grateful for the constructive criticisms on earlier drafts of this paper provided by L. C. Chen, I. de Zoysa,
R. Hogan, R. Martorell, M. Merson, A. Pradilla, P. M. Shah and A. Tomkins. Secretarial and bibliographic assistance was
most ably provided by Maelorwen Jones and Dianne Fishman.
RESUME
INTERVENTIONS POUR LA LUTTE CONTRE LES MALADIES DIARRH&IQUES
CHEZ LES JEUNES ENFANTS : PROGRAMMES D’ALIMENTATION COMPLfiMENTAIRE
Ce document est le deuxieme d’une sArie d’Atudes sur les
interventions possibles en vue de rAduire la morbidity et la
mortality par maladies diarrhAiques parmi les enfants de
moins de 5 ans dans les pays en dAveloppement. On admet
depuis de nombreuses annAes qu’il existe une synergie entre
les maladies diarrhAiques et 1’Atat nutritionnel, et d’importantes recherches ont AtA effectuAes en vue d’Alucider la
nature de cette synergie. D’aprAs certains experts, 1’amAlioration de I’etat nutritionnel grace A des programmes d’ali
mentation complementaire pourrait constituer une strategic
efficace pour rAduire les taux de maladies diarrhAiques chez
les enfants d’Age prescolaire. Par programme d’alimenta
tion complAmentaire, on entend ici la distribution planifiAe
de denrAes destinies A amAliorer I’apport alimentaire chez
les enfants d’Age prAscoIaire (la fourchette d’Age habituelie
des enfants cibles est de 6 mois A 5-6 ans). Les aliments
distribuAs peuvent etre soit «A emporter A domicile#, soit
destines A etre consommes sous surveillance dans des centres
d’alimentation. Ces programmes d’alimentation compIAmentaire peuvent viser la totalitA d’un groupe d’Age et de
sexe dAfinis ou bien des enfants atteints de degrAs particuliers de carence nutritionnelle.
Les preuves qu’un Atat nutritionnel mAdiocre predispose A
une incidence accrue de maladies diarrhAiques ou que des
programmes d’alimentation complAmentaire peuvent rAduire cette incidence sont assez fragiles. Toutefois, des ob
servations ont montrA qu’un Atat nutritionnel mediocre pre
dispose A des diarrhees plus graves et A une lAtalitA plus
elevee, et que les programmes d’alimentation complemen
taire sont capables de reduire la gravite des diarrhees et la
mortalite qu’elles causent. Ces programmes entrainent des
depenses elevees et sont trAs complexes au point de vue de la
logistique et de la gestion; en outre, ils n’ont pas reussi A
ameiiorer de maniAre notable 1’Atat nutritionnel d’enfants
agAs de 6 A 23 mois, c’est A dire de ceux justement parmi lesquels les taux de morbiditA et de mortalite par diarrhees sont
le plus AlevAs. Il est peu probable que les programmes d’ali
mentation complementaire soient une intervention d’un bon
rapport coQt/rendement pour les programmes nationaux de
lutte contre les maladies diarrhAiques.
L’alimentation thArapeutique n’a pas AtA incluse dans
cette Atude. Une telle alimentation peut sauver la vie d’un
enfant atteint de malnutrition sAvAre. Ne sont pas non plus
considArAs les programmes d’alimentation mis. eh oeuvre
dans les situations d’urgence ou de catastrophe, dans lesquelles la pAnurie d’aliments peut Aire une cause de malnu
trition pour la majoritA des enfants. Sont AtudiAs ici les pro
grammes d’alimentation complAmentaire visant A accroitre
I’apport alimentaire des enfants d’Age prAscolaire sur plusieurs annAes et sur la base d’une collectivitA tout entiAre. De
tels programmes sont coflteux, incapables de rAduire les taux
de morbiditA par diarrhAe, et leur efficacitA est douteuse en
ce qui concerne la rAduction des taux de mortalitA par
diarrhAe.
974
R. G. FEACHEM
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Anderson, M. A. et al. Supplementary feeding. In: 17. Gopaldas, T. et al. Project Poshak: an integrated
Austin, J. E. & Zeitlin, M., ed. Nutritional intervention
health-nutrition macro pilot study for preschool chil
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schlager, Gunn and Hain, 1981, pp. 25-48.
Delhi, CARE India, 1975.
2. Arole, R. S. Comprehensive rural health project, 18. Gordon, J. E.et al. Nutrition and infection field study
Jamkhed, India. Contact, No. 10, August 1972, pp.
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1-9.
disease and nutritional disorders in general disease
3. Arole, R. S. Comprehensive rural health project,
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424-437 (1968).
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Guzman, M. A. et al. Nutrition and infection field
Medical Research, 1978, pp. 95-101.
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4. Arole, M. & Arole, R. A comprehensive rural health
growth and development of preschool children.
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Archives of environmental health, 17: 107-118 (1968).
the people. Geneva, World Health Organization, 1975,
20. Gwatkin, D. R. et al. Can health and nutrition
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5. Ascoli, W. et al. Nutrition and infection field study in
Washington, DC, Overseas Development Council,
Guatemalan villages, 1959-1964. IV. Deaths of infants
1980.
and preschool children. Archives of environmental 21. Hofvander, Y. & Eksmyr, R. An applied nutrition
health, 15: 439-449 (1967).
program in an Ethiopian rural community. American
6. Baertl, J. M. et al. Diet supplementation for entire
journal of clinical nutrition, 24: 578-591 (1971).
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7. Beaton, G. H. Evaluation of nutrition interventions:
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ical nutrition, 35: 1280-1289 (1982).
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8. Beaton, G. H.&Ghassemi, H. Supplementary feeding
246-257 (1982).
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24. Kielman, A. A. et al. The Narangwal experiment on
American journal of clinical nutrition, 35 (4, sup
interactions of nutrition and infections. II. Morbidity
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trial in New Guinea highland infants. Journal of 25. Kielmann, A. A. et al. The Narangwal nutrition
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10. Black, R. E. et al. Glucose vs sucrose in oral rehy
nutrition, 31: 2040-2052 (1978).
dration solutions for infants and young children with
26. Koster, F. T. et al. Synergistic impact of measles and
diarrhoea on nutrition and mortality in Bangladesh.
rotavirus-associated diarrhea. Pediatrics, 67: 79-83
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(1981).
11. Chen, L. C. et al. Anthropometric assessment of
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McCord, C. & Kielmann, A. A. A successful pro
energy-protein malnutrition and subsequent risk of
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12. Chen, L. C. et al. Epidemiology and causes of death
among children in a rural area of Bangladesh. Inter 28. Martorell, R. et al. Acute morbidity and physical
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1^. Chen, L. C. et. al. A prospective study of the risk of
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diarrheal diseases according to the nutritional status of 29. Martorell, R. et al. Diarrheal diseases and growth
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284-292(1981).
ican journal of physical anthropology, 43:: 341-346
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14. Cole, T. J. & Parkin, J. M. Infection and its effect on
the growth of young children: a comparison of the
30. Palmer, D. L. et al. Nutritional status: a determinant
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of infectious diseases, 134: 8-14 (1976).
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15. Feachem, R. G. et al. Diarrhoeal disease control: 31. Parker, R. L. et al. The Narangwal experiment on
interactions of nutrition and infections. III. Measure
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16. Feachem, R. G. & Koblinsky, M. A. Interventions
(1978).
for the control of diarrhoeal diseases among young chil
dren: measles immunization. Bulletin of the World
Health Organization, 61: 641-652 (1983).
1.
SUPPLEMENTARY FEEDING FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
975
Rowland, M. G. M. et al. A quantitative study into 37. Taylor, C. E. et al. The Narangwal experiment on
interactions of nutrition and infections. I. Project
the role of infection in determining nutritional status in
design and effects upon growth. Indian
*
journal of
Gambian village children. British journal of nutrition,
medical research, 68 (suppl.): 1-20 (1978).
37: 441-450(1977).
33. Scrimshaw, N. S. et al. Nutrition and infection field 38. Tomkins, A. Nutritional status and severity of diar
rhoea among pre-school children in rural Nigeria.
study in Guatemalan villages, 1959-1964. III. Field
Lancet, 1: 860-862(1981).
procedure, collection of data and methods of measure
39. Trowbridge, F. L. et al. Nutritional status and
ment. Archives of environmental health, 15: 6-15
severity of diarrhoea. Lancet, 1, 1375 (1981).
(1967).
Wittmann, W. et al. An evaluation of the relationship
34. Scrimshaw, N. S. et al. Nutrition and infection field 40.
between nutritional status and infection by means of a
study in Guatemalan villages, 1959-1964. V. Disease
field study. South African medical journal (sup
incidence among preschool children under natural
plement— South African journal of nutrition), 41:
village conditions, with improved diet and with medical
664-682
(1967).
and public health services. Archives of environmental
41.
Wray, J. D. Direct nutrition intervention and the
health, 16: 223-234 (1968).
control of diarrhoeal diseases in preschool children.
35. Scrimshaw, N. S. et al. Interactions of nutrition and
American journal of clinical nutrition, 31: 2073-2082
infection. American journal of medical sciences, 237:
(1978).
367-403 (1959).
36. Snyder, J. D. & Merson, M. H. The magnitude of the
global problem of acute diarrhoeal disease: a review of
active surveillance data. Bulletin of the World Health
Organization, 60: 605-613 (1982).
32.
976
R. G. FEACHEM
Annex 1
SUMMARY OF SUPPLEMENTARY FEEDING PROGRAMMES THAT WERE EVALUATED
FOR IMPACT ON MORBIDITY OR MORTALITY
Country
Rural/
urban
Dates of
feeding
programme
Colombia
urban
Ethiopia
rural
Educational
programme
for mothers
Other
intervention
56% of children
enrolled failed
to participate
regularly
throughout 1 year
of programme
and were excluded
from impact
analysis
Yes
No
Weekly collection
of take-home
allocation to
provide 335 kcal
and 14 g of
protein per
child per day
Only children
receiving > 50%
of weekly
distributions
were included
in study
Yes
DPT, TB. and
and smallpox
vaccination;
general curative
care provided
Target
children
Feeding
programme
1964-65
Malnourished
children.
0-71 mo; plus
their siblings
and pregnant or
lactating mothers
Weekly collection
of take-home
allocation of
1 pound of dried
skimmed milk
per child per
week
1965-67
All children
0-11 years
Participation
Guatemala
rural
1959-64
All children
0-59 mo.
Daily supervised
feeding providing
350 kcal and 15 g
of protein per
child
52% of children
of 6-59 mo.
participated
> 50% of time.
Participation of
< 6 mo. children
was not expected.
Participation
declined during
5 yrs of
programme
Guatemala
rural
1969-76
All children
0-83 mo.
Twice daily
supervised
feeding at
feeding centres
No data
i
No
No
Curative and
preventive
health services.
supplementary
feeding for
pregnant or
lactating women
977
SUPPLEMENTARY FEEDING FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Control
community
Changes in
nutritional
status
Changes in
mortality'
Causes
of death
Morbidity
survey.
methods
Changes in diarrhoeal disease rates
*
Cost
Source
No
Malnutrition,
judged by weightfor-age decreased
substantially during
the 1 yr feeding
programme
No data
No data
Yes, 1-week
recall at visits
to nutrition
centre
Data on diarrhoea
incidence cannot be
interpreted owing to
lack of controls
No data
41
No
Clinical signs of
PCM decreased and
upper arm tircumfcrence-for-agc
increased. Weightfor-age and heightfor-age did not
change
No data
No data
Yes, 3-monthIy
or 6-monthly
examinations
and stool
microscopy
Data on diarrhoea.
Entamoeba histo
lytica, Ascaris,
and hookworms
cannot be
interpreted
owing to lack
of controls
No data
21
Yes
Proportion of
0-59 mo. children
< 90% weightfor-age declined
from 91% in 1959
to 83% in 1964.
A child in the
feeding village
could expect to
be 30 mm taller
and 1 kg heavier
at age 5 yrs
than a control
child
9 yrs prior to
intervention
compared with
5 yrs of inter
vention. Crude
mortality
declined from
25 to 16 per 1000
(36% reduction)
0-11 mo.
mortality
declined from
182 to 146 per
1000(19%
reduction), 12-59
mo. mortality
declined from
56 to 24 per
1000 (56%
reduction)
During 5 yrs of
programme, the
proportion of
deaths due to
diarrhoea was
around 20%
Yes, 2-week
recall at
home visits
Incidence of diar
rhoea cases, among
0-59 mo. children,
per year rose from
48 per 1000 in 1959
(control village 123) to 219 per 1000
in 1964 (control
village - 165). This
was attributable to
falling participation
in the feeding
programmes. Diar
rhoea case-fatality
ratios during 195964 were 0.8% in the
feeding village and
1.7% in the control
village. The pro
portions of cases
judged to be severe
(blood or mucous or
duration > 3 days)
were 10% in the
feeding village and
20% in the control
village
No data
5,18,19,
33,34
internal
controls
Children of
9-59 mo. who
regularly took
supplement had
weight and
height gains
10-15% higher
than other
children
Using beforeand-after
comparisons,
0-11 mo.
mortality
declined from
150 to 55 per 1000
(63% reduction)
and 12-59 mo.
mortality declined
from 28 to 6
per 1000 (79%
reduction).
70% of these
*
reduction
were
attributed to
health care and
30% to nutrition,
especially
nutrition of
pregnant mot hen
No data
No data
US$ 7.2 per
capita per year
for health
services. Nutrition
component costs
not available
No
20
All mortality rates for 0-11 mo. children are per 1000 live births. Other mortality rate
*
are per 1000 children in the stated age range.
All costs are given in 1982 USS. Costs in other currencies and years have been convened to 1982 USS using exchange rate
*
and ONP deflators computed from
data in International financial statistics.
978
R. G. FEACHEM
Country
Rural/
urban
Dates of
feeding
programme
*
Indi
(Punjab)
rural
1970-73
India (Madhya
Pradesh):
exploratory
phase
rural
intensive
phase
Target
children
Educational
programme
for mothers
Other
intervention
Feeding
programme
Participation
All children
0-35 mo. and
< 70V. weight
for age
Twice daily
supervized
feeding to provide
up to 400 kcal
and 11 g of
protein per child
per day
Attendance by
target children
averaged 22V. for
those aged 0-12
mo. and 41V. for
those aged
13-36 mo.
Yes
Prenatal care,
supplementary
feeding of
underweight
mothers
1971-72
All children
6-35 mo.
Weekly collection
of take-home
allocation to
provide 377 kcal
and 19 g of
protein per child
per day
53V. of
available food
was collected
Yes
Preventive
and curative
health care.
Supplementary
feeding for
pregnant and
lactating mothers
rural
1972-74
as above
as above
< 50V. of
available
food collected
No
No
India
(Maharashtra)
rural
1971-79
‘‘Deserving’’
children
0-59 mo
Daily supervised
feeding
No data
Yes
Curative and
preventive
health services,
supplementary
feeding for
pregnant women
Papua
New Guinea
rural
1961-62
All children
6-11 mo.
Weekly collection
of take-home
allocation
to provide
100-280 kcal and
10 g of protein
per child per day
35V. of children
enrolled missed
> 15 weeks and
were excluded
from impact
analysis
No
No
Peru
rural
1962-67
All children
and all adults
Weekly collection
of take-home
allocation to
provide 250 kcal
and 12.5 g of
protein per day
to all family
members
95 V. of families
collected their
supplement
every week
No
No
SUPPLEMENTARY FEEDING FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Control
community
Changes in
nutritional
status
Changes in
*
mortality
Causes
of death
Morbidity
survey,
methods
Changes in diar
rhoeal disease rates
*
Cost
979
Source
Yes
Target children
> 17 mo. were
significantly
heavier, and
target children
>21 mo. were
significantly
taller, than
controls
0-11 mo.
mortality was 89
per 1000 com
pared with 129
per 1000 in
control villages.
12-35 mo.
mortality was
10 per 1000
compared with
19 per 1000 in
control villages
44
*7
.
of deaths
due to diarrhoea
in 1970
Yes, l-week
recall at
home visits
No effect on diar
rhoea incidence
or duration
demonstrated
USS 47 per
0-35 mo. child
per year for
nutrition
intervention
24, 25, 27,
31,37
Yes
Significant
improvement in
weight-for-age
for regular
(> 50
*/.
of
collections)
collectors of food
No data
No data
Yes, 2-month
recall at start
and end of
intervention
Significant
reduction in diar
rhoea incidence
among 24-35 mo.
age group, but not
among younger
children
USS 57 per child
per year for the
complete inter
vention package
17
Yes
Significant
improvement
in weight-for-age
but not as great as
achieved by
complete package
(see above)
No significant
reduction
4.5'5'. of
deaths among
0—47 mo.
children
attributed to
diarrhoea
No
No data
USS 39 per child
per year for the
nutrition inter
vention alone
Yes
No data
In 1976,0-11 mo.
mortality was 39
per 1000 in
project area and
90 per 1000 in
control area
No data
No
No data
USS 2.5 per
capita per year
for complete
intervention
package
Yes
Supplementary
feeding did not
affect height or
weight gain
No data
No data
Yes, monthly
examination and
stool microscopy
Supplementary
feeding did not
influence the value
of a composite
"illness score" that
included diarrhoea
and dysentery
No data
9
Yes
No clear evidence
that the supple
mentary feeding
improved the
nutritional status
or growth of any
age group. This
poor response was
attributed to the
supplementary
foods displacing
traditional foods
0-11 mo.
mortality was
significantly lower
in intervention
villages (44-52
per 1000) than
in control
villages (104-165
per 1000). 12-59
mo. mortality was
not significantly
reduced
No data
No
No data
No data
6
2, 3.4
* All mortality rates for 0-11 mo. children are per 1000 live births. Other mortality rates are per 1000 children in the stated age range.
• All costs are given in 1982 USS. Costs in other currencies and years have been convened to 1982 USS using exchange rates and GNP deflators computed from
data in International financial statistics.
CH 3-2.
© World Health Organization 1983
Bulletin of the H arid Health Organization, 61 (4): 641 - 652 (1983)
Interventions for the control of diarrhoeal diseases
among young children: measles immunization
*
R. G. Feachem1 & M. A. Koblinsky2
The effects of measles immunization on diarrhoea morbidity and mortality are
reviewed using data from field studies and theoretical calculations. Two types of measlesassociated diarrhoea are distinguished: with-measles diarrhoea, which starts between 1
week pre-rash-onset and 4 weeks post-rash-onset, and post-measles diarrhoea, which starts
4-26 weeks post-rash-onset. The etiology of these measles-associated diarrhoeas is
unknown, but some evidence points towards a frequently severe and dysenteric form of
disease, with Shigella playing a major role. Theoretical calculations indicate that measles
immunization, at the age of 9-11 months, with coverage of between 45 % and 90% can avert
44-64% of measles cases, 0.6-3.8% of diarrhoea episodes, and 6-26% of diarrhoea deaths
among children under 5 years of age. The cost of measles immunization is in the range of
USS 2-15 (1982 prices) per child vaccinated. The impact of measles immunization on
diarrhoea mortality may be partly additional to the impact of oral rehydration because it
averts deaths that are not prevented by oral rehydration. Community research is urgently
needed to confirm or reject these theoretical suppositions, to clarify the etiology of measlesassociated diarrhoea, and to determine the cost-effectiveness of measles immunization as
an intervention to reduce diarrhoea mortality.
Measles immunization is now an integral part of the
Expanded Programme on Immunization (EPI) which
many developing countries are implementing with the
support of the World Health Organization. In some
developed countries, e.g., Czechoslovakia and the
USA, the elimination of measles may soon be
achieved (12). There is a marked association between
measles and diarrhoea in developing countries today,
as there was in developed countries in earlier times
(20). Since cases of measles complicated by diarrhoea
have a high fatality rate, measles immunization is a
potential intervention for diarrhoea control. This
review of the role of measles immunization in
diarrhoeal disease control is the first in a series of
reviews of potential anti-diarrhoea interventions
which will be published in the Bulletin of the World
Health Organization (9).
EFFECTIVENESS
either
a considerable pro
portion of diarrhoea
morbidity or mortality
in young children in
developing countries is
associated with measles
hypothesis
1
and
measles immunization
can reduce the
incidence of measles
hypothesis
2
measles immunization
can reduce diarrhoea
morbidity or mortality
rates in young children
hypothesis
3
For measles immunization to be an effective
diarrhoea control intervention, the following hypoth
eses have to be tested and proved:
• Requests for reprints should be sent to the Programme
Manager, Diarrhoeal Diseases Control Programme, World Health
Organization, 1211 Geneva 27, Switzerland.
1 Reader in Tropical Public Health Engineering, London School
of Hygiene and Tropical Medicine, Keppel Street, London WC1E
7HT, England.
2 WHO Consultant.
4322
—641 —
642
R. G. FEACHEM & M. A. KOBLINSKY
If hypotheses 1 and 2 are true, it could be appropriate
to field test hypothesis 3; whereas if hypothesis 3 is
known to be true, measles immunization could be
recommended as an operational component of
national diarrhoeal diseases control programmes.
The evidence for and against these hypotheses is
examined below.
Hypothesis 1. A considerable proportion of diar
rhoea morbidity or mortality in young children in
developing countries is associated with measles
Definitions
Two kinds of measles-associated diarrhoea are
distinguished in this review; with-measles diarrhoea
and post-measles diarrhoea. With-measles diarrhoea
is diarrhoea occurring in close association with an
attack of measles and is defined, arbitrarily, by the
period of time separating the appearance of the
measles rash and the onset of diarrhoea. Authors
differ in their definition of this time period. Scrim
shaw et al. (25) reported diarrhoea episodes in 127
measles-infected Guatemalan children, under 5 years
of age, which occurred from 2 weeks pre-rash-onset
to 2 weeks post-rash-onset and found that the great
majority of diarrhoea episodes started between 8 days
pre-rash-onset and 5 days post-rash-onset. These
authors subsequently defined the time limits of withmeasles diarrhoea as that starting between 7 days prerash-onset and 7 days post-rash-onset. In a study in
Nigeria of 142 children suffering from measles and
diarrhoea (20), it was found that the diarrhoea started
14-7 days pre-rash-onset in 5% of cases, 6-1 days prerash-onset in 19% of cases, 0-6 days post-rash-onset
in 25% of cases, 7-14 days post-rash-onset in 11% of
cases, and more than 14 days post-rash-onset in 40%
of cases. This high (40%) proportion of diarrhoea
occurring more than 2 weeks after the rash-onset may
be related to the phenomenon of post-measles diar
rhoea discussed below. Koster et al. (14), after study
ing 119 village children in Bangladesh who had
measles and diarrhoea over a 6-month period, re
ported a marked increase in diarrhoea starting be
tween 1 week pre-rash-onset and 4 weeks post-rash
onset. With-measles diarrhoea is defined, in the
present review, as that starting between 1 week pre
rash-onset and 4 weeks post-rash-onset, although it
must be cautioned that most studies do not report the
exact time frame but imply that with-measles diar
rhoea occurs shortly before or during the exanthem.
A second type of measles-associated diarrhoea,
called here post-measles diarrhoea, was hinted at by
some earlier writers and has recently been investigated
in Bangladesh. Morley et al. (20), for example,
reported from Nigeria that children “were susceptible
to diarrhoea for a long period after the measles itself
had subsided” and that “the diarrhoea may continue
or reappear over a period of many weeks”. More
recently, in Bangladesh, a substantial predisposition
to dysentery, though not to watery diarrhoea, was
found in children for a period of five months follow
ing an attack of measles.0 There is thus some evidence
for a phenomenon of post-measles diarrhoea, which
is defined here, arbitrarily, as diarrhoea occurring in
the period 4-26 weeks post-rash-onset, over and
above that which could occur in that age group at any
time.
In summary, the total of measles-associated diar
rhoea cases is defined here as the sum of with-measles
diarrhoea cases (starting between 1 week pre-rashonset and 4 weeks post-rash-onset) and post-measles
diarrhoea cases (starting 4-26 weeks post-rash-onset).
There is, as yet, very little information on the magni
tude or nature of post-measles diarrhoea.
Measles-associated diarrhoea morbidity
The proportion of diarrhoea episodes that are
measles-associated can be derived theoretically and
from the results of field studies.
Among children aged 0-59 months in developing
countries, there are on average 2.2 episodes of diar
rhoea per year per child (26). If we assume that every
child also has measles before 5 years of age and that
every measles case has one associated diarrhoea
episode, then in the first five years of life an average
child will have 11 episodes of diarrhoea, of which 1 is
measles-associated diarrhoea. Therefore a theoretical
upper proportion of measles-associated diarrhoea to
all diarrhoea in the first five years of life is 9%.
*
A
review of 10 community-based studies in 5 countries0
shows that only 15-63% of measles cases in children
have accompanying diarrhoea. Using these extreme
figures, the proportion of diarrhoea in the first 5 years
of life that is with-measles diarrhoea is 1.0-4.0%,
assuming that 70% of children have measles before
they are 60 months old (70% is the median figure
from 18 studies in 10 countries0). In addition, data on
post-measles diarrhoea from Bangladesh suggest that
18% of children who have measles will experience an
episode of diarrhoea in the following 6 months, which
they would not otherwise have had.rf By the addition
of these post-measles diarrhoea episodes, it is calcu
lated that 2.1-5.2% of diarrhoeal episodes in the first
5 years of life are measles-associated, assuming that
70% of children contract measles before the age of 60
° Shahid, N. S. ET al. Long-term complication in measles in
rural Bangladesh. International Centre for Diarrhoeal Disease
Research, Bangladesh, 1982 (unpublished report).
b This is not the theoretical maximum proportion since it is
possible that each measles attack is associated with more than 1 diar
rhoea episode.
& Tabulated data and sources arc available on request from
d See footnote a, above.
644
R G. FEACHEM & M. A. KOBLINSKY
demies occur in the cool, dry season when diarrhoea
incidence is at its lowest.
In summary, theoretical considerations indicate
that 1-7% of diarrhoea episodes in under-5-year-old
children may be measles-associated (Table 1), while
studies in Nigeria and Guatemala both report a figure
of 6%.
Measles-associated diarrhoea mortality
As with measles-associated diarrhoea morbidity,
the proportion of diarrhoea deaths that are measlesassociated may be derived theoretically and from field
pata.
Theoretically computed measles-associated diar
rhoea incidence rates are presented in Table 1. They
range from 3 to 14 cases per year per 100 children aged
0-59 months. By the application of case-fatality rates
to these incidences, mortality rates for measlesassociated diarrhoea may be derived. The case
fatality rates for measles-associated diarrhoea are
high. A review of 13 studies from 11 countries'’shows
that in hospitals, which tend to see more severe cases,
5-29% of young children with measles and diarrhoea
die, whereas fatality rates reported from community
studies are between 2% and 9%. In Table 2, three
possible case-fatality rates (3%, 6% and 9%) are
applied to three possible measles-associated diar
rhoea incidence rates (4, 8 and 12 per 100 children
aged 0-59 months) to obtain a range of measlesassociated diarrhoea mortality rates. These mortality
rates are then compared with an overall diarrhoea
mortality rate of 1.4 per 100 under-5-year-old chil
dren per year (26) to obtain the proportions of diar
rhoea deaths that are measles-associated. The range
of proportions is considerable (9-77%), and is subject
*to the important cautions given in the footnote to
Table 2.
Only one field report giving the proportion of diar
rhoea deaths that are measles-associated has been
located (14). It describes a one-year surveillance of
5775 rural Bangladeshi children under 10 years old, 29
of whom died of diarrhoea alone and 15 of diarrhoea
with measles (death within one month of rash-onset).
Thus, 34% of these diarrhoea deaths were measlesassociated. In this same study, a further 8 children
died with measles complicated by a combination of
diarrhoea and respiratory symptoms or by various
other complications. If 2 of these 8 deaths are
included as deaths from measles-associated diar
rhoea, the proportion of diarrhoea deaths that were
measles-associated rises from 34% to 37%. These
data relate to 0-9-year-oId children, not 0-4 years as
in Table 2. The effect of considering this older age
group may be to increase the proportion of diarrhoea
deaths that are measles-associated because the more Tabulated data and sources are available on request from
R.G.F.
Table 2. The proportion of diarrhoea deaths in the first
five years of life that is measles-associated, based on
various assumptions
Measlesassociated
diarrhoea
incidence
Case-fatality
per 100 chilrate for
dren aged
measlesassociated
0-59 months
per year
diarrhoea (%)
Measles
associated
diarrhoea
mortality
per 100
children aged
0-59 months
per year
Proportion of
all diarrhoea
deaths among
children aged
0-59 months
that are
measlesassociated (%)°
4
3
0.12
8.6
4
6
0 24
17.1
4
9
0.36
25.7
8
3
0.24
17.1
8
6
0.48
34.3
8
9
0.72
51.4
12
3
0.36
25.7
12
6
0.72
51.4
12
9
1.08
77.1
" These calculations assume that the annual mortality rate
from diarrhoea in the first five years of life is 1.4 per 100 children
(26). In areas where children die more frequently from diarrhoea
than this, the proportion of deaths that are measles-associated
will be lower, while in areas where the diarrhoea death rate is
lower, the proportion will be higher. It is further assumed that
measles-associated diarrhoea deaths are recorded as diarrhoea
deaths. In the case of post-measles diarrhoea deaths this is a
reasonable assumption, but many with-measles diarrhoea
deaths will be recorded as deaths from measles rather than
deaths from diarrhoea. If all with-measles diarrhoea deaths were
recorded as measles deaths, the proportions given in the final
column should be reduced by 50-86% (see Table 1). These
calculations also assume that the case fatality rates for withmeasles diarrhoea and post-measles diarrhoea are the same;
there is no evidence on which to judge the correctness of this
assumption.
tality rate from all diarrhoeas declines more rapidly
after 5 years of age than does the mortality rate for
measles. Expressing the mortality rate among 6-9year olds as a percentage of the rate among 4-5-year
olds, the same researchers (14) found that it was 6%
for diarrhoea and 23% for measles. This effect may
be partly counteracted by the exclusion from these
data of deaths due to post-measles diarrhoea.
In summary, theoretical considerations indicate
that perhaps 9-77% of diarrhoea deaths in the first 5
years of life are measles-associated, while the one
field study providing data on this suggests a figure of
37% (for 0-9-year-old children).
Etiology of measles-associated diarrhoea
The etiology of measles-associated diarrhoea
remains largely unknown. The high case-fatality
rates, however, suggest a severe form of the disease.
MEASLES IMMUNIZATION AND CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
months. This calculation is sensitive to the assump
tions made about the proportion of measles cases that
have with-measles or post-measles diarrhoea and to
the assumption that 70% of children have measles
before they are 60 months old. Table 1 presents the
proportions of diarrhoeas in the first 5 years of life
that may be measles-associated, based on different
values of these parameters. The range of proportions
is 1.4-6.6%, and is subject to the cautions given in the
footnote to Table 1.
Data from community studies support this theor
etical range. In Imesi, Nigeria, 259 children under 5
years old averaged 2.3 episodes of diarrhoea per year
per child over a 3-year period, of which 0.14 (or 6%)
were measles-associated (20). In Santa Cruz Balanya,
643
Guatemala, each child under 5 years of age was found
to suffer an average of 1.65 episodes of diarrhoea in
the year commencing April 1963 (JO). During a 4month period of that year, there was a measles epi
demic in the village and, during that time, a child
suffered on average 0.6 episodes of diarrhoea of
which 0.098 were with-measles diarrhoea. Therefore,
computed over the year and assuming that no measles
occurred outside the period of the epidemic, the pro
portion of diarrhoea episodes that were measlesassociated was 6%. The proportion over the period of
the epidemic only was 16%, thus illustrating the
manner in which measles-associated diarrhoea be.
comes more prominent during a measles epidemic anc
especially when, as commonly occurs, measles epi
Table 1. The proportion of diarrhoea episodes in the first five years of life that is measles-associated, based on
various assumptions
Proportion of
measles cases
having post
measles diarrhoea
(that they
would not other
wise have had)
(%)
Proportion
of children
contracting
measles before
age 60 months
(%)
20
10
20
10
20
Proportion of
measles cases
having withmeasles diarrhoea
(%)
Measles-associated
diarrhoea incidence
per 100 children
aged 0-59
months per year
Proportion of all
diarrhoea episodes
among children aged
0-59 months that is
measles-associated
(%)“
90
5.4
2.6
70
4.2
1.9
10
50
3.0
1.4
20
20
90
7.2
3.3
20
20
70
5.6
2.6
20
20
50
4.0
1.8
40
10
90
9.0
4.1
40
10
70
7.0
3.2
40
10
50
5.0
2.3
40
20
90
10.8
4.9
40
20
70
8.4
3.8
40
20
50
6.0
2.7
60
10
90
12.6
5.7
60
10
70
9.8
4.5
60
10
50
7.0
3.2
60
20
90
14.4
6.6
60
20
70
11.2
5.1
60
20
50
8.0
3.6
j
' These calculations assume that, on average, a child has 2.2 episodes of diarrhoea per year in the first five years of life 126}. In
areas where children have more frequent diarrhoea, the proportion that is measles-associated will be lower, white where diarrhoea is
less frequent, the proportion that is measles-associated will be higher. It is further assumed that measles-associated diarrhoea is
recorded as diarrhoea in surveillance data and thus forms a part of the 2.2 episodes of diarrhoea per child per year. In the case of post
measles diarrhoea this is almost certainly a correct assumption, but with-measles diarrhoea may be recorded as a complication of
measles rather than a case of diarrhoea.
646
R. G. FEACHEM & M. A. KOBLINSKY
Table 3. Reported coverage rates for measles immuniz
ation in some developing countries reporting > 50%
coverage as at 1982
Reported
coverage
(%)“
WHO Region
Country or area
Africa
Botswana
63
Gambia
61
United Republic of Tanzania
82
Argentina
60
Americas
Brazil
58
Chile
88
Costa Rica
68
Ecuador
67
Maldives
98
Mongolia
98
Europe
Turkey
52
Eastern
Mediterranean
Bahrain
63
Egypt
63
Islamic Republic of Iran
81
Israel
69
South-East Asia
Western Pacific
Kuwait
71
Libyan Arab Jamahiriya
65
Tunisia
65
American Samoa
86
Brunei
*
73
Hong Kong
*
74
Niue
*
77
Singapore
86
Trust Territory of the
Pacific Islands
*
53
° Coverage rates refer to the proportion of children vaccinated
by 12 months, except in cases marked * where they describe
immunization coverage by 60 months. For most countries the
figures refer not to the whole country but to selected regions
where measles immunization has been initiated on a pilot basis.
(Source: Data reported to WHO)
figure of 75%, bearing in mind that the relevant
coverage figure is not what is now being achieved in
countries with only limited immunization pro
grammes, but what might be reasonably expected in
countries committed to measles immunization and
with a national programme built up over several
years.
Thus, of the 756 children requiring measles
vaccine, 567 (75%) will be vaccinated. The remaining
189 will not be vaccinated and an estimated 66% / or
125 of these, will go on to contract measles before
month 60.
Of the 567 vaccinated children, a proportion would
have been immunized successfully. The not success
fully immunized ones will be those who were suscept
ible but failed to seroconvert, plus those who were not
susceptible because of persisting maternal antibodies.
The seroconversion rate at 9-11 months, based on
reports from developing countries, is generally
> 90% although lower figures have also been
reported (Table 4). High seroconversion rates are
reported from carefully organized research studies in
which the vaccine’s potency is well maintained. Sero
conversion rates in on-going immunization pro
grammes are probably lower because of operational
factors. In addition, a small proportion of children
(probably 1-5%) at ages 9-11 months are not suscept
ible owing to persisting maternal antibodies. Taking
these considerations into account, it may be assumed
for the present example that 90% of children without
a history of measles who are vaccinated at ages 9-11
months will seroconvert and be immune to measles.
In Table 5, two seroconversion rates have been
adopted for comparison (80% and 90%). Thus, of the
567 vaccinated children, 510 (90%) would have been
effectively immunized and 57 would not; 38 (66%) of
these 57 would then go on to contract measles before
month 60?
In summary, out of 1000 children born alive, the
following will get measles between months 0 and 60:
3 will have measles and then die before 9-11 months,
94 will have measles and recover before 9-11 months,
125 will not be vaccinated and will go on to get
measles before month 60, and 38 will be vaccinated
but will nevertheless get measles before month 60.
This makes a total of 260 measles cases.
The number of measles cases in the absence of an
immunization programme may be computed in a
similar manner. Of 1000 children born alive, 150 will
die before 12 months and 3 of these will have measles
before they die. Of the remaining 850, approximately
70% (or 595) will have measles before the age of 60
months. This makes a total of 598 measles cases in the
first five years of life. Therefore, in the first five years
of life, the number of measles cases averted per 1000
live births by a measles immunization programme will
be 338 (598-260), or 57%.
This calculation is presented in Table 5, using four
levels of programme coverage (45%, 60%, 75% and
90%), and two rates of successful seroconversion
after measles immunization at 9-11 months of age
(80% and 90%). A correction using infant mortality
J If 11 °7o have measles before 12 months, and 70% before 60
months, the proportion of those who have not had measles al 12
months but who will have it by 60 months is 66%.
MEASLES IMMUNIZATION AND CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Indications that with-measles diarrhoea may be pri
marily dysenteric in nature are based on reports from
several studies. Thus, blood was commonly present in
the stools of Gambian village children suffering from
with-measles diarrhoea (16). Hospital data from East
and West African countries found 62% (21) and 65%
(22), respectively, of with-measles diarrhoea to be
mucoid or mucoid and bloody, or to be associated
with anal prolapse. In the above reports, bloody and
mucoid diarrhoeas with measles were more fatal than
those described as mucoid only (11% vs 6% in East
Africa; 18% vs 11% in West Africa), although the
mucoid diarrhoeas were the majority of the dysenteric
diarrhoeas (68% and 72% respectively). Bacterio
logical examination detected Shigella species in
“approximately 50%” of faecal samples from chil
dren having with-measles diarrhoea in Bangladesh
(14). Although this observation was uncontrolled, it
may be contrasted with the typical 4-10% isolation
rates of Shigella from paediatric diarrhoea cases in
the same area of Bangladesh (2). In Bangladesh it was
also observed (14) that the with-measles diarrhoea
cases were of significantly longer average duration
(51 % of episodes lasting more than 6 days) than other
diarrhoeas (only 25% of episodes lasting more than 6
days). Immunological factors that may account for
the association between measles and diarrhoea have
been reviewed by Greenwood & Whittle (11).
With regard to post-measles diarrhoea, recent evi
dence from Bangladesh suggests the predominance of
dysentery/ In a comparison of children in the five
months after measles with matched controls, it was
found that the attack rates for watery diarrhoeas were
47% in the post-measles cases and 56% in the controls
(not significant), whereas the attack rates for mucoid
diarrhoeas were 42% among the cases and 19%
among the controls (P < 0.01) and the attack rates for
bloody diarrhoeas were 21% among cases and 9%
among controls (P < 0.05).
In contrast to these findings, a hospital study in
Kenya (23) reported that, of 200 rectal swabs taken
from children having with-measles diarrhoea, only 3
were positive for Shigella and 1 for Salmonella-, the
stools of these patients were described as bloody and
mucoid. The case-fatality rate in this Kenyan series
was, however, high at 29%. A study of 54 children
hospitalized with measles and diarrhoea in Rwanda
found Shigella in the stool of only 1 child, whereas
Salmonella was found in 16(7). A retrospective study
in Thailand found diarrhoea to be a common compli
cation of hospitalized measles (26%), but the diar
rhoea was reported to be rarely severe and almost
always responded to oral rehydration.8 Interestingly,
1 See footnote a, page 642.
r WARD, N. a. Survey to determine mortality and morbidity
patterns in measles, Thailand. Unpublished WHO document SEA/
EPI/5, 1979.
645
measles in general was not considered to be especially
life-threatening in Thailand, and the hospital case
fatality rate for all measles cases was only 2.3%.
The etiology of measles-associated diarrhoea, and
in particular the role of Shigella and other agents of
dysentery, requires urgent investigation. Such studies
are under way, with WHO support, in Rwanda and
should be conducted in other sociocultural and
environmental settings as well.
Hypothesis 2. Measles immunization can reduce the
incidence of measles
The experience of. some developed countries, such
as Czechoslovakia and the USA which are close t|
measles elimination, clearly shows that measles
immunization can reduce the incidence of measles
very greatly (12). In developing countries, however,
many factors intervene to reduce the overall impact of
a measles immunization programme.
Consider, for example, a group of 1000 children
born alive. By the age of immunization (usually 9-11
months), 150 will have died/ and a proportion of
those surviving will have had measles. Data from 18
studies in 10 developing countries show that the pro
portion of children contracting measles before the age
of immunization is 4-25% and that the figure is gen
erally higher in urban than in rural areas;' the figure
of 11 % will be adopted here as it is the median figure
from the data reviewed. Therefore, of the 850 chil
dren surviving to immunization age, 11 % or 94 would
have had measles and it will be assumed that a further
2%, or 3 of the 150 children who died earlier, had
measles before they died. Therefore, out of the 1000
children born in month 0, there will be 97 measles
cases by month 12.
During months 9-11, the 850 surviving children will
be the subjects of a measles immunization prc«
gramme; 756 (850-94) would not have had measles
and a proportion of these will receive the vaccine.
This proportion depends on the programme cover
age. Theoretically, this coverage can be 100% but in
practice it is lower. As many countries do not have an
effective measles immunization programme, the
coverage figures for a whole region are generally less
than 10%. The coverage figures for individual
selected countries can be higher (Table 3), although
some of the figures reported are very optimistic esti
mates. In subsequent tabulations (Tables 5 and 6),
four possible coverage figures have been adopted for
comparative purposes (45%, 60%, 75% and 90%).
For the present example, we shall assume a coverage
h The infant mortality rate varies greatly among countries.
A figure of 150 is adopted for the purposes of this illustrative
example. No allowance is made for mortality after 1 year of age.
' Tabulated data and sources are available on request from
R.G.F.
648
R. G. FEACHEM & M. A. KOBLINSKY
portion of measles cases averted in under 5-year-old
children, as a result of the measles immunization
programme.
Hy pothesis 3. Measles immunization can reduce diar
rhoea morbidity or mortality rates in young children
Field reports on the effect of measles immunization
on diarrhoeal disease rates have been looked for with
out success, although studies of this type are under
way in Bangladesh and possibly elsewhere.
The only approach, at present, to assessing hypoth
esis 3 is, therefore, a theoretical one using infor
mation computed during the assessment of hypoth
eses 1 and 2. If, among under-5-year-o!d children, 4%
of diarrhoea morbidity (Table 1) and 30% of diar
rhoea mortality (Table 2) were measles-associated,
and if 54% of the measles cases could be averted by
measles immunization with a coverage of 75% (Table
5), then measles immunization might reduce diar
rhoea morbidity by 2.2% and diarrhoea mortality
by 16% in children in this age group. Table 6 presents
the results of these computations for various values of
measles-associated diarrhoea morbidity (2%, 4% and
6%), measles-associated diarrhoea mortality (20%,
30% and 40%), and immunization programme cover
age (45%, 60%, 75% and 90%). It is concluded that
measles immunization among children aged 0-59
months may reduce diarrhoea morbidity by 0.6-3.8%
and diarrhoea mortality by 6-26%. These calcu
lations all depend on the assumption that, if a case of
measles is averted by immunization, the diarrhoea
(both with-measles and post-measles) associated with
that case of measles will also be averted. This is only
true if measles-associated diarrhoea is actually
“caused” by measles (not necessarily in the sense that
the measles virus causes the diarrhoea but in the more
general sense that measles infection leads to diarrhoea
by still unknown immunological or pathological
mechanisms) and not because the susceptibilities to
measles and diarrhoea are both dependent on some
other factor.
The proportions of diarrhoea morbidity and mor
tality averted in children under 5 years of age are
likely to increase as the immunization programme
continues and herd immunity rises, with a consequent
decrease in the proportion of children acquiring
measles before the age of immunization and an in
fable 6. Reduction of diarrhoea morbidity and mortality in the first five years of life by measles immunization at
various levels of coverage
Coverage
of measles
immunization
1
(%)
Proportion
of measles
cases averted
by measles
immunization
(see Table 5)
(%)
45
32
2
0.6
20
6.4
45
32
4
1.3
30
9.6
45
32
6
1.9
40
12.8
60
44
2
0.9
20
8.8
60
44
4
1.8
30
13.2
60
44
6
2.6
40
17.6
75
54
2
1.1
20
10.8
75
54
4
2.2
30
16.2
75
54
6
3.2
40
21.6
90
64
2
1.3
20
12.8
90
64
4
2.6
30
19.2
90
64
6
3.8
40
25.6
Proportion
of diarrhoea
episodes that
are measlesassociated
(see Table 1)
(%)
Proportion of
of diarrhoea
episodes averted
by measles
immunization0
(%)
Proportion
of diarrhoea
deaths that
are measlesassociated
(see Table 2)
(%)
Proportion
of diarrhoea
deaths averted
by measles
immunization0
(%)
a These calculations assume that measles-associated diarrhoea occurs with equal frequency among measles cases that are and
are not averted by measles immunization. If failure to be immunized and measles-associated diarrhoea are both associated with an
independent factor (say, low socioeconomic status), then this assumption does not hold and the impact on diarrhoea of measles
immunization will be lower than predicted here.
647
MEASLES IMMUNIZATION AND CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 4. Age-specific seroconversion rates following measles immunization
Seroconversion rate (%) at:
Country
Reference
—
6
7
8
9
months
10
52
72
86
95
98
12
11
Africa
Kenya
29
94°
Nigeria
South Africa
23
45
57
Upper Volta
76
Zimbabwe
59
90
80
86
74
63
44
United Republic of Tanzania
71
86
97
13
8
28
17
97
North America
80-85
USA
15
South America
Chile
57
59
3
5
99
3 countries:b
well nourishedc
59
69
84
87
93
94
97
undernourished4*
81
91
93
94
90
96
86
a Children aged 12-23 months
b Brazil, Chile and Ecuador
c > 85% weight-for-age
d 60-85% weight-for-age
rates is not shown in Table 5 because these rates affect
equally the communities both with and without a
measles immunization programme and they do not
change the computed proportions of measles cases
averted. The proportion of measles cases in children
aged 0-59 months averted by measles immunization
(Table 5) is between 30% and 68%, depending on the
programme coverage and, to a lesser extent, on the
assumed seroconversion rate. The reader who is
interested in a particular locality and knows that the
programme coverage, seroconversion rate and age at
immunization are different from those assumed
above may use his figures and make a calculation to
obtain the percentage of measles cases averted.
These calculations reflect the situation of a
community having no measles immunization and the
same community immediately after the implement
ation of a measles immunization programme with a
specified level of coverage. As this programme
continues, the age distribution of measles cases will
shift upwards, reducing the proportion of children
who acquire measles before the age for immunization
and increasing the proportion of unimmunized chil
dren who acquire measles after their fifth birthday.
Both these changes will cause an increase in the pro
Table 5. Proportion of measles cases averted in the first
five years of life by measles immunization, based on vari
ous assumptions on coverage and the proportion of chil
dren successfully immunized’
Measles
immunization
coverage
(%)
Proportion of
children
successfully
immunized ®
(%)
Proportion of
cases averted
among 0-4-yearold children
(%)
45
80
30
45
90
34
60
80
41
60
90
46
75
80
51
75
90
57
90
80
61
90
90
68
' The logic and assumptions underlying these computations
are set out in an illustrative example in the text.
’ The proportion of children not having had measles who,
when vaccinated at 9-11 months of age, are subsequently im
mune to measles.
650
R. G. FEACHEM & M. A. KOBLINSKY
most reliable. Unfortunately these costs refer to
BCG and DPT (rather than measles) immunization.
Measles immunization may be cheaper than BCG plus
DPT, since it is a single-dose vaccine. As only 10-20%
of the cost of an immunization programme is due to
the vaccines (6), the additional cost of adding measles
immunization to an existing EPl programme may be
low. A reason for the apparently high cost figure from
Ivory Coast (Table 7) is that the reverse approach was
taken, 75% of all shared EPI costs being allocated to
measles immunization. This has the effect of making
measles immunization appear expensive, while other
immunizations appear relatively cheap.
h Future research will generate improved data on the
Tost and impact of measles immunization and will
permit cost-effectiveness comparisons of measles
immunization with other diarrhoea control interven
tions. Care is required in the allocation of costs and
benefits between diarrhoeal disease control pro
grammes (CDD) and EPI programmes and it must be
recognized that many with-measles diarrhoea deaths
are recorded as measles deaths (see footnote to Table
2). On the other hand, measles immunization may
avert a considerable number of post-measles diar
rhoea deaths that are not currently accounted for in
evaluations of the impact of measles immunization
programmes (7).
CONCLUSIONS
A theoretical case has been made out that measles
immunization can substantially reduce diarrhoea
mortality among children under five years of age.
Immunization with a coverage of 60% may reduce
diarrhoea mortality in children aged 0-59 months by
9-18%, coverage of 75% may reduce diarrhoea mor
tality by 11-22%, and coverage of 90% may reduce
diarrhoea mortality by 13-26% (see Table 6). The
impact of measles immunization on diarrhoea mor
tality is likely to increase as the measles immunization
programme continues and the age distribution of
measles cases shifts upwards. The impact of measles
immunization on diarrhoea mortality may be partly
additional to the impact of oral rehydration because it
averts deaths that are not prevented by oral re
hydration. Community research is urgently needed
to confirm or reject these theoretical suppositions and
to clarify the etiology of measles-associated diar
rhoea.
If community studies confirm that measles immu
nization can reduce diarrhoea mortality, over and
above the reduction achieved by oral rehydration,
detailed cost-effectiveness analyses are required to
compare measles immunization with other possible
interventions for averting the same diarrhoea deaths.
ACKNOWLEDGEMENTS
The authors are grateful for the constructive criticisms of earlier drafts of this paper provided by 1. de Zoysa, S. Foster,
A. Galazka, R. Henderson, R. Hogan, M. Merson, D. Morley, D. Shepard and A. Tomkins. Secretarial and bibliographic
assistance was most ably provided by Ms Maelorwen Jones.
RfiSUME
STRATEGIES POUR LA LUTTE CONTRE LES MALADIES DIARRHEIQUES CHEZ LES JEUNES ENFANTS:
VACCINATION ANTIROUGEOLEUSE
Cette etude est la premiere d’une serie consacree aux stra
tegies susceptibles d’abaisser la morbidity et la mortality
dues aux maladies diarrheiques chez les enfants de moins de
cinq ans dans les pays en ddveloppement. On constate
actuellement dans ces pays, comme jadis dans les pays
aujourd’hui d6veloppes, une nette association entre la rougeole et la diarrhee; la vaccination antirougeoleuse represente done une arme possible dans la lutte antidiarrheique.
Sur la base de donndes provenant d’enquetes sur le terrain et
de calculs theoriques, les auteurs de 1’etude passent en revue
les effets de la vaccination antirougeoleuse sur la morbidity
et la mortalite dues aux maladies diarrhlques. De 1 Vo & 7 Vo
des episodes diarrheiques et de 9 Vo a 77Vo des deeds par
maladie diarrheique chez les enfants de moins de cinq ans
pourraient etre lies A la rougeole. Une distinction est faite
entre deux types de maladies diarrheiques assocides & la
rougeole: la diarrhee concomitante, dont le debut se situe
entre la semaine pr6c6dant 1’apparition de Irruption et les
quatre semaines consdcutives A celle-ci, et la diarrhee postrougeoleuse qui commence de 4 A 26 semaines aprds 1’ap
parition de reruption. L’etiologie de ces diarrhees liees A la
rougeole est inconnue, mais certains indices laissent penser
qu’il pourrait s’agir d’une forme frequemment severe et
dysenterique de la maladie, dans laquelle Shigella jouerait
un role primordial. Selon des calculs theoriques, la vacci
nation antirougeoleuse pratiquee entre 9 et 11 mois, avec
une couverture vaccinale comprise entre 45Vo et 90Vo, serait
a meme d’empecher de 44Vo i 64Vo des cas de rougeole, de
649
MEASLES IMMUNIZATION AND CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
crease in the proportion of unimmunized children
acquiring measles after their fifth birthday.
As the estimated mortality reduction is consider
able, there is a need for field studies to assess the role
of measles immunization in reducing diarrhoea mor
tality. If a considerable proportion of measlesassociated diarrhoea is dysenteric in nature, it may
respond poorly to oral rehydration therapy in the
home or at a peripheral health centre. Thus the mor
tality averted by measles immunization (6-26%) may
be, in part, additional to that averted by oral rehy
dration. This would make measles immunization an
especially attractive intervention, since certain other
interventions might only reduce the mortality that is
largely averted by oral rehydration.
Possibility that diarrhoea is caused by measles
immunization. It is necessary to consider whether the
above computations require modification because
diarrhoea in some children may be caused by measles
immunization. Only one controlled study on post
immunization diarrhoea using the further-attenuated
vaccine strains (Schwarz and Moraten) has been
located. This study, which was carried out in Israel
(27) among children aged 9-47 months, showed that
the period prevalence of diarrhoea during days 6-14
after immunization was 12-14% among children
receiving measles vaccines (Schwartz and Moraten)
and 12% among children receiving a placebo (sterile
saline). A survey of 10 035 children aged between 10
and 18 months, who had been immunized against
measles in England, showed that only one child (with
a congenital oesophageal atresia) was admitted to
hospital with diarrhoea and vomiting one week after
the immunization (IS). A recent review of experience
with 131 million cases of measles immunization in the
USA did not mention diarrhoea as an adverse reac
tion (19). This limited evidence suggests that diar
rhoea is not an adverse reaction to the measles
vaccines in current use.
The effect of undernutrition. The role of poor
nutritional status in the synergism between diarrhoea
and measles has not so far been mentioned in this
review. There is evidence that poor nutritional status
predisposes to death from both diarrhoea and measles
and so it is likely that the death rate from measlesassociated diarrhoea is higher among children who
are nutritionally deprived. The calculations in this
paper are based on data from Africa, Asia and Latin
America and reflect the situation in communities with
widely differing levels of undernutrition. The cal
culations are thus generalized across individual
countries and environments. In some communities
the key variables may approximate the median figures
used in this paper, in which case the impact of measles
immunization on diarrhoea may be as calculated
here. In other communities the key variables may
differ considerably from the values used here, in
which case the impact of measles immunization on
diarrhoea may be considerably greater or less than
our calculations. It is likely that in communities where
the prevalence of undernutrition is exceptionally
high, the impact of measles immunization on diar
rhoea mortality will be greater than estimated in this
review.
FEASIBILITY
Measles immunization is well established atw
highly successful in some developed countries (72)7
Some developing countries have initiated measles
immunization programmes that are achieving reason
able coverage in selected regions. The main oper
ational difficulties are maintaining vaccine potency
and achieving high coverage of children within the
target age range (typically 9-11 months). It is
expected that, as experience in measles immunization
in developing countries grows, and as its benefits to
child health become more widely appreciated, these
operational difficulties will be overcome.
COSTS
Few developing countries as yet have national
measles immunization programmes and there is little
reliable information on the cost of such programmes.
Table 7 provides cost data for five countries, of which
the comparative costings of the EPI programmes in
Indonesia, Philippines and Thailand are probably the
Table 7. Costs of immunization
Cost
per child
vaccinated"
(1982 US$)
Country
Immunizations
Indonesia
DPT, BCG
4
Ivory Coast
measles
15
Philippines
DPT, BCG
6
Thailand
DPT, BCG
14
Zambia:
rural
urban
measles
measles
8-14
2-5
Reference
6
30
6
6
24
“ Costs converted to 1982 USS using exchange rates and
GNP deflators computed from data in International Financial
Statistics.
MEASLES IMMUNIZATION AND CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
0,6% a 3,8% des episodes diarrheiques, et de 6% & 26% des
deces dus a des maladies diarrheiques chez les enfants de
moins de cinq ans. Une couverture vaccinale de 75% permettrait d’eviter 2% des Episodes diarrheiques et 16% des
deces dus & des maladies diarrheiques. Il n’existe pas de
donnees fiables sur le cout de la vaccination antirougeoleuse, mais d’apres des statistiques emanant de cinq pays il
pourrait se situer entre 2 et 15 dollars (prix de 1982) par
enfant vaccine.
L’impact de la vaccination antirougeoleuse sur la morta
lity d’origine diarrh&que devrait augmenter & mesure que se
651
developpera le programme de vaccination et que diminuera
la proportion des cas de rougeole concernant des enfants.
Cet impact viendrait s’ajouter a celui de la rehydratation par
voie orale puisque la vaccination tend & prevenir des deces
que n’dviterait pas le traitement. Il est urgent de procider A
des enquetes et etudes de population pour confirmer ou
infirmer ces suppositions theoriques, clarifier 1’etiologie de
la diarrhee li6e & la rougeole et determiner !’efficacit£, par
rapport au cout, de la vaccination antirougeoleuse en tant
que strategic visant d reduire la mortality due aux maladies
diarrheiques.
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CH 3.3
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Bulletin of the Wbrld Health Organization, 61(4):637 - 640(1983)
>
/
/
© World Health Organization 1983
Diarrhoeal disease control: reviews of potential
„ interventions
R. G. Feachem,1 R. C. Hogan,12 & M. H. Merson2
Diarrhoeal diseases are a major cause of sickness and death among young children in
most developing countries. Since effective interventions to control these diseases are
available, they are a priority target for the primary health care programmes being planned
or implemented in many countries. Governments and international agencies, including the
World Health Organization, have emphasized oral rehydration as an effective intervention
for reducing diarrhoeal disease mortality. Other interventions are, however, needed to
reduce morbidity, to reduce mortality not averted by oral rehydration, and to develop a
multifaceted approach in which oral rehydration is one of several anti-diarrhoea measures
being implemented simultaneously with mutally reinforcing and complementary impacts.
This paper presents a classification of potential interventions for the control of diarrhoeal
disease morbidity and/or mortality among children under 5 years of age and introduces a
series of reviews of these interventions. The first of these reviews, on measles immuniz
ation, also appears in this issue of the Bulletin of the World Health Organization.
The concept of primary health care involves the
delivery of a package of curative and preventive
health services at the community level. Various health
service needs have to be satisfied but, owing to man
power, budgetary and other resource constraints, it is
necessary to select those few that meet the priority
health needs and are, at the same time, affordable. A
number of approaches may be used to design an
appropriate primary care package in a specific
country or region. A rational approach is first to
define the major health problems and then select the
most cost-effective means of ameliorating them. This
approach has been discussed fully elsewhere (/, 2).
Identifying and ranking the major health problems
may be done, in defined age groups, by the use of
objective measures of the burden of death or illness
attributable to specific diseases. If this is done, diar
1 Reader in Tropical Public Health Engineering, London School
of Hygiene and Tropical Medicine, Keppel Street, London WC1E
7HT, England.
2 Diarrhoeal Diseases Control Programme, World Health Organ
ization, 1211 Geneva 27, Switzerland. Requests for reprints should be
sent to Dr M. H. Merson.
4321
rhoeal diseases emerge in most developing countries
as a major cause of sickness and death in young chil
dren (2). Recent estimates show that diarrhoeal dis
eases cause nearly 5 million deaths per year in children
under 5 years old in developing countries (excluding
China) where in every 100 children in this age group
there are, on average, 220 diarrhoeal episodes and 1.4
deaths from diarrhoea every year (5). For a health
problem to be a target for selective primary health
care, it must not only be a major cause of sickness and
death but it must also be controllable at a reasonable
cost. Diarrhoeal disease mortality can be effectively
reduced at reasonable cost by oral rehydration (4) and
possibly other measures.
INTERVENTIONS FOR DIARRHOEAL DISEASE CONTROL
In circumstances where diarrhoeal diseases have
been identified as a priority health problem, and a
commitment has been made to combat the problem, it
is necessary to decide how to reduce the mortality and
—637—
63S
R. G. FEACHEM ET AL.
morbidity they cause. The funds available in many
countries for the total primary health care package
are in the order of only USS 1-5 per capita per year,
and only a proportion of this may be devoted to the
control of diarrhoeal diseases. How should this
amount be spent?
This is not a new question. The Fifth Caribbean
Health Ministers’ Conference, meeting in Dominica
in 1973, called for a plan of action against diarrhoeal
diseases and malnutrition in children under 2 years
old. A group of experts was convened and recom
mended a 10-point programme designed to achieve
specified reductions in mortality and morbidity.'1 This
plan of action, although embracing several important
aspects of diarrhoea control, did not provide
guidance to governments on the comparative cost
effectiveness of the many different interventions
recommended.
More recently, Walsh & Warren (2) identified diar
rhoeal diseases as a priority target for selective pri
mary health care and emphasized oral rehydration as
the key intervention for the reduction of diarrhoeal
disease mortality. Chen (5) drew attention to the
importance of diarrhoea morbidity and to the need
for interventions (other than oral rehydration) that
are specifically addressed to this facet of the overall
diarrhoea problem.
It is widely agreed that oral rehydration, delivered
within a primary health care programme, is an effec
tive and relatively inexpensive intervention for the
reduction of mortality due to dehydrating diarrhoeas.
Other interventions are also required, however, for
three main reasons. First, like all health services
delivered at the community level, oral rehydration
programmes face operational constraints that may
militate against the achievement of their full potential
impact. Second, oral rehydration is of limited use in
the treatment of chronic or dysenteric diarrhoeas and,
in areas of the world where these are responsible for a
considerable proportion of diarrhoeal disease mor
tality, the effect of oral rehydration programmes on
the overall mortality from diarrhoeal diseases may be
modest. Third, oral rehydration can be expected to
have little or no impact on diarrhoea morbidity rates.
A multifaceted strategy is therefore preferable, in
which oral rehydration is but one of several anti-diarrhoea measures being implemented simultaneously,
with mutually reinforcing and complementary
impacts.
The Diarrhoeal Diseases Control (CDD) Pro
gramme of the World Health Organization has, since
its inception in 1978, advocated the following fourpart strategy for diarrhoea control:
a Strategy and plan of action to combat gastroenteritis and mal
nutrition in children under two years of age. Report of a Technical
Group Meeting on Malnutrition and Gastro-cnteritis, St Vincent,
8-11 January 1974 (Unpublished document).
— improved case management, with particular
emphasis on the early use of oral rehydration therapy
in acute diarrhoea and on appropriate feeding during
illness and convalescence;
— improved maternal and child health care, with
particular emphasis on breast-feeding, weaning prac
tices, personal and domestic hygiene, and maternal
nutrition;
— improved use and maintenance of drinkingwater and sanitation facilities, and improved food
hygiene;
— detection and control of epidemics.
In the first years of the CDD programme, greatest
emphasis was placed upon oral rehydration as the
primary intervention for reducing diarrhoeal disease
mortality among young children (5). The CDD pro
gramme has developed detailed recommendations for
oral rehydration therapy& and the production of oral
rehydration salts/ and has worked with governments
of Member countries in the planning, implementation
and evaluation of ora! rehydration and other diar
rhoea control measures.d With the implementation of
CDD programmes in over 35 countries, it is now
appropriate to supplement the emphasis on oral rehy
dration by developing, in detail, other interventions
for diarrhoea control and undertaking the necessary
field research and evaluation to establish their feasi
bility and cost-effectiveness.
The CDD programme has therefore undertaken a
systematic and comprehensive review of the effective
ness, feasibility and cost of the many possible anti
diarrhoea interventions available for the reduction of
morbidity and/or mortality among children under 5
years of age. A classification of such interventions is
shown in Table 1. Its purpose is to guide and sys
tematize the process of review and not to provide a
recommendation for diarrhoea! diseases control.
Each intervention listed in Table 1, and possibly
others that may subsequently be proposed, will be
reviewed using a standard format which places
emphasis on information concerning the effectiveness
of the intervention. If the intervention is known or
believed to be effective, available data on its feasi
bility and cost are also presented.
As a result of these reviews, each intervention listed
in Table 1 will be assigned to one of three categories,
each having different requirements for follow-up
action by the CDD programme. First are inter
ventions that are clearly shown to be effective, feas
ible and affordable. For these, the next step will be for
b A manual for the treatment of acute diarrhoea. Unpublished
document WHO/CDD/SER/80.2, 1980.
r Guidelines for the production of ora! rehydration salts.
Unpublished document WHO/CDD/SER/80.3, 1980.
'' Manual for the planning and evaluation of national diarrhoeal
diseases control programmes. Unpublished document WHO/CDD/
SER/81.5, 1981.
INTERVENTIONS FOR DIARRHOEAL DISEASE CONTROL
Table 1. Potential interventions for reducing diarrhoeal
morbidity or mortality among children under five years of
age
I.
III.
A.
By reducing transmission of the pathogenic agents of diar
rhoeal diseases
A.
By case management
1. Administration of oral rehydration in the home
Administration of oral rehydration at a medical
facility.
B.
B.
Non-oral rehydration therapy
Appropriate feeding
C
1. Promoting the appropriate feeding of children during
diarrhoeal illness and convalescence.
D.
Chemotherapy
D.
2. Administration of therapeutic agents at a medical
facility.
E.
2. Improving prenatal and postnatal
improve the quality of breast milk.
B.
nutrition
to
Child nutrition
Fly control
1. Control of flies, especially flies breeding in associ
ation with human or animal faeces.
Ma ternal nutrition
1. Improving prenatal nutrition to reduce the incidence
of low birth-weight.
Control of zoonotic reservoirs
1. Control of infection of domestic and farm animals by
pathogens causing diarrhoea in man.
By increasing host resistance to infection and/or Illness and/
or death
A.
Food hygiene
1. Promoting improved practices for the preparation
and storage of foods, both commercially and in the
home, and especially emphasizing the hygienic prep
aration of weaning foods.
1. Administration of therapeutic agents in the home.
II.
Personal and domestic h ygiene
1. Promoting specific features of personal and dom
estic hygiene, such as hand-washing, by appropriate
educational campaigns.
1. Administration of rehydration by intravenous or
other routes at a medical facility.
C.
Water supply and excreta disposal
1. Constructing water supplies that improve the quality
and availability of water for domestic purposes, and
improved excreta disposal facilities; and providing
the necessary educational support to ensure use and
maintenance of these new facilities.
Ora! rehydration therapy
2.
639
By controlling and/or preventing diarrhoea epidemics
IV.
A.
Epidemic surveillance, investigation and control
1. Improving the ability to identify and investigate an
epidemic early in its course and the capacity to
implement effective control activities.
1. Promoting exclusive breast-feeding up to age 4-6
months and partial breast-feeding thereafter.
2. Improving weaning practices for children aged 4-18
months (introducing non-milk foods not later than
the sixth month, continuing breast-feeding for as
long as possible, and using nutritious and locally
available weaning foods).
C.
3.
Supplementary feeding to improve the nutritional
status of children aged 6-59 months.
4.
Promoting the use of growth charts by mothers as
an aid to proper child nutrition and child care.
Immunization
1. Rotavirus and/or cholera immunization (when effec
tive and tested vaccines are available) of the child
and/or mother.
2. Measles immunization to reduce measles-associated
diarrhoea.
D.
Chemoprophylaxis
1. Chemoprophylaxis of children at special risk, such
as contacts of known cases, to reduce the incidence
and/or severity of diarrhoea.
the CDD programme to develop detailed guidelines
for their implementation within national primary
health care programmes and to promote any oper
ational research needed to improve their delivery or
impact. Second are interventions for which there is
good theoretical evidence of effectiveness but in
sufficient field experience to predict impacts precisely
or to judge feasibility and cost. For these the next step
will be for the CDD programme to promote field
research designed to fill the gaps in knowledge. The
results of this research will determine whether these
category 2 interventions are moved to category 1 or
category 3. Third are interventions which are shown
to be either ineffective, unfeasible or too costly. These
interventions will not be recommended by the CDD
programme as important elements of diarrhoeal dis
640
R. G. FEACHEM ET AL.
ease control activities or priorities for diarrhoeal dis
ease research. It is hoped that this review will help
focus the attention of governments, researchers and
international agencies on a few interventions of
known or suspected effectiveness which, if imple
mented along with oral rehydration therapy, could
markedly reduce the rates of both morbidity and
mortality due to diarrhoeal diseases among young
children.
Reviews of some of the interventions listed in
Table 1 will be published in the Bulletin of the World
Health Organization. The first of these is published in
this issue (pp. 641-652) and deals with measles immu
nization as an intervention for diarrhoeal disease con
trol (II.C.2 in Table 1). It is hoped to publish in
forthcoming issues of the Bulletin reviews on
supplementary feeding (II.B.3), breast-feeding
(II.B.I), and personal and domestic hygiene (III.B. 1).
Readers having suggestions to make on the classifi
cation of potential interventions in Table 1, or on the
individual reviews as they are published, are invited to
write to the Programme Manager, Diarrhoeal Dis
eases Control Programme, World Health Organiz
ation, 1211 Geneva 27, Switzerland.
RESUME
ANALYSE DES MODES D’INTERVENTION POSSIBLES DANS LA LUTTE CONTRE LES MALADIES DIARRHEIQUES
Les maladies diarrheiques constituent dans la plupart des
pays en developpemem 1’une des causes principals de mor
bidity et de monalite chez les jeunes enfants. Du fait que
1’on dispose pour luiter centre ces maladies de modes
d’intervention efficaces, ils doivent representer un objectif
prioritaire des programmes de soins de same primaires
planifies ou mis en oeuvre dans nombre de pays. Des gouvernements et des organismes internationaux, y compris
1’Organisation mondiale de la Same, ont souligne que la rehydratation par voie orale etait une intervention essentielle
pour reduire la mortalite due aux maladies diarrheiques.
Mais il est necessaire cependam de disposer d’autres fa?ons
d’intervenir encore pour diminuer la morbidity, abaisser le
nombre de deces que ne peut empecher la rehydratation par
voie orale et mettre au point une approche conjuguye, dans
laquelle la ryhydratation orale represente 1’une seulemem
des diverses mesures amidiarrheiques appliquees simultanement el dont les effets se renforcem et se completem
mutuellement. L’article qui suit contient une classification
des interventions possibles pour lutter contre la morbidity
et/ou la mortalite dues aux maladies diarrheiques chez les
enfants de moins de 5 ans, et annonce le d6but d’une sdrie
d’analyses de ces strategies, dont la premiere — sur la vacci
nation antimorbilleuse — est publiye dans ce meme numyro
du Bulletin de [’Organisation mondiale de la Sant#.
REFERENCES
1.
Evans, J. R.et al. Health care in the developing world:
problems of scarcity and choice. New England journal
of medicine, 305:1117-1127 (1981).
2. Walsh, J. A. & Warren, K. S. Selective primary
health care: an interim strategy for disease control in
developing countries. New England journal of medi
cine, 301: 967-974 (1979).
3. Snyder, J. D. & Merson, M. H. The magnitude of the
global problem of acute diarrhoeal disease: a review of
active surveillance data. Bulletin of the World Health
Organization, 60: 605-613 (1982).
Mahalanabis, D. et al Oral rehydration therapy:
recent advances. World health forum, 2: 245-249
(1981).
5. Chen, L. C. Control of diarrheal disease morbidity and
mortality: some strategic issues. American journal of
clinical nutrition, 31: 2284-2291 (1978).
4.
CH 3- h
© World Health Organization 1984
Bulletin of the World Health Organization, 62 (2): 271 -291 (1984)
Interventions for the control of diarrhoeal diseases
among young children: promotion of breast-feeding
R. G. Feachem1 & M. A. Koblinsky12
The literature on the relative risks of diarrhoea morbidity to infants on different
feeding modes suffers from several methodological problems. Thirty-five studies from 14
countries were reviewed; 83% ofstudies found that exclusive breast-feeding was protective
compared to partial breast-feeding, 88% that exclusive breast-feeding was protective com
pared to no breast-feeding, and 76% that partial breast-feeding was protective compared to
no breast-feeding. When infants receiving no breast milk are contrasted with infants on
exclusive or partial breast-feeding, the median relative risks are 3.0 for those aged 0-2
months, 2.4 for those aged 3-5 months, and 1.3-1.5 for those aged 6-11 months. Above 1
year of age no protective effect of breast-feeding on diarrhoea morbidity is evident. When
infants receiving no breast milk are contrasted with those on exclusive breast-feeding,
median relative risks are 3.5-4.9 in thefirst 6 months of life. The literature does not suggest
that the relative risks of diarrhoea morbidity for bottle-fed infants are higher in poor
families than in more wealthy families. The protective effects of breast-feeding do not
appear to continue after the cessation of breast-feeding. There is evidence of considerably
increased diarrhoea severity among bottle-fed infants.
There is a limited, and mostly pre-1950, literature on the relative risks of diarrhoea
mortality to infants on different feeding modes. Nine studies from 5 countries were
reviewed, most of which showed that breast-feeding protects substantially against death
from diarrhoea. When infants receiving no breast milk are contrasted with those on
exclusive breast-feeding, the median relative risk of death from diarrhoea during thefirst 6
months of life is 25. When partially and exclusively breast-fed infants are contrasted, the
median relative risk of death from diarrhoea is 8.6.
Breast-feeding can be promoted by changes in hospital routine and by giving
information and support to mothers. A review of21 studiesfrom 8 countries shows that, by
such promotion, the most likely reductions in the prevalence of non-breast-fed infants are
40% among infants aged 0-2 months, 30% among those aged3-5 months, and 10% among
those between 6 months and 1 year old. Theoretical calculations based on these data show
that such promotion can reduce diarrhoea morbidity rates by 8-20% and diarrhoea
mortality rates by 24-27% in the first 6 months of life. For children aged 0-59 months,
diarrhoea morbidity rates would be reduced by 1-4% and mortality rates by 8-9%. A recent
study in Costa Rica has documented a substantial impact of breast-feeding promotion on
neonatal diarrhoea morbidity and mortality, and on diarrhoea morbidity in infants aged
0-5 months. The Costa Rican data show good agreement with the theoretical computations
presented in this paper.
Several important aspects of breast-feeding and diarrhoea remain to be clarified by
research. However, the need for this research should not delay action to promote breast
feeding and to monitor its effects upon feeding practice and upon diarrhoea.
The long debate on the merits of breast-feeding
initially focused on the differences in mortality rates
1 Reader in Tropical Public Health Engineering and Head of
Department of Tropical Hygiene, London School of Hygiene and
Tropical Medicine, Keppel Street, London WC1E 7HT, England.
Requests for reprints should be sent to Programme for Control of
Diarrhoeal Diseases, World Health Organization, 1211 Geneva 27,
Switzerland.
2 Scientific Coordinator, International Centre for Diarrhoeal
Disease Research in Bangladesh, Dhaka, Bangladesh.
4401
between breast-fed and bottle-fed infants. Since
about 1930, and especially since 1955, increased
attention has been paid to differential morbidity
rates. Some studies on mortality and morbidity in
relation to feeding mode singled out particular infec
tious causes of death or illness — most commonly,
diarrhoeal and respiratory diseases. The literature
on the relationships between breast-feeding and
—271—
R. G. FEACHEM & M. A. K0BL1NSKY
diarrhoea is now substantial and permits an assess
ment of breast-feeding promotion as an intervention
for the reduction of diarrhoea morbidity or mortality
in infants. Several recent studies and reviews of
breast-feeding provide a useful background to the
present, more focused analysis (2, 17, 47, 51, 64, 66,
81, 86)“'c of the role of breast-feeding promotion in
diarrhoeal disease control. This review is the third in a
series of reviews of potential anti-diarrhoea inter
ventions now being published in the Bulletin of the
World Health Organization (19-21).
EFFECTIVENESS
For breast-feeding promotion to be an effective
diarrhoea control intervention, it must be true that:
either
breast-fed infants have
reduced diarrhoea
morbidity rates, mortality
rates, or severity
hypothesis
1
and
the prevalence of breast
fed infants can be
increased by appropriate
promotional activities
hypothesis
2
Definitions
th review of breast-feeding and diarrhoeal disease
rates requires clear-cut definitions of the various
feeding modes that are to be contrasted. The number
of feeding modes defined should be small (say, 3 to 5)
in order to increase the sample size of infants on each
feeding mode and in order that the operational signi
ficance of the comparisons will be apparent. How
ever, to assign all of the many permutations of infant
feeding practice to only 3-5 categories inevitably
introduces a degree of imprecision to the definitions.
In this review the following three categories have been
adopted:
— exclusive breast-feeding, which applies to
infants receiving only breast milk (and is thus not
usual in infants over 6 months old);
— no breast-feeding, which applies to infants
receiving no breast milk;
— partial breast-feeding, which applies to infants
who receive breast milk plus other milk or foods.
The feeding modes described in the literature are
assigned to one of these three categories. In several
studies the feeding modes have not been clearly
defined or do not correspond to any of the categories
listed above. In these cases, the feeding mode is
designated so as to minimize the computed protective
effect of breast-feeding.
Methodological problems
or
the promotion of breast
feeding can reduce
diarrhoea morbidity rates,
mortality rates, or severity
in infants
Hypothesis 1. Breast-fed infants have reduced
diarrhoea morbidity rates, mortality rates, or
severity
hypothesis
3
Most of the literature on this topic is addressed to
hypothesis 1 or 2. The potential effectiveness of
breast-feeding promotion would be suggested by a
demonstration either of the correctness of hypotheses
1 and 2 or of the correctness of hypothesis 3. The
evidence for and against these hypotheses is examined
below.
“ Evensen, S. Relationship between infant morbidity and
breast-feeding versus artificial feeding in industrialized countries:
a review of the literature. Copenhagen, WHO Regional Office for
Europe, 1982 (unpublished document 1CP/NUT 010/6).
6 Joint WHO/UNICEF meeting on infant and young child
feeding, Geneva, 1979 (unpublished document).
c WHO/UNICEF. Infant and young child feeding: current
issues, Geneva, 1981 (unpublished document).
The studies on breast-feeding and diarrhoea re
viewed here made use of different methods for the
collection and analysis of their data. Studies that were
judged to have serious methodological flaws were
rejected but the quality of those that were included
varies widely. The most commonly encountered
problem other than definition of feeding mode (see
above) was failure to control possible confounding
variables. The age of the infant is a confounding
variable encountered in all the studies; older infants
are less likely to be exclusively breast-fed than
younger infants and also have different diarrhoeal
disease rates for reasons other than feeding mode.
Emphasis has therefore been placed here on studies
that analyse breast-feeding and diarrhoea rates by
narrow age ranges (e.g., 0-2 months, 3-5 months,
etc.); studies that examine a wider age range of
infants, e.g., aged 0-11 months, are judged to be of
little value.
A second common set of confounding variables is
socioeconomic status and child care. Mothers who
breast-feed may be more or less educated and
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
wealthy, and may take more or less care of their child
than other mothers. Two distinct patterns emerged
from the studies that analysed the effect of these con
founding variables. In some poor communities,
especially in developing countries and in the devel
oped countries before 1930, breast-feeding was more
common among lower socioeconomic strata. In such
communities the confounding socioeconomic vari
ables tend to increase the diarrhoea rates and there
fore minimize the apparent protective effect of breast
feeding. In an uncontrolled study in such communi
ties the protection afforded by breast-feeding may be
underestimated. In certain more prosperous com
munities. especially in developed countries, breast
feeding is at present more common among the middle
classes because it is fashionable. Here the confound
ing socioeconomic variables tend to decrease the
diarrhoea rates and thus an uncontrolled study may
overestimate the protective effect of breast-feeding.
Several of the more recent studies that were reviewed
controlled for confounding socioeconomic and child
care variables, and such control should be regarded as
essential for any future studies of breast-feeding and
diarrhoea. These and other methodological problems
inherent in studies of breast-feeding and health are
reviewed elsewhere (9, 70, 84).d
Mechanisms of protection
If breast-fed infants experience less diarrhoeal ill
ness or death than other infants, it may be due to one
or more of the following factors:
— the immunological and antimicrobial properties
of breast milk;
— the “bifidus factor” (exclusively breast-fed
infants have an intestinal flora composed largely of
Gram-positive anaerobic bacteria (Bifidobacterium
species), which may inhibit colonization by Gram
negative facultative species such as Escherichia coli);
— infants receiving bottle-milk feeds are at risk
from contamination of the milk, the bottle, or the
teat, and infants receiving solid foods are at risk from
contamination of the food (these risks may apply es
pecially to bacterial pathogens that multiply in milk
and some foods);
— breast-fed infants may have a better nutritional
status than other infants, and thus a lesser risk of
death from diarrhoea.
The protective mechanisms of breast-feeding are a
complex subject, in which there is substantial ongoing
research. This is especially true of the first of the four
items listed above. It is probable that the mechanisms
of protection, and their relative importance, vary by
pathogen and by the age of the infant. It is not the
purpose of this paper to review the literature on prod See footnote a on page 272.
273
tective mechanisms, and the interested reader is refer
red to other publications (3, 4, 14, 17, 26, 30, 33,
40-42, 55, 58, 60, 65, 83).
Morbidity
Annex 1 lists 35 studies in 14 countries from which
the relative risk of diarrhoeal illness for infants on one
feeding mode, compared to infants on another
feeding mode, can be computed. Both methods and
findings vary greatly among these studies. For partial
breast-feeding compared to exclusive breast-feeding,
30 relative risks are computed of which 25 (83%) are
> 1. For no breast-feeding compared to exclusive
breast-feeding, 25 relative risks are computed of
which 22 (88%) are > 1. For no breast-feeding com
pared to partial breast-feeding, 45 relative risks are
computed of which 34 (76%) are >1. Thus the
pooled results from 35 studies indicate that in most
circumstances breast-feeding protects against diar
rhoea morbidity. More analysis on these pooled data
is not useful since the results are strongly influenced
by the age of the infants under study.
The age-specific relative risks derived are sum
marized in Fig. 1 and 2, which show clearly the effect
of age. When infants receiving no breast milk are
contrasted with infants on exclusive or partial breast
feeding (Fig. 1), the median relative risks are 3.0 for
ages 0-3 months, 2.4 for ages 3-5 months,e and
1.3-1.5 for ages 6-8 and 9-11 months. Above 1 year
of age, no protective effect of breast-feeding on
f The 0-3-months age group includes studies of both the 0-2months group and the 0-3-months group. This age group therefore
overlaps by one month (month 3) with the 3-5-months age group.
These remarks also apply to Fig. 1 and 2.
Fig. 1. Median relative risks of diarrhoea morbidity for
infants receiving no breast-feeding compared to infants
with partial or exclusive breast-feeding (data from
Annex 1).
274
R. G. FEACHEM & M. A KOBLINSKY
The discussion above deals only with the protective
effects of a particular feeding mode during the period
when this feeding mode is applied. It is conceivable
that breast-feeding confers some protection against
diarrhoea after breast-feeding has been discontinued.
Few studies present data that allow this possibility to
be analysed. The findings of Ferguson et al. (23) in
New Zealand are summarized in Table 1. All infants
described in Table 1 had ceased breast-feeding and
their period prevalences of diarrhoea are compared
according to their past experience of breast-feeding.
The data are weakened by the use of period preva
lence rather than incidence but, none the less, the
results do not suggest that a longer duration of breast
feeding was associated with a lower period prevalence
of diarrhoea. This cessation of protection after dis
continuation of breast-feeding has been reported also
in studies of all significant illness episodes (9) and of
total hospital admissions (15).
Severity
Fig. 2. Median relative risks of diarrhoea morbidity by
feeding mode (data from Annex 1).
diarrhoea morbidity is evident. When infants receiv
ing no breast milk are contrasted with those on exclu
sive breast-feeding (Fig. 2), the median relative risks
are 3.5-4.9 in the first 6 months of life. Beyond 6
months of age, exclusive breast-feeding is not a nutri
tionally recommended feeding mode and may be a
risk factor, rather than a protective factor, for diar
rhoea. This possibility is illustrated by the data from
Ethiopia and Uganda (Annex 1).
It is possible that the relative risks of diarrhoea for
bottle-fed infants are greatest in families of lowest
socioeconomic status where diarrhoea incidence is
high and nutritional status is low, and where there are
many opportunities for the contamination of bottle
milk. The data in Annex 1 were analysed (not shown)
to test this possibility and gave no grounds for
supposing that the relative risks of diarrhoea for
bottle-fed infants are lower in more wealthy families.
Breast-feeding appears to protect against diarrhoea
irrespective of the levels of hygiene. This suggests
either that the main protective mechanisms are the
immunological and antimicrobial properties of the
breast milk together with the “bifid” flora of the gut
or that contamination of bottle milk is an important
cause of infant diarrhoea even in families of upper
and middle socioeconomic status. The possible lack
of association between the relative protection af
forded by breast-feeding and socioeconomic status
should be further studied.
Only a few studies provide data from which the
relationship between breast-feeding and diarrhoea
severity may be assessed. Table 2 summarizes 5
studies of case-fatality ratios. Four of these (from
England in the 1930s, USA in the 1920s, and Rwanda
recently) show major differences in case-fatality
ratios by feeding mode. These results could be con
founded by other clinical problems of the children
who died; those not breast-fed could have been under
nourished or chronically ill, for instance. The data
from Birmingham, England, in the 1930s (73) show
that the prevalences of undernutrition (<80%
Table 1. Period prevalence of treated diarrhoeas and all
diarrhoeas in specified age groups, by duration of
previous breast-feeding"
Age group
(months,
inclusive)
4-11
12-23
Duration
of previous
exclusive
breast-feeding
(months)
Treated
*diarrhoeas
All
diarrhoeas'
Period prevalence (%)
0
22
44
0-3
25
48
0
29
63
0-3
32
64
4-7
31
64
8-11
29
65
" Data from Ferguson et al. (23).
h Diarrhoeas reported to a medical practitioner or hospital for
treatment.
r All diarrhoeas, including those managed at home.
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
275
Table 2. Case-fatality ratios for diarrhoea cases in four countries, by feeding mode
Country
and place
Date
of study
Socio
economic
status
Age
group
(inclusive)
Total
number of
diarrhoea
cases
(deaths)
Part BF°
No BF°
Ratio of
case
fatality
ratios
(No BF/
Part BF)
14
15
1.1
13
Case-fatality ratios (%)
Excl. BF°
Reference
Canada
*
Toronto
1939
?
0-11 mo.
England
Liverpool
1936
Lower/
middle
?
3-26 wk
130 (9)
5
9
1.8
69
?
0-9 mo.
500 (240)
26
77
3.0
73
Rwanda
*
Kigali
1977-78
?
0-23 mo.
849 (95)
7
22
3.1
50
USA
Chicago
1924-29
Lower
0-3 mo.
4-8 mo.
1877 (22)
0.9
0.3
20
2
22
6.7
35
36
*
Birmingham
314 (46)
0.6
“ For definitions of feeding modes, see footnote b to Annex 1
* Study of hospitalized diarrhoea cases only.
weight-for-age) among non-breast-fed infants who
died of diarrhoea, and among all diarrhoea cases,
were 41% and 37% respectively, suggesting that the
apparent effect of feeding mode on case-fatality ratio
(Table 2) was not confounded by malnutrition.
Grulee (35), commenting on the Chicago (1924-29)
study, wrote that “1924 to 1929 were the years of
plenty” and that “undernutrition does not enter into
the picture”. The Chicago study used data from the
surveillance of over 20 000 infants. Such data are less
likely to be confounded by undernutrition, and much
less likely to be confounded by chronic illness, than
data derived from hospitalized cases only.
An investigation of shigellosis in Bangladesh (77)
found that severity was related to feeding mode.
Breast-fed and non-breast-fed children under 2 years
old with shigellosis were compared; among the breast
fed group, fewer required intravenous therapy (16%
vs 38%) and fewer were admitted as inpatients (5% vs
19%).
Breast-feeding may play a role in reducing the
nutritional consequences of diarrhoea episodes in
young children. A study of children aged 6-35
months, hospitalized with acute watery diarrhoea in
Bangladesh, showed that those being breast-fed had
calorie and protein intakes (per kg of body weight) 1.5
and 2.5 times greater, respectively, than those not
breast-fed (45).
More information is required on the effects of
feeding mode on diarrhoea severity. Such studies
should control for age, nutritional status, and chronic
illness and should investigate the severity of diar
rhoeas of known etiology.
Mortality
Annex 2 lists 9 studies in 5 countries from which the
relative risks of diarrhoea mortality for infants on one
feeding mode, compared to infants on another
feeding mode, can be computed. The data are less
extensive than those on morbidity (Annex 1) and do
not permit such detailed analysis by age. For partial
breast-feeding compared to exclusive breast-feeding,
7 relative risks are computed, ranging in value from
1 to 10. For no breast-feeding compared to exclu
sive breast-feeding, 13 relative risks are computed,
ranging in value from 3 to 43. For no breast-feeding
compared to partial breast-feeding, 9 relative risks are
computed, ranging in value from 2 to 19. Thus the
pooled results from 9 studies suggest that breast
feeding may protect substantially against death from
diarrhoea.
The age-specific relative risks of diarrhoea mor
tality, from 2 studies in which age-specific analysis
is possible, are presented in Fig. 3. The relative risk
of death from diarrhoea for non-breast-fed infants
is greatly increased in the early months of infancy
compared to the later months. The relative risks of
diarrhoea mortality for infants 0-5 months old are
summarized in Fig. 4 by feeding mode. When infants
receiving no breast milk are contrasted with those on
exclusive breast-feeding the median relative risk of
death from diarrhoea during the first 6 months of life
is 25. When infants on mixed feeding modes (partial
breast-feeding) are contrasted with those on exclusive
breast-feeding the median relative risk of death from
diarrhoea is 8.6. It must be cautioned that these
R. G. FEACHEM & M. A. KOBLINSKY
276
30 -
Fig. 3. Relative risks of diarrhoea mortality for infants
receiving no breast-feeding compared to infants exclu
sively breast-fed (data from Annex 2).
No breast-feeding
vs
Exclusive breast-feeding
Partial breast-feeding
vs
Exclusive breast-feeding
No breast-feeding
vs
Partial breast-feeding
Number of results
-0-5
Age in months
Fig. 4. Median relative risks of diarrhoea mortality by
feeding mode (data from Annex 2, including studies of
0-2, 3-5 and 0-5-months age groups).
results are derived from only two studies (62, 69) and
mainly from the study of Newman (62). Comparison
of Fig. 2 and 4 shows that the relative risks of diar
rhoea mortality by feeding mode are 2-6 times greater
than those of diarrhoea illness. This implies a similar
difference in the case-fatality ratios by feeding mode.
Table 2 shows the ratios of no breast-feeding to
partial breast-feeding case-fatality ratios to be 1.1,
1.8, 3.0, 3.1, 6.7 and 22.
As with the case-fatality ratios (Table 2), the
mortality rates by feeding mode (Annex 2) could be
confounded with undernutrition or chronic illness.
A factor that causes the abandonment of breast
feeding, such as a chronic illness, could also increase
the risk of death from diarrhoea. Four studies listed in
Annex 2 controlled for these, or related factors, or
excluded infants who were disadvantaged from birth
owing to prematurity, low birth-weight, or congenital
defects. In addition, four of the studies in Annex 2
derived their mortality rates from records of over 100
deaths from diarrhoea. With sample sizes of this
magnitude it is unlikely that rare events such as
chronic illness would substantially alter the computed
effect of feeding mode.
Despite these comments, the data from which to
draw conclusions about the relative risks of diarrhoea
mortality by feeding mode are limited in extent and
quality. The studies are old (only one since 1947); all
except one are from what are now wealthy and tem
perate countries (Canada, England, Sweden, and the
USA); they provide poor breakdown of mortality
rates by age; and they do not adequately control for
potentially confounding variables. The age of the
studies is of concern first because their designs are
inadequate as judged by today’s epidemiological
standards, and secondly because the non-breast-fed
infants were not receiving modern infant milk for
mulae. The importance of this last point is uncertain.
Of the four potential protective mechanisms listed
above, only nutritional status is likely to be affected
by the type of breast-milk substitute.
Reliable data on the effect of feeding mode on
diarrhoea mortality rates in developing countries
today are not available. The collection of such data
through correctly designed studies is a priority item
for research programmes in both diarrhoeal diseases
and maternal and child health. Evidence that such
studies will find a significant relative risk of diarrhoea
mortality among bottle-fed infants comes from
studies of overall infant mortality by feeding mode.
For instance, a study in north-eastern Brazil found
that, when numerous confounding variables were
controlled, children who were never breast-fed were
1.7 times more likely to die in infancy than other
children (29).
Etiology-specific diarrhoea and breast-feeding
There is a growing literature on substances in
human colostrum and milk that act against specific
agents of diarrhoea. Most attention has been focused
on antibodies against rotavirus (71, 72, 90), anti
bodies against Escherichia coli and its toxins (1, 28,
277
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
48), and antibodies against Vibrio cholerae and its
toxin (55, 72).
Little is known of the relationships between feeding
mode and the epidemiology of diarrhoeas of known
etiology. High relative risks of cholera in Bahrain,
and of salmonellosis in Arkansas, USA, in infants
receiving no breast milk have been documented
(Annex 1). In a study of 5-day-old babies in London,
England, the prevalences of rotavirus infection
among breast-fed and non-breast-fed infants were
22% and 58% respectively (6). Only 14% of infected
breast-fed infants excreted > 109 virus particles per
gram of faeces, compared to 52% of non-breast-fed
infected infants. In a study of children under 1 year
old, hospitalized with diarrhoea in Mexico City,
Mexico, 5% of those with rotavirus infection were
breast-fed compared to 16% of those with other
diarrhoeas (76). In a study of children under 2 years
old with diarrhoea in Dhaka, Bangladesh, the propor
tion who were breast-fed was 59% in those with
shigellosis compared to 78% in those with other
diarrhoeas (77). A similar association with breast
feeding was not found for the other common enteric
pathogens.
This information is incomplete and partially con
tradictory. It is uncertain whether the protection
against diarrhoea morbidity and mortality associated
with breast-feeding (Fig. 1-4) extends to all diar
rhoeas or is due to high protection against some
agents and low protection against others. Studies on
feeding mode in relation to the incidence and severity
of specific diarrhoeas are needed to clarify the
situation and to guide intervention policy towards
geographical areas in which breast-feeding may be
especially important.
Hypothesis 2. The prevalence of breast-fed infants
can be increased by appropriate promotional acti
vities
The most recent and comprehensive account of
patterns of breast-feeding is provided by a WHO col
laborative study of 22 857 mothers in 9 countries
(86). The reader concerned with the details of breast
feeding trends and practices should study this report.
Simplified data on three contrasting patterns of
breast-feeding (dubbed here patterns A, B and C)
have been abstracted and are set out in Table 3.
Pattern A may be found in relatively urbanized and
wealthy communities in developing countries and in
some developed countries. It is a pattern where non
breast-feeding is prominent and it may be an increas
ingly common pattern in many developing countries,
especially in urban areas. Pattern C is a pattern of pre
dominant breast-feeding and may be found in many
poor and traditional societies in developing countries.
Table 3. Three contrasting patterns for breast-feeding1'
Pattern
of breast
feeding b
A
B
C
Countries and the
socioeconomic strata of the population studied
Urban
poor
All
strata
Upper/
middle
Hungary
Sweden
Chile
Ethiopia
Guatemala
Nigeria
Philippines
Chile
India
Nigeria
Guatemala
Philippines
Zaire
Ethiopia
India
Nigeria
Zaire
Rural
poor
Chile
Philippines
Ethiopia
Guatemala
India
Nigeria
Zaire
Type of
feedingf
Prevalence (%) of breast
feeding by age of infant
0-2 mo.
3-5 mo.
6-11 mo.
Excl. BF
30
10
0
Part BF
45
35
15
No BF
25
55
85
Excl. BF
50
30
5
Part BF
40
45
55
No BF
10
25
40
Excl. BF
75
50
20
Part BF
25
45
70
No BF
0
5
10
" All data drawn from Fig. 3 and Tables 3 and A5 of the WHO breast-feeding study (861. The data have been greatly simplified for
the purposes of this analysis on breast-feeding and diarrhoea; for the details of breast-feeding patterns, please consult the full report
(88).
b Patterns A, B, and C may be expected in 'modern', 'transitional', and 'traditional' communities, respectively. It is assumed that
these communities suffer low, medium, and high incidences of diarrhoea, respectively (see Tables 6 and 8).
c For definitions of feeding modes, see footnote b to Annex 1.
278
R. G. FEACHEM & M. A. KOBLINSKY
Pattern B is intermediate between patterns A and C
and may be found in societies that are transitional, in
terms of both social norms and wealth. This threepart categorization of breast-feeding patterns is a
considerable simplification of the actual global
picture as described by WHO (86). This simplifi
cation is necessary for the compulations on breast
feeding promotion and diarrhoea reduction that
follow below. The reader interested in a specific
community, where the breast-feeding pattern is
known, can insert local data in place of those given in
Table 3 and repeal the computations.
In some countries, most notably certain developed
countries (with breast-feeding pattern A, Table 3),
growing public awareness of the advantages of breast
feeding has caused substantial increases in the preva
lence of breast-fed infants over a short time period
(64). In Oslo, Norway, the prevalence of breast
feeding in infants aged 3 months was 14% in 1972-73
and 31 % in 1974-75. In Copenhagen, Denmark, the
median duration of breast-feeding doubled, from 2 to
4 months, between 1975 and 1977. In the USA the
prevalence of infants who were only breast-fed rose
from an all-time low of 26% in 1973 to 54% in
1980.
Promotion of breast-feeding can reduce the
prevalence of non-breast-fcd infants substantially.
Table 4 summarizes the impact on breast-feeding
of local breast-feeding promotions in Brazil, Czech
oslovakia, England, Guatemala, Scotland, Singa
pore, Sweden, and the USA. Because of the very
varied pre-promotion levels of breast-feeding, the
impacts are expressed as percentage reductions in the
prevalences of infants receiving no breast milk. In the
computations (see below) the most likely reductions
in the prevalences of non-breast-fed infants of
various ages due to breast-feeding promotion are
taken as 40% for the 0-2-months age group, 30% for
the 3-5-months age group, and 10% for the 6-11months age group (Table 4).
Table 4, The effectiveness of breast-feeding promotion
programmes in reducing the prevalence of infants
receiving no breast milk"
Age of
infant
(months,
inclusive)
No. of
results
% reduction in prevalence
of non-breast-fed infantsh
Range
Median
0-2
23
8-100
42
3-5
8
7-43
28
6-11
6
2-43
11
0 Data derived from Winikoff & Baer (85) (summary of 20
studies in 8 countries) and from Hardy et al. (43).
h If the prevalences of non-breast-fed infants of a given age
before and after the promotion are 70% and 50% respectively,
the % reduction is 28.6%.
Hypothesis 3. The promotion of breast-feeding can
reduce diarrhoea morbidity rates, mortality rates,
or severity in infants
Il is possible to calculate the theoretical impacts of
breast-feeding promotion using the data assembled
above on hypotheses 1 and 2. Median relative risks
of both morbidity and mortality by age have been
derived (Fig. 1-4), three contrasting patterns of
breast-feeding have been described (Table 3), and
the impact of breast-feeding promotion on breast
feeding has been reviewed (Table 4). The next step is
to characterize the impact on breast-feeding of breast
feeding promotions having three levels of success:
high impact, medium impact, and low impact. The
consequences to breast-feeding patterns of these three
levels of success are quantified in Table 5. The data on
medium impact are derived from Table 4, while high
and low impacts are assumed to influence twice and
one half, respectively, of the proportion of target
mothers.
From the data assembled in Fig. 1-4 and Tables 3-5
it is possible to compute the impact on age-specific
diarrhoea morbidity and mortality rates of breast
feeding promotions with a given level of success (say,
medium impact) in a community of known breast
feeding pattern (say, pattern A). For morbidity rates,
key assumptions are presented in Table 6 and the
reductions in age-specific diarrhoea morbidity rates
are set out in Table 7. Considering breast-feeding
promotions of medium impact, diarrhoea morbidity
rates in the first 3 months of infancy may be reduced
by 8-20%, and in the second 3 months of life by
9-17%, with the highest percentage reductions being
achieved in communities where breast-feeding is
initially least common (pattern A). Negligible reduc
tions in diarrhoea morbidity rates are achieved among
children over 6 months old. The computed reductions
in total diarrhoea morbidity for the first five years of
life are only 1-4%.
For mortality rates, key assumptions are presented
in Table 8 and the reductions in age-specific diarrhoea
mortality rates are set out in Table 9. Considering
breast-feeding promotions of medium impact, diar
rhoea mortality rates in the first 6 months of infancy
may be reduced by 24-27%, and diarrhoea mortality
rates for the first five years of life by 8-9%. Zero
reductions in diarrhoea mortality rates are computed
for children over 6 months old (Table 9) because of
the conservative assumption of a relative risk of 1.0
for this age group (see footnote d to Table 8). The
impacts on children aged 0-59 months are similar,
whatever the initial level of breast-feeding (patterns
A, B and C) because of the high diarrhoea mortality
rates assumed for 0-5-month old infants in com
munities having breast-feeding pattern C (Table 8).
The computed morbidity and mortality reductions
(Tables 7 and 9) for the total 0-59-months age group
279
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
Table 5. Data on the three levels of impact of breast-feeding promotion programmes"
Percentage changes in breast-feeding prevalence by age of infant and type of feeding
6-11 mo.
*
3-5 mo.
0-2 mo.
Level of
impact
From Part BF
to Excl. BF
From No BF
to Part BF
From No BF
to Excl. BF
From Part BF
to Excl. BF
From No BF
to Part BF
40
80
30
30
60
20
20
40
15
15
30
10
10
20
7.5
7.5
15
5
From No BF
to Part BFf
From No BF
to Excl. BF
High
40
Medium
20
Low
10
“ Explanation : Consider a promotion with medium impact on the 0 - 2 mo. age group. It is assumed that the behaviour of 40% of the
target mothers can be changed (Table 4). Thus 40% of Part BF switch to Excl. BF and 40% of No BF switch to Part BF or Excl. BF
(20% to each mode). For low impact it is assumed that only 20% of target mothers can be influenced, while for high impact it is
assumed that 80% of target mothers can be influenced.
b Since most authorities recommend supplementary feeding of infants over 5 months, it is assumed that the breast-feeding
promotion would encourage Part BF and not Excl. BF in this age group.
e For definitions of feeding modes, see footnote b to Annex 1.
Table 6. Assumptions made in calculating the impact of breast-feeding promotions on diarrhoea morbidity
Age group
inclusive)
Episodes of diarrhoea
per child per year, by breastfeeding pattern (Table 3IC
Relative risk of diarrhoea
morbidity by feeding mode0
Proportion (%) of
0-59 month-old
children falling
stated age group
Part BF vs
Excl. BF
*
No BF vs
Excl. BF
*
A
B
C
0-2
2.0
4.0
1.0
2.0
3.0
3-5
2.0
4.0
1.0
2.0
3.0
6
6-11
1.3
1.6
1.5
30
4.0
11
12-59
1.0
1.0
0.5
1.5
2.0
76
7
° See Annex 1 and Fig. 1 and 2.
b For definitions of feeding modes, see footnote b to Annex 1.
c Estimates derived from Snyder & Merson (74).
depend on the assumptions made on age-specific
morbidity and mortality rates in Tables 6 and 8 (see
footnotes b to Tables 7 and 9). These rates are based
on the assumption that breast-feeding pattern A
will most commonly be found in relatively wealthy
communities having relatively low diarrhoea rates,
whereas pattern C will be typical of very poor com
munities having the highest diarrhoea rates. Com
munities with breast-feeding pattern B are assumed to
have intermediate diarrhoea rates. This generaliz
ation does not reflect the situation in all countries.
There are areas having low breast-feeding prevalence
but high diarrhoea rates (for instance, in urban slums
in some Latin American cities), and there are areas
having high breast-feeding prevalences but low diar
rhoea rates (for instance, in Sweden).
The former case, of low breast-feeding prevalence
and high diarrhoea rates, is of particular interest.
A community was defined having breast-feeding
pattern A (Table 3), but with diarrhoea morbidity and
mortality rates the same as those assumed for com
munities with breast-feeding pattern C (Tables 6'and
8). Such a community might be found in an urban
slum in Latin America. The age-specific percentage
reductions in diarrhoea morbidity and mortality rates
due to breast-feeding promotion in this community
are exactly as calculated in Tables 7 and 9 for a
community with breast-feeding pattern A. This is
because the age-specific morbidity and mortality rate
reductions are not dependant on the assumed
diarrhoea rates; they depend rather on the relative
risks by feeding mode and it has been assumed
throughout these computations that these relative
risks are the same in communities having breast-feed
ing patterns A, B and C. The diarrhoea rate
reductions for the total 0-59-months age group are
R. G. FEACHEM & M. A. KOBLINSKY
280
Table 7. Percentage reductions in diarrhoea morbidity
rates, by age of child, due to breast-feeding promotions
of varying effectiveness
Pre-intervention
pattern
of breast
feeding"
Age of
children
(months,
inclusive)
A
B
C
Reduction (%) in diarrhoea
incidence by effectiveness
of breast-feeding promotion b
High
*"impact
Medium
*"
impact
Low
impact *"
0-2
39
20
10
3-5
34
17
8
6-11
4
2
1
12-59
0
0
0
0-59
8
4
2
0-2
31
15
8
3-5
29
14
8
6-11
2
1
0
12-59
0
0
0
0-59
5
2
1
0-2
16
8
4
3-5
21
9
6
6-11
1
0
0
12-59
0
0
0
0-59
3
1
1
0 See Table 3.
b For reductions in the 0-2, 3-5, 6-11, and 12-59 months
age groups the given percentage reductions are applicable,
whatever the incidence of diarrhoea or the age structure in the
community. The percentage reductions in the 0-59 months age
group are calculated using the assumptions on diarrhoea inci
dence and age structure given in Table 6.
e See Table 5.
dependent on the age-specific diarrhoea rates
assumed. However, similar percentage reductions are
computed for the urban community in Latin America
as for the more typical pattern A community (Tables 7
and 9), because the higher diarrhoea rates apply not
only to the first 6 months of life when changes in
breast-feeding are effective, but also to the next 4.5
years when they are not.
Clearly the absolute, rather than the proportional,
reduction in diarrhoea morbidity and mortality rates
will be higher in communities having higher initial
diarrhoea rates. For instance, a community having
breast-feeding pattern A and diarrhoea rates for that
pattern as shown in Table 6, will have 67 diarrhoea
episodes per 100 children under 5 years old per year.
Following a breast-feeding promotion of high im
pact, there will be 61.5 episodes per year, an 8%
reduction (Table 7) with only 5.5 episodes averted
annually per 100 children under 5 years old. The Latin
American slum community characterized above
(breast-feeding pattern A, but diarrhoea rates as
assumed for communities with pattern C), will have
initially 233 episodes of diarrhoea per 100 children
under 5 years old per year. Following a breast-feeding
promotion of high impact, there will be 216 episodes
per year, only a 7% reduction but with 17 episodes per
year averted. Precisely the same arguments hold for
mortality reductions.
A final note of caution is necessary. The impacts
computed in Tables 7 and 9 depend on median relative
risk data drawn from Annexes 1 and 2 and sum
marized in Fig. 1-4. In the relative risks of morbidity
(Fig. 1 and 2) one may have considerable confidence.
The studies are numerous, some are recent and some
have used sophisticated epidemiological methods. In
the relative risks of mortality one must have much less
Table 8. Assumptions made in calculating the impact of breast-feeding promotions on diarrhoea mortality
Age group
(months,
inclusive)
Diarrhoea deaths per 1000
children per year, by breast
feeding pattern (Table 3)f
Relative risk of diarrhoea
mortality, by feeding mode0
Proportion (%) of
0-59 month-old
children falling
within the
stated age group
Part BF vs
Excl. BF
*
No BF vs
Excl. BF
*
A
B
C
0-5
8.0
25.0
11
24
40
6-11
1.0''
1.0''
9
16
20
11
12-59
1.0
1.0
3
6
12
76
13
* See Annex 2 and Fig. 3 and 4.
b For definitions of feeding modes, see footnote b to Annex 1.
c Estimates derived from Puffer & Serrano (67) and Snyder & Merson (74).
d It is possible that the relative risk in this age group is > 1, but there is inadequate data on which to estimate a value and so a
conservative value of 1 has been adopted.
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
Table 9. Percentage reductions in diarrhoea mortality
rates, by age of child, due to breast-feeding promotions
of varying effectiveness
Pre-inter
vention
pattern
of breast
feeding0
Age of
children
(months,
inclusive)
A
B
C
Reduction (%) in diarrhoea
mortality rate by effectiveness
of breast-feeding promotion b
High
impacte
Medium
impactr
Low
*"impact
0-5
56
26
13
6-11r
0
O
0
12-59
0
0
0
0-59
17
8
4
0-5
54
27
16
6-11'1
0
0
0
12-59
0
0
0
0-59
18
9
5
0-5
44
24
14
6-1 r'
0
0
0
12-59
0
0
0
0-59
14
8
4
“ See Table 3.
b For reductions in the 0-5, 6-11, and 12-59 months age
groups the given percentage reductions are applicable, whatever
the diarrhoea mortality rates or the age structure in the com
munity. The percentage reductions in the 0-59 months age
group are calculated using the assumptions on diarrhoea mor
tality rates and age structure given in Table 8.
e See Table 5.
d See comment in footnote d to Table 8.
confidence for the reasons discussed above. Modern
studies are needed on diarrhoea mortality by feeding
mode to confirm or deny the substantial mortality
reductions predicted in Table 9.
A recent study in Costa Rica (56) has documented a
dramatic impact of breast-feeding promotion on
neonatal diarrhoea morbidity and mortality. Between
1976 and 1980 hospital routines were changed so as to
promote early breast-feeding and close mother-child
contact. Over the same period neonatal diarrhoea
morbidity fell by 91 % from 17.7 to 1.6 cases per 1000
live births, and neonatal diarrhoea mortality fell from
3.9 to 0 deaths per 10 000 live births. These changes
were attributed mainly to the emphasis given to the
ingestion of colostrum by neonates. Another report
of the same study (57) showed that the incidence of
diarrhoea among infants aged 0-5 months was 36%
lower in a population receiving intense breast-feeding
promotion (only 15% of infants aged 5 months
receiving no breast milk) than in a population receiv
ing less intense promotion (41% of infants aged 5
months receiving no breast milk).
281
These morbidity reduction data from Costa Rica
(57) agree closely with the theoretical calculations
described above. The level of breast-feeding pro
motion in this population (where the prevalences of
non-breast-fed infants were 10-19% at 0-2 months,
27-41% at 3-5 months, and 63% at 9 months) stands
mid-way between breast-feeding patterns A and B
in Table 3. It is predicted in Table 5 that a breast
feeding promotion of high impact would reduce these
prevalences to 2-4% at 0-2 months, 10-16% at 3-5
months, and 50% at 9 months. The actual prevalences
of non-breast-fed infants in the population where
there was intense promotion in Costa Rica were
5-11% at 0-2 months, 13-16% at 3-5 months, and
31% at 9 months. The reduction in diarrhoea mor
bidity among infants aged 0-5 months, caused by a
high-impact breast-feeding promotion, is predicted to
be 34-39% in communities having breast-feeding pat
tern A, and 29-31 % in communities having pattern B
(Table 7). The actual reduction in morbidity among
children aged 0-5 months in Costa Rica was reported
to be 36%. This agreement between theoretical
calculations and the Costa Rican experience suggests
that the morbidity and mortality reductions predicted
in Tables 7 and 9 may be achievable in practice,
especially the more modest reductions predicted for a
breast-feeding promotion with only medium impact.
FEASIBILITY AND COSTS
The promotion of breast-feeding, which has been
reviewed elsewhere (39, 51, 85)/ is generally of two
kinds: information and support programmes and
changes in hospital routine. The most cost-effective
designs for these interventions in various societies are
not known. Changes in hospital routine have to be
made only once and they may not involve any increase
in operating costs. However, such interventions will
be effective only in societies where a substantial pro
portion of deliveries take place in hospitals where they
are more likely to affect the initiation of breast
feeding than its duration. It is likely that a combi
nation of information and support programmes,
together with changes in hospital routine, will prove
to be the most cost-effective intervention in many
societies.
Costs of breast-feeding promotion activities have
not been documented but they are probably low in
comparison with most other anti-diarrhoea inter
ventions. Studies of both the financial and the
economic costs of breast-feeding compared to bottle
feeding have shown that breast-feeding is the cheaper
alternative (57, 52).
See footnote c on page 272.
2S2
R, G. FEACHEM & M. A. K0BL1NSKY
CONCLUSIONS
The literature on breast-feeding and diarrhoea is of
varied quality; sometimes the findings are contra
dictory and substantial areas of ignorance remain.
The purpose of this review is to attempt to draw a
consensus from the literature.
Breast-feeding, whether exclusive or partial, ap
pears to offer protection to children up to one year of
age, but not beyond (Fig. 1 and 4). Protection is great
est in the first 3 months of life and falls thereafter
(Fig. I and 3). During the first half year of life, exclu
sive breast-feeding is more protective than partial
breast-feeding and partial breast-feeding is protective
compared to no breast-feeding (Fig. 2 and 4).
The data summarized in Fig. 2 and 4 are suggestive
of the possible mechanisms of protection of breast
feeding. If protection were due solely to the immuno
logical and antimicrobial properties of the breast milk
itself, then the relative risk of no breast -feeding versus
partial breast-feeding might approximate that of no
breast-feeding versus exclusive breast-feeding. In fact
these relative risks are substantially different (Fig. 2
and 4). If protection were due solely to the contamin
ation of foods other than breast milk, then the relative
risk of no breast-feeding versus exclusive breast
feeding might approximate that of partial breast
feeding versus exclusive breast-feeding. This would
also be the case if protection was caused solely by the
dominant colonization of the intestine by Bifido
bacterium (a feature only of exclusively breast-fed
infants). In fact these relative risks are substantially
different (Fig. 2 and 4). Thus the relative risks com
puted suggest that the protection is caused neither by
breast-milk properties alone, nor by the “bifid”
factor alone, nor by food contamination alone, nor
by a combination of the last two mechanisms alone.
Some combination of these three mechanisms, to
gether with the non-specific nutritional benefits of
breast-feeding, may be responsible for the observed
degree of protection. The evidence that protection is
not caused by food contamination alone is further
supported by the protective effect of breast-feeding
for infants in families of high socioeconomic status
in developed countries, such as Canada, England,
Finland, New Zealand and the USA (Annex 1). It is
probable that the mechanisms of protection, and their
relative importance, vary by pathogen and by the age
of the infant.
The literature on breast-feeding promotion shows
that breast-feeding may become substantially more
common following changes in hospital routine com
bined with information and support programmes for
mothers. Theoretical calculations show that a typical
breast-feeding promotion may reduce diarrhoea mor
tality by 24-27% among infants aged Q-5 months
and by 8-9% among children under 5 years of age
(Table 9).
Only one study on the actual impact on diarrhoea
of breast-feeding promotion has been located (56,
57). This study, from Costa Rica, found substantial
reductions in neonatal diarrhoea morbidity and mor
tality and a 36% reduction in diarrhoea morbidity
among infants aged 0-5 months. A detailed com
parison between the Costa Rican data and the theor
etical calculations presented in this paper shows good
agreement and gives confidence that the predicted
morbidity and mortality reductions set out in Tables 7
and 9 can be achieved in practice.
This review has highlighted several areas of ignor
ance that require further research. The highest re
search priority is to determine the level of protection
against diarrhoea mortality afforded by partial or
exclusive breast-feeding among infants in various
socioeconomic settings in developing countries. Well
designed studies of diarrhoea morbidity by feeding
mode in developing countries are also urgently
needed. Studies are required into the relationships
between diarrhoea severity and feeding mode and into
the possible lack of association between the relative
risk of diarrhoea in non-breast-fed infants and the
socioeconomic status of their families. The relation
ships between breast-feeding and chronic diarrhoea,
and the protection against nosocomial diarrhoea that
may be afforded by the continued breast-feeding of
hospitalized infants, are worthy of investigation.
All these studies should be etiology-specific in
order tc clarify the undoubted differences in the levels
of protection provided by breast-feeding against
diarrhoeas of different etiology. The design of these
studies requires careful and detailed planning. Fine
age ranges must be used and several important con
founding variables must be controlled. These require
ments will tend to lead to study designs having many
cells and large overall sample sizes. A prospective
study may often be unduly expensive and complicated
and a case-control approach will be preferable in
these situations.
As regards operational research, more information
is needed on the design, effectiveness, and cost of
breast-feeding promotion in developing countries.
Where possible, effectiveness should be measured not
only by impact on breast-feeding patterns but also by
impact on diarrhoea rates. This latter kind of impact
measurement will typically require major prospective
studies, like that reported from Costa Rica. For these
studies to be worthwhile they must be very carefully
designed and must incorporate a detailed analysis of
the financial and economic costs of the breast-feeding
promotion.
Despite the limitations in the mortality data, and
the need for continued research as discussed above,
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
the evidence that breast-feeding protects young in
fants from diarrhoea is strong. Governmental and
other agencies with responsibility for diarrhoea con
trol should act to promote breast-feeding on the basis
283
of the evidence now available. Research will generate
new understandings, both fundamental and oper
ational, which will improve the effectiveness of these
breast-feeding promotions.
ACKNOWLEDGEMENTS
The initiation of this review was greatly assisted by the preparatory work of M. Pollack during her time as a WHO
Consultant. The authors are grateful for the constructive criticisms on earlier drafts of this paper provided by A. Ashworth,
M. Belsey, D. Blum, M. Carballo, I. de Zoysa, R. C. Hogan, N. J. Hoover, M. H. Merson, M. Moore, P. I. Nieburg and
P. M. Shah. Secretarial, bibliographic and editorial assistance was most ably provided by Maelorwen Jones, Lynne Davies
and Dianne Fishman.
RESUME
INTERVENTIONS POUR LA LUTTE CONTRE LES MALADIES DIARRHEIQUES CHEZ LE JEUNE ENFANT:
ENCOURAGEMENT DE L’ALLAITEMENT MATERNEL
Le present article est le troisieme d’une serie d’etudes sur
ce qu’on peut faire dans les pays en developpement pour
abaisser la morbidite et la mortalite dues a la diarrhee chez
1’enfant de moins de cinq ans. 11 existe unc documentation
ires fournie sur les risques relatifs de morbidite enfantine
selon les differents modes d’alimentation. Cette documen
tation souffre de plusieurs problemes mdthodologiques. On
a examine 35 etudes emanant de 14 pays. Quatre-vingt-trois
pour cent de ces etudes constatent que I’allaitement maternel total est plus protecteur que I’allaitement maternel partiel, 88% des eludes constatent que I’allaitement maternel
total est plus protecteur que 1’absence d’allaitement mater
nel et 76% constatent que I’allaitement maternel partiel est
plus protecteur que 1’absence d’allaitement maternel. Si 1’on
compare les enfants que ne re?oivent pas de lait maternel
avec ceux qui sont nourris au sein totalement ou partiellement, le risque median relatif est de 3 entre 0 et 2 mois, de
2,4 entre 3 et 5 mois et de 1,3 i 1,5 entre 6 et II mois. Audela d’un an d’age, il n’y a pas d’effet protecteur visible de
I’allaitement maternel contre la morbidite diarrheique. Si
1’on compare les enfants qui ne re?oivent pas de lait mater
nel avec ceux qui sont nourris entierement au sein, le risque
median relatif est de 3,5 A 4,9 dans les six premiers mois de la
vie. D’apres la documentation etudiee, rien n’indique que le
risque relatif de morbidite pour les enfants nourris au
biberon soil plus eleve dans les families pauvres que dans les
families plus riches. Par ailleurs, 1’effet protecteur de
I’allaitement maternel ne semble pas subsister apres la
cessation de cet allaitement. Par contre, il y a des signes
d’augmentation considerable de la gravite de la maladie
chez 1’enfant nourri au biberon.
Il existe peu d’ouvrages, et ils sont pour la plupart ant£rieurs a 1950, sur les risques relatifs de mortalite du nourrisson selon le mode d’alimentation. On a examine neuf
etudes emanant de cinq pays, et la plupart montrent que
I’allaitement maternel est une protection substantielle
contre le risque de mortalite. Si 1’on compare les nourrissons
qui ne re?oivent pas de lait maternel avec ceux qui sont
nourris uniquement au sein, le risque median relatif de deces
est de 25 dans les six premiers mois de la vie. Si 1’on compare
des enfants nourris totalement au sein et des enfants nourris
partiellement au sein, le risque tombe a 8,6.
On peut encourager I’allaitement maternel en changeant
les habitudes hospitalieres, ainsi qu’en eduquant et en
aidant les inches. L’examen de 21 etudes Emanant de 8 pays
montre que selon toute probability on peut ainsi abaisser la
prevalence de la maladie chez les sujets ne recevant pas de
lait maternel de 40% entre 0 et 2 mois, de 30% entre 3 et 5
mois et de 10% entre 6 mois et un an. Des calculs theoriques
fondes sur ces chiffres montrent qu’une action d’envergure
moyenne d’encouragement de I’allaitement maternel peut
faire diminuer la morbidite diarrheique dans une proportion
de 8% a 20% et la mortalite dans une proportion de 24% a
27% au cours des six premiers mois de la vie. Pour les
enfants ages de 0 a 59 mois, la morbidity serait reduite dans
une proportion de 1 % & 4% et la mortalite dans une propor
tion de 8% & 9%. Une etude rycente faite au Costa Rica a
demontre une incidence substantielle de 1’encouragement de
I’allaitement maternel sur la morbidite et la mortality du
nouveau-ny, et sur la morbidite du nourrisson de 0 b 5 mois.
Les donnyes costa-riciennes concordent avec les calculs
theoriques prysentys ici.
Plusieurs aspects importants de I’allaitement maternel et
des maladies diarrheiques doivent encore etre yclairys par la
recherche. Toutefois, la nycessite de cette recherche ne doit
pas retarder Taction en vue d’encourager I’allaitement
maternel et d’en surveiller les effets sur les pratiques alimentaires et sur la diarrhee.
284
R. G. FEACHEM & M. A. KOBLINSKY
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36.
Annex 1
Relative risk of diarrhoea morbidity by feeding mode
Relative risk of diarrhoea morbidity0
Socio
economic
status
Age group
(inclusive)
Bahraine
1978
7
0-11 mo.
7.0
Canada
Toronto
1939
7
0-11 mo.
5.80
1972-75
Lower
0-11 mo.
?
?
0-23 mo.
Manitoba
Indian
reservation
Urban
*
Winnipeg
Pan BF
vs
Excl. BF6
No BF
vs
Excl. BF"
No BF
vs
Part BF"
10 32
3.20
Factors controlled
Case-control study. Pairs
matched for age and place of
residence (rural/urban). Waterrelated habits and child care
practices were not risk factors
for cholera.
Reference
37
13
Marital status of mother,
occupation of father, and
family income were not
associated with breast-feeding.
Women who breast-fed for
> 12 mo. were older, had
more children, less education,
and lived in more crowded
houses than those who breast
fed for < 12 mo.
15
Feeding modality controlled
for socioeconomic status,
parental education, and family
size.
5
1976-79
All
0-16 mo.
1.41
38
Colombia
1964-65
Lower
0-5 mo.
6-11 mo.
2.37
2.37
2.91
1.64
1.33
0.69
88
Costa Rica
1979-82
Lower
0-2 mo.
3-5 mo.
6-8 mo.
9-11 mo.
1.37
3.31
6.47
6.92
4.73
2.09
1.29
1.00
59
England
Liverpoool
1936
Lower/
middle
3-26 wk
6.36
12.85
2.02
69
Nationwide
1946-48
Lower
0-3 mo.
4-8 mo.
9-23 mo.
2.57
3.20
1.24
0.79
0.91
12
7
7
2-11 mo.
2.98
2.33
0.78
76
Oxford
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
Date of
study
Country/place
South-east
1968-69
Upper/
middle
0-11 mo.
3.89
Sex, date of birth, birth
weight, ages of parents,
number of persons per house,
number of sibs, and number
of sibs at school, were not
associated with breast-feeding.
68
Nationwide
1970-75
All
0-11 mo.
1.55
Feeding modality controlled
for maternal age, child's sex,
birth weight, birth rank,
maternal smoking, and socio
economic status.
78
Ethiopia
Addis Ababa
1979
All
0-5 mo.
6-11 mo.
Finland
4 towns
1949
7
0-11 mo.
Guatemala
1964
Lower
3-5 mo.
0.85
6-8 mo.
1.14
9-11 mo.
1.32
9.14
0.67
80
1.48
1.99
89
3.04
32
1955-59
Lower
0-2 mo.
3-5 mo.
6-8 mo.
9-11 mo.
1.26
1.39
1.17
1.55
31
New Delhi
rural
?
Lower
3-5 mo.
6-8 mo.
9-11 mo.
1.39
1.02
0.95
27
urban
7
Middle
3-5 mo.
6-8 mo.
1.14
0.97
Rural
7
?
0-11 mo.
New Delhi
7
Lower
0-5 mo.
6-11 mo.
Israel
1971
Lower
0-5 mo.
Jamaica
1967-68
7
0-3 mo.
3.01
5.53
1.20
10.47
*
3.39
Feeding modality controlled
for socioeconomic status,
parental education, occu
pation, and family size.
5
Cases and controls were socio
economically matched and
both groups were hospitalized.
61
Twins and infants with low
birth-weight or birth defects
were excluded.
46
Lower socioeconomic status,
non-working mothers at 6 mo.
post-birth, and no cribs,- were
associated with breast-feeding.
34
i. FEACHEM & M . A. KOBLINSKY
India
Punjab
6.19
0.34
New Zealand
Christchurch
Christchurch
1977-79
Upper/
middle
Upper/
middle
(treated
diarrhoea)
0-3 mo.
2.41
1.60
1.49
(all
diarrhoea)
0-3 mo.
3.92
1.99
1.27
(treated
diarrhoea)
0-3 mo.
4-11 mo.
12-23 mo.
2.06
1.23
0.88
(all
diarrhoea)
0-3 mo.
4-11 mo.
12-23 mo.
2.81
1.21
0.97
22
Relative risks for 0-3 mo.
group remained significant
when controlled for child's
sex, maternal age, race,
education, smoking, family
size, number of parents, and
quality of child care.
23
1.71
0.64
82
1955
All
0-5 mo.
6-11 mo.
USA
Chicago
1924-29
Lower
2 wk-8 mo.
Chicago
1924-29
Lower
0 mo.
1 mo.
2 mo.
3 mo.
4 mo.
5 mo.
6 mo.
7 mo.
8 mo.
Boston
1930-40
All
0-11 mo.
1960
Lower
0-2 mo.
3-5 mo.
6-8 mo.
9-11 mo.
California
1973-75
Upper/
middle
0-2 mo.
5.77
Iowa
1973-78
Upper/
middle
0-5 mo.
4.15
Navajo Indian
reservation
Relative risks remained
significant when controlled
for maternal age, parity,
parental education, race,
number of parents, living
standard, gestation period.
and birth weight.
2.24
3.00
3.71
2.55
0.95
0.23
1.90
2.01
1.83
35
0.42
0.08
0.51
0.79
1.67
2.29
2.63
2.72
4.34
36
1.20
75
4.20 '
2.78'
1.38'
1.98'
25
49
Number of parents,
number of sibs, number of
clinic visits of infants with
no sibs and those with one
or more, parental education,
urban vs rural, were not
significantly associated with
breast-feeding.
63
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
Uganda
Villages near
Kampala
1977
Cooperstown,
NY
1974
Upper/
middle
0-11 mo.
1.97
Arkansas7
1977-78
0-11 mo.
96.0
Syracuse
1978
Upper/
middle
?
New York
City
?
Lower
0-5 mo.
2.72
Feeding modality was
controlled for mother’s age,
parity, ethnicity, and
education.
1979
All
0-11 mo.
2.01
Breast-feeding was associated
with maternal age and
education, home-ownership,
and ethnicity, but not with sex.
maternal career, family size,
water source, medical care
source, or day care.
24
18
2.70
0-3 mo.
7, 8, 9
Footnote g
10
e The relative risk of feeding mode X compared to feeding mode Y is computed by dividing the incidence of diarrhoea for children on feeding mode X by that for children on feeding
mode Y. When incidence data were not reported, prevalence was used or the relative risk was computed from data on the distribution of feeding modes among infants with diarrhoea
compared to healthy infants.
b Categories of feeding mode are defined as follows: Excl. BF = children receiving only breast milk throughout the stated age range; Part BF = children receiving breast milk and
other milk and/or food throughout the stated age range and children receiving only breast milk or breast milk plus other milk/food for part of the stated age range; No BF = children
receiving no breast milk throughout the stated age range.
c This study relates to cholera diarrhoea only.
d This study relates to rotavirus diarrhoea only.
' Children described as No BF included some who were Part BF and some who were No BF, but these two groups could not be separated.
7 This study relates to Salmonella diarrhoea only.
g SOLIMANO, G. ET AL. Morbidity patterns in breast-fed and non-breast-fed infants in a low socioeconomic urban U.S. population Poster session. 12th International Congress of
Nutrition, San Diego, CA, 1981.
Annex 2
Relative risk of diarrhoea mortality by feeding mode0
Relative risk of diarrhoea mortality6
Country/place
Date of
study
Socioeconomic
status
Age group
(inclusive)
Part BF
vs
Excl. BFC
No BF
vs
Excl. BFf
No BF
vs
Part BFC
Factors controlled
Reference
.. G. FEACHEM & M . A. KOBL1NSKY
Albuquerque,
New Mexico
Relative risks (of all illnesses)
remained significant when
parental education, maternal
age, family size, birth weight,
sex, Apgar score, and birth
month were controlled. Higher
relative risks (of all illnesses)
were associated with male
infant, lower maternal age,
larger family size, and lower
birth-weight.
Canada
Toronto
1939
?
0-11 mo.
Egypt
Menoufia
1979-80
Lower
0-11 mo.
3.33d
England
Derby'
1900-03
Lower
0-11 mo.
2.53
5.83
Liverpool
1884-86
1901-04
?
7
0-2 mo.
Finsbury'
0-2 mo.
6-8 mo.
9.82
25.24
10.99
2.57
62
62
Brighton
1903-05
7
0-2 mo.
3-5 mo.
7.33
29.15
43.24
3.98
62
13
6.48
79
2.31
Children born prematurely, or
with defects or malformations,
were excluded. Better housing
associated with bottle-feeding.
Croydon
1904
?
0-5 mo.
Liverpool
1936-42
Lower/
middle
3-26 wk
3/0z
6/0z
3.50
Premature and ‘weakly’
children were excluded.
Sweden
Stockholm
1943-47
All
1-11 mo.
2-11 mo.
1.08
3.25
6.79
18.75
6.27
5.77
Breast-feeding associated
with belter child care. Relative
risks (of total mortality) not
influenced by age of mother
or birth-weight.
1911
7
All
2 wk-11 mo.
8 cities'
All
1-8 mo.
9-11 mo.
0-11 mo.
Chicago
1924-29
Lower
2 wk-8 mo.
USA
Boston'
17.22
13.02
Relative risks (of total mor
tality) remained substantial
when race, nationality,
prematurity, maternal death,
and plural birth were
controlled. Relative risks (of
total mortality) was higher in
lower income groups.
11.3
3.5
7.71
18.82
62
69
54
11
87
35, 36
° All the studies summarized here contain severe methodological flaws and the relative risks derived should be regarded as indicative only.
b The relative risk of feeding mode X compared to feeding mode Y is computed by dividing the diarrhoea mortality rate of children on feeding mode X by that for children on feeding
mode Y. Where mortality rates were not reported, the relative risk was computed from data on the distribution of feeding modes among infants who died from diarrhoea compared to
healthy infants.
e For definitions of feeding modes see footnote b to Annex 1.
d To compute this relative risk it was necessary to assume that the distribution of feeding modes among infants who died from causes other than diarrhoea was
identical to that of infants in the general population. Provided that breast-feeding is not a risk factor for non-diarrhoea deaths, this assumption can only lead to an underestimation
of the relative risk.
' Rates based on over 100 diarrhoea deaths.
z There were 0 deaths in the Excl. BF group.
PROMOTION OF BREAST-FEEDING FOR CONTROL OF DIARRHOEAL DISEASES
15
44
Bulletin of the World Health Organization, 63 (I): 165 - 184 (1985)
© World Health Organization 1985
Interventions for the control of diarrhoeal diseases
among young children: prevention of low birth weight
*
Ann Ashworth1 & R. G. Feachem*
12
The effect of low birth weight (LB IV) on diarrhoea morbidity and mortality is analysed
and interventions to increase birth weights are reviewed. Birth weight is a major
determinant of infant mortality and, in developed countries at least, its effect on neonatal
mortality is independent of socioeconomic status. We have located no satisfactory data on
LBW as a determinant of diarrhoea mortality or morbidity. The strong association between
LBW and mortality, however, makes it likely that there is an association between LB W and
diarrhoea mortality in developing countries where diarrhoea is a major cause of infant
death. Poor maternal nutrition, certain infections, pre-eclampsia, arduous work after mid
pregnancy, short birth intervals, and teenage pregnancy are likely to be causally associated
with LBW in developing countries. Tobacco and alcohol consumption are additional risk
factors.
Of the interventions examined, maternal food supplementation has been the most
studied. If targeted to mothers at nutritional risk, and if thefood is consumed in addition to
the usual diet, the prevalence of LBW can be expected to be reduced. However, food
supplementation can be expensive and the results from carefully supervised feeding trials
may be better than those that can be achieved tn national programmes. The effect ofsupple
mentation with iron, zinc or folate requires further study. If it were possible to intervene in
maternal nutrition, health and life-style in a developing country in a way that reduced the
prevalence of LBWfrom around 30% to around 15 %, a fall in the infant mortality rate of
around 26 % would be expected. Thefall in infant diarrhoea mortality rate might be similar.
The scarce data on relative risk of morbidity by birth weight do not allow any comparable
computations for morbidity reductions to be made.
This review confirms that whatever its association with diarrhoea, LBW is an
important determinant of infant mortality. For the more general goal of reducing infant
mortality it is necessary to know more about the nature, etiology, and prevention of LBW
in developing countries.
In this review, the effect of low birth weight on
diarrhoea morbidity and mortality is analysed and
interventions to increase birth weight are reviewed.
While recognizing that the etiology of low birth
weight is multifactorial, emphasis is given to those
maternal factors that are believed to be of greatest
importance in developing countries and that may be
amenable to change in the short term. These include
inadequate dietary intake, infections, arduous
workloads, teenage pregnancy, short birth intervals,
and excessive tobacco or alcohol consumption. This
paper examines whether interventions that reduce the
prevalence of low birth weight might be effective in
reducing morbidity or mortality from diarrhoeal
diseases among young children. This review is the
fifth in a series of reviews of potential anti-diarrhoea
interventions being published in the Bulletin of the
World Health Organization (33-37).
• Requests for reprints should be sent to the Director, Diarrhoeal
Diseases Control Programme, World Health Organization, 1211
Geneva 27, Switzerland.
1 Lecturer, Department of Human Nutrition, London School of
Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT,
England.
2 Reader in Tropical Public Health Engineering and Head of
Department of Tropical Hygiene, London School of Hygiene and
Tropical Medicine, London, England.
4513
EFFECTIVENESS
If the prevention of low birth weight, by improving
the nutritional status, health or life-style of pregnant
women, is to be an effective diarrhoea control
-165—
Table 1. Percentage distribution of live births by birth weight in four countries
Percentage of live births
USA
< 1501
0.8
0.8
1.0
1.0
1.2
0.9
1.6
2.2
1.7
3.9
3.0 )
1501-2000
0.9
1.1
1.3
1.5
1.4
1.3
1.8
2.5
2.8
3.4
3.0 J•
Oregon USA (5
USA
(Portland) regions) (white)
New
York
USA
(non
white)
Brazil
(Recife)
Colorado
(Denver)
New
York
(black)
India
New
Delhi
2.8
North
Arcot
Palghar
Guatemala
(Santa
Maria
Cauqud)
1.1
5.2
1.2
5.5
9.4
6.5
2001-2500
3.5
4.2
4.5
5.1
5.1
5.7
6.6
8.3
10.0
8.0
9.8
20.2
25.3
23.2
34.0
2501-3000
15.6
17.8
17.2
19.1
18.5
22.7
23.9
25.3
33.0
24.9
28.4
45.8
41.2
37.4
48.1
3001-3500
38.1
39.2
38.1
39.5
38.0
40.6
39.6
37.1
35.0
36.9
36.6
25.8
21.5
22.4
10.0
3501-4000
30.4
27.7
28.2
26.0
26.8
22.6
21.0
18.9
14.8
18.4
15.8
4.8
4.8
>4000
10.6
9.1
9.6
7.8
9.0
6.2
5.5
5.8
2.6
4.5
3.5
0.6
0.7
2.4 |
>
0.0 )
0.2
% LBW
5.2
6.1
6.8
7.6
7.8
8.0
10.0
12.9
14.5
15.2
15.7
23.0
31.9
37.8
41.7
Reference
10
110
20
91
20
21
21
20
82
55
21
91
93
103
70
.. ASHWORTH & R.G. FEACHEM
California
New
York
(white)
Birth weight
(0)
167
PREVENTION OF LOW BIRTH WEIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
intervention, it must be true that:
Hypothesis 1. A considerable proportion of
diarrhoea morbidity or mortality in young children
in developing countries is due to low birth weight.
either
a considerable proportion of
diarrhoea morbidity or mortality in
young children in developing
countries is due to low birth weight
hypothesis
1
and
improving the nutritional status,
health or life-style of pregnant
women can reduce the prevalence
of low birth weight
hypothesis
2
or
improving the nutritional status,
health or life-style of pregnant
women can reduce diarrhoea
morbidity or mortality rates in
young children
hypothesis
3
The literature on hypothesis 2 is extensive, whereas
hypotheses 1 and 3 have been little studied. The
effectiveness of low-birth-weight prevention as an
intervention to reduce diarrhoea morbidity or
mortality would be suggested by a demonstration
either of the correctness of hypotheses 1 and 2 or of
the correctness of hypothesis 3. The evidence for and
against these hypotheses is examined below.
Prevalence and distribution of low birth weight.
The term low birth weight (LBW) is used to describe
infants who weigh less than 2500 g at birth. From
sample surveys and country reports, WHO has esti
mated that over 20 million LBW infants are born each
year. At the global level this represents 16% of all
births, but the proportion is not uniform and national
rates range from 4% in Scandinavia to around 50% in
parts of India and Bangladesh (124, 125). Table 1
compares birth weight distributions in 15 populations
with different LBW prevalence rates, ranging from
5% to 42%.
Infants with a low birth weight may be divided into
two broad subgroups: (a) those who are born
preterm, that is of less than 37 weeks’ gestation; (b)
those who are growth-retarded in ulero and are born
small for gestational age (SGA). Investigators are not
consistent in their definition of SGA, but it may be
defined as a birth weight of 2SD or more below the
mean birth weight for gestational age. Although most
preterm infants are appropriate for gestational age
(AGA), some LBW infants are both preterm and
SGA. In the developed countries the majority of
LBW infants are the result of a preterm delivery. In
contrast, in developing countries it would seem from
the limited information available that the majority of
LBW infants are small for gestational age. For
example, in 18 reports from the Indian subcontinent,
south-east Asia and Latin America, between 65% and
96% of LBW infants were small for gestational age
(124). In Africa, there are data for only 5 cities and
these show a more diverse pattern with between 34%
Table 2. Association of low birth weight and infant mortality in developing countries
Region or
country
Place
Prevalence
of LBW (%)
Percentage of deaths weighing
< 2500 g at birth
Reference
Neonatal
Latin America and
Caribbean
a
Postneonatal
Infant
—
47
—
42
11
-
Hyderabad
21
84
—
—
North Arcot
32
56
42
48
Santa Maria Cauqu6
42
87
58
70
Nigeria
Igbo-Ora
India
India
Guatemala
— denotes data not available.
89
4
80
93
69
Table 3. Relative risks of neonatal mortality by birth weight compared to birth weight of 2501-3000 g
Relative risk of neonatal mortality
USA
(1960)
47.5
55.0
32.8
52 6
94.2
46.2
41 4
16 T
20.6
19.6
9.4
18.2
30.8
13.9
23.3
4.4
27.3
5.2
4.4
4.4
2.1
4.2
4.5
3.3
4.0
1.4
3.4
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.4
0.5
0.4
04
0.3
0.7
0.5
0.8
0.3
0.2
0.2 )
0.4
0.3
0.3
0.3
0.5 >
0.4 I
0.6
0.4
0.4 1
0.7
1.1 )
0.4
0.2
0.3
0.8
0.9
1 7 /
0 5
1001-1500
52.7
99.9°
41.1
80.5
1501-2000
13.5
17.6
16.6
19.8
2001-2500
3.0
3.8
4.5
2501-3000
1.0
1.0
3001-3500
0.3
3501-4000
4001-4500
0.3
0.3 )
>4500
0.4 j
0.4
0.3 J
0.6
1
14
5.6
8.2
8.5
12.7
13.8
16.9
17.5
18.4
21.2
26.7
28.2
34.8
39.0
% LBW
unstated
6.1
5.2
unstated
5.2
6.8
15.2
7.8
23.2
12.9
8.7
31.9
41.7
No. of
births
290 000
234 000
700 000
44 700
40 000
3.6
million
14 400
4.26
million
4 590
657 100
18 200
4 220
416
Reference
123
110
30
90
10
20
55
20
41
20
90
93
69
Includes all births < 1500 g.
Deaths per 1000 live births, except for ref. 123 (per 1000 single vaginal births), ref. 30 (per 1000 total births), and ref. 10 (per 1000 single, white, live births).
.. ASHWORTH & R.G. FEACHEM
Colorado
(Denver)
(1974-80)
California
(1977)
Neonatal
mortality
rate6
Brazil
Guatemala
USA (non (Ribeirao
India
(Santa Maria
India
(N. Arcot)
Cauqu6)
(Delhi)
white)
Preto)
(1969-72)
(1960)
(1968-70) (1969-75) (1964-72)
USA
(white)
(1960)
USA (5
Oregon
regions
Norway
California (Portland)
(1974-75) (1967-78) (1969-70) (1959-66)
Birth weight
(g)
169
PREVENTION OF LOW BIRTH WEIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 4. Relative risks of post-neonatal mortality by birth weight compared to birth weight of 2501-3000 g
Relative risk of post-neonatal mortality
Guatemala
(Santa Maria
Cauqu6)
(1964-72)
Norway
(1967-68)
USA
(5 regions)
(1974-75)
USA
(white)
(1960)
USA
(1960)
USA
(non-white)
(1960)
India
(Delhi)
(1969-72)
India
(N. Arcot)
(1969-75)
1001-1500
2.6
12.2'
6.3
6.1
4.8
9.3
4.5'
1501-2000
3.0
3.7
3.5
3.4
3.0
5.3
2.3
7.0
2001-2500
1.8
1.9
1.9
1.9
1.8
2.2
1.1
0.8
Birth weight
(g)
2501-3000
1.0
1.0
1.0
1.0
1.0
3001-3500
0.6
0.6
0.6
0.6
3501-4000
>
(
4001-4500
0.5
0.4
0.7
0.7
)
(
>4500
0.5
J
Post-neonatal
mortality
rate6
3.2
4.3
% LBW
5.2
6.1
No. of births
700 000
234 000
Reference
30
110
0.5
0.5
1.0
1.0
1.0
0.6
0.5
0.4
0.5
0.5
0.5
0.4
0.7
0.5
0.5
0.7
5.4
6.9
15.1
25.3
51.6
60.0
6.8
7.8
12.9
23.2
31.9
41.7
657 100
4 590
4 220
416
20
41
93
69
*
3.6
million 4.26million
20
20
0.7
a Includes all births < 1500 g
6 Deaths per 1000 survivors, except for ref. 30 (per '1000 total births) and ref. 110 (per 1000 live births).
and 73% of LBW infants being small for gestational
age. More research is required to determine the rela
tive proponion of these two subgroups of LBW
infants in developing countries.
Association of low birth weight with mortality. In
developed countries, LBW infants comprise the
majority of infant deaths. For example, in a recent
report from the USA, although LBW infants repre
sented only 6% of live births they comprised 55% of
infant deaths (110)- Data from developing countries
are limited since death registration is frequently
incomplete and birth weights are rarely recorded.
Indications are, however, that LBW infants similarly
comprise a large proportion of infant deaths as shown
in Table 2.
Birth weight has a marked association with neo
natal mortality rates in both developed and
developing countries. The relative risks of neonatal
death among infants of different birth weights,
compared with infants weighing 2501-3000 g, are
shown in Table 3. The most favourable birth weights
were in the range of 3500-4500 g. Although there
were 7-fold differences in overall neonatal mortality
rates among the 13 studies, the relative risks in each
500-g birth-weight interval were similar, except for
Denver and North Arcot, where infants with birth
weights of < 2500 g had lower relative risks than in
the other places studied.
The association between birth weight and mortality
extends into the post-neonatal period and birth
weights of 3500-4500 g were similarly associated with
the lowest risk. Table 4 shows that among LBW
infants the relative risk of post-neonatal death in
North Arcot was somewhat lower than that observed
in developed countries, whereas in Delhi the relative
risk among LBW infants was higher than in
developed countries. In Santa Maria Cauque, the
relative risks were somewhat anomalous, perhaps
because of the small number of subjects in this
study.
It is possible that there is also an association
between birth weight and mortality in the 1-4-year
age group. In the Gambia, child mortality is signifi
cantly higher in children born in the wet season (when
the incidence of LBW is high) than in children born in
the dry season (55), and there is some indication from
Guatemala that SGA infants may have an increased
I-4-year mortality risk (6S, 71). In view of the limited
data available, however, it has been conservatively
assumed in the calculations which follow that low
birth weight confers no increased risk of death
beyond the first year of life.
In populations where the whole Gaussian distri
bution of birth weights is shifted to the left, leading to
a lower mean birth weight, it is possible that the defi
nition of LBW based on a cut-off point of 2500 g is
170
A. ASHWORTH & R.G. FEACHEM
Table 5. Neonatal and post-neonatal mortality rates by birth weight and gestational age
Mortality rate
Birth weight
(g)
Gestational
age
Santa Maria
CauquS
Delhi
North
Arcot
New York
City
Neonatal mortality rate
(deaths per 1000 live births)
< 2500
Preterm
323
87
73
93
Term {SGA)
28
27
41
44
Preterm
10
30
Term
4
21
> 2500
8
__b
_b
Post-neonatal mortality rate
(deaths per 1000 survivors)
Preterm
286
46
66
16
Term (SGA)
58
35
66
13
< 2500
> 2500
Term
Reference
_b
18
50
42
13
42
_b
69
41
93
117
Preterm
“ No infants in this category.
6 No data available.
too rigid (95). In such populations the relative risk of
neonatal or post-neonatal death among births of
< 2500 g may be lower than in populations with
higher mean birth weights. There is evidence for this
from the USA in populations living at high altitude
(e.g., Colorado, Tables 1 and 3) and from the United
Kingdom in populations differing in racial origin
(27). At present, however, there are insufficient birth
weight-specific mortality data to determine whether,
or to what extent, the relative risk of neonatal and
post-neonatal death among LBW infants in
developing countries differs from that in developed
countries.
Many of the factors affecting mortality are inter
related. Few studies have attempted to determine the
effect of one factor while controlling for the inter
related factors. In Baltimore, during 1960-64, a
cohort of 108 852 single live births of known birth
weight were followed for one year after birth. When
the effects of birth weight, race, socioeconomic
status, maternal age, birth order, and prenatal care
were separated, birth weight was the most important
factor in neonatal mortality, and factors such as race,
socioeconomic status and maternal age were
important only because they were related to birth
weight {102). Likewise birth weight was the most
important factor in post-neonatal mortality. How
ever, in this period the other factors (except for race)
were also important. In New York City during
1976-78, socioeconomic circumstances were also
found to have little effect on the probability of neo
natal death once birth weight was controlled (83). No
comparable analyses from developing countries have
been located.
Mortality among preterm versus SGA infants.
Although the data are limited, it would appear that in
both developed and developing countries preterm
infants have a considerably higher risk of neonatal
death than term SGA infants of similar birth weight
(9, 110 and Table 5). The reason for this is the greater
difficulty experienced by preterm infants in adapting
to the extrauterine environment owing to immaturity
of many of the body’s systems (117).
In the post-neonatal period, preterm infants may
also experience higher mortality rates than term SGA
infants (Table 5), but the difference is less marked and
less consistent than in the neonatal period.
The data on childhood mortality are very limited.
However, in New York, term SGA infants appeared
to be at slightly greater risk, their 12-23-month
mortality rate being 2.7 per 1000 compared with 2.3
for preterm infants (117). In Santa Maria Cauque,
term SGA infants had a higher mortality rate during
the second, third, and fourth years of life than
preterm infants (68).
Studies in the USA and United Kingdom have
shown that term SGA infants grow more slowly than
PREVENTION OF LOW BIRTH WEIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
preterm infants (25, 32, 81, 117), the difference in
their mean weight being 0.7 kg at 12 months (25,117)
and 5 kg at 10 years of age (32). Slower growth in
SGA infants compared with preterm infants has also
been reported from New Delhi (100). In conclusion, it
would seem that preterm infants are at greater risk of
death, especially neonatal death, in the first year of
life than term SGA infants, but that preterm infants
who survive may grow better than SGA infants and
have lower mortality rates after 1 year of age.
Association of low birth weight with infant
morbidity. At present only limited data are available,
although several long-term prospective studies of
preterm infants are in progress in developed
countries. In Oakland, California, LBW infants did
not experience significantly more episodes of acute
diseases in the first two years of life than infants of
higher birth weight (116).
Association of low birth weight with diarrhoea
morbidity or mortality. The association, if any,
between LBW and diarrhoea morbidity or mortality
is poorly documented. In the Inter-American Investi
gation of Mortality in Childhood (89), LBW was
examined as an associated cause of diarrhoea
mortality, but only in relation to the neonatal period.
Of 1269 neonatal diarrhoea deaths recorded in 8
countries, LBW was a contributory cause in 49%,
with a range from 28% in Bolivia to 80% in Jamaica.
In a prospective study from 1964 to 1972 in the Guate
malan village of Santa Maria Cauque, LBW infants
show’ed greater rates of diarrhoeal disease and greater
prevalence rates of infection with Shigella,
Entamoeba histolytica and Giardia in the first six
months of life than infants of higher birth weight (68,
69). These findings are not reported in a way that
allows diarrhoea incidence by birth weight to be cal
culated.
Since epidemiological data are limited, an alter
native approach is to examine physiological function.
It is known that the immune response of LBW infants
is severely compromised (19, 38) and is more
adversely impaired than that of postnatally
malnourished infants (38). In addition to defects in
cellular immunity, LBW infants have been found to
have a significant reduction in maternal-fetal transfer
of IgG (19, 100) and impaired synthesis of IgA, IgM,
and the Ca component of complement (100). In a
follow-up study of 30 LBW infants in New Delhi,
impaired immunity was associated with recurrent
attacks of diarrhoea in the first 6 months of life. The
impairment was most marked in SGA infants (700). It
may be tentatively concluded from these limited data
that LBW infants, especially if they are small for
gestational age, may be predisposed to increased
diarrhoea morbidity rates. Furthermore, since mal
171
nourished infants are more likely than well nourished
infants to die from diarrhoea (33), it is reasonable to
expect that LBW infants, especially if they are SGA,
will experience increased diarrhoea mortality rates.
Further research is warranted to confirm these
tentative conclusions.
Evidence suggests that breast-feeding protects
young infants from diarrhoea (36). In some coun
tries, especially where babies are born in hospital, a
greater proportion of LBW infants may be fed artifi
cially compared with infants of heavier birth weight.
Feeding mode may therefore also contribute to an
increased risk of diarrhoea among LBW infants.
Conclusions on hypothesis 1. Birth weight is a
major determinant of infant mortality and, in
developed countries at least, the effect of birth weight
on neonatal mortality is independent of socio
economic status. Where information is available, and
this shows considerable local and regional variations,
the majority of LBW infants in developed countries
are preterm, whereas in developing countries the
majority are small for gestational age. Preterm AGA
infants suffer higher infant mortality rates than SGA
infants, and this difference is especially marked in the
neonatal period. On the other hand, preterm AGA
infants may grow better post-neonatally than SGA
infants.
We have located no satisfactory data on LBW as a
determinant of diarrhoea mortality or morbidity. The
strong association between LBW and mortality
(Tables 3 and 4) makes it likely that there is an
association between LBW and diarrhoea mortality in
developing countries where diarrhoea is a major cause
of infant death. Immunity is severely impaired in
LBW infants, especially SGA infants. Data from
India and Guatemala indicate that SGA infants may
be predisposed to increased diarrhoea morbidity.
Hypothesis 2. Improving the nutritional status,
health or life-style of pregnant women can reduce
the prevalence of low birth weight.
Etiology of low birth weight. Low birth weight is
caused by factors that shorten the length of gestation
and/or impair fetal growth. Factors affecting the
latter are more pertinent to this review since SGA
infants probably comprise the majority of low-weight
births in developing countries. Some factors, for
example altitude, are not amenable to change. Other
factors including socioeconomic status, multiple
pregnancy, maternal height, and pregravid weight
can only be influenced by long-term interventions. In
this review, only factors that are more readily
amenable to change and might respond to short-term
172
A. ASHWORTH & R.G. FEACHEM
interventions in developing countries are examined.
The factors selected arc poor nutritional status,
physically demanding work, maternal health,
maternal age, birth interval, and tobacco and alcohol
consumption. Only the first of these is discussed in
any detail.
Nutritional status. There is ample evidence that an
inadequate dietary intake during pregnancy adversely
affects birth weight. In the conditions of severe food
shortage that occurred in parts of Europe during the
Second World War, average birth weights fell by
185 g to 600 g (3, 28, 105).
In developing countries with seasonal food short
ages, considerable fluctuations in birth weight occur.
In the village of Keneba in the Gambia, for example,
the mean monthly weight gains of pregnant women
were 0.4 kg in the wet season (July-October) and
1.4 kg in the dry season, and the corresponding
prevalences of LBW were 35% and 13% (86). In July
the average birth weight was 480 g less than in May
(94). However, the rainy season is not simply a time
of food shortage, it is also a period of increased
prevalence of maternal infection, including malaria,
and a period of increased agricultural activity. The
seasonal decrease in birth weight is thus likely to be
the result of several adverse factors which together
affect both maternal nutritional status and health.
A major focus of maternal and child health pro
grammes has been the provision of additional food to
pregnant women. Unfortunately, few such interven
tions have been evaluated. One exception is the
nationwide special supplemental food programme for
low-income American women, infants and children
(the WIC programme), which encourages clinic atten
dance and provides individual nutrition counselling in
addition to the WIC foods (milk or cheese, eggs, ironfortified cereal, and fruit juices) through the Food
and Nutrition Service of the US Department of Agri
culture. This programme has been associated with an
increased weight gain in pregnancy, an increase in
birth weight (+ 136 g, if supplemented for more than
6 months), and a decrease in the prevalence of LBW
from 10% to 6% (11, 29, 54). Of the services pro
vided, only food supplementation had a significant
effect on birth weight (54).
Several small-scale feeding trials have been
evaluated and the results of nine such studies are
summarized in Table 6. In four of the studies the
observed improvement in birth weight was statisti
cally significant although not always large (Mexico,
+ 213 g; Keneba, + 120 g; Guatemala, + 117 g; and
Montreal, +40 g). In the three developing countries
where the prevalence of LBW was > 15% (the
Gambia, Guatemala, and Mexico), supplementation
led to a statistically significant reduction in the pro
portion of low-weight births." In China (Province of
Taiwan), the existing prevalence of LBW was low and
prc-supplementation birth weights were relatively
good, especially if one takes into account maternal
short stature (65). The participants in this study may
therefore not have been at much nutritional risk. It
may be concluded that, where maternal nutritional
status is poor, food supplementation that effectively
increases net intakes can improve birth weights and
reduce the prevalence of LBW.
In Harlem (New York City) a decrease in mean
birth weight was observed with a high-protein, highmineral supplement (99). Since similar findings have
been reported from San Francisco with the same sup
plement (2) and from Motherwell (Scotland) when
pregnant women were advised to cat a predominantly
protein diet (44), caution has been expressed about
possible deleterious effects of excessively high protein
intakes in pregnancy. The apparent decrease in mean
birth weight with a protein-free supplement in
Birmingham (England) was probably due to imper
fect matching of the groups (119).
The provision of a food supplement, however, does
not necessarily lead to its consumption. In some
societies pregnant women may purposely restrict their
intake in anticipation of an easier delivery, and thus
traditional dietary customs may limit any effort to
improve maternal nutrition, whether by dietary
advice or by direct food supplementation. For
example, in Project Poshak in India, food collection
rates were poor in pregnancy and 90% of the ration
which was collected was subsequently dispersed
among other family members (43). In Colombia
where food supplements were provided for each
family member, pregnant women consumed only
57% of their allocation. Moreover, the supplement
replaced some of their regular diet so that despite very
generous rations there was a relatively small incre
ment in net intake (50). In contrast, in the Gambia a
high uptake of the supplement was achieved which
was attributed to its palatability and to the fact that it
was offered in the early morning when the women
would not normally have eaten at home (88). Its highenergy density assisted in achieving a substantial net
increase in energy intake.
The magnitude of the response in birth weight to
supplementation may appear disappointingly low.
However, where the data have been disaggregated,
the response among inadequately nourished mothers
is substantial. For example, supplementation
increased the mean birth weight during the wet season
in the Gambia by 225 g and decreased the prevalence
of LBW from 28% to 5% (88). In Colombia,
0 Similar results have also been reported from India, where
supplementation in the third trimester was associated with a
significant increase in birth weight (+170 g) and a 48°7o reduction in
the prevalence of LBW (129).
Habitual
daily intake
Country
Daily allocation
of supplement
Place
kcal
protein
(g>
Canada
Montreal
2250 (9.41)°
68
Colombia
Bogota
1610 (6.74)
Gambia
Keneba
1470 (6.15)
35
_/
Guatemala
4 villages
1500 (6.28)
40
Mexico
Rural areas
1950 (8.16)
50
China
(Province
of Taiwan) Sui-Lin
United
Kingdom
USA
kcal
protein
(g)
Net increase
in energy
intake
(kcal/day)
Duration of
supple
mentation
(weeks)
Increase in
mean birth
weight (g)
Dose response
g/10 000 kcal
or 41.84 MJ'
Reference
_/
self-selected
40“
16
_/
97
860 (3.60)a
38
155 (0.65)“
13
51
21
41
1000 (4.18)
37
430 (1.80)
24
120“
68c
17
149 (0.62)
self-selected
117“
41d
29
275 (1.15)
34
213“
80c
28
50, 76
86-88
46, 58, 60,
61
22, 23
> 40
16
48
individualized
self-selected
300 (1.26)
20
800 (3.35)
40
Aberdeen
2060 (8.62)
70
290 (1.21)
15
189 (0.79)
12
37
Birmingham
—
—
425 (1.78)
0
—
10
-120
425 (1.78)
11
—
10
2060 (8.62)
80
320 (1.34)
6
207 (0.87)
> 10
470 (1.97)
40
261 (1.09)
> 10
Harlem
Reduction in
LBW births
(%)
12, 65
17
]
-
—
330
—
—
(
41
28
—
1
-32
-
-
1
° Figures in parentheses are equivalent units in megajoules (MJ), which is the approved SI unit to replace the thermochemical kilocalorie (kcal).
b Statistically significant increase in mean birth weight (P< 0.05).
e Statistically significant decrease in % of LBW births (P< 0.01).
d Statistically significant decrease in % of LBW births (P< 0.05).
f Grams of birth weight per 10 000 additional kcal (or 41.84 MJ) consumed.
1 — denotes data not available.
119
MENTION OF LOW BIRTH W EIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 6. Effect of food supplementation on mean birth weight and prevalence of LBW
174
A. ASHWORTH & R.G. FEACHEM
supplementation increased the mean birth weight by
181 g among mothers of low weight-for-height (50).
When the Guatemalan data were disaggregated by
socioeconomic score, supplementation reduced the
prevalence of LBW only among the more dis
advantaged mothers. The reduction was from 29% to
13% (59). These examples emphasize the importance
of targeting food supplements to those most at risk.
Unfortunately, relatively little attention has been
directed towards identifying meaningful and practical
criteria for selecting pregnant women who would
benefit from dietary supplementation. Anthro
pometric indices are likely to be the most appropriate
criteria (46, 121). Dynamic criteria such as weight
gain are preferable, but the necessity for at least two
measurements limits their feasibility.
Energy, rather than protein, appears to be the main
factor limiting fetal growth, and the total additional
calories consumed during pregnancy seem more
important than the trimester in which supplement
ation is initiated (62). Where data permit, dose
response values have been calculated in terms of the
mean increase in birth weight for every additional
10 000 kilocalories (41.84 MJ) consumed during
pregnancy (Table 6). The average values vary between
17 gand44 gper41.84 MJ (10 000 kcal). Where data
are disaggregated, the response increases with
decreasing nutritional status of the mother.
Space does not permit a full discussion of the
possible relationships between other specific nutri
tional deficiencies and birth weight here. Anaemia in
pregnancy is common in developing countries (5) and
severe anaemia (haemoglobin of <3.7 mmol/1 or
60 g/1) is associated with LBW (104). Although there
may be a relationship between haematological status
and birth weight (40, 104, 122, 128), studies in dev
eloped countries (49) and in India (109) suggest that
the administration of iron during pregnancy has no
detectable effect on birth weight or length of
gestation. These studies, however, have not examined
the effect of iron supplementation on birth weight in
severe anaemia, as opposed to mild anaemia. The
relationship between maternal folate status and birth
weight is not clear (96, 122, 128), but folate supple
mentation may enhance birth weight (8, 52) and
further research is warranted. Poor maternal zinc
status is associated with SGA births (72,84). Prenatal
supplemental iron or folate may adversely affect
maternal zinc status (47, 74, 108).
Physically demanding work. A seasonal increase in
the energy expenditure of pregnant women may have
a greater impact on birth weight than a seasonal
decrease in energy intake. For example, in Keneba in
the Gambia, the decrease in birth weight preceded the
decrease in energy intake and mirrored the increase in
physical work (94), and in the village of Ikwiriri in the
United Republic of Tanzania no seasonal decrease in
birth weight was observed in 1979 when flood rains'
delayed field work (7). In a review of the pattern of
work during pregnancy in 112 traditional societies, in
45% of them the women continued full duties until
the onset of labour (53).
In the US Collaborative Perinatal Project, continu
ation of employment during the third trimester was
associated with a reduction in mean birth weight of
between 150 g and 400 g. The effect was greatest for
women whose work involved standing, and those with
a low pregravid weight, hypertension, or a low weight
gain (78). In a Bombay cotton mill during 1925-28,
the mean birth weight was 139 g lower among women
mill-workers than among the non-working wives of
mill-workers, all of whom lived in similar grossly
overcrowded conditions. During 1928-29, when there
was a general strike for 6 months and the women
workers had an enforced rest, the mean birth weight
increased by 151 g and the prevalence of LBW
(< 5 pounds or 2268 g) decreased from 23% to 13%
(6). In Dakar, birth weights were found to be
relatively low in women involved in strenuous
physical work but whose nutritional status was
considered adequate (13). It is known that exercise
and an upright posture adversely affect placental
blood flow and it is for this reason that statutory
maternity leave was first introduced in the United
Kingdom. If exercise is undertaken in the heat, blood
has to be diverted to the skin as well as to the muscles,
thus reducing placental perfusion still further. Thus
certain types of work after mid-pregnancy may
impair fetal growth by reducing placental blood flow
and/or by affecting energy balance.
In many developing countries it is likely that a
reduction in the work load of pregnant women would
reduce the prevalence of LBW. Clearly this would
involve technological innovations and a radical
change in social attitudes and in the work patterns of
both men and women (31). Changes in social
attitudes and work patterns are unlikely to be
achieved in the short term.
Maternal health. Untreated maternal infections,
hypotension, and hypertension may affect fetal
growth. In endemic regions malaria is associated with
LBW. In a study in southern Nigeria, 24% of par
turient women had malarial infection of the placenta
and the mean birth weight of their infants was 145 g
lighter than the infants of non-infected women (14).
Parasitaemia rates are highest among primigravidae
(120). In the Gambia, the difference in mean birth
weight between the infants of infected and non
infected women was approximately 150 g for
firstborn infants and 60 g for all other births (67). In
the Solomon Islands, the mean birth weight rose sub
stantially within months of starting anti-A nopheles
175
PREVENTION OF LOW BIRTH WEIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
spraying (66). Between 1969 and 1971 the mean birth
weight increased by 252 g for babies of primigravidae
and by 153 g for all other babies. The overall
prevalence of LBW fell from 21% to 12%. Infections
of the urinary tract are associated with preterm
delivery (77) and with SGA births (48). In rural
Guatemala, the incidence of urinary tract infection
was 27 per 100 pregnancies (115). A number of
studies have reported a reduction in the prevalence of
LBW by antibiotic treatment of pregnant bacteriuric
women (7). Amniotic fluid infections are common
especially in undernourished gravidae, and infection
within the amniotic cavity may initiate preterm labour
(75). Poor maternal nutrition appears to interfere
with the normal antibiotic activity of the amniotic
fluid. In Ethiopia, antimicrobial activity was absent
in 75% of randomly selected urban women at term,
possibly as a result of zinc deficiency (113), and 31%
of women had localized chorioamnionitis at delivery
(79).
Maternal hypotension and hypertension are associ
ated with reduced uteroplacental perfusion. In the
British Perinatal Mortality Survey, severe pre
eclampsia
(diastolic
pressure
of
14.7 kPa
(110 mmHg) or more, or of 12 kPa (90 mmHg) or
more with proteinuria) was associated with a 3.3
relative risk of a LBW delivery and with a mean birth
weight reduction of 225 g (75). In Ethiopia, severe
growth retardation was found in fetuses whose deaths
were ascribed to pre-eclampsia (112).
Antenatal care of good quality is likely to improve
maternal health and thereby reduce the prevalence of
LBW. Such an effect has been documented in India
(80, 103), the United Republic of Tanzania (7), and
the USA (45). Unfortunately the existing coverage of
antenatal services is very low in most developing
countries and of the few women who use the services,
most do so only in the last trimester.
Maternal age. Teenage mothers have a higher
frequency of low-weight births for any given parity
(90). In 1976 in the USA, teenage mothers had a
relative risk of LBW of approximately 1.5 compared
with mothers aged 20-24 years (114). In New Delhi
the relative risk was 1.4 (97). A reduction in the pro
portion of teenage pregnancies should reduce the
prevalence of LBW, but will be difficult to achieve in
the short term in some societies.
Birth interval. Studies in the United Kingdom (18),
the USA (Table 7), and Guatemala (69) have shown
that a short birth interval, especially of < 12 months,
is associated with an increased risk of LBW. In
developing countries, short birth intervals are becom
ing more common especially in urbanized areas where
reduced breast-feeding is associated with a shortened
duration of postpartum amenorrhoea (118).
Table 7. Percentage of low-weight births among Black
and White populations, by interval since last birth, in 43
States of the USA, 1976°
Birth interval
(months)
Prevalence of LBW (%)
Black
White
<12
26.9
14.8
12-23
12.1
5.0
24-35
9.9
3.9
36-47
9.7
3.8
>48
9.8
4.7
° All data from ref. 114.
Tobacco smoking and chewing. It is well estab
lished that maternal smoking reduces birth weight
(42) and that there is a linear dose-effect relationship
in which the more cigarettes are smoked, the greater is
the reduction (16, 39). The putative mechanisms
responsible are discussed elsewhere (26,51,57,63,64,
73, 127). Smoking more than 15 cigarettes/day
doubles the incidence of LBW. It has been shown that
the adverse effect of smoking is independent of social
class, maternal age, and parity (16,24,42). In a recent
review, average reductions in birth weight ranging
from 120 g to 430 g are reported (57). Tobacco
chewing also reduces birth weight (56), although this
has been little studied. In a prospective, randomized
experiment (101), a specific antismoking campaign
directed at pregnant smokers was associated with a
significant increase in mean birth weight ( + 92 g).
There was also a 24% reduction in the prevalence of
LBW, from 8.9% to 6.8%, although this was not
statistically significant.
Alcohol consumption. Animal studies suggest that
alcohol is embryotoxic and teratogenic. The ‘fetal
alcohol syndrome’ is found only among infants of
mothers who regularly consume over 80 g alcohol/
day. Characteristically these infants are growth
retarded at birth and show a consistent pattern of
congenital anomalies (107). Whether more moderate
alcohol consumption, before or during pregnancy,
adversely affects birth weight is less clear. Failure to
allow for confounding variables and difficulties in
obtaining accurate drinking histories may have con
tributed to the apparently conflicting results. A recent
prospective investigation of 900 pregnancies in
London, which was well controlled for confounding
variables, has found that women consuming more
than 100 g alcohol/week (1-2 drinks/day), around
the time of conception, were more than twice as likely
as light drinkers to have a LBW infant (126). There
was no apparent benefit, in terms of birth weight,
176
A. ASHWORTH & R.G. FEACHEM
from reducing such drinking once pregnancy was con
firmed. The effects of heavy binge drinking are cur
rently being analysed. Moderate drinking (50-100 g
alcohol/week) was not associated with a significantly
increased risk of LBW.
Conclusions on hypothesis 2. Poor maternal nutri
tion, certain infections, pre-eclampsia, arduous work
after mid-pregnancy, short birth intervals, and teen
age pregnancy are likely to be causally associated with
LBW in developing countries. Tobacco and alcohol
consumption are additional risk factors. It follows,
therefore, that interventions that reduce the preval
ence of these ‘causes' or their relative risks will reduce
the prevalence of LBW. Of the interventions
examined, maternal food supplementation has been
the most studied. If targeted to mothers at nutritional
risk, and if the food is consumed in addition to the
usual diet, the prevalence of LBW can be expected to
be reduced. However, food supplementation can be
expensive and the results from carefully supervised
feeding trials may be better than those that can be
achieved in national programmes. The effect of sup
plementation with iron, zinc, or folate requires
further study.
Hypothesis 3. Improving the nutritional status,
health or life-style of pregnant women can reduce
diarrhoea morbidity or mortality rates in young
children.
The only true test of this hypothesis would come
from a study in which pregnant women received food
supplementation, improved health care, or some
other relevant intervention, and where the impact of
this on LBW and on the diarrhoea rates in their
children was monitored. A randomized controlled
trial would be ideal, but might encounter ethical and
logistical difficulties. No study of this type has been
located, although in the Gambian prenatal supple
mentation study the preliminary findings
*
show
that there has been a sustained improvement in the
nutritional status of the wet season cohort. The most
likely explanation is that their increased birth weight
resulted in fewer, or shorter, episodes of diarrhoea. A
few studies have been reported in which food supple
mentation for pregnant women, combined with other
interventions, was introduced and the impact of the
combined intervention on diarrhoea rates was
recorded. These results cannot be used to test
hypothesis 3 because the other interventions, such as
food supplementation for infants, are ones that may
well have independent effects upon diarrhoea rates.
Hypothesis 3 must be examined, therefore, by theor
etical calculations of the reductions in diarrhoea
morbidity and mortality rates that might be achieved
by levels of birth-weight enhancement that may result
from improved maternal nutritional status, health or
life-style.
Three hypothetical populations are defined. First,
a relatively wealthy population having a prevalence
rate of LBW of < 10%; we call this population 1.
Second, an intermediate population, such as a poor
community in a developed country or a more wealthy
urban community in a developing country, having a
prevalence rate of LBW of 10-20%; we call this popu
lation 2. Third, a relatively poor community having a
- PRENTICE, A. M. ET AL. Effect of prenatal supplementation
on birth weight and subsequent growth of infants. Paper presented at
the Fourth Asian Congress of Nutrition, Bangkok, 1-4 November
1983.
Table 8. Standardized birth-weight distributions for populations at three different socioeconomic levels
Percentage of live births
Birth weight
(g)
< 1501
1.0 X
1501-2000
1.5 >
5.0 '
2001-2500
Population 2
(intermediate)
% LBW= 10-20
Population 1
(relatively wealthy)
% LBW =<10
Population 3
(relatively poor)
% LBW= > 20
1.5 x
7.5
3.0 >
10.0
1.5 x
14.5
5.0 >
25.0 ’
2501-3000
20.0
28.0
45.0
3001-3500
40.0
36.0
20.0
3501-4000
25.0
17.0
3.0
>4000
7.5
4.5
0.5
3200
3000
2700
Estimated mean
birth weight (g)
31.5
PREVENTION OF LOW BIRTH WEIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 9. Standardized relative risks of neonatal mortality
and post-neonatal mortality by birth weight compared to
birth weight of 2501-3000 g
Relative risk
Birth weight (g)
Neonatal
mortality"3
Post-neonatal
*
mortality
50.0
6.1
177
term this will clearly not be true and as LBW preval
ence rates decline, so also will birth-weight-specific
mortality rates. It is the correct assumption to make
here, however, in order to separate out the impact of
interventions to increase birth weight from the impact
of other curative and preventive interventions.
These calculations do not take full account of the
fact that the amenability of LBW to change, and the
choice of interventions that will cause that change,
34
18.0
1501-2000
depend on three characteristics of the low-weight
1.8
4.0
2001-2500
births under consideration. First, amenability to
1.0
1.0
2501-3000
change and choice of intervention will depend on the
0.6
0.5
3001-3500
degree of LBW. Births of < 1500 g are unlikely to be
reduced by the improvements in maternal nutritional
0.4
0.5
3501-4000
status, health and life-style discussed here. To
0.5
0.6
> 4000
account for this, the prevalence rates of < 1500 g
° Median values from Table 3.
births have been set at 1.0% in population 1, and
b Median values from Table 4.
1.5% in populations 2 and 3 (Table 8), despite the fact
that the rates are actually > 2% among non-whites in
the USA (Table 1). Second, amenability to change
and choice of intervention will depend on the ratio of
prevalence rate of LBW of > 20%; we call this popu
preterm to SGA births. SGA births are likely to be
lation 3. Using the data on birth-weight distributions
more responsive to the interventions discussed here
in Table 1, each of these three populations is assumed
than are preterm births. Third, and closely related to
to have a birth-weight distribution as set out in Table
the last point, as the overall LBW prevalence falls, the
8.
ratio of preterm to SGA births will rise and so the
The reductions in infant mortality rates in popu
LBW pattern will become less amenable to change
lations 2 and 3 that may result from interventions that
increase birth weight can now be calculated on the through improvements in maternal nutritional status,
health and life-style. Thus, it is likely to be much
basis of the following assumptions.
easier to shift the birth-weight distribution of
(1) The effect of birth weight on risk of death does population 3 to population 2, than to shift that of
not extend beyond the first year of life. This may not population 2 to population 1 (Table 8).
be true but the assumption is necessary owing to lack
No data on the risk of diarrhoeal death by birth
of data. It is a conservative assumption.
weight have been located. It is therefore assumed that
(2) A LBW prevention programme in population 3 the relative risks of diarrhoeal death by birth weight
will shift the birth-weight distribution to that of popu are the same as those for all death (Tables 3, 4 and 9).
lation 2 (Table 8).
This assumption is unlikely to be correct for infants of
(3) A LBW prevention programme in population 2 very low birth weight (say, < 1500 g). However, such
will shift the birth-weight distribution to that of babies are assumed to make up a small and relatively
population 1 (Table 8). This is much less likely than unchanging proportion of all births in the 3 popula
assumption 2, as discussed below.
tions being considered (Table 8). For higher birth
(4) The relative risks of neonatal and post-neonatal weights, and especially for post-neonatal mortality,
mortality by birth weight are as set out in Table 9, the assumption that all deaths and diarrhoeal deaths
derived from the median values in Tables 3 and 4. have the same risk pattern by birth weight is not
This may bias the relative risk towards that prevailing unreasonable and is supported by data from the
in developed countries where LBW infants are pre Dutch famine study where infant diarrhoeal deaths
dominantly preterm. Using the median value may and overall infant mortality increased in a similar
overestimate the impact of a LBW prevention pro manner in the SGA cohort born during the famine
gramme in North Arcot for example, where the UH).
relative risks appear to be less than the median. Until
The effects of shifting the birth-weight distribution
more data are available, this assumption is unavoid of population 3 to population 2, and that of popula
able.
tion 2 to population 1, on the neonatal, post-neo
(5) A LBW prevention programme changes the dis natal, infant, and 0-4-year age group diarrhoea death
tribution of birth weight (see assumptions 2 and 3) but rates are shown in Table 10. A population 3 to popu
the neonatal and post-neonatal death rates for a speci lation 2 shift is what might be anticipated by a LBW
fied birth weight remain constant. In the medium prevention programme in a poor community in a
< 1501
178
A. ASHWORTH & R.G. FEACHEM
Table 10. The impact on diarrhoea mortality rates of shifting the distribution of birth weights11
% reduction in diarrhoea
birth-weight
distribution
shiftb
Population 3 to
population 2
Population 2 to
population 1
Neonatal
mortality
Post-neonatal
mortality
Infant
mortality^
% of 0-4 years
diarrhoea deaths
that occur in
infants
% reduction in
diarrhoea mortality
among 0-59-monthold children^
30
25
26
40
10
32
17
19
60
16
80
21
40
8
60
11
80
15
0 All calculations assume that the relative risks of diarrhoea death by birth weight are the same as the relative risks of all death by
birth weight (see text) and are as set out in Table 9.
b See Table 8 for the birth-weight distributions of populations 1, 2 and 3.
c Calculated by assuming that 14% of Infant diarrhoea deaths occur in the neonatal period (median figure obtained in 8 studies).
d Calculated by assuming that either 40%, 60% or 80% of diarrhoea deaths in children under 5 years old occur in children under
1 year, and that birth weight has no effect on the risk of diarrhoea death beyond 1 year of age (see text).
developing country. It presumes a reduction in LBW
from 31.5% to 14.5% (a 54% reduction, see Table 8),
which has been achieved in the Gambia and Mexico
(Table 6). It further presumes an increase in mean
birth weight of 300 g, something that appears far
harder to achieve on the evidence presented in Table
6. A population 2 to population 1 shift is what might
be anticipated by a LBW prevention programme in a
Third World city or in a relatively wealthy, develop
ing country. It presumes a reduction in LBW from
14.5% to 7.5% (a 48% reduction, see Table 8), which
has been achieved in China (Province of Taiwan)
(Table 6). It further presumes an increase in mean
birth weight of 200 g, something that appears harder
to achieve on the evidence of Table 6.
Expected reductions in diarrhoea mortality rates
are 30-32% in the neonatal period, 17-25% in the
post-neonatal period, and 19-26% for the entire first
year of life (Table 10). Expected reductions in
diarrhoea mortality rate in the 0-4-year age group are
8-21%, assuming that LBW confers no excess risk of
diarrhoea death after 12 months of age (Table 10).
This last expected reduction is sensitive to the
proportion of 0-4-year diarrhoea deaths that occur in
the first year of life. Widely differing proportions are
reported; for instance, 90% in Recife, Brazil (91),
81% in Latin America (89), 68% in Ludhiana, India
(91), 55% in North Arcot, India (92), and around
40% in a number of studies in Asia and Latin America
where active surveillance was employed (106). Three
proportions (40%, 60% and 80%) are adopted for
comparison in Table 10.
There is no good evidence to suppose that either
a population 3 to population 2, or a population 2
to population 1, birth-weight-distribution shift is
achievable on a national scale by interventions in
maternal nutrition, health and life-style. As noted
above, the second of these shifts is especially unlikely
in the short term. The impacts computed in Table 10
are those expected if the birth-weight changes under
discussion were achieved. Lesser birth-weight
increases would result in lesser reductions in
mortality.
Conclusion on hypothesis 3. If it were possible to
intervene in maternal nutrition, health and life-style
in a developing country in a way that reduced the
prevalence of LBW from around 30% to around 15%
(Table 8), a fall in infant mortality rate of around
26% would be expected (Table 10). The fall in infant
diarrhoea mortality rate might be similar. The scarce
data on the relative risk of morbidity by birth weight
do not allow any comparable computations for
morbidity reductions to be made.
FEASIBILITY AND COST
In the consideration of hypothesis 2 above, a range
of interventions were shown to be likely to decrease
the prevalence of LBW. These interventions would
seek to increase energy intake, decrease arduous
work, improve antenatal health care, and reduce
tobacco and alcohol consumption in pregnant
women. Interventions would also seek to discourage
teenage pregnancies and increase the birth intervals.
We have reviewed five small-scale feeding trials in
developing countries (Table 6). We have no know
PREVENTION OF LOW BIRTH WEIGHT FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
ledge of any regional or nationwide programmes for
LBW prevention in developing countries using any of
the interventions mentioned above that have been
evaluated. We can therefore say little about the feasi
bility and cost of such programmes.
Energy supplementation for pregnant mothers at
nutritional risk is perhaps the most likely of the inter
ventions listed above to achieve reductions in LBW
prevalence in the short term. However, such an inter
vention suffers from the very considerable cost,
logistical and other disadvantages of all supple
mentary feeding programmes (33). Changes in work
patterns and attitudes towards work during
pregnancy may be extremely resistant to change in the
short term. Antenatal care is gradually improving in
most developing countries, and it is unlikely that a
LBW prevention programme could significantly
accelerate this process. Vigorous educational pro
grammes may be able to reduce tobacco and alcohol
intake during pregnancy, but we know of no docu
mented examples of such campaigns in developing
countries. Discouraging teenage pregnancy, and pro
moting longer birth intervals, are part of existing
birth control programmes in several developing coun
tries. They should have a beneficial effect upon birth
weights but this is secondary to the primary goal of
reducing the birth rate.
CONCLUSIONS
A substantial reduction in the prevalence of low
birth weight is theoretically possible and would lead
179
to a substantial reduction in infant mortality rate
(Table 10). The effect on diarrhoeal mortality or
morbidity rates is unknown, however. In this paper it
has been assumed that the relative risk of diarrhoeal
death by birth weight is the same as that for all death
(Table 9). Data are so scarce on the risk of morbidity,
diarrhoeal or other, by birth weight that no
computations have been possible.
Prospective studies are required that record from
birth the diarrhoea morbidity rates, and if circum
stances permit, the diarrhoea mortality rates, of
groups of infants having known birth weights. These
infants should be followed for at least 12 months, and
preferably 24 months to determine if LBW confers an
excess risk of diarrhoea in the second year of life. The
relative risk values obtained may be used to compute
the reductions in diarrhoea morbidity and mortality
that would follow from a given improvement in birth
weight distribution.
At the same time, greater attention should be paid
to the problem of LBW in developing countries. This
review has confirmed that, whatever its association
with diarrhoea, LBW is an important determinant of
infant mortality. For the more general goal of
reducing infant mortality it is necessary to know more
about the nature (preterm vs small for gestational
age), etiology, and prevention of LBW in developing
countries. In particular, it is necessary to know
whether interventions to reduce LBW are feasible at a
national or subnational scale in developing countries
and whether such interventions are cost-effective in
comparison with other strategies for reducing infant
mortality rates.
ACKNOWLEDGEMENTS
The authors are grateful for the constructive criticisms of earlier drafts of this paper provided by D. Blum, M. Campbell
Brown, I. de Zoysa, R. Hogan, B. McCarthy, L. Mata, M. Merson, A. Pradilla, A. Prentice, P. Shah, and D. Silimperi.
Editorial, bibliographical and secretarial assistance was most ably provided by Lynne Davies, Dianne Fishman, Maelorwen
Jones, Caprice Mahalla and Suzanne O’Driscoll.
RESUME
INTERVENTIONS CONTRE LES MALADIES DIARRHPlQUES CHEZ LE JEUNE ENFANT: PREVENTION D’UN FAIBLE
POIDS DE NAISSAANCE
Le present article constitue la cinquidme mise au point
d’une s£rie sur les interventions possibles en vue de reduire la
morbidity et la mortality associies aux maladies
diarrheiques chez les enfants de moins de cinq ans dans les
pays en developpement. On itudie ici 1’influence d’un faible
poids de naissance (FPN) sur la morbidity et la mortality par
diarrhies ainsi que les interventions visant A augmenter ce
poids. Tout en reconnaissant que 1’itiologie du FPN est
multifactorielle, 1’accent est mis sur les facteurs matemels
dont on pense qu’ils ont lq plus d’importance dans les pays
180
A. ASHWORTH & R.G. FEACHEM
en developpement et qu’ils sont susceptibles d’Svoluer dans
un proche avenir, moyennant des interventions convenables.
Sur 1’ensemble des naissances, on compte 16% de FPN
(< 2500 g). D’apres les observations, la majorite des cas de
FPN seraient des prematures dans les pays d6velopp6s, et
des enfants petits par rapport A leur age gestationnel (PAG)
dans les pays en developpement. Le poids de naissance
conditionne largement la mortalite infantile et, au moins
dans les pays developpes, son influence sur la mortality
neonatale ne depend pas de la situation socio-dconomique.
Chez les prematures de poids normal pour leur age
gestationnel (NAG), on observe un taux de mortalite
infantile plus elev£ que chez les nourrissons PAG mis &
terme, la difference 6tant particulierement marquee & la
periode neonatale. Aucune donn^e convaincante n’a pu etre
trouvee quant au role etiologique du FPN dans la morbidity
ou la mortalite d’origine diarrheique. L’association 6troite
entre FPN et mortalite fait qu’il existe probablement un lien
entre FPN et mortalite d’origine diarrheique dans les pays
en developpement ou les diarrhdes sont I’une des grandes
causes de mortalite infantile. L’immunite est gravement
amoindrie chez les nourrissons de faible poids de naissance,
specialement les nourrissons PAG.
Une nutrition mediocre chez la mere, certaines infections,
la nephropathie gravidique, un travail penible au-dete du
milieu de la grossesse, des naissances rapprochees et le jeune
age de la future mere, encore adolescente — tous ces facteurs
ont certainement un lien de cause & effet avec le FPN dans
les pays en developpement. L’usage du tabac et la consommation d’alcool sont des facteurs de risque supplementaires.
Il s’ensuit que les interventions qui rendent ces “causes”
moins frequentes ou qui abaissent le risque relatif
correspondant, sont de nature A r£duire la prevalence du
FPN. Parmi les interventions examinees, radministration ci
la mere de supplements nutritionnels a et6 la plus 6tudiee.
Cette intervention est en principe efficace si elle vise les
femmes en cause du fait de leur nutrition et si les aliments
distribu^s viennent completer leur ration habituelle.
Cependant, la distribution de supplements nutritionnels
peut etre couteuse, et des essais soigneusement supervises
pourraient donner de meilleures resultats que ceux qu’on
obtient dans les programmes nationaux. L’effet de
supplements de fer, de zinc ou de folate necessite des etudes
compiementaires.
Si 1’on pouvait agir sur la nutrition, 1’etat de sante et le
mode de vie des meres dans un pays en developpement de
fa?on & ramener la prevalence du FPN d’environ 30% &
15%, on devrait obtenir une baisse du taux de mortalite
infantile de 1’ordre de 26%. Le taux de mortalite infantile
par diarrhee devrait enregistrer une chute similaire. Les
rates donnees dont on dispose sur le risque relatif de
morbidite associe & un faible poids de naissance ne
permettent pas de faire des calculs analogues quant i la
reduction A attendre pour le taux de morbidite.
Il est indispensable de realiser des etudes prospeclives ou
seront enregistres des la naissance le taux de morbidite par
diarrhee (et, si les circonstances le permettent, le taux de
mortalite correspondant) dans des groupes de nourrissons
ayant un faible poids de naissance, de valeur connue. En
meme temps, il faudra se preoccuper davantage du
probleme du FPN dans les pays en developpement. La
presente etude a confirme que le FPN constitue, quel que
soit son lien avec la diarrhee, un determinant important de la
mortalite infantile. S’agissant de i’objectif, plus general,
d’un recul de la mortalite infantile, il faudrait en savoir plus
sur la nature (prematures ou enfants petits pour leur age
gestationnel), 1’etiologie et la prevention du FPN dans les
pays en developpement. En particulier, il convient de savoir
si les interventions visant ci limiter les cas de FPN sont
praticables dans ces pays, A l’6chelle nationale ou infra
nationale, et si elles ont un rapport coOt/efficacite favorable
par comparaison & d’autres strategies envisageab’.es pour
faire reculer la mortalite infantile.
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119. Viegas, O. A. C. et al. Dietary protein-energy 126.
Wright, J. T. et al. Alcohol consumption,
supplementation of pregnant Asian mothers at
pregnancy, and low birthweight. Lancet, 1: 663-665
Sorrento, Birmingham. II. Selective during third
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(1983)
trimester only. British medical journal, 285: 592-595
127. Wynn, M. & Wynn, A. The prevention of handicap of
(1982).
early pregnancy origin. London, Foundation for
Education and Research in Child Bearing, 1982.
120. Watkinson, M.& Rushton, D. 1. Plasmodial pigmen
128. Yusufji, D. et al. Iron, folate and vitamin Bu
tation of placenta and outcome of pregnancy in West
African mothers. British medicaljournal, 287:251-254
nutrition in pregnancy: a study of 1000 women from
(19S3).
southern India. Bulletin of the World Health Organiz
121. Wharton, B. A. et al. Selection, compliance and
ation, 48: 15-22(1973).
logistics —lessons from the Sorrento supplementation
129. Bhatnagar, S. etal. Effect of food supplementation
study. In: Campbell, D. M. & Gillmer, M. D. G., ed.,
in the last trimester of pregnancy and early post-natal
Nutrition in pregnancy. London, Royal College of
period on maternal weight and infant growth. Indian
Obstetricians and Gynaecologists, 1983, pp. 101—111.
journal of medical research, 77: 366-372 (1983).
122.
Whiteside, M. G. et al. Iron, folic acid and vitamin
Bn levels in normal pregnancy, and their influence on
birthweight and the duration of pregnancy. Medical
journal of Australia, 1: 338-342 (1968).
117.
CH 3.5~
Bullerinofthe World Health Organization,62(3):467-476(1984)
© World Health Organization 1984
Interventions for the control of diarrhoeal diseases
among young children: promotion of personal and
domestic hygiene
*
R. G. Feachem*1
The effects of improving personal and domestic hygiene on diarrhoea morbidity are
reviewed using data from studies in hospitals, day-care centres, and communities. There is
evidence that low educational attainment and certain religious customs predispose to diar
rhoea, presumably because of behavioural factors. The specific hygiene-related behaviour
that has been most studied is hand- washing. Hospital studies suggest that enteric infections
can spread via contaminated hands and that hands can be decontaminated by washing with
soap and water. Three studiesfrom Bangladesh, the USA, and Guatemala on the impact of
hygiene education programmes on diarrhoea are reviewed in detail. Reductions in
diarrhoea incidence rates of between 14% and 48% were documented in these studies. Little
is known on the impact of hygiene education programmes on diarrhoeas ofspecific etiology
or of their impact on diarrhoea mortality. Information is lacking on the optimal design of
such programmes, on their costs, and on their dependence on pre-existing levels ofsanitary
facilities. The available evidence suggests that hygiene education programmes may be a
cost-effective intervention for diarrhoea morbidity reduction. Research is necessary to
fill the current gaps in understanding and to clarify the operational aspects of these pro
grammes.
Most of the pathogenic organisms that cause diar
rhoea, and all the pathogens that are known to be
major causes of diarrhoea in many countries, are
transmitted primarily or exclusively by the faecaloral route. For some enteric pathogens, man is the
principal reservoir and thus most transmission orig
inates from human faeces; examples are enterotoxi
genic Escherichia coli, Shigella spp., Vibrio cholerae,
Giardia lamblia and Entamoeba histolytica. For
other enteric pathogens, animals are important reser
voirs and transmission originates from both human
and animal faeces; examples are Campylobacter
Jejuni, Salmonella spp. and Yersinia enterocolitica.
For viral agents of diarrhoea the role of animal reser
voirs in human disease remains uncertain.
Faecal-oral transmission may be water-borne,
food-borne, or direct. Water-borne transmission may
occur when water contaminated by faeces is drunk.
Food-borne transmission may occur when food con
taminated by faeces is eaten. Direct transmission is
used here to describe an array of other faecal-oral
• Requests for reprints should be sent to the Director, Diarrhoeal
Diseases Control Programme, World Health Organization, 1211
Geneva 27, Switzerland.
1 Reader in Tropica! Public Health Engineering and Head of
Department of Tropica! Hygiene. London School of Hygiene and
Tropical Medicine, Keppel Street, London WC1E 7HT, England.
4420
routes such as via fingers, or objects such as eating
utensils, or bed linen, or dirt which may be ingested by
young children.
The interruption of water-borne and food-borne
transmission requires specific measures which will be
reviewed separately. Interrupting direct transmission
depends primarily on improved hygiene and on
improved facilities, such as better water supplies and
latrines that facilitate improved hygiene. Such
improved hygienic behaviour may also lessen the
chances of contamination of food by food handlers,
and may therefore reduce food-borne transmission.
Ideally governments will promote educational
measures to improve hygiene, as well as water and
sanitation projects to improve the physical facilities,
in integrated programmes. Such integrated pro
grammes are advocated as part of the International
Drinking Water Supply and Sanitation Decade. In
practice, however, there are substantial operational
differences between hygiene education programmes
and water supply and sanitation projects: the two are
usually implemented by different ministries and
agencies, they require different types of personnel'
and, in particular, they have very different costs. It is
useful therefore to review the effectiveness of hygiene
education alone as an intervention for the reduction
—467 —
46S
R. G. FEACHEM
of diarrhoea morbidity or mortality. This review of
the role of hygiene education in diarrhoeal disease
control is the fourth in a series of reviews of potential
anti-diarrhoea interventions being published in the
Bulletin of the World Health Organization (6-9).
— studies that show an association between diar
rhoea rates and levels of education;
— studies of diarrhoea epidemiology that inci
dentally comment upon behavioural factors in trans
mission;
— studies of behaviour and the transmission of en
teric pathogens.
EFFECTIVENESS
These three types of study are considered in turn.
Hypothesis i. The transmission of enteric pathogens,
and thus the incidence of diarrhoea, are increased by
specific behaviours.
Diarrhoea rates and educational levels. The liter
ature contains many observations that diarrhoea rates
are highest in families with the lowest levels of edu
cational attainment. Hygiene and literacy may be
closely related (22). Such observations in themselves
are not useful because families with the lowest edu
cational attainment will tend to be those with the low
est income, poorest housing, most crowding, and
worst sanitary facilities. These confounding variables
will also promote the transmission of enteric path
ogens.
In Bangladesh, Levine et al. (15) showed that fam
ilies with no formal education had a 1.7 times higher
incidence of non-cholera diarrhoea, and a 1.8-3.4
times higher incidence of cholera, than families with
at least one high-school graduate. Although these
comparisons were controlled for tubewell usage, they
were not controlled for socioeconomic factors.
Levine et al. stated that families with high-school
graduates were relatively wealthy, judged by living
space, type of house construction, and possession of a
radio or watch. An interesting finding from earlier
studies on cholera in rural Bangladesh (17) was that
cholera incidence was higher among Hindus than
among Muslims. The incidence among Hindus was
3.0 times higher in 1963-64, 1.1 times higher in
1964-65, and 5.3 times higher in 1965-66 than among
Muslims.
This evidence is fragmentary and inconclusive.
Studies are required that compare diarrhoea rates by
literacy, educational attainment, or religious cus
toms, with the environmental and wealth variables
controlled. If significant differences are found, the
most likely reason is that the educational or religious
differences cause behavioural differences that affect
the transmission of enteric pathogens. Detailed
anthropological studies will be needed to describe
'these behavioural differences. If such differences are
found, it remains to be shown whether the specific
behaviours can be changed by hygiene education in
the short-term (rather than by general education in
the longer-term or by changing certain religious
customs).
The anecdotal and descriptive evidence on this
topic is extensive; the rigorous and quantified evi
dence is very limited. The evidence is mainly from
three sources:
Behavioural factors in diarrhoea epidemiology.
Numerous studies of diarrhoeal disease epidemi
ology, and investigations of diarrhoea outbreaks,
comment on behavioural factors that may have in-
For hygiene promotion to be an effective diarrhoea
control intervention it must be true that:
either
the transmission of
enteric pathogens, and
thus the incidence of
diarrhoea, are increased
by specific behaviours
hypothesis
1
and
these specific behaviours
can be altered by appro
priate hygiene education
programmes
appropriate hygiene
education programmes
can cause behavioural
changes which can reduce
the transmission of
enteric pathogens and
thereby reduce diarrhoea
morbidity or mortality
rates
hypothesis
2
hypothesis
3
Most of the literature on this topic deals with one or
more of these specific hypotheses. The potential
effectiveness of hygiene education would be sug
gested by a demonstration either of the correctness of
hypotheses 1 and 2 or of the correctness of hypothesis
3. The evidence for and against these hypotheses is
examined below.
469
PROMOTION OF HYGIENE FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
fluenced the pattern of spread. An exhaustive review
of these comments would be unproductive since in
general they are speculative and do not firmly as
sociate specific behaviours with specific levels of risk.
Most comments in studies from developing countries
draw attention to a complex of poverty, ignorance,
illiteracy, and crowding and suggest that associated
with these circumstances are behaviours that promote
the transmission of enteric pathogens. In developed
countries the two most commonly mentioned factors
are crowding, as may occur among lower socioecon
omic groups or during exceptionally cold weather,
and poor hygienic practices of young children and
those who care for them. The risk of pathogen spread
from young children to other members of the family,
either directly or via the hands of the parent who
cleans them, is stressed repeatedly. The importance of
|hand-washing by staff in controlling the spread of
enteric infections in hospitals, day-care centres, and
other institutions is also emphasized.
Behaviour and the transmission of enteric path
ogens. The specific behaviours that have received
most attention with regard to their role in promoting
the transmission of enteric pathogens are water
handling behaviour, food-handling behaviour, and
hand-washing. Water-handling and food-handling
behaviours will be treated separately in the context of
interrupting water-borne and food-borne transmis
sion and will be discussed in later reviews in this series.
Here, information on hand-washing is reviewed.
Concern about the possible role of hospital staff in
the spread of nosocomial infections has led to several
studies of hand-washing behaviour in medical insti
tutions in developed countries. Three such studies
are summarized in Table 1. In some settings hand
washing was found to be inadequate, both in fre
quency and thoroughness. The data from Seattle are
particularly striking and suggest a lax attitude to per
sonal hygiene even among those, such as physicians.
with a high level of theoretical understanding of the
need to maintain scrupulous hygiene in intensive care
units. This illustrates that knowledge is not neces
sarily translated into practice. No studies on hand
washing behaviour in the home, either in developed or
developing countries, have been located.
Studies on the occurrence and survival of enteric
pathogens on the hands are summarized in Table 2.
The hands of hospital staff in developed countries are
commonly contaminated and contamination takes
place easily during a variety of nursing procedures.
The hands of children were readily contaminated
by Shigella sonnei during shigellosis outbreaks in
England. Enteric bacteria on hands survive for at
least 3 hours in detectable numbers and can be trans
ferred to food and to other hands. A study in Dhaka
(26) found that the hands of attendants of hospital
ized children with rotavirus diarrhoea were com
monly contaminated with rotavirus, and that this
contamination was more likely among those who
attended younger children.
Studies on the cleansing of hands by washing with
water and soap are summarized in Table 3. Hand
washing with water and unmedicated soap removes
90-100% (below the limits of detection) of inoculated
bacteria. Washing with water alone removes a con
siderable but lesser proportion. Some washing pro
cedures with disinfectants do not achieve greater bac
terial removals than washing with water and soap.
The opinion is often expressed in the literature that
the effectiveness of hand-washing is determined more
by its thoroughness (time taken and attention to all
parts of the hands) than by the types of soap or water
used. No data have been located on the effectiveness
of hand-washing in the home, or in developing coun
tries, or using other procedures such as rubbing the
hands with sand or soil.
The studies summarized in Tables 1-3 are mainly
conducted in hospital settings. They indicate that
Table 1. Hand-washing and enteric pathogen transmission: hand-washing behaviour
Study
Findings
Reference
1
1. Hand-washing frequency by medical staff at
an intensive care unit in Seattle, USA, was
covertly observed.
Hand-washing occurred after only 41 % of
patient contacts. Physicians washed after
significantly fewer contacts (28%) than
nurses (43%).
2. Hand-washing behaviour among staff at a
radiotherapy clinic and a neonatal unit in
Helsinki, Finland, was observed over several
weeks.
Average hand-washing frequencies per person
per 8-hour shift were 10-20 at the radio
therapy clinic and 27-42 at the neonatal unit.
21
3. Thoroughness of hand-washing by nurses in
England was studied by inviting them to wash
with a dye.
89% of nurses missed some part of the hand
surface; the most neglected areas were the
thumbs, backs of the fingers, and backs of
the hands. Right-handed nurses washed the
left hand better than the right hand, and vice
versa.
28
470
R. G. FEACHEM
Table 2. Hand-washing and enteric pathogen transmission: occurrence and survival of enteric pathogens on the
hands
Findings
Study
Reference
4
1. The transmission of Klebsiella spp. in an
intensive care unit in London, England, was
studied.
Klebsiella were commonly passed from
2. Occurrence and survival of Shigella sonnei on
the hands of children in Southampton,
England, during shigellosis outbreaks were
investigated.
In 4 studies, 0-49% children had S. sonnei on
their hands following a visit to the toilet for
urination. S. sonnet on the hands survived for
at least 3 hours. S. sonnei in stools passed
through double thickness of several brands of
toilet paper onto the hands.
10
3. Contamination by Gram-negative bacteria of
the hands of nurses at an intensive care
nursery in Florida, USA, was studied.
151 hand cultures were made from 13
nurses. 86% of cultures and 100% of nurses
were positive for Gram-negative bacteria.
Klebsiella pneumoniae and Escherichia colt
accounted for 55% of isolates. Evidence was
obtained that some Gram-negative bacteria,
including E. coli, could multiply and persist on
the hands of some nurses.
13
4. Occurrence and survival of enteric bacteria on
finger-tips were studied at the Central Public
Health Laboratory in London, England.
Escherichia coli were not isolated from the
23
A known number of coliforms were placed on
the hands of the author.
After three hours the number of coliforms
was "virtually unchanged".
24
6. Bacterial contamination of the hands of staff
on the general surgical and medical wards at a
hospital in New York, USA, was investigated.
Coliforms were found in 23% of hand rinses
from physicians, 55% from nurses, 67% from
nurse aides, and 67% from other staff. 18%
of cultures revealed > 103 coliforms per 2
hands. 88% of coliforms isolated were in the
Klebsiella-Aerobacter group and the
remainder were Escherichia coli. 92% of
coliforms isolated were resistant to one or
more antibiotics.
25
7. Contamination of the hands of the attendants
of 147 children under 5 years hospitalized
with acute diarrhoea in Dhaka, Bangladesh,
was studied. 70 of the children had rotavirus
diarrhoea.
Rotavirus antigen was detected in the hand
rinses from 79% of the attendants of children
with rotavirus diarrhoea, and from 20% of the
attendants of children with non-rotavirus
diarrhoea.
26
8. Effect of baby handling on hand bacteria of
nurses was studied in a hospital nursery in
New York, USA.
Changing soiled diapers increased the
coliforms on the hands by 10’— 105-fold.
27
5
patients (especially patients' hands) to
nurses' hands during simple and 'clean' nursing
procedures. Over 90% of Klebsiella on dry
hands could survive for at least 2.5 hours.
finger-tips of 100 laboratory staff but were
isolated from the finger-tips of 12% of
butchers in a meat factory. E. coli inoculated
onto finger-tips decreased by 99% or more
a.fter 1 hour. Salmonella inoculated onto
finger tips decreased by 96-99.8% after 1
hour. With an initial inoculum of 530 per
finger-tip, S. anatum were still detectable
after 3 hours. S. anatum were frequently
isolated from corned beef and cooked ham
that had been touched for 5 seconds by
contaminated finger-tips.
knowledge of the importance of hand-washing does
not necessarily lead to adequate hand-washing; that
hands become easily contaminated by faecal bacteria
and viruses even under conditions of good hygiene
and high awareness; that enteric bacteria on hands
can survive for at least 3 hours and can be transferred
to food and other hands; and that washing with soap
and water is an effective method of cleansing the
hands.
Conclusions on hypothesis 1. Much of the evidence
presented bears only indirectly on hypothesis 1. Low
educational attainment and certain religious customs
predispose to diarrhoea, presumably because of be
havioural factors. The specific behaviour that has
been most studied is hand-washing. Hospital studies
suggest that enteric infections can spread via contami
nated hands and that hands can be decontaminated by
washing with soap and water. Thus it is probable that
471
PROMOTION OF HYGIENE FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 3. Hand-washing and enteric pathogen transmission: cleansing the hands by washing with water and soap
Study
Findings
Reference
1. Experiments were conducted to determine
whether ordinary toilet soap, without anti
bacterial additives, could act as a vehicle for
the dissemination of bacteria. Bacteria used
were Escherichia coli. Staphylococcus aureus.
two Gram-positive micrococci and Serratia
Bacteria inoculated onto the surface of soap
bars declined in number by at least 5 logio
units in 15 minutes. Washing massively
contaminated hands transferred bacteria to
the soap bar, but these bacteria did not
subsequently transfer to the hands of the
next user. Bars of soap under ordinary heavy
use did not accumulate appreciable bacterial
populations, although bars kept in non
draining trays became somewhat more
contaminated than those which were allowed
to drain.
2
2. Effect of hand-washing with water (rubbing
hands together under 45 °C running tap
water for 20 seconds) and soap and water
(rinsing in warm water for 5 seconds,
washing with soap for 15 seconds, rinsing for
5 seconds) on removal of inoculated Klebsiella
from hands of staff in an intensive care unit
was studied.
Washing with water alone removed < 98% of
Klebsiella. Washing with plain soap removed
> 98% of Klebsiella in 50% of experiments
Washing with medicated soap removed
> 98% of Klebsiella in 77% of experiments.
4
3. Hands were contaminated with Staphylo
coccus aureus or Pseudomonas aeruginosa
and then washed for 30 seconds with soap
and running water. Bacterial counts were
compared with those on unwashed (control)
hands that had been similarly contaminated.
Washing with soap and water reduced the
geometric mean counts of S a. by 99 7%,
and of P a. by 99.8%. Some washing
procedures using disinfectants did not remove
more bacteria than did washing with soap.
16
4. Hands were contaminated with Staphylo
coccus aureus and then rinsed for 30 seconds
in distilled water. Bacterial counts were
compared with those on unrinsed (control)
hands that had been similarly contaminated.
Rinsing with distilled water reduced the
geometric mean counts of S. a. by 89.8%.
Rinsing with hypochlorite solution did not
remove significantly more S. a. than did
distilled water.
16
5. Effect of hand-washing (with soap and
running water for 15 seconds and then drying
on a paper towel) on removing inoculated
Salmonella anatum from finger-tips was
studied.
Proportion of experiments in which S. anatum
could be isolated from the finger-tips after
hand-washing depended on the initial
inoculum and was 100% for 106 S. anatuml
finger-tip, 30% for 10J-104 S. anatum/Hngertip, and 0% for < 10J S. anafi/m/finger-tip.
23
6. A variety of experiments on the removal of
resident and transient skin flora from hands
by scrubbing with soap and water were
conducted.
Bacterial removal was not affected by water
temperature (24-56 °C), type of soap, drying
on a sterile towel or bacteriological water
quality. Inoculated bacteria were reduced by
50% after washing with soap and warm
water for 30 seconds.
24
7. Effect of rapid hand-washing with soap and
water, or water alone, on removing naturally
acquired coliforms from the hands of nurses
in a hospital nursery was studied.
Hand-washing with soap and water removed
67-100% of coliforms (median, 96%). Hand
washing with water alone removed 93-100%
of coliforms (median, 98%). The use of
disinfectants in rapid hand-washing did not
improve coliform removal.
27
marcescens.
certain specific behaviours do promote the trans
mission of enteric pathogens and that failure to wash
the hands is one such behaviour.
Hypothesis 2. Specific behaviours (that promote the
transmission of enteric pathogens) can be altered by
appropriate hygiene education programmes.
The literature on the methods and efficacy of hy
giene education is mainly comprised of theoretical
discussions of approaches likely to succeed or of
qualitative descriptions of field experience (77, 20,
29). Few reports that quantify the impact of a given
hygiene education programme on a specific set of
personal or domestic hygiene behaviours have been
located.
Torun (30) reports an evaluation of a hygiene edu
cation programme in a village in the Pacific lowlands
of Guatemala during 1979-80. The programme was
directed at 106 mothers, all of whom had a child
under 6 years old; 32 similar mothers acted as con
trols. The programme consisted of nine 1-hour
sessions between educators and groups of mothers
472
R. G. FEACHEM
(9-27 per group), using stories and discussions
assisted by radio plays and evocative pictures. The
mothers were encouraged to reflect upon their hy
giene problems and to commit themselves to specific
actions. The content of the educational programme
covered the recognition and treatment of diarrhoea,
excreta disposal, hand-washing, breast-feeding, food
hygiene, care of drinking water, and diet. The propor
tions of mothers giving correct answers to questions
on prevention were 56% before the programme, 90%
immediately after the programme, and 88% 6 weeks
later. A significant increase was observed in the pro
portion of target families that were judged to have
correct hygiene behaviour with respect to diaper dis
posal, kitchen hygiene, water storage, latrine hygiene,
garbage disposal, and child cleanliness. Hygiene prac
tices that would have required expenditure (e.g.,
improvements to wells and animal enclosures) were
not significantly changed. Diarrhoea incidence was
reduced in the children of target mothers compared to
control mothers, and these data are reviewed below
under hypothesis 3.
The body of both theoretical and qualitative evi
dence, taken together with evidence from other
spheres of health education (for instance, smoking,
obesity, breast-feeding), strongly suggests that the
adoption of hygienic behaviour can be achieved by
sustained and culturally appropriate educational pro
grammes. Research is urgently needed to measure the
behavioural impact of various types of hygiene edu
cation in various cultural and socioeconomic settings.
Such research should not prove unduly difficult or
expensive.
Hypothesis 3. Appropriate hygiene education pro
grammes can cause behavioural changes which can
reduce the transmission of enteric pathogens and
thereby reduce diarrhoea morbidity or mortality
rates.
Three studies (from Bangladesh, the USA, and
Guatemala), documenting the impact on diarrhoea
rates of hygiene education programmes, have been
located. In two cases, Bangladesh and USA, the edu
cation focused exclusively on hand-washing, while in
the third, in Guatemala, the programme sought to
improve several aspects of personal and domestic
hygiene.
The Bangladesh study. In Dhaka, Khan (/2)
selected patients with culture-confirmed shigellosis
attending a clinic and allocated their families to four
groups: a soap and water group that were provided
with 2-4 pieces of soap and 1-3 water pitchers and
were urged to wash their hands after defecation and
before eating; a soap group that was provided with
soap only; a water group that was provided with
pitchers only; and a control group that was provided
with nothing. Rectal swabs of family contacts of the
index shigellosis cases in the four groups were ob
tained daily for 10 days. Contacts infected by the
same type of Shigella as the index case were termed
secondary infections, and those who were also sick
(3 or more episodes of diarrhoea or dysentery in 24
hours) were termed secondary cases. The secondary
case rate was 2.2% for the soap and water group and
14.2% for the control group, and Khan concluded
that the intervention had lowered the secondary case
rate by 84%. In the soap and water group, secondary
infection rates were significantly higher among those
who used less water for washing and bathing. This dif
ference was less apparent among the control group.
The reduction in secondary infection rates was less for
Sh. dysenteriae type 1 than for other Shigella species,
possibly because of the lower infectious dose of that
organism. Attack rates of non-Shigella diarrhoea
were 37% lower in the soap and water group than in
the control group over the 10-day period of surveil
lance.
To make the reduction in the shigellosis secondary
case rate more nearly comparable with the reduction
in the non-Shigella diarrhoea attack rate, the second
ary case rate reduction was converted to an attack rate
reduction." On the assumption that the hand-washing
promotion had no influence on the incidence rate of
index cases, an 84% secondary case rate reduction is
equivalent to a 35% reduction in attack rate in the
families under study.
The USA study. In Atlanta, GA, Black et al. (3)
investigated the impact of hand-washing on diarrhoea
incidence in four day-care centres. Two groups of
children, one aged 6-17 months and the other aged
18-29 months, were studied at each day-care centre.
Two of the centres were randomly selected to receive a
hand-washing promotion campaign which encour
aged staff to wash their hands after arriving at the
centre, before handling food, and after helping a
child to use the toilet or using the toilet themselves.
When children entered the centre, used a toilet, had
their diapers changed, or were prepared to eat, staff
washed the children’s hands using bar soap and paper
towels. Children using the toilet were supervised by
staff to ensure that they did not place their hands in
their mouths. These practices were rigorously moni
tored. The other two day-care centres received no
hygiene promotion and served as controls. It had been
observed, prior to this investigation, that the practice
of hand-washing and of toilet supervision of young
children in these centres was generally lax. The inci
dence of diarrhoea among the selected children in the
four centres was monitored for 10 months; this incidence among children aged 6-29 months was reduced
" Assumptions and computations used to make this conversion
are available on request from the author.
473
PROMOTION OF HYGIENE FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 4. The effect of hygiene education on diarrhoea incidence and the percentage of days ill with diarrhoea in a
village in Guatemala*1
Proportion of days ill
Diarrhoea incidence
Age
group
(months)
Full year'’
or peak
diarrhoea
seasonr
0-23
Full year
Peak season
0-71
Full year
Peak season
Target or
control
group
Mean
number of
children
studied
per month
Mean
monthly
incidence
(episodes/
100
children/
month)
Percentage
reduction
in incidence
Mean
number of
child-days
studied
per month
Mean
monthly %
of days
with
diarrhoea''
Percentage
reduction
in % of
days with
diarrhoea
14
1433
4.5
24
906
5.9
1752
4.1
872
9.2
4457
3.0
2577
3.4
5378
2.7
2253
5.2
Target
49
36
Control
32
42
Target
60
38
Control
32
59
Target
152
25
Control
92
29
Target
185
25
Control
82
37
36
14
32
55
12
48
4 Reanalysis of data from Torun (30).
6 September 1979 to August 1980.
c March-June 1980.
d (Number of child-days with diarrhoea x 100) - Total number of child-days observed
by 48% in the hand-washing day-care centres com
pared with the control centres.
The Guatemalan study. In Florida Aceituno, a
village in the Pacific lowlands of Guatemala, Torun
(30) promoted health awareness and hygienic
behaviour among mothers and studied the impact on
their knowledge and behaviour and the effect on diar
rhoea rates in their children under 6 years old. The
promotion, and its impact on knowledge and hygienic
practice, are reviewed above under hypothesis 2. The
impact on diarrhoea rates in children is summarized
in Table 4. The target group comprised the children of
106 mothers who participated in the educational pro
gramme, and the control group comprised the chil
dren of 32 mothers who did not participate. Twelve
(38%) of the 32 control mothers were of above
average socioeconomic status, being the wives of
store-owners, preachers or community leaders. The
impact on the proportion of days with diarrhoea (a
measure combining possible impacts on incidence and
duration of episodes) was higher than the impact on
incidence. For both impact measures, impact was 2-4
times greater in the peak diarrhoea season (March to
June) than throughout the whole year.
Conclusions on hypothesis 3. These 3 studies from
Bangladesh, the USA, and Guatemala provide 5
measures of the impact of hygiene education on diar
rhoea rates:
— a 35% reduction in the incidence rate of shig
ellosis among all ages in urban families in Bangla
desh;
— a 37% reduction in the incidence rate of nonShigella diarrhoea among all ages in urban families in
Bangladesh;
— a 48% reduction in the incidence rate of all
diarrhoea among children aged 6-29 months in day
care centres in the USA;
— a 14% reduction in the incidence rate of all diar
rhoea among children aged 0-71 months throughout
the year in a Guatemalan village;
— a 32-36% reduction in the incidence rate of al!
diarrhoea among children aged 0-71 months during
the peak diarrhoea season in a Guatemalan village.
Thus the reduction of diarrhoea incidence rate to be
anticipated from hygiene education lies in the range
14-48%. Other studies support the general conten
tion that hygiene education can reduce diarrhoea
474
R, G. FEACHEM
rates, but do not allow a calculation of the reduction
in incidence achieved by a clearly defined educational
intervention (14, IS, 19).
It might be supposed that the commonness of direct
person-to-person transmission of Shigella would
make shigellosis especially sensitive to reduction by
hand-washing. The evidence presented here does not
support this. First, the computed reduction in the
shigellosis incidence rate in Dhaka was 35%, whereas
in the same families the reduction in the incidence rate
of non-Shigella diarrhoea was 37%. Second, in the
Atlanta study a 48% reduction was recorded and, out
of 85 diarrhoea stools cultured, none contained
Shigella.
The three studies summarized above suggest that
hygiene education, especially hand-washing pro
motion, has a marked impact on diarrhoea morbidity
rates. These studies should be repeated in different
socioeconomic and environmental settings and
should also quantify the impact on diarrhoea due to
rotavirus, enterotoxigenic Escherichia coli, Campylo
bacter jejuni. Shigella. Giardia lamblia and other
agents that are of known local importance.
FEASIBILITY AND COST
There is such little documented experience of hy
giene education programmes that their feasibility is
difficult to judge and their costs are unknown.
Experience with other types of health education sug
gests that such programmes are feasible on either a
national or local level and that they can employ a com
bination of mass media techniques and direct inter
action between target families and hygiene promoters
(5). Costs of hygiene education are probably low
compared to some other interventions for diarrhoea
morbidity reduction — such as the provision of im
proved water supplies and sanitation facilities. The
effectiveness of hygiene education may depend, how
ever, upon the presence of such facilities. In Dhaka
the provision of soap, which would be costly on a con
tinuing basis, may have been an essential part of the
intervention, and in Atlanta modern facilities for
washing and defecation were already available. Oper
ational research is needed to clarify the most effective
and feasible types of hygiene education programme,
to detail their costs, and to assess their dependence on
pre-existing levels of sanitary facilities.
CONCLUSIONS
Interest in the role of education in disease control
has increased considerably in recent years. It is prob
able that better educated communities enjoy relative
protection against several diseases compared to less
educated, but otherwise similar communities. This
protection may be conferred both by general edu
cation (as measured, for instance, by school attend
ance, adult literacy or education of heads of house
holds) and by disease-specific education. Disease
specific education can be preventive or therapeutic in
content.
The evidence marshalled in this paper suggests that
hygiene education can improve hygiene and can re
duce diarrhoea morbidity rates by 14-48%. These are
hopeful findings. Many countries, especially in subSaharan Africa and Asia, are having extreme diffi
culty in sustaining the development of their health
infrastructure. In the water and sanitation sector, for
instance, the rate of construction of new projects
barely keeps pace with population growth and the rate
of breakdown is alarming. In these circumstances,
educational interventions appear especially attrac
tive. They may be cheap compared to infrastructure
projects and they may achieve lasting changes in
health-related behaviour. Most importantly, as indi
cated by this review, they may achieve substantial
impacts.
Hygiene education programmes are being con
ducted in many countries and should continue. Coun
tries not having such programmes should seriously
consider launching them. Research is necessary, how
ever, to improve the cost-effectiveness of hygiene edu
cation. This research is of three main types. First,
more information is needed on the associations be
tween specific behaviours and risks of diarrhoea mor
bidity and mortality of known etiology. Second, oper
ational research is needed to clarify the most effective
and feasible types of hygiene education programme,
to detail their costs, and to assess their dependence on
pre-existing levels of sanitary facilities. Third, impact
studies should be conducted to clarify the impact on
diarrhoea of carefully designed hygiene education
programmes. These impact studies should be eti
ology-specific and, where possible, should document
impacts on diarrhoea mortality rates as well as
morbidity rates.
ACKNOWLEDGEMENTS
The author is grateful for the constructive criticisms of earlier drafts of this paper provided by R. C. Ballance, R. Black,
D. Blum, I. de Zoysa, R. Hogan, M. U. Khan, M. Merson, A. Moarefi, S. C. Pal, G. Schultzberg, D. Silimperi and
1. Tabidzadeh. Secretarial and bibliographical assistance was most ably provided by Maelorwcn Jones.
PROMOTION OF HYGIENE FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
475
RESUME
LUTTE CONTRE LES MALADIES DIARRHEIQUES CHEZ LES JEUNES ENFANTS:
PROMOTION DE L’HYGIENE PERSONNELLE ET DOMESTIQUE
Cet article est le quatrieme d’une serie portant sur les
mesures qui permettraient de red u ire la mortalite ct la mor
bidite par diarrhee chez les enfants de moins de 5 ans dans
les pays en developpement. On a etudie les effets d’une meilleure hygiene personnels et domestique sur la morbidite par
diarrhee en se basant sur des donnees recueillies dans des
hopitaux. des garderies d'enfants et des collectivities. Ces
donnees montrent qu’un faible niveau d’instruction et
certaines coutumes religieuses predisposent aux maladies
diarrheiques, probablcment en raison de certains factcurs
comportementaux. La pratique d’hygiene qui a cte le plus
etudiee a cet egard est celle qui consiste a se laver les mains.
Les etudes faites en milieu hospitalier demontrent que les
infections intestinaies peuvent etre propagees par des mains
contaminecs et que Ton peut eliminer cc risque en se lavant
les mains a 1’eau et au savon. Trois etudes faites au Bangla
desh, aux Etats-Unis d’Ameriquc et au Guatemala sur
1’impact que les programmes de promotion de 1’hygiene ont
sur la diarrhee sont passees en revue dans Particle. Ces
etudes ont mis en Evidence des reductions des taux de mor
bidite par diarrhee allant de 14% a 48%. On sait peu de
chose des effets des programmes d’hygiene sur les diarrhees
d’etiologic determinee ou sur la mortalite par diarrhee. On
ne dispose pas non plus de renseignements sur la conception
optimale de tels programmes, sur leurs couts, non plus que
sur la mesure dans laquelle leur succes depend de 1’existence
prcalablc d’installations sanitaires. D’apres les donnees
disponiblcs cos programmes constituent probablcment une
mesure d’un bon rapport cout-efficacite pour la reduction
de la morbidite par diarrhee. Des rccherches doivent etre
faites pour combler les lacunes existantes dans les connaissances et pour eclairer les aspects operationncls des pro
grammes d’cducation en maticre d’hygiene.
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Bulletin of the H orld Health Organization, 63 (2): 295-315 (1985)
World Health Organization 1985
Interventions for the control of diarrhoeal diseases
among young children: chemoprophylaxis
*
1. DE ZOYSA*1 & R. G. FEACHEM2
A number of situations place young children at increased risk of diarrhoea. Among
these, the best documented in developing countries is contact with a diarrhoea case in a
family or household. The most common application of chemoprophylaxis in developing
countries is to prevent cholera or shigellosis among household contacts of known cases.
There is little evidence that chemoprophylaxis is effective in reducing diarrhoea morbidity
and mortality, except perhaps in travellers. Theoretical calculations in this paper (based on
optimistic assumptions) suggest that chemoprophylaxis of household contacts of known
cholera cases in Bangladesh might reduce overall diarrhoea incidence rates in children
under 5 years of age by 0.02-0.06% and diarrhoea mortality rales by 0.4-1.2%.
Chemoprophylaxis of household contacts of known shigellosis cases might reduce overall
diarrhoea incidence rates by 0.15-0.35 % and diarrhoea mortality rates by 0.3-0.7% in the
same age group. The correct identification of index cases of cholera and shigellosis,
followed by the rapid distribution of drugs to their household contacts, requires skills and
resources that are scarce in the developing countries. Chemoprophylaxis can contribute to
the widespread emergence and dissemination of antimicrobial resistance. The available
evidence suggests that chemoprophylaxis is not feasible in many settings and that, even if
successfully implemented, it is not a cost-effective intervention for national diarrhoeal
diseases control programmes.
The main application of drugs in the control of
diarrhoeal diseases is in the treatment of selected cases
in order to reduce the duration and severity of illness
and prevent death. Additionally, because the
duration of excretion of the infectious agent may
sometimes be reduced, mass chemotherapy, or the
widespread administration of drugs to cases and to
infected asymptomatic persons, has been recom
mended (90) for the purpose of reducing the pool of
excreters and thereby the potential for transmission.
Drugs may also be used to protect uninfected indivi
duals from infection or illness. In this way, antimicro
bials have been given prophylactically to individuals
at high risk, such as close contacts of known cases or
travellers to endemic areas. In practice, mass
chemotherapy and individual chemoprophylaxis
repeated on a large scale merge into each other
because the presence of infection is not always
ascertained or recognized.
In this review, we define chemoprophylaxis of
diarrhoea as the administration of drugs to persons
exposed to a recognized risk, whether infected or not,
to prevent diarrhoea in these persons and to reduce
the sources of infection. We consider here the role of
chemoprophylaxis in national programmes to reduce
diarrhoea morbidity and mortality among children
under 5 years of age. This paper is the sixth in a series
of reviews of potential anti-diarrhoea interventions
published in the Bulletin of the World Health
Organization (3, 38-42).
■ Requests for reprints should be sent to the Director, Diarrhoeal
Diseases Control Programme, World Health Organization, 1211
Geneva 27, Switzerland.
a considerable proportion of
diarrhoea morbidity or mortality
in young children occurs in
hypothesis
children who are exposed to a
1
recognized risk, such as contact
with a known case
EFFECTIVENESS
For chemoprophylaxis to be an effective inter
vention to control diarrhoeal diseases it must be true
that:
either
1 Save the Children Fund Research Fellow, Department of
Tropical Hygiene, London School of Hygiene and Tropical
Medicine, Keppel Street, London WC1E 7HT, England.
- Reader in Tropical Public Health Engineering and Head of
Department of Tropical Hygiene, London School of Hygiene and
Tropical Medicine, London, England.
4526
— 295 —
296
I. DE ZOYSA & R. G. FEACHEM
Table 1. Additional cases and infections among household contacts of index cases having diarrhoea of known
etiology
Etiology of index case
Country
Infection
rate
(%)
Reference
21
29
10
10
23
Age group
of contacts
(years)
Case
rate
(%)
0-1
2-4
Enterotoxigenic Escherichia coli
ST/LT strains
Bangladesh
ST strains
All strains
Giardia lamblia
Norwalk agent
Rotavirus
15
4
10
0-4
8
42
All ages
1
9
Canada
All ages
2-5
7-13
70
USA
All ages
17
ND"
119
USA
All ages
30-32
ND"
USA
0-4
40
ND"
1
5
Thailand
All ages
19
ND"
Canada
All ages
21
46
New Zealand
0-12
66
75
All ages
38
46
0-14
62
62
All ages
36
44
0-12
15
22
All ages
13
24
34
147
55
59
151
USA
Adults
8
35
66
USA
Adults
8
55
USA
Adults
71
ND"
78
121
USA
All ages
15
ND"
119
United Kingdom
0-14
24
ND"
149
All ages
18
ND"
Bangladesh
type 1
Bangladesh
Bangladesh
Bangladesh
Marshall Islands
Shigella flexneri & sonnei
22
10
USA
Shigella flexneri
11
22
2-4
Sweden
Shigella dysentenae
4
0-1
All ages
Norway
Salmonella spp.
All ages
USA
USA
0-4
30
48
All ages
19
35
0-4
31
31
All ages
13
20
0-4
11
11
All ages
4
7
124
76
77
0-4
0
11
All ages
4
21
0-4
33
50
All ages
13
32
All ages
6
ND"
144
0-4
68
ND"
103
All ages
56
ND"
0-14
50
40
All ages
36
31
75
77
111
297
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 1 {continued}
Etiology of index case
Country
Shigella sonnei
United Kingdom
USA
USA
USA
Shigella spp.
Bangladesh
Age group
of contracts
(years)
Case
rate
(%)
Infection
rate
(%)
0-7
34
45
All ages
16
33
0-4
81
ND"
All ages
51
ND"
Reference
23
86
157
0-5
45-54
ND"
All ages
27-36
ND"
All ages
46
ND"
146
0-4
24
ND"
73
All ages
14
ND"
Bangladesh
All ages
14
32
71
USA
All ages
26
ND"
119
Classical
Bangladesh'■
All ages
4-16
11-24
37
El Tor
Six countries7'
All ages
2-25
4-32
Vibrio cholerae
“ No data.
h Feachem (37) reviewed 20 studies of cholera attack rates in households of index cases in Bangladesh. India. Hong Kong, Israel.
Philippines and China (Province of Taiwan).
Hypothesis 1. A considerable proportion of
diarrhoea morbidity or mortality in young children
occurs in children who are exposed to a recognized
risk, such as contact with a known case.
and
individuals receiving chemo
prophylaxis have lower
diarrhoea morbidity rates
or mortality rates or severity
than otherwise similar
individuals
hypothesis
2
or
chemoprophylaxis in young
children exposed to a
recognized risk, such as contact
with a known case, can reduce
overall diarrhoea morbidity
rates or mortality rates or
severity in young children
hypothesis
3
The potential effectiveness of chemoprophylaxis
would be suggested by a demonstration either of the
correctness of hypotheses 1 and2orof the correctness
of hypothesis 3. We examine below the evidence for
and against the three hypotheses and we consider the
magnitude of reductions in diarrhoea morbidity and
mortality in young children that may be achieved by
chemoprophylactic measures.
Several recognized situations place young children
at increased risk of diarrhoea. We describe here these
high-risk situations and consider their significance
with regard to overall diarrhoea morbidity and
mortality in young children.
Contact with a known case in the family or
household. Numerous studies have been conducted
on the transmission of diarrhoeal diseases within
households. Data on additional cases and infections
among household contacts of a known index case are
set out in Table 1 (in this context, the index case is the
first recognized case in the household). These studies
used different methods. Most were prospective, with
observation periods ranging from 1 to 65 days. AU
index cases had diarrhoea of known etiology and, in
some studies, only cases and infections caused by the
same organism as the index case were included in the
analysis. In other studies microbiological surveillance
of contacts was not carried out and all additional
cases of diarrhoea were included.
AU additional cases and infections among house
hold contacts following the identification of an index
case were recorded and therefore both co-primaries
and secondaries are included. We are concerned here
with the risk of disease among contacts after
identification of an index case and it is of no
298
I. DE ZOYSA & R. G. FEACHEM
importance whether the additional cases and
infections resulted from a common-source exposure
or secondary spread. The terms additional case and
additional infection, rather than secondary case and
secondary infection, are used throughout this
paper.
Additional case rates among household contacts
ranged from 1 c7o to 71% and additional infection
rates ranged from 4% to 55%. Both rates tended to be
higher in the younger age groups. When infected,
young children were also more likely to have
symptoms than older children and adults. Not only
were young children at greater risk of contracting
diarrhoea after introduction of the disease into the
household, but they also played a major role in the
introduction and spread of the disease in the house
hold (70, 52, 74, 77, 95, 149, 157).
Household contacts, therefore, are at considerable
risk of contracting diarrhoea after identification of an
index case. This risk is highest immediately after onset
of diarrhoea in the index case, and wanes rapidly
thereafter. Among household contacts of known
cholera cases, 12-43% of additional cases were
identified on the first of 10 days of observation and
85-88% by the sixth day (8, 95, 116, 139).
In the above studies, the household was the unit of
investigation and it was usually assumed that all
household contacts were members of a single family.
Increased risk of cholera, enterotoxigenic Escherichia
coli (ETEC) diarrhoea, and shigellosis has also been
reported among persons in the same cluster of houses
or neighbourhood as an index case (18, 34, 61).
Attendance at day-care centres and schools. A
number of studies from industrial countries have
examined the role of day-care centres and schools in
the spread of diarrhoeal diseases. It has been shown
that children attending these centres have a higher risk
of contracting diarrhoea than children who remain at
home (9, 25, 28). Black et al. (11) found that children
were at increased risk of diarrhoea two to four weeks
after enrolment in a day-care centre, which suggests
that illness follows contact with other infected or ill
children. Investigations within day-care centres have
shown a pattern of repeated outbreaks caused by a
variety of pathogens and sometimes having high
attack rates (Table 2). Studies from the United
Kingdom and North America provide evidence that
young children in close contact with other children in
day-care centres or schools play a major role in
introducing diarrhoea into their households and
spreading it to other young children (9, 23, 25, 70,
119, 146, 157, 158).
No prospective studies of this kind from developing
countries have been located. Outbreaks of diarrhoeal
disease in day-care centres and schools have been
described in countries such as Brazil (145) and China
Table 2. Attack rates during
recorded in day-care centres
diarrhoea
outbreaks
Etiology
Country
Attack rate
(%)
Reference
Astrovirus
Japan
52
80
Campylobacter
jejuni
Belgium
20-50
83
Clostridium
difficile
Giardia lamblia
USA
20-58
Canada
20-39
79
70
USA
27-35
USA
17
Rotavirus
Shigella spp.
Multiple
etiologies
Belgium
58-78
USA
100
USA
71
United Kingdom
51
USA
73
USA
38-51
USA
33
USA
36-50
USA
51-57
USA
14-92
9
119
43
121
119
150
48
158
119
146
119
35
(136), and it is probable that day-care centres, schools
and informal neighbourhood play groups where
many children congregate constitute high-risk
situations for children everywhere.
Contact with a known case in institutions and
hospitals. Institutions such as residential homes for
children and institutions for the mentally retarded are
associated with a high risk of diarrhoeal disease in
industrial countries, where diarrhoea incidence rates
are low in the community. Despite the prophylactic
and therapeutic use of drugs and the application of
isolation techniques, diarrhoeal diseases (particularly
shigellosis, giardiasis and amoebiasis) continue to be
a significant health problem among institutionalized
children in these countries. Children are at highest
risk of infection and illness shortly after admission
(19, 29).
Hospital-acquired diarrhoeal diseases are well
documented in industrial countries and may well
represent a significant problem in developing
countries. In a recent review of publications on
nosocomial infections originating from developing
countries (159), most reported diarrhoea outbreaks in
nurseries for premature babies and paediatric wards.
Hospital outbreaks may be serious (115) and may
lead to considerable disruption of patient services
(81). In industrial countries at least, a considerable
299
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
urban (95) and rural areas (106, 138). fs recent report
from Tanzania (99) has documented the role of a
hospital in the spread of cholera in an urban centre.
proportion of the diarrhoeal diseases treated in
hospital may be nosocomially acquired (100, 113,
127, 140). The etiological agent implicated is often
rotavirus (127), reflecting its importance as a cause
for hospitalization among young children.
Importance of these high-risk situations with
regard to overall diarrhoea morbidity and mortality.
We have described various situations associated with
a high risk for diarrhoea, but it is not clear, from the
evidence presented so far, what proportion of all
diarrhoea morbidity and mortality occurs in these
situations. There are limited data on the importance
of these high-risk situations in the epidemiology of
cholera and shigellosis. We here summarize some of
these reports:
— Cholera. Detailed studies from Hong Kong,
China (Province of Taiwan), and the Philippines
suggest that cholera did not spread easily, if at all,
within households or among households in a com
munity (44, 90, 104, 118, 148, 154, 164). Reported
cases were in general sporadic, dispersed throughout
the community, and contact-tracing identified few
additional cases or infections. In Bangladesh, on the
other hand, active transmission within households
and from household to household within neighbour
hoods has been reported and most cases tended to
appear in short family or community outbreaks in
— Shigellosis. Data from industrial countries
suggest that young children attending day-care
centres and schools may play a major role in the
spread of shigellosis to the community at large by
spreading infection in their own households and from
household to household (103, 126, 146, 150, 157,
158). Institutions, on the other hand, have not been
demonstrated to be a source of infection for the
community at large. Shigellosis in institutions may,
nonetheless, represent a substantial proportion of all
cases (20, 123). Data from developing countries on
the mode of spread of shigellosis through com
munities are limited to epidemic situations in which
whole communities are suddenly at high risk of
diarrhoeal disease. High attack rates and death rates
have been recorded (94, 120) but clustering by
household or neighbourhood does not appear to be
prominent (47, 144).
Conclusions on hypothesis 1. We have described
several situations that place young children at
increased risk of diarrhoea. Among these, the best
documented in developing countries is contact with a
known case in a family or household. The most
common application for chemoprophylaxis in
Table 3. Detectable index and additional cholera cases for various values of hospitalization rate, household size and
additional case rate
No of detectable
additional cases
per 100 cases
*'
No. of detectable
index plus additional
cases per 100 cases
24
6
30
17
13
30
25
13
17
30
10
5
21
9
30
30
10
15
13
17
30
30
10
25
9
21
30
Additional
case rate"
(%)
No. of detectable
index cases
per 100 cases'’
6
5
6
15
30
6
30
Hospitalization
rate (%)
Household
size
(persons)
30
30
50
6
5
40
10
50
50
6
15
29
21
50
50
6
25
22
28
50
50
10
5
34
16
50
50
10
15
21
29
50
50
10
25
15
35
50
" See Table 1.
h A detectable index case is an index case who is hospitalized.
r A detectable additional case is one occurring in the household of a detectable index case in the 10 days following the reporting of
the index case.
I. DE ZOYSA & R. G. FEACHEM
300
Table 4. Detectable index and additional shigellosis cases for various values of hospitalization rate, household size
and additional case rate
No of detectable
additional cases
per 100 cases1’
No. of detectable
index plus additional
cases per 100 cases
2.5
2.5
5.0
2.0
3.0
5.0
40
1.7
3.3
5.0
10
20
1 8
3.2
5.0
5
10
30
1.4
3.6
5.0
5
10
40
1 1
3.9
5.0
Hospitalization
rate (%)
Household
size
(persons)
Additional
case rate1'
(%)
No. of detectable
index cases
per 100 cases"
5
6
20
5
6
30
5
6
5
10
6
20
5.0
5.0
10.0
10
6
30
4.0
6.0
10.0
10
6
40
3.3
6.7
10.0
10
10
20
3.6
6.4
10.0
10
10
30
2.7
7.3
10.0
10
10
40
2.2
7.8
10 0
” See Table 1.
b A detectable index case is an index case who is hospitalized.
r A detectable additional case is one occurring in the household of a detectable index case in the 10 days following the reporting of
the index case.
developing countries is to prevent cholera or
shigellosis among household contacts of known
cases. We here estimate on a theoretical basis the
proportion of all cholera and shigellosis cases that
occurs among household contacts of known cases,
and is thus potentially preventable by chemo
prophylaxis.
In most circumstances, a case of cholera or
shigellosis will only be identified if he or she is
hospitalized. The calculations for cholera are set out
in Table 3." Data from Bangladesh and the
Philippines indicate that hospitalization rates for
cholera vary between 23% and 74% (4, 6, 72, 74, 92,
105, 116, 160, 161). Hospitalization rates of 30% and
50% are adopted in Table 3. Two household sizes,
comprising 6 and 10 persons, are used. Six is
approximately the mean family size in many
developing countries while ten represents the larger
extended families, or households comprising, on
average, just under two families. Three additional
cholera case rates (5 %, 15 % and 25 %) are adopted on
the basis of data summarized in Table 1. The pro
portions of all cholera cases that are detectable
additional cholera cases are 6-21% for a hospitali
zation rate of 30% and 10-35% for a hospitalization
rate of 50%.
• The formula used to make these calculations is available on
request from R.G.F.
Similar calculations for shigellosis are presented in
Table 4.“ A hospitalization rate for shigellosis of 8%
has been reported from rural Bangladesh (13, 14) and
rates of 5% and 10% are used in Table 4. Three
additional shigellosis case rates (20%, 30% and 40%)
are adopted on the basis of data summarized in Table
1. The proportions of all shigellosis cases that are
detectable additional shigellosis cases are 2.5-3.9%
for a hospitalization rate of 5%, and 5.0-7.8% for a
hospitalization rate of 10%.
The proportions of all cases that are detectable
additional cases, and thus potentially preventable by
chemoprophylaxis, are 6-35% for cholera and
2.5-7.8% for shigellosis. These proportions are
correlated both with the additional case rate and with
the hospitalization rate. Thus for shigellosis, despite
the fact that additional case rates are high (20-40%),
the proportion of detectable additional cases is low
because the hospitalization rates are low (5-10%).
Hospitalization rates depend on the severity of the
symptoms and on the hospital facilities available in
the area. The hospitalization rates adopted in Tables 3
and 4 are mainly derived from studies in the Matlab
area of Bangladesh. The longstanding presence of a
hospital specializing in acute diarrhoeal diseases, and
the availability of ambulance services in this area,
may lead to higher hospitalization rates than in most
other rural areas of developing countries.
Results
Country
(place)
Bangladesh (Dhaka)
Period of
follow-up
10 days
Drug
Tetracycline
V. cholerae (%)
Proportion of samples
from household contacts
which were positive
for V cholerae (%)
4 doses daily x 5 days
0
-
Single dose daily x 5 days
1
—
Dosage
Single dose
Placebo
India0 (Calcutta)
10 days
Tetracycline
2 doses daily x 3 days
Placebo
India (Calcutta)
15 days
10 days
8
-
13
-
-
1.5
-
3
Sulfadoxine
Single dose
19"
3
Tetracycline
2 doses daily x 3 days
21"
3
42"
7
Placebo
India (Calcutta)
Proportion of household
contacts who excreted
Doxycycline
Placebo
Single dose
15'
2
*
23
4
° V. cholerae was isolated from only 60% of index cases.
b Excluding contacts infected only on day 1 but including contacts infected on day 1 and on subsequent days.
c Excluding contacts infected on day 1.
Reference
91
62
24
134
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 5. Summary of trials of chemoprophylaxis among household contacts of cholera cases
302
I. DE ZOYSA & R. G. FEACHEM
Hypothesis 2. Individuals receiving chemo
prophylaxis have lower diarrhoea morbidity rates
or mortality rates or severity than otherwise similar
individuals.
Chemoprophylaxis of diarrhoea has been
recommended and used in numerous situations: to
limit the spread of cholera epidemics (22, 46, 90, 98),
to control shigellosis in institutions, such as
institutions for the mentally retarded in the USA (7,
49, 50, 84, 163), and to prevent travellers’ diarrhoea
(141). Yet, despite such widespread use, few
controlled trials have been conducted to assess the
effectiveness of chemoprophylaxis in limiting
transmission and reducing diarrhoea morbidity and
mortality. The evidence is mainly from three
sources:
— studies of chemoprophylaxis among household
contacts of cholera cases;
—studies of the prolonged use of antimicrobials to
prevent infections in young children;
—studies of chemoprophylaxis of travellers’
diarrhoea.
These three types of studies are considered in turn.
Chemoprophylaxis among household contacts of
cholera cases. Four studies, one from Bangladesh and
three from India, have assessed the impact of
chemoprophylaxis on infection among household
contacts of a cholera index case (24, 62, 91, 134).
Different methods were used to analyse the data but
the study design was similar in all cases. Families of
hospitalized cholera cases were assigned to one of
various drug groups or to a control group. Household
contacts were followed bacteriologically over a period
of 10-15 days. Clinical information was reported in
only one study (62) where it is stated that all Vibrio
cholerae excreters were healthy. These studies
therefore assessed the effect of chemoprophylaxis on
the duration of excretion of V. cholerae among
infected contacts and on transmission of infection
within the household. They did not assess the
protective effect of chemoprophylaxis on diarrhoeal
illness. The drugs tested were effective in reducing the
prevalence of infection on successive days and the
proportion of infected household contacts (Table 5).
This effect, however, was of short duration and after
a period of 5-6 days the infection rates were similar in
the treatment and control groups. The only study (24)
that analysed the data by age groups reported that the
maximum impact of chemoprophylaxis was observed
in children under 5 years of age and in adults.
Only one study (72) has been located that tested the
value of chemoprophylaxis in the prevention of
diarrhoea among close contacts of cholera cases. In
this trial from Bangladesh, two doses of tetracycline
were administered to household contacts of hospi
talized cholera cases. A similar control group was
visited but did not receive any medication. All
families were revisited after 10-12 days to check on
any new cases of diarrhoea and hospitalization. The
attack rate of diarrhoea among household contacts
was similar in the treatment (13%) and control groups
(14%). The occurrence of cases requiring hospitaliz
ation was, however, significantly lower in the treat
ment group (4%) than in the control group (8%). The
presence of V. cholerae in the stools of contacts was
not assessed.
Results from these studies suggest that chemo
prophylaxis is effective in reducing the prevalence of
infection among household contacts of cholera cases.
This effect appears to be greatest shortly after
initiation of the course and wanes rapidly so that after
5 to 6 days the infection rates are similar in the
treatment and control groups. Maximum effective
ness is observed, nonetheless, during the period of
greatest risk of infection. Presumably the observed
effect is due to a shortening of the duration of
excretion among contacts already infected and to a
reduction in transmission of infection to other
contacts. Khan (72), in contrast, found no impact of
chemoprophylaxis on the attack rates of diarrhoeal
illness among household contacts of cholera cases.
The observed reduction in hospitalization rates for
diarrhoea in the treatment group is ascribed to a
possible effect on the severity of the illness. No
placebo was given in Khan’s study and the increased
tendency to report to the hospital with diarrhoea may
have been associated with the absence of medication
in the control group. If the difference is real, a con
comitant decrease in the attack rates of milder
diarrhoea would be expected. Only a study that
combines bacteriological surveillance with regular
clinical assessment can clarify this issue.
Prolonged use of antimicrobials in young children.
Low-dose antibiotic feeding is common practice in
livestock and poultry husbandry. The addition to feed
of small daily doses of broad-spectrum antibiotics has
been shown to stimulate growth and to prevent
infections, especially in weak animals reared in
insanitary conditions or fed deficient diets (88, 110).
The prolonged use of antimicrobials in children has
been studied in a number of circumstances, such as
during surveillance of recurrent attacks of rheumatic
fever (93) or in the management of dietary
deficiencies (65). These studies yield conflicting
results, but suggest that the prolonged use of anti
microbials may occasionally be associated with
improved growth and decreased morbidity and
mortality, especially in malnourished children or in
children suffering from a chronic disease (122).
No. of children
receiving the drug
Duration of
study
Country
Study population
Age group
India
Hospitalized
malnourished
children
6 months
to 7 years
10
Chlortetracycline
or oxytetra
cycline
2 months
Faster recovery, reduced
incidence of diarrhoea,
reduced mortality.
87
Kenya
Hospitalized
malnourished
children
2 years
(average)
38
Chlortetracycline
2-7 weeks
Faster weight gain, reduced
incidence of intercurrent
infection, reduced frequency
of weight faltering or
weight loss during infection,
reduced duration of diarrhoea
89
Honduras
Village children
6 months
to 6 years
54
lodoxychloroquinoline or
metronidazole
Four 16-week
periods
Reduced incidence of diarrhoea
in children
2 years old.
155
USA
Children in an
Apache community
1-42
months
81
Colistin sulfate
13 weeks
Children < 7 months old,
increased prevalence of
diarrhoea; 7-30 months old,
reduced prevalence;
31-42 months old, no effect.
60
Drug
Results
Reference
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 6. Effect of long-term chemoprophylaxis on diarrhoea morbidity in young children
304
I. DEZOYSA& R. G. FEACHEM
Table 7. Controlled trials of the chemoprophylaxis of travellers' diarrhoea
Diarrhoea
attack rates
(%)
Percentage
reduction
Study
population
Duration
of trial
Drug
groups
Egypt and
Far East
Danish tourists
25 days
Mecillinam
13
75
Placebo
53
-
Honduras
Peace Corps
volunteers
3 weeks
Doxycycline
33
NS"
Placebo
45
-
Peace Corps
volunteers
3 weeks
Doxycycline
32
68
Placebo
100
-
Peace Corps
volunteers
3 weeks
US students
2 weeks
Country
Honduras
Kenya
Mexico
Mexico
Mexico
Mexico
Mexico
Mexico
US students
US students
US travellers
US students
US students
2 weeks
3 weeks
Reference
Doxycycline
6
86
Placebo
43
-
Clioquinol
39
NS"
Neomycin (with kaolin
and pectin)
20
39
Placebo
34
-
Neomycin
16
NS"
Phthalylsulfathiazole
12
50
Placebo
24
-
Bismuth subsalicylate
23
62
Placebo
61
-
For duration of
voyage
(4-13 days)
Erythromycin
0
100
Placebo
29
-
3 weeks
Trimethoprimsulfamethoxazole
16
71
Placebo
55
-
Trimethoprimsulfamethoxazole
2
94
Trimethoprim
14
58
-
2 weeks
Placebo
33
US Navy
personnel
For duration of
exposure
(0.5-2.5 days)
Doxycycline
4
81
Placebo
21
-
Peace Corps
volunteers
3 weeks
Doxycycline
Sri Lanka6
and Kenya
Swiss tourists
2 weeks (duration
of voyage:
2-4 weeks)
Streptotriadc
16
58
Placebo
38
-
Various
destinations6
British airline
personnel and
their families
3 weeks (duration
of voyage:2 days
to over 6 weeks)
Streptotriadc
12
25
Neomycin-sulfonamidesd
19
NS"
Placebo
16
-
Mexico
Morocco
Placebo
" No significant difference in diarrhoea attack rates compared with the control group.
b Poorly controlled and supervised trial.
f Streptomycin + sulfadimidine + sulfadiazine + sulfathiazole.
d Neomycin + sulfadimidine + sulfadiazine + sulfathiazole.
8
83
46
-
15
132
131
129
67
68
30
2
31
32
45
130
141
152, 153
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Four controlled trials have been located that
document the effect of the prolonged administration
of antimicrobials on diarrhoea morbidity in young
children. They are summarized in Table 6. The first
two studies, conducted in India and Kenya, report the
effect of chemoprophylaxis on the recovery of
children hospitalized for malnutrition (87, 89). Both
document faster recovery and reduced incidence of
diarrhoea in children receiving antibiotics. The study
from Kenya also noted a decreased duration of
diarrhoea. Two further studies, from Honduras (155)
and the USA (60), investigated the protective effect of
prolonged administration of antimicrobials on
diarrhoea morbidity among children in the com
munity. The results suggest that the prolonged
administration of antimicrobials to young children in
endemic areas may have an impact on diarrhoea
incidence or duration in certain age groups. Detailed
etiological investigations were not conducted. Also,
the children were randomized within age groups to the
different treatment cells and we cannot therefore
assess the effect of chemoprophylaxis on the
transmission of diarrhoea within households.
Chemoprophylaxis of travellers’ diarrhoea.
Travellers’ diarrhoea may affect from 10% to 60%
(30, 125) of travellers from low-risk to high-risk areas
during their first few weeks of travel. The condition is
primarily infectious, with ETEC as the most common
pathogen, isolated from 30% to 70% of cases (30, 51,
56, 97, 125, 128, 131, 135). Fourteen controlled trials
that investigated the effectiveness of chemopro
phylaxis of travellers’ diarrhoea are summarized in
Table 7. Early studies with poorly absorbed anti
microbials, such as neomycin and phthalylsulfathiazole (67, 68, 152, 153), showed a modest effect.
With improved understanding of the etiology of
travellers’ diarrhoea, doxycycline was tested in a
number of trials. Sack et al. (129, 130) showed that a
single daily dose of doxycycline was highly effective in
preventing diarrhoea in Peace Corps volunteers
travelling to Kenya and Morocco. Protection from
ETEC and other diarrhoeas was observed during the
treatment period and for the first week after cessation
of doxycycline. In the Moroccan study, however, the
volunteers were followed over a longer period of time
and a significant increase in the attack rate was later
observed in the treatment group compared with the
control group. In a study in Honduras (132),
biweekly prophylaxis with doxycycline was only
marginally effective, an outcome that may be due to
the decreased dosage or to the increased prevalence of
resistant Escherichia coli found in Honduras. In a
subsequent study in Honduras (131), a daily dose of
doxycycline was found to be effective in reducing
diarrhoea attack rates, although it did not prevent
diarrhoea caused by doxycycline-resistant ETEC.
305
Doxycycline also significantly reduced the severity of
the illness in those who had diarrhoea. Freeman et al.
(45) demonstrated the effectiveness of daily
doxycycline in US Navy personnel making a short
port call to Mexico. No rebound disease in acute
diarrhoea was noted in the treatment group after
departure from the high-risk area. Other antibiotics
found to be effective in controlled trials are erythro
mycin (2), mecillinam (15), trimethoprim
sulfamethoxazole, and trimethoprim alone (31, 32).
In the latter two studies among US students who
remained in Mexico on completion of the trial,
rebound diarrhoea was noted in the first week follow
ing cessation of the treatment. Finally, a non-specific
drug, bismuth subsalicylate, has been found to have
some protective effect when ingested in doses too
large to be taken routinely (30).
In all of these studies, the drug was administered
only for the first few weeks of residence in the highrisk area, and both effectiveness and the development
of resistance during longer periods of chemoprophy
laxis were not evaluated. Most studies were conducted
in small groups of similar individuals, such as US
students and Peace Corps volunteers, visiting a single
high-risk area. These individuals were often in close
contact with each other, sometimes eating together or
sharing the same accommodation. Transmission of
diarrhoea within the study groups may have been
facilitated under such conditions. There is some
evidence of this in one study (68). On the other hand,
it is possible that the potential for transmission was
reduced within the study group owing to the adminis
tration of drugs to some members of the group. No
well controlled trials of chemoprophylaxis in large
groups of travellers to multiple destinations have yet
been carried out.
Conclusions on hypothesis 2. Numerous studies
have been conducted but there is little evidence that
chemoprophylaxis can reduce diarrhoea morbidity,
except perhaps in travellers. No studies have been
located that consider the effect on diarrhoea
mortality. Chemoprophylaxis among household con
tacts of cholera cases has been shown to reduce the
prevalence of infection during the period of most
active transmission, but no impact on diarrhoea
attack rates has been documented. There is some
indication, however, that the severity of diarrhoea
may be reduced in the treated household contacts.
Broad-spectrum
antibiotics
administered
to
malnourished children have been shown to prevent
nosocomial diarrhoea, but the impact of prolonged
chemoprophylaxis among young children in the
community remains unclear. Studies on travellers’
diarrhoea indicate that chemoprophylaxis may be
highly effective in reducing the incidence of diarrhoea
among adult travellers making short visits to high-risk
306
I. DE ZOYSA & R. G. FEACHEM
Table 8. Reduction in cholera incidence following chemoprophylaxis of household contacts of known cholera
cases
Additional
case rate"
(%)
Proportion of all cholera
cases that occur as
detectable index and
additional cases6
(%)
6
5
30
20
1.2
6
5
30
40
2.4
6
5
30
60
3.6
6
5
50
20
2.0
6
5
50
40
4.0
6
5
50
60
6.0
2.6
Household
size
(persons)
Reduction in additional
case rate due to
chemoprophylaxis
(%)
Reduction in cholera
incidence rate due to
chemoprophylaxis
(%)
6
15
30
20
6
15
30
40
5.1
6
15
30
60
7.7
4.3
6
15
50
20
6
15
50
40
8.6
6
15
50
60
12.8
6
25
30
20
3.3
6
25
30
40
6.7
6
25
30
60
10.0
6
25
50
20
5.6
6
25
50
40
11.1
16.7
6
25
50
60
10
5
30
20
1.9
10
5
30
40
3.7
10
5
30
60
5.6
10
5
50
20
3.1
10
5
50
40
6.2
10
5
50
60
9.3
10
15
30
20
3.4
10
15
30
40
6.9
10
15
30
60
10.3
10
15
50
20
5.7
10
15
50
40
11.4
10
15
50
60
17.2
10
25
30
20
4.2
10
25
30
40
8.3
10
25
30
60
12.5
10
25
50
20
6.9
10
25
50
40
13.8
10
25
50
60
20.8
a See Table 1.
b See Table 3.
307
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
Table 9. Reduction in shigellosis incidence following chemoprophylaxis of household contacts of known shigellosis
cases
Additional
case rateJ
(%)
Proportion of all shigellosis
cases that occur as
detectable index and
additional cases''
(%»
6
20
6
20
6
Reduction in additional
case rate due to
chemoprophylaxis
(%)
Reduction in shigellosis
incidence rate due to
chemoprophylaxis
(%)
5
20
0.5
5
40
1.0
20
5
60
1.5
6
20
10
20
1.0
6
20
10
40
2.0
6
20
10
60
3.0
6
30
5
20
0.6
6
30
5
40
1 2
6
30
5
60
1.8
6
30
10
20
1.2
6
30
10
40
2.4
Household
size
(persons)
6
30
10
60
3.6
6
40
5
20
0.7
6
40
5
40
1.3
6
40
5
60
2.0
6
40
10
20
1.3
6
40
10
40
2.7
6
40
10
60
40
10
20
5
20
0.6
10
20
5
40
1.3
10
20
5
60
1.9
10
20
10
20
1.3
10
20
10
40
2.6
10
20
10
60
3.9
10
30
5
20
0.7
10
30
5
40
1.5
10
30
5
60
2.2
10
30
10
20
1.5
10
30
10
40
2.9
10
30
10
60
4.4
10
40
5
20
0.8
10
40
5
40
1.6
10
40
5
60
2.3
10
40
10
20
1.6
10
40
10
40
3.1
10
40
10
60
4.7
" See Table 1.
h See Table 4.
30S
I. DE ZOYSA & R. G. FEACHEM
areas if the appropriate drug is used in the correct
dosage, and if the causative enteric pathogens
(particularly ETEC) are susceptible. The severity of
illness may also be reduced. Of concern, however, is
the rebound increase in diarrhoea incidence that has
been documented when travellers remain in the highrisk area after discontinuation of the drug.
Hypothesis 3. Chemoprophylaxis in young children
exposed to a recognized risk, such as contact with a
known case, can reduce overall diarrhoea
morbidity rates or mortality rates or severity in
young children.
The test of this hypothesis would come from a
study in which chemoprophylaxis was given to young
children exposed to one of the high-risk situations
described in hypothesis 1, and where the impact on
overall diarrhoea rates among young children was
monitored. No study of this kind has been located.
The two studies described in hypothesis 2, which
considered the effect on diarrhoea morbidity of the
prolonged administration of drugs to children in the
community, cannot be used to test hypothesis 3
because the children in the treatment groups were not
selected on the basis of their exposure to high-risk
situations.
Hypothesis 3 must be examined, therefore, by
theoretical calculations of the reductions in diarrhoea
rates that may result from chemoprophylaxis of
young children exposed to a recognized risk. Let us
consider the most common of the identified high-risk
situations: contact in the household with a known
case of cholera or shigellosis, and calculate the
potential impact of chemoprophylaxis on the
incidence of specific diarrhoeas.6
The calculations for cholera are set out in Table 8.
Two household sizes (6 and 10) and three additional
case rates (5%, 15% and 25%) are used as before. For
the purposes of this discussion, optimistic assump
tions are made on the reduction in additional case
rates due to chemoprophylaxis and three values
(20%, 40% and 60%) are adopted on the basis of the
data summarized in Table 5. The expected reduction
in cholera incidence rates due to chemoprophylaxis,
computed on the basis of these assumptions, ranges
from 1.2% to 16.7% for a household size of 6 and
from 1.9% to 20.8% for a household size of 10.
Similar calculations for shigellosis are presented in
Table 9. The expected reduction in shigellosis
incidence rates due to chemoprophylaxis ranges from
0.5% to 4.0% for a household size of 6 and 0.6% to
4.7% for a household size of 10.
The impact of chemoprophylaxis on overall
b The formula used to make these calculations is available on
request from R.G.F.
diarrhoea incidence rates depends on the prominence
of cholera and shigellosis as a cause of diarrhoea and
this varies greatly from country to country. For
cholera, we may take the extreme example of
Bangladesh, where cholera is endemic and accounts
for approximately 0.4% of all diarrhoea cases in
children under 5 years (12, 14, 92, 102, 106). If we
take values of 5-15% from Table 8 as estimates of the
expected reduction in cholera incidence rates due to
chemoprophylaxis of household contacts of known
cholera cases, the intervention might reduce overall
diarrhoea incidence rates in children under 5 years by
0.02-0.06%. In developing countries shigellosis
accounts for approximately 10% of all diarrhoea
cases in children under 5 years (12, 14, 57, 64, 102).
Chemoprophylaxis of household contacts of known
shigellosis cases might reduce shigellosis incidence
rates by an estimated 1.5-3.5% (Table 9), and there
fore might reduce overall diarrhoea incidence rates in
children under 5 years by 0.15-0.35%.
In the absence of other information, it may be
assumed that the reductions in cholera and shigellosis
mortality rates caused by chemoprophylaxis of
household contacts of known cases are the same as the
reductions in incidence rates shown in Tables 8 and 9.
We have calculated elsewhere (27) that, in
Bangladesh, cholera may account for 8% of
diarrhoea deaths in children under 5 years of age. If
chemoprophylaxis of household contacts of known
cholera cases reduces the cholera mortality rates in
children under 5 years by 5-15%, then this inter
vention might, in Bangladesh, reduce the overall
diarrhoea mortality rate in the same age group by
0.4-1.2%. Where shigellosis is responsible for 20% of
diarrhoea deaths in children under 5 years (a
speculative but reasonable assumption), if chemo
prophylaxis of household contacts of known
shigellosis cases reduces the shigellosis mortality rate
in children under 5 years by 1.5-3.5%, then this
intervention might reduce the overall diarrhoea
mortality rate in the same age group by 0.3-0.7%.
FEASIBILITY
The likely effectiveness of chemoprophylaxis in the
control of diarrhoeal diseases should not be
considered in isolation from the unwanted effects of
the drugs used and obstacles to the widespread
implementation of the intervention.
The use of prophylactic drugs. No prophylactic
drug has yet been identified which is universally safe
and effective. A number of drugs, such as neomycin
(63, 69) and the halogenated hydroxyquinolines (109,
114, 133), previously in common use, are now out of
CHEMOPROPHYLAXIS FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
favour because of their potential adverse reactions.
Antimicrobials are popular, but they have selective
action against certain bacteria and protozoa only. A
number of other agents, such as phage preparations
(82, 107, 112), lactobacilli preparations (21, 26), and
bismuth subsalicylate (30, 53) have been considered
for the chemoprophylaxis of diarrhoea but are
probably of limited value.
Antimicrobials are all associated with adverse
reactions, some of them severe, and their use may be
contraindicated in certain persons; for example, the
administration of tetracyclines to children and to
pregnant or lactating women is discouraged because
of their dental staining effect (156). Antimicrobials
may also increase host susceptibility to some enteric
pathogens (16, 96), and alter the activity of pancreatic
enzymes (17) and the metabolism of bile acids (58).
Of greatest concern, however, is that the use of anti
microbials provides an advantage to resistant strains
and imposes selective pressure to assist in their spread
(36, 85, 101, IOS, 142, 162). There is also the sinister
possibility that the emergence of resistance is
associated with increased virulence or communi
cability of certain strains (33, 117, 137, 143, 165).
Finally, antimicrobials may mask other bacterial
infections and complicate their therapy. Their
extensive use cannot be recommended in the absence
of monitoring for adverse reactions.
Implementation. The application of chemoprophy
laxis among family contacts of known cholera and
shigellosis cases requires the correct identification of
the index cases followed by the administration of
drugs to their family contacts. Under normal
circumstances, only hospitalized diarrhoea cases are
likely to be investigated and correctly diagnosed. As
discussed earlier, hospitalization rates vary widely
from area to area and will often be lower than those
adopted in our calculations. Outbreaks of diarrhoeal
disease that need intensified control measures should
be detected as soon as possible, but reporting systems
based on routine data collected from health facilities
are not very sensitive (54) and the laboratory services
needed to make an accurate diagnosis of etiology and
to test for antimicrobial sensitivity may not always be
available (47, 94). Once the index case of cholera or
shigellosis is recognized, the at-risk family members
must be located for the distribution of drugs. Time is
at a premium here, as the additional case rate among
household contacts is highest on the first day of
observation in the studies reported in Table 1 and falls
rapidly thereafter. The distribution of drugs may be a
complex task, especially in rural areas and when a
multiple-dose drug regimen is used.
In short, the detection of cases and the rapid
follow-up of their contacts and distribution of drugs
require skills and resources that are scarce in
309
developing countries. The workload may be
especially heavy in epidemic situations when the
number of contacts to be reached will be very high.
Chemoprophylaxis might then direct attention from
other, more effective, control measures.
COST
The costs of chemoprophylaxis have not been
documented. The costs involved fall into four main
categories:
— The cost of the drugs. Drug bills place a con
siderable burden on the health budget of most govern
ments. There are large cost variations between drugs
and even for the same drug, depending on the price
per unit for that particular drug, the quantity
required, the preparation chosen, and the purchasing
and distribution systems used.
— The cost of surveillance (including laboratory
surveillance). This cost is difficult to determine as few
reporting systems for health expenditure list these
items separately. This cost would be shared with other
interventions.
— The cost of the distribution of the drugs,
including manpower and logistics.
—The cost of unwanted effects. These include the
cost of treatment of adverse reactions due to the drugs
used in chemoprophylaxis and the increased cost of
new drugs used in therapy to replace old ones that
become inadequate because of the emergence of anti
microbial resistance.
CONCLUSIONS
There is little evidence that chemoprophylaxis is
effective in reducing diarrhoea morbidity and
mortality. The most common application of chemo
prophylaxis in developing countries is to prevent
cholera or shigellosis among selected high-risk
groups, such as household contacts of known cases. A
theoretical case has been made out, based on
optimistic assumptions, that chemoprophylaxis of
household contacts of known cholera cases in
Bangladesh might reduce overall diarrhoea incidence
rates in children under 5 years of age by 0.02-0.06%
and diarrhoea mortality rates by 0.4-1.2%. Chemo
prophylaxis of household contacts of known
shigellosis cases might reduce diarrhoea incidence
rates by 0.15-0.35% and diarrhoea mortality rates by
0.3-0.7% in the same age group.
The correct identification of index cases of cholera
and shigellosis, followed by the rapid distribution of
drugs to their household contacts, requires skills and
resources that are scarce in the developing countries.
310
1. DE ZOYSA & R. G. FEACHEM
All the drugs currently used have side-effects that
should be carefully monitored. Chemoprophylaxis
can contribute to the widespread emergence and
dissemination of antimicrobial resistance. The costs
of chemoprophylaxis have not been documented but
are likely to be high and no long-term benefits may be
derived. The available evidence suggests, therefore,
that chemoprophylaxis is not feasible in many settings
and that, even if successfully implemented, it is not a
cost-effective intervention for national diarrhoeal
disease control programmes.
ACKNOWLEDGEMENTS
We are grateful for the constructive criticisms on earlier drafts of this paper provided by D. Barua, P.F. Beales,
D. Blum, B. Cvjetanovic, H. G. Dam, R. C. Hogan, M. H. Mcrson, H. Mosley, S. C. Pal and Y. Watanabe. We thank J.
Seaman of the Save the Children Fund, United Kingdom, for his support and encouragement. Secretarial, bibliographical
and editorial assistance was most ably provided by Alison Hinchley and Susanne O’Driscoll.
RESUME
INTERVENTIONS DESTINEES A LA LUTTE CONTRE LES MALADIES DIARRHEIQUES CHEZ LES JEUNES ENFANTS:
CHIMIOPROPHYLAXIE
Cet article est le sixieme d’une serie passant en revue les
interventions possibles en vue de reduire la morbidite et la
mortalite par diarrhee parmi les enfants de moins de 5 ans
dans les pays en developpement. Un certain nombre de
situations font courir aux jeunes enfants un risque accru de
diarrhee. Parmi celles-ci la mieux etudiee dans les pays en
developpement est le contact avec un cas connu dans la
famille ou le menage. L’application la plus frequente de la
chimioprophylaxie dans ces pays vise a pr6venir le cholera
ou les shigelloses parmi les contacts de cas connus dans les
menages. Il ne semble pas que la chimioprophylaxie puisse
reduire efficacement la morbidite et la mortalite
*
par
diarrhee, sauf peut-etre chez les voyageurs. D’apres les
calculs theoriques du present article (fondes sur des
hypotheses optimistes), la chimioprophylaxie appliquee &
des contacts dans les menages comptant des cas connus, au
Bangladesh, pourrait reduire de 0,02-0,06% les taux
d’incidence globaux de la diarrhee et de 0,4-1,2% les taux de
mortalite par diarrhee chez les enfants de moins de 5 ans. En
ce qui concerne les shigelloses, la chimioprophylaxie
administree a des contacts de cas connus dans des menages
pourrait reduire de 0,15-0,35% les taux d’incidence globaux
de la diarrhee et de 0,3-0,7% les taux de mortalite par
diarrhee dans le meme groupe d’age.
Le depistage correct des cas initiaux de cholera et de
shigellose suivi d’une distribution rapide de medicaments A
leurs contacts dans les menages demande des competences et
des ressources qui sont rares dans les pays en developp
ement. Tous les medicaments actuellement en usage
presentent des effets secondaires qui doivent etre minutieusement surveilles. En outre, point capital, la chimio
prophylaxie peut contribuer a 1’apparition et d la dis
semination de la resistance aux antimicrobiens sur une
grande echelle. On ne connait pas les couts de la
chimioprophylaxie, mais ils sont probablement elev6s et 1’on
ne peut en attendre d’avantages A long terme. D’apres les
donnees existantes, la chimioprophylaxie est done irrealisable dans de nombreuses circonstances et, meme si elle est
appliquee avec succes, ce n’est pas une intervention rentable
pour les programmes nationaux de lutte contre les maladies
diarrheiques.
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CH 3.8
Bulletin ofthe H orla Health Organization, 63 (4): 757-772 (1985)
© World Health Organization 1985
Interventions for the control of diarrhoeal diseases
among young children: improving water supplies and
excreta disposal facilities
*
S. A. Esrey,1 R. G. Feachem,*12 & J. M. Hughes3
A theoretical model is proposed that relates the level of ingestion of diarrhoea-causing
pathogens to the frequency of diarrhoea in the community. The implications of this model
are that, in poor communities with inadequate water supply and excreta disposal, reducing
the level of enteric pathogen ingestion by a given amount will have a greater impact on
diarrhoea mortality rates than on morbidity rates, a greater impact on the incidence rale of
severe diarrhoea than on that of mild diarrhoea, and a greater impact on diarrhoea caused
by pathogens having high infectious doses than on diarrhoea caused by pathogens of a low
infectious dose. The impact of water supply and sanitation on diarrhoea, related infections,
nutritional status, and mortality is analysed by reviewing 67 studies from 28 countries. The
median reductions in diarrhoea morbidity rates are 22% from all studies and 27% from a
few better-designed studies. All studies of the impact on total mortality rates show a median
reduction of 21%, while the few better-designed studies give a median reduction of 30%.
Improvements in water quality have less of an impact than improvements in water
availability or excreta disposal.
Of the several interventions that may reduce
diarrhoea morbidity and mortality rates (38), the
improvement of water supply and excreta disposal
facilities has attracted particular interest. These
environmental
improvements,
together
with
improvements in living standards, played a major
role in reducing diarrhoea rates and controlling
epidemic typhoid and cholera in Europe and North
America between 1860 and 1920. It is anticipated that
the improvement of water supply and excreta
disposal in poor communities in developing countries
today will have a substantial impact on diarrhoea
morbidity and mortality rates in those communities.
This expectation provides part of the motivation for
the International Drinking Water Supply and Sani
tation Decade (1981-1990), the aims of which are to
increase the rate at which new water supply and
excreta disposal facilities are constructed and to maxi
mize the probability that they will be correctly opera
• Requests for reprints should be sent to the Director, Diarrhoeal
Diseases Control Programme, World Health Organization, 1211
Geneva 27, Switzerland.
1 Division of Nutritional Sciences, Cornell University, Ithaca,
New York 14853, USA.
2 Head, Department of Tropical Hygiene, London School of
Hygiene and Tropical Medicine, Keppel Street, London WCIE7HT,
England.
3 Director, Hospital Infections Program, Center for Infectious
Diseases, Centers for Disease Control, Public Health Service, US
Department of Health and Human Services, Atlanta, GA 30333,
USA.
4581
ted, maintained and used.
The potential impacts of improved water supply
and excreta disposal on diarrhoea and other waterrelated diseases in developing countries have been
discussed and debated at length over the past decade.
White et al. (86) provided a conceptual framework
for the debate in the context of studies in East Africa;
McJunkin (56) reviewed the topic extensively;
Saunders & Warford (70) summarized the water
supply impact studies; Feachem et al. (39)
summarized the excreta disposal impact studies; and
Blum & Feachem (13) and Esrey & Habicht (28)
considered the methodological difficulties inherent in
attempts to measure the impact of water supply and
excreta disposal projects on diarrhoea.
In this review we analyse the effectiveness of water
supply and excreta disposal improvements for
reducing diarrhoea rates in young children in
developing countries. We also examine their impact
on diarrhoea-related infections, nutritional status,
and mortality. We make no attempt to analyse other
impacts of water supply and excreta disposal
improvements or to compute an overall cost-benefit
ratio for these investments. This paper is the ninth in a
series of reviews of potential anti-diarrhoea inter
ventions (2, 25, 26, 32, 34-36, 38).“
• ASHWORTH, A. & FEACHEM. R. G. Interventions for the
control of diarrhoeal diseases among young children: improving
lactation. Unpublished WHO document CDD/85.2, 1985.
— 151 —
75S
S. A. ESREY ET AL.
EFFECTIVENESS
For improved water supply or excreta disposal
facilities to be an effective diarrhoea control
intervention, it must be true that:
either
water supply or excreta disposal
improvements can reduce the inges
tion by young children of pathogens
causing diarrhoea
hypothesis
1
and
a reduction in the ingestion of these
pathogens by young children can
reduce diarrhoea morbidity or
mortality rates
hypothesis
2
or
water supply or excreta disposal
improvements can reduce diarrhoea
morbidity or mortality rates among
young children
hypothesis
3
The effectiveness of improved water supply and
excreta disposal would be suggested by a demonstra
tion either of the correctness of hypotheses 1 and 2 or
the correctness of hypothesis 3. In some other reviews
in this series (for instance, 35, 36), most of the
literature bears on hypotheses 1 and 2, and hypothesis
3 must be handled by theoretical calculations. Here
the reverse is the case: there are few data on
hypotheses 1 and 2 and an extensive literature on
hypothesis 3. The evidence for and against the three
hypotheses is examined below.
Hypothesis 1. Water supply or excreta disposal
improvements can reduce the ingestion by young
children of pathogens causing diarrhoea.
There is some evidence to suggest that three types of
water and excreta disposal improvements (improved
water quality, increased water availability and
quantity associated with better hygiene practices, and
improved excreta disposal facilities) may reduce the
ingestion of pathogens causing diarrhoea (33).
All the major infectious agents of diarrhoea are
transmitted by the faecal-oral route, and all can be
transmitted via contaminated water. For most agents
water-borne transmission has been documented. For
some agents there is good evidence that, at least in
some places at some times, water is a major vehicle of
transmission. Notable examples are Salmonella
typhi, Vibrio cholerae, and Giardia lamblia (39).
Traditional water sources are often highly con
taminated with faecal matter. Improved water
sources may be free of contamination or considerably
less contaminated than unimproved water sources
(30, 77). Uncontaminated source water may become
polluted by the time it is ingested, and water storage
in home containers may result in increased con
tamination depending on storage conditions (37, 66,
72).
Increased water availability and quantity,
associated with improved hygiene, may reduce faecal
contamination of the hands. Proper cleaning of
utensils, food, and home environments is also likely
to reduce transmission of faecal matter. The
transmission of all the main diarrhoea-causing agents
is probably influenced to some degree by increased
water availability and quantity, but it is Shigella
transmission that has been particularly associated
with poor personal and domestic hygiene (45, 78).
This may be because of the low infectious dose of
Shigella relative to other bacterial enteric pathogens,
or it may be only because Shigella has been most
studied. The relationship between personal hygiene
and the newly-recognized diarrhoea agents
(especially Campylobacter jejuni, enterotoxigenic
Escherichia coli, and rotavirus) should be studied.
All the major infectious agents of diarrhoea are
shed by infected persons via the faeces, and therefore
hygienic disposal of human excreta plays a role in
controlling them. Use of toilets by all members of the
community should reduce faecal contamination of
houses, yards and gardens, and the neighbourhood.
In addition, proper treatment and disposal of human
excreta would prevent faecal contamination of fields,
crops, and receiving water-bodies, which would in
turn further reduce the transmission of faecal
pathogens. The hygienic disposal of the faeces of
children too young to use the toilet is of the utmost
importance, because such children constitute an
important reservoir of several agents of diarrhoea
(for instance, rotavirus and enterotoxigenic E. coli).
Hypothesis 2. A reduction in the ingestion of these
pathogens by young children can reduce diarrhoea
morbidity or mortality rates.
The ingested dose of a pathogen required to cause
diarrhoea depends upon the particular properties of
the pathogen and upon a number of host factors. The
general relationship between ingested dose and
proportion of exposed persons contracting diarrhoea
IMPROVING WATER SUPPLIES AND EXCRETA DISPOSAL FOR CONTROL OF DIARRHOEAL DISEASES
759
Fig. 2. Dose-response relationship for young children
under various levels of exposure to an array of enteric
pathogens.
Fig. 1. Dose-response relationship for a group of
susceptible persons, all exposed to an equal dose of
pathogen X.
is shown in Fig. I. In the dose range below A, no one
becomes ill.
*
In the dose range above B, all
susceptible persons develop diarrhoea. Between A
and B lies an intermediate range in which some
persons become ill and others do not. The dose at
which 50% of challenged persons become ill is known
as the median infectious dose (IDso), which is the
figure generally reported from volunteer studies.
Little is known about the shape of the curve in the
intermediate range and, for this reason, a broken line
is shown in Fig. 1. Both the shape of the curve and the
values of A, B, and the ID50 depend upon the
particular pathogen, its method of ingestion (in water
or in food), and a variety of features of the exposed
group of people, such as age and immunity.
Available ID50 and other infectious dose data have
been recently reviewed for all the major diarrhoea
causing pathogens (39). For bacterial agents there is a
wide range of lD<o values—from around 103 for
Shigella to 108-10" for Vibrio cholerae. Less is
known about the viral and protozoal agents of
diarrhoea, although there are grounds for assuming
that the IDso values are relatively low (< 102). Nearly
all infectious dose data are derived from studies on
volunteers in which the subjects were healthy adults
from developed countries. The doses necessary to
infect children, particularly malnourished children,
may be very different. ID50 values also depend on the
food or drink with which the pathogens are ingested;
therefore, they may differ among countries with
differing dietary and child-feeding practices. In
* Despite the representation in Fig. 1, it may be that for some
pathogens A = 0.
addition, in situations where large numbers of
persons are exposed to diarrhoea-causing pathogens,
the 1D| or IDo.t values may be of greater
epidemiological relevance than the IDso values. More
reliance can be placed on the relative ranking of
pathogens by IDso than on the absolute dose values
obtained from studies on volunteers.
The relationship depicted in Fig. 1 may be
generalized to a group of young children having
different levels of water supply and excreta disposal
services and, consequently, different levels of
ingestion of enteric pathogens (Fig. 2). Consider first
the incidence rate of mild diarrhoea. At low levels of
ingestion (A-B), there remains an appreciable
incidence of mild diarrhoea, made up of an
irreducible minimum of infectious diarrhoea, plus
diarrhoea not due to enteric pathogens. This situation
is exemplified by children in wealthy communities in
developed countries. When ingestion rises above
point B, the incidence rate of mild diarrhoea also
rises. At point D saturation is reached, and further
increases in the ingestion of pathogens do not result in
an increased incidence rate of mild diarrhoea. As in
Fig. 1, the shape of the curve between points B and D
on the “mild diarrhoea incidence” line in Fig. 2 is
unknown, so a broken line is shown. Poor com
munities in developed and developing countries, with
their elevated diarrhoea incidence rates, clearly lie to
the right of point B.
The incidence rate of severe diarrhoea, which may
be defined by stooling rate, stool volume, duration,
degree of dehydration or other measures, is indicated
on Fig. 2 by the distance between the two lines (the
shaded band). The incidence rate of severe diarrhoea
is less than that of mild diarrhoea, but it represents an
increasing proportion of the total diarrhoea incidence
rate as the ingestion of enteric pathogens rises above
760
S. A. ESREY ET AL.
the level represented by point C.c The incidence rate
of severe diarrhoea is shown in Fig. 2 to be constant in
the range A-C, to rise in the range C-E, and to be
constant in the range E-F. The breakpoints for severe
diarrhoea incidence rate (C and E) are offset to the
right of the equivalent points for mild diarrhoea inci
dence rate (B and D), on the assumption that for a
single pathogen a higher ingested dose is necessary to
produce severe diarrhoea than mild diarrhoea. There
is direct experimental confirmation of this for entero
toxigenic E. coli (27) and for Vibrio cholerae (19).
Indirect evidence is also available for Salmonella, for
which there is an inverse relationship between dose
and incubation period (12) and an inverse rela
tionship between incubation period and severity (10).
Fig. 2 assumes that the IDso for severe symptoms is
higher than the IDso for mild symptoms for most
enteric pathogens.
The model put forward in Fig. 2 is tentative and
grossly simplified. It may be more applicable to
young children than to a whole community. The
complex role of immunity is not specifically
addressed in the model and, for certain pathogens, the
improvement of hygienic conditions may lead to an
increase in diarrhoea incidence rates in older age
groups. A more complete modelling of the
interrelationships between hygiene levels and
diarrhoea incidence is difficult because of the wide
differences in epidemiology and immunology among
the major diarrhoea-causing agents. This simplified
model provides some theoretical basis for the
explanation of a number of observed features of
childhood diarrhoea. We hope that it may stimulate
others to conduct studies to define more precisely the
complex reality.
The implications of Fig. 2 for diarrhoea control by
reducing pathogen ingestion are as follows. If
pathogen ingestion is reduced within the range F-E,
the incidence rates of mild or severe diarrhoea may
not change. In the range E-D, severe diarrhoea rates
may fall, but mild diarrhoea rates may not. Because
severe cases usually represent a small proportion of all
cases, surveillance of all cases may fail to detect a fall
in incidence rate in this range. For instance, if a water
supply and excreta disposal project reduced the dose
of ingested pathogens from E to D, Fig. 2 suggests
that the incidence rate of severe diarrhoea might fall
by about 44% but the incidence rate of all diarrhoea
by only about 12%. Many diarrhoeal disease studies
are unable to detect a 12% fall in total incidence rate
or to show it to be statistically significant. In the range
D-E an impact is more likely to be documented if data
on the incidence rate of severe diarrhoea (however
f The highest ratios of severe diarrhoea to all diarrhoea have been
recorded in some epidemics, which may be associated with excep
tionally high average doses of pathogens ingested by an exposed
population.
defined) are collected. Measures of diarrhoea or total
mortality are also more likely to detect an impact in
this range (see below).
In the range D-C in Fig. 2, both mild and severe
diarrhoea incidence rates are falling, and a change
may be detected by surveillance of all cases. Severity,
child growth, or mortality parameters are also likely
to change in this range. In the range C-B, only the
incidence rate of mild cases is declining but, since
most cases are mild, surveillance of all cases may
detect an impact. In the range B-A, reductions in
pathogen ingestion have no effect on diarrhoea of any
type.
This discussion of the implications of the model
presented in Fig. 2 may be restated in two other ways.
First, since it is severe episodes that lead in some
instances to death, the mild diarrhoea incidence rate
in Fig. 2 may be replaced by the total diarrhoea
incidence rate and the severe diarrhoea incidence rate
by the diarrhoea mortality rate. Diarrhoea mortality
rates may therefore be a more responsive indicator in
the range D-E or ranges overlapping with the range
D-E than diarrhoea morbidity rates. Diarrhoea
mortality rates will not, however, be a good measure
of impact in areas where oral rehydration therapy is
widely available and averts most deaths from
dehydration. Second, since there are putative
differences in IDso values, not only between degrees
of severity of diarrhoea caused by a single pathogen,
but also among different pathogens, the mild
diarrhoea incidence rate may be replaced by the
incidence rate of etiologies having low ID$o values,
and the severe diarrhoea incidence rate by the
incidence rate of etiologies having high IDJ0 values/
This model is consistent with known facts, in that
developed countries, which may lie in the range A-C,
have a small proportion of cholera and enterotoxi
genic E. coli diarrhoea (high IDso), a high proportion
of rotavirus diarrhoea (low IDso), and an
intermediate proportion of shigellosis (intermediate
ID50).f
It must be emphasized that the model presented in
Fig. 2 is hypothetical and grossly simplified. It is,
however, consistent with several established facts
and, as discussed below, it is helpful in explaining
some of the variation in the recorded impacts of water
supply and excreta disposal projects on diarrhoeal
diseases. A somewhat similar model has been
previously published (73)._____________________
d It is not implied here that pathogens having relatively low IDso
values cause relatively mild diarrhoea and vice versa. This is clearly
untrue in the cases of rotavirus and Shigella, both of which have
relatively low IDso values but cause relatively severe diarrhoea.
' This analysis probably only applies to the anthroponotic agents
mentioned here. For the zoonotic diarrhoea agents, such as
Salmonella and Campylobacter, most transmission in developed
countries is from infected animals to man via contaminated food
products, and so levels of pathogen ingestion depend more on
farming methods, food handling practices, and diet than on domestic
water supply and human excreta disposal facilities.
IMPROVING WATER SUPPLIES AND EXCRETA DISPOSAL FOR CONTROL OF DIARRHOEAL DISEASES
Hypothesis 3. Water supply or excreta disposal
improvements can reduce diarrhoea morbidity
or mortality rates among young children.
Numerous attempts have been made to measure the
impact on health of improved water supply or
sanitation. We selected for review those 67 studies
from 28 countries-^ that measured health impact in
J Studies were identified from previous reviews, supplemental
enquiries to workers in the field, computer searches in five
languages, and from unpublished papers presented at the Inter
national Seminar on Measuring the Health Impact of Water and
Sanitation Programmes, Cox’s Bazaar, Bangladesh, 21-25
November 1983 (sponsored by the International Centre for
Diarrhoeal Diseases Research, Bangladesh, and the Ross Institute,
London).
761
terms of diarrhoea morbidity, Shigella infection or
disease, cholera, Entamoeba histolytica infection,
Giardia lambda infection, nutritional anthro
pometry, diarrhoea mortality, or total mortality.
These studies are grouped in Table 1 according to the
health impact indicator measured and ordered alpha
betically by country within each group.
The data abstracted from the studies listed in Table
1 are summarized in Tables 2-5. All the studies in
Table 1 display methodological deficiencies (73, 28)
although some studies were better than others. The
total number of studies is large (67), but only a few are
reported in sufficient detail to allow an objective
assessment of their methodological and analytical
Table 1. Studies on the impact of water supply or excreta disposal on diarrhoea morbidity and mortality, enteric
infections, total mortality, and nutritional status reviewed in this paper
Indicator
Diarrhoea morbidity
Country
Reference
Bangladesh
22, 54, 74,°
24
Chile
Ethiopia
51, 88
62
82
40
Gambia
See below6
Guatemala
16, 72
79
53. 66, 67, 81
82
Colombia
Costa Rica
Egypt
Haiti
India
Iran (Islamic Rep. of)
Lesotho
86,c
37
Mozambique
See belowd
Sri Lanka
82
Saint Lucia
44,g
Sudan
6, 82
17
8, 15, 55, 64, 69, 71, 84
Kenya
United Kingdom
USA
Venezuela
Zambia
Cholera
Entamoeba histolytica
infection
82, 87
4
Philippines
22, 46, 49, 50, 54, 76, 77
3
Costa Rica
62
Egypt
India
20
59, 66
Kenya
See belowr
Libyan Arab Jamahiriya
41
15, 29, 57
Bangladesh
USA
Table 1: continued on next page
762
S. A. ESREY ET AL.
Table 1: continued
Indicator
Country
Reference
Giardia lamblia
Costa Rica
62
Egypt
India
20
66
Kenya
See belowr
Libyan Arab Jamahiriya
41
USA
29
Bangladesh
22, 48, 65“
62
infection
Shigella
infection or disease
Costa Rica
Egypt
Guatemala
India
Iran (Islamic Rep of)
Libyan Arab Jamahiriya
Venezuela
52
82
82
45. 55, 71, 78, 84
82
Panama
Sri Lanka
Sudan
USA
Nutritional status
Diarrhoea mortality
Bangladesh
See below"
Colombia
21
Fiji
See below
*
-
Nigeria
80
Philippines
See below/
Saint Lucia
See below"
Brazil
83
89
India
Total mortality
82
7
66
82
41
Brazil
Costa Rica
61
43
Sri Lanka
85
1
18
60, 63
Sudan
6
Egypt
Guatemala
Malaysia
|
Rahaman, M. M. The Teknaf Health Impact Study: methods and results. Paper presented at the International Workshop on
Measuring the Health Impacts of Water Supply and Sanitation Programmes, Cox's Bazaar, Bangladesh, 21-25 November 1983.
h PICKERING, H. The role of anthropologists in studying diarrhoea epidemiology: a case study from The Gambia. Paper presented at
the International Workshop on Measuring the Health Impacts of Water and Sanitation Programmes, Cox's Bazaar, Bangladesh, 21-25
November 1983.
FENWICK, K. W. H. The short-term effects of a pilot environmental health project in rural Africa: the Zaina scheme re-assessed
after four years, (undated manuscript).
d CAIRNCROSS, S. & Cliff, J. Water and health in Mueda, Mozambique. Paper presented at the International Workshop on
Measuring the Health Impacts of Water and Sanitation Programmes, Cox’s Bazaar, Bangladesh, 21 -25 November 1983.
YEE, V. S. Household level correlates of child nutritional status in Fiji. MPS thesis. Division of Nutritional Sciences, Cornell
University, Ithaca, New York, 1984.
1 MAGNANl, R. J. & TOURKIN, S. C. Impact of improved urban water supplies in the Philippines: methods and results. Paper
presented at the International Workshop on Measuring the Health Impacts of Water and Sanitation Programmes, Cox's Bazaar,
Bangladesh, 21-25 November 1983.
K Henry, F. J. Health impact of water and sanitation interventions in St. Lucia. Paper presented at the International Workshop on
Measuring the Health Impacts of Water Supply and Sanitation Programmes, Cox's Bazaar, Bangladesh, 21 -25 November 1983.
764
S. A. ESREY ET AL.
Table 3. Percentage reductions in diarrhoea morbidity
rates attributed to water supply or excreta disposal
improvements by adult literacy rate of the country and
magnitude of service improvement
Small service
*improvements'
Adult
literacy
rate"
(%)
No. of
results
Median
(%)
Large service
*improvements'
No. of
results
Median
(%)
<40
11
18
7
46
40-75
4
20
8
39
> 75
10
16
13
32
‘ Data on adult literacy, by country, from World development
report, 1983 (Washington. World Bank)
,p See footnote g. page 762.
anticipated that the impact on enterotoxigenic E. coli
will be considerable and on rotavirus negligible. The
latter prediction is indirectly supported by data show
ing that the incidence rate of rotavirus diarrhoea
among children under 2 years of age is 0.3-0.4
episodes per child per year in both Bangladesh (11)
and Winnipeg, Canada (42).
Impact on nutritional anthropometry. If water
supply and excreta disposal improvements reduce
diarrhoea incidence rates or duration among young
children, then nutritional anthropometric indicators
should also improve because of the inverse relation
ship between time spent with diarrhoea and child
growth (58, 68). Six studies that investigated the
relationship between water supply or excreta disposal
improvements and nutritional status are summarized
in Table 5. All six studies reported an association
between improved water supply or excreta disposal
and improved nutritional status. In two studies, in
Fiji and the Philippines, attempts to control for
extraneous risk factors reduced the differences
between the control and intervention groups, but
some of these differences were nonetheless found to
be statistically significant.
to small service-level improvements (Table 3). If a
large service-level improvement is made, the
percentage reduction in diarrhoea morbidity rates
achieved is inversely related to the pre-intervention
level of hygiene (Table 3). The greatest impact is
achieved when the pre-intervention hygiene level is
Impact on mortality. Only two studies were located
worst. For small improvements in service level,
impacts appear less dependent upon the pre that reported the impact of water supply or excreta
intervention hygiene level. These conclusions are disposal improvements on diarrhoea mortality rates
consistent with the hypothetical model depicted in (Table 1); a 41% median reduction in diarrhoea
Fig. 2 and suggest that the impact of water and mortality rate was calculated from them. Both studies
sanitation improvements depends in part on the were concerned with the impact of improved water
supplies in urban areas, and in neither was the study
presence and interaction of other risk factors.
method well described. A further eight studies
reported impacts of water supply or excreta disposal
Impact on specific infections. When impact on
improvements on mortality from all causes (Table 1),
total diarrhoea morbidity is broken down by etiology,
it is likely, as discussed above, that different specific and they indicated a 21% (range, 0-81%) median
.diarrhoeas will be reduced by different amounts.
reduction in mortality rate.
Table 4 presents data on impacts on cholera, Shigella
infection or disease, and infection by Ent. histolytica
and G. lamblia. Since the distinction between the
severe and mild diarrhoea bands in Fig. 2 is merely
one of infectious dose (ID), in ranges including D-E, Table 4. Percentage reductions in morbidity or infection
any reduction in pathogen ingestion will produce a rates of cholera. Shigella, Entamoeba histolytica, and
greater percentage reduction in the incidence rate of Giardia lamblia attributed to water supply or excreta
the high ID etiologies than the low ID etiologies. Thus disposal improvements
the impact of a water supply and excreta disposal
Percentage
improvement (in ranges including D-E) on specific
reduction
etiologies may be in the following descending order of
magnitude: cholera, enterotoxigenic E. coli, Shigella,
Median
Range
No.
of
Disease or
the protozoa, rotavirus. The relative impacts on infection
results
(%)
(%)
Shigella and the protozoa are supported by the data in
41
0-91
11
Table 4. The anomalous cholera data are discussed Cholera
48
0-81
elsewhere (31).
27
Shigella
Data on the impact of water supply and excreta Entamoeba histolytica
2
0-80
17
disposal projects on enterotoxigenic E. coli and Giardia lamblia
10
0
0-20
rotavirus incidences are not yet available, but it is
IMPROVING WATER SUPPLIES AND EXCRETA DISPOSAL FOR CONTROL OF DIARRHOEAL DISEASES
765
Table 5. Improvements in nutritional status attributed to various types of water supply or excreta disposal improve
ment
Value of indicator
Country
Nutritional
indicator"
Bangladesh
Percentage with H/A > 90% of standard
Percentage with W/A > 75% of standard
Colombia
Percentage with W/A > 90% of standard
Percentage with H/A > 95% of standard
Fiji
Age
(months)
Type of
intervention''
Control
group
Target
group
Reference
See below d
0-11
Q+A+E
75
76
12-23
Q+A+ E
50
51
24-35
Q+A+E
45
48
0-11
Q+A+E
59
63
12-23
Q+A+E
44
43
24-35
Q+A+E
47
50
6-30
E
26
47
6-30
A
22
51
6-30
E
26
48
6-30
A
20
53
21
See below
*'
Mean percentage of:
standard W/A
urban
0-59
E
102
100
rural
0-59
E
95
102
urban
0-59
E
100
100
rural
0-59
E
99
103
W/A > 75% of standard
6-59
A
50
69
H/A > 90% of standard
6-59
A
80
69
W/H > 80% of standard
6-59
A
63
90
74
75
standard H/A
Nigeria
Philippines
Saint Lucia
80
Percentage with:
See below7
Percentage with W/A > 75% of standard
pre-intervention
6-54
post-intervention
6-54
Q+A
71
80
1-3
A (A + E)
93
92 (86)f
72
90 (88)
Percentage with W/A > 90% of standard
4-6
7-9
51
78 (76)
10-12
44
76 (73)
13-15
50
76 (58)
16-18
51
74 (57)
19-21
53
75 (66)
22-24
54
79 (71)
See below
*
a W/A = weight for age; W/H = weight for height; H/A = height for age.
b Q = water quality improvement, A = water availability improvement, E = excreta disposal improvement.
c Figures not in parentheses refer to the communities receiving water availability improvements (A). Figures in parentheses refer to
communities receiving water availability improvements plus excreta disposal facilities (A + E).
d See footnote a to Table 1.
* See footnote e to Table 1.
7 See footnote / to Table 1.
* See footnote g to Table 1.
766
S. A. ESREY ET AL.
Fig. 2 predicts a larger impact on diarrhoea
mortality than morbidity over a wide range of
conditions. The impact on total mortality will depend
on the proportion of all mortality that is due to
diarrhoea and the degree to which water supply and
excreta disposal improvements affect the causes of
death other than diarrhoea. Since water supply and
excreta disposal improvements will have little impact
on some major causes of death (for instance,
respiratory infection, measles, malaria, and neonatal
tetanus), it is to be expected that the impact on
diarrhoea mortality is considerably greater than the
impact on all mortality.
Results from selected studies. For the analyses so
far, we have used pooled data from all studies listed in
Table 1 to give an overview of all documented
experiences on the impacts of water supply and
excreta disposal improvements on diarrhoea. It is
instructive to compare these findings with the results
of a few of the better studies. Criteria for judging the
quality of each study have been developed and are
reported elsewhere (28).
The first finding from this selective analysis was
that all studies that reported a negative impact were
flawed in one or more major respects. In other words,
the better studies consistently reported positive
impacts.
The best studies were on total mortality (18, 43,
60), and the median impact on total mortality rates
reported from these studies was a reduction of 30%.
Analysis for statistical interactions revealed a range
of reductions in mortality rates of 8-64%, depending
on the type of intervention and on the presence of
other risk factors, such as poor feeding practices and
low literacy rates. For example, in one study (18)
excreta disposal improvements were reported to have
a larger impact on infant mortality rates than water
supply, but the magnitudes of these impacts were
greatly affected by whether the infants were breast
fed. The impact of the environmental interventions
was greater for non-breast-fed infants than for breast
fed infants. Thus, it is likely that non-breast-fed
infants were further to the right along the horizontal
axis in Fig. 2 than were breast-fed infants. Another
study reported that excreta disposal improvements
had a greater impact on mortality in families with
literate mothers than in families with illiterate
mothers (60). This may reflect an increased ability of
literate mothers to make correct use of the new
excreta disposal facilities.
Two studies on nutritional status also examined
statistical interactions. In one/ excreta disposal was
reported to have more impact in rural than in urban
* Y EE, V. S. Household level correlates of child nutritional status
in Fiji. MPS thesis. Division of Nutritional Sciences, Cornell
University, Ithaca, New York, 1984.
areas. In the other,' water quality improvements had
an impact only among higher income households.
Studies on diarrhoea morbidity were not as well
controlled as the mortality studies referred to above.
A median reduction in diarrhoea morbidity rates of
27% (range, 0-68%) was found in the studies judged
to be most satisfactory (40, 51, 55, 71). **
''
This brief review of selected studies of superior
design leads to two conclusions. First, the median
reductions in diarrhoea morbidity rates (27%) and
total mortality rates (30%) are a little higher than the
values found by analysing all studies. Second, the
magnitude of the impact depends greatly on the
presence of other risk factors. More knowledge of
these interactions would enable the appropriate type
of intervention to be targeted to families that are
likely to benefit the most.
FEASIBILITY
Nearly all developing countries are currently
engaged in substantial programmes to improve water
supplies in both rural and urban areas. The urban
programmes date back, in many cases, to the 1920s or
earlier, while many of the rural programmes were
initiated in the 1960s. This considerable experience in
water supply programmes throughout the world has
been copiously documented (e.g., 23) and is con
tinuously monitored by WHO."1 Improved water
supplies can be provided to almost all people in al!
developing countries, and the technologies for
achieving this are, for the most part, well established.
Several problems remain, however, such as poor
operation and maintenance, inappropriate choice of
technology, inadequate revenue collection, failure to
sustain community participation, and high rates of
water leakage and wastage.
All countries have experience in excreta disposal!
MaGNANI, R. J.&TOURKIN, S. C. Impact of improved urban
water supplies in the Philippines, methods and results. Paper
presented al the International Workshop on Measuring the Health
Impacts of Waler and Sanitation Programmes, Cox’s Bazaar,
Bangladesh, 21—25th November 1983.
‘ CAIRNCROSS, S. & CLIFF, J. Waler and health in Mueda,
Mozambique. Paper presented al the International Workshop on
Measuring the Health Impacts of Water and Sanitation Programmes,
Cox’s Bazaar, Bangladesh, 21-25 November 1983.
* PICKERING, H. The role of anthropologists in studying
diarrhoea epidemiology: a case study from the Gambia. Paper
presented al the International Workshop on Measuring the Health
Impacts of Water and Sanitation Programmes, Cox’s Bazaar,
Bangladesh, 21-25 November 1983.
1 RAHAMAN, M. M. The Teknaf Health Impact Study: methods
and results. Paper presented al the International Workshop on
Measuring the Health Impacts of Waler Supply and Sanitation
Programmes, Cox’s Bazaar, Bangladesh, 21-25 November 1983.
See, for example, World Health Statistics Report, Vol. 26, No.
11, 1973; World Health Statistics Report, Vol. 29, No. 10, 1976; and
The International Drinking Water Supply and Sanitation Decade.
Review of national baseline data (as al 31 December 1980), Geneva,
World Health Organisation, 1984 (WHO Offset Publication No.85).
IMPROVING WATER SUPPLIES AND EXCRETA DISPOSAL FOR CONTROL OF DIARRHOEAL DISEASES
programmes in urban areas, in some cases dating
back thousands of years. Rural excreta disposal
programmes are typically a new phenomenon, and
some countries still lack concerted efforts in this
sector. Problems commonly encountered in excreta
disposal programmes include the inappropriate
choice of technology, poor operation and main
tenance, inadequate revenue collection, and the lack
of perception in many rural communities of the
importance of improved excreta disposal practices.
Research into the technical, economic, and social
aspects of excreta disposal in developing countries
(e.g., see 47) over the past decade has led to some
promising new approaches.
COSTS
Despite the extensive experience with water supply
and excreta disposal projects throughout the world,
the cost data on these projects are often of poor
quality and not strictly comparable. Data on
operation and maintenance costs, on institutional
overhead costs, and on the costs of community
mobilization and education, are especially deficient.
Table 6 presents cost data from 87 developing
countries. Costs vary widely depending upon the
design criteria adopted in different countries and
767
upon the costs of labour and materials. The costs of
operation and maintenance (recurrent costs) must be
added to the construction costs, and data on these
costs are not readily available. One study of excreta
disposal in 12 countries estimated that operation and
maintenance accounted for between 4% and 52% of
the total project costs per year, depending on the
technology under consideration (47). Several widely
used technologies (for instance, sewerage and pour
flush latrines) had operation and maintenance costs
that comprised approximately 30% of the total
annual project costs. For rural water supplies, data
assembled by a UNDP/World Bank project'1 suggest
that the same figure, 30%, is a reasonable estimate of
the proportion of the total annual costs taken up by
operation and maintenance. The 30% figure is
adopted in Table 6 for both water supplies and excreta
disposal." Reliable data on the costs of software
support (such as the promotion of community par" UNDP project 1NT/81/026.
” The computation of the percentage of total annual costs due to
operation and maintenance requires the adoption of a discount rate
(or opportunity cost of capital). Choosing the discount rate is partly a
matter of judgement, and different economists may advocate
different rates for the analysis of the same project. The choice of a
high discount rate (say, 20%) will reduce the apparent importance of
recurrent costs within total project costs. If a low discount rate (say,
5%) is chosen, perhaps to reflect the scarcity of recurrent funds (5),
the proportion of total costs that is attributed to operation and
maintenance will be greatly increased.
Table 6. Costs for urban and rural water supply and excreta disposal projects
Lifetime
*
(years)
Annual
construction
cost per
capita
(1982, US$)f
Annual
total
cost per
capita
(1982, USSI"
116
20
14
20
66
20
8
11
60
20
7
10
Sewerage
174
50
18
26
Other
66
20
8
11
19
10
3
4
Construction cost
per capita
(1982, US$)a
House connection
Public tap
Type of service
^Vater supply
Urban
Rural'
Sanitation
Urban
Rural
a Median values of the costs from 87 developing countries reported to WHO. For further information, see The International Drinking
Water Supply and Sanitation Decade. Review of national baseline data fas at 31 December 1980), Geneva, World Health Organization, 1984
(WHO Offset Publication No. 85).
b Commonly assumed values.
f Assuming an opportunity cost of capital (discount rate! of 10%.
d Assuming that construction costs are 70% of the total annual costs (see text).
' A variety of technologies are included here, but predominantly public taps and handpumps.
768
S. A, ESREY ET AL.
ticipation or hygiene education) and of apportioned
institutional overheads have not been located, and so
these costs, which are not trivial, have been omitted
from the calculations.
Total annual costs per capita are derived in Table 6,
assuming that recurrent costs comprise 30% of the
total annual costs, that project lifetimes are between
10 and 50 years (depending upon the technology), and
that the appropriate discount rate is 10%. The total
annual costs per capita in Table 6 may be aggregated
to derive the costs of complete water supply and
excreta disposal interventions. For instance, a rural
water supply and excreta disposal project might cost
USS 14 per capita annually (S10 + S4), whereas a
combination of in-house water and sewerage in an
urban area might have an annual cost of USS 46 per
capita (S20 + S26).
A goal of this series of reviews (38) is to derive cost
effectiveness estimates for each intervention. Special
difficulties are inherent in applying the cost
effectiveness analysis to interventions having multiple
benefits, and water supply and excreta disposal
interventions present these difficulties in an extreme
form (9, 14). In addition to their impact on diarrhoea
rates among young children, these interventions may
avert diarrhoea in other age groups, reduce the
incidence of other infectious diseases, and have a
variety of benefits unrelated to health. In view of this,
a treatment of the cost-effectiveness of water supply
and excreta disposal in relation to other diarrhoea
control measures will be left to a later publication.
CONCLUSIONS
The results in Tables 2-4 show that substantial
reductions in diarrhoea morbidity and mortality rates
can be expected from investments in water supply and
excreta disposal. Table 2 suggests that investments
that improve both water quality and availability are
especially effective. There are no adequate data on the
impact of improvements in water quality plus
availability together with excreta disposal. Likewise,
the available data do not permit an assessment of the
advantages of adding a hygiene education component
to a project, but analysis of hygiene education alone
suggests that it may further enhance the impact (34).
Taking all this evidence together, and in view of the
impact of large service-level improvements shown in
Table 3, it is possible that well-designed projects
combining water supply, excreta disposal and hygiene
education may achieve diarrhoea morbidity rate
reductions of 35-50%. It is to be expected that, in any
given project, the impact on diarrhoea mortality rates
will be larger than that on diarrhoea morbidity rates,
except in areas where other interventions, such as oral
rehydration programmes, have substantially reduced
the risk of death from diarrhoea.
This review highlights some of the deficiencies in
our knowledge of the impacts of water supply and
excreta disposal on diarrhoea. More studies of these
impacts are required, and it is expected that current
advances in methodology'’ will enable such studies to
be undertaken retrospectively and at reasonable cost.
The model discussed under hypothesis 2 suggests that
there may be advantages in measuring the impact on
severe diarrhoea rather than all diarrhoea. Where
etiology-specific studies are being conducted, they are
more likely to record impacts on diarrhoea due to
agents having high infectious doses than on diarrhoea
due to agents having low infectious doses. The most
pressing research need is to document the impact on
diarrhoea of projects that combine improvements in
water quality, water availability and excreta disposal
with hygiene education that are functioning satis
factorily and are being utilized by the intended bene
ficiaries.''
'' BRISCOE, J. ET AL. Measuring (he impacts of water supply and
sanitation projects on diarrhoea: prospects for case-control method^
(in preparation).
fl
'' Minimum evaluation procedure (MEP) for water supply ana
sanitation projects. Unpublished document WHO/ETS/83.1,
1983.
ACKNOWLEDGEMENTS
We are grateful for the constructive criticisms of earlier drafts of this paper provided by R. C. Ballance, D. Blum,
J. Briscoe, A. M. Cairncross, I. de Zoysa, B. H. Dieterich, F. L. Golladay, M. B. Grieveson, R. C. Hogan, J. S.
Koopman, L. Laugeri, D. D. Mara, M. H. Merson, R. N. Middleton, M. Phillips, M. M. Rahaman, G. Schultzberg,
S. Unakul, and A. M. Wright. Secretarial, bibliographic and editorial assistance were most ably provided by Caprice
Mahalla, Susanne O’Driscoll, and Dianne Fishman.
IMPROVING WATER SUPPLIES AND EXCRETA DISPOSAL FOR CONTROL OF DIARRHOEAL DISEASES
769
RESUME
LA LUTTE CONTRE LES MALADIES DIARRHEIQUES DU JEUNE ENFANT: INTERVENTIONS VISANT A AMELIORER
L’APPROVISIONNEMENT EN EAU ET L'ELIMINATION DES EXCRETA
Cei article esi le neuvieme d’une serie d’analyses
consacrees aux mesures possibles pour lutter contre les
diarrhees. Dans les pays en developpemenl, 1’impact des
projeis d’approvisionnemem en eau et d’evacuation des
excreta sur les maladies diarrheiques a 6te au centre de tres
nombreuses discussions et recherches. Quelques observa
tions donnent a penser que des ameliorations portant sur la
qualite de 1’eau, 1’approvisionnement en eau, 1’hygiene
individuelle et 1’evacuation des excreta, reduiraient
1’ingestion des agents pathogenes a 1’origine de diarrhees.
On expose ici un modele theorique qui etablit une relation
entre la quantite ingeree d’agents pathogenes responsables
de diarrhees et la frequence de ces affections dans la
communaute.
Ce modele montre que, dans des communaul6s pauvres,
mal approvisionnees en eau et ou 1’evacuation des excreta se
fail de fa?on insalubre, la diminution de la quantite d’agents
enieropaihogenes ingeree exerce, a valeur 6gale, un impact
plus grand sur les taux de mortalite que sur ceux de
morbite. Elie ameloire davantage les diarrhees graves que
les diarrhees benignes et plutot cellos dont les agents etiologiques agissent a dose elevee.
Le recensement de 67 etudes effectuees dans 28 pays
permet d’analyser 1’impact de 1’approvisionnement en eau et
de 1’evacuation des excreta sur les maladies diarrheiques, les
infections apparentees, 1’etat nutritionnel et la mortalite.
Toutes ces eludes montrent une diminution mediane de 22%
des taux de morbidite associes aux maladies diarrheiques, la
diminution atteignani 27% dans quelques etudes mieux
con?ues: pour le taux de mortalite global, la diminution
mediane a ete de 21%, atteignani 30% dans les quelques
eludes mieux contjues. L’ameiioration de la qualite de 1’eau
importante moins que celle de 1’approvisionnement ou de
1’evacuation des excreta. Mieux vaut ameliorcr la qualite de
1’eau et 1’approvisionnement qu’un seul de ces elements ou
que I’eiimination des excreta. Les projets d’approvisionnement en eau et d’evacuation des excreta ont un impact plus
important sur la shigellose que sur les infestations a
Entamoeba histolytica ou a Giardia lambda, mais on ignore
quelles peuvent en elre les repercussions sur les diarrhees
causees par Escherichia coli enterotoxigene ou les rotavirus.
Les six etudes portant sur les repercussions de 1’approvision
nement en eau ou de 1’evacuation des excreta sur 1’etat
nutritionnel ont fait etat d’une amelioration.
L’article presente ensuite une analyse des donnees sur les
couts de construction pour les projets d’approvisionnemem
en eau et d’assainissement dans 87 pays en developpemenl.
Si 1’on ajoute les couts d’exploitation et d’entretien, sans
tenir compte des couts lies a la mobilisation et a reducation
de la communaute ni des frais generaux institutionnels, on
arrive a un total median de 14-46 dollars E.-U. (prix de
1982) par tete, selon 1’importance du service.
Il faudra effectuer davantage d’etudes concernant
1’impact des projects d’approvisionnemem en eau et
d’evacuation des excreta sur les maladies diarrheques. En
lout premier lieu, on etudiera 1’impact de projeis combi
nant une amelioration de la qualite de 1’eau, de 1’appro
visionnement en eau et de 1’evacuation des excreta A une
education en matiere d'hygiene, en s’imeressant & des
installations qui donnent satisfaction et sont effectivemenl
utilisees par les personnes visees.
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CH 3H
Bulletin oj the B arid Health Organization. 63 (3): 569-583 (1985)
fc> World Health Organization 1985
Interventions for the control of diarrhoeal diseases
among young children: rotavirus and cholera
*
immunization
I. deZoysa1 & R. G. Feachem*12
The potential effects of rotavirus and cholera immunization (with an improved
vaccine) on diarrhoea morbidity and mortality among young children are reviewed using
data from field studies and theoretical calculations. In developing countries rotavirus may
be responsible for about 6% of all diarrhoea episodes and 20% of all diarrhoea deaths in
children under 5 years of age. In industrial countries these proportions may be higher.
Rotavirus immunization may reduce overall diarrhoea morbidity rates by 2-3 % and
diarrhoea mortality rates by 6-10% among children under 5 years of age in developing
countries, depending on vaccine efficacy and programme coverage. The impact of
improved cholera vaccines depends on the prominence of cholera as a cause of diarrhoea,
and this varies greatlyfrom country to country. Taking the extreme example of Bangladesh,
where cholera is endemic and may account for about 0.4% of all diarrhoea episodes and 8 %
of all diarrhoea deaths in children under 5 years ofage, cholera immunization might reduce
overall diarrhoea morbidity rates by 0.06-0.13 % and diarrhoea mortality rates by 1-2%
among these children. The similar incidence rates in industrial and developing countries
suggest that rotavirus diarrhoea may not be controlled by improvements in water supply,
sanitation, or hygiene. Control may depend upon the widespread use of an effective
vaccine.
Over recent years substantial resources have been
invested into research to develop a vaccine against
rotavirus diarrhoea and an improved vaccine against
cholera. Rapid progress has been made and field trials
of candidate vaccines against these diseases are under
way. It is timely, therefore, to examine the potential
role of rotavirus and cholera immunization in
national programmes to reduce diarrhoea morbidity
and mortality among children under 5 years of age. In
this review we do not examine the potential benefits of
rotavirus and cholera immunization that might
extend to older children, adults, or especially
susceptible or at-risk groups, nor do we consider the
potential role of cholera immunization in epidemic
control. Several recent reviews on the epidemiology
and control of rotavirus diarrhoea (41, 83) and
cholera (13, 16, 17, 33, 46) provide a useful back
ground to this more focused analysis. This paper is
the seventh in a series of reviews of potential anti
• Requests for reprints should be addressed to the Director,
Diarrhoeal Diseases Control Programme, World Health
Organization, 1211 Geneva 27, Switzerland.
1 Save the Children Fund Research Fellow, Department of
Tropical Hygiene, London School of Hygiene and Tropical
Medicine, Keppel Street, London WC1E 7HT, England.
2 Head, Department of Tropical Hygiene, London School of
Hygiene and Tropical Medicine, London, England.
4555
diarrhoea interventions published in the Bulletin of
the World Health Organization (1, 15, 18-22).
EFFECTIVENESS
For rotavirus or cholera immunization to be an
effective intervention for the control of diarrhoeal
diseases it must be true that:
either
a considerable proportion of
diarrhoea morbidity or mortality
in young children is caused by
rotavirus or Vibrio cholerae 01
hypothesis
1
and
vaccines against rotavirus,
V. cholerae 01, or their products
have the potential to reduce
morbidity rates or mortality rates
or the severity of diarrhoea caused
by these organisms
-569-
hypothesis
2
570
I. DE ZOYSA & R G. FEACHEM
rotavirus or cholera immunization
(when effective vaccines are avail
able) has the potential to reduce
overall diarrhoea morbidity rates
or mortality rates or the severity
of diarrhoea in young children
diarrhoea. The data in Table 1, as far as possible,
refer only to episodes where rotavirus was the sole
recognized enteric pathogen. In some studies, stools
were not examined for some common pathogens such
as enterotoxigenic Escherichia coli (ETEC) (49) and
Campylobacter jejuni (6, 7, 31, 49, 68).
Recorded incidence rates of rotavirus-associated
diarrhoea ranged from 0.2 to 0.8 episodes per child
per year. Incidence rates were low in children aged 0-5
months, reached a peak in children aged 6-11
months, remained high in children aged 12-23
months, and dropped to low levels thereafter. It is
notable that the incidence rate of rotavirus-associated
diarrhoea found in the study from Winnipeg, Canada
(0.3 episodes per child per year among children aged
0-23 months) (31) was similar to the rate reported
from Bangladesh in the same age group (0.4 episodes
per child per year) (6). The incidence of all
diarrhoeas, however, was lower in Canada and the
proportion of diarrhoea episodes associated with
rotavirus was accordingly higher.
We estimate that, in developing countries,
rotavirus accounts for about 8% of all diarrhoea
episodes in children aged 0-5 months, 10°7o in
children aged 6-23 months, 1% in children aged
24-59 months, and 6% in children under 5 years.
These figures are used in the computations below. In a
particular country, where more reliable age-specific
proportions are available, other figures may be
substituted. It will be noted that the incidence rate of
rotavirus-associated diarrhoea found in different
studies (Table 1) did not vary as much as the incidence
hypothesis
3
The potential effectiveness of rotavirus or cholera
immunization in the control of diarrhoeal diseases
would be suggested by a demonstration either of the
correctness of hypotheses 1 and 2, or of the correct
ness of hypothesis 3. The evidence for and against the
three hypotheses is examined below.
Hypothesis 1. A considerable proportion of
diarrhoea morbidity or mortality in young children is
caused by rotavirus or V. cholerae Ol.
Rotavirus
Rotavirus-associated morbidity. We have located
in the literature only 7 prospective, community-based
studies that have assessed the importance of rotavirus
diarrhoea among children in the community (Table
1). Four studies (6, 7, 31, 49) report the incidence
rates of rotavirus-associated diarrhoea and rotavirus
isolation rates, and three others (30, 53, 68) give only
the isolation rates. Multiple infections were common
in all the studies: other enteric pathogens were detec
ted in up to half of all episodes of rotavirus-associated
Table 1. Community-based studies of rotavirus-associated diarrhoea
Country
Bangladesh
Bangladesh
Age
(months)
Number of
person-years
Number of episodes of:
Diarrhoea
from all
causes
Diarrhoea
associated with
rotavirus alone
Proportion of
diarrhoea episodes
associated only
with rotavirus
(%)
Reference
6
0-23
112
377 (3.4)"
43 (0.4)
11
24-59
112
243 (2.2)
0
0
7
2-23
77
497 (6.4)
32 (0.4)
6
24-59
92
444 (4.8)
3 (0.03)
0.7
Brazil
All ages
765
1097 (1.4)
- <0.151“
11
30
Canada
0-23
139
165 (1.2)
40 (0.3)
24
31
El Salvador
0-35
-
-
-
7
68
Guatemala
0-35
132
1050 (7.9)
109 (0.8)
10
49
USA
0-23
-
-
-
10
53
" Figures in parentheses are the number of episodes per person-year.
“ Estimated incidence rate.
rotavirus and cholera immunization for control of diarrhoeal diseases in children
rate of diarrhoea from all causes. The proportion of
all diarrhoea episodes attributable to rotavirus is
likely to be greater than our estimate in settings where
the incidence rate of diarrhoea from all causes is low,
and smaller where the incidence rate of diarrhoea
from all causes is high.
To assess the impact of rotavirus diarrhoea on the
health services, rotavirus isolation rates reported in 77
hospital-based studies from 37 countries have been
reviewed." Caution is necessary in the interpretation
and comparison of these rates. Different diagnostic
methods were used for the detection of rotavirus and
the findings were reported in different age groups.
Many studies did not span an entire year, and large
seasonal fluctuations in rotavirus isolation rates are
well documented. Bearing these factors in mind, we
see that in nearly all the studies rotavirus was the
single most common enteric pathogen identified in
children attending hospital for the treatment of
diarrhoea.
In studies of hospitalized children that lasted at
least one year, the median isolation rate was 34%
(range, 12-71%). The median rate was similar in
studies from developing and industrial countries
(respectively, 35% and 34%; with ranges, 16-71%
and 12-65%). In general, the age-specific isolation
rates were low in infants aged 0-5 months, reached a
peak in infants aged 6-11 months, remained high in
children aged 12-23 months, and dropped rapidly
thereafter. Because a considerable proportion of all
diarrhoea cases that are admitted to hospital occur in
infants, most rotavirus-positive cases were found in
this age group. Indeed, in a number of studies, large
numbers of rotavirus-positive cases were found
among hospitalized children aged 0-5 months,
despite low isolation rates in this age group. Among
the 19 studies that reported these data the proportion
of all rotavirus-positive cases among hospitalized
children aged 0-23 months that occurred in the first 6
months of life ranged from 4% (62) to 73% (57), with
a median of 35%. We have located only 5 studies in
which the data are examined in narrower age-bands.
In these studies, the proportion of all rotavirus
positive cases among infants (0-11 months) admitted
to hospital for diarrhoea that occurred in the first 3
months of life ranged from 11% to 37%, with a
median of 26% (2, 36, 57, 58, 74).
Studies conducted among children treated for
diarrhoea on an outpatient basis or in short-stay
rehydration units reported lower rotavirus isolation
rates. In studies that lasted at least one year the
median rate found among these patients was 28%
(range, 10-49%). Where outpatients and inpatients
were examined concurrently the rates were found to
" Tabulated data and sources arc available on request from
R.G.F.
571
be lower among outpatients. This finding is difficult
to interpret because the two groups of patients were
not strictly comparable in all studies (S).
Two studies have assessed population-based
hospital case rates. In Washington, DC, USA (66), a
population of about 29 000 children aged 0-14 years
was defined whose primary health care was provided
by a health maintenance organization. Over a period
of 27 months, 38 children from the health mainten
ance organization were admitted to hospital for the
treatment of diarrhoea. Rotavirus was recovered
from 60% of cases. Yearly population-based
hospitalization
rates
for rotavirus-associated
diarrhoea were 3.7 per thousand in infants and 2.2 per
thousand in children aged 12-23 months, and
dropped to 0.2 per thousand in children aged 24-59
months. Hospitalization for rotavirus-associated
diarrhoea was not observed after 5 years of age. In a
district of Copenhagen County, Denmark (32),
rotavirus was detected among 37% of children aged
0-14 years admitted to the district hospital because
of diarrhoea over a 12-month period. Yearly
population-based hospitalization rates for rotavirusassociated diarrhoea were 5.4 per thousand in infants,
4.1 per thousand in children aged 12-23 months, and
1.4 per thousand in children aged 24-47 months. No
admissions for rotavirus-associated diarrhoea were
observed in children over 4 years of age.
Thus, despite low isolation rates in the community,
rotavirus is responsible for about one-third of
diarrhoea episodes that require hospital admission
among young children, suggesting that diarrhoea
caused by rotavirus is of above-average severity.
Prospective studies of diarrhoea episodes acquired in
the community provide evidence that rotavirusassociated diarrhoea leads more frequently to
dehydration and attendance at a health facility than
all other diarrhoeas in the same age group (6, 7, 49,
81). In these studies, although the incidence of
rotavirus-associated diarrhoea was low, rotavirus was
responsible for about half of all dehydrating
episodes.
Rotavirus-associated
mortality.
Rotavirusassociated diarrhoea may therefore take on severe
forms and is clearly responsible for a proportion of all
deaths due to diarrhoea. Diarrhoea mortality rates
are low in industrial countries, yet fatal episodes of
diarrhoea associated with rotavirus have been
described. Over a 5-year period, 21 deaths associated
with rotavirus were recorded among young children
in Toronto, Canada (10). The severe course of the
diarrhoea was highlighted by the fact that all deaths
occurred within 3 days of onset of symptoms and that
the parents of 16 of the children had had some contact
with a physician during the course of their child’s
illness. Similarly, in the course of an explosive
I. DE ZOYSA & R. G. FEACHEM
572
Table 2. The proportion of diarrhoea deaths in the first five years of life associated with rotavirus in developing
countries, based on various assumptions
Age
(months)
Distribution of
100 diarrhoea
deaths"
Proportion that
are acute watery
diarrhoea deaths'1
(%)
Number of
acute watery
diarrhoea deaths
Proportion of acute
watery diarrhoea deaths
that are associated with
rotavirusc
(%)
Number of
rotavirus-associated
diarrhoea deaths
0-5
29
60
17
20
3.4
6-11
16
60
10
50
5.0
12-23
35
60
21
50
10.5
24-59
20
50
10
10
0-59
100
1.0
19.9
58
° These calculations assume that diarrhoea mortality rates are 20 per 1000 per year in the 0-11 -month age group, 18 per 1000 per
year in the 12-23-month age group, and 4 per 1000 per year in the 24-59-month age group (derived from ref. 67}. Overall mortality
rates vary greatly from country to country. Values adopted here are: infant mortality rate 120 per 1000 live births, mortality rate 40
per 1000 per year in the 12-23-month age group, and 10 per 1000 per year in the 24-59-month age group. It is further assumed that
66% of infant diarrhoea deaths occur in the first 6 months of life (the median figure from 8 studies).
* Estimates based on data from Oberle et al (60) and Chen et al. (72).
c Estimates based on data in the text on the proportion of hospitalized diarrhoea cases and the proportion of dehydrated diarrhoea
cases seen in the community, which were associated with rotavirus.
outbreak of 3439 reported cases of rotavirusassociated diarrhoea in an isolated Pacific island
group (24), 7 children died, all from dehydration due
to diarrhoea and vomiting and all within the first 4
days of illness.
For developing countries, where mortality due to
diarrhoea is considerable (67), we have theoretically
derived the proportion of all diarrhoeal deaths that
are associated with rotavirus. On the basis of the
calculations set out in Table 2, rotavirus may, in dev
eloping countries, account for about 12% of all
diarrhoea mortality in infants aged 0-5 months, 30%
in children aged 6-23 months, 5% in children aged
24-59 months, and 20% in children under 5 years.
Cholera
The prominence of cholera varies greatly from
country to country. In this review we consider the
extreme case of Bangladesh, where cholera is endemic
and has been studied intensively over a number of
years.
Cholera morbidity in Bangladesh. Table 3 sum
marizes data from six studies from Dhaka and Matlab
Table 3. Community-based studies of cholera in Bangladesh
Place
Dates of
study
Age
groups
Cholera
incidence rate
(episodes per
1000 per
year)
Proportion of
diarrhoea episodes
associated with
V. cholerae 01
(%)
Dhaka
Sep. 75
to Dec. 76
All ages
3
0.7
Matlab
Nov. 63
to June 66
0-59 months
All ages
10
3
0.7
Matlab
July 69
to June 70
0-11 months
1 2-59 months
All ages
0
9
3
—
—
—
56
Matlab
Dec. 77
to Nov. 78
0-23 months
2-9 years
—
—
< 2"
< 3"
6
Matlab
March 78
to March 79
2-59 months
-
0.3
7
Reference
54
50
This proportion refers to alt infections with enteric pathogens other than ETEC. Shigetla and rotavirus, and to mixed infections.
ROTAVIRUS AND CHOLERA IMMUNIZATION FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
573
Table 4. Vibrio cholerae isolation rates among diarrhoea cases in hospitals in Bangladesh
Dates of
study
Type of
patient
Age
groups
V. cholerae 01
Dhaka
July 64
to June 66
Inpatients
All ages
40
48
Dhaka
Dec. 79
to Nov. 80
Outpatients
and inpatients
0-11 months
12-59 months
All ages
1
6
6
69
Matlab
Nov. 63
to June 66
Inpatients
All ages
25
50
Matlab
July 69
to June 70
Outpatients
and inpatients
All ages
27
56
Matlab
Jan. 75
to Dec 75
Inpatients
0-11 months
12-59 months
All ages
1
27
28
60
Matlab
Feb. 77
to Jan. 79
Outpatients
and inpatients
0-23 months
2-9 years
All ages
2
31
13
5
Place
in which surveillance of cholera was conducted in the
community. Three studies recorded cholera incidence
rates, which were very low at 3 episodes per thousand
per year. Rates were highest in children aged 12-59
months and lowest in infants. Overall, the proportion
of all diarrhoea episodes associated with V. cholerae
O1 was less than 1%. For the computations that
follow it will be assumed that, in Bangladesh, cholera
accounts for O.S^o of diarrhoea episodes in children
under 2 years of age, 0.6% in children aged 24-59
months, and 0.4% in children under 5 years of age.
Table 4 lists the V, cholerae O1 isolation rates
reported in hospital-based studies conducted in
Dhaka and Matlab. The proportion of diarrhoea
episodes associated with V. cholerae ranged from 6%
to 40% according to the hospital and the year of
study. We cannot tell from these data whether the
V. cholerae isolation rates were lower in outpatients
than inpatients, but there is evidence to suggest that
patients presenting to hospital with cholera have a
greater risk of moderate or severe dehydration requir
ing inpatient therapy than other patients (5, 69).
V. cholerae isolation rates were low in the first 2 years
of life and reached a peak in children over 5 years of
age.
Three studies have assessed population-based
hospital case rates. Martin et al. (48) analysed the
admissions to the Dhaka diarrhoeal diseases hospital
between July 1964 and June 1966 and found a
hospitalization rate for classical cholera of 0.4
admissions per thousand population per year with a
peak rate of 0.7 per thousand per year in children
below 5 years of age. The hospitalization rate for
Reference
isolation rates
(%)
cholera (mainly eltor) in the same hospital was 1.7
admissions per thousand population in 1974 and 1.4
in 1975 (44), with the highest rates in children aged
2-9 years. Glass et al. (25) examined the attendance at
Matlab hospital for the 15-year period between
January 1966 and December 1980. In that period,
V. cholerae O1 was isolated from 7141 of the more
than 50 000 patients who presented to the hospital
with diarrhoea. From 1966 to 1973, 97% of the
V. cholerae isolates were of the classical biotype. The
eltor biotype was first identified in the Matlab area in
1969 and was the only biotype present from 1973 to
the end of the study. There was great year-to-year
variation in the number of cases, particularly during
the eltor period. The overall attendance rate for
cholera in the classical period was 1.3 patients per
thousand per year and in the eltor period 2.9 patients
per thousand per year, with the highest rates in
children aged 2-9 years.
Cholera, then, presents an extreme case of a diar
rhoeal disease that is rare in the community but may
nevertheless place a considerable burden on the health
services. In a study conducted in Matlab (50), cholera
accounted for only 0.7% of all diarrhoea episodes
acquired in the community, yet 25% of all hospital
admissions for treatment of diarrhoea during the
same period were associated with V. cholerae. Other
data from Bangladesh indicate that the proportion of
cholera cases that require hospitalization varies
between 23% and 74% and is higher for classical than
for eltor cholera (3, 42-44, 61, 78, 79). These
findings support the view that cholera is an unusually
severe disease.
574
l.DEZOYSA&R G. FEACHEM
Cholera mortality in Bangladesh. There are no data
on cholera mortality rates in Bangladesh. In the study
areas, deaths due to acute diarrhoea are very rare in
hospital and those that occur in the community have
no etiological diagnosis. For the computations that
follow it will be assumed that, in Bangladesh, cholera
accounts for 5% of diarrhoea deaths in children
under 2 years of age, 20% in children aged 24-59
months, and 8% in children under 5 years of age.
These estimates are based on data summarized in
Table 4 on the proportion of hospitalized diarrhoea
cases that is associated with V.cholerae in different
age groups in Bangladesh.
Hypothesis 2. Vaccines against rotavirus, V.cholerae
Ol, or their products have the potential to reduce
morbidity rales or mortality rates or the severity of
diarrhoea caused by these organisms.
Rotavirus vaccines. Mechanisms of immunity to
rotavirus and advances in rotavirus vaccine develop
ment have recently been reviewed (41). To date,
research has focused on the development of live
attenuated human rotavirus vaccines, live rotavirus
vaccines from animal hosts, and live attenuated
reassortant vaccines, for delivery by the oral route.
Each of the four recognized human rotavirus sero
types has now been successfully cultivated (85), and
live attenuated human rotavirus vaccines can be
prepared by conventional tissue-culture methods. A
tissue-culture-adapted mutant of the Wa strain of
human rotavirus (82) is under evaluation for
immunogenicity and safety in susceptible volunteers
(39,40). Cold-adapted strains of human rotavirus are
also under investigation as attenuated human
rotavirus vaccines (Kono, personal communication,
1984). In addition, strains obtained from
asymptomatically-infected neonates are under study
as naturally attenuated strains (Bishop, personal
communication, 1984). These strains are promising
candidate vaccines in view of the evidence that
immunity induced by neonatal infection prevents the
development of clinically severe illness for at least the
first 3 years of life (although it does not protect
against infection) (4).
Another approach is to prepare vaccine material
from animal rotavirus strains that are antigenically
related to human rotavirus (35, 38, 84). Bovine rota
viruses grow well in tissue culture (51) and have been
used to prepare candidate vaccines. The feasibility of
this approach was demonstrated in experimental
studies in animals (80, 86, 88). A rotavirus vaccine of
bovine origin (strain RIT 4237) was shown to be
immunogenic and safe in young children (75) and a
field trial in a group of Finnish children aged 8-11
months using one dose of vaccine of high titre
(1O8 iTCIDso) showed a protective efficacy of 50%
for all rotavirus-associated diarrhoea and of 88% for
rotavirus-associated diarrhoea lasting more than 24
hours (76). In a subsequent trial in which 2 doses of
vaccine were given one month apart to Finnish
children aged 6-12 months, vaccine efficacy was
found to be 58% for all rotavirus-associated diar
rhoea and 82% for rotavirus-associated diarrhoea
that was clinically significant (Vesikari, persona!
communication, 1984). Infants who seroconverted
appeared to have the highest level of protection, but
protection was also observed in infants who did not
seroconvert. Seroconversion rates may be improved
by giving a milk feed (infant formula or diluted cow’s
milk) immediately before and after vaccination (77).
Further field trials with this vaccine are under way in
Peru and the Gambia. Another promising candidate
vaccine is a rhesus rotavirus strain (70, 84) which has
been tested for immunogenicity and safety in human
volunteers and is now under field trial in the USA.
Finally, reassortant viruses have been recovered from
mixed tissue-culture infection (27-29), opening the
way to the development of a live attenuated
reassortant rotavirus vaccine.
In conclusion, good progress has been made in the
development of candidate rotavirus vaccines using
different approaches. Further candidate vaccines
may be developed using recombinant DNA tech
nology. Field trials of rotavirus vaccines of bovine
and simian origin are under way. These vaccines
appear to prevent or modify rotavirus-associated
illness. Studies in progress will assess the duration of
protection induced by these vaccines and their strain
specificity. The optimal age of vaccination must be
determined, bearing in mind the need to vaccinate
infants in the first 6 months of life, and the possible
interference of breast-feeding or of residual maternal
antibodies on seroconversion rates. Information is
also needed on the number of doses required in order
to determine the most appropriate vaccination
schedule, with regard to production and delivery costs
and eventual combination with oral polio vaccine.
Other issues to be addressed concern the stability of
the rotavirus vaccine, its cold-chain requirements,
and its possible interaction with oral polio vaccine.
Cholera vaccines. Advances in cholera vaccine
development have recently been reviewed (46). The
ideal antigenic composition of an effective oral
cholera vaccine is not at present known (13) and work
is under way to identify the major protective somatic
and toxin-derived antigens. The only vaccines
currently available for general use are killed whole
cell vacci'nes for parenteral administration. Field
trials with these vaccines have established that
induced protection is moderate (50-70%) and of
short duration (3-6 months), depending on the age
group, quality of the vaccines, and dosage schedule
ROTAVIRUS AND CHOLERA IMMUNIZATION TOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
(23). Current research efforts are centred on the
development of a cholera vaccine for oral use, in
order to stimulate local intestinal immunity and to
avoid a possible suppressive effect of parenteral
immunization on local antigenic stimulation (64, 87).
Whole-cell vaccines taken orally afford some (56%)
degree of protection against experimental cholera and
reduce the severity of diarrhoea in ill volunteers (//;
Levine, personal communication, 1984). A whole-cell
vaccine for oral use is currently under field trial in
Bangladesh. Another killed oral vaccine has been pre
pared by ultrafiltration of the culture supernatant of
two eltor strains of y. cholerae OI. Results from a
field trial in Zaire suggest that this vaccine may have
protective properties against natural disease.
*
The immunogenicity and efficacy of toxin
derivatives have also been evaluated. Field trials of
parenterally administered toxoids, consisting of
purified cholera toxin inactivated with either
formaldehyde or glutaraldehyde, have demonstrated
slight or no protection against cholera (14, 59). In
volunteers, large, multiple oral doses of purified
toxoid are safe and immunogenic but have failed to
provide protection against experimental challenge
(45). Procholeragenoid, a heat-induced aggregate of
cholera toxin (46) and the purified B subunit of
cholera toxin (26, 72) are safe and immunogenic in
volunteers but their protective effects have not yet
been reported.
Animal studies have shown that antibacterial and
antitoxic intestinal antibodies are synergistically
protective (63, 65 , 71), suggesting that a vaccine
prepared from a combination of somatic and toxinderived antigens holds promise. One approach is to
develop attenuated K. cholerae strains for use as oral
vaccines. Studies have been carried out on Texas StarSR, an attenuated strain derived by chemical
mutagenesis from an eltor Ogawa organism (34).
Texas Star-SR produces the B subunit of cholera
toxin but no detectable A subunit. In US volunteers it
was shown to provide a moderate (61%) degree of
protection against experimental challenge with
V'.cholerae and to reduce the stool volume in ill
vaccinees (47). Unfortunately, 24% of vaccinees had
mild or moderate diarrhoea. Of further concern is the
fact that the precise genetic lesion responsible for the
inability of the strain to elaborate cholera toxin is
unknown, and reversion is theoretically possible.
Recombinant DNA techniques have been applied
to develop attenuated K cholerae oral vaccine strains
incapable of genetic reversion (37, 52). Precise
deletions of the genes encoding both the A and B
subunits of cholera toxin have produced a strain
b Bwanga, M. [First controlled trials of oral anticholera
vaccine during a cholera epidemic in the zone of Matemba — Nkulu
(Shaba-Zaire).] Bulletin de la Social# de Pathologie dxotique, 77:
13-16 (1984) (in French).
575
(JBK-70) that protects volunteers from subsequent
challenge to a degree (89%) similar to recovery from
the disease (46). This strain, however, was also
associated with diarrhoea in an unacceptable propor
tion of recipients. Research is under way to identify
the factors responsible for the observed side-effects.
Another approach is to prepare an oral killed
vaccine containing a combination of somatic and
toxin-derived antigens. Studies in volunteers of
vaccines prepared from killed whole-cell vibrio com
bined with procholeragenoid or glutaraldehydetreated toxoid have demonstrated complete safety
and protective efficacy ratesof27% (with procholera
genoid) and 67% (with toxoid) (46). A combined B
subunit and killed whole-cell oral vaccine has been
shown to be safe in volunteers in Bangladesh and
Sweden, and capable of inducing in Bangladeshi
volunteers a local immunological response com
parable to that evoked by the disease (73).
Subsequent challenge studies among US volunteers
demonstrated a vaccine efficacy of 64% and complete
protection against severe disease (46). Field trials of
the combined B subunit/whole-cell vaccine and
whole-cell vaccine alone are in progress in Bangladesh
to determine the protective efficacy of the vaccines
and the duration of protection in an endemic area. A
number of issues remain unresolved, as with rotavirus
vaccine, concerning especially the influence of age,
breast-feeding practices, and residual maternal anti
bodies on protection.
Hypothesis 3. Rotavirus or cholera immunization
(when effective vaccines are available) has the
potential to reduce overall diarrhoea morbidity rates
or mortality rates or the severity of diarrhoea in
young children.
At present, the only approach to assessing hypothe
sis 3 is a theoretical one using information computed
during the assessment of hypotheses 1 and 2.
Rotavirus immunization. The potential impact of
rotavirus immunization on overall diarrhoea rates in
children under 5 years will depend upon the age of
immunization, vaccine efficacy, and programme
coverage. The recommended vaccination schedule
will be determined when data are obtained on dose
requirements, the effect of breast-feeding and
residual maternal antibodies, and the effect of inter
action with antigens delivered in the context of the
Expanded Programme on Immunization (EPI). The
goal of rotavirus immunization programmes will be
to vaccinate children as early as possible, but
operational and immunological factors may prevent
the achievement of full immunization before 6
months of age. Field trials of the RIT 4237 rotavirus
vaccine in Finland have shown efficacies of 50-58%
576
I. DU ZOYSA & R. G. FEACHEM
Table 5. Maximum impact of rotavirus immunization on diarrhoea morbidity and mortality rates among children
under 5 years of age in developing countries, assuming 100% vaccine efficacy, 100% programme coverage, and an
average age of full immunization of 6 months'7
Age
(months)
Proportion of diarrhoea episodes
Caused by
rotavirus"
(%)
Proportion of diarrhoea deaths
Averted by
rotavirus
immunization
(%)
Caused by
*
rotavirus
(%)
Averted by
rotavirus
immunization
(%)
0 5
8
0'1
12
0"
6-23
10
10
30
30
24 59
1
1
5
5
0-59
6
5'-
20
16'
" The computed proportions of episodes and deaths averted are directly proportional to the vaccine efficacy and the programme
coverage, and thus the effects of different values for these parameters may be readily computed.
h See text.
' See Table 2.
'' Average age of full immunization assumed to be 6 months.
*‘ These calculations assume that diarrhoea morbidity rates are 3 per child per year in the 0-5-month age group, 4 per child per
year in the 6-11-month age group. 4 per child per year in the 12-17-month age group, 3 per child per year in the 18- 23-month age
group, and 2 per child per year in the 24-59-month age group (derived from ref. 67).
' Based on age-specific diarrhoea mortality rates given in footnote a to Table 2.
against all rotavirus-associated diarrhoea and
82-88% against rotavirus-associated diarrhoea of
clinical significance in children aged 6-12 months (76;
Vesikari, personal communication, 1984). In an
ongoing immunization programme aimed at younger
children the efficacy rates may be lower. An efficacy
of rotavirus vaccine of 80% is assumed here. The
proportion of children who would receive the vaccine
depends on programme coverage. Three coverage
figures are adopted here (45%, 60% and 75%),
bearing in mind that these figures are not now being
achieved in countries with limited immunization
programmes, but may be expected in countries
committed to the EPI and with a national programme
built up over several years.
The proportions of all diarrhoea cases and deaths
averted by rotavirus immunization are directly pro
portional to both vaccine efficacy and programme
coverage, but not to age of immunization. Table 5
presents computations of the maximum impact of
rotavirus immunization at 6 months of age on overall
diarrhoea morbidity and mortality rates in developing
countries, assuming 100% efficacy and 100% pro
gramme coverage. Under these ideal conditions, rota
virus immunization might reduce diarrhoea
morbidity rates by 5% and diarrhoea mortality rates
by 16% among children under 5 years of age. With a
vaccine having 80% efficacy and levels of coverage of
45%, 60% and 75%, rotavirus immunization might
reduce diarrhoea morbidity rates, respectively, by
1.8%, 2.4% and 3.0% and diarrhoea mortality rates
by 6%, 8% and 10%. If immunization against
rotavirus is completed at a younger age, say 3 months,
the potential reductions in diarrhoea morbidity and
mortality rates may only be marginally greater:
1.9-3.3% for morbidity and 6-11% for mortality
(assuming that half of the diarrhoea episodes and
deaths that occur in the first 6 months of life occur in
the first 3 months of life; calculations not shown).
The proportional impact of rotavirus immunization
on diarrhoea morbidity rates among young children
in industrial countries is likely to be greater because
the proportion of diarrhoea episodes attributable to
rotavirus in those countries is higher. The difference
may not be marked for reductions in mortality rates,
however, judging from the similar isolation rates for
rotavirus found among young children admitted to
hospital for severe diarrhoea in developing and
industrial countries.
Two major hospital-based studies have been
examined to assess the potential reduction in hospital
reporting rates for diarrhoea that might be achieved
by a rotavirus immunization programme. Data from
a one-year study of patients reporting to the
diarrhoeal diseases hospital in Dhaka, Bangladesh
(69) suggest that rotavirus immunization might have
averted 7-12% of attendances for diarrhoea to the
hospital among children under 5 years of age. Data
from an 8-year study of inpatients in a children’s
hospital in Washington, DC, USA (9) suggest that
ROTAVIRUS AND CHOLERA IMMUNIZATION FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
577
Table 6. Maximum impact of cholera immunization on diarrhoea morbidity and mortality rates among children under
5 years of age in Bangladesh, assuming 100% vaccine efficacy, 100% programme coverage, and an average age of
full immunization of 2 years3
Age
(months)
Proportion of diarrhoea episodes
Proportion of diarrhoea deaths
Caused by
V. cholerae 01 h
(%)
Averted by
cholera
immunization
(%)
Caused by
V. cholerae 01f
(%)
Averted by
cholera
immunization
(%)
0-23
0.2
0"
5
0d
24-59
0.6
0.6
20
20
0-59
0.4
0.3'
8
4'
“ The computed proportions of episodes and deaths averted are directly proportional to the vaccine efficacy and the programme
coverage and thus the effects of different values for these parameters may be readily computed.
b See text.
1 See text.
3 Average age of full immunization assumed to be 2 years.
' Based on age-specific diarrhoea morbidity rates given in footnote e to Table 5.
' Based on age-specific diarrhoea mortality rates given in footnote a to Table 2.
rotavirus immunization might have averted 9-14% of
admissions for diarrhoea over that period. These
calculations assume a vaccine efficacy of 80%,
coverage of 45-75%, and an average age of full
immunization of 6 months.
Cholera immunization. In Bangladesh, cholera
may account for about 0.4% of all diarrhoea
morbidity and 8% of all diarrhoea mortality in
children under 5 years of age. Again, values for the
efficacy of a new cholera vaccine have to be assumed.
A protective efficacy of 64% has been found in
challenge studies among adult US volunteers
receiving 3 oral doses of combined B subunit/wholecell vaccine (46). A value for the efficacy of a new
cholera vaccine of 70% is assumed here. The vac
cination schedule for this vaccine is unknown at
present. If a new vaccine does not give long-lasting
protection, the optimal age of administration may be
around 24 months, before the peak in age-specific
cholera incidence rate. In this case it will not be
delivered within the existing EPI and so coverage may
be low. Three coverage figures are adopted here:
30%, 45% and 60%.
Table 6 presents computations of the maximum
impact of cholera immunization at 2 years of age on
overall diarrhoea morbidity and mortality rates in
Bangladesh, assuming 100% vaccine efficacy and
100% programme coverage. Under these ideal condi
tions, cholera immunization might reduce overall
diarrhoea morbidity rates by 0.3% and diarrhoea
mortality rates by 4% among children under 5 years
of age in Bangladesh. With a vaccine having 70%
efficacy and levels of coverage of 30%, 45% and
60%, cholera immunization at 2 years of age might
reduce diarrhoea morbidity rates by 0.06%, 0.09%
and 0.13% and diarrhoea mortality rates by 0.8%,
1.3% and 1.7%. If immunization against cholera is
achieved at a younger age, say 6 months, and
accordingly better coverage figures are adopted
(45%, 60% and 75%), the potential reductions would
be 0.11-0.19% for diarrhoea morbidity rates and
2.1-3.4% for diarrhoea mortality rates (calculations
not shown).
In this review, we do not examine the benefits of
cholera immunization that might extend to older
children and adults in endemic areas if immunity
induced by an improved vaccine is long-lasting, nor
do we consider the potential role of cholera immuniz
ation in epidemic control' and in the protection of
especially susceptible or at-risk groups. Finally, there
are insufficient data to assess the exciting possibility
that a vaccine prepared from antigens derived from
cholera toxin may induce cross-protection against
ETEC (LT-only or LT-ST) diarrhoea.
Cholera immunization may not have a measurable
impact on hospital attendance rates for diarrhoea
among young children. Data from the hospital-based
study in Dhaka cited above (69) suggest that cholera
immunization might have averted only 0.6-1.2% of
attendances for diarrhoea among children under 5
years of age. Among older patients these potential
reductions in attendances are 2-4%, assuming
repeated vaccinations or long-lasting immunity.
c The role of immunization in the prevention and control of
cholera epidemics will be considered in another review (Blake and
Feachem, under preparation).
I. DE ZOYSA & R G. FEACHEM
578
These calculations assume a vaccine efficacy of 70%,
coverage of 30-60%, and an average age of full
immunization of 2 years.
FEASIBILITY
The delivery requirements of the candidate rota
virus and cholera vaccines are at present unknown.
The simultaneous administration of rotavirus vaccine
with another vaccine currently included in the EPI
would facilitate its delivery. Three doses of oral polio
vaccine are usually recommended in the first 6 months
of life and it is hoped that rotavirus vaccine can be
combined with one or all 3 doses of oral polio vaccine
without interference with seroconversion to either
virus. The cold-chain and handling requirements of
rotavirus and oral polio vaccines are likely to be
similar. In this optimal case, rotavirus immunization
would require few additional inputs for its delivery.
The delivery requirements of cholera vaccine are
more speculative. A killed cholera vaccine may prove
to be relatively temperature-stable, whereas a live
cholera vaccine may have stringent cold-chain
requirements. Cholera immunization with an
improved vaccine may be indicated in the second year
of life and may involve multiple doses. Cholera
vaccine would not, in this case, be delivered within the
EPl, but would require additional immunization
services. The main operational difficulty would be
achieving high coverage of children in this older age
group. If a new cholera vaccine can induce longlasting protection, its delivery will be greatly simpli
fied.
Finally, a major constraint on the successful
delivery of oral vaccines against both rotavirus
diarrhoea and cholera would be the need to protect
the vaccine against gastric acidity, in order to assure
its safe passage into the small intestine.
COSTS
Rotavirus and improved cholera vaccines are still
under development, so the cost estimates must be
derived from data on current immunization pro
grammes. In a recent review, Creese (under prep
aration) has estimated the likely costs of delivering
these new vaccines on the basis of data from 9 cost
appraisal studies of immunization programmes in
developing countries. Costs depend heavily on the
extent to which the new vaccines can be incorporated
into an existing immunization programme. The
actual vaccine costs for current EPI vaccines account
for only a small proportion (around 10%) of total
programme costs.
Assuming an optimal delivery strategy for rota
virus immunization, in which a single dose of
rotavirus vaccine is administered within an existing
EPI programme without increased frequency of
contacts, the likely marginal cost is USS 2 (1982
prices) per fully immunized child. If cholera
immunization requires additional contacts because it
is targetted at a different age group than the EPI,
estimated costs are from USS 5 (if a single dose is
required) to USS 15 (if three doses are required) per
child fully immunized against cholera (1982 prices). It
is here assumed that the cost per vaccinated child is
independent of the number of children vaccinated,
within likely limits.
These cost estimates can be brought together with
the effectiveness data computed above in order to
calculate the likely cost-effectiveness range of the
proposed interventions in developing countries. Two
indicators of cost-effectiveness are considered here:
cost per case averted and cost per death averted/
For rotavirus immunization at age 6 months with a
vaccine having 80% efficacy and a marginal cost of
USS 2 per fully immunized child, the cost-effective
ness figures are:
— USS 4 (1982 prices) per diarrhoea case averted in a
child aged 0-59 months;
— USS 312 (1982 prices) per diarrhoea death averted
in a child aged 0-59 months.
For cholera immunization at age 2 years in
Bangladesh with a vaccine having 70% efficacy and a
cost of USS 5-15 per fully immunized child, the cost
effectiveness figures are:
— USS 183-549 (1982 prices) per diarrhoea case
averted in a child aged 0-59 months;
— USS3571-10 714(1982 prices) per diarrhoea death
averted in a child aged 0-59 months.
If cholera immunization is achieved at 6 months of
age at the marginal cost of USS 2-6 per fully
immunized child, the likely cost-effectiveness of the
intervention is greatly improved (cost per case averted
USS 61-183 and cost per death averted USS
872-2617).
CONCLUSIONS
In developing countries, rotavirus may be respon
sible for about 6% of all diarrhoea episodes and 20%
of all diarrhoea deaths in children under 5 years of
age. In industrial countries these proportions may be
higher. A theoretical case has been made, based on
various assumptions about vaccine efficacy and
d The formulae used to calculate these cost-effectiveness figures
are available on request from R.G.F.
ROTAVIRUS AND CHOLERA IMMUNIZATION FOR CONTROL OF DIARRHOEAL DISEASES IN CHILDREN
programme coverage, thai rotavirus immunization
might reduce overall diarrhoea morbidity by 2-3%
and diarrhoea mortality by 6-10% among children
under 5 years of age in developing countries.
The impact of improved cholera vaccines depends
on the prominence of cholera as a cause of diarrhoea
and this varies greatly from country to country.
Taking the extreme example of Bangladesh, where
cholera may account for about 0.4% of all diarrhoea
episodes and 8% of all diarrhoea deaths in children
under 5 years of age, cholera immunization might
reduce overall diarrhoea morbidity by 0.06-0.13%
and diarrhoea mortality by 1-2% among these
children, based on various assumptions.
These vaccines are under development and vac
cination schedules and delivery requirements are at
present unknown. If an immunization programme
can incorporate rotavirus vaccine at a marginal cost
of USS 2 (1982 prices) per fully immunized child, the
likely cost-effectiveness values for the intervention
are USS 4 per diarrhoea case averted and USS 312 per
diarrhoea death averted in children under 5 years. For
cholera immunization which may require additional
immunization services at a cost of USS 15 (1982
prices) per fully immunized child, the likely cost
effectiveness values are USS 549 per diarrhoea case
averted and USS 10 714 per diarrhoea death averted
579
in children under 5 years. These estimates are
extremely tentative and are subject to revision as more
is learnt about the epidemiology of rotavirus
diarrhoea and cholera, and the features of
immunization programmes against these diseases. In
areas where more accurate epidemiological and
economic data are available other estimates of cost
effectiveness can be computed.
The prominence of rotavirus diarrhoea in
industrial countries, and the similar incidence rate in
industrial and developing countries, suggest that rota
virus diarrhoea may not be controlled by improve
ments in water supply, sanitation, or hygiene.
Control may depend upon the development, trial, and
widespread use of an effective vaccine. It is hoped
that rotavirus vaccine can be delivered within existing
EPI programmes, and rotavirus immunization may
prove to be a cost-effective intervention for national
diarrhoeal diseases control programmes.
The cost-effectiveness of cholera immunization, as
an intervention to reduce overall diarrhoea morbidity
and mortality rates among young children, is more
doubtful, even in Bangladesh, although it may have
other applications. More data are required on vaccine
efficacy and the duration of protection before firmer
conclusions can be reached.
ACKNOWLEDGEMENTS
We are grateful for the constructive criticisms on earlier drafts of this paper provided by R. F. Bishop, R. E. Black,
D. Blum, R. I. Glass, R. H. Henderson, R. C. Hogan, J. Holmgren, A. Z. Kapikian, M. H. Merson, N. F. Pierce, and
D. A. Sack. We thank J. Seaman of the Save the Children Fund, United Kingdom, for his support and encouragement.
Secretarial, bibliographical and editorial assistance was most ably provided by Alison Hinchley, Susanne O’Driscoll and
Dianne Fishman.
RESUME
INTERVENTIONS DANS LE CADRE DE LA LUTTE CONTRE LES MALADIES DIARRHEIQUES DU JEUNE ENFANT:
VACCINATION ANTICHOL^RIQUE ET VACCINATION CONTRE LES ROTAVIRUS
Cet article est le septieme d’une serie d’etudes concernant
les interventions susceptibles de reduire la morbiditc et la
mortalite imputables aux maladies diarrheiques chez les
enfants de moins de cinq ans dans les pays en d^veloppcment. Nous avons etudie les effets potentiels de la vacci
nation contre les rotavirus et de la vaccination anticholerique (a I’aide d’un vaccin ameliore) sur la morbiditc et
la mortalite diarrheiques, en utilisant des donnees provenant
d’enquetes de terrain et de calculs theoriques. Dans les pays
en developpement, les rotavirus sont probablement responsables d’environ 6% de tous les episodes morbidcs et de 20%
de Pensemble des deces d’origine diarrheique chez les
enfants de moins de cinq ans. Ces proportions sont peut etre
plus elevees dans les pays industriels. Les effets potentiels
d’une immunisation a 1’egard des rotavirus sur le taux
gdndral d’atteinte diarrheique chez les enfants de moins de
cinq ans dependra de Page auquel se pratique la vaccination,
de Pefficacite du vaccin utilise et de la couverture assuree
par le programme. Avec un vaccin efficacc i 80% et un taux
decouverture de Pordre de45 & 75%, une vaccination contre
les rotavirus pratiquee a Page de six mois peut diminuer les
taux de mortalite diarrheique de 1,8 a 3,0% et les taux de
mortality de 6 & 10%. Si cette vaccination est pratiqude i un
age moins avance, par exemple trois mois, le gain sur cette
5S0
1. DE ZOYSA & R. G. EEACHEM
baisse des taux peut n’avoir qu’une importance marginale:
1.9-3,3% pour la morbidite et 6-11% pour la monalite
Les effets d’une amelioration des vaccins anticholeriques
dependent du role preponderant du cholera cn tant que
cause des maladies diarrheiques— role qui varie considerablement d’un pays a (’autre. Au Bangladesh, le cholera est
probablement responsable d’environ 0,4% de (’ensemble de
la morbidite diarrheique et de 8% de la totalite des deces
d’enfants de moins de cinq ans imputables a ces maladies.
Dans le cas particulier, on a suppose que le nouveau vaccin
anticholerique etait efficace a 70%. Le schema d’adminis
tration utilise pour ce nouveau vaccin est actuellement
inconnu. Lorsqu'un nouveau vaccin ne confere pas de
protection durable, 1’age optimal pour son administration sc
situe aux alentours de 24 mois, e’est-a-dire avant
(’apparition du pic d’incidence cholerique specifiquc pour
cette classe d’age. En pareil cas, le vaccin ne sera pas administre dans le cadre du PEV existant et, de la sorte, la
couverture sera peut-etre faible. Avec un vaccin efficace a
70% et un taux de couverture de I’ordre de 30 a 60%, la
vaccination anticholerique pratiquee a Lage de deux ans au
Bangladesh pourrail diminucr les taux de morbidite diar
rheique de 0,06 a 0,13% et les taux de monalite de 0,8 a
1.7%. Si la vaccination anticholerique est pratiquee a un age
moins avance, par exemple six mois, et si par consequent
une meilleure couverture pent etre assuree (45-75%), la
reduction potentielle serait de I’ordre de 0,11 a 0,19% pour
la morbidite diarrheique et de 2,1 a 3,4% pour la mortalite.
S’il est possible d’englober dans un programme de vacci
nation une immunisation a 1’egard des rotavirus moyennant
un cout marginal de USS2 (prix de 1982) pour la vaccination
complete de chaque enfant, le rapport cout-efficacite de
cette intervention sera de I’ordre de USS4 pour chaquc cas
de maladie diarrheique qu’il a etc ainsi possible de prevenir,
et de USS312 par deces evite chez les enfants de moins de
cinq ans. Pour une vaccination anticholerique qui peut
exiger un renforcemcnt des services de vaccination d’un cout
s’elevant a USS 15 (prix de 1982) pour la vaccination
complete de chaque enfant, le rapport cout-efficacite au
Bangladesh sera vraiscmblablemcnt de USS549 pour chaque
cas de maladies diarrheiques qu’il sera possible de prevenir
et de USS10 714 pour chaquc deces evite chez les enfants de
moins de cinq ans.
L’importance des maladies diarrheiques a rotavirus dans
les pays industriels, et (’analogic de leur taux d’incidence
ent re pays indust riels et pays en developpement, suggerent
qu’une amelioration des approvisionnements en cau, de
I’assainisscment ou de (’hygiene ne suffit peut-etre pas pour
juguler les affections de cc type. Leur maitrise depend sans
doute de (’elaboration, de 1’essai et de (’utilisation generalisee d’un vaccin efficace. II est permis de penser qu’un
vaccin contrc les rotavirus pourrait etre administre dans le
cadre du Programme elargi de Vaccination et que cette
intervention se revelera interessante, sur le plan du rapport
cout-efficacite, pour les programmes nationaux de luttc
centre les maladies diarrheiques. La vaccination anti
cholerique, en revanche, peut exiger un renforcement des
services de vaccination entrainant des couts eleves pour un
faible taux de couverture. Meme au Bangladesh, le rapport
cout-efficacite des interventions en faveur d’une diminution
de la morbidite ci de la monalite diarrheiques chez les jeunes
enfants ne sera peut-etre pas positif, bien que d’autres
applications puissent etre envisagees dans ce cadre.
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