DIARRHEA
Item
- Title
- DIARRHEA
- extracted text
-
RF_DIS_23_SUDHA
Special SLrticCes
Iihown that only a little r
’under 4 months are exclui
1 third of children 6-9 n
plemcntary feeding. Impr
younger children is emt
In the programme. The pas
ng In the management of
incorporate advise to
Oral Rehydration Therapy Programme in
India : Standard Case Management of
Acute Watery Diarrhoea
O CJ j^&clusive breastfeeding at
'UJ' SB W^g&nt feeding practices, i
V K Manchanda*
The Diarrhoeal Diseases Control Programme in this
country was started in 1978 with the objective of reduc
ing mortality and morbidity due to diarrhoeal diseases.
In 1985-86, with the inception of the National Oral
Rchydration Therapy (ORT) Programme the focus
shifted to strengthening case management of diarrhoea
for children under the age of 5 years and improving
maternal knowledge related to the use of home available
fluids, use of oral rehydration salts (ORS) solution and
"ontinued feeding. Ensuring availability of ORS packets
at health facilities and in the community is an important
aspect of the programme. Since 1992-93, the programme
has become part of the Child Survival and Safe Mother
hood (CSSM) Programme. All programme activities are
now integrated with those of the CSSM Programme.
SITUATION IN 1985:
A nationwide study in 1978 by the Registrar General
of India1 identified diarrhoea as a major killer and cause
of illness among children. In a study carried out in 19852,
in urban and rural areas in eleven States, the median
diarrhoea incidence among children under 5 years, un
adjusted for seasonality, varied from 1.5 episodes/
cbild/year (Ep/Ch/Yr) in urban areas to 4.7 in rural areas.
Based on the findings of this survey it was estimated
that on an average each child suffered 3 attacks of diar
rhoea per year thus totalling to an estimated 300 million
episodes of diarrhoea in the 100 million children under
Jibe age of 5 years3,4. Assuming that one in 200 episodes
was fatal, the data obtained from field investigations5
providers must be utilise:
CURRENT SITUATION:
In subsequent surveys in 1991 and 19927’8 incidt^jkATlONALE FOR STANDAF
of diarrhoea varied from 1.2 Ep/Ch/Yr in Bihar to!®- Studies conducted dut
in J&K and Tamil Nadu. In the slum areas around tuffifonclusively demonstrate
towns an incidence of 10.5 Ep/Ch/Yr was reported. SiCal diagnosis is not necess
though there are pockets where the incidence of diantz^ for diarrhoea cases . Maj,
continues to be high, surveys indicate a declining
ass fully managed by f<
in the average number of episodes per child per jtstandard case managem
compared to 1985.
prevention of dehydratio
The surveys carried out in 1992 also revealed Ilf It home using home avail
the proportion of deaths due to diarrhoea compared pf cases with dehydratic
total deaths in children under 5 years of age to be M’ttbydration salts (ORS)
and 11.9% respectively for Maharashtra and Orisst.I^ propriatc feeding during
overall child mortality (0-4) rate in the country wifi:five use of intravenous
was 41.2 in 1981 has also declined to 26.5 in 1991.C esses and of antibiotics
a result of this drop an estimated 16.8 lakh lives e-and dysentery. This case
being saved annually. Based on this and the estiroiifcto the treatment of acui
decline in diarrhoea associated imortality it is estirnilhind persistent diarrhoea.
that deaths due to diarrhoea have
ve declined from u®1,----- - - - .
f.JirndonZ case manage.
timated 1.5 million in 1985 to about 0.6-0.7 milliotf
[programme of control
1991.
f
\ country. This approach
MALNUTRITION EMERGING AS AN IMPORTANT ISSUE: j : types of diarrhoea : AcOf all infectious diseases, the diarrhoeal disuA [’««</persistent diarrhoea.
(along with measles) have the greatest adverse effect? f management of acute ><•.
growth of young children. This is the result of fief
such as malabsorption of nutrients caused by theiiS
tious process in the small bowel and reduced diets
STANDARD CA
ACUTE W/)
intake resulting from anorexia and food withdurf
Diarrhoea is the pas
during diarrhoea as a consequence of traditional practiiE?Il00]S- These liquid stoo
suggested that an estimated 1.5 million children under
5 years died due to diarrhoeal diseases each year. Nearly
one third of all causes mortality among these children4
and improper advice from health workers. Malnoutiiktj |||UCS a day. However
children in turn have more severe diarrhoea, settiri$fijjslcllCy anj character c
a vicious circle which often leads to persistent fonu^‘uf stools that is more i
was due to diarrhoea associated causes. These findings,
along with the fact that two-thirds of these deaths oc
curred due to dehydration and could be reliably averted
with effective oral rchydration, formed the basis of the
action plan for the ‘National Programme of Oral
Rchydration Therapy for Children under 5 Years’6
diarrhoea, with high case-fatality rates and long hiSstge watery stool in a j
effects on the quality of life9.
bjhoea.
launched in 1985-86.
Feed back from hospitals and results of the Nairi rz
Family Health Survey (NFHS) 1992-9310 indicate^
p
DEl'TNITIC
•
f.
•
who contribute significantly to morbidity and mart
*
jj’.
it is the younger children in the age group 6-11 meet/1j
due to diarrhoea. Malnutrition is being increase
*.
Three Or mure h,
Change in consu
_______________
passagC of frequent
recognised as a major contributor to these deaths. IMj,eMtfe(1 infants> stools
•Ml). Assistant Commissioner (ORT). Department of Family Wel studies also suggest that the proportion of deaths
loose grecilish yeli
fare. Ministry of Health and Family Welfare, Government of India,
persistent diarrhoea is also increasing. NFHS hasip
New Delhi 11000!
220
J
'■
ORT NUMBER
that only a little more than half of the infants
t5der 4 months are exclusively breastfed and less than
1 (bird of children 6-9 months, receive timely comfjernentary feeding. Improvement of nutritional status
jf younger children is emerging as a major area of focus
£ the programme. The past emphasis on continued feedPg in the management of diarrhoea has to be expanded
B Incorporate advise to mothers of young infants on
^elusive breastfeeding and appropriate weaning and in(mt feeding practices. All contacts with the health
providers must be utilised for this purpose.
f
RATIONALE FOR STANDARD CASE MANAGEMENT :
Studies conducted during the past two decades have
conclusively demonstrated that establishing an aetiologiCil diagnosis is not necessary to provide correct treatment
for dM^oea cases9. Majority of these cases can be suc-
«sslWF managed by following simple principles of
jur.dard case management strategy which comprises
prevention of dehydration through proper management
it borne using home available fluids and ORS; treatment
of cases with dehydration due to diarrhoea using oral
tthydration salts (ORS) solution; continued and ap
propriate feeding during and after diarrhoea; and selec
tive use of intravenous fluids for severely dehydrated
esses and of antibiotics for suspected cases of cholera
and dysentery. This case management approach applies
to the treatment of acute watery diarrhoea, dysentery
and persistent diarrhoea.
pfamfcrtF case management forms the basis of the
programme of control of diarrhoeal diseases in the
[country. This approach applies to the treatment of all
I types of diarrhoea : Acute watery diarrhoea, dysentery
i end persistent diarrhoea. In this article the standard case
■ ! tuanagenient of acute watery diarrhoea is discussed.
Standard Case Management of
Acute Watery Diarrhoea
Diarrhoea is the passage of loose liquid or watery
‘tools. These liquid stools are usually passed more than
3 limes a day. However, it is the recent change in contatency and character of stools rather than the number
stools that is more important Passage of even one
krge watery stool in a young child may constitute diar
rhoea.
;
DEFINITION OF DIARRHOEA
;! ‘Three or more-loose or watery stools in a day
!. *
Change in consistency and character of stools
.
Passage of frequent formed stools, pasty stools in
p'astfed infants, stools during or immediately after feedloose greenish yellow stools on the 3rd to 7th day
221
of life (transitional stools) may at times be erroneously
considered to be diarrhoea. Infants during initial 3-4
months of life may pass 3-6 formed or semi-formed
stools daily; this is also not diarrhoea11, if they are gain
ing adequate weight In most cases the mother knows
what is an abnormal stool for her child.
TYPES OF DIARRHOEA :
~
Ci-ASSIrjCATiON OP DIARRHOEA
-
(by <l:nal syndromw)
. •
•
•
watery diarrhoea
Dysentery (blood ia the stools)
Persistent diarrhoea
Acute watery diarrhoea — It starts suddenly and is
characterised by passage of loose watery motions. Most
episodes of acute diarrhoea recover within 3 to 7 days.
More than three-fourths of all diarrhoeal episodes in the
community are acute watery episodes.
It is important to understand that cholera is a form
of acute watery diarrhoea. Recognising cholera early is
important in order to start treatment promptly. If treat
ment is delayed or is inadequate, death may occur quickly
from dehydration and circulatory collapse. Cholera
should be suspected when a patient older than 5 years
of age develops severe dehydration from acute watery
diarrhoea (usually with vomiting) and in any patient who
comes with symptoms of acute watery diarrhoea from
an area where there is an outbreak of cholera.
Dysentery — This is diarrhoea with visible blood in
faeces. The presence of blood may also be accompanied
with abdominal cramps, fever, anorexia and rapid weight
loss.
Persistent diarrhoea — An acute episode of watery
diarrhoea or dysentery may last up to 14 days. If it
persists longer, it is classified as persistent diarrhoea.
These cases require careful management.
The relative contribution to diarrhoea-associated
mortality in children under 5 years of age by each type
of diarrhoea is shown in Fig 1.
ASSESSMENT OF A CHILD WITH DIARRHOEA :
Clinical assessment is sufficient to initiate appropriate
therapy 11'. Routine determination of the aetiology of
diarrhoea in a laboratory is neither necessary nor prac
tical. Microscopy and stool culture is of little value in
the routine management of diarrhoea. The management
of a case of diarrhoea is based on the clinical features
of the disease.
A careful history must be taken to determine whether
the child has diarrhoea or not, type of diarrhoea (whether
it is acute watery, dysentery or persistent diarrhoea). Did
the child vomit during the preceding 6-8 hours ? History
of feeding is important and it must be ascertained if
222
J INDIAN MED ASSOC. VOL 93, NO 6, JUNE, 1995
The physiological basis of ORT is that glucose linked ?
sodium transport is largely intact in diarrhoeas ofvarj^ I
aetiology. Thus any solution, that provides glucose (q. £
starch which release glucose after hydrolysis) and
1.
would promote absorption of sodium and water. Furth^ s
some amino acids or dipeptides derived from dietary 1
protein, eg, 1-glycine, I-alanine and others also help j |
sodium co-transport similar to glucose11.
ORS is the best available solution for Quid
electrolyte replacement. In the early stages of diarrhoea
or when ORS packets are not immediately available
home available fluids and water can be used.
Fig 1 — Showing Mortality hy Type of Diarrhoea
feeding has been reduced or modified in a way that the
child is receiving reduced quantity of energy intake.
Child’s immunisation status especially as regards meas
les immunisation must also be determined1".
History should be followed by physical examination
of the child to assess the degree of dehydration, nutri
tional status of the child and presence of infections like
pneumonia, otitis media or other associated infections.
The assessment of the degree of dehydration helps
to classify the cases into those with no signs of dehydra
tion, those with signs of dehydration and those with signs
of severe dehydration. The classification, based on the
presence of physical signs, is done with the help of the
simple chart developed for this purpose and being ex
tensively used in the National Programme.
SIGNS OF DEHYDRATION
’
\
(two or more signs Including at least one marked )
•
*
•
•
«
•
Restlessness, irritability
*
Increased thirst
*
Decreased skin turgor
*
Dry mouth and tongue
Tears absent
.
Sunken eyes
SIGNS OF SEVERE DEHYDRATION
Lethargic or unconscious, floppy '
Unable to drink
PRINCIPLES OF THE MANAGEMENT OF ACUTE DIARRHOEA:
Fluid
therapy
for
prevention
and
treatment of
dehydration, feeding, rational use of drugs and ap
propriate advice to mothers form the basis of manage
ment of a child with diarrhoea.
Fluid therapy — Fluid and electrolyte replacement
is necessary for all types of diarrhoea and is the mainstay
ol the. treatment of a case with diarrhoea. Oral rehydration therapy (ORT) for replacement of fluid losses is a
simple, cost-effective, easily accessible, and scientifically
appropriate remedy for dehydration, due to diarrhoea .
-!
PURPOSE OF FLUID THERAPY
Prevention of dehydration for cases with no sijim of ■
dehydration.
’
,;J
•
Provide for normal daily intake
,.i
•
Replace on-going losses
Treatment (rchydmtion) ofcases with signs ofdehydrator]
•
•
♦
Correct existing water and electrolyte deficit
Provide for normal daily intake
Replace on-going losses
,cute
Main0
deficiL
solutio
uanspc
petnbr
IjCSS
itaininj
■
ORS
■ fonnulal
the last
proven b
; of prepai
giucose .
.
-1
HOME AVAILABLE FLUIDS (HAF) :
Home available fluids (HAF) are appropriate fort
child who does not show any clinical signs of dchydnlion and should be given frequently and also after eid
loose stool to prevent dehydration. A good HAF is one
which is safe when used in large quantities. Some o( ■
these fluids which are commonly used in the homes nn4
have a sound physiological basis are : Food based solfr
lions like, rice water, dal or dal water with salt, inf
butter milk (lassi) with salt. Other fluids which can be
used are lemon water, soups, coconut water and pll'a ‘
the respt
' only thos
ire presc
flhan 20g
■ increasinj
used. Coi
■reduce its
Ccacy pa
The ORS
ing instru
ORS solu
water. Water is a good home available fluid if take*
* i
with food11.
These fluids are generally more effective when give
*
along with food (ie, feeding should be continued), thus
providing for starch (ultimately glucose) and protein (in
timately amino acid), to promote absorption of lurnirwi
sodium. These fluids together with food provide ORT-
guidelines
rational fc
mothers o
on the qua
ORS form
' been foun
In younger infants breastfeeding is an ideal fluid
; ORS b
that ORS
should be frequently given.
I Soft drinks, sweetened fruit juices and sweetened. tu.
should not be used. These have a high osmolarity a*>4
| can lead to worsening of dehydration.
fcj
ORAL REHYDRATION SALTS (ORS) :
ORS is a balanced mixture ofglucose and electrolj'11*
for prevention and treatment of dehydration.
The presence, of potassium in the mixture is impo
ill view of the large potassium losses associated
t
“ot offcr s
Scientific
health co
freparutiglucose s
Osmotic g
{’tetructio
‘hat adeq.
lhe child .
i^tfldnda
ORT NUMBER
cllte diarrhoea1 , especially in malnourished infants.
glucose linJcs-g
hoeas of varj<^
les glucose (^
•lysis) and
I water. Furtb^
d from dietarj
•rs also help
Malnourished children also have a chronic potassium
deficit. The function of citrate or bicarbonate in ORS
solution is to correct acidosis. Glucose hi ORS helps in
uansporting sodium and water across the intestinal
■ucnibrane during diarrhoea.
COMPOSITION OF ORS
(per litre of ORS sciatica)
for fluid
;es of diarrhot®
ately availably
used.
Sodium chloride
3SS
Potassium chloride
1,5g
Sodium citrate
23g
Or,
Sodium bicarbonate
*
23g
Glucose anhydrous IP
20.0g
• Less preferred. In the National Programme ORS containing sodium citrate Is used
I
PY
th no signs
ORS conforming to the above composition (WHOfo.mulation) has been used all over the world during
the last 25 years and its efficacy and safety has been
. proven beyond all doubts by its large scale use. A number
of preparations of ORS with different concentrations of
gkicose and sodium are available in the market It is
the responsibility of treating physicians to ensure that
ppropriate foci s ' only those conforming to the recommended formulation
gns of dehydn- i
■ire prescribed. Higher concentration of glucose (more
1 also after ead » ’than 20g/I increases the risk of osmotic diarrhoea thus
nod HAF is cat g
increasing the risk of dehydration and should never be
itities. Some 4
used. Concentrations of sodium <3.5 g/1 (90 mEq/1) may
n the homes ad
•reduce its rate of intestinal abosrption and clinical ef
ood based soil- a
ficacy particularly in the presence of high purge rates.
r with salt, a»! :;
The ORS packets available in the market also cany vary
ds which can •
ing instructions for mixing and use. As with all drugs,
water and pies
ORS solution has to be used according to prescribed
e fluid if tafcs
guidelines. It is therefore important not only to use the
of dehydnrtioKf
'yte deficit ,
rational formulation of ORS but also to properly advise
mothers on mixing of ORS from a one litre packet and
on the quantities of the solution to be given. Rice based
ORS formulations which arc available in the market have
1 t*
en found to be good in cases of adult cholera but do
dive
£'vet
continued), th®
) and protein (’k
ption of lunti®
*
>d provide ORT
not offer substantial clinical benefits to children.
ORS in newborns — Several studies have shown1'
dut ORS solution can be used to treat dehydration in
ideal fluid
sweetened
osmolarity
5
eand electrol)'
*
f
ration.
|
dure is import
associated v'
' ’WO recommended formulation of ORS is the most
[Scientific practical and appropriate choice for doctors and
Care providers managing patients with diarrhoea.
f Preparations of ORS containing more than 20gtl of
glucose should NEVER he used as these can lead to
Osmotic diarrhoea and worsen the condition of the child.
Instructions to mothers on proper mixing and ensuring
that adequate quantities of ORS solution are given to
[
I w child with diarrhoea are the must important aspects
standard case management.
223
neonates who can drink or who accept oral fluids. ORS
can be safely used in this situation when amounts of
ORS appropriate for the degree of dehydration and plain
water is offered in a (2 : 1) ratio of ORS and water.
Breastfeeding must be continued.
CASES WITH NO SIGNS OF DEHYDRATION :
In early stages, when fluid loss is less than 5% of
the body weight, children may not show any clinical
signs of dehydration, but may still have sub-clinical or
incipient dehydration. The purpose of fluid therapy in
such cases is to prevent dehydration by giving HAF or
ORS. ORS should invariably be advised to all cases who
are brought to the health facilities/clinics. Mothers must
be advised on how to prepare ORS solution and on how
much ORS should be given. The quantities of fluids to
be given are shown in Table 1.
Table 1 — Showing Amount of ORS to be Given for Replacement
of Ongoing Stool Losses to Prevent Dehydration (Maintenance
Therapy)
Age
After each liquid stool
56 months
7 months - 2 years
>2 to 5 years
Quarter glass (50 ml)
Quarter to half glass (50 to 100 ml)
Half to one glass (100-200 ml)
It is important to advise mothers to continue giving
additional quantities of HAF or ORS solution as long
as diarrhoea lasts. Breastfeeding must be continued in
infants. In exclusively breastfed babies frequent breast
feeding is usually enough to prevent dehydration. If milk
other than the mother’s milk is being consumed, this
should not be diluted. Food normally taken by the child
should be continued.
CASES WITH SIGNS OF DEHYDRATION :
The purpose of fluid therapy in such cases is to cor
rect fluid deficit and to provide for ongoing losses and
normal daily requirement. Children who have dehydra
tion should be kept under observation in the health
facility/clinic for a few hours and given a prepared ORS
solution during this period. During the first 4 hours, the
child should receive 100 ml per kg of body weight of
ORS. The quantities of ORS solution to be given by
age and weight of the child is shown in Table 2.
If the child vomits, wait for 10 minutes and then
continue to give ORS, but more slowly. If the child
develops puffiness of the eyelids, stop ORS, continue
to give plain water (or breastmilk) till puffiness disap
pears. After 4-6 hours of treatment the child should be
reassessed for signs of dehydration. If the child has im
proved (as will happen in most cases ), put the child on
maintenance therapy as indicated in Table 1.
If the child still has some signs of dehydration after
4 hours of fluid therapy with ORS, continue therapy
224
J INDIAN MED ASSOC, VOL 93, NO 6, JUNE, 1995
Table 2 — Showing the Approximate Amount of ORS Solution to
be Given in the First 4 Hours according to Age and Weight of the
Child (Rehydration Therapy)
<4
months
4-11
months
12-23
months
Weigh: (kg)
<5
ORS (ml)
200-400
Measure (glass)
1-2
5-8
400-600
2-3
11-16
16-30
8-11
600-800 800-1200 1200-2200
6-11
3-4
4-6
Age
2-4
years
5-14
years
*If the child wants more ORS than shown, give more
••Inform mother to give the child breastmilk in between the feeds
of ORS
•••For infants who are not breastfed, also give 100-200 ml clean
waler during this period
with ORS solution for another 4 hours. Inform mother
to give the child breastmilk in between the feeds of ORS.
If the child is not breastfed, give 100-200 ml of water,
before starting the therapy. After rehydration has been
achieved, ORS must be continued for replacement of
ongoing losses (maintenance therapy) as indicated in
Table 1.
If the condition of the child improves with thearpy
but the mother has to leave before the child is fully
recovered, she must be given enough' quantity of
prepared ORS solution for the next 4 hours. She should
be advised to continue ORS till diarrhoea stops and also
to continue feeding the child. Mothers must also be ad
vised on how to prepare ORS solution and on how much
HOW TO l’REPARE~ORS SOLUTION EROM A ONE LITRE
PACKET
Mother must be taught how to measure one litre of water.
It is important that a measure which is commonly avail
able in the houses is identified and the mothers told the
exact number of such measures that will make one litre.
There is no need to boil the water for preparing the ORS
solution. Clean water which the household normally uses
for drinking purposes can be used.
Hands must be washed with soap before making the ORS
solution.
Full packet of ORS must be used. Generally the mothers
will tend to save a part of the packet in order to use it
later, fl is important to emphasise that the whole packet
is to be mixed in one litre of water.
The container should be kept covered. The Solution can
be used for 24 hours and should be discarded if not
consumed within this period. Fresh solution should be
prepared, if required.
SHOW TILE MOTHER HOW TO GIVE ORS SOLUTION’
Give at least one tea spoonful every 1-2 minutes. .Give
frequent sips from a cup for an older child.
If the child vomits, wait for 10 minutes, then give the
solution more slowly.
If diarrhoea continues after ORS packets are used up
tell the mother to give home availablefluids and get more
ORS packets.
ORS should be given.
CASES WITH SIGNS OF SEVERE DEHYDRATION :
Children with signs of severe dehydration must be
admitted for inpatient care. These signs appear when the
fluid and electrolyte losses are excessive. The condition
of the child in such cases is critical and it is essentia]
that the child is rehydrated quickly by using intravenous
(IV) infusions. IV therapy may also be required in cases
where ORT has proved to be ineffective in correcting
dehydration.
A number of IV solutions are available in the market
However, most of them do not contain the optimal
amounts of the electrolytes required to correct the deficits
associated with acute diarrhoea. The IV infusions recom
mended for use during acute diarrhoea are :
Preferred solutions : Ringers Lactate solution (also
called Hartman’s solution for injection).
Acceptable solutions : Normal saline and half normal
saline with 5% dextrose.
Unsuitable solutions : Plain glucose (dextrose).
The rate of administration of IV fluids is important
and is indicated in Table 3. After signs of severe dehydra
tion disappear and the child is able to drink, further
therapy should be continued with ORS. The child should
be kept under observation for at least 6 hours after dis
continuation of IV therapy. Before the mother leaves
Table 3 — Showing Rates and Quantities of IV Infusion for Cor
recting Severe Dehydration
Total
100 m!A(
Age
First give
30ml/kg in
Then give
70 ml/kg in
Infants
First hour
Next 5 hours
6 hours
Older children
First 30 minutes
Next 2~ hours
3 hours
the hospital enough packets of ORS should be given
and the mother told how to use these packet.
During IV therapy, the patient must be reassessed
every 1-2 hours. If hydration is not improving, give IV
infusion more rapidly. If the patient can drink, ad
ministration of ORS solution must also be started along
with the IV infusion. The patient must be evaluated after
the completion of the therapy (100 ml/kg body weight).
If signs of severe dehydration have disappeared, continue
treatment with oral therapy. If signs of severe dehydra
tion persist, IV fluid therapy must be continued. If it >s
not possible to start the IV infusion for some reason,
the patient can be given ORS solution through *
nasogastric tube.
FEEDING IN DIARRHOEA:
Feeding during and after diarrhoea is the other es
sential component of standard case management Diaf-
ORT NUMBER
is physiologically sound and prevents or mini■ itiitrt the deterioration of nutritional status that normally
gecompanies diarrhoea. It is the responsibility of treating
physicians to utilise the contact with diarrhoea cases as
gppprumities for educating mothers on correct feeding
practices.
YDRATION :
dehydration must be
.igns appear when the
cssive. The condition
al and it is essential
by using intravenous
o be required in cases.
ffective in correcting
f.
W
,tr
^a"is known to worsen nutritional status of the child
s
1.
|
because of the decreased food intake due to anorexia,
withholding of food by mothers and intestinal malab
sorption of nutrients. The traditional concept of resting
vailable in the market
|
[be bowel in the belief that children fed during diarrhoea
will have increased volume and frequency of stools hascontain the optimal
J
d to correct the deficits
| been challenged by the findings of recent studies. It has
le IV infusions recom1 been clearly shown that feeding does not worsen diar
rhoea or increase risk of dehydration and that malab
rhoea are :
sorption itself is corrected by feeding since it facilitates
Lactate solution (also
|
:ctior^^
|- mucosal recovery ,14.
saline and half normal
|
Feeding prevents or minimises the deterioration of
nutritional status that normally accompanies diarrhoea.
Jucose (dextrose).
k At least two-thirds of calories given during convales
cence get absorbed15. Early and-adequate feeding during
IV fluids is important
!
diarrhoea enables children to gain weight and grow nor
igns of severe dehydraable to drink, further
; mally in spite of frequent diarrhoeal episodes
Energy dense foods with least bulk, which are
ORS. The child should
least 6 hours after disj routinely available, in the households should be given to
the child in small quantities but frequently, at least once
fore the mother leaves
every 2-3 hours interval. To make foods energy dense
ties of TV Infusion for Cor■ these can be enriched with fats and oil or sugar, eg,
yciration
khichri with oil, rice with milk or curd and sugar, mashed
Then give
Total
banana with milk or curd, mashed potatoes with oil and
70 ml/kg in
IQO mlAt
lentils.
Next 5 hours
6 hours
,
Next 2^ boors
3 hours
S even during rehydration with ORS. Milk should not be
ORS should be given
thes^bcket.
ient must be reassessed
not improving, give IV
Breastfeeding should be continued uninterrupted
diluted with water during any phase of acute diar
rhoea11’16. Milk can also be given as milk cereal mix-
patient can drink, ad
tores, eg, dalia, sago, milk-rice mixture. This reduces
toe lactose load while preserving energy density. Routine
(•close free feeding viz, soy formula is not recommended
during acute diarrhoea even when reducing substances
ust also be started along
t must be evaluated after
100 ml/kg body weight)-
•rc detected in the stools.
If the child is more than 4 months of age, mother
ibould be advised about breastfeeding and proper weau-
«ve disappeared,continue,'
signs of severe dehydralust be continued. If it15
“’?• After the child recovers and normal appetite reap
ers, the child may be given more food than normal
[fusion for some reason,
RS solution through >
^TIONAL USE OF DRUGS:
liarrhoea is the other es
case management. Di’(
” regain lost weight.
ORS is the drug of choice for all cases of diarrhoea.
8 life saving when used timely and in adequate quan' 1CI- Clinical studies have shown that antibiotic therapy
¥ J?8 not offer any significant clinical benefit in acute
v '’’rltoca except in cases of suspected cholera. Use of
225
specific antibiotics in cholera have been found to
diminish the severity and duration of diarrhoea and short
en the duration of excretion of pathogens. The other
indications for use of antibiotics are dysentery and as
sociated non-gastro-intestinal infections, if present
(Table 4). Amoebiasis and giardiasis are rare in children
and drug therapy should be started only when trophozoite
of Ent histolytica or Giardia lamblia are seen in the
feaces17.
Antidiarrhoeal drugs (antimotility drugs, binding
agents, stimulants, steroids and other drugs) did not pro
vide any clinical benefits and were found to be poten
tially dangerous when used in children. Their marketing
has been banned in India.
DIARRHOEA ASSOCIATED WITH OTHER ILLNESSES:
Children with diarrhoea may also have other poten
tially serious illnesses. Some of the common illnesses
associated with diarrhoea are measles, pneumonia and
fever. The management of diarrhoea following measles
is same as described earlier. The child should be ex
amined for signs of vitamin A deficiency. If such signs
are present, treatment should be started with therapeutic
doses of vitamin A. If the child has pneumonia, the
recommended treatment for pneumonia should be started
along with rehydration. Fever is frequent in patients with
diarrhoea. Treat fever with paracetamol. These patients
should be carefully evaluated for any associated infection
and treated promptly.
ADVICE TO THE MOTHER:
Mother plays a key role in the treatment of the child.
She is responsible for feeding and caring for the child.
She must be told that use of ORS and home available
fluids in increased quantities along with continued feed
ing are crucial for saving her child’s life. It is extremely
Talite 4 — Showing Antimicrobial Used in the Treatment of
Specific Causes of Acute Diarrhoea in Children
Causes
Drug (s) of choice
Doxycycline 6 mg/kg/day in a
single dose x 3 days or,
tetracycline 50 mgAg/day in 4
doses daily x 3 days
Shigella
Paediatric co-trimoxazole J .
dysentery
tablet twice a day x 5 days
(under 2 months)
’2 tablets twice a day x 5 days
(2-12 months)
3 tablets twice a day x 5 days .
(>l-5 years of age)
Acute intestinal Metronidazole
*
30 mg/kg/day in
amoebiasis
3 divided doses x 5-10 days
Acute giardiasis Metronidazole
*
15 mg/kg/day in
3 divided doses x 5 days
Cholera
•lanidazole can also be used
Alternative
Erythromycin
30 mg/kg/day in
3 doses x.3 days
Nalidixic acid
55 mg/kg/day in
4 doses x 5 days
fej. ■
<^2-
..
........... ■: -____
,
,
;
J INDIAN MED ASSOC, VOL 93, NO 6, JUNE, 1995
226
important that she knows how to prepare ORS solution
and how much of ORS to give to the child. She must
be told that ORS will prevent and treat dehydration and
that diarrhoea will take some time to recover and that
ORS should be continued as long as diarrhoea lasts.
Presence of blood in stools, many watery stools,
repeated vomiting, marked thirst, eating or drinking
ly, fever, floppiness and difficulty to wake or unco^.
sciousness are danger signs which the mother must kno^
to enable her to seek immediate treatment It is the duty
of the treating physicians to ensure that mothers are cdu,
cated about these signs.
’Registrar General, India — Survey on Infants and Child Mortality,
9Claeson M, Merson MH — Global progress in the control of diarrhoea
1979. New Delhi: Ministry of Home Affairs, 1979.
National Institute of Communicable Diseases — Diarrhoeal Diseases
diseases. Pediatr Infect Dis J 1990; 9: 345-55.
10National Family Health Survey, India 1992-93. Bombay: Intent
Status in Urban and Rural Areas in 1985. New D^lhi: Directorate
General of Health Services, Government of India, 1986.
^Vishvanathan H, Rhode EJ — Diarrhoea in Rural India: A Nationwide
tional Institute for Population Sciences, 1994.
’’Guidelines for Management of Diarrhoea in Children. Bombay: k
Study of Mothers and Practitioners, 1990.
National Programme for Control of Diarrhoeal Diseases, National
Health Programme Series 9. New Delhi : National Institute of
Health and Family Welfare, 1990.
^Bhan MK, Arora NK, Ghai OP, Ramachandran K, Khoshoo V, Bhan-
dari N — Major factors in diarrhoea related-mortality among rural
children. Indian J Med Res 1983; 77: 9-12.
Action Plan, National Diarrhoeal Diseases Control Programme
(Programme of ORT for Children under Five Years). New Delhi:
Department of Family Welfare, Ministry of Health and Family
Welfare, Government of India, 1988.
ORS-findings of a study on supply and demand and factors affecting
demand, MODE, September 1991.
National Child Survival and Safe Motherhood Programme. New Delhi:
Government of India, 1994: 79-85.
dian Academy of Pediatrics.
12Readings on Diarrhoea: Student Manual. WHO/CDD/SER/90.13.
’^Herschhorn N, Greeoough III WB — Progress in oral rehydratjoj
therapy. Scientific American 1991; 5: 264.
wMolla AM, Molla A, Khatun N — Absorption of macronutrient
*
a
children during acute diarrhoea and after recovery. Proceeding!
of the XIII International Congress of Nutrition. London: Libbey
1986: 113-5.
15Brown KH, Gastanaduy AS, Saavedra JM, el al — Effect of continued
Oral feeding on clinical and nutritional outcomes of acute diarrhoea
in children. J Pediatr 1988; 112: 191-200.
16Chew F, Penna FJ, Preet Filho LA, et al — Is dilution of cow’s
milk formula necessary for dietary management of acute diarrhoea
in infants aged less than 6 months? Lancet 1993; 341: 194-7.
17WH0 — The Rational Use of Drugs in the Management of Acute
Diarrhoea in Children. Geneva: WHO, 1990.
A School of the University of London
NARGIS DUTT MEMORIAL FOUNDATION
INC NEW YORK (USA)
NDMF, a Charitable Trust is aimed at finding of
areas in India for providing help to needy hospitals
and to help scholars engaged in cancer research and
improving medical care. The Foundation also donates
cancer-care equipment to hospitals.
NDMF will render all possible help (financial
and otherwise) to various organisations to :—
transfer techniques and technology for disadvantaged patients
in India :
(2)
provide equipment to hospitals :
(3)
provide fellowship for training in specialised areas for fully
trained physicians for a period of three to four months in
USA :
(4)
send medical experts for teaching and training from abroad
to India.
(1)
For further detailed information write at the fol
lowing address:
Dr GS Paul
C-4/4, Vasant Vihar,
New Delhi-110057
Royal Postgraduate
Medical School
Diploma in Perinatal
Paediatrics
Applications are invited for this nine-month, full-time course which
commences on 2 October 1995. The course provides detailed knowledge of
the modem .practice of pennatai paediatrics, particularly neonatal intensive
care. Twenty-eight hours of forma] teaching each week takes place in the
neonatal units, outpatient clinics, laboratories and seminar rooms of the
Paediatric Department. Clinical skills such as the performing and
interpretation of cranial ultrasound scans, gestational age and neurological
assessment of the newborn infant will be taught. All the senior paediatric staff
at Queen Charlene’s and Chelsea Hospital and Hammersmith Hospital take
part in teaching. Students will be expected to prepare an individual project
and case studies under the supervision of a full-time lecturer assigned to the
course. The students will be assessed throughout the course on the bads of
their oral presentations and case commentaries and a final examination
consisting of a “short answer" written paper and a clinical viva of ft
equivalent standard to Part II MRCP will be held.
To allow effective small-group teaching as well as participation in the chmol
activities of the Department, the group size is limited to a maximum of 10
*
Medical graduates from all parts of the world who have had at least two yean
experience in paediatrics including care of the newborn, and who arc
committed to neonatal medicine, are invited to apply.
For application forms and further details, please contact!
The School Registry, Royal Postgraduate Medical School.
Hammersmith Hospital, Du Cane Road, London W12 ONN
*
Tel: +44 (0) 181 740 3118. Fax: +44 (0) 181 743 6764.
Tie RPMS is an exempt charity and a national centre of excellence in
research and postgraduate teaching.
:77
',I ■ ’
INDIAN JOURNAL OF
PUBLIC HEALTH
VoLXXXVHI, No.2
April - June 1994
! '
to . ..
a.
: .. pj?-,:
r
,
MATERNAL BEHAVIOUR AND FEEDING PRACTICES AS
'
. DETERMINANTS OF CHILDHOOD DIARRHOEA : SOME. . .
V- ■■ OBSERVATIONS AMONGST RURAL BENGALEE MOTHERS
...
S.Ghosh, P.G.Sengupta, S.K.Mandal, B. Manna, S.N. Slkder and
(<’■■■
Introduction s
I
B.K.Strkar
<
. .
Diarrhoeal disease is one of the
| important cause of childhood morbidity
| and mortality specially amongst children
below five years of age1. Estimated
I Incidence of diarrhoea was found to be
i virtually same by Bern el at in 1992 (2.6
episodes per child per year) as that
estimated by Synder and Merson In 1982
although diarrhoeal mortality was found
to be lower2-3. A community based
longitudinal study revealed that a large
number of children do not suffer from
diarrhoea within a year living in more or
less same environment as that of
■diarrhoeal children4. It has been observed
that certain behavioral pattern of family
^e.g. storage of water and handwashing
practices
with
soap
are
major
determinants
for
incidence
and
transmission of diarrhoeal disease5 ®. We
describe in this communication some
demographic
and
epidemiological
variables and behavioral pattern of
diarrhoeal families as compared to nondiarrhoeal families.
Materials and method :
A total of 980 rural families near
Calcutta having children below 3 years
were longitudinally followed for one year
for occurrence of diarrhoea. These families
were kept under twice-a-week active
surveillance by local resident surveillance
workers. They were trained to deliver ORT
services for prevention, management of
dehydration and prompt referral of
intractable cases to the nearest health
facility.
Initial
demographic
and
epidemiological information about the
study families were collected by house to
house visit, entered in the computer and
were analyzed using case control method.
Families were divided into two groups on
the basis of occurrence of diarrhoea.
Families having a diarrhoeal child were
regarded as ‘case families’ where as
families having study children without
diarrhoea were considered as ‘control
families'. At the end of one year, 570
(58.2%) of 980 families had diarrhoea
cases and 410(42.8%) families had no
study children with diarrhoea.
As soon as a diarrhoea case occurred
amongst study families, we undertook an
observational study to observe mother’s/
family behaviour for 6 hours in the
morning and afternoon. An age matched
Division of Epidemiology, National Institute of Cholera and Enteric Diseases,
P33 C.LT. Road, Scheme XM, Beliaghata, Calcutta 700010
Maternal Behaviour.......... Ghosh el al.
78
neighbourhood child and his family was
similarly observed as control. However, if
the control child developed diarrhoea, the
family was eliminated from analysis as
control family and included as case family.
In these cases observational study was
repeated and change(s), if any, from
previous observation, was incorporated in
the schedule. Initially we studied 76 case
families and equal number of control
families. However 29 control families
where subsequently diarrhoea developed
in a study child were analysed as case
families. We could, therefore study
prospectively the mothers behavior in 105
diarrhoeal families and compare with 47
non-diarrhoeal families. The variables
studied were personal and domestic
hygiene, food hygiene, sanitation and
water storage habits.
Results and discussion :
The summary results of demographic
and epidemiological variables of study and
control families have been presented in
table I. It would be evident that Kuchcha
housing, lower income (<Rs,500/- pei
month), illiteracy of mother were more
prevalent in diarrhoeal families a.compared to control group. Presence o
soap for washing hands and sanitarj
latrine were observed more frequently h
non-diarrhoeal families. Birth spacing
> = 4 years) appeared to play a significan
contributory role in preventing diarrhoea
Mothers behaviour in respect of certaii
hygienic habits have been comparec
between diarrhoeal and control families h
table II. More mothers were found to us,
soap or detergent for washing feeding
container, maintained better persona
hygiene for themselves and their chlldrei
in non-diarrhoeal families compared tmothers in diarrhoeal families. Leftove
food and wlde-mouth containers fo
storing drinking water were less used li
non-diarrhoeal families than their counte
parts. Those mothers who used left ove
Table - I
Some demographic and epidemiological variables of study families
Variables
Diarrhoeal
families
( n=570 )
Non-diarrhoeal
families
( n=410 )
P-value
Housing (kuchcha)
Income (< 500/- )
Education
illiterate father
illiterate mother
Birth spacing
(4 vts. or more)
Presence
of sanitary latrine
Soap used
a. for ablution
b.before food handling
feeding children
Presence of animal
255 (44.7)
252 (44.2)
139 (33.9)
150 (36.6)
0.0006
0.016
131 (23.1)
304 (53.5)
84 (14.7)
80 (19.5)
186 (45.4)
84 (20.5)
NS
0.013
0.018
288 (50.5)
262 (63.9)
0.000031
82 (14.4)
17 (03.0)
14 (02.5)
185 (32.5).
94
29
26
- -116
(22.9)
(07.1)
(06.3) . ..
(28.3)
0.0005 ■
0.0046
0.0041
NS
Indian Journal of Public Health Vol.XXXVIIl, No.2, April - June, 1994
79
Table - II
Significant difference of mothers behavior in Diarrhoeal & non-diarrhoeal families
Mothers behavior
i
Feeding Container
washed with soap
Use of left, over
food in next feed
Body and clothes
not clean
Indiscriminate
stool disposal
S^^ing common
latrine
Storage of dr. water
in wide mouth container
Diarrhoeal
families
( n=105 )
Non-Diarrhoeal
families
( n=47 )
32
(30.4)
40
(38)
42
(40.0)
77
(73.7)
38
(36.2)
89
(84.8)
23
(48.9)
9
(19.1)
9
(19.1)
26
(55.3)
7
(15.9)
31
(66.0)
P-value
0.03
0.02
0.01
0.02
0.008
0.008
Figures in parenthesis indicate percentages
food for next feeding of their children or
disposed children's stool indiscriminately
also showed a significantly higher
prevalence of diarrhoea.
In this study we have identified certain
demographic
and
epidemiological
variables which appeared to have a direct
relationship
with
causation
of
diarrhoea. It is generally well understood
i®n various studies that poor feeding
techniques and sanitary practices can lead
to contamination of weaning foods and it's
ill effects eg. diarrhoea and malnutrition7 8.
In our study we also observed
significant
contribution
of feeding
practices, washing of feeding container,
use of left over food and status of personal
hygiene in causation of diarrhoea amongst
children.
It appears that poverty,
Ignorance, illiteracy, unavailability and
sharing of latrine and food hygiene all
contribute
towards
occurrence
of
diarrhoea. Similar observation was made
by other investigators from Srilanka0.
However we feel that further welldesigned
anthropological studies of observational
nature are required to determine mother’s
beliefs and attitude, facilities available in
and around home behind high risk
behaviors in the family which need to be
intervened.
Acknowledgement :
The
authors
acknowledge
the
assistance provided by Reserch Fellows
and staffs of Epidemiology Division during
the study.
References :
1.
2.
Interim program report of CDD. WHO
Geneva 1986; WHO/CDD187. 26: pp
27.
Bern C., Martines J., de Joysa I. and
Glass R I. The magnitude of the globed
problem of diarrhoeal diseases: a ten
year update. Bull WHO 1992; 70: 705714.
Maternal Behaviour.......... Ghosh el al.
3.
6.
Synder J D. and Merson M H. The 7. Barrel RA. and Rowl MGM. Infant food
magnitude of the global problem of
as a potential source of diarrhoeal
acute diarrhoeal diseases: A review of
illness in a rural West Africa. Trans R
active surveillance data. Bull WHO
Soc Trap Med Hyg 1979; 73 : 85-90
1982; 60: 605-613.
8. Black RE., Brown KH., BeckerS., Alim
Sircar B K., Deb B C., Sengupta P G. el
A R., Merson M H. Contamination of
al. A longitudinal study of diarrhoea
weaning foods and transmissions of
among
children
in
Calcutta
Enterotoxigenic
Escherichia
coli
Communities. Indian J Med Res 1984:
diarrhoea in children in rural
80: 546-590.
Bangladesh. Trans R Sod Trop Med
Hyg 1982: 76: 259-264
Deb B C.. Sircar B K., SenGupta P G. et
al. Studies on intervention to prevent 9. Wijewardene Kumudu.,
Fonseka
ElTor cholera transmission in urban
Pushpa. and Wijasiri W A A. Risk
slums. Bull WHO 1986;64:127-131.
factors
contributing
to
acute
Sircar B K., Sengupta P G., Mandal S
diarrhoeal disease in children below
K. el al. Effect on hand washing on the
five years. Ceylon Med J 1992: 37:
116-119
incidence of diarrhoea in Calcutta
slum. J DlarrDis Res 1987; 5: 112-114
—
OBITUARY
It is a matter of great distress and sorrow to announce that DR. RADHAKRISHNA
BANERJEA, founder member and Fellow of Indian Public Health Association
(FIPHA, 1971) has passed away on 23 April, 1994. Dr. Banerjea started his
career as Asst. Clinical Pathologist in Medical College, Calcutta; then as
Demonstrator of Pathology and Bacteriology, in National Medical Institute; as
Asst. Professor, Public Health Laboratory and also as Officer-in-Charge, Rural
Public Health Laboratory (Singur) of All India Institute of Hygiene and Public
Health, Calcutta. He was a close associate of Dr. U.N. Brahmachari in research
on Kalaazar. In death of Dr. Banerjea, the country has lost a capable public health
bacteriologist.
<
I:
o:
b
8
m
n;
in
in
m
P1'
h<
th
to
pr
a\\
of i
A
CO'.
ha;
CE
es;
Tr;
an.
dia
exp
Im]
hos
paj
bei:
'Pr
E
C4-f3b-.
fc;ology
acute diarrhoea among children in
Roping countries: a multicentre study in five
{jjuntnes
l^ilan,1 Lu Guang Zhen,1 M.M. Mathan,2 M.M. Mathew,2 J. Olarte,3
'spejo,3 Khin Maung U,4 M.A. Ghafoor,5 M.A. Khan,5 Z. Sami,5 &
• ^Sutton6
— etiological survey of acute diarrhoea in children aged 0-35 months who were attending treatment
• L jyas carried out using a standardized protocol in five hospitals in China, India, Mexico, Myanmar,
-'-tfstan. A total of 3540 cases of diarrhoea and 3279 age- and sex-matched controls were studied;
of the patients were aged less than 1 year and 60% were male. An enteric pathogen was
-'■d in 63%
cases sr,h ,n 3<7% °f fho controls. In all the study centres, the pathogens most
-1associated with disease were rotavirus (16% of cases, 2% of controls), Shigella spp. (11% of
••
of controls) and enterotoxigenic Escherichia coli (16% of cases, 5% of controls). Rotavirus was
■■-r-.est among 6-11-month-olds, accounting for 20% of all cases in this age group; 71% of all rotak episodes occurred during the first year of life. Shigella spp. were commonest among those aged
. i-onths and 24-35 months, accounting for 22% and 27% of the cases, respectively. The proportion of
b - that yielded no pathogen was inversely related to age, being highest (41%) among infants below 6
' i s of age and lowest (19%) among those aged 24-35 months. These results suggest that microbe:'<C intervention strategies for the control of childhood diarrhoea! diseases in developing countries
•.-■Hocus on rotavirus. Shigella spp. and enterotoxigenic E. coli.
: ioduction
’ A.ijrfge of the etiology of acute diarrhoea is rele•A sx planning diarrhoea! disease control straespecially vaccine development. The possi■> for the etiological diagnosis of diarrhoea were
enhanced in the 1970s through a scries of
persons also contributed to this study: Shi Ou
Mai Wen, Duan Shu Cheng. Xia Lu Di. and Wang Shun
S.M. Pereira, T. Raghupathi, C. Kirubakaran, C.
D-P. Rajan, R. Martin and V.l. Mathan (Vellore); A.
Ga,indo- C. Soler, and M. del Carmen Bezualdo
\Nyunt Nyunt Wai. Myo Khin, Thane Toe, Daw Tin
-t ■i‘tjarWar Nyein. Phyu Phyi Win. Mi Mi Khin, Kyaw Moe.
S°0 ^hein, May La Lin, Daw Khin, and Than Nu
.. ’ ;
■
and Anti-epidemic Centre, Shanghau^hina.
h^eSearC^ Unit, Christian Medical College Hospital.
•
nlest*na* Bacteriology, Hospital Infantil de
Gomez" and Institute de Investigaciones BioMeX‘C0 DF* Mexico.
■
•
hDivision, Department of Medical Research,
ry •
*
'vision. National Institute of Health, Islamabad.
g3a3es Control Programme. World Health Organc*teif ft.nLava 271 Switzerland. Requests for reprints
this author.
w- •
ft • ‘
ealth Organization. 69 (5). 549-555 (1991)
advances, the most important of which were the
discovery of rotaviruses and Campylobacter jejuni,
the discovery and development of diagnostic tests for
enterotoxigenic Escherichia coli (ETEC), and the
detection by electron microscopy of several noncultivable enteric viruses. With improved diagnostic
methods, it became possible to detect an etiological
agent in 70-75% of acute cases of diarrhoea in children treated at hospitals in developed countries (4,
13). In comparable etiological surveys in developing
countries, the rate of positive identification of micro
organisms has been slightly lower, and compared
with viruses the role of bacterial agents has been
greater (1-3, 5-12). Moreover, in developing coun
tries it has been recognized that enteric pathogens
can frequently be encountered also in healthy child
ren, making it more difficult to determine their true
etiological role in causing diarrhoea (5, 5)- Further
more, in developing countries it is not uncommon to
isolate more than one enteric pathogen from the
same child (7, 3, 5, 6-8,10).
To define more carefully and compare the eti
ology of acute diarrhoea in young children in differ
ent areas of the world, the WHO Diarrhoeal
Diseases Control (CDD) Programme initiated and
supported a multicentre study in five developing
countries. Standardized protocols for sampling
patients and controls and for the laboratory pro
cedures were used to allow comparison between sites
£, World Health Organization 1991
549
Sima Huilan et al.
and permit more general conclusions to be drawn.
This article summarizes the main results from the
study.
Methods
The hospitals and laboratories outlined below par
ticipated in the study.
o Shanghai, China: Shanghai Hygiene and Anti
epidemic Centre, and the Shanghai Children’s Hos
pital.
o Vellore, India: Wellcome Research Unit of the
Christian Medical College Hospital.
o Mexico City, Mexico: Hospital Infantil de Mexico
“Federico Gomez”.
o Yangon. Myanmar: Department of Medical Re
search and the Yangon Children’s Hospital.
o Islamabad and Rawalpindi, Pakistan: National
Institute of Health (Islamabad), and the Rawalpindi
General Hospital and Holy Family Hospital
(Rawalpindi).
The standardized protocol, which is sum
marized below, was developed by the CDD Pro
gramme's Scientific Working Groups on Bacterial
Enteric Infections and Viral Diarrhoea. All partici
pating laboratories had prior experience in micro
biological studies of enteric infections; in some
instances assistance was provided to establish spe
cific diagnostic tests at the study site. Although each
study lasted 2 years, not all centres participated at
the same time. The first study (in Myanmar) began
in February 1982, and the last (in Pakistan) in
October 19S5.
Selection ot cases
The patients were children aged 0-35 months who
were seeking treatment for diarrhoea at the out
patient clinics of the participating hospitals. Accord
ing to the original study protocol, children with a
history of acute diarrhoea (an increase in the number
or volume of stools) that lasted for 72 hours or less
and clinical evidence of dehydration were eligible for
the study. In practice, however, dehydration was not
recorded, and most of the children probably were
not clinically dehydrated. Also included were child
ren with a history of blood or mucus in stools and a
temperature of at least 38.5 °C. Children were
excluded if they had an associated complicating
illness or had received an antibiotic or antiparasitic
drug within the preceding 10 days.
Cases were selected each week for 104 consecu
tive weeks. Based on records from previous years, a
month-by-month sampling proportion was deter
mined that took into account normal seasonal varia
tions in disease incidence.. The objective was to
sample 5-12 cases per week throughout the study
period, with the exact number varying acc athe seasonal incidence of diarrhoea so that th
portion of total cases sampled each month
nearly constant. Provided children met the c
nition given above, their age, sex and type Jr
rhoea (watery or dysenteric) were not 7 °‘(W.
when they were selected for the study; thus the^
*
studied reflected the proportions actually s
each age group, sex and type of diarrhoea.
■
Each child admitted to the study was mat t"‘
with a control—a healthy child from the same
graphical area and of the same sex, age (+30?°^
for those aged 1-11 months and ±60"day3°u
others), socioeconomic status, and ethnic group
had not had diarrhoea within the previous mondt"
A questionnaire was completed for each patiw
giving details of the clinical history, pre-iU^
feeding practice, household environment, and dem>
graphic information (age, sex, and ethnic groupi
Most of the patients were from an urban/periurba
environment, except in Vellore, where the study wa
carried out in a periurban/rural environment.
Laboratory procedures
The laboratory procedures have been described else
*
where."
At least 5 ml (5 g) of faeces was collected froa
each patient within 1 hour of admission. RccuJ
swabs were used with dysenteric patients or control
if stools could not readily be obtained. Specim®
were brought to the laboratory and divided to
immediate culture and examination (2 g) and to
virological studies (1 g diluted 1 : 5 in phosphaU
*
buffered saline). A spare specimen (2 g) was stored
frozen ( — 70 °C) for future use.
A portion of each stool was examined mi®
*
scopicaliy for trophozoites (Entamoeba histolytkq
and cysts (Giardia lambda and E. histolytica). Ct)?
tosporidium spp. were not routinely sought, s*nct. .
importance of these pathogens was not recogn.
when the protocol was developed.
.
For bacteriological examination the fo1°^
media were inoculated: selenite bwffi (sa
enrichment), alkaline peptone water (Vibrio c
enrichment), McConkey agar (22 °C for £
enterocolitica; 37 °C for E. coli. Shigella SPP'„
monella spp.), TCBS agar (V. cholerae), an,
or Skirrow’s medium (Campylobacter)..A
selective media for Salmonella spp. and
were inoculated as desired by the Par
laboratory.
_ ________________________ _ ________
* Manual for laboratory investigation of acute ent0^s f0(
WHO unpublished document CDD/83.3.Rev.1. ReqU®
copies should be addressed to Diarrhoeal Disease
gramme. World Health Organization. 1211 Genev
land.
WHO Bullelin 0M&
550
Etiology of acute diarrhoea among children In developing countries
p^liminary identification of suspicious colonies
• cqIried out using standard biochemical tests.
nreliminar?’ identification of E. coli was comenterotoxin production was demonstrated
rr the Biken test or, in Mexico, using the Y-l
s"aj cell assay, for heat-labile toxin (LT), and the
1 *Yjj ng mouse assay for heat-stable toxin (ST).
'teropathogenic E. coli (EPEC) were tentatively
Ratified by serogrouping with O-antigen antisera6
•ng both slide and tube agglutination techniques.
tjteroinvasive E. coli (EIEC) were studied by testing
J" colonies (including atypical lactose-negative
rains) for invasiveness using the Sereny test. Iso■•sof V. cholerae 01 were serotyped.
All stools were examined by electron micros„3y for rotavirus, Norwalk-agent-like particles, and
jbnovirus. Initially, negatively-stained specimens
ttre screened for all virus particles. This was fol’jT'td by immune electron microscopy using pooled
s:s fiM^indigenous donors. In addition, most
KjaissWire tested for rotavirus antigen using an
©pie-linked immunosorbent assay (ELISA) pro
fited by the WHO Collaborating Centre for Human
lotavirus, Birmingham, England.
Results
(total of 3640 cases and 3279 controls were investipted; this represents approximately 10"<> of the
total number of diarrhoea cases seen in the five
centres during the 2-ycar study (Table 1). ThroughM their respective study periods, no centre recog---d unusual epidemics that would have distorted
is findings.
hitel: Distribution of cases of diarrhoea in the five
My Bites
.
^^Jo. of diarrhoea
I Mysite^B
cases
tuico
j ’a-«an
6192
5862
6376
NAB
9438
No admitted into the study
__________________________
Cases
Controls
594 (10)'
916 (16)
559 (9)
813
758 (8)
562
587
559
813
758
*n Parentheses are percentages of the total number of
cases in each site.
* not available.
j jjaP1? a8e distribution of cases was generally
ln all five centres (Table 2); however, the proiz.n °f cases aged 0-5 months was greater in
500 (40%) than Myanmar (16%), while the proOratories. Detroit. Ml. USA.
^OMS. Vo! 69 1991
Table 2: Distribution of diarrhoea cases, by age and sex
In the study sites
Sex
distribution
(all ages)
% of cases in age
group (months):
Study site
0-5
6-11
12-23
24-35
Males
(%)
Females
(%)
China'
India
Mexico
Myanmar
Pakistan
28
33
40
16
27
31
28
35
31
38
32
30
22
43
28
6
9
3
10
7
63
61
57
59
56
37
39
43
41
All sites
28
32
32
7
60
40
4*,
' Age was not reported for 2".. of cases.
portion of children aged 12-23 months was greatest
in Myanmar (43"..) and least in Mexico (22%).
Overall, aboui 60".. of the patients were aged less
than 12 months, 30".. were aged 12-23 months, and
less than 10% were aged 24-35 months.
In all the study centres approximately 60 ■ of
all cases were boys (Table 2). Two centres (Shanghai
and Vellore) determined the correlation of sex with
the diarrhoeal etiological agent. In both instances.
males predominated for all agents except isolates of
Shiuella spp. from Shanghai, which were detected
equally frequently from males and females.
An enteric pathogen was detected in 6S . of
diarrhoea cases, with a bacterial agent being
detected in 4S
*I •>. a viral agent in 23'!... and G iamhlio
in 3".. of cases; these included cases from which
more than one pathogen was isolated More than
one enteric pathogen was found in at least 20"o of
diarrhoea episodes in Mexico City. Shanghai, and
Vellore, but in only about 5% in Islamabad and
Yangon. An enteric pathogen was detected in
approximately 303.. of healthy controls, the highest
prevalence being 49% in Vellore.
The only agents that were consistently and sub
stantially more prevalent in cases than in controls
were rotavirus. Shitjella spp. and ETEC (Table 3 and
Table 4). The prevalence of EPEC was relatively
high in controls, and. with the exception of Islama
bad. nearly equal to that in cases. Salmonellae spp.
were more frequently detected in cases than controls
in Islamabad and Shanghai, but not at the other
study sites. C. jejuni was clearly more prevalent in
cases than controls in Islamabad, Mexico and
Shanghai, but not in Vellore or Yangon. Mixed
infections were detected approximately three times
more frequently in cases than controls. G. lamblia
and E. histolytica were seldom found in the study
cases (Table 4).
551
Sima Huilan et al.
Table 3: Distribution of bacterial agents detected In children aged under 3 years with diarrhoea and In healthy
In the five study sites
*
y COr>bo«l
% of individuals from whom the agent shown was detected:
Escherichia
coli (ETEC)
E. coli
Salmonella
Shigella
(EPEC)
spp.
spp.
Vibrio
cholerae 01
CarPpyloba^.
Study site
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Controls
Cases
China
India
Mexico
Myanmar
Pakistan
6
14
17
26
17
2
7
7
7
4
3
9
10
8
14
3
7
9
5
8
5
4
4
1
3
2
6
3
1
0.3
18
20
11
3
6
0.4
3
1
1
1
0
2
0
0.5
2
0
0.2
0
0
0.8
17
15
15
2
10
All sites
16
5
9
6
3
2
11
1
1
0.2
11
Contns,
2
14..:
10
a
5
7
* In some instances two or more agents were isolated from the same individual. ETEC = enterotoxigenic E. coli;
enteropathogenic E. coli.
Table 4: Distribution of viral and parasitic agents detected In children aged under 3 years with diarrhoea and
healthy controls In the five study sites'
”"T»
% of individuals from whom the agent shown was detected:
Norwalk-like agent
Adenovirus
Rotavirus
Giardia lambha
Entamoeba histotyti# '
Study site
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Control
China
India
Mexico
Myanmar
Pakistan
13
18
13
22
14
1
1
2
1
4
2
6
3
_
3
3
5
_ t>
4
2
2
_6
2
1
0.2
7
5
0.1
3
0
7
1
0 1
3
0
0.1
0.7
0
0.6
0
02
6
1
2
1
—0
3
0.4
All sites
16
2
4
2
3
2
3
3
0.3
0.1
0
0
.
' In some instances two or more agents were isolated from the same individual
° Not stated.
The effect of age on the prevalence of specific
pathogens was evaluated by determining the rate of
isolation of a specific pathogen (or no pathogen)
from children within defined age groups, e.g., the
Table 5: Age-specific Isolation rates for the major
enteropathogens In four of the study sltesi.
________________________________ ss.______ _____
Enteropathogen
% of cases that were positive for specific
pathogens in different age groups
(months)
-----------------------------------------------------------------------0-5
6-11
12-23
24-35
Rotavirus
ETECC
Campylobacter
jejuni
Shigella spp.
None detected
13 (28)°
11 (26)
11 (26)
20 (43)
14 (34)
14 (34)
12 (25)
15(31)
16 (33)
12 (5)
18(9)
17(8)
5(12)
41 (44)
10 (26)
25 (28)
22 (49)
25 (24)
27(14)
19(4)
* Yangon was excluded, as noted in the text.
b Figures in parentheses show the % of all isolates of specific
pathogens, by age group.
c Enterotoxigenic Escherichia coli.
proportion of diarrhoeic children aged 6-11 monte
who were positive for rotavirus; and by determine
the distribution by age group of all isolates of spe
*
cific agents, e.g., the proportion of all rotavirus IK
lates from diarrhoeic children aged 6-11
Table 5 summarizes these data from f°ur ®
study centres for children aged 0-5, 6-11,12-23,
24-35 months; no data are shown for the fifth Ct
Yangon, which reported age-specific data on
ology for only 0-11-month-olds and 12-35olds. Nevertheless, the general pattern in
was similar to that in the other centres.
commonest enteropathogens ’s°iated r°. j
month-olds were rotavirus, ETEC, and
data for 0-6-month-olds from these stuT^
further analysed by monthly age groups ( a
The main results from the analysis o
specific data are summarized below.
o Rotavirus was the most frequently det^earo(£i
gen in diarrhoea episodes during the firs
and most episodes that were rotavirus-po
WHO Bulletin OM?-'
552
--- r
■ ■
■
■
" ---- ----------
Etiology ol acute diarrhoea among children in developing countries
.5. Combined data for four of the study sites on the detection of rotavirus, ETEC and Campylobacter from cases
^controls in the first 6 months of life'
Data from cases in age group (days)
0-29
30-59
60-89
90-119
120-149
150-179
Total
•^0. of isolates
♦i of cases in age
group 0-5 months
5(3)“
10 (4)
24 (6)
20 (4)
26 (2)
33(1)
118 (20)
4
9
20
17
22
28
100
No. of isolates
% of cases in age
group 0-5 months
^pylobacter
No. of isolates
% of cases in age
group 0-5 months
7(3)
7 (5)
16 (16)
22 (8)
21 (14)
27 (10)
100 (56)
7
7
16
22
21
27
100
5(2)
13 (5)
25 (9)
13(7)
25 (10)
24 (11)
105 (44)
5
12
24
12
24
29
100
rETEC = enterotoxigenic Escherichia coli.
»r^yresin parentheses refer to data from controls.
iocJ^’ed during the first year of life (Table 5).
The highest incidence of rotavirus was among 6-11^ath-olds, for whom it was detected in 20% of all
farhoea cases. A total of 28% of al) rotavirussociated cases occurred among under-6-month-i (Table 5), 87% of these being in infants aged
i)-J79 days.
• Most isolates of Shigella spp. were from cases aged
bMmonths and these were the most frequently iso
gal pathogens in diarrhoeic children aged 12- 35
soaths (Table 5). These findings were observed in all
*;dycentres and were most striking where the pro
X-rtion of cases with shigellosis was highest—
Airghai, Vellore, and Mexico. Shigella spp. were
isolated from controls (29 isolations from over
ICO healthy control children).
•ETECs were detected at a relatively constant rate
4oughout the first 3 years of life. In three of the five
jStfts they were, with Shigella spp., the agent most
A~ntUjolated from children over 1 year of age.
J'-°hl
of ETEC strains from cases that were
produced only ST. 23% only LT, and 10%
1.. ST and LT. In less than 5% of cases, strains
? Produced only ST and only LT were found in
f
patient. A predominance of strains produc.
ST was observed in all centres. Among con■
ETEC produced only LT and 57%
Ife., and 7% produced both toxins. Altogether,
cases with ETEC were infants aged less than
I *Bmr ’ however, ETEC was also common among
• C°-lnfants *n this age group.
' Was *s°lated at a relatively constant rate
the first 3 years of life. The rate of isoYangon (2% of cases) was much lower than
.e other centres. A total of 26% of C. jejuni
^(<1° 01 cases were frorn infants aged 0-5
•*
' ata from four centres excluding Yangon).
_°MS. Vol 69 1991.
The difference in the isolation rates of C. jejuni
between cases and controls was greater for this age
group than that for older children.
Tabic 5 also shows the age distribution of diar
rhoea cases whose etiology was undetermined. The
proportion of such cases was highest among the
youngest children, i.c.. those aged less than 6 months.
and this occurred in all the study centres. Eor this
age group, 41".. of all cases were of undetermined
etiology, whereas for those aged 12-35 months only
19".. of cases did not yield a potential pathogen.
Information on clinical findings was not consistcntly collated for each case tn terms of specific eti
ology or the age of the child. However, the obser
vations outlined below could be made about the
clinical features of cases.
—Only 1.8% of cases presented with severe dehydra
tion, and these were due mostly to rotavirus, I'.
cholcrae 01, or ETEC.
—Stools from more than 80% of the patients were
described as "loose”; watery diarrhoea occ^red in
less than 20% of cases. Watery diarrhoea was
recorded in 8% of cases in Myanmar, 13% in
Pakistan, and 32% in Mexico City. Apart from the
few cases of cholera, watery diarrhoea was most
frequently associated with rotavirus (27-36% of
cases), ETEC (25-37%), and Campylobacter (2429%).
—Overall, visible faecal blood was reported in
approximately 20% of cases, ranging from 4% in
Myanmar to 29% in Mexico. As expected, it was
most frequently associated with illness caused by
Shigella spp. (45-67% of cases) and Campylobac
ter (35-37%). Blood was rarely observed for illness
caused by rotavirus, ETEC, or V. cholerae 01.
553
Sima Hullan et al.
—Vomiting was reported as “relatively rare” among
Indian cases, but was recorded for 43% of cases in
Mexico and 51% in Myanmar. In Pakistan and
Mexico, vomiting was reported in 61% and 69%
of rotavirus-associated cases, respectively.
Discussion
We have focused on the clinical features and etiology
of acute diarrhoea in young children seen at the five
participating centres, and have attempted to draw
broad conclusions where possible. This approach
appears justified because the data were collected
from a large number of patients using the same
study protocol. The findings at each centre were
similar with regard to the age and sex distribution of
the diarrhoea cases and the overall etiological
pattern. While some regional differences in the eti
ology of diarrhoea occurred, they were minor rela
tive to the general pattern found and also with
respect to other comparable studies in developing
countries (1-3, 5-12). On the other hand, it should
be recognized that this multiccntre study was geo
graphically limited, particularly because no centre
from Africa or South America was included.
The results show that by using appropriate
methodology it is possible to detect a potential
microbial cause in nearly 70% of children with acute
diarrhoea or dysentery who .attend a treatment
centre in developing countries; this proportion is
similar to that in developed countries, although the
distribution of individual agents is different (4. 13). It
should nevertheless be borne in mind that 30% of
cases could not be attributed to a specific microbial
agent. The highest proportion of such cases at all
sites involved infants aged less than 6 months;
further studies are required to more fully determine
the causes of acute diarrhoea in this age group.
In all the participating centres the high rate of
isolation of identifiable enteric pathogens from
healthy control children emphasizes the need for
caution in interpreting the results of stool cultures
for individual cases. The agents with the highest
case: control ratios for isolation rates were rotavirus
and Shigella spp., followed by ETEC; on the basis of
this study, only these three could unequivocally be
regarded as important causes of childhood diarrhoea
in all five centres. Campylobacter was associated
with diarrhoea in some study sites, but mainly
among 0-5-month-olds.
Rotavirus was detected in 16% of the cases; this
is a lower proportion than that found in surveys of
hospitalized children in developing countries
(median, 35%), but higher than that in community
based longitudinal surveys in developing countries
(8-10%) (75). The higher proportion of rol f
cases in hospital-based studies is consistent •
finding, confirmed by the present study, th^'^
virus diarrhoea is of above-average seventh
lower proportion of rotavirus cases found '
study compared with other hospital-based
probably reflects the relative mildness of dia
among the participating children, many of ThOei
were not hospitalized, but treated as outpatient^
*
081
The present study also confirmed that^
developing countries rotavirus is a significant n
gen among infants aged 2-5 months; in contrast/
developed countries few episodes of rotavirus d'
*
rhoea involve this age group (15). This finding clearh
has implications for research towards a rotavirm
vaccine: a candidate rotavirus vaccine for use ‘
developing countries should be efficacious in infaafi
aged 1-2 months. This requirement has been cosidcred in designing trials of such vaccines supported
by the WHO Diarrhoeal Diseases Control Pro.
gramme (14).
The second most important etiological agent a
this study (Shigella spp.) was the most common
pathogen in children over I year of age. Accordingly,
Shigella spp. (particularly the S. dysenteriae and j
flexncri serotypes) should also be regarded as a pri
ority target for vaccine development, especially since
dysenteric illness is not treated primarily with oril
rchydration salts, but usually requires antimicrobial
therapy. ETEC may also be regarded as a candidate
for vaccine development on the basis of this study
Campylobacter emerged as a significant pathogtA
mainly among under-6-month-olds. Further studic
*
arc needed to assess the role of novel diarrhoci
viruses in developing countries; the present study
however, failed to demonstrate any significant rc«
for viruses (other than rotavirus) that were deteef'
able by electron microscopy. G. lamblia and E.hld^
lytica were not important causes of P^raa^
diarrhoea among young children in the study,
role of Cryptosporidium spp. was not investigated.
In summary, the major findings of th|S
multicentre study were as follows:
. .
—over 60% of cases of acute diarrhoea in^°
children under 3 years of age were among
month-olds;
,
—about 60% of the patients were male; an
.
—rotavirus, Shigella spp. and ETEC were
important causative agents.
t'olop31
While V. cholerae was an uncommon e
agent, it is an important cause of severe de
in endemic areas. As targets for vaccine
ment, priority should be given to rotavirus, ^..
spp., ETEC and K. cholerae. For the grea
candidate vaccines should be efficacious
infants.
•-WHO Bulleli" OMS'd
554
-
Etiology of acute diarrhoea among children In det
gesum®
^ologle de la diarrhee aigue de I’enfant
jjns les Pays en developpement tune etude
I jKjlllcentrique dans cinq pays
gamene pendant 2 ans, au moyen d'un protoco> u normalise, une enquete sur I'etiologie de la
^arrhee aigue chez des enfants ages de 0 a 35
Iois amends pour consultation dans cinq hopitaux
ijtuSs en Chine, en Inde, au Mexique, au Myanmar
» ■- au Pakistan. Au total, 3640 cas de diarrhee et
jj/g temoins apparies selon Page et le sexe ont
etudies; environ 60% des malades avaient
■wains d'un an et 60% etaient des garqons. Un
I j=rnie enterique a ete decele chez 68% des
jalades et chez 30% des temoins. Les germes les
I
souvent associes a la diarrhee aigue dans
K-uS ie^jntres etaient les rotavirus (16% des cas,
M de^remoins). Shigella sp. (11% des cas, 1".
temoins) et Escherichia coli enterotoxinogene
(15% des cas, 5".. des temoins). Chez les 6-11
cois, ce sont les rotavirus qui etaient les plus courjr.ts, representant 20% de tous les cas dans ce
jroupe d’age; 71% de tous les episodes de diaririie a rotavirus sont survenus chez les moms
fun an. Chez les 12-23 mois et les 24-35 mois.
Shigella sp. etait le germe le plus courant. representant respectivement 22".. et 27".. des cas. Le
nombre de cas dans lesquels aucun germe n'a ete
tole est inversement proportionnel a I'age.
fhaximal (41%) chez les nourrissons de moms de
4mois, il devient minimal (19%) chez les 24-35
■fols. Ces resultats indiquent que pour letter
I Mre les diarrhees infantiles dans les pays en
, feveloppement, les strategies d'intervention dev'lient etre axees sur les rotavirus, Shigella sp. et
tKherichia coli enterotoxinogene.
Terences
'• Black, R.E. et al. A two-year study of bacterial, viral
afl(i parasitic agents associated with diarrhoea in
ru,al Bangladesh Journal of infectious diseases,
660-669 (1980).
a°k. R.E. et al. Incidence and severity of rotavirus
^Escherichia coh diarrhoea in rural Bangladesh:
r
*
i
implications for vaccine develop
141-143 (1981).
3. Colro, J.F.R. et al. Pathogens associated with acute
enteritis in Brazilian children. Journal of diarrhoeal
disease research, 5: 110-111 (1987).
4. Ellis, M.E. et al. Microorganisms in gastroenteritis.
Archives of disease in childhood, 59: 848-855 (1984).
5. Georges, M.C. et al. Parasitic, bacterial and viral
enteric pathogens associated with diarrhoea in the
Central African Republic. Journal of clinical micro
biology, 19: 571-575 (1984).
6. Guerrant, R.L. et al. Prospective study of diarrhoeal
illnesses in northeastern Brazil: patterns of disease,
nutritional impact, etiology, and risk factors. Journal
of infectious diseases. 148 : 986-997 (1983).
7. Lokxomboon, U. et al. Viruses and bacteria in pedi
atric diarrhoea in Thailand: a study of multiple
antibiotic-resistant enteric pathogens. American
journal of tropical medicine and hygiene. 30: 1281—
1290 (1981).
8. Mata, L. at al. Diarrhoea associated with rotaviruses,
enterotoxigenic Escherichia coli, Campylobacter. and
other agents in Costa Rican children 1976-1981
American journal ot tropical medicine and hygiene,
32: 146-153 (1983)
9 Mohandas, V. et al. Aetiology and clinical features ot
acute childhood diarrnoea m an outpatient clinic in
Vellore. India Annals of tropical paediatrics 7
167-172 (1987)
10 Poocharoen, L. et al. The relative importance of
various enteropathogens as a cause of diarrnoea
in hospitalized children in Chiang Mai. Thailand
Journal of diarrhoeal disease research. 4 10-15
(1986)
11 Soonarto, Y. et al. Bacteria, parasitic agents and
rotaviruses associated with acute diarrhoea in hospi
tal inpatient Indonesian children. Transactions of tne
Royal Society of Tropical Medicine and Hygiene. TT
724-730 (1983).
12. Stoke, B.J. et al. Surveillance of patients attending a
diarrhoeal disease hospital in Bangladesh British
medical journal. 285. 1185-1188 (1982).
13. Veslkarl, T. et al. Rotavirus, adenovirus and nonviral
enteropathogens in diarrhoea. Archives of disease in
childhood. 56: 264-270 (1981).
14. Veslkarl, T. Clinical and immunological studies of
rotavirus vaccines Southeast Asian journal of tropi
cal medicine and public health. 19.437-447 (1988).
15. De Zoysa, I. et al. Interventions for the control of
diarrhoeal diseases among young children: rotavirus
and cholera immunization. Bulletin of the World
Health Organization. 63. 569-583 (1985).
' ar.
7 Of
;
gotavirus and other viral diarrhoeas
*
■■ie;
'•^r £
the- >
: i
M
-- V
WHO Scientific Working Group1
Recent evidence indicates that viruses are an important cause of acute diarrhoea
in infants and young children in both developed and developing countries. This article
reviews the available information on the epidemiology,^ clinical features, and
laboratory diagnosis of acute diarrhoea due to two of themore important and recently
discovered viruses, namely rotaviruses and the Norwalk and Norwalk-like agents, or
to other viral agents. Research priorities are also recommended that will help to
elucidate the epidemiology, pathophysiology, and means of preventing viral
diarrhoeas. Foremost among these research priorities is the development of a rotavirus
vaccine for use in man.
■>
cu- ■■.■■■
few, •■.<■
ica i’
.bb r
*.
tet
V
■ ■ The problem of viral diarrhoea is a particularly important topic since recent evidence has
indicated that viruses are responsible for the majority of diarrhoeal episodes in infants and
to- B joung children in both developed and developing countries and may account to a considercu <■ ' able extent for malnutrition owing to associated malabsorption. Identification and
jfe' h characterization of these viruses and a clear understanding of their epidemiology are
.innecessary in order to be able to prevent their transmission and, especially, to develop
and |. suitable vaccines.
r-
n
k
and
ROTAVIRUS DIARRHOEA
liD’ S'
M f
I- Rotavirus diarrhoea in man
8;
■ flit virus
Rotavirus was first detected in man in Australia in 1973 by thin-section electron microk'opic examination of duodenal biopsies obtained from children with acute diarrhoea, and
.. toon afterwards in Australia, Canada, the United Kingdom, and the United States of
America by electron microscopic examination of diarrhoeal stool specimens. The virus is
in size, contains RNA, and has an inner and outer capsid. It derives its name from the
a,« |
■
i-f
"rota”> meaning wheel, which it resembles in appearance. Initially, it was also
I
,',ne. Oas “orbivirus”, “duovirus”, “reovirus-like agent”, and “infantile gastrofa|entis virus”.
s
, ieiraal'an ro.tav’ruses are morphologically similar and share certain common antigens with
£ ilosdu10^71111565- By complement fixation (CF) the human rotavirus has been shown to be
to at least 4 animal rotaviruses: Nebraska Calf Diarrhoea Virus (NCDV),
agent flarr^oea °f Infant Mouse virus (EDIM), Simian Agent (SA)-ll, and the offal
:s*'
T
detect? Saeep a°d calves. In fact, these four animal antigens can be used as CF antigens
N
ser°l°gIcaI evidence of rotavirus infection in man; this has been useful for
•Jf. | ■ ’Mdcmiol
f;iJSnProna^1Ca^ stucVes since the supply of human rotavirus is limited because it has not
L- ^Vinises^3^ efficiently in cell culture. (The relationship between animal and human
•-^-^^jsjliscussed further on pages 186-188.)
prints should be addressed to Programme Manager, Diarrhoeal Diseases Control (CDD) Programme, World
tr- I~1!-Tide- ’
GeneVa 27 ’ SwitzerlandW^ing."1*10 Report a Sub-group of the Scientific Working Groupon Epidemiology and Etiology, CDD Proin a fun, "’PC ln March 1979. The participants in the Sub-group are listed on page 198. A French translation
.
Iure edl'ion of the Bulletin.
— 183 —
viral diarrhoeas
' m st cases are children 6-24 months old with a peak incidence at 9-12 months. In a
f°rof hospital-based studies carried out in infants and young children in developed
nU‘?7 eloping countries, rotavirus has been detected in approximately 50% of diarrhoea
.. sometimes
enmetimes witn
with seasonal variation (see below).
oeiowj. tn
In some studies tne
the numoer
number ot
of male
caS£S’|ias been up to 20% higher than that of female cases, but whether this is due to a
cases susceptibility or exposure of male children, or to a higher likelihood of their being
eht for medical care is not known. Data from community-based studies are much more
• ’ted but one carried out in Guatemala and one in Bangladesh suggest that rotavirus
ounts for approximately 10-20% of all community diarrhoea cases.
. A number of serosurveys have been made to determine the frequency of rotavirus
• fection in early life. In a study of persons living in the Washington, DC, area, rotavirus
antibody was detected by CF and immunofluorescence in over 90% of children by the third
of life. In Melbourne, Australia, 40% of infants 2 months of age or less possessed
rotavirus CF antibody; by 3-5 months of age the percentage with antibody had increased
and approached 70% by the age of 3 years. Approximately 70% of adults were also shown.
to have antibody. Workers in Toronto have reported similar results(Qn a serosurvey done in
■jifiUore, India, in which rotavirus antibody was measured by counter-immunoelectro®resis, 85% of newborns were shown to have antibody; by the fifth month 30% and by
the third yearof life nearly 90% had evidence of prior infection^Using the more sensitive
enzyme-linked immunosorbenTassay (ELISA), rotavirus antibody prevalence was found to
be 100% in European and Aboriginal populations 2-60 years of age living in the same area
in Australia and in adults and children living in an area of southern India. Other surveys
using a variety of serological techniques have been carried out in other geographical areas
and have shown similar results, namely that the prevalence of rotavirus antibody is high in.
newborns due to transfer of passive antibody from the mother, then diminishes in the first 6
E months of life, is again very high by the age of 2-3 years, and is maintained throughout life.
This pattern of rapid acquisition of antibody is comparable to that observed with
respiratory syncytial and parainfluenza type 3 viruses.
The high prevalence of antibody in later childhood and adult life can be explained by the
results of family studies from Canada, Norway, and the USA, in which up to 55% of older
siblings and household contacts of paediatric patients with rotavirus gastroenteritis showed
■
evidence of infection on the basis of serological studies. Most of the cases are asymptomatic
and probably represent reinfection. It-is not known whether it is the infected younger child
■■
or the usually asymptomatic adult member who is most likely to introduce rotavirus into the
Afcilyunit. '
necent evidence has demonstrated the existence of more than one serotype of human
rotavirus. Workers in Belgium using a CF assay and immune electron microscopy, in
England using neutralization of immunofluorescent foci, and in the USA using ELISA
ave defined two distinct serotypes. These serotypes appear to be widely distributed
Biographically. In the Washington, DC, metropolitan area, the sera of most children aged 2
| years contained antibodies to both serotypes, and in hospitalized patients type 2 rotavirus
■ seen more frequently. In addition, studies of patients who had experienced sequential
ec ions revealed that illness caused by one serotype did not provide protection against
&
in - caused by the other serotype. It is not certain whether other serotypes exist; workers
£ana using a fluorescent neutralization test have claimed to have found two other
serotypes.
?■
Seasonality
■ thatint^een c'ear'y demonstrated in studies in Australia, England, and North America,
Oneexce Jerate c^mates rotavirus disease is much more prevalent in the colder season.
P 'on may be infection in newborns; in Svdney, Australia, no seasonal variation
184
WHO SCIENTIFIC WORKING GROUP
Clinical features
The incubation period of rotavirus enteritis ranges from 1 to 7 days, but is usually]
than 48 hours. In one volunteer study the onset of diarrhoea occurred 2-4 days after n ■
administration of the rotavirus-containing inoculum. In the usual case of rotayin <
enteritis, vomiting is a prominent early symptom and in many cases precedes the onset
watery diarrhoea. Mucus is found in the stool in up to 25% of cases but blood is rare. Mil
temperature elevation occurs in about 30-50% of cases. Respiratory symptoms havet>3
reported but there has been no evidence to indicate that they were caused by the virus. Asa
*
other enteric infections, the severity of symptoms varies. The average duration of illness^
5^7 days and virus shedding continues not infrequently for up to 10 days. In the moresevere
cases seen at treatment centres, severe dehydration and electrolyte imbalance have been’
observed. Deaths from rotavirus diarrhoea have been reported, although the impact of'
rotavirus disease on infant mortality in developing countries has yet to be determined. '■
In adults infected with rotavirus, mild diarrhoea or, more commonly, subclinic^I
infection occurs, probably because of active immunity (see page 185). For reasons that are
unknown, newborns infected with rotavirus are also often asymptomatic or have only mild
disease.
Treatment of rotavirus disease generally requires standard rehydration therapy. This caa
be administered orally in all but the most severely dehydrated patients who are unable to
drink, or in patients with intractable vomiting. The glucose-electrolyte oral rehydratinn
solution (ORS) developed originally for the treatment of cholera has been used successfully
for the rehydration of rotavirus diarrhoea cases in a number of developing countries.0
An understanding of the pathophysiology of rotavirus diarrhoea has been derived froma
sequential biopsy study of gnotobiotic colostrum-deprived calves challenged with humaa
rotavirus. This study revealed a sequence of events in the small intestine consisting of
infection of the absorptive villous epithelial cells, replacement of the tall columnar villotis
epithelial cells with cuboidal_cells, shortening of the villi, lymphocytic infiltration of the
villous lamina propria, and repair. Such changes appeared in a cephalocaudal direction and
suggest that much of the diarrhoea may be related to a loss of absorptive capacity in tlx
small intestine. Similar morphological findings were observed in small intestinal biopsy
studies in infants.
Human rotavirus can also induce diarrhoeal illness in other newborn, colostrum
deprived animals, including gnotobiotic and conventional piglets, rhesus monkeys, an?
gnotobiotic lambs. It can also infect but not induce illness in newborn puppies. This finding
that only newborn animals are susceptible to human rotavirus has not been explained. Onhypothesis is that this predilection may be the result of higher lactase concentrations in tb>
infant animal, the lactase acting as a receptor and an uncoating enzyme for the rotavirus
A question of considerable interest is whether rotavirus could be responsible for casest
chronic diarrhoea, but no studies have been done to test this hypothesis. Patients withacu
rotavirus diarrhoea usually have increased reducing substances in their stool, reflectir
defects of absorption and of digestion of carbohydrates. This is not surprising giveD ■
pathophysiology of the disease, but these abnormalities do not prevent hydration"
glucose-electrolyte oral solutions.
Incidence
Rotavirus enteritis is generally a disease of infants and young children and aPPea^
have a worldwide distribution. It has been the most frequently observed virus in the 5
of infants and young children with diarrhoea in almost all areas where it has beenl
___________ _ ______________________ ___________ __________________________________________________________________________________ ^Jjl
° Report of the Scientific Working Group on Clinical Management of Acute Diarrhoea, 1978, unpublished
WHO/DDC/79.3.
186
WHO SCIENTIFIC WORKING GROUP
I
was found when rotavirus infection was studied in nurseries for the newborn. Whether th'
seasonal pattern occurs in developing countries with tropical climates is unclear. In studi^ |
from Costa Rica‘and Venezuela little or no seasonal variation in occurrence has bee
*
5
observed; however, in studies in Bangladesh and in Calicut and Vellore, India, rotaviruf- '£
have been found most frequently in stool samples collected from diarrhoea cases betwe? f
November and March, which are the coolest months of the year. In the Vellore study, rotan. f
viruses were present in the neonatal nursery throughout the year, as was observed in the ? *
Australian study cited above. In one small study conducted in"Mexico City, where there is I
almost no seasonal difference in temperature, there was a peak of cases in the autuiffB
months.
fl
r
■ ■
"I
Transmission
"■ J
All evidence to date indicates that rotavirus infection spreads by faecal-oral transits. 1
sion; this has been confirmed by volunteer and animal experiments. There is no evidence to s
suggest that rotavirus multiplies with production of infectious particles anywhere else than; i
in small bowel enterocytes.
::f I
Although IgA specific antibody has been found in the colostrum and breast milk of |
lactating mothers in a number of countries, it is not clear what role breast milk playsift protection against rotavirus disease, especially in developing countries where breast feeding ;
frequently continues past the sixth month of life, when rotavirus disease is common. ■ i
Outbreaks of rotavirus diarrhoea have been documented in nurseries, especially those 1
providing special care, and in a number of paediatric hospital wards. This problem of
nosocomial transmission of rotavirus has been a difficult one to control.
Role of rotavirus in disease other than acute enteritis
Rotavirus infection has been described in children with intussusception and children with
gastroenteritis and self-limited gastrointestinal bleeding. Clinical findings compatible with
Henoch-Schoenlein purpura developed in one child in the latter group. In another reports
child with rotavirus-associated gastroenteritis had a severe central nervous system manifes
tation and developed fatal Reye’s syndrome. In another child, encephalitis was reported.
Several children with rotavirus infection have developed the haemolytic uraemic syndrome
or disseminated intravascular coagulation. Elevated SGPT and SGOT levels havealsobea)
reported in some cases. In addition, there are reports that rotavirus has been isolated from
intestinal tissue obtained from patients with Crohn’s disease. One such report could not be
confirmed in another laboratory, in which a contaminating, fastidious Mycoplasma
detected from such a patient. The isolation inT^ll culture of a rotavirus from extractso>
mesenteric lymph nodes from a patient with Crohn’s disease has been described recentlyThe role of rotavirus in the above conditions is unclear and needs further study.
Rotavirus diarrhoea in animals
Epidemiological features
fl
Rotavirus has been shown to be a common intestinal infection in animals and has be?
demonstrated as a cause of diarrhoea in mice, calves, piglets, foals, young rabbits,
pronghorn antelope, chickens, turkeys, goats, kittens, a chimpanzee, and a gorilla- The
also evidence that it can infect other animals, as shown by virus isolation studies in tnon ■
and dogs, and serological studies in goats, dogs, and guinea pigs. From virologies
serological studies it is evident that infection occurs in early life in 90-100% of
calves, as is the case in man, but at a lower level (38% in one study) in sheep- This
infection rate in sheep may reflect the different systems of husbandry; the sheep stu
VIRAL DIARRHOEAS
j under less crowded conditions which may have reduced the probability of transmis■ n Laboratory colonies of rabbits and guinea pigs show a wide variation in the number of
flj.nals with antibody to rotavirus (0-100%). However, under natural conditions of
husbandry, where populations have an urban distribution or where many young are
•ongregated, the incidence of rotavirus infection in these species frequently reaches 100%.
1 In pigs and calves the severity of rotavirus infection, as judged by mortality, is usually less
ihan that associated with Escherichia coli or coronavirus infections, although epizootic
disease has had a reported mortality of up to 90%. However, it should be borne in mind that
whereas E.coli and coronavirus infections can be diagnosed efficiently by staining of
intestinal tissue obtained at autopsy, rotavirus infection cannot be so diagnosed and often
requires electron microscopy for its detection. Some veterinarians have observed an
apparent association of other agents, including bacteria and viruses, and also
environmental stress with increasing severity of disease in naturally occurring epizootics.
The epidemiology of rotavirus infection in animals is not well understood. Although the
disease usually occurs in infants or neonates, diarrhoea has been seen in adult animals in
whom the rotavirus serum antibody titres are zero or low; often both the dam and her
offs^g have concurrent illness. It is probable that intestinal immunity of a level sufficient
to prevent reinfection of the gut lasts not more than 6 months following infection, and thus
the virus may be circulating constantly in the adolescent and adult population. In addition,
the great stability of the rotavirus in faeces and its resistance to pH changes (pH 2-9.5),
temperature (60°C), and a number of commonly used disinfectants, probably result in
prolonged survival of the virus in contaminated buildings and water supplies.
It has been suggested that rotavirus may cross the placenta and infect the fetus, which
would then be born either with infection or with actively acquired immunity. This hypoth
esis was based on reports, largely unpublished, that antibody to rotavirus was found in
fetuses and that calves were frequently ill within 48 hours after birth. However, of the many
hundreds of calves and pigs obtained by Caesarean section for rotavirus research from
herds in which rotavirus infection was common, none has been shown to possess serum
antibody, to be immune to experimental infection, or to be actively excreting virus. Since
the incubation period for rotavirus infection is short (1-2 days), it is more probable that
most infections in early life occur as a result of postpartum contact with an infected person
or environment.
Immunological considerations
Preliminary data suggest that, although all rotaviruses have a common antigen, a wide
ringe of antigenic subtypes can be differentiated by laboratory tests (see page 190). At
Present, these are recognized mainly among isolates obtained from different mammalian
although at least two subtypes have been reported among human rotaviruses (see
185). Most rotavirus strains tested under experimental conditions show cross-infection
een mammalian species (e.g., human, bovine, equine, porcine, and ovine rotaviruses
.Iect Piglets; human rotaviruses can infect monkeys; human and equine rotaviruses
Paste
ca^ves). Some, but not all, of these cross-infections cause diarrhoea (see
^ural There has been no evidence to prove that rotaviruses cross species barriers under
faund Coaditions. However, in England one human rotavirus isolated from a child was
^icall° be seroI°g'cally dose t0 a bovine strain, and one isolate from a pig was serofifferei^t m°re c*osely related to a bovine than to a porcine strain. Thus it appears that
iatigeni rota'?rus strains exist wyth different antigenic specificities. Whether the different
^l’nowSPeC1fiCat’ons wou^ he likely to cause problems in a vaccination programme is
n- However, with a closely related virus, blue tongue of sheep, there are at least
1SS
WHO SCIENTIFIC WORKING GROUP
22 strains which, although they share a'common antigen, show relatively p00r Cro f
protection. This virus infection is limited to sheep (virulent infection), to cattle (large».?- J
subclinical), and possibly to wild ungulates. In comparison, rotaviruses are more wide?
distributed in the animal kingdom and thus can be expected to show as wide, or widl'T
antigenic variations.
Cross-protection studies between different animal species in different laboratorieshav-^4
given conflicting results. In one study, 3 gnotobiotic calves were inoculated with foal rota'-virus and 3 with human rotavirus within 3 days after birth and none in either group dgffiE
oped a diarrhoeal illness; however, on challenge with bovine rotavirus 21 days after
initial inoculation, 2 of 3 animals in each group developed a diarrhoeal illness, suggest^?’
that only limited, if any, protection was induced by the initial inoculum. In two more recent i J
studies in pigs, bovine rotavirus and human rotavirus were ineffective in protecting piglets' 1
from later challenge with porcine virulent rotavirus. In another study of the relationship'i
between human, ovine, equine, and porcine rotaviruses in pigs, all of which are separable ■1
by a neutralization test, there was poor evidence of cross-protection. In contrast to these
studies, other workers have reported good evidence of cross-protection, including the-.demonstration that (a) bovine colostrum can protect pigs against challenge with a porcine.isolate of rotavirus, (b) bovine rotavirus vaccine can induce protection against human type'-.
2 rotavirus in calves, and (c) pigs infected with human rotavirus type 2 are protected against:?
later challenge with porcine rotavirus. In none of these studies were the isolates used of the~:
same origin, nor was the 1D6O of the challenge virus determined.
It is thus evident that further studies are required to determine the amount of cross
protection between rotavirus strains of different species. Even if cross-protection between
strains is demonstrated experimentally, the efficiency of the protection may be less under
field conditions as most reports of experimental studies indicate a lower mortality frOH.
rotavirus infections than that seen in natural outbreaks, except in newborn piglets.
In contrast to the conflicting data on cross-protection, there is good experiment#
evidence that animals can be effectively immunized against disease induced by rotaviruses
their own species. Although limited, all the work published to date has shown that animak
that are inoculated with rotavirus and allowed to recover are, on challenge 3 weeks later.
immune to rotavirus illness and shedding. Similarly, calves vaccinated with an attenuate?
live rotavirus are immune to challenge with the parent virulent virus or with another bovine
virulent rotavirus of close antigenic relationship. Also, virulent virus in the presence«
colostral antibody in the intestine induces a subclinical infection that immunizes &
animals against illness and rotavirus shedding for at least a limited period. It cant
*
concluded from the available evidence that rotavirus infection in mammals results in >
development of immunity to illness and rotavirus shedding, and it is most likely that K
vaccines to be effective they will need to protect against each serotype that can infect!?
particular mammalian species under consideration.
■
Laboratory diagnosis
Methods for the detection of rotavirus in stools
In human infections large numbers of rotavirus particles are excreted in the stooloptimal period for virus detection is within the first 3-5 days after onset of sympto^5-^
virus particles can usually be seen easily by negative-stain electron microscopy (EM)
• ing differential centrifugation; in many instances they may be seen without centrifu§a '
The size and the characteristic double-capsid structure of the particles can be readily
nized. In stools that contain few virus particles the use of immune electron rn'cr°tjCj
(IEM), i.e., the addition of specific antiserum to the stool extract to aggregate the P
may occasionally make them easier to identify.
VIRAL diarrhoeas
189
f electron microscopy is an efficient way of detecting rotavirus infection, but it is
time and equipment, and most developing countries do not have such facilities.
other methods to detect virus particles have been explored.
of these is immunoelectro-osmophoresis; this method is rapid and cheap but its
°'tivitv depends on the quality of the antiviral serum used. Although some workers find
a-1 re sensitive than EM, most have found it either as good or somewhat less sensitive.
'The use of a special modified complement-fixation test (CF) to detect rotavirus in stool
■■ inension has also been reported and has been found to be almost as sensitive as EM. One
\jr problem is that many stool extracts are anti-complementary, although the addition
fetal calf serum may overcome this difficulty. With this method, high-titred human sera
' -e found to be better than rabbit sera for the detection of human rotavirus.
Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) have been
•rdsuccessfully for the detection of human and calf rotaviruses. The methods are claimed
Wk at least as sensitive as EM and probably more sensitive. With ELISA, the specificity of
stive specimens has to be established with appropriate “blocking” reagents. The
.Ants with RIA are that sophisticated equipment is required and radioactive material
■; be hazardous. In this respect, ELISA shows more promise, especially because it can be
ssd under field conditions to examine a large number of stool specimens.
immunofluorescence (IF) has been used to stain cells or cell debris excreted in stools from
ejected calves. The problem of non-specific fluorescence has prevented its widespread use
human stools, but this can be overcome if the virus antigen is first separated by immune
precipitation prior to staining. However, this method is laborious and time-consuming
then done on a large scale. A simpler method is needed to make the use of IF more
IKeptable.
A new test termed solid-phase aggregation of coated erythrocytes (SPACE) has been
scitibed, which combines some of the features of ELISA and of solid-phase radiot sStunoassay. This method involves the coating of microtitration U-plates with specific
rr-iiviral antibody and the addition of 1 OTo faecal suspensions. The absorbed viral antigens
Allien detected by the addition of erythrocytes coated with specific antiviral IgG. The
plaits are read in the same manner as the conventional haemagglutination test. This test
been shown to give very good agreement with both EM and IF, but appears to be limited
--^plication because of the need for frequent preparation of coated erythrocytes.
| wWtioned previously, one of the most urgent needs is to find a simple method for the
■
propagation of human rotavirus in cell culture; this would undoubtedly also
- r-ose diagnostic tests. Enhancement of virus growth in cell cultures by adding proteo| C'cnzymest0 Reculture medium has been reported. A-cell culture method that is capable
r ^7anonstrat‘n6 the presence of human rotavirus antigen, usually in a single passage, has
. P °yed successfully; this involves centrifugation of stool specimens on to a guineaI ^stiru^ Cf H l-'ne ^owed by IF staining. This is a relatively simple way of diagnosing
v -i-jri .tntection, titrating virus infectivity, and estimating neutralizing antibodies in
K
ena proPagation of human rotavirus by this technique, alone has not been
B'A
measurement of rotavirus antibody
was used^ °1'teStS have been developed for the measurement of rotavirus antibody.
I-^sysorfor
S-Ome earher studies on human sera; however, for general serological
B
test (pF?d’agnosis a simpler and quicker method was needed and the complementK^nrotaviru ?assh°wn t0 meet this requirement. Initially the CF antigen used was
B^^Ooreread'i°°ta'neC^ from st°ol extracts, but it was found that this could be replaced
0 age yavaihble bovine rotavirus grown in cell culture, or even more efficiently
n (see page 183). One limitation of the CF test is that it does not
190
WHO SCIENTIFIC WORKING GROUP
distinguish between antibodies of different species origin. Another simple and ch ‘
method for detection of group-specific rotavirus antibody is radial immunodiffu$i0n,T$.i
With ultracentrifuged concentrates of stools as antigen, a single strong line common teM
the rotaviruses can be seen against antisera from convalescent children and animals. Th’ S j
test has been used to measure serum antibody titres against human rotavirus. Antib^I
have also been quantitatively detected by RIA and ELISA using the “double-anti^^?
very sensitive and have the added advantaoe
advantage often)
sandwich” technique. These tests are verv
adaptable to measure specific immunoglobulin
oplobnlin classes of antibody.
antibodv. Anti-rotaviral
Anti-rotavirai 1^3
also been measured by IF.
•
Methods for the identification of rotavirus strains and serotypes
CF, IF, ID, and IEM techniques have shown that rotaviruses share a common grog
antigen that is associated with the inner capsid of the virus particle. However, human^'
animal rotaviruses can be distinguished by neutralization of immunofluorescent foci'll
ELISA blocking techniques. A one-way serological relationship between human and sung]
rotaviruses has been reported as a result of IEM studies; a one-way ELISA blocking"^]
showed these viruses to be distinct.
The existence of two rotavirus serotypes in man has been demonstrated by neutralizatiQ
tests, CF, and ELISA. Two additional serotypes have been described by workers usingfe
neutralization technique (see page 185).
Electrophoretic migration of viral nucleic acid has been useful for distinguishing virag
and is based on differences in the migration of RNA segments on polyacrylamidegels.RNi
analyses can be carried out directly on most stool samples in which rotavirus particles®
visible by EM. However, a correlation between serotypes and ‘‘clectrophoretypes” hass?.
been established and a difference detected by this technique may not necessarily reflate
antigenic difference.
5WI
■ t-.'Tt'
DIARRHOEA DUE TO NORWALK AND NORWALK-LIKE AGENTS T;
Description and characteristics of the Norwalk-like agents
I-',-
Since 1972, a new group of agents, of which the 27-nm Norwalk particles a?r,°Lrf
has been discovered and found to be associated with outbreaks of generally mild^
enteritis occurring in school, community, and family settings. In antibody Pr
studies employing a newly developed immune-adherence haemagglutination assa^ •La
it has been found, in the Washington, DC, metropolitan area, that antibody to the \
agent is acquired gradually in childhood and more rapidly in adult life, so that an >
present in 5O°7o of the population in the fifth decade of life. This pattern of
acquisition contrasts markedly with that of rotavirus infection and suggests
Norwalk agent and probably other morphologically similar agents are not a major-f.
gastroenteritis in infants and young children but are more likely to be primarily
with illness in older children and adults.
ritis^
The Norwalk agent was initially discovered in an outbreak of gastroen
occurred in Norwalk, Ohio, in which 50% of the pupils and teachers in an e
school and 32% of the family contacts became ill. A filtrate made from a r
obtained from a secondary case was administered .orallyHo three adult volu .. .
VIRAL DIARRHOEAS
191
d disease in two; it was subsequently successfully passaged serially. The agent could
J" ropagated conclusively in any cell or organ culture system and was first visualized
f'- une electron microscopy (IEM) in an inoculated volunteer’s infectious stool filtrate.
recently also been detected in vomitus from 4 of 5 volunteers who developed gastro■■^tis after administration of a 2% filtrate of the agent.
'"Articles resembling the Norwalk agent morphologically and in density were
, anently discovered by IEM in individuals in two family outbreaks of gastroenteritis,
L.
-~>7nHawaii (Hawaii agent) and the other in Montgomery County, Maryland (MC agent).
-, 'EM and cross-challenge studies, the Hawaii and Norwalk agents were found to be
t‘"act the Norwalk and MC agents to be related, and the relationship between the Hawaii
--4.MCagents was inconclusive. Viruses resembling the Norwalk agent in morphology and
-tq’ were later observed in faecal specimens from: (a) a gastroenteritis outbreak in a
•^ciaiy school in Ditchling, England; (b) a volunteer who became ill after administration
-?the‘'W” agent that had been obtained from a boy who developed gastroenteritis during
■-outbreak in a boarding school; and (c) individuals developing gastroenteritis after
--gcockles. By IEM, the Ditchling and “W” agents are related but are distinct from the
Norwalk agents, whereas the cockle agent appears to be distinct from the
Sswaffagent. However, the relationship of the cockle agent to the other agents is
Conclusive. Thus, besides the cockle agent, there appear at present to be three serotypes of
group of agents.
These agents have a diameter (shortest diameter) of 25-27 nm. They are not perfectly
rsfid, the Norwalk agent, for example, averaging 27 nm in its shortest diameter and 32 nm
3its longest; they are similar morphologically to the picorna or parvoviruses and the
bpiiitis A virus. A clear-cut substructure is not visible by electron microscopy (EM). They
y-.?not yet been propagated definitively in vitro and therefore must be detected by EM,
EM or, in addition, for the Norwalk agent, bv the recently developed radioimmunoassay
(HA) or IAHA.
. Rcse agents have a buoyant density in caesium chloride of 1.37-1.41 kg/litre as deterTSed by ultracentrifugation and IEM or EM. Their nucleic acid and protein contents are
i-fiown. The Norwalk agent is stable after exposure to pH 2.7 for 3 hours at room
^erature, as determined from infectivity studies in volunteers. Similar studies have
nthat the Norwalk and “W” agents are stable after exposure to 20% ether at 4°C for
*
^
-fid 18 hours, respectively. The Norwalk agent is relatively heat-stable, retaining infec■?TwtfUnteerS after heating at 60°C for 3° minutes.
■ -Sts^^ents have not yet been classified. However, since the Norwalk agent shares
■ acter'st’cs w’th the parvoviruses, such as morphology, density, and ether, acid,
tlve heat resistance, it appears to be parvovirus-like. It should be emphasized
taat none this group of agents has had its nucleic acid content identified; thus
be c'ass’fied into any group.
■.■».?( t?. a2ent has been administered to mice, guinea pigs, rabbits, kittens, calves,
d lmpanzees> and rhesus, marmoset, owl, patas, and cebus monkeys; none of the
^'ness- When paired sera from monkeys, baboons, and chimpanzees
Qh- *Or a Norwalk serological response, only the chimpanzee developed such a
^' ’•'4terchallPanZeeS Were a'so ^oun(dt0 he shedding Norwalk antigen when examined by
epidemiological characteristics
L%
g the 604 nr'
j?'*42,84%
and secondary cases in the original Norwalk outbreak, 85% had
miL1ng, 52% abdominal cramps, 57% lethargy, 44% diarrhoea, 32% fever,
192
WHO SCIENTIFIC WORKING GROUP
and 5% chills. Symptoms lasted 12-24 hours in the majority of cases and seldom |0 ’
than 48 hours; none of the patients was hospitalized. The average incubation period w
hours. The signs and symptoms of illness observed in 32 of 55 volunteers whodevel
illness following the administration of 2% filtrates of stool containing Norwalk agent vr
very similar to those observed under natural conditions: incubation period 10-5] fever (37.4°C) in 16 (50%), diarrhoea in 27 (84%), vomiting in 20 (63%), abdomh
discomfort in 23 (72%), anorexia in 30 (94%), headache in 27 (84%), and myalgia
malaise in 20 (63%). The clinical manifestations usually lasted for 24-48 hours. TheiK
was generally mild and self-limited, although a volunteer who vomited approximately-^
times within a 24-hour period required parenteral administration of fluid. Sheddingof^,
Norwalk particle in volunteers, as determined by 1EM, was at a maximum during thefif72 hours after onset of clinical illness and occurred only infrequently afterwards. Thesis
and symptoms of illness observed in volunteers following administration of the Hawaj
MC, and “W” agents have been similar to those observed with the Norwalk agent.
In volunteer studies with the Norwalk agent short-term and long-term immunity
been observed. It appears that mechanisms other than that mediated by serum antibody^
of primary importance in immunity to Norwalk gastroenteritis.
In volunteers challenged with the Norwalk or Hawaii agents, characteristically, therej
broadening and blunting of the villi of the jejunal mucosa; the mucosa itself is histological
intact. Moderate amounts of mononuclear cell infiltrates and cytoplasmic vacuolizatioocf
epithelial cells have also been observed. Examination of thin sections of the jejunal mucos
by transmission electron microscopy has revealed intact epithelia! cells with shortening?
microvilli, dilatation of rough and smooth endoplasmic reticulum, swelling of nifa
chondria, and an increase in lysozymes; virus particles were not seen inside these
Biopsies taken 6 or more weeks after infection have been normal. During Norwalkillns
the gastric mucosa appeared normal histologically. Small intestinal brush-borderenzye
(including alkaline phosphatase, sucrase, and trehalasc) were decreased; significant:
adenylate cyclase activity in the jejunal mucosa during Norwalk or Hawaii illness waste
not to be elevated.
The role of the Norwalk agent in outbreaks of gastroenteritis has recently been invef
gated employing the newly developed Norwalk RIA and radioimmuno-blocking assay.!
of 23 outbreaks were found to be associated with the Norwalk agent; of these, twooccuf
on college campuses in the USA, one in a primary school in Japan, two on cruise shipSH^
one in two members of a family, one of whom was involved in an elementary s#
OStbreak while the other, a secondary case, developed a serological response and sh>
morphologically Norwalk-like particle. If one includes the original Norwalk outbreak
well as the serologically related outbreak in Montgomery County, both of which
associated with Norwalk-like particles as determined by IEM, 8 separate outbreak
gastroenteritis (32%) have been identified among 25 studied. If suitable serological
had been available for Hawaii and “W” agents, it is possible that the majority,^
outbreaks would have had an assignable etiology. In addition, a recent study *n
suggests that at least part of another outbreak of gastroenteritis related to the & .
oysters was associated with the Norwalk agent.
■
Laboratory diagnosis
Methods for direct detection in stool of Norwalk and Norwalk-like agents
■
- .Ug
Immune electron microscopy (IEM) was used for the initial detection ot u
agent. To detect the Norwalk agent in stool material, a stool suspension or
,
*flct
viral diarrhoeas
193
l,ated with a convalescent Norwalk serum or immunoglobulin. The mixture is then
' (rjfiiged,
*
supernatant poured off, and the pellet or sediment reconstituted with
: ^-tilled water and examined with a negative stain by electron microscopy.
, '"phe Norwalk group of agents cannot be identified directly by electron microscopy (EM)
•.^ause they do not have a sufficiently distinct morphology. However, the Ditchling and
(and cockle) agents have been examined by EM after concentration by ultracentri•jjgation, followed by density gradient centrifugation in caesium chloride: for EM, a drop
■•(fluid from a fraction was placed on a slide covered with 0.9% agarose, a grid was
'-'bsequently placed on the drop for 30 minutes to permit the caesium chloride to diffuse
^•o the agarose, before examining the grid with a negative stain.
A radioimmunoassay (RIA) has recently been developed for detection of Norwalk
»ent in faecal specimens and appears to be even more efficient than IEM. The assay is
' tew on a differential binding of stool suspensions containing Norwalk particles to a
•srotitration well coated with convalescent and another coated with preinfection antiSorwalk antibody. By this method, non-specific interaction can be separated from specific
Jicrwalk binding. The assay can detect soluble viral antigen as well as particulate material.
I ftifo^ately, some stool specimens (less than 5%) have high non-specific activity that
| raksspecific Norwalk binding. The success of this technique is dependent on the
I availability of specific reagents, and the only available, satisfactory antisera to the Norwalk
| agent have been obtained from human subjects or chimpanzees infected with the Norwalk
. igent. High-titred convalescent and antibody-negative preinfection sera from the same
| jerson or chimpanzee must be used. At present, these sera arc not available commercially.
E ftlhods for measurement of antibody to Norwalk and Norwalk-like agents
Until recently IEM was the only method for detecting a serological response to the
I Norwalk agent. Since IEM is employed for the detection and recognition of the Norwalk
j 't|tnt, an IEM serological assay with appropriate paired sera is essential to determine the
l ^iUficance of a particle visualized as a result of reaction with convalescent serum or
| 83iune serum globulin.
.;More recently, an immune adherence haemagglutination assay (IAHA) has been
‘
In this technique, the Norwalk antigen is prepared from human stool containing
■C
particle using various extractions and concentration procedures. The test
oys several reagents and human O erythrocytes, and has similarities to both a
| T-P.ement-fixation (CF) and a haemagglutination test. It has been quite specific for
i JCtlng ser°i°gical responses as it has a high degree of concordiSce with IEM and RIAPtujfti Ow)’ but IEM and RIA-BL are slightly more efficient. In addition, IAHA cannot
^HA f ° detect Norwalk antigen in stool specimens. A major drawback with the use of
u1, Ser°Iogical studies is the lack of an adequate supply of Norwalk antigen.
loathe Ri Areclu'res considerably less antigen than CF, it still uses considerably more
I^Aa <?• BL testaddition, not all human O erythrocytes react comparably in the
I’a.ts with11 may be necessary to screen numerous donors’ erythrocytes to find a donor that
I & rad’ e-nough sensitivity to a known antigen.
&%rwalka °!!”munoassay for detecting Norwalk antigen has been modified to identify
i^ionth '
y *n the form °f a radioimmunoassay blocking test (RIA-BL). The assay is
fe>;itRahiSy of a test serum to block the binding of 125I IgG antiNorwalk to Norwalk
»• 'y sensitive and specific and was found to be slightly more efficient than
j^A-BL test ‘lri8 sFr°I°g'ca’ responses in volunteers challenged with Norwalk agent. The
jn.ls, suitable for large-scale studies and can theoretically be used to detect
y fluids other than serum (i.e., intestinal secretions or milk).
194
WHO SCIENTIFIC WORKING GROUP
OTHER VIRAL DIARRHOEAS
'< -,'Z.J
-rt
'
A number of viral agents have been identified whose role as etiological agents of
diarrhoea is not clear. These can be divided into two groups. One includes those virus^^l
as adenoviruses, coronaviruses, and enteroviruses that are universally recognjdfz
mammalian viruses; the other includes particles or agents that have been described
number of investigators and termed astrovirus, calicivirus, and mini-rotavirus. Thea2*
'
able knowledge on these agents is summarized below.
Adenovirus
"'^.'..'1
Adenoviruses are well established as respiratory viruses (33 serotypes have jj^l
recognized in cell culture) and the common serotypes can be isolated from stools inttf
culture. Recently, a number of workers have reported visualizing by electron micros^
(EM) morphologically indistinguishable viruses in stool which could not be grtej
subsequently in cell culture. The reason for this phenomenon is unknown, but it^
prevented more than tentative identification of such strains. Adenoviruses have
isolated from many animal species but none has been clearly implicated as a caused *
diarrhoea.
In several studies adenoviruses have been found by EM in stools from 5-8% ofnorc^
children; in some, prolonged excretion was common. No one serotype has been assodj'4
convincingly with diarrhoea. In one recent outbreak the virus could be identified only^
immune electron microscopy (IEM) and could not be grown. The role of adenovinisa
especially those that do not grow or grow poorly in cell cultures, as etiological agentJSf
diarrhoea needs further study. In volunteer studies, which have been confined to wellesBJ
lished strains, viruses were grown from faeces but gastrointestinal symptoms were noise?
Astrovirus
Astrovirus was first described in Scotland in 1975 in the diarrhoeal faeces of.inW
examined by EM and has subsequently been observed elsewhere in the United Kingd&
Very similar, but possibly not identical, particles have been reported from Australia
*?
Canada. These particles cannot be grown in routine cell cultures but limited grow
*
occurred in human embryo kidney (HEK) cells; growth was detected by immunoiwj
escence using an antiserum prepared in guinea pigs. No evidence has yet been found 01 existence of more than one serotype.
. .
The role of astrovirus as an etiological agent is unclear. In one study, they were 1
more frequently in the stools of infants with diarrhoea than in controls; they ^avea'S^
implicated in two outbreaks in the United Kingdom. Postinfection increases in a?3|
have been detected by IEM. In adult volunteers challenged with astrovirus,
common and was accompanied by excretion of large amounts of virus and by serOv<
sion, but illness occurred in only a small number of individuals.
j
Morphologically similar viruses have been found in the faeces of lambs and calv V
lamb virus has been shown to cause diarrhoea in gnotobiotic lambs, but the c
induced only seroconversion in gnotobiotic calves. Astroviruses from man, lain |
calves have been reported to be serologically distinct.
Calicivirus
This agent was first described in a community survey in Scotland in 1976,
detected by EM in the faeces of infants, and similar viruses have been reported by
VIRAL DIARRHOEAS
195
ries in the United Kingdom. Apparently similar particles have been reported by two
‘j^tories in Canada, but in both cases they were labelled astroviruses and thus the
$tora
somewhat confused. No growth of this agent in cell cultures of human or feline
has been reported, and different serotypes have not been described.
e report, calicivirus particles were detected in the faeces of children involved in a
I outbreak of “winter vomiting”. The particle was found only in the faeces of patients
A'j°not m contacts. One adult teacher was also affected, but did not seroconvert. Other
“■ t, have indicated a less definite association between calicivirus and gastroenteritis. No
■■'unteer studies have been reported. Morphologically similar viruses have been isolated
'-•'in pigs cats, an<^ sea'I'ons> though none of these agents has been shown to cause
•■^rrhoea in the natural host. It is not yet clear whether there is more than one serotype of
feline virus.
Coronavirus
Th^mportance of coronavirus as a cause of diarrhoea remains unknown. In one report
.• lioWFiruses were detected by EM in stools obtained from 3 outbreaks of gastroenteritis in
Uults and the particles in a stool from one of the outbreaks were propagated in organ and
id!cultures. No volunteer studies with the virus have been done. Coronaviruses, however,
mturally infect many animals (chickens, mice, pigs, calves, dogs, rats, and cats) in w hich
,-y cause a variety of clinical symptoms including diarrhoea in certain animals.
Enterovirus
Sixty-eight enteroviruses have been identified, all of which, with the possible exception of
J, can be isolated from faeces. Electron microscopy showed them to be small (25-nm)
futureless spheres indistinguishable from one another. Techniques for isolating entero, nfUSCS have been available for over 10 years and numerous investigations have attempted to
' implicate them as causes of diarrhoea. In general, no convincing evidence has accrued,
Cough from time to time outbreaks apparently involving well-characterized types have
KCT reported (for example, echovirus types 11, 14, 18, and 19). Whether such outbreaks
■ »ttedue to the enterovirus or to an undetected agent is not known. There is no evidence that
■.CCWjLknown pathogenic enteroviruses like the polioviruses and coxsackieviruses cause
! SarrWa.
fhe absence of any clear association between enteroviruses and diarrhoea has stimulated
| ”-£~nteer studies. Some studies have been performed using strains of echoviruses and
‘ Sis 'e A v'ruses isolated from the throat, but these caused little or no gastrointestinal
found in a number of animal species but there is no evidence that they
larrhoea in their natural host.
small, round, virus-like objects (SRVs)
11 So
SStehave been shown to contain other virus-like particles 25-35 nm in
isy have C k° S°me *nvest’gators are clearly different from the background materials;
'■ ^'^dationwhh
®rown *n ce^ cultures. These SRVs have been reported mostly in
■Mffeak the SR^ut^rea^s °f gastroenteritis in communities or institutions. Within each
^Wan s Were consistent m size and appearance, but they differed between one
’poradic^not^er- Several investigators have reported SRVs in the faeces of patients
arrhoea (e.g., the “mini-rotaviruses” described in Canada, which were
196
WHO SCIENTIFIC WORKING GROUP
morphologically similar to the viruses observed in an outbreak in Scotland) and •
absence of associated outbreaks it has been difficult to obtain enough material f ln
detailed investigation. Similar SRVs have been seen in the faeces of dogs and P’gS V,j
diarrhoea, but their relationship to human SRVs, if any, is unknown.
RECOMMENDATIONS FOR RESEARCH
Rotaviruses have emerged as the most important viral agents associated etiologically ■-<
severe diarrhoeal disease in infants and young children, and simple techniques areavaifev
for their identification. Therefore, priority should be given to research aimed at elucidat‘d
the epidemiology, pathophysiology, and means of prevention of illnesses caused by
viruses. Norwalk and Norwalk-like agents have also been recognized as a caused
diarrhoeal diseases, predominantly in older children and adults.
The following recommendations are made for further research:
Rotavirus diarrhoea
1. Studies are needed to define more completely the mortality and morbidity attribute
to rotavirus diarrhoea in different geographical areas. Any factors, either host orenvfe
mental, that affect the severity of the disease need to be identified.
2. The epidemiological characteristics of rotavirus diarrhoea in different geography
areas also need elucidation. Studies should seek to define the following: relative incite
of the two recognized serotypes; seasonal occurrence of the disease; its modes of tri?
mission; natural history of the disease; reinfection rate; incidence of asympto®
infection; the relationship between nutritional status and the incidence of disease; pos®
association of the virus with chronic diarrhoea; the natural reservoir of human rotavifiS"
factors influencing the survival of rotaviruses in the environment and the physicochecs
stability of the virus.
3. Studies are needed to determine why human neonates infected with rotavirus^
experience mild disease or subclinical infection. The relative infrequency of severe due1
in human neonates with rotavirus infection is in direct contrast to the natural history
infection in older infants and in young children; in the animal world also, the new
experience the most severejotavirus illness. These studies should consider such facto??
immune status, virulence ?5f the virus, diet, and influence of other faecal organisms-#?
mation is also needed to learn whether human neonates with initial subclinical
susceptible to reinfection and/or disease from the same or another serotype later in ?
whether they are rendered immune by the initial infection.
.Jg
4. Further studies are needed to determine the pathophysiology of rotavirus diR|
5. The effect of feeding during diarrhoea on the clinical course of rotavirus m.<
needs to be determined.
.
6. The role, if any, of rotavirus disease in malabsorption and subsequent nu .<
deficiencies should be ascertained.
7. More research should be undertaken on the serotyping of rotaviruses iso1^..
animals and humans, to better define possible reservoirs of infection. Under exp
conditions, rotavirus virulent for one mammalian species may infect an0tnc(Js
subclinically. Thus, under natural conditions, it is possible that human con
represent a source of infection for animals and that animal contacts are a source
for humaris.
197
VIRAL DIARRHOEAS
arch is needed to find methods for determining the virulence of rotavirus in
i- nd humans, both as a means of comparing different isolates and also as a method
.•’jinas m:nina whether a causal relationship exists between a virus present in the faeces
% the clinical syndrome.
ejnce human rotaviruses do not grow to sufficiently high titre to allow them to be used
" ia
vaccine
development effort, a high priority should be given to studies of
111
’ C-V
-nhods for more efficient propagation of these agents.
Although intestinal IgA rotavirus antibody is known to be of prime importance in
-ventin’rotavirus illness, additional studies are needed to establish the duration of, and
■ -ms of enhancing, the immune response. Studies of rotavirus antibody levels in
--■retions such as saliva and breast milk are required to determine whether they reflect
Aibody content in small-intestinal fluid.
H Studies should be carried out to determine the influence of breast feeding on the
mural history of rotavirus infection. Epidemiological, immunological, and social factors
-jiould be investigated. Knowledge gained from such studies would help to determine
whether a rotavirus vaccine should be administered to women of child-bearing age.
•> Since passive administration of rotavirus antibody by the alimentary route has
in resistance to rotavirus challenge in various animal models, studies in humans on
the effect of oral administration of human rotavirus antibody might be considered.
Another approach might be the oral administration of purified separated fractions of cow’s
"immune milk” (containing antibody to rotavirus).
13, An experimental animal in which disease could be induced beyond the early period of
life should be sought. This is important for studying the safety and efficacy of candidate
rotavirus vaccines and for studies of virulence.
14. The group recognizes the need to support studies aiming at the development of a rota
virus vaccine. In that regard it endorses the recommendations of the Scientific W orking
■. Croup on Immunity and Vaccine Development.''/
15. There is a need for further development and evaluation of simple and reliable
ffthniques for the detection of rotavirus and for the identification of serotypes.
16. In order to conduct most of these studies, a supply of high-quality reference reagents
aUil be available. WHO should immediately assume the preparation and distribution of
following standard reagents:
(fl) Pre-immunization and hyperimmune serum to rotavirus, prepared in eoats and
t ganea pigs.
< J4jtfre;infection and convalescent (3-4 weeks) antiserum to rotavirus prepared in
^oiODiotic calves.
&iznn\°laV*rUS ant’^en f°r use ’n ELISA and other immunological tests. To standardizefechar 1Ctests.w?r^w'de, a single antigen should be used in the preparation of (a) and (d)”"
I Health
1S 'n t'le process
preparation under contract to the National Institutes of
f ®distribut ’ an^
Pan ^rner'cari Health Organization, and every effort should be made
f liable 6
°bally as a WHO reference reagent. At a later date, when techniques are
I iXelAnJiSPIC hyperimmune antiserum to the two human rotavirus serotvpes should be
' ■ H Trainin
aVailable through WH0'
v- iiboratnru ’ng,materials should be developed and workshops conducted for training
f
°rkers to perform diagnostic tests.
• ftirrh
ue to -Norwalk and Norwalk-like agents
'
$lnce the iq
c • i;!sade to find0™3^ group agents do not grow in a cell culture system, efforts should
g
way or' propagating these agents.
|.
---------------------------------------------------------------------------------------- -:----------------------------------------------------------------------
Organization, 57 (5): 719-734 (1979).
'
.1 -fe
19S
WHO SCIENTIFIC WORKING GROUP
2. Attempts should be made to find additional, serologically distinct 27 nnt-lft ’
&
associated with viral gastroenteritis.
h
3. Practical detection methods and serological assays for other Norwalk-like
f
such as Hawaii, “W” or Ditchling agents, have to be developed so that their natural
can be further elucidated.
4. Additional efforts should be made to discover animal models for the study of ti 1
caused by the Norwalk group of agents.
5. The observed absence of long-term immunity to Norwalk agent in one pro ; ■
volunteers in contrast to another which had such immunity has raised important queX'T'’
in connection with intestinal immunity. The reasons for this lack of immunity inbneF^S
need elucidation.
• V;
Other viral diarrhoeas
Research should be carried out to determine the significance of astroviruses,
•
viruses, coronaviruses, enteric adenoviruses (untyped), and other virus-like pari&i' ■
detected in stools from acute cases of human diarrhoea. This should include longitufeST
and case-control epidemiological studies, and laboratory studies to find a way topropjfe
them in vitro for their further identification. Such studies should include an exchan^t^specimens between laboratories in order to agree on the identification of these differ
morphological entities.
?J /
Members
A. Z. Kapikian, National Institute of Allergy and Infectious Diseases, National InsW-j
of Health, Bethesda, MD, USA (Chairman)
, J ..
S. K. Lam, Department of Medical Microbiology, Faculty of Medicine, Univeryl!!| .
Malaya, Kuala Lumpur, Malaysia
/
C. R. Madeley, Department of Infectious Diseases, University of Glasgow, Gfe 5 ■,
Scotland
■
Minnie Mathan, Department of Pathology, Christian Medical College and nOSfe - .
Vellore, India
?
P. K. Middleton, Department of Virology, Hospital for Sick Children, Toronto,
jp
Canada (Rapporteur)
•’’’
G. N. Woode, College of Veterinary Medicine, Iowa State University of Sciencean?
nology, Ames, Iowa, USA
■
Secretariat:
J. Bond, Communicable Diseases, WHO Regional Office for the Americas,. .
DC, USA
M. H. Merson, Diarrhoeal Diseases Control Programme, Division of Co . >
Diseases, WHO, Geneva, Switzerland (Co-Secretary)
J. Rust, Communicable Diseases, WHO Regional Office for the Americas,
DC, USA
H0
O. Sobeslavsky, Virus Diseases, Division of Communicable Diseases, wn > fefefe’
Switzerland (Co-Secretary)
.
''VTf
K. Western, Communicable Diseases, WHO Regional Office for the Amertc
ton, DC, USA
rw
B
|
::1 Hir,]
XvaaMgga;-;.;
.,a„
WtkS
I Med Res 104. Julv 1996, pe 103-114
[nd‘an
>
in'sl(
Ne^y
i' Epidemiology & management of persistent diarrhoea in children of
developing countries
-“ring
’■ionai
\(K Bhan, N. Bhandari, S. Bhatnagar, & R. Bahl
/Offl Advance Centre for Diarrhoeal Disease Research, Department of Pediatrics
HI India Institute of Medical Sciences. .Vew Delhi
Accepted June 24, 1996
Diarrhoea that begins acutely but lasts longer than two weeks is defined to be persistent. Revised
estimates in developing countries including India showed that acute diarrhoea accounts for 35 per
cent, dysentery 20 per cent and non-dysenteric persistent diarrhoea (PD) for -15 per cent of total
diarrhoeal deaths. PD also often changes marginal malnutrition to more severe forms. Factors that
increase the risk of acute diarrhoea becoming persistent have been identified in India and other
developing countries. These include antecedent malnutrition, micronutrient deficiency particularly
for zinc and vitamin A, transient impairment in cell mediated immunity, infection with entero
aggregative Escherichia coli and cryptosporidium, sequential infection with different pathogens and
lack of exclusive breast feeding during the initial four months of life particularly use of bovine milk.
Several issues regarding the management of persistent diarrhoea in hospitalized children in India
have been resolved. Diets providing modest amounts of milk mixed with cereals are well tolerated.
In those who fail on such diets providing carbohydrate as a mixture of cereals and glucose or sucrose
hasten recovers. The role of antimicrobial agents and individual micronutrients in PD is currently
being investigated. A management algorithm appropriate for India and other developing countries has
been developed and found to substantially reduce case fatality in hospital settings to about 2-3 per
cent. Recent epidemiological and clinical research related to persistent diarrhoea is also reviewed.
Key words Impaired immunity - incidence - lactose intolerance - mortality micronutrient deficiency - persistent diarrhoea
,
■.Al though the majority of episodes of acute diar^■ea are self limiting, a small proportion last sev
eral weeks1. These episodes persistent diarrhoea are
important because of a substantially higher case
f atality rate than in acute diarrhoea, impact on nu, 'dtional status and the fact that these adverse out; comes may not be prevented bv oral rehydration
merapy alone'-7.
■
(WHO) has now defined persistent diarrhoea as an
episode that begins acutely and lasts for at least 14
days'. The use of 14 days cut-off to partition acute
and persistent episodes seems justified. In India for
instance, in a longitudinal study the case fatality
rates were similar for diarrhoeal episodes of I and 2
wk duration (0.61 and 0.8% respectively) and this
increased to 14 per cent as the duration exceeded two
weeks7. The term persistent diarrhoea does not in
clude specific disorders, such as hereditary syn
dromes, celiac disease or surgical conditions and
these are not considered in this review'.
Tta d'Slribution of the duration of diarrhoeal epi
cs is a continuum8. As such, delineating a sub
dop of diarrhoeal episodes as persistent by any cut
's arbitrary. The World Health Organization
103
104
INDIAN J MED RES. JULY 1996
Incidence of persistent diarrhoea
Estimates indicate that 3-20 per cent of episodes
of acute diarrhoea become persistent'. The incidence
of persistent diarrhoea obtained in several longitudi
nal studies varied considerably from 7-150 episodes
per 1-00 child years5’’14. In most settings the inci
dence of persistent diarrhoea peaked between 7
months and 2 yr of age; in countries with very high
diarrhoea attack rates, the incidence was as high even
in the first six months of life'114-15. The disease inci
dence declined rapidly after the fourth year. This
high variability in attack rates across countries may
be due to differences in disease definitions and inten
sity of household surveillance, apart from true geo
graphical differences.
Mortality and growth faltering related to persis
tent diarrhoea
Recent research has led to a revision of the earlier
estimates of the contribution of different types of
diarrhoea to diarrhoea related mortality. In an inter
national study that compared clinical patterns of di
arrhoea among diarrhoea related deaths in India,
Bangladesh, Brazil and Senegal, a similar pattern
was observed; acute diarrhoea accounted for 35 per
cent (range 25 to 46%), dysentery 20 per cent (range
8 to 24%) and non-dyscnteric persistent diarrhoea 45
per cent (range 23 to 62%) of the total diarrhoeal
deaths14-16. The dysenteric deaths included those re
lated to acute as well as persistent illness. In India
the cause specific mortality rates (per 1,000) in chil
dren aged less than five years for acute watery diar
rhoea56, dysentery4’ and non dysenteric persistent
diarrhoea56 were similar (Table I)7. While efforts to
promote oral rehydration therapy and antibiotic treat
ment of dysentery must be sustained, persistent diar
rhoea needs greater attention than at present.
Antecedent malnutrition, lack of brpast feeding,
and associated systemic infection increase the risk of
death during persistent diarrhoea2-7-14-17’1’. In a com
munity based study in north India, nearly a third of
fatal cases of persistent diarrhoea had associated
pneumonia7.
In Bangladesh, malnourished children had a 68
fold higher risk of death from persistent diarrhoea
than those who were better nourished and residing in
the same communities17.
Table 1. Cause specific mortality rate
*
among children under jyears of age’
Type of diarrhoea
No. of deaths
Cause specif
mortality
8
5 7""
Acute dysentery
3
2.1
Dysenteric PD
4
2.8
All dysentery
7
4.9
Non-dyscnuic PD
8
5.6
All persistent diarrhoea
12
8.5
Acute watery
* (number of deaths in a year/mid population) x 100
PD. Persistent diarrhoea
Superscript number indicates the reference no.
The contribution of dehydration to persistent diar
rhoea associated deaths is uncertain but available
data indicate that it is much less important than in
acute watery diarrhoea7-14-1’.
Role of enteric pathogens in persistent diarrhea
Several theoretical models for the role of micro
bial agents in the genesis of persistent diarrhoea ws
be conceived’-20. Firstly, an acute enteric infectio:
may result in non infectious complications e.g., lac
tose intolerance which leads to prolonged symptoms
Secondly, persistent diarrhoea may occur as a reset
of sequential acute infections with different patho
gens. Lastly, prolongation of diarrhoea may resut
from persistence of intestinal infection; the failure^
eliminate the organisms from the intestinal tract ms)
be related to the characteristics of the pathogen, te
host factors or to both.
Across various studies, one or more pathogen
*
were detected in half to two-thirds of children
j
persistent diarrhoea during the initial few days®
illness2-5-'5'4-2'-22. The interpretation of these isol
*
tions is difficult because the pathogens were al<
commonly excreted by asymptomatic children.
general, the pathogens excreted during persist
diarrhoea were the same as those reported in acU,f
diarrhoeal episodes with the exception of rotavi^
which was often detected in acute episodes, but ra^in those that became persistent. To identify ente^
pathogens which may have a predilection for caus^j
prolonged diarrhoea, the approach commonly adoP
has been to compare their initial excretion rates
: PERSISTENT DIARRHOEA IN CHILDREN
BHAN ci
episodes that last less than 14 days with those that
last for a longer period (Table II). Among the many
pathogens examined, enteroaggregative Escherichia
coli and cryptosporidium were isolated with a sig
nificantly greater frequency in persistent episodes in
some studies14.
Enteroaggregative E. coli infection may be par
ticularly important given a high rate of isolation in
one-third to half the cases of persistent diarrhoea in
India, Bangladesh and Mexico; these rates were
higher than in acute diarrhoea13-23’25. However, this
pathogen was excreted with a similar frequency in
persistent and acute episodes in some studies21-22.
Notably, enteropathogenic E. coli. diffusely adherent
E coli, shigella and Giardia lamblia were detected
widfc similar frequency in acute and persistent di
arrhoea in most reported studies. The importance of
shigella infection in persistent diarrhoea may have
been masked by the timely and appropriate antibiotic
treatment of acute dysentery.
105
Studies in Bangladesh and Peru where sequential
stool cultures were obtained, suggest that persistent
infection with the same organism is an uncommon
phenomenon21-22. A more frequent occurrence was
tite isolation of different pathogens at various phases
of the persistent episode. In persistent diarrhoea as
sociated with AIDS, Cryptosporidium parvum,
Isospora belli, Enterocytozoon bieniusi and Myco
bacterium avium - intracellulare are the most fre
quently identified pathogens26. The importance of
these pathogens in persistent diarrhoea among HIV
negative children has not been well investigated.
Nutritional status, immune mechanisms and
persistent diarrhoea
An increased diarrhoeal incidence in malnourished
children has not been consistently observed2’’31. On
the other hand studies have consistently shown that
malnutrition is associated with a substantial increase
in the average duration of diarrhoea and the inci
dence of persistent diarrhoea32’34.
Table II : Per cent of enteric pathogens identified in acute or persistent diarrhoea during cither the firs t or third week of illness1'
Persistent episode culture
da> s
Pathogen
Persistent episode culture
> 14 days
India
(n=43)
Bangladesh
(n=251)
Bangladesh
In=l84)
Peru
(n=!6l)
Bangladesh
(n=153)
Bangladesh
(n=!70)
Peru
(n=35)
Rotavirus
2.3
2.S
1.6
0.7
5.9
0.6
2.9
Aeromonas sp.
0
4.8
3.3
9.0
2.6
1.8
20.0
12.0
32.2
8.2
11.2
22.9
Campylobacter sp.
4.7
7.1
E/^AA
34.9
27.4
18.6
12.0
24.5
17.0
EAEC-DA
0
9.6
16.4
12.8
11.3
20.8
EAEC-LA
2.3
0
4.5
4.3
0
3.8
ETTC
9.3
4.8
24.2
2.6
12.5
Salmonella sp.
4.7
0.4
0
0.7
Shigella sp.
2.3
5.6
7.6
5.2
5.9
5.7
Mn’o sp.
0
0.4
0
1.2
2.9
0
o
Cryptosporidium
Entamoeba histolytica
2.3
0
Giardia lamblia
2.3
1.6
„
14.6
5.4
1.1
2.1
5.6
0.8
0
0
1.2
22.9
25.7
0
1.0
0
0
4.1
4.2
42.9
enteroadherent Escherichia coli: AA, aggregative; DA, diffuse adhering; LA. localized adhering; ETEC. enterotoxigenic
erichia coli. Superscript no. indicates the reference no.
‘
- -------------------------------------------------------------------------------------------------------------
/■
t-
..
i
I
■'/
........... L.„-....... -J
106
INDIAN J MED RES. JULY 1996
Malnourished children are more likely to have
subclinical deficiency of individual micronutrients
and the deficiency of some of these may explain, at
least partly, the increased risk of persistent diarrhoea
in the undernourished. In a recent Indian study, chil
dren 6-36 months of age attending a community
clinic with acute diarrhoea were supplemented with
zinc gluconate or placebo during the enrollment epi
sode and for a 6 months period thereafter; zinc supple
mentation resulted in a significant reduction in the
average duration of the acute enrollment episodes
and in the proportion that became prolonged35. Over
the ensuing 6 months the incidence of persistent
diarrhoea was reduced by 49 per cent in zinc supple
mented children older than 11 months but there was
no such effect in those below this age36. Zinc supple
mentation was previously shown to reduce the dura
tion and severity of acute diarrhoea by others37-38.
A positive association between vitamin A defi
ciency and diarrhoeal morbidity has been reported in
only some studies3'’-40. In Brazil, routine administra
tion of vitamin A (200,000 IU) at 4 monthly intervals
to children aged 1-5 yr reduced the incidence of
severe diarrhoea by 20 per cent and diarrhoea preva
lence by 23 per cent; the incidence of persistent
diarrhoea was not reported41. Micronutrients such as
zinc and possibly vitamin A reduce the severity and
duration of diarrhoea either by a rapid and effective
repair of the intestinal epithelium following an acute
enteric infection due to its role in the regulation of
cell division or by enhancing the immune re
sponse4-43.
Immuno incompetence, particularly decreased cell
mediated immunity is one of the likely underlying
mechanisms for the increased incidence of persistent
diarrhoea among malnourished children31-34-40-44. In
Peru and Bangladesh, however, reduced delayed hy
persensitivity responses (DHR) to several skin anti
gens were found to be associated with an increased
risk of persistent diarrhoea, even after controlling for
nutritional status31-34. The impairment in DHR was
often transient. Transient cell mediated immunosup
pression may be the result of acute viral infections45-46.
Anergy has also been reported following bacterial
infections such as tuberculosis and pneumonia47-48.
Diminished cell mediated immunity could also be
related to decline in micronutrient status42.
Recent morbidity and persistent diarrhoea
It has been seen that children are at an increase
risk of persistent diarrhoea following an episode (
measles or acute diarrhoea but not acute lower
piratory tract infection49-50. The basis for an increase
risk of persistent diarrhoea over the 2 to 3 month
period following an acute diarrhoeal episode is ur
clear. A possible explanation may be that childre
who develop persistent diarrhoea are a subgroup wit
a high overall diarrhoea burden51. Alternatively,;,
acute diarrhoeal episode may induce alterations I
the intestinal epithelium or in immune responsive
ness that renders the subsequent diarrhoeal episode
to be more severe or prolonged. Acute diarrhoea
characterized by excessive faecal zinc losses42. It ha
been postulated that the impaired epithelial cell rt
newal and immuno incompetence associated wit.
subclinical zinc deficiency may be the basis fort!
increased susceptability to persistent diarrhoea fo
lowing acute diarrhoea. These hypotheses need to I
examined in future studies.
Type of feeding and persistent diarrhoea
It is important to identify feeding practices th;
increase the risk of persistent diarrhoea as these ai
potentially modifiable.
Factors that increase the overall risk of diarrhoe
are also likely to cause more persistent diarrhoea. I
infants under 3 months of age by feeding mode* (Ref 18) ♦atthei’l
of 1 wk; *’reference group : exclusively breast-fed.
BHAN rial: PERSISTENT DIARRHOEA IN CHILDREN
107
Brazil, breast feeding was protective against persis
tent diarrhoea even after controlling for socio-eco
nomic status'5. In early infancy, use of milk supplements in addition to breast feeding increased the risk
of persistent diarrhoea by three fold. The risk was
even greater among the non breast-fed (Fig. 1).
When viewed together, the reported data indicate
that the use of mixed diets including low to moderate
amounts of milk during acute diarrhoea promote
weight gain without increasing the episode duration.
Once an acute diarrhoeal illness has occurred, the
mode of feeding during the acute phase may influ
ence the severity and duration of symptoms. Breast
feeding during acute diarrhoea reduces the severity
and duration of the episode5-.
Rice-based ORS was shown to substantially re
duce the stool output in cholera in comparison to
standard ORS. but its effect on stool output and
episode duration in non cholera acute diarrhoea has
been relatively small60. In a study from Bangladesh.
the use of rice ORS during acute diarrhoea was re
ported to have reduced the proportion of episodes
that became persistent61.
A highly contentious issue is whether the use of
bovine milk or infant formula during acute diarrhoea
increases the episode duration and severity. Several
factors may influence the response to milk feeding
acute diarrhoea: the source of milk, amount.
type of processing, other foods consumed during the
illness, severity of the infection and factors related to
the host53. The lack of consistency in the findings on
this issue across studies is therefore understandable.
There is evidence that feeding of non human milk as
the sole or predominant nutrient source during acute
diarrhoea may increase the episode severity and du
ration54. In many of the studies where milk intake
during acute diarrhoea was moderate, or when milk
was offered as a part of a mixed diet containing
cereals, a significant increase in the episode duration
or Severity was not observed55-56. Lactose malabsorp
tion is dose dependent and it is likely that milk in
moderate amounts particularly when mixed with
other foods is well tolerated by most children with
acute diarrhoea.
Indian study, the risk of persistence of acute
diarrhoea was more with bovine milk than with an
infant formula57. This seems plausible as bovine milk
has a higher lactose content and osmolarity and the
sensitization capability of milk protein in the infant
formula is reduced due to spray drying during the
manufacturing process.
Fermented products of milk such as yoghurt have
been shown to be better accepted by lactose intoler
ant subjects and by children with persistent diar
rhoea58. In a recently completed trial however, the
feeding of yoghurt instead of milk to malnourished
children during acute diarrhoea was not associated
W|th a reduction in the episode duration or the risk
°fpersistent diarrhoea (Singh et al unpublished data).
Type of oral rehydration salts (ORS) solution and
persistent diarrhoea
in recent clinical trials, where feeding was care
fully standardized, there was no significant differ
ence in the outcome of episodes treated with rice
based ORS than with standard ORS6'. Thus, in the
presence of optimal feeding, rice-based ORS during
acute diarrhoea is unlikely to substantially reduce the
risk of development of persistent diarrhoea.
In a recent multi-centre WHO sponsored clinical
trial including India, the effect of a reduced osmolar
ity ORS (22-1 inmol/litrc) on the stool output and
episode duration was examined in comparison to the
standard WHO ORS (31 I mmol/litre). Stool output
was reduced by 30 per cent and the average episode
duration by 22 per cent in the children treated with
reduced osmolarity ORS6-’. Data on the proportion of
episodes that became persistent were not reported.
There are few community-based reports on the risk
of development of persistent diarrhoea in relation to
antibiotic use during the first week of diarrhoeal ill
ness. In a study from India, antibiotic use during the
initial days of illness was equally common in episodes
that were eventually' classified as acute or persistent5'.
In another study, initial antibiotic treatment was sig
nificantly less common in the episodes that became
persistent, raising the possibility of a beneficial ef
fect12. Nevertheless it is important to recognize tha:
unwarranted antibiotic treatment for acute diarrhoea
could lead to Clostridium difficile associated pseudo
membranous colitis and hasten the emergence of an
tibiotic resistant pathogens.
Specific causes and their role in the pathogenesis
The common causes of persistent diarrhoea as
seen in developing countries are persistent infection
IOS
INDIAN J MED RES. JULY 1996
with one or more enteric pathogens, sequential en
teric infection, disaccharide and rarely monosaccha
ride malabsorption and dietary protein intoler
ance5-14—The hallmark of the disorder is persis
tent mucosal damage which may result from failure
to eliminate the causative agent or delayed and inef
fective mucosal restoration. Protein energy malnutri
tion and micronutrient deficiency in humans are
known to be associated with abnormalities in intes
tinal structure and function. Delayed regeneration of
the epithelium with reduced cry pt cell multiplication
and ineffective maturation of cells during their mi
gration up the villi following an enteric infection has
been demonstrated in experimental malnutrition67.
Pathogenic bacteria cause mucosal damage and diar
rhoea through mucosal effacement or invasion and
action of enterotoxins or cytotoxins; malnutrition in
the host prolongs the healing of the injured mucosa,
the state of malabsorption and diarrhoea. In a propor
tion of cases, an immunological response to luminal,
bacterial or dietary antigens has also been proposed
as the basis for gut mucosal damage in persistent
diarrhoea but the data are still inconclusive68.
The role of dietary protein intolerance in persis
tent diarrhoea is highly contentious. Cased on stud
ies in India and other developing countries, it is
unlikely to be of significance in the pathogenesis of
persistent diarrhoea63’6-5-69-70. Although, increased in
testinal uptake of intact proteins has been demon
strated following acute gastroenteritis in early in
fancy, the clinical significance of this phenomenon is
not established70.
There is a substantial impairment of fat and pro
tein absorption during persistent diarrhoea; carbohy
drate malabsorption is only moderately affected on
diets that are predominantly cereal based71. Second
ary malabsorption of sugars, particularly of lactose is
common. In a proportion of cases, disaccharides other
than lactose are also malabsorbed to a clinically sig
nificant degree.
Clinically significant monosaccharide malabsorp
tion is fortunately infrequent62-63-66. The causes of
carbohydrate malabsorption are acute or persistent
enteric infection and malnutrition by decreasing brush
border enzymes. Unabsorbed sugars are osmotically
active and induce water and electrolyte secretion into
the intestinal lumen.
Faltered growth in persistent diarrhoea is not or!
the result of nutrient malabsorption; inadequate fl
etary intake due to anorexia, a continuation of fault}
pre-illness feeding practices or as a response ^
diarrhoeal illness itself by the family or the phySj.
cians, are all important.
Management
The initial step is to determine the appropriatt
place for care. Patients with persistent diarrhoea re.
quire hospitalization in the presence of dehydration,
associated systemic infection requiring intravenois
antibiotics or when anorexia is severe. Intravenon
fluid therapy may be required initially when dehy.
dration is severe, to correct major electrolyte abnor
malities or acidosis, and in extremely cachexies
systemically infected infants who accept oral fluid;
poorly.
Children with some but not severe dchydratioi
can be effectively treated with oral rehydration sal
solutions. It is important to provide additional po
tassium supplements to those severely mainour
ished.
W hen clinical dehy dration is not associated. liont
*
available fluids are appropriate for replacemento
ongoing stool losses.
Basis for dietary management
Several general principles have been establisher
through recent studies in persistent diarrhoea.
In developing countries, the need to use total m
travenous nutrition arises very rarely. Optimal ora'
feeding, based on an appropriately constituted dietti
well tolerated and achieves recovery and catch up
growth in the vast majority of these patients. A1
though there is some malabsorption of nutrients111
persistent diarrhoea, about 80-90 per cent of carbo
hydrates and 70-75 per cent of fats and proteins at
actually absorbed from mixed diets based on local.
available ingredients.
Breast feeding is safe and well tolerated dun11
diarrhoea. Although, a few predominantly breast
infants with acute diarrhoea may continue to P3
stools with more than the usual frequency or st°°
of somewhat liquid consistency for more than
weeks, physical growth is well maintained.
BHAN el al: PERSISTENT DIARRHOEA IN CHILDREN
Should milk be withdrawn in persistent diar
rhoea?
Table III. Comparison of milk-based and milk-free diets in
persistent diarrhoea71
In the non breast-fed babies, an important issue is
whether milk should be totally eliminated or simply
reduced in amount during persistent diarrhoea.
Brown and colleagues reported increased stool
wei°hts on diets predominantly based on whole milk
as compared to lactose hydrolysed milk72. The milk
intakes were equivalent to about 6 g/kg/day or more
of lactose; few children in Indian communities take
such large quantities of milk. The issue of whether
lower intakes equivalent to 2.5 g/kg lactose load per
day would also be poorly tolerated has been recently
examined in a clinical trial: preliminary analysis
sho'^bsignificantly greater weight gain in the group
receiving a mixture of cereals with milk in which the
latter provided 35 per cent of the total calories than
in the other group consuming isocaloric cereal-based
diet without milk. There was only a modest 15 per
cent increase in the stool output in the milk group but
the treatment failure rates were similar (Table 111
Similarly, Bhutta et aF
* reported lower stool out
put and greater weight gain in persistent diarrhoea
with curds cereal mixtures than with lactose free soy
based diets. Together, these studies make a case for
reduction rather than total elimination of milk as the
initial step. A modest amount of milk in cereal diets
improves their protein quality, trace elements and
mineral content. Further, the consistency and pay
ability ensures higher intakes of these diets than with
pure^^ereal-based diets. The possibility of occasionwRiilk protein allergy is out weighed by the
benefits offered by adding modest amounts of milk
to cereal based diets.
Specific recommendations for the initial diet
Once a child is ready for oral feeding after few
hours of stabilization, the choice of an initial diet
would be milk rice mixtures with added oil, yielding
an energy density of about 85-95 kcal/lOOg with 3035 percent calories from milk. The diet provides the
ideal minimal 10 per cent energy from a protein
source. The composition of one such diet is given in
Table IV.
In a small proportion of patients with very severe
'arrhoea where some clinicians fee) reluctant to use
109
Milk
cereal
(n=47)
Milk free
cereal
(n=46)
DifTerer.ee in
median
(95% C!)
1.7
(0.9. 2.5)
1.5'
(0.6. 2.4)
0.23
(-0.26. G.
*3)
0-120 h
1.6
(0.9. 2.7)
1.3
(0.61. 2.39)
0.26
(-0.19. 0.74)
% change in
weight at 120 h’
2.8
(0.8. 5.9)
2.3
(-0.1. 4.3)
0.91
(-0 4S. 2.4)
Stool output >200g/kg
ill any 24 h period
3
1
Reappearance of
dehydration during studs
4
Stool output >60g/kg
on da) -7
2
Weight on day-7
< rehydration weight
1
Treatment failures
by an) of the above (%)
17.2
Median stool weight
in males'(g/kg/h)
0-48 h
Number with :
-
t z—
23.6
tc.24.:.s")
Median (range)
*’ Odds ratio (95% Cl)
Superscript no. indicate the reference no.
Table IV. Composition of diet A
Ingredients
Amout-4 IS
Puffed rice
12.5
Milk
40-
Sugar
2.25
Oil
2.0
Water to make
100
Energy density (cal/lOOg)
96
Per cent protein
10.0
Per cent carbohydrate
55.87
Per cent lactose
1.73
Per cent fat
33.9
Amino acid score
1.0
milk even in small quantities, rice sugar oil based
diets are appropriate. Egg is well tolerated and pro
vides useful animal protein in such diets.
110
INDIAN J MED RES. JULY 1996
Nearly 25 per cent of hospitalized patients show a
poor response to diet A. Useful criteria for defining
treatment failure are reappearance of dehydration at
any time, passage of 7 or more liquid stools in a day
at the end of 7 days treatment and weight loss or poor
weight gain despite an oral intake of at least I 00 cals/
kg/day over the previous three days. Poor oral intake
as a result of systemic infection is more often the
cause of weight loss than true dietary failure in hos
pitalized children. In milder cases that are managed
at the household level, a common reason for poor
weight gain is the offering of only small quantities
of thin foods to the child by the family.
The factors related to treatment failure on low
lactose (milk) cereal based diets arc systemic infec
tion. severe carbohydrate intolerance involving not
only lactose but also other disaccharides and starch.
Therefore, dietary modification should be made only
after effective treatment of associated systemic in
fection. The second line diet should be milk free with
substitution of part of the starch by sucrose or glu
cose (diet B; Table V). This mixture of sugars
achieves the right balance between dietary osmolar
ity, digestibility and energy density. In such a diet,
egg or chicken is a suitable protein source. Monosac
charides as the only carbohydrates in the diet should
be used for the few patients who are treatment fail
ures on diet B as it is difficult to provide sufficient
energy density with the permissible 2-3 per cent
glucose concentration; at higher concentrations os
motic diarrhoea may develop.
Until their role in the management of persistent
diarrhoea is well established, generous but safe
amounts of micronutrients equivalent to 2 times the
RDA should be provided. These may include vitamin
A, zinc, iron, folate and when feasible others. Se
verely malnourished children should receive magne
sium 1-1.5 ml/kg body weight of a 50 per cent solu
tion, given IM for 2-3 days. Patients on a milk free
diet should also receive calcium supplementation.
Several commercial diets are also available. For
reasons that are not fully explained, home based low
lactose or lactose free diets perform much better than
commercial soy based formulations74. Semi elemen
tal diets like Nutramigen or Progestimil are useful
but expensive. They usually contain protein hydroly
sate or calcium caseinate, mixture of disaccharides
Table V. Composition of diet B
Amount (g)
Ingredients
PufTed rice
13.50
Egg
11.0
Glucose or Sucrose
'
"S,
3.50
Oil
3.50
Water to make
100
Energy density (cal/100g;1
95.22
Per cent protein
9.51
Per cent carbohydrate
56.9
Per cent fat
33.29
Amino acid score
1.00
and oligosaccharides and part or whole of the fatsg
medium chain triglycerides. Micronutrients and vitamins are already added. The diet B is based ot
similar principles and is at least as effective. It
advantage is that the concentration of the individut
sugars can be tailored to each individual child, itit
cheap and can be easily prepared by mothers at honti
and in small hospitals, the disadvantage is that vib
mins and minerals need to be supplemented.
The role of antimicrobial agents against enteri
pathogens in terms of improved nutrient absorption
decreased stool output or shortened illness duratia
is undecided. In a recent Indian study large dosesc
nonabsorbable, broad spectrum antibiotic were ad
ministered based on the hypothesis that it wool
*
eradicate aerobic bacterial overgrowth. There wasu
improvement in purge rates or weight gain with mat
sive doses of oral gentamicin as compare to a pl*
cebo. despite clearance of stool pathogenic orgi
isms including adherent E. coliis. It was conceivab
that systemic antibiotics may be of greater benefit
persistent diarrhoea. However, a recently conclui
double blind field trial done to evaluate the effi03'
of metronidazole given alone or in combination"'1'
nalidixic acid in comparison to a placebo has sho>
no significant clinical benefit (Behl et al, ul1Pb
lished data). Metronidazole was evaluated f°.r
action against anaerobes. Other controlled trials"’
co-trimoxazole have shown similar results. I*
pears that when the mucosa is already severely^3,
aged, whatever the initiating factors, nutritional5’
port is the key to its rapid repair.
BHAN ci ci ■. PERSISTENT DIARRHOEA IN CHILDREN
An effective antishigella agent should be used in
the presence of blood or numerous pus cells in the
stools. Treatment for giardiasis and amoebiasis is
indicated when a stool examination reveals tropho
zoites. Currently, there is no suitable treatment for
cryptosporidium infection.
Cholestyramine, which binds unconjugated bile
salts or bacterial toxins, has not proved to be useful.
There is also little evidence of clinical benefit when
lactobacilli are administered to replace intestinal
microflora.
Systemic antibiotics are required to treat associ
Fig. 2. Practical alaorithm lor the treatment ol persistent diarrhoea.
112
INDIAN J MED RES, JULY 1996
ated pneumonia, septicemia, meningitis or urinary
tract infection in patients with persistent diarrhoea.
These infections are detected in nearly 60 per cent of
patients with associated severe malnutrition usually
seen in a hospital setting, they are much less com
mon when malnutrition is only of moderate severity,
as is likely with those being treated as outpatients.
The search for such infections should be vigorous,
even in the absence of fever; useful indicators are
persistent anorexia, refusal of liquids and breast milk
and dehydration despite modest stool losses.
These recommendations are summarised in a treat
ment algorithm (Fig. 2). This algorithm was evalu
ated in an international study including the group at
the All India Institute of Medical Sciences (AIIMS),
New Delhi. The success rate for the evaluated 460
children with persistent diarrhoea while on diet A
was 70 per cent (95% CI 65%, 75%) and it was 84
percent (95%C1 76%, 93%) for those evaluated while
on diet B. Weight gain was achieved in over 90 per
cent and associated illnesses requiring antibiotics
were found in 61 per cent of the children. The chil
dren at greatest risk were the youngest, those se
verely malnourished, with highest initial purging
rates and associated infection.
As diarrhoea is common in children residing in
poor communities where family feeding habits con
tribute to malnutrition, an interaction with health
care providers during the illness offers a good oppor
tunity to improve the nutrient intake through pur
poseful nutritional counselling. Mixtures of milk and
cereals or of cereals and legumes fortified with oil
are well tolerated during acute and persistent diar
rhoea. They have the required energy density and
palatability. About 30-40 per cent of calories can be
derived from fat sources without any deleterious
effect. Mothers must receive nutritional counselling
from health care providers that is practical and takes
into account the family views and realities and in
cludes clear instructions on the frequency of meals,
the amounts to be fed at each and the solutions to
problems of the individual child and family. This is
currently the weakest link in the sick child - health
care provider interaction.
The vast majority of patients with persistent diar
rhoea are unable to avail of hospital care due to
physical and situational constraints of the family.
Therefore, it is the outpatient care of patients wi^
persistent diarrhoea that needs strengthening instead
of the current over focus on sophisticated treatment
of the few patients who actually get to hospitals.
References
1.
World Health Organization. Diarrhoeal diseases control.
Persistent diarrhoea in children. CDD/DDM/85.1. Geneva;
World Health Organization.
2.
Bern C. Martines J. de Zoysa I. Glass Rl. The magnitude of the
global problem of diarrhoeal disease: a ten year update. Bull
WHO 1992; 70: 705-14.
3.
Black RE. Lopez de Rornana G, Brown KH. Bravo N. Bazalar
OG.KanashiroHC. Incidence and etiology of infantile diarrhoea
and major routes of transmission in Huascar, Peru. Am J
Epidemiol 1982; 115 : 305-14
4.
Black RE. Brown KH. BeckerS. Effects of diarrhea associated
with specific enteropathogens on the growth of children io
rural Bangladesh. Pediatrics 1984; 73 : 799-805.
5.
Bhan MK. Bhandari N. Sazawal S. Clemins J, Raj P. Levine
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'I..
Brief Reports
piarrhea Management in Some
Jhuggi Clusters of Delhi
DJGTaneja
Fauna Lal
C.S. Aggarwal
A. Bansal
V. Gogia
■
Oral rehydration therapy (ORT) is the
basis of the Diarrheal Diseases Control
Programme in India. It aims at reduction
in 70% diarrhea deaths among the underfives^). It is felt that the continuing high
mortality due to diarrhea is to a large
extent because of low ORT use, lack of
knowledge for correct preparation of oral
rchydration solution (ORS), traditional
misbeliefs and practices among mothcrs(2). Antimicrobial agents have only a
limited role and anti-diarrheals have no
role in the treatment of acute diarrhea(3),
: . . yet due to deficient clinical training of doctors and expectation of mothers there is
tendency to lay stress on drugs than oral
\ tehydration(4,5).
,
'
——---------------------------------------------
From the Department of Preventive and Social
• ' Medicine, Maulana Azad Medical College, New
Delhi no 002.
'
"quests: Dr. D.K. Taneja, Associate
kf^SOr' Department of Preventive and Social
' Medicine, Maulana Azad Medical College, New
:MMhill0 002.
pu,blication: MaV 9,1994;
‘naxPted. April 17,1995
The present study was undertaken to
obtain information on the action taken at
home and health facility, in case of acute
diarrhea and assesses the knowledge of the
households in preparation of ORS and
sugar salt solution.
Subjects and Methods
The study was conducted in three large
JJ. clusters, viz., Sanjay Amar Colony,
Hathi Park, and Jai Prakash Colony situ
ated in the vicinity of Maulana Azad Medi
cal College, New Delhi. A total of 6285 per
sons residing in 1090 households were
studied. A responsible person, mostly a
housewife, present in the household at the
time of visit, was interviewed by the
interns with the help of pre-structured and
pre-tested questionnaire. Enquiry was
made on occurrence of diarrhea in the
household in previous two weeks. In
households where a case of diarrhea had
occurred, detailed information was
obtained regarding action taken by the
household and nature of treatment given
by private/govemment health agencies.
Respondents were also asked to show the
preparation of sugar salt solution and ORS
using'usehold measures.
Results
Amongst 6285 persons surveyed, 183
(2.9%) had diarrhea in the previous two
weeks. Majority were under-fives (68.3%).
Blood in the stool was associated in 24
(13.1%) cases. Table I shows the first action
taken by the households when diarrhea
occurred. One-fourth received ORT as
ORS solution (3.3%), sugar salt solution
(10.4%), dal water (5.5%) or shikanji
BRIEF RETORTS
(5.5%). There was no significant difference
in management between under and overfives (p >0.05).
The correct preparation of sugar salt
solution by using finger pinch, scoop or
spoon and glasses was known to 36.6%
households. However, only 11.5% house
holds could measure correctly the water
required to prepare one litre of ORS.
The first action was often delayed upto
the second (13.1%) or third day (18.0%).
During the course of diarrhea, as first
action or subsequently 102 (55.7%) cases
were taken to private practitioners and 13
(7.1%) to a government health facility. The
pattern of treatment provided by them is
shown in Tabic II. All cases of dehydration
were given ORT or intravenous fluids.
However, to prevent dehydration, home
available fluids (HAF) e.y., dal water,
shikanji, lassi or sugar salt solution were
advised by government health facilities in
20.0% and private practitioners in 15.7%
cases only.
Discussion
The continued poor use of ORT(2,6)
calls for a fresh look at its implementation.
The preferences for the private practitior
ners even though government health facili
ties were nearby, in this and other
studies(6) emphasize the need for their
involvement in the programme.
Use of ORT to prevent dehydration
needs more emphasis as this was often not
advised. The excessive use of drugs in
cluding antimicrobials and antidiarrheals
by private practitioners(81.4%) and gov
ernment health facilities (61.5%), even
though antimicrobials were indicated only
in the 13.1% cases of dysentery, is alarm-
TABLE I—First Action Taken by Households in Diarrhea
Action taken
*
S 5 Years
(n = 125)
> 5 Years
(n = 58)
Total
(n = 183)
Home available fluids/ORS
Stopped food/fluids
Household remedies
Visited private doctor
Visited government health facility
33
10
13
46
9
12 (20.6)
4 (6.8)
11 (18.9)
29 (50.0)
0 (0.0)
45 (24.6)
14 (7.6)
24 (13.1)
75 (40.9)
9 (4.9)
(26.4)
(8.0)
(10.4)
(36.8)
(7.2)
* In 14 (11.2%) under-fives and 2 (3.4%) over-fives no action was taken when diarrhea occurred.
Figures in parenthesis indicate percentages.
TABLE W-Treatment Received From Health Agencies
*
Treatment
Drug
ORS/Home available fluids
Intravenous fluids
*
Private practitioner
(n = 102)
83 (81.4)
28 (27.4)
1 (0.9)
Responses not mutually exclusive.
Figures in parenthesis indicate percentages.
118
Govt, health facility
(n = 13)
8 (61.5)
8 (61.5)
1 (7.7)
Total
(n = 115
91 (79.1
36 (31-3
2 (I-7
--------
VOLUME 33-FEBRUAiO 1996
INDIAN PEDIATRICS
•i
ing. The misuse of drugs leads to adverse
reactions,
resistant organisms,
and
increase in the cost of treatment. It also
delays the initiation of appropriate treat
ment and complicates the condition of the
patients.
Our results emphasize the need for
frequent re-orientation training of private
practitioners and in-service doctors on
appropriate case management and rational
use of drugs in acute diarrhea. The families
also need to be informed and demon
strated the correct preparation and use of
ORT for prevention and treatment of diar
rhea and restriction on the use of drugs.
2.
Dhawan S, Singhal PK, Taneja DK. Diar
rhea beliefs and practices among rural
■ mothers of Delhi. Indian Pediatr 1988,
25: 195-197.
3.
Dutta P, Bhattacharya SK, Dutta
D. Management of acute diarrhea. Indian
J Public Health 1990, 34: 38-40.
4.
Patwari AK, Anand V, Kumar H, Aneja
S, Mullik D. Knowledge and perceptions
of residents regarding case management
of acute diarrhea. Indian Pediatr 1991,
28: 887-892.
5.
Azad Chowdhury AK, Matin MA,
Amirul Islam M, Faruk Khan O. Prescrib
ing pattern in acute diarrhea in three
districts in Bangladesh. Tropical Doctor
1993, 33: 165-166.
6.
Mishra CP, Kumar S, Tiwari 1C, Prasad
DN. A study on some diarrhea related
practices in urban Mirzapur. Indian J
Public Health 1990, 34: 6-10.
REFERENCES
1.
ft-
National Child Survival and Safe Mother
hood Programme. Module on the Inter
ventions, Ministry of Health and Family
Welfare, New Delhi, 1992, p 42.
&
Calf Circumference as a Predictor
of Low Birth Weight Babies
V. Gupta
S.K. Hatwal
S. Mathur
V.N. Tripathi
S.N. Sharma
S.C. Saxena
A. Khadwal
The prevalence of low birth weight
(LBW) in India ranges from 30-40%. The
perinatal mortality among LBW babies
From the Department of Pediatrics, G.S.V.M.
Medical College, Kanpur 208 002.
Reprint requests: Dr. Veena Gupta, Department of
Pediatrics,
G.S.V.M.
Medical
College,
Kanpur 208 002.
Received for publication: December 21,1993;
Accepted: April 1,1995
(188.8/1000) is about 8 times higher than
that in the infants weighing more than
2500 g(l). Birth weight is used as a mea
sure of LBW because of its correlation with
gestation and ease of recording in hospital
setting. However, in our country 70-90%
deliveries are conducted at home by tradi
tional birth attendants and untrained rela
tives and weight recording is a problem.
The present study was conducted with an
aim to find an alternate, cheap and reliable
predictor of LBW babies that can be used
by a trained or untrained person.
Subjects and Methods
The study was conducted on 1600 new
borns in the Department of Pediatrics,
G.S.V.M. Medical College, Kanpur. The
birth weight, crown-heel length and
midarm, head, chest, thigh and calf cir
cumferences were measured by standard
techniques(2). Weight of the nude baby
was recorded in a beam type weighing
119
35
Ababa;
INDIAN JOURNAL OF
Vol. XXXX, No.2
PUBLIC HEALTH
April -June 199 6
10g>r Of.
Ababa.
EmJ 4
INCIDENCE OF DIARRHOEA AND SOME RELATED EVNIRONMENTAL
AND BEHAVIOURAL FACTORS IN JHUGGIS OF DELHI
service
3.
1 Mors rates
7FAE/I
I
lassifi;
•ty J
East.'
go.
;
:n the
ania.i
1974
wal
the
jtta
nity
Ar
md
a :
P. Lal, A. K. Ban sal, C. S. Aggarwal, D. K. Taneja, V. Gogia
Summary
A total of 6285 persons residing in 1090 households in three Jhuggi clusters
of Delhi were studied for Incidence of diarrhoea by 2 weeks recall method and
enviommental and behavioural factors affecting it. Overall incidence of Diarrhoea
was 29.1 per thousand persons, and was selectively predominant among under
fives (60.2 per thousand). Tills low incidence of diarrhoea could be attibuted to
safe drinking water availability and common practice of handwashing by most
of the people. But unsafe storage of drinking water at household level (70.5%)
and peridomcstlc open air dcfaecatlon by children (22.9%) are potential threat
for transmission of the disease.
Introduction
Materials & Methods
Diarrhoea is a leading cause of child
hood morbidity and mortality k Extensive
promotion of Oral rehydration therapy has
resulted in preventing over one million
deaths each ycar^. 1 lowcver, globally one
billion cases of diarrhoea and more than 3
million deaths due to diarrhoea among
underfives arc still occurring every ycar^.
In India diarrhoea is responsible for 2333% of all deaths below five years of age^.
Incidence of diarrhoea is maximum
among jhuggi cluster
as these have in
adequate basic civic amenities. Delhi has
1080 Jhuggi Clusters having about 4.8
lakhs Jhuggi’s4. The present study was
undertaken in three Jhuggi clusters to
study the incidence of diarrhoea and some
environmental and behavioural factors af
fecting it.
The present study was conducted in
three Jhuggi dusters of Delhi, viz. Sanjay
Amar Colony, I laathl Park and Jal prakash
Colony situated within 2 km. from Maulana
Azad Medical College, New Delhi. All the
Jhuggis were covered except those found
locked, or where no adult member was
present at tlic time of visit. A total of 6285
persons residing in 1090 households were
surveyed. A responsible person, mostly a
housewife present in the household was
interviewed with the help of pretested ques
tionnaire. Information was obtained for
occurrence of diarrnoca in the household
in previous two week. In case of occurrence
information regarding source of water, stor
age of water, practice of handwashing and
dcfaccation was obtained.
Acute diaiThoea was defined as the pas-
bepartnient of Preventive & Social Medicine, Maulana Azad Medical College, New Delhi.
36
Indian Journal of Public Health Vol. XXXX. No.2 April - June 1996
sage of 3 or more loose/watcry stools in a
24 hour period. Episodes that lasted more
than 14 days were defined as persistent.
Dysentry was diagnosed when stool mixed
with blood was reported®.
Results
The overall incidence of diarrhoea was
29.1 per thousand persons. It affected chil
dren underflve years of age (60.2 per thou
sand) more than the older subjects (13.8
per thousand). Persistent diarrhoea was
found to 7.3 per thousand in the underfives
whereas none of the overlives had persis
tent diarrhoea. Dysentry was observed in
13.1%.
The various sources of drinking water
were community tap (53.0%), municipal
water tankers (34.4%) and hand pumps
(12.6%).
Water was stored unhygicnically in ma
jority of the household (70.5%) in the open
buckets kept on floor without a laddie to
draw it.
Most of the adults were using public
(68.9%) or their own (8.2%) latrines
whereas, 22.9% adults were still practic
ing openfield defaccatlon. Contrary to this
majority of the children were defaecation
either into the drains Just outside their
jhuggi (44.3%) or open field (26.8%) and
only 20.8% children used private/public
latrine.
Most of the household members (96.2%)
washed their hands after defaecation. Vari
ous materials used for hand washing were
soap4(56.8%), plain water (24.1%), rakh
(10.9%) and mud (6.6%). Handwashing
before meals was practised by 76.5%
household.
Discussions
The Incidence of diarrhoea among
underflve (60.2 per thousand) was lower
than observed in other studies (87-467 per
thousand)®’Main reason for this
seems to be the use of safe water supply
for drinking by; the majority of the house
holds (87.4%) which was either from mu
nicipal taps or tankers.
Use of tap water instead of shallow hand
pumps is associated with decrease in di
arrhoea incidence®. Though storage of
water was tn unhygienic manner, probably
it did not affect the consumers due to short
period of storage (2-3 hours) required dur
ing the study period and action of residual
chlorine in municipal water supplies?.
However, during summer months when
water supplies arc cut of for long periods,
storage of water under the existing condi
tions, as well as use of unsafe sources like
shallow hand pumps poses a threat of out
break of diarrhoea.
Season is another factor that would have
contributed to lower incidence as the cur
rent study was done in the month of March,
Just prior to seasonal increase in diarrhoea;
similar observation^ have been made by
others®’®.
Practice of handwashing after
defaecation and before meals by most of
the households is also a contributory
factor.
Lower Incidence of diarrhoea and nc
case of persistent diarrhoea among ovei
fives is consequent to developing some de
gree of immunity & consequent a symp
tomatic or less severe infections?.
The proportion of persistent diarrhoea
to that of acute diarrhoea was within the
known range1®, while proportion of dys
entery was higher than others®.
Lower incidence of diarrhoea observe!
among the residents of some Jhuggi clus
ters of Delhi is a positive finding. This 1-
Incidence of Diarrhoea and some related.... P. Lal et al.
attributed to the use of safe drinking
water, practice of hand-washing after
defaecation and before meals and seasonal
variation.
However, unsafe storage of water and
peridomestic defaecation by children holds
potential threat of an outbreak during sum
mer months when there is shortage of tap
water supply. These finding have implica
tions for the contents of health education.
References :
Bern C.. Martines J., De Zoya, I.
Glass R.I. : The magnitude of the
9 Global Problem of Diarrhoeal Dis
eases : A Ten Year Up-Date. Bull
WHO. (1992). 70(6), 705.
2. WI IO: WI IO Programme For COntrol
of Diarrhoeal Diseases: Interim
Programme Report. CDD/9 1.3G,
WHO, Geneva. 1991:17.
3. Bcnerjee. K. B. : National
Programme for Control of
Diarrhoeal Diseases National Health
Programme scries No.9. N1IIFW. N.
Delhi.
4. List of Identified Jhuggi clusters in
Delhi. Slum wing. Municipal Cor
poration of Delhi, personal commuA nication. 1988.
5. WHO. Readings on diarrhoea, stu
dent manual, manual WHO Geneva.
1992.
1.
CHANGE
IN
37
Bhatnagar, S., Dosaijh U. :
Diarrhoeal Disease Morbidity in
Children Below 5 years in Urban
Slums of Delhi. Ind. J. Med. Res.,
84:53.
7. Olivieri, V.P., Snead. M.C., Cruse,
C.W. Kwaata. K. : Stability and ef
fectiveness
of
chlorine
disinfectatants in water distribution
system. Environ. Health Perspect.
1986. 69:15.
8. Reddaih, V.P. Kapoor, S.K. :
Epidemiology- of Diarrhoea and its
Implications For Providing Services.
Ind. J. Paed. 58 : 1991, 205 MarchApril.
9. Chakraborty. A. K., Das, J. C. : Com
paralive Study of Incidence of Diar
rhoea Among children in Two Dif
ferent Environmental Situations in
Calcutta. Ind. Paed. 1983. 20. 907.
10. WHO : Persistent diarrhoea in chi!
dren in developing countries. Bull
WHO 1988. 66 : 709.
11. Sircar, B. K., Deb. B.C.. Scngupta.
P.G.. Mandal. S. : A Longitudinal
Study of Diarrhoea Among Children
in Calcutta Communities. Ind. J.
Med. Res. 1984. 80:546-550.
12. Mandal, A.K., Tiwari, I.C. and
sanyal, S.C. : A Profile of Diarrhoea
in an Urban Slum Area. Ind. Pub.
Health 1990, 34(l):66-67..
6.
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