ICMR BULLETIN VOL. 28-No.-11-NOVEMBER-1998
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- ICMR BULLETIN VOL. 28-No.-11-NOVEMBER-1998
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ISSN 0377-4910
ICMR
BULLETIN
November, 1998
A Vol. 28, No. 11
NUTRITION: A CRITICAL DETERMINANT OF RESPONSE TO
VACCINES IN CHILDREN
Information available from epidemiological and
clinical studies supports the association of inadequate
diet and infection and forms the basis for the modern
concept of the vicious cycle of malnutrition and infec
tion1’2 (Fig.l).
already marginally nourished child. While nutritional
supplements bridge the dietary deficits, prevention and
control of infections ensure optimal utilisation of the
nutrients. Thus, prevention of infections should take an
important place in national programmes aimed at con
trolling malnutrition in children.
POVERTY
Immunization is the most powerful and cost-effective
tool for preventing infections and promoting child
survival and health in developing countries. However,
the efficacy of various vaccines depends upon the ability
of the host to mount an adequate and appropriate immune
response to the concerned vaccine. Nutrition is an
important modulator of immune response. Severe protein
energy malnutrition (PEM) among preschool children
is a nutritional problem of public health concern which
induces immunosuppression and increases the
susceptibility of the child to infections. It also contributes
to the severity of illness in a malnourished child.
POOR ENVIRONMENT
INFECTION
INADEQUATE DIET
<--------------- >
MALNUTRITION
IMMUNOSUPPRESSION
Fig. 1. Malnutrition-infection. The vicious cycle.
Poverty through food deprivation is the root cause
of malnutrition while infectious diseases act as aggra
vating factors. This interaction assumes greater signifi
cance in developing countries where both malnutrition
and infection are widely prevalent and often co-exist.
Infections precipitate malnutrition particularly in an
The host's immune mechanisms may generally be
classified as innate and acquired immune responses. While
innate mechanisms are non-specific and do not carry
memory of the infecting organisms, acquired immune
mechanisms are endowed with the characters of speci
ficity and memory to the concerned antigen. These two
fundamental characters of acquired immune mechanism
form the basis for vaccination.
Division of Publicahon & Information, ICMR, New Delhi - 110029
Acquired Immune Responses of Children with Severe
pem
Humoral Mechanisms
Children suffering from severe forms of clinical PEM,
such as kwashiorkor/marasmus, have poor response to
typhoid vaccine and certain other bacterial and viral
antigens3. Nevertheless, these children are found to raise
adequate antibody responses to protein antigens like
diphtheria and tetanus and certain viral antigens like
measles4. Total immunoglobulin levels of IgG, IgM and
IgA classes have been documented to be normal or el
evated in such children5. Their B lymphocyte counts
also remain unaltered. This indicates that humoral mecha
nisms in children with severe PEM are partly impaired
and the magnitude of the response probably depends
upon the nature of the antigen administered, the route of
administration, dose and cellular interactions required
for raising optimal immune response.
Cell Mediated Immune Mechanisms
Thymolymphatic atrophy has been well documented
in autopsy studies conducted on children dying during
the acute phase of kwashiorkor6. The peripheral blood
T cell count, along with the helper cell subset (CD\)
and their in vitro response to various mitogens and antigens
were found to be impaired, which explain their increased
susceptibility to viral, fungal and intracellular bacterial
infections like tuberculosis78.
poliomyelitis in underprivileged communities has been
attributed to the prevailing malnutrition. Concern has
also been expressed regarding the efficacy and safety of
using live attenuated vaccines in malnourished children
for fear of precipitating vaccine induced illness. I Ise of
live measles vaccine has been viewed with concern in
communities which are endemic for both malnutrition
and tuberculosis because of the potential danger of
activation of latent tuberculosis in immunocompromised
children.
Severe PEM is considered a public health problem
in India. It constitutes only the tip of the iceberg of the
problem of malnutrition among preschool children. A
recent report on the profile of PEM in the country, by
the National Nutrition Monitoring Bureau (NNMB), in
dicated that the extent of severe PEM (<60% weight for
age) in the community is not more than 10% of the
preschool child population, while more than 80% of the
children look apparently normal but suffer from mild to
moderate grades of malnutrition presenting with growth
retardation (Fig. 2)H. These children constitute the major
beneficiaries of any national health programme, includ
ing the immunization programme, and their response tc
various vaccines determines the success of the latter.
Macrophage Function
Children with severe PEM also exhibit a number of
functional deficits of macrophages. Macrophages which
play a significant role as accessory cells in cell medi
ated immune reactions, carry out the functions of anti
gen processing and presentation to T cells in addition to
providing maturation signals (through interleukins) to
the T cell. This apart, macrophages are powerful phago
cytic and bactericidal cells. On in vitro activation, pe
ripheral blood monocytes, obtained from children with
kwashiorkor were significantly less mobile and less bac
tericidal compared to those in normal children. Their
ability to produce nitrite, an important intracellular
bactericidal agent, was low013.
Based on extrapolation of these results on
immunosuppression in severe PEM, doubts have been
expressed whether immunization programmes would be
successful in communities where malnutrition is widely
prevalent. Persistence of infections like measles and
106
Fig. 2. Prevalence of malnutrition in children (1-5 years).
Source: NNMB Report of Repeal Surveys (1988-90).
Mu d-moderate Malnutrition and Immune Response
Clinical and experimental studies have been conducted
at the National Institute of Nutrition (NIN), Hyderabad,
using immunological methods to determine the degree
of nutritional status that modulates immune responses
in children in general, and the response to various vac
cines used in the National Immunization Programme in
particular. Children aged 1-5 years were investigated and
their nutritional status assessed using Gomez classifica
tion and’NCHS Standards. Humoral and cell mediated
immune responses to various vaccines were investi
gated. Immune responses of children with severe and
mild-moderate grades of malnutrition compared to nor
mal children are summarised in the Tabic.
Table. Effect of various grades of malnutrition on immune
response.
antibody titres were determined prior to the admin
istration of the first dose and one month after the second
dose. The antibody titres to both these antigens were
found to be in the protective range and the mean titres
were comparable among all groups of children irre
spective of their nutritional status.
Effect observed
Severe
malnutrition
Mild- moderate
malnutrition
INNATE IMMUME MECHANISMS
Phagocyte Response
Neutrophil
Macrophage
impaired
Chemotaxis
impaired
Nitrite production
impaired
Interleukin-1 production
impaired
No change
TAB vaccine
Antibodies to 4H’ and 'O’ antigens of Salmonella
typhi were measured in response to two doses of TAB
vaccine administered one month apart. Children with
severe PEM had low mean titres of antibodies to both
these antigens, while mild and moderately malnour
ished children had higher antibody titres which were
comparable with that of normal children.
BCG vaccine
Humoral Response
Complement & Lysozyme Reduced
Not altered
CELL MEDIATED IMMUNE RESPONSES
T cell number
T cell function
decreased
decreased
not altered
not altered
HUMORAL IMMUNE MECHANISMS
Total immunoglobulin
levels
not altered
not altered
D and T antigens
not altered
not altered
TAB vaccine
(H and 0 antigens)
impaired
not altered
BCG vaccine
not altered
not altered
Measles vaccine
not altered
not altered
Response to vaccines
General Cellular and Humoral Immune Response
Contrary to the observation of immunosuppression
in severe PEM. children with mild and moderate mal
nutrition showed both T cell number and proliferative
responses adequate on stimulation with mitogens/antigens and were comparable to those of normal children.
IgG, IgM and IgA levels were also in the normal ranges’.
Immune Response to Specific Antigens
Diphtheria and tetanus vaccine
Two doses of diphtheria and tetanus toxoid were
administered at an interval of one month and specific
Though BCG vaccine has been in use for a long
time, its efficacy has been under constant debate, par
ticularly in children of developing countries. How
ever, in view of its protective efficacy against
extrapulmonary forms of tuberculosis in children, rou
tine BCG vaccination is recommended.
Response to BCG vaccine is generally measured
by (Mantoux) skin reaction to PPD following
administration of the vaccine. Very often the Mantoux
reaction is negative in children with severe PEM
and is attributed to the observed immunosuppression.
Contrary to this, children with mild and moderate
grades of malnutrition have positive Mantoux
conversion as in normal children15. Positive response
to a skin test depends on two components v/z., the
inflammatory response and immune reaction to the
injected antigen.
Studies were conducted to assess the status of these
two components under the influence of PEM. Inflam
matory response to a superficial injury was studied
in children with kwashiorkor, using the skin win
dow technique. Mobilisation of neutrophil leuko
cytes and monocytes to the site of injury was stud
ied periodically over 72 h. In normal children, initially
the neutrophils move to the site of inflammation in
large numbers and are replaced by monocytes by 24
h which persist even at the end of 72 h9. The mono
nuclear infiltration is responsible for the induration
observed. However, in children with kwashiorkor,
mononuclear mobilization was impaired, and this
107
dysfunction of macrophages could be contributing
to the negative skin test reactions in these children
(Fig. 3).
progressive forms of tuberculosis in malnourished
children as effectively as in wellnourished children16.
Measles vaccine
Fig. 3. Cutaneous inflammatory response in kwashiorkor
N: Normal; K: kwashiorkor
Further studies were also conducted to explore the
effect of malnutrition on immune response to PPD.
Lymphocytes, collected from severely malnourished chil-.
dren 12 weeks after they had received BCG vaccine,
were stimulated in vitro with PPD and the production of
leukocyte migration inhibition factor (MIF) was mea
sured. It was observed that despite severe malnutrition,
these children were able to produce a positive migration
inhibition response. This study demonstrated that the
sensitization of the lymphocytes to tubercular antigens
is successful even in children with severe malnutrition15.
However, due to lack of macrophage mobilisation, the
Mantoux test was negative. Children with milder grades
of malnutrition developed both inflammatory and im
mune responses positively. These results indicate that
BCG vaccination even in a malnourished community
could achieve the expected degree of protection against
tuberculosis. This observation was further strengthened
by recent clinical studies by Bhaskaram et al'6 in chil
dren suffering from tuberculosis.
BCG vaccinated children had a more localised
infection confined to either the cervical or the medias
tinal lymphnodes. While most of the unvaccinated mal
nourished children suffered from more severe/progressive forms of tuberculosis, BCG vaccination produced
similar effects of localising the disease even in children
with malnutrition. This observation further strength
ened the laboratory studies. BCG was found to prevent
108
It is well established that measles is a major con
tributor to malnutrition in Indian children. Measles
infection is known to cause severe and persistent immu
nosuppression leading to recurring morbidity in the post
measles period17. Activation of latent tubercular lesions
and worsening of the existing forms of tuberculosis are
common phenomena observed after measles. Doubts have
therefore been expressed and concern has been voiced
regarding administration of measles vaccine to malnour
ished children living in communities where tuberculo
sis is prevalent. Specific immune responses were deter
mined in children after administering measles vaccine
and were correlated with the nutritional status.
Haemagglutination inhibition (HI) antibodies to measles
and in vitro T cell proliferative response to measles antigen
were measured. The results showed that both the anti
body production and T cell responses were adequate in
all the children irrespective of their nutritional status4.
This also suggests that unlike infection with natural measles
virus, vaccine induced infection did not have immuno
suppressive properties. Further, malnourished children
did not exhibit any side-effects following vaccination and
there was no evidence of any activation of latent tuber
cular lesions over a 3 month period of follow up. These
observations indicate the effectiveness of measles vac
cination and its safety even in communities simultaneously
carrying the load of malnutrition and tuberculosis.
Measles vaccination and morbidity
Apart from these beneficial effects, measles vacci
nation was found to significantly reduce morbidity in
children probably due to non specific stimulation of
immune mechanisms by activating macrophages4. It has
been reported that measles vaccine not only reduces
morbidity and mortality related to measles but also
prevents the risk of -severe malnutrition in children who
are already undernourished18.
Measles vaccine was introduced in India through the
Universal Immunization Programme (U1P) during 198586. Ina recent retrospective case analysis (Bhaskaram
P. et al, Unpublished observation), it was observed that
the hospital admissions of children with measles and its
' complications were significantly (69%) reduced from the
prevaccination to the postvaccination period. However,
this reduction was far from the mid decade goal of
90% reduction of measles from the prevaccination preva
lence. Mortality, however, registered a decline of 90%
from the prevaccination to the postvaccination period.
The observations also demonstrated that the incidence
of measles significantly increased in older children (above
5 years) compared to the prevaccination period where
almost 100% of the children were affected by measles
before 5 years of age. Though the UIP focuses on in
fants, the prevalence of measles in infancy has not shown
any significant decrease over the years. These observa
tions demonstrate the changing pattern of measles in the
community following the introduction of the immuniza
tion programme. Persistence of measles in infants de
spite vaccination at 9 months suggests inadequate cov
erage while periodic large outbreaks in the community
indicate the accumulation of susceptible children who
trigger the outbreaks. However, to achieve the goal of
elimination of measles by at least 2010, there is need to
intensify the measles vaccination programme and modify
it so as to cover all susceptible children upto 5 years of
age. This strategy is very essential not only to promote
child survival but also to reduce malnutrition.
Poliomyelitis
Persistence of poliomyelitis in India has often been
attributed to associated malnutrition. In a recent outbreak
in Andhra Pradesh, it was observed that the prevalence
of the infection was not related to the nutritional status19.
Out of 400 patients of acute paralytic poliomyelitis
investigated, 49.5% were wellnourished and 50.5%
malnourished. In addition, it was observed that oral polio
vaccine (OPV) conferred low herd immunity20. Lower
antibody titres and also inadequate local immune response
were noticed in natural infection as well as with OPV21.
These impaired responses were not related to the
nutritional status of the children. Thus, sub-optimal
vaccine efficacy and interference by the enteroviruses
in the gut, both being unavoidable problems in tropical
countries, could be the factors responsible for the
development of low levels of immunity leading to
persistence of poliomyelitis in the country. Malnutrition
does not seem to play any role in the persistence of
poliomyelitis. Though the load of poliomyelitis has been
significantly reduced following the implementation of
the Pulse Polio Programme, a strong disease system has
to be established to prevent resurgence of the disease.
Role of Nutrient Supplements in Vaccine Responses
Certain nutrients like B carotene, vitamins A and D3
are known to act as immune adjuvants. Among these,
B carotene and vitamin A have been found to reduce mor
bidity and mortality due to certain clinical conditions
characterised by immunosuppression.
Immune Adjuvant Effects of Vitamin A
The immunological adjuvant effects of administra
tion of vitamin A/p carotene are well documented . In l
a study carried out in preschool children, administra
tion of 100,000 and 200,000 units of vitamin A was
found to significantly enhance the production of bacte
ricidal molecules like hydrogen peroxide (H2O2) by ph
agocytes. Non specific activation of immune cells re
sulted in increase in antibody production on antigenic
challenge22. The large dose of 100,000 IU also led to
increase in interleukin 1 production by in vitro acti
vated macrophages22.
Interactions between Vitamin A and the Viral Vaccines
Vitamin A deficiency is widely prevalent among
children in developing countries. Apart from
xerophthalmia in 5-10% of preschool children, there
appears to be a much larger problem of subclinical
vitamin A deficiency as evidenced by lowered serum
retinol levels without obvious clinical manifestations
in nearly 30-40% of the children including infants.
Several studies have reported that even mild/subclinical
forms of vitamin A deficiency could increase child
morbidity by increasing susceptibility to mucosal
infections and also increase mortality23’24. Vitamin A
supplements were found to reverse these effects
significantly 25. In view of these beneficial effects of
vitamin A, WHO has recommended the routine
administration of 100,000 IU of vitamin A to infants
above 6 months of age in developing countries to improve
vitamin A status and also child survival. To achieve
the maximum cost-effectiveness, this supplementation
programme is linked with the Universal Immunization
Programme26.
Vitamin A supplements and seroconversion to measles
vaccine
Recent studies from Indonesia, however, raised con
cerns about the possible immunosuppression that could
be caused by large dose vitamin A administration along
with measles vaccine in young infants who still possess
transplacentally acquired maternal antibodies27. Thus the
combined schedule of large dose vitamin A administra
tion along with live viral vaccine administration to young
infants has become a subject of intense debate28.
109
In India, administration of 100,000 IU of vitamin A
to infants of 9 months age at the time of measles vacci
nation has been introduced into the Expanded Programme
on Immunization.
In a recent study conducted by Bhaskaram and Rao29,
seroconversion rates and vitamin A status of infants who
received vitamin A dose at the time of measles vaccine
were compared with those of the infants who received
only the vaccine. Under existing field conditions,
seroconversion to measles vaccine is generally low.
However, in children who received vitamin A, a signifi
cantly higher percentage seroconverted to measles (84%)
compared to those who received only the vaccine (63%).
Vitamin A status of all the infants improved over the
one month period of the study, the improvement being
significantly higher in children who received vitamin A29.
Vitamin A administration to mothers in puerperium and
response to neonatal dose of OPV
In recent times, in countries with endemic vitamin
A deficiency, the usefulness of administering a large
dose of vitamin A with each dose of DPT and OPV to
infants below the age of 6 months is suggested as a strat
egy to improve their vitamin A status. However, such
an exercise frequently resulted in the intracranial ten
sion being raised in a number of infants. Though the
neurological significance of a transient rise in intracra
nial tension at this age is not known, it is not an ac
ceptable phenomenon. Administration of about 200,000
IU of vitamin A to mothers soon after delivery has been
suggested as an alternative strategy to improve the vi
tamin A status of the breastfed infants30.
The WHO has recommended the routine adminis
tration of a dose of OPV to new boms within the first 3
days of life to supplement the routine 3 dose schedule in
order to achieve better seroconversion rates31.
About 100 women along with their infants were stud
ied to examine the effect of administering a large dose
-of vitamin A to the mother soon after delivery and the
sero-response to OPV administered to the breastfed new
borns. Administration of a large dose of vitamin A to
lactating mothers increased vitamin A levels in breast
milk for a short period, thus increasing the vitamin A
intakes of the infants. There was, however, no effect on
the sero-response to OPV. Seroconversion rates to all
the 3 types of polio viruses in the vaccine were compa
rable between infants belonging to mothers who received
vitamin A and those who did not32. Thus, these studies
110
document the safety of administration of live viral vac
cines along with a large dose of vitamin A. This obser
vation is of practical relevance in developing countries
where the interactions between infection and malnutri
tion pose a serious threat to child health and survival.
Thus, malnutrition does not appear to be a contrain
dication to immunization programmes. Judicial supple
mentation of nutrients having immunoadjuvant proper
ties could improve the results with certain vaccines.
References
1.
Venkatachalam, P.S., Srikantia, S.G. and Gopalan, C. Clinical
features of nutritional oedema syndrome in children. Indian J
Med Res 42: 555, 1954.
2.
Brown, K.H., Gilman, R.H., Gaffar, A., Alamgir, S.M., Strife,
J.L., Kapikian, A.Z. and Sack, R.B. Infections associated with 48h
severe protein calorie malnutrition in hospitalised infants and
children. Nutr Res. 1: 33,1981.
'3.
Reddy, V., Jagadeesan, V., Raghuramulu. N., Bhaskaram, C.
and Srikantia, S.G. Functional significance of growth retarda
tion in malnutrition. Am J Clin Nutr 29: 3,1976.
4.
Bhaskaram, P., Madhusudan, J., Radhakrishna, K. V. and Raj,
S. Immunological response to measles vaccination in poor
communities. Hum Nutr Clin Nutr 40 C: 295, 1986.
5.
Rosen, E.V., Geefhuysen, J. and IPP, I. Immunoglobulin levels
in protein calorie malnutrition. SAfrMedJ45: 980,1971.
6.
Smythe, P.M., Schon land, M., Brereton-Stiles, G. G., Coovadia,
H.M., Grace, H.J., Loening, W.E.K., Mafoyane, A., Parent,
M.A. and Vos, G.H. Thymolymphatic deficiency and depres
sion of cell mediated immunity in protein calorie malnutrition.
Lancet ii: 939, 1971.
7.
Bhaskaram, C. and Reddy, V. Cell mediated immunity in protein
calorie malnutrition. J Trop Paediatr Environ Child Health 20:
284, 1974.
. ...
8.
Chandra, R.K., Gupta, S. and Singh, H. Inducer and suppressor
T cell subsets in protein energy malnutrition: Analysis by
monoclonal antibodies. Nutr Res 2: 21, 1982.
9.
Bhaskaram, P. and Reddy, V. Cutaneous inflammatory response
in kwashiorkor. Indian J Med Res. 76: 849, 1982
10.
Bhaskaram, P. Macrophage function in severe protein energy
malnutrition. Indian J Med Res. 71: 247, 1980.
11.
Bhaskaram, P. and Reddy, V. Macrophage functions in kwash
iorkor. Indian J Paediatr. 49: 497, 1982.
12.
Bhaskaram, P. and Sivakumar, B. Interleukin-1 in malnutrition. Arch Dis child. 61: 182, 1986.
13.
Bhaskaram, P. Nitrite production by lymphokine activated
peripheral blood monocytes in malnourished patients with tu
berculosis. J Nutr Immunol. 4: 71, 1995.
14.
Reddy, V., Rao, N.P., Sastry, J.G. and Kasinath, K. Nutrition
Trends in India, National Institute ofNutrition, Hyderabad P.31,
1993.
A
f
15.
Satyanarayana, K., Bhaskaram, P., Chitti Seshu, V. and Reddy,
V. Influence of nutrition on postvaccinial tuberculin sensitivity. Am J Clin Nutr. 33: 2334, 1980.
16.
Bhaskaram, P., Hemalatha, P. and Rao, K.V. BCG vaccination
in malnourished child population. Indian Paediatr 29:39,1992.
17.
Bhaskaram, P., Raj, S. and Reddy, V. Effect of measles on cell
mediated immunity. Indian J Med Res 77: 83, 1983.
18.
Faechem, M and Koblinsky, M. A. Interventions for the control
of diarrhoeal diseases among young children. Measles immu
nization. Bull WHO 61: 641, 1983.
19.
Murthy, N., Bhaskaram, P., Murali, M. V., Sukanya, M and
Srinivasa Rao, C.R. An outbreak of poliomyelitis in Andhra
Pradesh, south India. Indian Paediatr 31: 533, 1994.
20.
Murthy, N. and Bhaskaram, P. Serology of unvaccinated popu
lation against polio viruses - A study from Andhra Pradesh,
south India. Infect Dis Immunol. 4: 60, 1994.
21.
Bhaskaram, P., Nair, M., Murthy, N., Hemalatha, P., and Nair,
P. Efficacy of administration of OPV in the new bom period.
J Trop Paediatr 43: 232, 1997.
22.
Bhaskaram, P., Jyothi,A. S., Rao, K.V. and Narasinga Rao, B.S.
Effects of subclinical vitamin A deficiency and administration
of vitamin A as a single large dose on immune function in chil
dren. Nutr Res 9: 1017, 1989.
23.
Sommer, A., Katz, J. and Tarwotjo, I. Increased risk of respi
ratory disease and diarrhoea in children with pre existing mild
vitamin A deficiency. Am J Clin Nutr 40: 1090, 1984.
24.
Milton, R.C., Reddy, V. and Naidu, A.N. Mild vitamin A de
ficiency and childhood morbidity - An Indian experience. Am
J Clin Nutr 46: 827, 1987.
25.
Sommer, A., Tarwotjo, I., Djunaedi, E., West, K.P. Jr., Loeden,
A.A., Tilden, R.,.Mele, L. and The Aceh study group. Impact
of vitamin A supplementation on childhood mortality: A
randomised controlled community trial. Lancet i: fl69, 1986.
26.
World Health Organization. Using Immunization Contacts to
Combat Vitamin A Deficiency. A discussion document submit
ted to EPI Global Advisory Group Meeting, Jakarta. (October
12-16, 1992). Expanded Programme on Immunization, World
Health Organization, Geneva 1992 .
27.
Semba, R.D., Munasir, Z., Beeler, J., Akib, A., Muhilal, Audet,
S. and Sommer, A. Reduced seroconversion to measles in in
fants given vitamin A with measles vaccination. Lancet 345:1330
1995.
28.
Ross, D. Vitamin A plus measles vaccination. The downside
of convenience? Lancet 345: 1317, 1995.
29.
Bhaskaram, P. and Rao, K.V. Enhancement in seroconversion
on simultaneous administration of measles vaccine and vita
min A in 9 months Indian infants. Indian J Paediatr 64: 503,
1997.
30.
WHO/UNICEF/IVACG Task Force. Vitamin A Supplements: A
Guide to Their Use in the Treatment and Prevention of Vitamin
A Deficiency and Xerophthalmia. World Health Organization,
Geneva, 1988.-
31.
Expanded Programme on Immunization. Global Advisory Group
Summary of Conclusions and Recommendations. Wkly Epidemiol
Rec 60: 13, 1985.
32.
Bhaskaram, P. and Balakrishna, N. Effect of administration of
200,000 IU of vitamin A to women 24 h after delivery on re
sponse to OPV administration to the new bom. Indian paediatr
35: 217, 1998.
This write-up has been adopted from the article entitled
“Nutrition - immunization interactions and relevance to
child health” by Dr. P. Bhaskaram, published in the
Nutrition News 17(4): 1996.
ABSTRACTS
Some Research Projects Completed Recently
Role of ‘S’ transactivator in hepatocarcinogenesis: In
vitro expression and purification of transactivating
proteins.
The study was carried out to elucidate the effect of
‘S’ (463-851) transactivator on various promotor enhancer
systems; raise monoclonal/polyclonal antibodies against
this transactivator protein prepared either by recombi
nant DNA method or by using synthetic peptides; and
demonstrate and localize the transactivator protein in
hepatocarcinoma cells.
The association of hepatitis B virus (HVB) in hepa
tocellular carcinoma (HCC) is well established. Insertional mutagenesis, transactivation by truncated X or pre
S2/S regions and activation of growth regulated genes
or oncogenes have been suggested as possible mecha
nisms for carcinogenesis. The transactivating properties
of a frequently detected fragment, which form part of
the ‘S’ reading frame, extending from 426 nt. to 855 nt.,
has been reported.
The clones were sequenced and subcloned into
pRSET vectors in all the three reading frames and
expressed using IPTG induction. A Western blot analysis
was done using polyclonal anti HBsAg and the presence
of 19.24 kDa functional protein in the correct reading
frame was obtained. The expressed protein was checked
for by commercial ELISA. However, the antigen could
not be detected by ELISA in any of the three reading
111
frames. The ‘S’ protein was purified by SDA-PAGE
and was used to raise polyclonal antibodies in rabbits.
These polyclonal antibodies were then used to screen
the presence of‘S’ protein in hepatocellular carcinoma
tissues. The ‘S’ region being a very small part of the
surface region of the virus (426-824 ntds), could not be
detected by immunofluorescence. The region, extending
from 426-824 ntds was proved to be a generalized
transactivator ofthe viral promoters and enhancers. Using
chloramphenicol acyl transferase as a reporter gene, in
transfection assays it was found to be capable of activating
HIV promoter, HTLVI promoter, RSV promoter and
enhancer, c-Fos and c-Jun promoter to a high degree.
S.K. Panda
Department of Pathology
All India Institute of Medical Sciences
New Delhi.
summer - extended light conditions). The human
volunteers, divided into two groups were given either
beta adrenergic blocker (atenolol) or placebo.
The results of both the animal and human studies
showed that under the influence of constant dark and light,
sympathetic innervation to the pineal primarily has tonic
inhibitory influence on the suprachiasmatic nucleus, the
biological clock, which alters the amplitude and mean
level of various rhythms to keep the synchrony and
coupling of various physiological and hormonal rhythms.
The rat study also provided convincing data for the presence
of extra-sympathetic inputs (probably neuropeptide-Yergic
and cholinergic) to the pineal which are stimulated only
if melatonin level is severely depressed as in cases of
absence of sympathetic innervation or on exposure to
continuous light.
U. Sachdeva
Department of Physiology
All India Institute of Medical Sciences
New Delhi.
Interaction of melatonin and circadian rhythmicity in
Antarctic conditions.
The study was carried out to evaluate the coupling
pattern of melatonin and other circadian rhythmicity in
the human subjects in Antarctic conditions and on rats
under simulated Antarctic exposure of diversifying light
and dark cycle. The experimental study was carried out
on 42 male Wistar strain rats (200-300 g) divided into 3
groups viz normal (control without surgical
intervention);sham operated; and superior cervical
ganglionectomized. The human study was conducted on
eight volunteers from the 12th Indian scientific expedition
to Antarctica (Antarctic winter - extended dark conditions)
and six volunteers from the 13th expedition (Antarctic
Publications:
1.
Mehta, N., Naidu, M. and Sachdeva, U. Desynchronisation of
circadian rhythms in winter over Antarctic expeditioners. In:
Scientific Report - Txvelth Indian Expedition to Antarctica. Ed.
VJG Dhargalkar. Technical Publication NO. 12 Department of
Ocean Development, New Delhi, p.291, 1996.
2.
Sachdeva, U., Naidu, M. And Sundaresan, G. Biorhythms: Role
of photoperiodicity in regulating hormonal rhythms of human
subjects in Antarctica. In: Pigment Cell and Photobiology :
Proceedings ofGrowth Disorders ofPigment Cells. Ed. B. lyenger.
Livingstone, New Delhi, pl, 1996.
ICMR NEWS
The following meetings of various technical groups/
committees of the Council were held:
Enterovirus Research Centre,
Mumbai
Meetings of the Scientific Advisory Committees of the
following ICMR Institutes/Centres:
Rajendra Memorial Research November 16-17, 1998
Institute for Medical Sciences,
Patna
National Institute of Cholera
and Enteric Diseases, Calcutta
October 25-26, 1998
Central JALMA Institute
for Leprosy Agra
November 13-14, 1998
National AIDS Research
Institute, Pune
November 16-17, 1998
112
November 16-17, 1998
Meeting of the Project Review Committee (PRC) held
at New Delhi:
PRC for Cardiovascular
Diseases, Urology,
Gastroenterology, Nephrology,
Geriatrics and Ophthalmology
October 30, 1998
Participation of ICMR Scientists in Scientific Events:
Dr. D.A. Gadkari, Director, National Institute of
Virology, Pune, participated in a joint meeting of the
United Nations Programme on HIV/AIDS (UNAIDS),
WHO Global Programme on Vaccines and Immuni
zation and the Japanese National Institute of Infec
tious Diseases, to discuss AIDS Vaccine in Asia: Needs
and Opportunities at Tokyo (October 28-30, 1998).
Dr. Kamala Krishnaswamy, Director, National in
stitute of Nutrition (NIN), Hyderabad, participated in a
consultative meeting on Severe Anaemia in Pregnancy
in India and Bangladesh at Dhaka (November 15-17,1998).
Dr. B. Sivakumar, Dy. Director (Sr.Grade), NIN,
Hyderabad, participated in a workshop on Micronutri
ent Fortification at Dhaka (November 18, 1998).
Workshop:
Dr. Z.M. Patel, Dy. Director and Officer-in-Charge,
ICMR Genetic Research Centre, Mumbai, participated
in the VIII International Conference on Ultrasound at
London (November 1-5, 1998).
Dr. N.K. Ganguly, Director-General, ICMR,
delivered the keynote address at the International
Symposium on Biotechnological Approaches to
Parasitic and Bacterial Diseases at the Indian Institute
of Chemical Biology, Calcutta (November 6, 1998).
Dr. K.D. Ramaiah, Sr. Research Officer, Vector
Control Research Centre, Pondicherry, participated in
a workshop on Economic Research Agenda for the
Global Programme to Eliminate Filariasis at Atlanta
(November 12-13, 1998).
The ICMR-WHO Workshop on New Challenges in
Intellectual Property Rights in Medical Research was
organised in New Delhi during November 17-18,1998.
It was attended by Directors of ICMR Institutes, Chiefs
of Technical Divisions of ICMR Hqrs, senior professionals
from sister agencies and WHO representatives.
Annual Day Celebrations:
As part of the ICMR’s Annual Day celebrations, the
Council organised orations on (i) Molecular Biology: The
Continuing Challenge by Prof. Asis K. Datta, Vice
Chancellor, Jawaharlal Nehru University, New Delhi, and
(ii) Perspectives in Medical Research in India by Prof.
P.N. Tandon, Emeritus Professor, All India Institute of
Medical Sciences, New Delhi on November 19, 1998.
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/COURSES/CONFERENCES
Symposium/Seminar/Workshop/
Course/Conference
Date & Place
Contact Address
International Symposium on Major Histocompatibility
Complex.
October 29 November 1,1998;
(at New Delhi)
Dr. N.K. Mehra, Prof, and Head, Department of
Histocompatibility and Immunogenetics, All India
Institute of Medical Sciences, New Delhi-110029.
Precongress Workshop on Andrology and Male Infertility
and National Congress on Andrology and Reproductive
Medicine.
October 29 November 2,1998;
(at Calcutta)
Dr. A.K. Bhattacharya, Organising Secretary ofthe
Congress, Department of Biochemistry, University
College of Science, Calcutta-700019.
Continuing Medical Education-cum-Workshop on Brachy
therapy for Head and Neck Cancers and Breast Cancer
October 30 November 1,1998;
(at Imphal)
Dr. Th. Tomcha Singh, Organising Secretary of the
Workshop, Department of Radiotherapy, Regional
Institute of Medical Sciences, Imphal-795004.
International Congress and Workshop on Recent Advances
in Medical Toxicology and Legal Medicine
November 2-7,1998;
(at New Delhi)
Dr. O.P. Murthy, Organising Secretary of the
Conference, Department of Forensic Medicine and
Toxicology, All India Institute of Medical
Sciences, New Delhi-110029.
International Conference on Medical Physics and XIX
Annual Conference of Association of Medical Physicists
of India
November 6-9,1998;
(at New Delhi)
Dr. M.M. Rehini, Organising Secretary of the
Conference, Medical Physics Unit, Institute Rotary
Cancer Hospital, All India Institute of Medical
Sciences, New Delhi-110029.
Indo-Japanese Symposium on Frontiers of Electron
Microscopy in the 21st Century and XXII Annual Meeting
of Electron Microscopy Society of India
November 9-11, 1998;
(at Hyderabad)
Dr. P.D. Gupta, Convenor of XXII EMSI Meet
ing, Centre for Cellular and Molecular Biology,
Hyderabad-500007.
International Workshop on Adverse Drug Reaction
Monitoring
November 9-12,1998;
(at Aligarh)
Prof. K.C. Singhal, Organising Secretary
of the Workshop, Department of Pharmacology,
J.N. Medical College, Aligarh-202002.
113
Symposium/Seminar/Workshop/
Date & Place
Contact Address
Course/Conference
International Workshop on Medical Mycology
November 16-21,1998;
(at Chandigarh)
Dr. A. Chakrabarti, Organising Secretary of the
Workshop, Department of Microbiology, Post
graduate Institute of Medical Education and
Research, Chandigarh-160012.
Seminar on Integration of Advances in Biostatistics
into Medical Research
November 19-21, 1998;
(at Vellore)
Dr. J. Richard, Prof, and Head. Department of
Biostatistics, Christian Medical College, Vellore632002.
International Conference on Organization and
Management of Blood Transfusion Service, Plans and
Policies
November 22-24,1998;
(at Mumbai)
Dr. Z.S. Bharucha, Prof, and Head, Department
of Transfusion Medicine, Tata Memorial Hospital,
Mumbai-400012.
Workshop on Ending Malnutrition by 2020: An Agenda
for Change in the Millennium
November 23-26,1998;
(at Chennai)
Dr. S. Rajagopalan, Distinguished Fellow, M.S.
Swaminathan Research Foundation, Chennai600113.
Symposia on (i) Public Health Nutrition Problems;
(ii) Frontiers in Nutrition Science; and (iii) Growth and
Development of Children of South- East Asia
November 26-28,1998;
(at Hyderabad)
Dr. T.C. Raghu Ram, Joint Secretary, Nutrition
Society of India, National Institute of Nutrition,
Hyderabad-500007.
XI Annual Conference of Indian Society for Atherosclero
sis Research and International Symposium/CME on
Prevention of Coronary Artery Disease : Concerns and
Perspectives
November 27-29,1998;
(at New Delhi)
Dr. S. uwivedi, Organising Secretary of the
Conference, Prevention Cardiology Clinic, Univer
sity College of Medical Sciences, Delhi-110095.
XXXV Guha Research Conference 1998
December 1-5,1998;
(at Port Blair)
Dr. Lalji Singh, Convener, GRC 1998, Centre for
Cellular and Molecular Biology, Hyderabad500007.
All India Workshop/Training Course on Application of
Direct Methods in Crystallography for Solving Small/
Medium sized Molecules
December 1-21,1998;
(at Chennai)
Dr. D. Velmurugan, Convener of the Workshop,
Department of Crystallography and Biophysics.
University of Madras, Chennai-600025.
International Conference on Quality of Psychiatric Care
December 2-4,1998;
(at Calcutta)
Dr. A.N. Chowdhury, Prof, and Head, Department
of Psychiatry, Institute of Postgraduate Medical
Education and Research, Calcutta-700025.
Seminar on Responsiveness in Pulmonary Tuberculosis Clinical Relevance
December 12,1998;
(at Chandigarh)
Dr. S.K. Jindal, Head, Department of Pulmonary
Medicine, Postgraduate Institute of Medical
Education and Research, Chandigarh-160012.
XXVIII Annual Conference of the Endocrine Society of
India
December 14-16, 1998;
(at Varanasi)'
Dr. S.K. Singh, Organizing Secretary of the Con
ference, Department of Endocrinology, Institute of
Medical Sciences, Banaras Hindu University,
Varanasi-221005.
XXXI Annual Conference of the Indian Pharmacological
Society
December 17-20,1998;
(at Lucknow)
Dr. V.N. Puri, Organisng Secretary of the Confer
ence, Division of Pharmacology, Central Drug
Research Institute, Lucknow-226001.
V International Symposium on Biochemical Roles of
Eukaryotic Cell Surface Macromolecules
January 4-8. 1999;
(at Bangalore)
Dr. A. Surolia, Convener of the Symposium.
Molecular Biophysics Unit, Indian Institute of
Science, Bangalore-560012.
National Symposium on Biological Control of Insects in
Agriculture, Forestry, Medicine and Veterinary Science
January 21-22,1999;
(at Coimbatore)
Dr. K. Murugan. Organising Secretary of the
Symposium, Division of Entomology, Department
of Zoology. Bharathiar University. Coimbatore641046.
Vll Annual Meeting of Molecular Immunology Forum 1999
February 13-15,1999;
(at Hyderabad)
Dr. Ashok Khar, Convener of the Meeting, Centre
for Cellular and Molecular Biology, Hyderabad500007.
i
114
COUNCIL’S TRAINING PROGRAMMES
Leprosy
•
At the Central JALMA Institute for Leprosy, Agra:
•
Multidrug Therapy Orientation Course in Leprosy for
Medical Officers (October 26-November 6; and
December 7-18, 1998).
Occupational Health
At the National Institute of Occupational Health,
Ahmedabad:
•
Reproductive Biology
At the Institute for Research in Reproduction, Mumbai:
•
Workshop on Andrology for Clinicians (November 1630, 1998)
Postgraduate Certificate Course in Nutrition
(December 1, 1998-February 28, 1999).
Training Course on Environmental Hygiene Practice
(November 16-20,1998).
Biomedical Statistics
At the Institutefor Research in Medical Statistics, Chennai:
Nutrition
•
At the National Institute of Nutrition, Hyderabad:
Basic Course in Statistics for Medical Officers
(November 3 O-December 6, 1998).
ICMR PUBLICATIONS
Price(Rs.)
Nutritive Value of Indian Foods (1985) by C. Gopalan, B.V. Rama Sastri and S.C. Balasubramanian,
Revised and Updated (1989) by B.S. Narasinga Rao, Y.G. Deosthale and K.C. Pant (Reprinted 1996)
23.00
Growth and Physical Development of Indian Infants and Children (1972, Reprinted 1989)
10.00
Studies on Weaning and Supplementary Foods (1974, Reprinted 1996)
15.00
A Manual of Nutrition (Second Edition 1974, Reprinted 1995)
6.00
Low Cost Nutritious Supplements (Second Edition 1975, Reprinted 1996)
5.00
Menus for Low-Cost Balanced Diets and School-Lunch Programmes Suitable for North India
(Second Edition 1977, Reprinted 1994)
4.50
Menus for Low-Cost Balanced Diets and School-Lunch Programmes Suitable for South India
(Fourth Edition 1996)
6.00
Some Common Indian Recipes and their Nutritive Value (Fourth Edition 1977, Reprinted 1995)
by Swaran Pasricha and L.M. Rebello
10.00
Nutrition for Mother and Child (Fourth Edition 1994, Reprinted 1996) by P.S. Venkatachalam and
L.M. Rebello
11.00
Japanese Encephalitis in India (Revised Edition 1980)
5.00
Some Therapeutic Diets (Fifth Edition 1996) by Swaran Pasricha
7.00
Nutrient Requirements and Recommended Dietary Allowances for Indians (1990,Reprinted 1995)
16.00
115
Fruits (Second Edition 1996) by Indira Gopalan and M. Mohan Ram
20.00
Count What You Eat (1989, Reprinted 1997) by Swaran Pasricha
15.00
•The Anophelines of India (Revised Edition 1984) by T.Ramachandra Rao
150.00
Depressive Disease (1986) by A. Venkoba Rao
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•Medicinal Plants of India Vol.2 (1987)
136.00
Diet and Diabetes (Second Edition 1993, Reprinted 1997) by*T.C. Raghuram,Swaran Pasricha and
R.D. Sharma
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Dietary Tips for the Elderly (1992, Reprinted 1997) by Swaran Pasricha and B.V.S. Thimmayamma
5.00
Diet and Heart Disease( 1994,Reprinted 1995) by Ghafoorunissa and Kamala Krishnaswamy
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Dietary Guidelines for Indians - A Manual (1998)
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* 25 per cent discount allowed to individuals
These publications are available on prepayment of cost by cheque, bank draft or postal order (bank and postal charges will
be extra) in favour of the Director-General, Indian Council of Medical Research, New Delhi. Money orders are not acceptable.
All correspondence in this regard should be addressed to the Chief, Division of Publication and Information, Indian Council
of Medical Research, Post Box No.4911, Ansari Nagar, New Delhi-110029 (India).
EDITORIAL BOARD
Members
Dr. Padam Singh
Dr. Lalit Kant
Dr. Bela Shah
Dr. R. Ravi
Dr. V. Muthuswamy
Chairman
Dr. N.K. Ganguly
Director-General
Editor
Dr. N. Medappa
Printed and Published by Shri J.N. Mathur for the Indian Council of Medical Research, New Delhi
at the ICMR Offset Press, New Delhi-110 029
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