ICMR BULLETIN VOL. 25-No.-3-MARCH-1995
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- ICMR BULLETIN VOL. 25-No.-3-MARCH-1995
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ISSN 0377-4910
ICMR
BULLETIN
婪
March, 1995
VoL25, No.3
BCG : DO WE HAVE AN ALTERNATIVE
Vaccination is generally used as a form of immunopro
phylaxis, so that administration of the vaccine even a
long time before exposure to the wild-type infectious
organism should afford protection. Since effector T
and B cells are short-lived, a prime requisite for a
vaccine is to generate immunological memory.1 In the
case of organisms such as mycobacteria which are
obligate intracellular pathogens and which elicit
granulomatous tissue reactions, artificial immunisation
with live bacteria is required to induce protection.2,3
The only existing vaccine against tuberculosis is the
BCG (Bacille Calmette - Guerin), an attenuated strain
of M.bovis and it is mandatory or officially recom
mended in 182 countries or territories. Under the
Expanded Programme on Immunisation (EPI) started
by the Government of India in 1978, BCG is recom
mended to be given to ail infants 3-9 months after
birth.4
History of BCG Vaccine
The history of BCG vaccination and the trials
conducted to assess its effectiveness in humans have
been reviewed by many workers.5"10 BCG, the biletolerant, attenuated strain of M.boyis, was isolated by
Calmette and Guerin.11 Ox-bile was originally added
to these cultures to prevent clumping of bacilli. This
led to the fortuitous observation that growth in the
presence of bile also resulted in attenuation or gradual
loss of virulence.
Such attenuated organisms will
multiply only to a limited extent in the animal or human
body and can bring about an increase in the resistance
of the host to a subsequent fully virulent infection by
the same or other antigenically closely related organ
isms. Calmette further attenuated this strain by cul
tivation of the organism on a potato-glycerol-bile medium
fbr 230 serial transfers between the years 1908 and
1918.
'
The bacilli resulting from this attenuation have
never been cloned. The original strain of BCG has been
lost and has been replaced by a variant while it was
being transferred serially on artificial culture media at
the Pasteur Institute12 and have since been maintained
by many different laboratories, using many different
methods. As a result, the BCG strains used today are
not bacterioiogically identical.13,14 In 1966, a WHO
Expert Committee on Biological Standardisation adopted
a series of recommendations for the production of BCG
vaccine.15..These recommendations stated that the vaccine
should be freeze-dried, and that the vaccine strain
should be maintained by the seed-lot-system whereby
no vaccine is produced from a seed more than 12
most laboratories and this eliminated the possibility of
more attenuated variants in later BCG vaccine lots.16
BCG Vaccine Production in India
In India, the BCG Vaccine Laboratory was started
in Madras in 1948 for the production of BCG vaccine
for use in India and also for supply to some of the
neighbouring countries. Since 1966, Danish strain
1331 is being used here for the preparation of both the
liquid and the freeze-dried BCG vaccines, based on the
seed-lot-system17.
For preparing the liquid and freeze-dried vaccine,
the BCG Laboratory, Madras, uses the method followed
at the State Serum Institute, Copenhagen, but using
Sauton potato medium for maintaining the BCG strain.
The prepared vaccine is tested for purity by ZiehlNeelsen smear for acid fast bacilli, and by culture on
nutrient broth, th ioglycol late medium and Sabouraud's
agar medium. Total bacterial count and the number
of culturable particles in the preparation are estimated.
Biological tests are carried out in guineapigs to estimate
the degree of virulence of the BCG vaccine, allergenicity
and safety. In addition to the above tests, in the case
of the freeze-dried vaccine, tests are carried out to
estimate residual moisture and heat stability. Both
types of vaccines are to be stored at refrigeration
temperature, protected from light. Under these con
ditions of storage, the liquid vaccine can be used for
4 weeks from the date of manufacture while the freezedried vaccine can be used for 3 months.
BCG can be administered intracutaneously, orally,
by scarification or by multiple puncture. The most
widely used method of administration is by intracutaneous injection. The dose is usually 0.1 ml and the
site of injection is the upper arm. In the newborn, the
dose used is 0.05 ml. The liquid BCG vaccine prepared
by the BCG Laboratory, Madras, is to be administered
by an intracutaneous injection of 0.1 ml of the vaccine
containing 0.075 mg (moist weight) of BCG. The
freeze-dried vaccine prepared here is reconstituted by
the addition of sterile distilled water or sterile saline
to contain 0.1 mg (moist weight) in 0.1 ml of vaccine
which is given intracutaneously.
Efficacy of BCG Vaccine
BCG was used successfully in humans for the first
time in 1921 by Weil-Halle, a colleague of Calmette
34
and Guerin.18 Scepticism concerning the safety and
efficacy of BCG vaccine, and the Lubeck disaster in
which 72 of 240 children vaccinated with BCG died
as a result of being fed a batch of vaccine containing
virulent tubercle bacilli, delayed the acceptance of
BCG. A series of controlled trials were begun in the
1930s. Despite inconsistent results from the trials,
WHO encouraged widespread dissemination of BCG
vaccines, starting in the 1950s.7 By the 1970s, BCG
became the most widely used vaccine in the world.
About 3 billion doses have been given in the last four
decades, and more than 70 per cent of the world's
children now receive BCG.3,19
Between the years 1935 and 1955, at least eight
controlled trials were conducted to assess the efficacy
of BCG vaccine against tuberculosis. The protective
efficacy obtained ranged from none to 80 per cent
(Table).8
Table: Protective efficacy of BCG vaccine against tuber
culosis
Period of intake
Protective
efficacy (%)
North American Indians
1935-1938
80
Chicago infants
Georgia school children
1937-1948
1947
75
Illinois children
1947-1948
1949-1951
None
Georgia and Alabama
general population
1950.
14
British children
1950-1952
78
South Indian
rural population
1950-1955
31
Population group
Puerto Rico
general population
None
31
The South Indian Trial
A study was started in Chingleput, south India, in
1968 in an attempt to avoid the methodologic errors
that might have affected previous trials. ^*20,21 The south
Indian BCG trial was organised by the Indian Council
of Medical Research (ICMR) in collaboration with the
WHO and Centre for Disease Control (CDC), US
Public Health Services. The intake for the study started
in 1968 and was completed in 1971, including about
2.6 lakh participants out of a population of 3.6 lakhs.
The entire population of all ages was eligible and
tuberculin reactors were not excluded, in contrast with
previous trials. Two BCG strains, Copenhagen and
Paris, were tested at two doses, 0.1 mg and 0.01 mg.
Neither of the vaccines, whether in full or reduced
dosage, had given any protection against the bacillary
form of pulmonary tuberculosis as assessed over a 7.5
year follow up period. No data are available from the
study to evaluate protection in children. Very little
disease was observed in the period immediately after
infection.22 Incidence peaks were absent in young
children and in young adults but the incidence increased
logarithmically with age.
The findings of the south Indian trial were disappoint
ing. The ICMR convened an expert committee meeting
to scrutinise the trial methodology, wherein it was
agreed that no errors in the conduct of the field op
erations or in the data processing could have been so
serious as to invalidate the results.10 In the first meeting
of the ICMR/WHO Scientific Group23 it was stated that
the data obtained in this trial are unique and of great
importance for tropical countries, and should be con
sidered as the starting point fbr further intensive in
vestigations into the epidemiological, bacteriological
and immunological problems related to BCG vaccine
and tuberculosis, as well as studies to test certain
hypotheses, eg, that the immune response of the popu
lation was unusual, that the vaccine were inadequate
to confer immunity, that the south Indian variant of M.
tuberculosis acted as an attenuated immunising agent,
and that mycobacteria other than M. tuberculosis may
have partially immunised the study population.
Explanations for the Varying Efficacy of BCG
The explanations and hypotheses fbr the varying
efficacy of BCG have been discussed in detail5-7. BCG's
varying efficacy due to interactions with the immune
responses to other mycobacterial infections still re
mains one of the most popular explanations. Palmer and
associates24,25 showed in animal experiments, and in
studies of US navy personnel, that infections with
certain non-tuberculous mycobacteria could impart some
protection against infection with the tubercle bacillus
and such naturally acquired protection could mask any
protection due to BCG vaccination, partially or totally.
This explanation was criticised by Hart26 as being
inadequate to explain all the differences between the
various BCG vaccine trials. Comstock et aP also couii
not find any evidence for lowered protection by BCG
in those with intermediate levels of tuberculin reactiv
ity, and this was thought to be due to non-tuberculous
mycobacterial infection, in the Puerto Rico trial.
In the 1980s, Rook, Stanford and associates28*30
proposed that exposure to non-tuberculous mycobacte
ria (NTM) can result in two types of cell-mediated
responses, the 'Listeria type, and the 'Koch type'.
Which of these two types of responses is evoked de
pended, among other factors, on the mycobacterial
species inducing the response and the immunomodulating
cells and the pathway brought into play. They further
proposed that the 'Listeria type' of response enhances
the protective effect of subsequent vaccination with
BCG while the 'Koch type* response opposes the pro
tective effect of BCG. Once Koch-like responsiveness
is present, this blocks subsequent recognition of further
species by Listeria-like responses. BCG vaccination of
a person with a pre-existing Koch-like response will
temporarily boost this response, but completely fail to
reconvert to Listeria-like responsiveness or induce
protection from pathogenic challenge. According to
them, this is likely to have been the situation in the
south Indian trial?1-32
Investigations carried out since then have been able
to produce some evidence supporting the hypothesis
that infection with NTM induces a protective response
and does not interfere with the immunity produced by
BCG. Attempts to demonstrate that prior infection with
any of the mycobacteria induced a suppressive effect
against BCG have failed.33'36
The study population in the south Indian BCG trial
was characterised by a very high prevalence pf nonspe
cific sensitivity.37 Further, nearly 20 per cent of the
NTM obtained from sputum samples of subjects in this
area belonged to the Mycobacterium avium-intracellularescrofulaceum (MAIS) complex,38 and a recent study on
the isolation profiles of environmental mycobacteria
present in soil, water and dust samples, and sputum
samples of symptomatics in this area has shown that
isolates belonging to the MAIS complex are predomi
nant in water, dust and sputum samples while organisms
of the M.fortuitum complex are predominant in soil
samples.39
The hypothesis that oral immunisation with M. avium
intracellulare complex might induce tolerance which
35
might interfere with the immune response to subsequent
BCG immunisation was studied at the Tuberculosis
Research Centre (TRC)40 in guineapigs challenged with
M.tuberculosis, and* it was found that there was no
interference with the protective immunity induced by
BCG. A later study using intradermal route showed
that while there was no interference with the immunity
due to BCG by prior exposure to NTM on the early
course of challenge infection, modulation could be
taking place during the later course.41
The variation in the efficacy of BCG has also been
attributed to the differences between the BCG prepa
rations.42,43 Another view is that BCG is more effective
in stopping haematogenous spread of the bacteria as
occurring in primary progressive disease and endog
enous reactivation versus exogenous reinfections.44 Other
explanations include the genetic or physiological dif
ferences between the trial populations.
More recently, another explanation fbr the varying
efficacy of BCG has been proposed based on the ob
servation that a subgroup of the population may be
actually adversely affected by vaccination.45 Several
trials include in the assessment many subject with weak
initial tuberculin sensitivity, due either to environmen
tal mycobacterial infection or to infection with
M.tuberculosis.
While it is accepted that vaccine
efficacy may be moderately reduced in the former
subgroup, it has been postulated that the I attar subgroup
may be at risk of reactivation of tuberculosis soon after
vaccination perhaps from focal reactions due to en
hancement of their weak sensitivity. The low levels of
efficacy in several trials, and the early adverse effect
in the south Indian trial are broaaly consistent with this
hypothesis.
In a search fbr identifying the correlates of vaccineinduced protective immunity, more than 70000 subjects
in northern Malawi were skin tested with soluble an
tigens of the tubercle and leprosy bacilli, and then
followed up for 5 years for tuberculosis and leprosy
incidence. Incidence rate ratios were calculated to compare
subjects with different levels of prior skin test sensi
tivity.46 It was found that delayed type hyper-sensitivity
to mycobacterial antigens has different implications fbr
tuberculosis and leprosy: low level hypersensitivity,
probably attributable to environmental mycobacteria,
was associated with protection, but persistent vaccine
associated hypersensitivity to mycobacterial antigens
36
was not a correlate of vaccine derived protection against
mycobacterial diseases.
BCG Vaccination and HIV Infection
With regard to BCG vaccination in HIV infected
individuals, there are reports of BCG abscesses in HIV
seropositives, and of disseminated infection due to BCG
in at least one case given BCG.47 However, in all these
cases,, the infection could be successfully treated.
Since the risks and known consequences of natural
infection with tubercle bacilli are likely to be more
serious than the risks associated with live attenuated
vaccines, the WHO has recommended that all asymptomatic
HIV infected children should receive all standard vac
cines both live and inactivated; and those with symp
toms of AIDS Related Complex (ARC)ZAIDS should
receive all vaccines other than BCG. However, in
developing countries like India, where extensive HIV
testing is not possib!°, the WHO Expert Group has
recommended that all infants should continue to receive
immunisation against all the major preventable dis
eases.48
There is no evidence that BCG activates HIV in
fection.49 Further, it has been observed that the inci
dence of disease due to M.avium intracellulare (MAI)
in AIDS patients varies from region to region and it
has been postulated that this difference is the result of
a protective effect of neonatal BCG vaccination.50 In
the USA, 30 per cent of patients with AIDS develop
MAI disease in contrast to only 10 per cent of AIDS
patients in Sweden. This difference in incidence be
tween the two countries could be due to BCG vacci
nation: most Swedish patients with AIDS would have
received BCG in infancy while those in the USA would
be unvaccinated. This is further supported by the fact
that over 50 per cent of AIDS patients m Netherlands.
where BCG vaccination is not given, developed disease
due to MAI or M.scrofulaceum. Also, in a limited
.follow up of HIV infected individuals at the TRC,
Madras, it has been found that while a few HIV infected
• individuals developed disease due to M. tuberculosis no
case has been encountered so far with disease due to
MAI (Tuberculosis Research Centre - Unpublished
observations). It has been suggested that MAI disease
in AIDS is not due to direct infection but that it arises
from long standing silent fbci of MAI in the lymphatic
tissue of the patient.51 It is possible that neonatal BCG
vaccination prevents overt infection by MAI and may
therefore prevent inapparent persisting infection of
lymphoid tissue thus removing the internal reservoir of
these bacilli from which AIDS-related MAI disease
may arise later in life.52
BCG as an Immunopotentiating Agent
The widespread use of BCG has demonstrated its
safety and its potent immunogenicity. This has also
led to its suggested use as a carrier to vaccinate against
other diseases.53,54 BCG and other mycobacteria are
highly effective adjuvants. It is one of the few
vaccines that can be given at birth, and with a single
dose it induces long-lived immune responses. Till now,
nearly 3 billion vaccinations have been carried out
using BCG with a long record of safe use in man. There
is also a worldwide distribution network with experi
ence in BCG vaccination. The adjuvant properties of
BCG and its cell wall components have previously been
made use of in experimental vaccines. Mixtures of
BCG and schistosomal antigens have been used success
fully to protect mice in a model of schistosomiasis.55
Mixture of muramyl dipeptide, which is one of the
mycobacterial cell wall components that contributes to
the adjuvant properties, and killed simian immunodefi
ciency virus (SIV) has been shown to provide partial
protection against SIV infection in monkeys.56 Mix
tures of BCG and killed M.leprae have been used in
large scale trials to assess the efficacy of this leprosy
vaccine candidate.57
Recombinant BCG and BCG as a Multiple Vaccine
Vehicle
Recently developed genetic engineering techniques
for mycobacteria have provided the means for the
introduction and expression of foreign genes in BCG.53,58
Recombinant BCG vaccine vehicles can induce immune
responses to foreign proteins produced by the bacillus,
indicating that BCG can act simultaneously as an ad
juvant and as a vehicle to produce and deliver specific
antigens to the immune system. A BCG recombinant
may provide a longer lasting immunity to a pathogen
than a simple mixture of BCG and the antigen because
the antigen continues to be produced by BCG multi
plying in the host.
There is no ready answer for the question whether
there is an alternative for BCG vaccine for protection
against tuberculosis. It is possible to improve the
protective efficacy of the existing BCG vaccine agatfist
tuberculosis by using the tools of genetic engineering
even though very little has been achieved in this di
rection to date. Such an approach requires a full
understanding of the factors important in the virulence
of M.tuberculosis, pathogenesis of tuberculosis, and
protective response against tuberculosis. Genetic de
letion or modification of mycobacterial virulence fac
tors or the addition of appropriate mycobacterial an
tigens important for protection might improve the ef
fectiveness of BCG as an antituberculosis vaccine.
CONCLUSION
Fine and Rodrigues7 state that several factors, es
pecially the differences in BCG strains and regional
differences in mycobacterial ecology, in addition to
differences in trial methods, have all contributed to the
observed variation in BCG*s efficacy. They conclude
that despite our inability to predict its precise effect,
BCG is still judged worthwhile in many countries
because there is a possibility that the vaccine might
provide reasonable levels of protection against child
hood forms of the disease in most populations.7 Recent
retrospective studies of BCG vaccine efficacy among
newborns and children have reported a protective
effect against all forms of tuberculosis ranging from 17
to 90 per cent, and protection against tuberculous
meningitis and against cavitary, miliary and bone and
joint tuberculosis has been estimated to be 75 per cent
or great er,59-61 BCG vaccine, when effective, apparently
does not prevent infection but interferes with the
haematogenous spread of tubercle bacilli, thus reducing
the risk of severe primary disease and its compli
cations.60 A meta-analysis of 14 trials and 12 case
control studies showed that the protective effect of BCG
against tuberculosis was 51 and 50 per cent respec
tively.62 Combining data from 7 trials reporting on
deaths from tuberculosis, the relative risk for death
among the vaccinated was 0.29 (71 % protective effect).
Five case-control studies reporting on tuberculous
meningitis showed a 64 per cent protective effect, and
3 case-control studies reporting efficacy of BCG in
preventing disseminated tuberculosis showed a 78 per
cent protective effect. The conclusion was that BCG
reduces the risk fbr active tuberculosis on an average
by 50 per cent, and the risk for tuberculosis death,
meningitis and disseminated tuberculosis. The fact that
37
BCG provides variable though significant protection
against leprosy increases its value in those countries
with high prevalence of leprosy.63 ,
10. Ten Dam, H.G.
Research on BCG vaccination. Adv Tuberc
Res, 21, 79, 1984.
11. Calmette, A. and Guerin, C. Sur quelqucs proprietes du
bacille tubercluleux cultive sur la bile.
It has been concluded that vaccination alone, at
least with the present vaccine, cannot substantially
influence the epidemiological situation but should be
continued for children when its use is justified for
prevention.64 BCG vaccination of the newborn usually
protects against serious forms of tuberculosis, is safe
and cheap and should be used in developing countries,
including India, where tuberculosis is more prevalent.
In such highly endemic areas, due to the frequent
occurrence of exogenous reinfection and also due to the
waning of protective effect over the years after vacci
nation, BCG vaccination of the newborn may not offer
protection in the later years of life when revaccination,
perhaps at the school going age, may have to be
considered. In developed countries with low preva
lence of tuberculosis, BCG should be given to high risk
groups such as immigrants, their newborn, contacts of
patients with tuberculosis and hospital staff.65
CR Acad Sci, 147:
1456, 1908.
12. Guerin, C. In: BCG Vaccination Against Tuberculosis Ed.
S.R. Rosenthal. Little, Brown, Boston, Massachussets. 1957,
p.48.
13. Frappier, A., Portelance, V., St Pierre, J. and Parisset, M.
BCG strains: Characteristics and relative efficacy. In: Status
of Immunisation in Tuberculosis Ed. E.C. Chamberlayne,
Fogarty Int Cent Proc 14. Washington, 1972, p.157.
14. Milstein, J.B. and Gibson, J.J. Qualify*control of BCG vac
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that may influence vaccine effectiveness and safely. WHO/
EPI/GEN/89: 3, 1989.
15. WHO Expert Committee on Biological Standardisation. Re
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16. Collins, F.M. Tuberculosis.
In: Bacterial Vaccines Ed. R.
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BCG trial area during 1981.
Tubercle, 66: 9, 1985.
55. Pcarle, EJ., James. S.L., Hicny. S., Lanar, D.E. and Sher,
A. Induction of protective immunity against Schistosoma
39. Kamala, T., Paramasivan, C.N., Herbert, D., Venkalesan, P.
and Prabhakar, R. Isolation and identification of environ
mental mycobacteria in the Mycobacterium bovis BCG trial
mansoni by vaccination with Schistosoma parainysin (Sm97),
a nonsurfacc parasite antigen. Proc Nall Acad Sci USA, 85:
5678, 1988.
area of south India. Appl Environ Microbiol, 60: 2180, 1994.
56. Desrosiers, R.C., Wynad, M.S., Kodama, T., Ringler, DJ .
40. Narayanan, S., Paramasivan, C.N., Prabhakar, R. and Nara
Arthur, L.O., Schgal, P.K., Letvin, N.L., King. N.W. and
yanan, P.R. Effect of oral exposure of Mycobacterium avium
inlracellulare on the protective immunity induced by BCG.
Daniel MD. Vaccine protection against simian immunodefi
ciency virus infection. Proc Natl Acad Sci USA, 86: 6353,
J Biosci, 10: 453, 1986.
1989.
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57.
Bloom, B.R. Learning from leprosy: A perspective on immu
nology and the third world. J Immunol, 737: 1, 1986.
58.
Jacob, W.R., Tuckman, R. and Bloom. B.R. Introduction of
foreign DNA into* mycobacteria using a shuttle plasmid.
Nature, 327: 532, 1987.
59.
Padungchan, S., Konjanarat, S., Kasiratta, S., Daramas. S.
and ten Dam, H.G. The effectiveness of BCG vaccination
of the newborn against childhood tuberculosis in Bangkok.
Bull WHO, 64: 247, 1986.
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Snider, D.E. Jr.» Rieder, H.L., Combs, D., Bloch, A.B.,
Hayden, C.H. and Smith M.H.D. Tuberculosis in children.
Pediatr Infect Dis J, 7: 271, 1988.
Tidjani, O., Amedome, A. and ten Dam, H.G. The protective
effect of BCG vaccination of the newborn against childhood
tuberculosis in an African community. Tubercle, 67: 269.
1986.
Colditz, G.A., Brewer, T.F., Berkey, C.S., Wilson, M.E.,
Burdick, E., Fineberg, H.V. and Mostcllcr, F. Efficacy of
BCG vaccine in the prevention of tuberculosis: Meta-analysis
of the published literature. J Am Med Assoc, 271: 698, 1994.
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Ponnighaus, J.M., Fine, P.E.M., Sterne,
Wilson, R.J.,
Msosa. E., Gruer, PJ.K., Jenkins, P.A., Lucas. S.B., Liomba,
N.G. and Bliss, L. Efficacy of BCG vaccine against leprosy
and tuberculosis in northern Malawi. Lancet, 339: 636, 1992.
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This write-up has been contributed by Dr. C.N. Paramasivan,
Dy. Director (Sr. Grade), Dr. Daniel Herbert, Research
Officer and Dr. R. Prabhakar, Director, Tuberculosis
Research Centre, Madras.
ABSTRACTS
Some Research Projects Completed Recently
Study of delayed type hypersensitivity in enteric fever
using outer membrane proteins of Salmonella typhi
as the eliciting antigens:
Immune response specific to outer membrane pro
teins (OMPs) of Salmonella typhi was studied in vitro
in 30 bacteriologically proven patients of typhoid in the
acute phase and at follow up after 3 months. Fifteen
normal healthy controls matched for age and sex and
15 bacteriologically proven patients of septicaemia caused
by Gram negative bacteria other than S. typhi were also
studied. Cell mediated immunity (CMI) against S.
typhi was studied by leucocyte migration inhibition test
(LMIT), lymphocyte transformation test (LTT), and
production of interleukin-1 (IL-la) and IL-2, and
leukotriene B4 and C4 (LTB4 and LTC4). Enumeration
of per cent and absolute peripheral lymphocyte sub
populations was performed using fluorescein-isothiocyanate
conjugated mouse monoclonal antibody.
It was observed that S. typhi induced specific CMI
response in typhoid, both in the acute phase and on
follow up. Of the various in vitro parameters of CMI,
LMIT showed significant inhibition response to OMPs
of S.typhi compared to OMPs of S. typhimurium. The
inhibition was more singificant to OMP of S. typhi in
40
the typhoid group than in the septicaemic group.
Lymphoproliferative response was also higher to OMP
of S. typhi in typhoid patients in the acute phase as well
as follow up compared to normal controls. OMPs of
S. typhi induced lower amounts of IL-la and IL-2
during the acute phase of typhoid than on follow up,
though proliferative response to these antigens was
significant. Lipopolysaccharide (LPS) which formed
an integral part of OMPs induced only transient im
mune response in the acute phase of typhoid. In. vitro
IL-la and IL-2 production in response to OMPs and
LPS was impaired.
Transient immuno-suppression in the acute phase
of typhoid was observed by LMIT and LTT using PHA
. as mitogen. On follow up these parameters of CMI
reverted to normal, possibly due to rise in T helper
'cells. Antibodies specific to OMPs of S. typhi were
present in both acute phase and follow up in all typhoid
patients. There were few cross reactions with OMP
of S. typhimurium.
The study thus provided evidence of elicitation of
specific cellular immune response by OMPs of S.typhi
in typhoid. It also indicated that though there may be
cross reactive antigen moieties in OMPs of Salmonella,
OMPs of S. typhi have the ability to elicit specific CMI
in typhoid. These OMPs contained proteins which
were specific for S. typhi. The role of these proteins
in the pathogenicity and protection in typhoid need to
be studied further.
A. Prasad
P.K. Pillai
Department of Microbiology
Lady Hardinge Medical College
New Delhi.
Cervico-vaginal flora in pregnancy and its relation
with perinatal outcome:
The study was carried out to determine the preva
lence of Chlamydia trachomatis, Mycoplasma hominis,
Ureaplasma urealyticum, Gardnerella vaginalis, Neisseria
gonorrhoeae and other aerobic and anerobic organisms
in pregnant women and the effect of these on perinatal
outcome and maternal morbidity. An effort was also
made to evaluate the effect of treatment on perinatal
outcome and maternal morbidity.
Initially 200 apparently healthy pregnant women
attending the antenatal clinic were screened twice fbr
cervical and vaginal flora, once in the second trimester
and once in the late third trimester. Iliese women were
fbllowed up intrapartum and postpartum. Women with
history of recent antibiotic use, obstetrical compli
cations like APH, toxaemia, gestational diabetes, mub
tiple gestation, etc. and those with severe anaemia,
diabetes, chronic hypertension, renal diseases, etc were
excluded . The women (116) who were positive fbr any
pathogenic organism formed the study group while
those (84) with no evidence of pathogenic organisms
served as controls.
In order to evaluate the effect of treatment on
perinatal outcome, 59 women of a group of 92 screened
in the later part of the study were treated. For
Candida the treatment comprised cotrimoxazole pessaries
fbr the women and candid ointment for their husbands;
erythromycin stearate 500 mg 6 hourly for one week
was given to both wife and husband for the other
pathogens.
Initially C. trachomatis, M. hominis, U. urealyticum,
and G. vaginalis were detected in 5.0, 8.5, 28.5 and
15.5 per cent women respectively. The prevalence of
Candida sp and Group B streptococci was found to be
18.0 and 0.5 per cent. Lactobacilli alone were present
in 42.0 per cent, streptofaecalis in 1.5 mobiluncus in
0.5 and Staphylococcus epidermidis in 9 per cent of
women. Anaerobic organisms were detected in 4.5 per
cent, staphylococci, diphtheroids and acinetobacter in
1.0 per cent each and Escherichia coli in 0.5 per cent
of women. Sixty eight (58.62%) women had single
pathogen while 48 (41.38%) had multiple organisms
in various combinations.
The incidence of premature rupture of membrane
(PROM) was slightly higher in the study group (10 out
of 116 : 8.62%) as compared to control (5 out of 84;
5.25%). The incidence of preterm labour was signifi
cantly more in the study group compared to control.
There was no significant difference in the mean birth
weight of neonates in patients compared to controls.
Evidence of vertical transmission of infection ie neo
nates being colonized with the same organism as the
mother, was seen in 18.96 per cent of the cases (22
of the 116). Clinical manifestations of neonatal infec
tion in the form of oral thrush was sigificantly more
(9 out of 116) in the study group compared to control
(2 out of .84), while no significant difference was seen
with conjunctivitis, pneumonia, and septicaemia. Post
partum fever occurred in 7.5 per cent (9 out of 116)
women in the study group and 5.95 per cent in the
control group, but this difference was not significant.
Treatment resulted in the lowering of incidence of
PROM, preterm labour, incidence of low birth weight,
oral thrush in neonates and postpartum fever in moth
ers.
S. Dhillon
S. Malhotra
Department of Obstetrics and Gynaecology
Postgraduate Institute of Medical
Education and Research
Chandigarh.
41
ICMR NEWS
The following meetings of various technical committees/groups of the Council were held:
ICMR-NIC Centre for
Biomedical Information,
New Delhi
Meetings of Scientific Advisory Committees of the
ICMR Institutes/Centres:
Meetings of Scientific Advisory Groups (SAGs)/
Scientific Working Groups (SWGs)ZProject Review
Groups (PRGs)ZProject Advisory Committees (PACs)/
Project Review Committees (PRCs)/Task Forces (TFs)
held at New Delhi
Desert Medicine Research
Centre, Jodhpur
February .20, 1995
(at Jodhpur)
Regional Medical Research
Centre fbr Tribals, Jabalpur
February 20, 1995
(at Jabalpur)
Tuberculosis Research Centre,
Madras
February 22, 1995
(at Madras)
Vector Control Research
Centre, Pondicherry
February 23, 1995
(at Pondicherry)
Centre fbr Research in
Medical Entomology, Madurai
February 24, 1995
(at Madurai)
Rajendra Memorial Research
Institute fbr Medical Sciences,
Patna
SWG of the Division of
Human Resource
Development Research
March 7, 1995
(at New Delhi)
February 21-22, 1995
PRC on Anatomy, Allergy,
Haematology, Human
Genetics, Immunology and
Physiology
February 21, 1995
PRC on Pharmacology
February 22, 1995
PAC of the Task Force
Project on Liver Diseases
February 28, 1995
March 1, 1995
(at Patna)
TF on Integrated
Reproductive Health Care
Package
March 1-2, 1995
Institute of Pathology,
New Delhi
March 6, 1995
(at New Delhi)
SAG of the Division of
,
Non-Communicable Diseases
March 7, 1995
March 8, 1995
(Port Blair)
Institute fbr Research in
Medical Statistics, Delhi
and Madras Chapters
March 8, 1995
(at New Delhi)
TF on Improving Reproductive
Health Care (MCH/FP) by
Decentralisation of Targets and
Minimum Care at Sub-Centre
Level .
March 7, 1995
Regional Medical Research
Centre* Port Blair
March 8-9, 1995
Institute of Im mu noh aem atol o gy,
Bombay
March 9, 1995
(at Bombay)
Project Review Group of the
Division of Human Resource
Development Research
Enterovirus Research Centre,
Bombay
March 11, 1995
(at Bombay)
Meetings of Scientifc Advisory Committees of Centres
for Advanced Research: »
Centre for Advanced Research
in Ocular Infections, New
Delhi
42
February 22, 1995
(at New Delhi)
、
participation of ICMR Scientists in Scientific Even算
Dr. V. Kumaraswami, Asstt. Director, Tuberculosis
Research Centre, Madras, participated in a meeting on
Clinical Protocols for Amocarzine in Onchocerciasis
and Lymphatic Filariasis at Geneva (February 20-21,
1995). He also participated in the meeting of the Task
Force for Filariasis Field Trials of the WHO Special
Programme fbr Research and Training in Tropical Diseases
at Geneva (March 13-16, 1995).
Dr. G.V. Satyavati, Director-General, ICMR,
delivered the IV Prof. Prem Chand Dandiya Endow
ment Trust Oration entitled MWhither Pharmacology
Research in India" at New Delhi (March 7, 1995).
National Science Day Celebrations:
ICMR Headquarters and ICMR Institutes/Centres
located in Delhi celebrated the National Science Day
(NSD) on February 24, 1995. Apart from an exhibition
on various health problems of national relevance
viz. malaria, cancer, mental health, etc. The activities
included display/demonstration of specimens of medi
cinal plants/household herbal remedies and various
common food items of daily use. In addition, a general
science quiz and a computerized quiz on nutrition were
also organised fbr school children.
ICMR AIDED SYMPOSIA/SEMINARSAVORKSHOPS/COURSES/CONFERENCES
Symposium/ScminarAVorkshop/
Course/Conference
Contact Address
Date & Place
I Congress of Federation of Indian Physiological
Societies (FIPS).
March 1-3, 1995;
(at New Delhi)
Dr. W. Selvamurthy, Chairman, Organising
Committee of the Congress, Defence Institute of
Pliysiology and Allied Sciences, Delhi.
National Conference on Adolescent Health-cumWorkshop on AIDS/H1V Infection Prevention amongst
Adolescent and Youth.
March 4-5, 1995;
(at New Delhi)
Dr. Prcma Bali, President, Indain Association for
Adolescent Health, A-5, Greater Kailash-II, New
Delhi.
TV Convention of Indian Society of Agricultural
Biochemists and Symposium on Recent Dcveolpments
in Biochemistry
March 20-21, 1995:
(at Varanasi)
Dr. R S. Diibey, Organising Secretary of the
Convention, Department of Biochemistry, Faculty
of Science, Banaras Hindu University, Varanasi.
XI National Symposium on Developmental Biology.
March 25-27, 1995:
(al Rohtak)
Dr S.K. Gakhar, Organising Secretary of the
Svmposium, Department of Biosciences, Maharishi
Dayanand University, Rohtak
COUNCIL'S TRAINING PROGRAMMES FOR 1995-96
Virology
At the National Institute of Virology, Pune:
•
Endocrinology
At the National Institute of Nutrition, Hyderabad:
Diploma in Medical Virology (June 1995 - May 1996).
•
Reproductive Biology
At the Institute for Research in Reproduction, Bombay:
•
Training Course on Techniques in Human Semenology
(May 15 - June 2, 1995).
Annual Training Course on Endocrinological Tech
niques and their Application (August/September, 1995).
Nutrition
At the National Institute of Nutrition, Hyderabad:
•
Training Course on Techniques in Immunology, Cell
Biology and Molecular Biology (November 2-25,1995).
•
M.Sc. in Applied Nutrition (June 1, 1995 - February
28, 1996).
•
Training Course on Techniques in Neuroendocrine Re
search (February 6-10, 1996).
•
Annual Training Course in Nutrition (December 1,
1995 - February 28, 1996).
43
Training Course on Air Pollution Monitoring and Risk
Assessment (December 13-19, 1995).
Oncology
•
At the Institute of Cytolpgy and Preventive Oncology,
New Delhi:
Medical Entomology
•
Workshop on Molecular Biology ofVi ruses and Cancer
alongwith Oligo DNA Synthesis and Polymerase Chain
Reaction (September 18-22, 1995).
Occupational Health
At the Veaor Control Research Centre,Pondicherry:
•
M.Sc. in Medical Entomology (From August 1995: for
2 years).
Laboratory Animal Technology
At the National Institute of Occupational Health,
Ahmedabad:
At the Laboratory Animal Information. Services Centre,
National Institute of Nutrition, Hyderabad:
•
•
Orientation Course on Occupational Health for Indus
trial Medical Officers (November 13-24, 1995).
Training Course for Laboratory Animal Technicians
(June - July, 1995).
Editorial Board
Chairperson
Members
Dr. G.V. Satyavati
Director-General
Dr. Badri N. Saxena
Dr. C.R. Ramachandran
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-! 10029
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