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BULLETIN
Vol. 24, No. 2
February, 1994
IMMUNITY IN LEPROSY : II. CELL MEDIATED IMMUNITY
A large body of evidence suggests that in
lepromatous leprosy (LL) there is a selective unres
ponsiveness (anergy) of T cell response to Mycobac
terium leprae antigens and therefore, the host is unable
to mount an adequate cell mediated immunity (CM!)
which could protect the host from the infection. In this
form of the disease macrophages, primarily in the
nerves, skin and mucous membranes get heavily
infiltrated with the bacilli.
Cellular interactions in cmi
The phagocytic cells (macrophages, Langerhans
cells, dendritic cells), known to engulf and process the
invading pathogens and their soluble products and also
designated as antigen presenting cells (APCs) are
capable of presentation of the^precessed antigens to the
T cells through their receptors150. It has been well
documented that at the initial stages of CMI response. T
cells duster around the surface of the APCs before
transforming into blast cells. Thereafter. APCs release
interleukin (IL-1) which induces the production of
interleukin-2 (IL-2) by T cells alongwith expression of
IL-2 receptors for multiplication by replication of these
antigen specific lymphocytes for clonal expansion151.
While such a cional expansion goes on, the cellular inter
action further liberates a variety of other interleukins
(IL-1, IL-3. IL-4 to 8) and lymphokines [granulocyte
monocyte colony stimulating factors, interferon-y
(JFN-y). tumour necrosis factor-a (TNF-a)] which
influence the morphological and functional behaviour
of various CMI inducing cells. In general, all these cells
consisting of activated mononuclear phagocytes,
cytotoxic T cells, natural killer (NK) cells and
lymphokine activated killer (LAK) cells create an
environment of cell mediated immune effector
population. Effector molecules like IFN-y and TNF-a
are known to activate macrophages to make them more
armed with enhanced production of toxic reactive
oxygen intermediates (RO1), superoxide anions153 and
also by generation of reactive nitrogen intermediates
(RNI)153 for more effective killing of both intracellular
and extracellular microbial agents. Further. IL-2 and
IL-6 influence T-, NK- and LAK-cells to become
cytolytic by increasing the perforin (pore forming
protein) contents and leukolexin154 in them. These
interleukins are also known to modify the functions of
other cells like endothelial cells, keratinocytes and
Langerhans cells. All these factors collectively influence
the cellular functions in situ and also further recruit
appropriate cells from the circulation and ultimately
lead to an immune granuloma formation fordestruction
of the invaders.
CMI IN LEPROSY
Generalised Defect
Over more than two decades ago, researchers often
reported on a generalised defect for CMI responses in
LL. A majority of LL patients from different geographic
origins and belonging to different ethnic groups ha^e
Division of Publication & Information, ICMR, New Delhi - I 10 029
been shown to exhibit lowered intradermal skin
reactions to a variety of reagents134>*55-165, allergic skin
sensitization to a hapten,5^,5l9,6,_,64>166 and homograft
rejection167. In addition to this,a lowered response to
antigen168-172 or mitogen155^69-181 induced lymphocyte
transformation, number of T lymphocytes in the
peripheral bloodl80-185 and prod uction of
lymphokine157*163 have been noted. However, from a few
of the above studies it was also noted that within a
group, showing generalised depression in CMI, many of
the individuals actually did not exhibit any depression in
CMli6?,L66. Further, in many studiesi57J5&i78>i84 no
depression of CM1 was observed in the entire LL
population although the patients remained
unresponsive to M： leprae antigen.
It was further revealed that those who showed
improvement in generalised CM1 improved
considerably after antileprosy treatment162*177 but still
showed unresponsiveness to lepromin reaction185/186. In
a recent study of skin reactions against new tuberculin
and lepromin in untreated LL patients, all have been
shown to induce a very strong tuberculin reaction
equivalent to those of controls while being negative to
lepromin reaction187. This indicates that the state of
unresponsiveness- in LL patients is so specific to M：
leprae that they are able to respond even to other
mycobacterial antigens. The mechanism responsible for
the generalised depression in CMI, if any, in LL is
largely unknown. Muthukkdnuppan et a/,88»189 using
OKT11 monoclonal antibody, a marker for CD2+ cells
or SR'BC receptor, noted a significant lowering in the
number of T cells in tHe circulation as observed by
earlier workers180*185. However, using a pan- T cell
marker (0KT3) they failed to find a reduction in the T
cell number in the peripheral blood of LL patients. This
observation alongwith a recent observation of the lack
of alteration in the CD4/ CD8 ratio in the peripheral
blood of LL patients190 strengthened the view that
generalised CM I in LL remains almost unimpaired.
However, the reported association of other diseases
alongwith leprosy is very difficult to interpret. High
incidence of tuberculosis191, basal cell carcinoma192 and
lymphoma193 in leprosy patients is very rare and may be
related to some local environmental factors. Generally,
it has been noted that whenever there is a generalised
depression in CM1, an opportunistic infection take an
upper hand which consequently invades the host, as is
being observed in HIV-I and HIV-2 infected
individuals194*196.
Specific Defect
,..
,
1mmunological basik* fbr understanding the disease
led to the establishment of a poiar concept6 in leprosy.
Further, the finer classification of the disease spectrum
has also taken into account the CMI response of the host
(o M. leprae antigen and has been reviewed elsewhereK.
The depression for CMI in leprosy has always been
determined using either whole or soluble antigen of M.
leprae in vivo or in vitro.
In vivo use of M. leprae
M. leprae suspension designated as lepromin197 or
soluble M. leprae antigen193*199 have been used to
determine the CMI status of patients being classified
under the Ridley-Jopling scaled6.
The lepromin reaction is an immunological skin
lest for leprosy first reported by Mitsuda200. This
oreparation termed Mitsuda antigen, now a whole(
bacillary suspension (40 million/ml) in normal saline,
when injected intradermally evokes a weak 24-48 hour
skin reaction and a strong 3-6 week skin reaction in
sensitized individuals. Later Dharmendra201 reported on
a lepromin preparation of defatted bacillary suspension
which has been subsequently standardised202. This
antigen evokes both 24-48 hour and 3-4 week skin
reaction equally well. After the successful purification of
M. leprae from the infected armadillo tissue203 it was
possible to sonicate a large number of bacilli and the
cell-free extract of M. lepraecou\d be standardised by its
protein content (lOjug/ml),9x. This soluble antigen
evokes only 24-48 hour skin reaction.
Although a lepromin test has no diagnostic
potential197, it has a considerable prognostic value6 and
provides confirmatory evidence for classification of the
disease. In most TT/ BT patients the test is strongly
positive while in BL/ LLeases it is negative. The negative
reaction in BL/ LL leprosy patients tends to become
positive after the reversal reaction. On the contrary, the
positive reaction in tuberculoid leprosy tends to become
negative before the occurrence of downgrading reaction.
It has been accepted that 24-48 hour skin reaction is
an expression of pre-existing delayed type of
hypersensitivity (DTH) to protein antigen of M, leprae.
Although two kinds of soluble proteins were isolated
from leprosy nodules by Abe204, these proteins did not
induce Mitsuda reaction. It has been proved beyond
doubt that for generation of the 3-4 week skin reaction,
the presence of whole intact bacilli in the skin antigen is
essential205
Use of M. leprae antigen in vitro
As early as in 1973, Godal and Negassi206 while
studying the lymphoproliferative response to M, leprae
antigen in different categories of people noted that
individuals who were not in contact with the disease
generally remained unresponsive whereas 80 per cent
people who were exposed to leprosy for more than one
year responded to the antigen. This observation pointed
to the sensitization effect of normal individuals who
were subclinically infected due to contact with patients.
Myrvang et al201 studied the lymphoblastic respoflse of
patients in the Ridley-Jopling seal" and noted a
gradual fall in the lymphoproliferative response in TT
through LL. Further, various in v/voand in v//ro studies
carried out earlier confirmed that iepromatous patients
exhibit a long lasting anergy to M. leprae antigens,
which has been extensively reviewed elsewhere-08^209.
，
Doubt has been expressed as to whether the
lymphoproliferative response to specific antigen is an in
vivo correlate of CM I or a measure of hypersensitivity
and not a measure of resistance at alP,^2H
Experimental prooP,2 is available in mice where
challenge with different doses of M. lepraemurium ima
susceptible strain resulted in infection (at a certain dose.)
alongwith a strong skin DTH reaction against the same
pathogen. Moreover, human lymphocyte responses to
antigen has been found to be variable on several
occasions due to the presence of suppressive factors in
the plasma of mothers with leprosy213 and DDS in DDS
treated patients214. Subsequently, it was also indicated
that variability in the lymphoproliferation and leucocyte
migration inhibition could be due to the heterogeneous
nature of the antigens used in these assays21^21^216
It has been recently noted that a significant number
of rcactional BT patients (type I reaction) shoved
lowered M.
尸qpantigen induced lymphoproliferative
response, suppressor cell generation and lymphokine
production217. On the other hand, the lymphocyte
responses showed much improvement in type 1 reaction
of BB and BL patients216. Similarly, LL patients wjth
ENL (type II reaction) generally showed heightened T
cell reactivity to M. leprae antigen18^218.
The status of T cell subsets and in situ profile of
ACCESSORY CELLS AND CYTOKINES
In Peripheral Blood
Bach ei a/'朴 and Wallach et t?/219 noted, while
studying the pattern of distribution of T cell subsets, a
reduction in percentages of helpe(/inducer OKT4+ or
CD44-) and suppressor/cytotoxic (OKT8+ or CD84-)
ceils in bacilliferous leprosy patients. On the other hand.
the bacillary negative LL patients showed CD4+ and
CD84- cell numbers equivalent to those of controls. An
increase in CD4+/CD8+ ratio was also noted in ENL
patients which returned to normal after subsidence of
reaction. In 1982, Mshana et ar/190 while observing no
change in the percentage of pan T (OKT3+ or CD3+)
cells in TT. untreated LLand ENL patientsand controls
reported a reduced percentage of OKT4+ cells and
increased percentage of OKT84- cells resulting in a
red need OKT4+, OKT8+ ratio only in untreated LL
patients. Further, they also established that during ENL
reactions, the helper/suppressor ratio gets heightened
due to the increase of helperand corresponding decrease
in suppressor cell percentage. .However, at the*same
lime. Van Voorhis ei al22^ reported an unaltered
helper/suppressor cell population in all the disease
types.
These studies gave an account of the percent
population of the T cell subsets rather than their
absolute values in the blood. While enumerating the
absolute values of these subsets in a mixture of treated
and untreated lepromatous patients. Bullock et al2^
noted a reduction in the total number ofT cells and their
helper and suppressor subsets. However, like the
previous workers they also failed to record any change in
the helper/suppressor ratio. Rea222 using the same
ya rd sticks observed a significant cytopenia of pan T.
helper and suppressor cells in leprosy patients compared
to normal individuals. However, when the results were
expressed as percentage of total lymphocytes the
differences in the groups were abolished. Even when the
values of these parameters of ENL patients were
compared with their control values no signifeant
differences were observed.
Hence, from the afore-mentioned studies it
becomes clear that the observed reduction in CDR cells
with an increase in CD8+cells simply indicates a state of
immunosuppression. On the other hand, enumeration
of absolute numbers of these cells demonstrated a pa» Tcefl cytopenia but failed to find any abnormalities in
CD4+/Cl)8+ ratios. Considering that lepromatous
patients are not prone to get other infections which are
known to inflict immunosuppressed individuals196^223-227,
it is more rational to assume that in lepromatous leprosy
there is no real alteration in the CD44- CD8+ ratios in
the pe iphcral blood.
25
In lesions
盘
In situ distribution of the T cell subsets with resnect
to their praportiens and pattern of distribution in the
tissues, the granuloma has been widely studied22^28^31
Van Voorhis e-t aP20 noted large number of T cells in
leprosy lesions and the helper/suppressor ratio was
found to be 5.6:1 in tuberculoid granuloma whereas |n
the Icpromatous granuloma they rioted this ratio to be as
1:1.8. In addition, they observed clusters of 0KT4+ cells
distributed in the form of rings in tuberculoid
granuloma. OKT64- cells, on the other hand, were
scattered (in both tuberculoid and lepromatous
granuloma. In contrast to this, Narayanan et aP32 and
Modlin et
could not account for such a large
number of T cells in the granuloma and the
helper/suppressor ratio ranged mostly from 1
tuberculoid and 0.2 to I in ,*\pronratous lesions232.
Moreover, Narayanan a 刃顼 unlike Van Voorhis et
al220 found th^t m tuberculoid granulomas (concentric
variety) 0KT8+ cells were scattered in a "ring like"
fastlion amongst lymphocytes. Conversely, OKT4+ cells
showed a scattered distribution either singly or in
clusters within the lymphocyte cuff as well as in
association with epithelioid cell aggregates. Similarly,
Modlin et at230 found lymphocytes expressing CD8+
cells predominantly in the mantle, while CD4+ cells
were seen in large numbers within the epithelioid cell
aggregates. This type of histological distribution• of. T
cell subsets has also been noted in tuberculoid
granuloma of sarcoidosis230, tuberculosis230 and DTIJ
skin reactions233*236. In addition, all. these studies
unequivocally.-showed all lymphocytes and
macrophages of leprosy granulomas to be la positive.
Recently Narayanan and colleagues257^59 isolated
the granuloma infiltrated cells in vitro a nd studied their
characteristics and functions24*1. The OKT4+/OKT8+
ratios were found to be similar to those in in situ
situations. Functionally, the immune cells obtained
from tuberculoid granulomas exhibited a high
incorporation of
thymidine and ,4C leucine. In
contrast, cells from the lepromatous granulomas
showed poor division without any impairment in their
protein synthesis. A similar study241 was carried out to
compare the characteristics of infiltrates in skin and
nerve granulomas of tuberculoid and lepromatous
types. With the use of phenotypic markers, CD4+ and
CD8+ cells of nerves showed similar distribution and
proportions as observed with those of skin granulomas.
Moreover, in tuberculoid granulomas' a higher
26
proportion of lymphocytes of both skin and nerves were
activated T cells as compared to those in lepromatous
granulomas. In both the types, granulomas were
populated with mature macrophages which expressed
HL A-DR (la) antigens. With regard to the
helper/suppressor ratio in lesions of both type I and type
reactional cases it was noted that the ratio was more
than 2 in the lesions232. Further, in type I reaction in BT
leprosy, there was fall in the mean value of
helper/suppressor when compared to that of untreated
leprosy.
While working with T cell receptor (TCR) in the
granulomas across the leprosy spectrum, reversal
reaction and lepromin reaction, Modlin et a" noted
25・" per cent of CD3+ cells in the granulomas of
lepromin reaction and reversal reactions while in other
types of leprosy these cells were ~5 per cent in the
lesions. When sections of lesions were immunostained
for TCRy6 positivity, a 5 to 8-fold increase in the
concentration of these cells was noted in granulomatous
lesions, as compared to normal skin, lymphoid tissues
and peripheral blood. Further, these TCRy5+ T cells
isolated from skin were shown to be specifically
responsive to mycobacterial antigens. Finally, the
finding of" the supernatant of these activated cells to
contain colony stimulating factor indicated that the yd
bearing T cells may play a role in immune response by
formation of a granuloma. Further, while expanding the
T cells with M. tuberculosis (H37Ra) stimulus it was
noted that expansion of y6+ T cells was greater (32±4%)
in TT patients than in LL .patients (9±2%p43.
Accessory cells (Langerhans cells, keratinocytes)
other than macrophages are known to play a pivotal rol6
in the presentation of antigens to T cells and also have
been shown to be associated with allergic contact
sensitivity and hypersensitivity reactions24*547. Using
phenotypic markers for T6 and la like antigens,
Langerhans cells have been identified in leprosy lesions.
While adequate numbers of these cells were noted in
polar tuberculoid leprosy, the cells were virtually absent
in polar lepromatous leprosy. However, la like antigens
were also found to be associated with macrophages in
these lesions248. Recent observations249*250' have
documented that during type I and type II reactions
there is also a significant increase in Langerhans cells, la
was seen in all keratinocytes in type 1 reaction whereas in
ENL patients a patchy distribution of la positive ,
keratinocytes was observed. AH these events are
indicative of a temonrary T cell reactivity in the lesions
during manifestation of reactional phase. Further.
Cooper el al25] using mRN A probes for IFN-v in in situ
hybridisation in reversal reactional biopsy specimens
have elegantly shown that there was a 10-fold rise in
IFN-y containing cells as compared to lepromatous
patients who are not in reaction. When a probe for
human serine esterase gene (huHF), a marker for
cytotoxic T cells, was used, it was noted that expression
of huHF serine esterase was four times more in the
reversal reaction and tuberculoid lesions than those
present in lepromatous lesions. Their study further
confirmed a selective increase of CD4+ and CD8+ cells
indicating a rise in DTH response which helps in killing
bacilli and results in tissue damage. On rhe other hand,
reduction in the expression of 1 FN-y ana serine esterase
in an atmosphere of CD4+ rise and transient fall in
CD8+ cells suggested a partial or transient boost in the
CM 1 which may be sufficient for antibody production
without any effect on bacillary clearance.
Very recently252, the functional parameters for
cytokine production for the locally proliferated immune
cells have been worked out extensively in TT and LL
groups. It was noted that while mRNAs encoding for
IL-2 and IFN-y were most evident in the TT
granulomas, in LL granulomas mRNAs for IL-4. IL-5
and IL-10 were observed predominantly. Although
definite cytokine profiles have been found to be
associated with resistant and susceptible types of
leprosy, no definite conclusion could be made towards
the role of these lymphokines in the etiopathology of
such lesions in leprosy.
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195. Kovacs, J.A. and Masur, H. Pneumocystis carinii pneumonia:
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211. Bamctson, R.StC., Bjune, G.» Pearson, J.M.H. and Kronvall,
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inGltrates of leprosy. CeDular characteristics and the predomi
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223. Whelan, W.L., Kirsch, D.R., Kwon-Chung,K.J., Wahl, S.M.
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213. Bjunc, G., Duncan, E.» Bamctson, R.StC. and Melsom, R.
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Tb be contd.
ABSTRACTS
Some Research Projects Completed Recently
^ssay of antibiotics in the body fluids of patients
undergoing antibiotic therapy.
The study was uridertaken to - determine the
broavailability of antibiotics in relevant body fluids in
order to correlate in vitro susceptibility of the organisms
and in vivo concentration of antibiotics with clinical
30
response. Efforts were made to monitor the presence of
ligh concentration of the antibiotics which may have
toxic effects and to formulate modified dosage schedule
in such patients as also to prevent certain antibiotics
from reaching toxic levels especially in patients with
impaired renal function.
In a group of 114 hospitalized patients of chronic
lung diseases studied for serum levels of cephalexin, 26
(22.81%) showed normal levels (13-18 “g/ml), 48
(42.11%) less than normal levels and 40 (35.08%) above
normal levels of cephalexin. Seventy (61.40%) patients
showed good clinical response, 11 (9.65%) moderate and
33 (28.95%) poor clinical response after cephalexin
therapy. Of the 40 patients showing above normal levels
of cephalexin, 11 (27.5%) showed very high levels (more
than 35 “g/ml). Schedule of therapy was modified in
these patients to avert toxic effect.
were investigated. Efforts were also made to
demonstrate the development of hypersensitivity and
correlate the development of mycotic disease with pre
existing/ pre-disposing disease or environment. The
patients studied had haematological malignancies (51),
bronchogenic carcinoma (9), pulmonary tuberculosis
(110),.pneumonia (85), lung abscess with pneumothorax
(32). 'chronic bronchitis with bronchiectasis (26),
bronchial asthma (32), allergic bronchopulmonary
aspergillosis (98), aspergilloma (6) and other conditions
such as chronic obstructive airways disease,
seconadaries in the lung, pulmonary eosinophillia etc.
(220).
'
*
Forty isolates of Klebsiella pneumoniae and 40 of
beta haemolytic streptococci were isolated from' 80
patients of chronic lung disease whereas the cultures
were negative in 32 patients. All isolates of K.
pneumoniae were sensitive to gentamicin, kanamycin
and penicillin whereas 4 showed resistance to
cephalexin. On the other hand all isolates of beta
haemolytic streptococci were sensitive to cephalexin.
ampicillin, gentamicin, and kanamycin but 11 were
resistant to chloramphenicol.
Of the 51 patients with haematological
malignancies, 19 showed significant growth of Candida
albicans^ one for C. tropicalis and 3 for Aspergillus
Jlavus. Serology confirmed presence of Candida in 13
and Aspergillus in all 3 patients. In the case of
bronchogenic carcinoma, 2 patients showed significant
growth of C. tropicalis and one C. albicans. Serology
was positive in two patients.
Patients of typhoid on chloramphenicol (10)
amoxycillin (10) and a combination (10) showed good
clinical response in those on combination therapy. They
had above normal serum levels of drugs. Patients with
normal serum levels of drugs showed moderate clinical
response. The Study showed that the combination of
drugs have a synergistic effect and patients showed
better clinical response than the individual drug
regimens.
Of the 110 patients of pulmonary tuberculosis, 53
showed significant growth of C. albicans, 5 of C.
tropicalis, I each for €. krusei, C. guilliermondii, A.
flavus and A. fumigatus. Serology performed in 26
patients showed higher titres of Candida agglutinin in 12
patients, 11 of whom showed significant C. albicans
isolation. Precipitin against Aspergillus was observed in
5 patients, with significant detection of A. fumigatus by
smear and culture in one patient only.
In hospitalized patients with varying degrees of
renal failure (30) and normal renal function (4), serum
concentrations of gentamicin were below toxic levels
«IO “g/ml) in 28 (82.5%) whereas it reached toxic
levels (>10 jug/ml) in 6(17.5%). The results suggest that
.regular antibiotic assays are essential to monitor the
presence of high concentration of antibiotics which may
have toxic effects in patients with impaired renal
function.
Significant growth of C. albicans (11 patients), C.
tropicalis (7), C. parapsilosis (!) and A. flavus (1) was
found amongst 85 patients of pneumonia. Serology
done in 25 patients confirmed Candida in 14 and A.
flavus in one patient.
S. Subramanian
Department of Microbiology
Dr. A.L.M. Postgraduate
Institute of Basic Medical
Sciences, Madras.
Of the 58 patients with lung abscess and chronic
bronchitis, growth of C. albicans was observed in 22, C.
tropicalis, C. glabrata and Trichosporon cutaneum in
one each and A. flavus in 2 patients. Serology performed
in 14 patients confirmed.Candida in 4 and Aspergillus in
2 patients.
Pathogenic fungal isolations from respiratory tract bf
patients with chronic lung diseases and malignancies.
Amongst 220 patients with iniscellaneous disorders
significant growth of Candida was seen in 102, A. flavus
and A.fumigatus in 2 each and Cryptococcus neoformis
in one. Serology done in 60 patients confirmed Candida
in 22 patients and A. fumigatus and Cryptococcus
npoformis in 八ne e«ch.
A totql of 66*9 patients with chronic lung diseased
a nd ma tenancies with suspected fungal Jung infections
Of the 32 patients of bronchial asthma, sputum
satnple of 7 patients showed significant growth of C.
31
ilbiCans only, whereas of the 98 patients of allergic
brbnchopulmonctpy aspergillosis signiHcant growth of
C. albicans was observed in 15 patients from sputum and
in 3 from throat swab. Culture of sputum grew A.
funiigaius in 9, A. flavus in 5, A. niger in one and all
these fungi in 2 patients. Amongst 6 patients of
Aspergilloma, confluent growth of A. fumigatus was
seen in 3 and Aspergillus sp. (unidentified) in 3 patients.
Serology, skin test as also total and specific IgE
against Aspergillus were studied in 19 patients of
bronchial asthma, 23 patients of allergic
bronchopulmonary aspcjgillosis (ABPA) and 6 patients
of aspergilloma* All the 19 bronchial asthma patients
were negative on culture and immunodiffusion (ID) test.
Type I hypersensitivity was observed in 7 patients who
also had raised total serum IgE. Six of the 7 patients
showed specific IgE by both RIA and ELISA. Of the 23
patients of ABPA, type I hypersensitivity was observed
jn 18 and type III in 3. Raised total IgE was observed in
17 of 18 patients, whereas specific IgE was observed by
RIA in 6, ELISA in9and AB-ELISA in 7of 12patients.
In case of patients of aspergilloma, type I
hypersensitivity and raised total IgE was observed in 3
patients.
Significant fungal isolation was found in 38 percent
patients with testing of single sample as compared to
61.5 percent with 2-4samplesand 77.3 percent with 5 or
more samples. Thus 5 or more samples on consecutive
days helped in detecting more respiratory fungal
infections.
P. Talwar
Department of Medical Microbiology
Postgraduate Institute of
Medical Education and Research
Chandigarh.
ICMR NEWS
The following meetings of various Scienntic
Advisory Groups (SAGs)/Task Forces (TFs)/Expert
Groups (EGs)/ Project Review Committees (PRCs) and
Review Panels of the Council were held:
TF on Epidemiology and
Management of Glaucoma
January 19, 1994
(at New Delhi)
PRC on ICRC Leprosy
Vaccine Trials
January 19, 1994
(at New.-Delhi)
EG on Assisted Repro
ductive Technologies
January 24, 1994
(at Bombay)
Meeting of the Toxicology
Review Panel of the
Division of Human
Resource Development
Research
January 28, 1994
(at New Delhi)
Inter-departmental meeting
of TF on Product Develop
ment for Indigenization of
Copper 1' 200B Materials
January 28, 1994
(at New Delhi)
SAG of the Division of
Epidemiology and
Communicable Diseases
February 3, 1994
(at New Delhi)
SAG of the Division of
Basic Medical Sciences
February 8, 1994
(at New Delhi)
32
PRC on Human Genetics,
Immunology, Allergy and
Physiology
February 9, 1994
(at New Delhi)
Participation of ICMR Scientists in Scientific Events:
Dr. Arti Roy, Asstt. Director, Malaria Research
Centre, Delhi, participated in the meeting on Clinical
Disease and Pathogenesis of Malaria jointly organized
by the Rockfeller Foundation and Special Programme
for Research and Training in Tropical Disease of the
WHO at Colombo (January 16-19, 1994).
Dr. D.K. Shukla, Asstt. Director-General, ICMR,
New Delhi, participated in the Regional Scientific
meeting of the International Epidemiological
Association at Chiangmai, Thailand (January 23-28,
1994).
Dr. R. Prabhakar, Director, Tuberculosis
Research Centre, Madras, participated in the 12th
Annual Scientific meeting of the International
Epidemiology Network at Chiangmai (January 23-29,
1994).
Dr. Veena Shatrugna, Asstt. Director, National
Institute of Nutrition, Hyderabad, participated in the
International Women's Health Conference (Cairo ^94)
at Rio de Janeiro (January 24-28, 1994).
Honours/Awards:
.
Dr. Sekhar Chakrabofti, Deputy Director,
National Institute of Cholera and Enteric Diseases,
Calcutta, who is the recipient of Prof. S.R. Maitra
Memorial Oration Award of the Physiological Society
of India (1993) delivered the Oration on the "Quest for
Prevention of AIDS: Drug and Vaccine Approaches**
dOring the fifth Annual Conference of the Physiological
Society of India held at Izatnagar on November 26,
1QQ3
Conference/Workshop:
An International Conference on Dengue
Haemorhagic Fever and also a National Brain Storming
Session on Dengue was organised by the National
Institute of Virology, Pune on February 7-8, 1994.
ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS/COURSES/CONFERENCES
Symposium/Seminar/ Workshop/
Course/ Conference
Date & Place
Contact Address
National Symposium on Reproductive Health
Care.
February 4-6, 1994;
(at Jaipur)
Dr. N.K. Lohiya, Organising Secretary of the Sym
posium, Department of Zoology, University of Rajas
than, Jaipur.
VI Biennial Conference of the Indian Society of
Oncology.
February 4-7, 1994;
(at Calcutta)
Dr. Jayasree Roy Chowdhury, Organising Secretary
of the Conference, Chittaranjan National Cancer
Institute, Calcutta.
National Thalassemia Conference.
February 5-6, 1994;
(at New Delhi)
Dr. V.P. Chaudhary, Additional Professor, Depart
ment of Haematology, All India Institute of Medical
Sciences, New Delhi.
Brain Storming Session on Dengue and Inter
nationa! Seminar on Qengue. Haemorrhagic
Fever and Shock Syndrome.
February 7-8, 1994;
(at Pune)
Dr. Kalyan Baneijee； Director, National Institute
of Virology, Pune.
Workshop on Palliative Care in Oncology.
February 8-9, 1994;
(at New Delhi)
Dr. G.K. Rath, Organising Secretary ofihe Workshop,
Institute Rotacy Cancer Hospital, All India Institute
of Medical Sciences, New Delhi.
National Symposium on Recent Advances in
the Management of Viral Diseases.
February 8*10, 1944;
(at Hisar)
Dr. R.N Srivastava, Organising Secretary of the
Symposium, Department of Veterinary Microbiology,
CCS Haryana Agricultural University, Hisar.
International Symposium
Human Development.
February 8-10, 1994;
(at Hyderabad)
Dr. R. Rudrama Devi, Organising Secretary of the
Symposium, Genetic Toxicology Division, Depart
ment of Zoology, Osmania University, Hyderabad.
1 National Conference of Alzheimer's and
related Disorders Society of India (ARDSI)
on Trends in the Management of Dementia.
February 9, 1994;
(at Madras)
Sri Ravi Samuel, Organising Secretary of the Con
ference, Department of Psychiatry, Govt. General
Hospital, Madras.
National Convention on Reqent Advances on
Environmental Management for Vector-borne
Diseases Control.
February 10-12, 1994;
(at Dehradun)
Dr. R.K. Jauhari, Organising Secretary of the Con
vention, Department of Zoology, D.A.V. (Postgradu
ate) College, Dehradun.
National Symposium on Pigment Metabolism
in relation to Disorders of Skin and Hair.
February 12-13, 1994;
(at Calcutta)
Prof. D.P. Chakraborty, Convenor of the Symposium,
Indian Science Congress Association, 14, Dr. Biresh
Guha Street, Calcutta.
1 National Symposium on Trauma, Anaesthesia
and Critical Care.
February 18-19, 1994;
(at Delhi)
Dr. R. Chawla, Organising Secretary of the Sym
posium, Department of Anaesthesia and Critical
Care, University College of Medical Sciences,
Delhi.
on
Genes and
33
Date & Place
Contact Address
February 18-20. 1994;
Dr. J J. Nadkarni. Convenor of the meeting. Indian
Women Scientists Association, Plot No. 20.Sector
Symposium/Seminar/ Workshop/
Course/Conference
VI All India Meeting for Women in Science.
(at New Bombay)
I0A. Vashi. New Bombay.
'National Symposium of Chronobiology and
IX Biennial Meeting of Indian Society for
Chronobiology.
February 21-23. 1994;
(at Lucknow)
XI National Congress of Parasitology.
February 22-24. 1994;
(at Udaipur)
Dr. Vinod Kumar. Convenor of the Symposium,
Depart me nt of Zoology. University of Lucknow,
Lucknow.
Dr. P.N. Sharma. Organising Secretary of the Congress.
Department of Zoology. College of Science, Mohan
Lal Sukhadia University. Udaipur.
National Symposium on Alzheimer's Dementia.
February 25. 1994;
(at New Delhi)
Dr. S.K. Khandelwal. Additional Professor. Depart
ment of Psychiatry. All India Institute of Medical
Sciences. New Delhi.
1 Conference of Vidarbha Chapter of the
Anatomical Society of India and Symposiumcum-Workshop on Cytogenetics.
February 28. 1994;
(at Sevagram)
The Head. Department of Anatomy, Mahatma
Gandhi Institute of Medical Sciences. Sevagram.
Ward ha.
International Conference on Safe Motherhood
in South Asia : Challenges Ahead.
March 3-5, 1994;
(at Chandigarh)
Dr. R.S. Goyal. Conference Director. SID Inter
national Conference on Safe Motherhood. SCO-809810. Chandigarh.
Indo-Gcrman Training Course and Workshop
on Application of Flow-Cytometry in Cellular
and Molecular Biology.
March 14-16. 1994;
(at Delhi)
Dr. V.P. Bhardwaj. Course Coordinator. Institute of
Nuclear Medicine and Allied Sciences. Delhi.
National Symposium on Cellular and Mole
cular Biophysics.
March 15-17, 1994;
(at Chandigarh)
Dr. M.P. Bansal. Organising Secretar)\ Biophysics
Symposium, Department of Biophysics. Punjab
University. Chandigarh.
COUNCIL'S TRAINING PROGRAMMES FOR 1994-95
Leprosy
Endocrinology
At the Central Jalnia Institute for Leprosy, Agra:
& the National Institute of Nutrition, Hyderabad:
...
...
Orientation Course in Leprosy for Medical
Officers (January 31-February 11, !994).
Virology
Annual Training Course on Endocrinological
Techniques and their Applications (August,/
September 1994).
At the National Institute of Virology, Pune:
...
Diploma in
Mayl995).
Medical
Virology (June
1994-
Reproductive Biology
Nutrition
/U the National institute of Nutrition, Hyderabad:
...
M.Sc in Applied Nutrition (June I J994-Februarv
28, 1995).
...
Annual T raining Course in Nutrition (December 1.
1994-February 28, 1995).
At the Institutefor Research in Reproduction, Bombay:
....
Workshop on Gynaecologic Cytology and Immu
nocytochemistry (September 26-October I, 1994).
Occupational Health
...
At the National Institute of Occupational Health,
Ahmedabad:
...
Orientation Course on Occupational Health for.
Industrial Medical Officers (September 19-24,
1994).
Short-term Course on Malaria, Filariasis and
Urban Vector Control for in-service candidates
(June 1994).
Laboratory Animal Technology
At the Laboratory Animal Information Service Centre,
National Institute of Nutrition, Hyderabad:
...
Training Course on Air Pollution Monitoring and
Risk Assessment (October 19-25, 1994).
...
Training Course for Laboratory Animal Techni
cians (June 15-JuIy 31, 1994).
...
Training Course in Pesticide Residue Analysis
(December 5-9. 1994).
...
Training Course for Laboratory Animal Super
visors (September 12- December 10, 1994).
Medical Entomology
Clinical Pharmacology
At the I ector Control Research Centre, Pondicherry:
At the Seth G.S. Medical College, Bombay:
...
M.Sc in Medical Entomology (from August 1994:
,for 2 years).
Training Course in Clinical Pharmacology (March
1-25, 19)4).
SOME AVAILABLE ICMR PUBLICATIONS
Price
Rs.
Nutritive Value of Indian Foods (1985), by C. Gopalan,
B. V. Ramasastri and S.C. Balasubramaniam, Revised and Updated (1989),
by B.S. Narasinga Rao. K.C. Pant and Y.G. Deosthale
18.00
Growth & Physical Development of Indian Infants and Children (1972), Reprinted 1989
10.00
Studies on Weaning & Supplementary Foods (1974), Reprinted 1984
6.00
Studies on Pre-School Children (1974), Reprinted 1984
6.00
A Manual of Nutrition, Second Edition (1974), Reprinted 1990
4.50
Low Cost Nutritious Supplements, Second Edition (1975), Reprinted 1990
3.00
Menus for Low Cost Balanced Diets and School Lunch Programmes Suitable for South India
Third Edition (1977), Reprinted 1991
4.50
Menus for Low Cost Balanced Diets and School Lunch Programmes Suitable for North India
Third Edition (1977). Reprinted 1984
2.00
Some Common Indian Recipes and their Nutritive Value, Fourth Edition (1977),
Reprinted 1991. by Swaran Pasricha and L.M. Rebello
10.00
Nutrition for Mother and Child, Third Edition (!978), Reprinted 1991,
by P.S. Venkatachalam and L.M. Rebello
9.00
Japanese Encephalitis in India,Revised Edition (1980)
5.00
Some Therapeutic Diets. Fourth Edition (1981), Reprinted 1983, Revised 1988,
by Swaran Pasricha
4.50
Nutrient Requirements and Recommended Dietary Allowances for Indians (1990)
13.00
I athyrisni: A Preventable Paralysis. Revised Edition (1983)
3.50
A Manual of laboratory Techniques (1983), Edited ty N. Raghuramulu, K. Madhavan Nair
J nd S. Kahanasundaram
30.00
35
Fruits (1983), by Indira Gopalan and M. Mohan Ram
7.00
Count What You Eat (1989), by Swaran Pasricha
9.00
Dietary Tips for Elderly (1992), by Swaran Pasricha and B.V.S Thimmayamma
3.50
♦Depressive Disease (1986), by A. Venkoba Rao
58.00
,•The Anophelines of India,Revised Edition (1984), by T. Ramachandra Rao
150.00
**Medicinal Plants of India, Vol.2 (1987)
136.00
• !0 per cent discount allowed to individuals.
•• 25 per cent discount allowed to individuals.
These publications are available on prepayment of cost by cheque or postal order (bank and postal charges will be extra) drawn in favour of the DirectorGeneral. 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.4508. Ansari Nagar. New Delhi-110029.
Statement about ownership and other particulars of the ICMR Research Information Bulletin as required under
Rule 8 of the Registration of Newspapers (Central) Rules 1956.
Place of Publication
:
Indian Council of Medical Research
Ansari Nagar, New Delhi-110029.
Periodicity of Publication
:
Monthly
Printer's Name
:
Shri J.N. Mathur
Nationality
:
Indian
Press Man裾er
Indian Council of Medical Research
Ansari Nagar, New Delhi-110029.
Address
Publishers Name
Nationality
Address
:
Same as above
Editor's Name
:
Dr. N. Medappa
Nationality
:
Indian
Address
:
Indian Council of Medical Research
Ansari Nagar, New Delhi-110029
.
I, J.N. Mathur, hereby declare that the particulars given above are true to the best of my knowledge and belief.
SdA J.N. Mathur
Publisher
Editorial Board
Chairman
Members
Printed and Published by Shri J.N. Mathur for the Indian Council of Medical Researcfi^7^ "
New Delhi at the ICMR Offset Press, New Delhi
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