ICMR BULLETIN VOL.7-No.-2-APRIL-1977

Item

Title
ICMR BULLETIN VOL.7-No.-2-APRIL-1977
extracted text
Vol. 7 No. 4

COMMUNITY HEALTH CELL
326, V Main, I Block
Koramangala
Bangalore-560034
India

RESEARCH IN MALARIA -

Research in malaria has today assumed a
degree of urgency perhaps not equalled at any
time before.
Malariology in all its aspects,
including methods of control,underwent gradual
expansion and change from the days of Sir
Ronald Ross at the beginning of the present
century,
to the advent of DDT in the early
1940s, which led to the most spectacular re­
duction in the incidence of malaria in most
parts of the world. India was in the forefront
both in research in malariology as well as in
the application of the relevant results of re­
search for the control and subsequent eradica­
tion of the disease,
on a nation-wide scale.
The initial successful use of DDT on a limited
scale was followed by its application in the
National Malaria Control Programme (NMCP)
in
• 1953 and later in the National Malaria Eradi­
cation Programme (NMEP)
during 1958,
and a
near eradication of malaria in vast parts of
the country was achieved by 1965.
However,
for reasons now well-known, reversal of the
results started and in 1976 nearly seven
million parasite-positive cases were detected
in the country.
The over-confidence in the
ability of the two major control measures viz.
indoor residual spraying,
and radical treat­
ment of malaria cases detected through active
and passive surveillance operations, generated
such a degree of complacency amongst the
workers that there was near cessation of re­
search in malariology.
However, the disturb­
ing new dimensions which malaria has now
acquired, such as the resistance of vectors to
conventional insecticides and the emergence of
strains of P. falciparum resistant to 4-amino­
quinolines, have considerably added to the
gravity and urgency of the problem.
The

April, 1977
AN OUTLINE

situation calls for the use of the most effec­
tive
scientific and
technological tools.
Recent advances in molecular biology,
immuno­
logy and chemotherapy offer new opportunities
for the development of such tools.

The situation today is that the scien­
tists of the country not only have to make up
for the quiescence of the past two decades or
more but also to forge ahead in research in
this field with newer ideas and innovations.
Malaria cannot be allowed to confront India as
one of its foremost public health problems as
before and to handicap the country‘s over-all
national development in various spheres.
To
combat the disease now and to overcome it
completely in the near future it would be
necessary to mobilize and utilize all the
available talents and resources . to the maxi­
mum.
Research in all aspects, basic and
applied,
is of utmost importance and no time
can be lost in determining the lines of re­
search and embarking on the same.
The Government has made in-depth studies
on the positive causes
for the reversal and
has now taken steps to reorganise the malaria
control activities on the basis of a modified
plan.
The organisational as well as the
technical aspects which needed attention have
been looked into.
A new order of priorities,
commitments
and
administrative
responsi­
bilities
has been defined.
- While these
measures can be expected to halt a further
deterioration of the situation,
it has been
amply clear that the programme is in dire need
of additional and newer data on many aspects

in order that it may be tailored to deal with
the new dimensions of the problem.

resistance,
as it happens to be the beginning
of drug resistance in parasites.

The information required covers a wide
range of subjects,
including those related to
basic knowledge on the malaria parasites,
the
vectors,
the drugs,
control methods, socio­
economic impacts and financial and logistic
constraints.

At least in two States in India the prob­
lem of chloroquine resistant P. falciparum
has already been detected.
The other areas
with
chloroquine resistant
P.
falciparum
strains are still to be identified and demar­
cated .

In view of the obvious financial and man­
power limitations, only the most relevant as­
pects can be studied.
It becomes imperative
that specific problems worthy of being selec­
ted for investigation should be identified for
purposeful action
with the least possible
delay.

1.1.1

Eight Task Forces and the Expert Commi­
ttee on Malaria met from 28th February to 3rd
March, 1977, at the Council and deliberated on
the problems which needed immediate attention.
The deliberations and recommendations of the
Task Forces and the Expert Committee, which
form the basis on which the overall research
policy of the Council has been developed,
are
highlighted in the following pages:
1.

RESEARCH ON OPERATIONAL ASPECTS OF MALARIA
CCNTROL:

Operational
research studies
are of
considerable importance since efforts in this
area may be expected to yield rich dividends
towards the effective control of the disease.

1.1

Mapping
and monitoring
resistant areas:

Considering the results of the in vivo
tests as obtained by the WHO, difficulties are
likely to be encountered for classifying the
strains into R1,
R2 and R3 levels of resis­
tance.
It is agreed that while R2 and R3
types of resistance or susceptibility of the
strain can be established easily, major diffi­
culty may crop up in identifying strains with
R1
degree of resistance.
In case active
transmission of the disease is taking place
subsequent parasitaemia may be due to re­
infection.
Detection of R1 type of resis­
tance is of great practical importance to the
programme because this indicates the beginning
of resistance.
This may be established by an
in vivo test, by interrupting malaria trans­
mission through insecticide application or by
carrying out the studies during the non­
transmission season. In vitro test recommended
by the WHO is also suitable for this purpose.
The latter will furnish quick information and
also has a high degree of reliability.

P. falciparum

Between complete sensitivity and complete
resistance there is gradation in the response
of P. falciparum to chloroquine, ranging from
a loss of effect demonstrable only by occa­
sional recrudescence to a level of resistance
at which the drug apparently has no effect on
severe infection.
In cases where the parasite
is sensitive(S) to the drug there is clearance
of asexual parasitaemia within seven days of
initiation of treatment,
without subsequent
recrudescence.
In Ri low degree of resistance
there is clearance of asexual parasitaemia
followed by recrudescence.
When the drug
resistance is moderate of R2 type,with chloro­
quine administration,
marked reduction in
asexual parasitaemia takes place but no clear­
ance.
In case the degree of resistance is of
high R3 type there is no significant reduction
of asexual parasitaemia after the start of
treatment.
It is useful to detect R1 type of

2

In vivo and in vitro tests for determi­
nation of chloroquine resistance in P.
falciparum:

Considering the fact that it would take
some time before in vitro testing could be
taken up widely,
the in vivo field
tests
recommended by the WHO should be put into
immediate use. The NMEP machinery may be uti­
lised-for collection of blood slides, adminis­
tration of drugs and examination of slides
collected before and after treatment.
1.1.2

Monitoring Teams:

Monitoring teams should be deployed in
three types of areas (i) where drug resistance
in P. falciparum has already been identified
or strongly suspected e.g.
districts on the
southern bank of Brahmaputra in Assam, Megha­
laya, Tripura, Mizoram, Manipur, Nagaland and
Arunachal Pradesh;
(ii) states which are in
the neighbourhood of the above areas e.g. dis­
tricts on the northern bank of Brahmaputra in
Assam and north Bengal and (iii)
other parts
of India (a) where P. falciparum incidence is
high,
(b) where persistent transmission of P.

falciparum is prevalent and
(c) from where
reports about lack of response to chloroquine
are being received.

representative and problem areas of the coun­
try, in different types of epidemiological
situations in order to study contemporary epi­
demiology. Hence, it would be useful to carry

Studies for evaluating the efficacy of
various drug schedules in P. falciparum
cases resistant to chloroquine:

out investigations in one full district in
each selected area where a medium sized town
also exists.
Different types of areas are:

1.2

Studies should be undertaken to find out
the shortest and most effective course of drug
combination that could be used for the cure of
chloroquine resistant P. falciparum cases.
A
great deal of work has already been done in
this country by the Armed Forces, who have
evaluated the various regimen of drugs. Their
results have shown that:

(a) Hyperendemic forested foothill areas
of North East India e.g. Mikir Hills.
(b) Hyperendemic hilly
forested areas
with tribal population e.g. Dandakaranya area.

(i) Quinine plus tetracycline is the best
combination;

(c) Hyperendemic semi-forested sub-hilly
areas e.g.
Thana Palghar - Bulsar
complex.

(ii) The next best is quinine plus
methamine plus sulphadiazine;

(d) Mesoendemic areas of
of West Bengal.

pyri­

Gangetic plain

(iii) The addition of chloroquine to the
above two schedules makes the combi­
nations more potent.

(e) Epidemic irrigated belt areas like
Mathura - Meerut - Kurukshetra - Karnal.

The treatment schedule however,
is very
long i.e.about two weeks.
There is,
there­
fore, need for shorter courses of treatment,
to be employed in the field.
The following
drug combinations have therefore, been sugges­
ted for field trial:

(f) Hypo-meso- endemic areas with tendency
for epidemics in Deccan plateau e.g.
Gulbarga.

(i) Quinine sulphate/hydrochloride
minocycline for seven days;

plus

(ii) Single day course-Pyrimethamine plus
sulphadoxine or sulphalene or dapsone
(all in single dose);
(iii) Quinine hydrochloride/sulphate plus
sulphadoxine or sulphalene plus pyri­
methamine for seven days;
(iv) Quinine hydrochloride/sulphate plus
tetracycline for seven days; and

(v) Quinine hydrochloride/sulphate
doxycycline for seven days.

plus

In the above index areas after obtaining
baseline data on the epidemiological and ento­
mological aspects of malaria,
the studies
which can be initiated are as follows:

(i) Effectiveness of integrated
control measures;

malaria

(ii) Dynamics of P.
transmission;

malaria

falciparum

(iii) Studies to improve the operational
efficiency of the ongoing programme;

(iv) Studies to devise methods of assess­
ment of various components of the
malaria control programme including
malariometric indices to be used by
the programme;

(Seriously ill patients should not be
included in the study).

(v) Value of radical treatment in differ­
ent localities;

Investigations on the epidemiological and
entomological aspects of malaria:

(vi) Studies
on mass chemotherapy
in
selected areas to find out its impact
on transmission;

It is essential to undertake a comprehen­
sive study on all aspects of malaria in some

(vii) Studies to find out alternative app­
roaches to reduce transmission e.g.

1.3

3

•

application of selective antilarval
measures during the pre-transmission
season with usual surveillance or
with mass chemotherapeutic measures
carried out concomitantly;

(viii) Control of malaria by adoption of
larvicidal measures
in the rural
areas throughout the year;
(ix) Malarth control by the application of
space spray (pyrethrum spray) in some
double insecticide resistant vector
areas;

(x) Comparative study of the effective­
ness of DDT suspension and DDT emul­
sion;

(xi) Control of malaria by improving the
water management practices; and
(xii) Identification and the use of larvivorous fish for the control of mosquitoes.

1,4

integrated malaria control programme with
involvement
of the community through
part-time village health workers:

It is
felt that
part-time
village
workers, selected by the community itself
(partly supported)
and trained in primary
health care and basic skills linked to the
infrastructure of the health services at the
grass-roots level
and supervised
through
multipurpose supervisors and health workers,
may be utilised for case detection,
drug
distribution, administration of presumptive
and
radical treatment,
slide collection,
spraying and supervising of spraying and anti­
larval and environmental sanitation measures.
Some states like Maharashtra have ex­
perience of such projects and it is felt that
controlled experiments can be undertaken in
such areas. The size of the experimental area
may vary from a few community development
blocks to a district, depending on the avai­
lability of finances.

1.5

Studies in forecasting
malaria:

of epidemics

1.6

Studies on the use of antilarval opera­
tions in rural areas of arid and semiarid zones of A. culicifacies malaria:

It is known that breeding grounds of A.
cuLicifacies in arid and semi-arid zones are
extremely limited during the summer months
(March through May). Transmission starts when
there is a good build-up of the vector den­
sity.
Hence it is reasonable to expect that
suppression of A. caiicifacies breeding during
summer period may retard eventual build-up and
delay the onset of malaria
transmission.
Antilarval measures may be undertaken in some
pilot project areas from March to May by

•

either using Paris green or organophosphorus
compounds.
This can also be supplemented by
chemotherapy e.g.
single dose treatment with
600 mg chloroquine in predominantly P. faLciparum
areas,
or chloroquine 600 mg
plus
primaquine 45 mg in predominantly P. vivax
areas. Results of such an investigation can
provide useful information for malaria control
in similar areas in other parts of the country.
2.

ECOLOGY AND CONTROL OF VECTORS OF MALARIA:

India is a vast country with several
marked zooecological regions with different
patterns of prevalence and behaviour of the
vectors.
It has long been recognised that the
knowledge of the vectors and their behaviour
in one region would not be applicable to other
regions and the control measures would have to .
be developed with the needs of a particular •

locality in view.
The variations are so many
that the total picture of the vectors is
rather complex and would need investigations
in several types of situations.
However, for
practical reasons it is essential to select a
few representative areas for intense study
supplemented by additional,
limited investi­
gations in other areas.

of

Studies may be carried out to forecast
malaria epidemics in the north western states
of the country.
This can help the organisa­
tion to take precautionary measures for the
prevention of the epidemics.
A Research Cell
may collect and analyse relevant epidemiologi­

4

cal and other data and attempt to forecast
epidemics of malaria.
Considerable informa­
tion is available on the subject from the
state of Punjab in undivided India and the
same can be made use of after modification,
keeping the present situation in view,

2.1

Field studies on the bioncmics
mosquitoes:

of vector

The specific studies to be undertaken in
selected representative areas may include the
composition of the anopheline fauna,
their
distribution, seasonal and relative densities,
determination of the vectors by dissection,

and epidemiological
the fact that there
diary vectors.

studies keeping in view
may be major and subsi-

Information and data may be obtained on:
(i) seasonal prevalence and density;
(ii)
breeding habits and habitats;
(iii) adult
resting places;
(iv) feeding habits and pre­
ferences i.e.
degree of anthropophily, and
time and place of biting
(endophagy or exophagy),
degree of contact with man etc.3
(v)
mating behaviour,
gonotrophic cycles;
(vi)
dispersal;
(vii) longevity and survival under
natural conditions;
(viii) susceptibility to
insecticides;
(ix)
laboratory colonization;
and (x) ecology of male mosquitoes with parti­
cular reference to feeding behaviour.
These studies should be conducted taking
into consideration the socio-economic condi­
tions in the rural or urban mileu,
including
housing,
presence of domestic animals and
agricultural practices which have a bearing on
the problem.
The degree of malaria prevalence
in these areas should be periodically assessed
so that
the entomological studies
yield
meaningful results.

For this purpose,
the following areas
have been considered suitable for initiating
studies:

(i)

Tamil Nadu
(Salem area)

Problem of persistent
malaria,
with
A.
culicifacies, A. ste­
phens i as known vec­
tors and A. subpictus
and A. Varuna as sus­
pected vectors.

(ii) Madhya Pradesh
(Ratlam)

Persistent
trans­
mission area with A.
culicifacies as known
vector.

(iii)West Bengal and
Assam

Persistent
trans­
mission
with
A.
philippinensis,
A.
annularis
and
A.
baldbacensis.

(iv) Maharashtra and
Karnataka
(Gulbarga, Bijapur, Nira Canal
Zone)

(v)

Andamans

Epidemic areas
and
irrigation
malaria
with A. culicifacies,
A. fluviatilis
and
A. stephensi as known
vectors.

Problem
connected
with A. sundaicus and
A. ba labacens is.

Well-equipped and adequately manned field
stations should be established in these areas
on a long-term basis, at least for an initial
period of five years.

2.2

Species complexes and
Anopheles:

sibling species in

DDT spray has brought to light the vari­
able behaviour of vector species indicating
the existence of sibling species.
In eastern
India,
A. philippinensis populations were
known to transmit malaria only in Deltaic
Bengal and not in Assam.
Recently it has been
established that A. philippinensis is a vector
of major importance in Assam and not in
Bengal.
The species is further confused with
A. nivepes known to be present in Assam.
Similarly, A. leucosphyrus complex is repre­
sented by A. batabacensis and A. elegans and
their role in the transmission of malaria over
the range remains to be determined.
A. macu"Latus which is known to be associated in
transmission of malaria in Assam,
exists as a
polymorphic species and requires a compre­
hensive study to establish the precise role of
its members.
Anopheles subpictus, A. tesselatus and A. sundaicus are other species,
which need detailed study.
2.3

Field studies in insecticide
in vector mosquitoes:

resistance

While the entomological staff under the
new set up in the states, will continue to
monitor the status of insecticide resistance
in vector mosquitoes as a part of their
routine activities,
the field studies on
resistance particularly on such sophisticated
aspects as genetic analysis of the mosquito
population, would have to be undertaken.
Such
studies would help in understanding the tota­
lity of the resistance problems and give leads
for development of methods to overcome or
mitigate them.
Suitable technical facilities
should be built into the
regional field
stations.

2.4

Biochemistry and genetics
resistance:

of insecticide

Research on the mechanism of resistance
and the methods of overcoming it needs to be
taken up on a priority basis.
It is recog­
nised that this would involve the development
of expertise of a high order in biochemistry
and genetics.
Obviously such studies cannot
be undertaken in many places but may be con­
centrated in a couple of properly equipped and
well staffed institutions.
It is proposed

5

that Cells for the study of these aspects be
developed which will also be able to cytotoxonomically analyse the genetic basis of resis­
tance.
2.5

Experiments in the use of space sprays:

In the pre-DDT era, very intense studies
had been undertaken on the use of indoor space
sprays with pyrethrum extract. Very promising
results had been obtained
in controlling
malaria transmitted by A.
culieifacies and
studies on other vectors, particularly A.
fUcoiabilis and A. minimuB had been initiated.
With the advent of DDT and its spectacular
success, the use of pyrethrum was abandoned in
public health practice.
However, pyrethrum
space sprays can offer a very practical solu­
tion in many types of malaria situations,
particularly in localities with a short dura­
tion of transmission or in A. cuVteifaeles
transmitted malaria.
It is considered essen­
tial to re-test the utility and applicability
of this method in suitable rural situations.
It is proposed to initiate a few carefully
controlled studies
on the mechanism
and
effectiveness of this method.

2.6

Biological control of mosquitoes:

While principles of source reduction by
simple engineering methods such as filling,
drainage, channelling, use of larvicides etc.
are fairly well known, they are not applicable
in many types of situations, particularly
where the total elimination of stagnant water
is not practicable because of technical, eco­
nomic or social reasons.
In many such situ­
ations, use of biological control methods has
been known to. be useful.
Extensive programme
of biological control has not hitherto been
possible because of inadequate knowledge of
these
agents,
their
potentialities
and
hazards.
The need for research in this field
has now been recognised and it has become a
major activity of the Vector Control. Research
Centre, Pondicherry.
It is proposed
that
these studies should be
intensified with
carefully controlled field studies.
The use
of biological control agents i.e. fish, nema­
todes, fungi, bacteria etc.
should be ex­
plored.
It is, however, recognised that bio­
logical control can be effective only when
used in conjunction with other methods.

source reduction,
chemical and biological
methods, all used in. a coordinated manner has
been often postulated but so far, not well
demonstrated.
As the cumulative effect of
these methods Will be substantial and may
bring about a permanent improvement, it should
be demonstrated in a few localities. The work
can be entrusted
to the
regional field
stations being .set up in index areas or to the
local authorities in a few urban areas.

2.8

While it is appreciated that the synthe­
sis of new insecticides requires extensive
facilities which are not available,
it is
essential that the country should have at
least well equipped laboratories to test not
only indigenous insecticides, but also in­
secticides of promise referred to it by other
institutes or organisations.

2.9

2.10 Bedbugs:
Though bedbugs are not directly related
in anyway with the transmission of malaria,
they have assumed a negative force working
against the success of the malaria control
programme, because of the refusal of house­
holders to have DDT sprayed in their houses
under an impression that the increase in bed­
bugs is due to DDT.
Studies on the ecology
and control of bedbugs should be undertaken to
find methods of overcoming this problem.
CHEMOTHERAPY OF MALARIA.

Integrated control:

The control of insect pests or vectors of
diseases by an integrated control method which
includes improvement
of the
environment,

6

Antilarval measures in rural areas:

Antilarval measures in rural areas have
generally been regarded as economically not
justifiable
though
sometimes
technically
feasible. In the changed context of the country’s economic policies for rural development,
it is essential
to
initiate measures or
methods of control of the vectors in suitable
rural and semi-urban areas.
A few areas
should be selected where methods of larval
control using Paris green, minor engineering
methods and water management (such as inter­
mittent irrigation) can be tested.
This can
be undertaken as a part of the activities of
the special field stations.

3.

2.7

Testing of new insecticides:

Use of antimalarial drugs plays a vital
role in the treatment and control of malaria.
Chemotherapy,
therefore,
is to be considered
in .its various aspects.

3.1

Production of antimalarials:

With the proper and effective use of
known drugs a considerable measure of success
can be achieved in the control of malaria.
Effective steps should be taken to ensure the
availability of the drugs in order of priority
viz.
Chloroquine
(300 tonnes);
Primaquine
(4 tonnes); Quinine (8 tonnes);
Pyrimethamine
(3.5 tonnes);
Sulphadoxine (5 tonnes); and
Tetracycline (5 tonnes).

A trial should also be undertaken with
chloroquine and pyrimethamine in all fever
in­
cases for radical cure, with and without
secticidal coverage.
A trial should be carried out in P. fal­
ciparum resistant areas with one intramuscular
injection of cycloguanil embonate and acedap­
sone.

3.3
The present production of chloroquine is
only 30 tonnes which is very inadequate and
though a number of private pharmaceutical concems have been licenced, it will take a long
time before the required quantity of chloro­
quine is manufactured by them.
It is, there­
fore, necessary that a large quantity of this
drug should be manufactured in the public
sector.
Although the production of quinine in the
country is around 16 tonnes, most of it is
exported and not enough is available foi
distribution within the country.
Hie Govern­
ment must take steps to ensure availability of
at least eight tonnes of quinine to the
National Malaria Eradication Programme and
only the balance may be exported.
Sulphadoxine is useful for the treatment
of chloroquine resistant cases of P. falci­
parum and hence steps should be taken for its
production in the country.

3.2

Studies on
malarials :

the

effectiveness

of

anti­

For the effective treatment of malaria
careful selection of the drugs to be used, is
imperative and the regimen would depend upon
the
epidemiological
and
other
logistic
requirements in different areas.
It is nece­
ssary to carry out field trials using differ­
ent dosage schedules for different areas with
drugs given alone and in combination, parti­
cularly
with primaquine and
fansidar in
different parts of the country.

Efforts made by the Walter Reed Army
Research and Development Agency have led to
the development of some new drugs. Mefloquine,
one of the new drugs, appears particularly
promising.
This drug should be obtained
directly from the source or through some
international agency and a field trial carried
out in the country, particularly to assess its
value as a single dose treatment for cases of
both P. falciparum and P. vivax malaria.

Development of repository forms of drugs:

Long acting drugs would be of great
advantage in a predominantly rural country
like India.
The production of repository
forms of primaquine which is the most effec­
tive weapon for radical cure of malaria in
India, needs to be encouraged. Development of
repository forms of quinine should also be
investigated.

3.4

Development of newer drugs:

In the development of new drugs major
emphasis should be given to (i) drugs which
are both casual prophylactic and curative and
effective against exo-erythrocytic (EE) stage;
and (ii) Gametocytocidal drugs active against
resistant forms, preferably those which act by
mechanism different from those of the known
ones.

3.5

Screening of drugs:

At a few centres in the country complete
models for screening new antimalarial drugs,
including sporozoite induced infection should
be established. This should include models in
(i) rodents against P. berghei;
(ii) chicks
against P. gallinaceum;
(iii) monkeys against
P. "knanlesi and P. cynomolgi; and (iv) against
P. falciparum and P. viuox in owl monkeys.
3.6

Studies on the establishment of
malaria infection in animals:

human

Steps should be taken to import Macacca
fasicularis monkeys from Malaysia and Aotus
trivigatus (owl monkey) from Latin America and
establish their colonies at a few laboratories
in the country.

While attempts should be made to import
Aotus monkeys from Columbia, simultaneous in­
tensive efforts should be made to establish
human infection in some of the monkeys avail­
able in the country, particularly those which
are similar to Aotus monkeys.

7

of anti-

mechanism of development of drug resistance in
the parasite should be studied.

Models for in vitro screening should be
established, which should include continuous
culture of P. falciparum and P. vivax in human
erythrocytes, culture of E.E. stages of P.
gallinaceum in embryonic chick and of P.
berghei in mouse liver cells.

For some of the above studies it would be
necessary to look into the possibility of
developing in vivo and in vitro models

3.7

Models for

in vitro

screening

malarials:

4.

DRUG RESISTANCE IN MALARIA PARASITE:

The problem of drug resistance in malaria
parasite involves mainly the failure on the
part of the parasite to respond to normal
doses of the antimalarial drugs.
This ex­
cludes other aspects such as immunity and
natural
non-susceptibility
of
different
species, strains or phases of malaria parasite
to drugs.
With the finding of P. falciparum
strains resistant to chloroquine,the matter of
drug resistance has acquired significance.
Therefore,
the following studies may be taken
up:
4.1

Monitoring of drug resistance:

It would be necessary to identify and
demarcate areas in which chloroquine resistant
strains of P. falciparum prevail, in order to
assess the extent of drug resistant in our
country.
This would also help in evolving a
programme for continuous monitoring of drug
resistance.

4.2

Problem of drug absorption, distribution
and metabolism in various conditions:

It is necessary to undertake pharmaco­
logical studies on
different antimalarial
drugs in relation to conditions like anaemia,
malnutrition, malabsorption,
liver disease,
hypoproteinaemia etc.
The studies may be
carried out in
volunteers or in malaria
patients.
It should include aspects like drug
distribution
between the
plasma and the
erythrocyte infected with malaria parasite,
bio-physical characteristics of drug distri­
bution and other related fields.

4.3

Biochemistry of malaria parasite:

Indepth studies may be carried out on the
biochemistry of malaria parasite particularly
with a view to assess the extent of differ­
ences, if any, between the sensitive and the
resistant strains of the parasite.
The bio­
chemistry of the parasite as well as the mode
of action of the various antimalarials and the

8

5.

SEROLOGY OF MALARIA:

The purpose of serological tests should
be to identify the infecting species, differ­
entiate between present and past infections
and between primary infections and reinfec­
tions and indicate the immune status of the
host.
A test that fulfils these criteria
should be not only a sensitive diagnostic
method but also a valuable tool for the study
of epidemiology of malaria.
Further,
the
test should be simple enough to be carried out
with minimal equipment under peripheral field
conditions.
5.1

Serological tests for malaria:

Several tests are being tried but none
satisfies all the above criteria.
As such it
may be desirable to concentrate on a few of
them, vix. , passive haemagglutination test,
indirect
immunof luores cent
antibody test,
enzyme-linked immunosorbent assays and counter
immunoelectrophoresis.

Antigens commonly used in the above tests
are primarily erythrocytic schizonts, extracts
of schizonts, or soluble antigens recovered
from sera of heavily infected individuals.

For a serological test to be sensitive
and specific it is essential to have purified
antigens.
With such antigens, tests can be
standardized and reference reagents made avai­
lable. As far as malaria is concerned no such
antigen is available so far.
In order to develop a reliable serological test the following investigations are
necessary:

(i) Purification of specific stages of
the malarial parasite populations and
the determination of the serological
properties of the antigens derived
from them;
(ii) Further development of the four tests
viz., passive haemagglutination test,
indirect immunofluorescent antibody
test,
enzyme-linked
immunosorbent

assay and counter Immunoelectrophore­
sis and
their evaluation, parti­
cularly when specific antigens become
available;

(iii) Active search for new animal hosts of
human malaria parasites and develop­
ment of improved methods of cultiva­
tion to obtain sufficient quantities
of antigens; and

(iv) The prevalence
of
antibodies to
sporozoites in sera from populations
living in highly endemic areas when
adequate supplies of sporozoites of
human malaria become available.

6•

CULTIVATION OF MALARIA PARASITES IN VITRO:

Malaria parasites have three distinct
cycles of multiplication viz.,
the sporogonic
cycle in the mosquito and the exoerythrocytic
and erythrocytic cycles in the vertebrate
host.
Considerable work has been done on the
in vitro cultivation of the different stages
of avian, rodent, simian and human malaria
parasites.
Recently it has been possible to
cultivate the erythrocytic stages of P. falci­
parum in continuous culture.

(ii) Exoerythrocytic cycle:
In most mammalian malarias and parti­
cularly in that due to P. falciparum,
the
exoerythrocytic cycle in the liver is a self
limiting one but the corresponding cycle in
avian malaria is not self limiting. Therefore,
by modifying the in vitro culture conditions
continuous propagation of the exoerythrocytic
stage of P. falciparum in tissue culture may
be possible. This should be investigated.
With several species of avian malaria it
has been shown that the exoerythrocytic cycle
can be carried on indefinitely and that large
numbers
of parasites can be produced in
tissue culture.
If the exoerythrocytic stages
of
avian malaria
were
cross-immunogenic
against human malaria it may lead to a practi­
cal method of vaccine production.
As such it
is necessary to study the species specificity
of the immunity produced by exoerythrocytic
stages.

Attempts should be made to establish in
vitro tissue cultures of mammalian malarial
parasites.
Liver cell cultures should be ex­
posed to a small number of sporozoites.

(iii) Erythrocytic stages:

6.1

Studies on the
parasite:

cultivation

of

malaria

It has been demonstrated that effective
immunity could be produced in experimental
animals by the inoculation of sporozoites,
exoerythrocytic or erythrocytic forms. As such
the in vitro cultivation of all or any one of
these stages of malaria parasite would help in
the ultimate development of a vaccine against
malaria.
(i) Sporogonic cycles:

Attempts at in vitro cultivation of the
sporogonic cycle have not been very successful
so far,
either in vertebrate or invertebrate
tissue cultures.

However, with a view to obtain sporo­
zoites in a sufficient quantity, insect tissue
cultures should be inoculated with gametocytes
for
securing viable
ookinetes in vitro.
Aseptically reared mosquitoes fed on gemetocyte carriers should be used as a source of
ookinetes or early oocysts to be placed in
culture.

Recently it has been possible to grow the
erythrocytic stages of the parasite in vitro^
offering hope for continuous propagation and
ultimately for quantity production.
In view of the species specificity of the
immunity produced by
erythrocytic stages,
attempts should be made to cultivate the
erythrocytic stages of P. falciparum in a sus­
pension of human or Aotus red monkey cells.
Where P. falciparum is not available, P.
coatneyi with a similar 48 hours cycle and
sequestration of schizonts, could serve as a
model.
Attempts should be made to induce
gametocyte formation in cultures of erythro­
cytic forms.

(iv) Cell
fusion
material:

techniques

of

genetic

The possibility of producing
malarial
antigens using cell
fusion techniques or
transfer of genetic material should be kept in
mind.
It is obvious that the in vitro cultiva­
tion of malaria parasites is still an open
field inspite of the large amount of basic

9

work already carried out in this direction.
Any further progress, viz., the preparation of
a pure antigen for serological tests, in vitro
testing of anti-malarials,
production of a
potent vaccine as well as the understanding of
the basic aspects of the disease, will depend
to a large extent on the successful in vitro
cultivation of the parasite.
7.

IMMUNOLOGICAL ASPECTS OF MALARIA:

For the ultimate development of malaria
vaccine, extensive studies need to be under­
taken on immunology of malaria. Similarly for
the formation of effective treatment of the
disease, investigations are necessary on the
pathology in the various organs affected.

7.1

Immunoprophylaxis against malaria:

Recent work has revealed that there is
increased immunoglobulin synthesis in
the
population as a result of malaria infection.
Antibody specific to malaria may comprise only
a third of this immunoglobulin, of which less
than five per cent is functional.
Neverthe­
less, studies with rodents and monkeys have
demonstrated that immune serum exerted protec­
tive activity against malaria infection.
The
presence of enhancing antibody is also indi­
cated in recent studies with immune sera.

T cells, largely as helper cells, seem to
be intimately involved in conferring resis­
tance to malaria infection.
Apart from B and
T cells, macrophages have a critical role in
limiting the infection.
Macrophages,
in
addition to their participation in processing
malaria antigens seem to exert
antibody­
dependent cytotoxicity to parasites.
In the light of these observations there
is an urgent need to study the immune response
to malaria infection and the role of humoral
and cell mediated immunity in malaria.

7.1.1

Studies
malaria:

on

immunization

against

There is considerable information avail­
able on the possibility of inducing immunity
to malaria infection using different parasite
stages and their antigens.
These include
sporozoites, asexual stages in the blood,
sexual stages and non-living parasite anti­
gens .

(i) Sporozoites:

It has been demonstrated

10

that irradiated

sporozoites induce a near complete protection
against malaria with P. berghei infection.
But the results were less dramatic with P.
eynomo1/gi.
Studies with human volunteers and
P. falciparum
indicate that
this method
offers considerable promise.
It is found that while sporozoite immu­
nized animals are fully protected against
challenge with sporozoite stage, they remain
susceptible to the erythrocytic stages of the
same plasmodial strain.
Also,
immunization
with sporozoites of any given rodent malarial
species produced a broad range of protection
against challenge with sporozoites of all
rodent malaria species and subspecies.
In these studies various methods were
used for treating sporozoites for immunization
i. e. ultrasonication, freezing and thawing,
heat inactivation, trituration and irradiation
by X-rays or Y rays.
Only irradiated sporo­
zoites produced protective immunity.

The important investigations which could
be undertaken with sporozoites are:
(a) puri­
fication of
sporozoite preparations;
(b)
characterization of the protective
antigen;
(c) development of methods to enhance and pro­
long the duration of sporozoites induced pro­
tection through the use of adjuvants; and (d)
study of sporozoite induced immunity in a
simian malaria model that resembles P. falci­
parum infection in man.

(ii) Asexual stages:

The effect of immunization with irra­
diated parasitized erythrocytes
and para­
sitized erythrocytes in adjuvants has been
tried and a significant increase in resistance
to challenge has been reported.
Immunization of monkeys with merozoites
of P. knowtesi resulted in very good protec­
tion of the animals against the homologous
strain.
With the recent advances in the in
vitro
cultivation
of the parasite, this
approach appears to be most promising in deve­
loping a vaccine.
The important lines of work which should
be undertaken with merozoites are:(a) the pro­
tective value of irradiated or formulinized,
freeze dried preparations of merozoites in an
acceptable adjuvant;
(b) sporozoite challenge
of merozoite vaccinated animals;
(c)
the
effect of merozoite immunization in esta­
blished chronic malarial infections;
and (d)

the possibility of the occurrence of cross-.
immunization between merozoites of simian and
other plasmodial species and the human para­
site P. falciparum.

(iii) Sexual stages:
Recently successful attempts in immuniza­
tion against the sexual stages of P. gallinaceum using radiation attenuated gametes have
been reported. This line of study may be pur­
sued further.

to be undertaken at selected insti­
tutions using a common protocol;
(ii) Experimental immunological study of
. brain and other viscera in a monkey
model; and

(iii) Immunological studies of the brain
and other viscera in fatal cases of
malaria.
These studies could be
carried out in institutions where
satisfactory
autopsy
»facilities
exist.

(iv) Non-living parasite antigens:
Several non-living parasite antigens have
been tried with varying success. These include
P. berghei parasites passed through Hughes
press in rats,purified antigens of P. knowlesi
in monkeys,
and purified antigens of P. cynomolgi isolated from infected liver of rats
against homologous strains.
These important
studies need to be confirmed and extended.

An analysis of the results of the above
immunization procedures reveals considerable
species, strain and stage specificity in the
protection conferred. Further, the protection
is, in general, not total with any of these
methods.
There is obviously great need for
extensive research in this area which could
eventually lead to the most promising method
of immunization, keeping in view various fac­
tors such as availability of the material,
feasibility of the technique and protean mani­
festations of the parasite.

7.2

Immunopathology of malaria:

Information on the immunopathology of P.
vivax and P. falciparum infection is meagre.
Hence,
it is stressed that studies to be
carried out in this regard should highlight
the role of different types (I to V) of hyper­
sensitive reactions in the causation of renal
and cerebral lesions with special emphasis on
type III hypersensitive reaction.

7.2.1

Immunopatho logical studies:
(i) Cl inico-immunopathological studies of
cases of malaria with renal manifes­
tations.
Collaborative studies are

7.2.2

Immunosuppressive activity of malaria:
(i) Immunosuppressive effect of malaria
on a monkey model
using tetanus
toxoid; and

(ii) A pilot study of immunosuppressive
effect of malaria in a sample popu­
lation.
It
would be seen that the research
studies to be undertaken as a support to the
National Malaria Eradication Programme, are of
considerable practical importance and are as
much result oriented as possible.
Studies on
the operational aspects of malaria control
have been designed with a view to get solu­
tions to the problems encountered in the
actual implementation of the programme.
The
emphasis all through is to find methods of
tackling the disease, under varying conditions
of its epidemiology and spread.
It is envi­
saged to identify and demarcate areas of
chloroquine resistant P. falciparum and to
find out the most effective and at the same
time shortest drug regimen to cure cases of
this strain.
For the formulation of a sound
strategy for control of malaria,its diagnosis,
epidemiology, prevention and treatment, atten­
tion has necessarily to be paid to basic
studies on ecology of vector mosquitoes, sero­
logy of malaria, cultivation of parasite and
development of newer drugs and insecticides.
It is expected that with determined efforts
in research in the field of. malaria, it would
be possible to meet the challenge adequately,
by a multi-disciplinary approach.

ICMR NEWS
A Seminar on * Immunisation against poliomyeli­
tis 1 was held at the Indian Council of Medical
Research,
New Delhi on 28th March, 1977. The

participants included virologists, microbio­
logists, pediatricians, maternal and child
health experts,
epidemiologists,
health

11

administrators and those involved in the pro­
duction and quality control of vaccines.
The
current status regarding epidemiology,
inci­
dence, age distribution, control and preven­
tion
of poliomyelitis were
reviewed and
recommendation made with regard to survei­
llance of poliomyelitis, virological and sero­
logical studies
and immunisation
against
poliomyelitis.

A symposium on
‘Hospital' infections with
special reference to Pseudomonas aeruginosa ‘
was held at the Indian Council of Medical
Research,™ New Delhi on 31st March,
1977.
There were 20 participants from all over the
country.
The various aspects highlighted at
the symposium were the biology and epidemio­
logy of Pseudomonas aeruginosa and the inci­
dence and control of hospital infections due
to Pseudomonas aeruginosa.

Dr. M.S. Bamji was appointed as Deputy Direc­
tor at the National Institute of Nutrition,
Hyderabad, w.e.f. 1st April, 1977.
Dr. F.M. Rodrigues and Dr. S.N. Ghosh, were
appointed as Deputy Directors at the Virus

Research
1977.

Centre,

Poona,

w.e.f.

1st

April,

Dr. C. Gopalan,
Director-General,
Indian
Council of Medical Research, chaired the third
session of the WHO Regional Advisory Committee
on Medical Research held at Colombo,Sri Lanka,
between 4th and 7th April, 1977.

Dr. C. Gopalan, participated in the Inter­
national Symposium on 'The Diet of Man - Needs
and Wants’, organised by the Rank Prize Funds
at Bath, UK, between 17th and 22nd April,
1977.
Dr. R.A. Vaidya,
Senior Research Officer,
Institute for Research in Reproduction,Bombay,
participated in the Ninth World Congress of
Fertility and Sterility held at Miami Beach,
Florida, between 12th and 16th April, 1977
and in the International Symposium on
‘Human
Ovulation' held at Detroit, Michigan, USA from
19th to 21st April, 1977.
Dr. K. Krishnaswamy,
Assistant
Director,
National Institute of Nutrition,
Hyderabad,
proceeded on a one year WHO fellowship to the
G.D.R., to work in the field of
Drug Meta­
bolism in Malnutrition.

ICMR AIDED SYMPOSIA/SEMINARS/WORKSHOPS
A symposium on ‘Carcinoma breast and its
Comprehensive Approach' was held in connection
with the 30th Annual Congress of Radiology at
Chandigarh, between 1st and 4th January, 1977.
A symposium
on 'Atherosclerosis' was
organised during the 3rd Annual Conference of
the Association of Biochemists of India at the
Medical College, Baroda, between 7th and 9th
January, 1977.
A symposium on 'Nutrition and Functional
Performance' was organised by the Nutrition
Society of India, at the National Institute of
Nutrition, Hyderabad on 28th January, 1977.
The Indian Council of Medical Research
National Workshop on ‘Newer perspectives
in
microbiological
investigations of strepto­
coccal infections and their sequelae1, was
held at the Lady Hardinge Medical College,
New Delhi between 21st and 26th February,
1977.

An International Symposium on ‘Venom and
Toxins1 was organised by the Haffkine Insti­
tute, Bombay between 4th and 6th March, 1977.

12

As part of the fifth All India Conference
of Physical Medicine and Rehabilitation,
sym­
posia on various aspects
of Rehabilitation
Medicine
were
organised
at the Medical
Rehabilitation Centre, Patna between 20th and
22nd March, 1977.
A workshop and a symposium on ‘Hospital
infections with special reference to Pseudo­
monas aeruginosar
were organised
by the
Department of Microbiology, All India Insti­
tute of Medical Sciences, New Delhi between
23rd and 31st March, 1977.

A symposium on ’Filariasis′, organised by
the Department of Microbiology,
All India
Institute of Medical Sciences,is being held on
4th June, 1977, at the Indian Council of Medi­
cal Research, New Delhi.
A study group on
'Human tu ours in
tissues with European cell tissue and organ
culture'
is being organised at the Tata
Management Training Centre, Poona, between
16th and 18th August, 1977.

A workshop on •Electron Microscopy for
Medical Postgraduates and Teachers1 is being
organised at the K.G. Medical College,Lucknow,
in September/October, 1977.
A symposium on
•Relationship of patho­
logical states and metabolism of drugs in in­
fants and children1 is being held at the Post­
graduate Institute of Medical Education and

Research, Chandigarh,on 20th and 21st October,
1977.

An International Symposium on ‘Biomolecular structure,
conformation,
function and
evolution* is being organised at the Univer­
sity of Madras, between 4th and 7th January,
1978.

PROGRAMME OF SCIENTIFIC LECTURES AT THE
INDIAN COUNCIL OF MEDICAL RESEARCH, NEW DELHI

Speaker

Topic

Date

1.4.1977

Epidemiology of Streptococcal infections
in north India

Dr. K.B. Sharma,
New Delhi.

15.4.1977

Functional significance of growth retardation
(Basanti Devi Amir Chand Prize Oration, 1977)

Dr. S.G. Srikantia,
Hyderabad.

29.4.1977

Brain catecholamines in hypertension
and cardiac arrhythmia

Dr. K.P. Bhargava,
Lucknow.

COUNCIL’S TRAINING PROGRAMMES FOR 1977
Leprosy:
At the Central Jal ma Institute for
rosy, Agra.

Technicians Training Course in Amoebia­
sis: (October 1 to December 31, 1977).

Lep­

Reproductive Biology:

medical

Training course in Leprosy for
officers: (December, 1977).

At the Institute for
duction, Bombay.

Research in

Repro­

Virology:
At

(1)

Diploma course in Virology of
versity: (July, 1977) .

(2) *Training Course for
period of one year.
(3)

(1)

Course on Immunological Techniques:
ruary, 1977) .

(2)

Course in Hormone Assays:
to April 30, 1977) .

(3)

Course in Endocrinology and
Control: (September, 1977).

(4)

Course on Human Cytogenetics: (September,
1977) .

(5)

Course in Reproductive Biology and Ferti­
lity Control: (November,1977 to February,
1978) .

the Virus Research Centre, Poona.
Poona Uni­

Technicians

Short-term course in
(June 13 to 26, 1977).

Tissue

(Feb­

(March, 1, 1977

for a
Fertility

Culture:

Amoebiasis:

At the School
Calcutta.

of

Tropical

Medicine,

13

Nutrition and Endocrinology:

Biostatistics:

At the National Institute of
Hyderabad.

Nutrition,

(1)

Annual certificate course in Endocrino­
logical Techniques and their Application:
(August, 1977 to September, 1977).

(2)

Annual certificate course in Human Nutrition for Teachers in Agricultural Univer­
sities: (August, 1977 to October, 1977).

(3)

M.Sc.
(Applied Nutrition) course:
1977 to February, 1978).

(4)

Annual certificate course in Nutrition:
(December, 1977 to February, 1978).

(1)

(2)

Nutrition,

Annual Training course in Biostatistics
for Statisticians: (November, 1977).

Laboratory Animal Technology:

Cl)

At the Virus Research Centre, Poona.

Short-term course in Breeding and Mainte­
nance of
Laboratory Mouse
Colonies:
(March, 1977).

(June,

Haematology:

At the
Bombay.

At the National Institute of
Hyderabad.

(2)

At the National Institute of
Hyderabad.

Nutrition,

Laboratory Animal Technicians Training
Course: (August, 1977 to September, 1977)

Blood

Group

Reference

Centre,

A certificate course in Blood Banking
Technology and Basic Haematology
for
medical officers:
(February 1, 1977 to
March 31, 1977).
Training course in Blood Banking Methodo­
logy for Technicians:
(May 2 to May 14,
1977) .

Occupational Health:

Immunological Techniques:
At the Department of Biochemistry, All
Indianinstitute of Medical Sciences, New
Delhi:
(January 24, 1977 to February 5,
1977) .

Clinical Chemistry and Instrumentation:

At the National Institute of Occupational
Health, Ahmedabad.
(1) *ICMR/WHO training
Toxicology.

COURSES FOR TALENT SEARCH SCHEME FELLOVS:

course in

Industrial

(2) *Refresher course in Occupational
for E.S.I. medical staff.

Health

(3) *Training course on Chemical Hazards in
Chemical Industry organised jointly by
the NIOH and the National Safety Council.

At the National Institute of Nutrition,
Hyderabad:
(February 28, 1977 to March
12, 1977).
Use of Radioisotopes in Medicine:

At the National Institute of Nutrition,
Hyderabad: (June 20-30, 1977).
Cell-Biology and Cyto-Genetics:

At
the Indian Institute
Bangalore:
(June 29, 1977
1977).

of
to

Science,
July 12,

Clinical Pharmacology:
At the Department of Pharmacology,
G.S. Medical College, Bombay.

Seth

Training course in Clinical Pharmacology:
(January 15 to February 28, 1977).

14

*Haemato logical Techniques:

At the Department of Haematology,
Post­
graduate Institute of Medical Education
and Research, Chandigarh.

♦Principles and Methods in Medical Statistics:

♦Clinical Pharmacology:

At the Tuberculosis Chemotherapy Centre,
Madras.

At the Department of Pharmacology,
G.S. Medical College, Bombay.

Seth

*Dates to be announced later

ICMR

PUBLICATIONS
TECHNICAL REPORTS
Price
Rs.

Research in Medical Education (1970)

4.00

Research in Health Practices (1970)

4.00

Acute Encephalopathy Syndrome in Children (1970)

4.00

Exfoliative Cytology (1971)

4.00

Symposium on Nutrition and Heart Disease (1971)

4.00

Developments in Industrial Psychology in India (1971)

4.00

Proceedings of Seminar on Immunity and Immunoprophylaxis in Cholera (1971)

4.00

Diagnosis and Treatment of Pesticide Poisoning (1971)

4.00

Symposium on Clinical Evaluation of New Drugs (1972)

4.00

Techniques in Blood Group Serology (1972)

4.00

Laboratory Methods in Investigation of Thyroid Diseases (1972)

4.00

Proceedings of the First Annual Meeting of the Indian Academy of
Cytologists (1972)

4.00

Review of Work Done in Rural Water Supply in India (1972)

4.00

Genetics and our Health (1972)

4.00

All India Conference on Research in Reproduction and Fertility (1973)

4.00

A study of Morbidity Patterns and Standard of Medical Care in the
Rural Centres of West Bengal (1973)

4.00

Proceedings of the First All-India Workshop Conference on Stroke (1973)

4.00

Seminar on Infectious Hepatitis and Study Group on Australia Antigen (1973)

4.00

Atlas of Histopathology of Liver: Hepatitis and Cirrhosis (1974)

10.00

Medicinal Plants of India - Vol. 1 (1976)

30.00

e

SPECIAL REPORTS

Results of Diet Surveys in India 1935-48 (1951)

2.00

Memorandum on the Treatment of Leprosy with Sulphones (1952)

0.37

A Supplement to the Results of Diet in India by K. Mitra (1953)

1.00

Review on Haematology with a note on criteria for averages and
normals (1953)

1.00

15

Price
Rs.
Treatment and Hygienic Disposal of Lac Wastes by T.R. Bhaskaran (1954)

0.62

A review of Work on Indian Medicinal Plants by R.N. Chopra and
I.C. Chopra (1955)

3.00

A review of work Done on Infant Mortality by D.M. Satur and S. Bhatia (1957) 1.00
Proteins in Foods by S. Kuppuswamy, M. Sriniwasan and V. Subramanyan (1958) 12.00

Tuberculosis in India: A Sample Survey, 1955-58 (1959)

2.00

Physiological Norms in Indians: Pulmonary Capacities in Health by
M.N. Rao, A. Sen Gupta, P.N. Saha and A. Sita Devi (1961)

3.00

Treatment and Disposal of Sugar Factory Effluents by T.R. Bhaskaran,
R.N. Chakraborty, N. Das and S.N. Sinha (1961)

1.00

Nutrition for mother and child by P.S. Venkatachalam and L.M. Rebellow
(1962), 2nd Edition 1971

1.50

Manual of Standards of Quality for Drinking Water Supplies (1962),
Second Edition 1975

1.00

Utilization of Liquid Wastes from Molasses Distillery for Recovery of
Potassium Salts by R.N. Chakraborty and T.R. Bhaskaran (1964)

4.50

Occupational Health Research in India: A Second.Review by M.N. Rao and
B.B. Chatterjee (1964)

Gratis

Nardostachys Jatamansi - A Chemical, Pharmacological and Clinical
Appraisal by R.B. Arora (1965)

4.50

Dietary Allowances for Indians by C. Gopal an and B.S. Naras inga Rao
(1968) Reprinted in 1974

4.00

EDITORIAL BOARD
Cha-Limcni
Dr. C. Gopalan
Director-General
Editor
Dr. G.V. Satyavati

Members
Dr. S.V. Apte
Dr. Usha K. Luthra
Dr. V.N. Rao
Dr. A.D. Taskar
Dr. Sabita Tejuja

Printed and Published by Shri Prem Chand for the Indian Council of Medical
Research, New Delhi at the ICMR Offset Press, New Delhi.
R.N. 21813/71
Media
ICMR BULLETIN VOL.7-No.-2-APRIL-1977.pdf

Position: 1894 (15 views)