contents - LRS Institute of Tuberculosis & Respiratory Diseases

GENERAL ARTICLES
CONTENTS
PAGES
SIGNIFICANCE OF PATIENTS WITH X-RAY EVIDENCE OF ACTIVE TUBERCULOSIS NOT BACTERIO-
LOGICALLY CONFIRMED
BY S.S. NAIR … … … … … … … … … 3
PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR PANCHAYAT
UNION, CHINGLEPUT DISTRICT, SOUTH INDIA
BY A.S. BAGGA, M.S. KRISHNA MURTHY, AND K.R. RANGASWAMY … … … 6
THE ROLE OF ZIEHL—NEELSEN AND FLUORESCENT STAINS IN TISSUE SECTIONS IN THE
DIAGNOSIS OF TUBERCULOSIS
BY HEMALATHA KRISHNASWAMY AND C.K. JOB … … … … … … 18
TUBERCULOSIS IN ANIMALS IN INDIA: A REVIEW
BY H.V.S. CHAUHAN, D.P. DWIVEDI, S.S. CHAUHAN AND D.S. KAIRA … … … 22
TOXIC EPIDERMAL NECROLYSIS DUE TO THIACETAZONE
BY F. HANDA, KAMLESH KUMAR AND RADHA RANI … … … … … 36
THE 22nd INTERNATIONAL TUBERCULOSIS CONFERENCE
BY S.P. PAMRA … … … … … … … … … 39
THE THIRD PACIFIC CONGRESS ON DISEASES OF THE CHEST
BY H.B. DINGLEY … … … … … … … … … 46
TAI GOLD MEDAL 59
BACTERIOLOGICAL STUDY OF TUBERCULOSIS LYMPHADENITIS
By K.G. KULKARNI … … … … … … … … … 60
RELAPSE IN PULMONARY TUBERCULOSIS AFTER MEDICAL TREATMENT
BY S.P. PAMRA, GOVIND PRASAD AND G.P. MATHUR ... … … … … 85
INTERPRETATION OF PHOTOFLUROGRAMS OF ACTIVE PULMONARY TB PATIENTS FOUND IN
EPIDEMIOLOGICAL SURVEY AND THEIR FIVE YEAR FATE
BY G.D. GOTHI, A.K. CHAKRABORTY & G.C. BANERJEE … … … … 90
TUBERCULOSIS AND DIABETES
BY D.C. LAHIRI AND P.K. SEN … … … … … … … 98
A STUDY TO EVALUATE THE CONTRIBUTION OF AN ADDITIONAL THIRD DRUG AS AN INITIAL
SUPPLEMENT IN THE TREATMENT OF PULMONARY TUBERCULOSIS
By S.P. PAMRA, B.B. SURPA AND G.P. MATHUR … … … … … 104
SOCIAL AND PSYCHOLOGICAL ASPECT OF TUBERCULOSIS CONTROL PROGRAMME
BY TAHIR MIRZA … … … … … … … … … 109
SUMMARIES OF PAPERS PRESENTED AT MADRAS CONFERENCE ... ... ... ... … 112
PROBLEM OF THE SPUTUM NEGATIVE PATIENTS
By N.L. BORDIA … … … … … … … … … 125
HISTOPLASMIN SENSITIVITY IN SOUTH INDIA
BY A.S. BAGGA, M.S. KRISHNA MURTHY AND B.N. APPE GOWDA … … … … 129
ABSCESS DUE TO MYCOBACTERIUM FORTUITUM
BY C.C. MUKHOPADHYA, L.R. DAS GUPTA, S.L. NARASIMHAN AND
V.N. BALKRISHNA SHARMA … … … … … … … … 133
A CLINICO-PATHOLOGICAL STUDY OF PLEURO-PULMONARY AMOEBIASIS AND ITS MANAGEMENT
BY N.L. PATNEY, R.K. TANDON AND V.K-SRIVASTAVA … … … … … 137
BCG VACCINATION INDURATION SIZE AS AN INDICATOR OF INFECTION WITH MYCOBACTERIUM
TUBERCULOSIS
BY G.D. GOTHI, S.S. NAIR, KUL BHUSHAN, G.V.J. BAILY AND RUPERT SAMUEL ... ... 145
A CONCURRENT COMPARISON OF AN UNSUPERVISED SELF-ADMINISTERED DAILY REGIMEN AND
A FULLY SUPERVISED TWICE WEEKLY-REGIMEN OF CHEMOTHERAPY IN A RUOTINE OUT
PATIENT TREATMENT PROGRAMME
BY G.V.J. BAILY, G.E. RUPERT SAMUEL AND D.R. NAGPUAL … … … ... 152
COST OF ESTABLISHING AND OPERATING A TUBERCULOSIS BACTERIOLOGICAL LABORATORY
By N. NAGANATHAN, K. PADMANABHA RAO AND R. RAJALAKSHMI ... … … 181
A RETROSPECTIVE ANALYSIS OF YIELD OF CASES BY Two METHODS OF SPUTUM COLLECTION
IN SUSPECTS OF PULMONARY TUBERCULOSIS AMONGST SYMPTOMATICS ATTENDING A TB
CENTRE
BY D.C. PANDE, K.D. GAUTAM, M.L. MEHROTRA AND J.P. MISRA … … 191
MANAGEMENT OF SPONTANEOUS BRONCHO PLEURA FISTULA IN CHILDREN—STUDY OF 30 CASES
BY R.K. TANDON … … … … … … … … … 196
ELECTROPHORETIC PATTERN OF SERUM PROTEINS IN CHILDHOOD TUBERCULOSIS
BY M. NAGRAJ RAO … … … … … … … … … 199

ii
THE INDIAN JOURNAL OF TUBERCULOSIS
HYPOGENESIS OF RIGHT LUNG ASSOCIATED WITH PULMONARY TUBERCULOSIS AND
CORPULMONALE
BY J.N. RAZDAN, K.C. MATHUR AND K.L. TANWAR ... ... ... ... ... 206
Loss OF TUBERCULIN SENSITIVITY IN TUBERCULOUS PERITONITIS
BY U. Shankar RAU ... ... ..... ... ... ... … … … 209
LETTER TO THE EDIOR ... ... ... ... ... ... ... ... ... 212
TUBERCULAR OSTEOMYELITIS OF SKIN BONES
BY D. RAJA REDDY, SUGUNA RAMMOHAN, A. KRISHNACHRIAND K. SATYANARAYANA 213
EDITORIAL
DOMICILIARY TREATMENT-A RE-APPRAISAL
THE MADRAS CONFERENCE ... ... ...
...
...
...
...
...
...
...
...
...
...
...
...
1
57
SPUTUM NEGATIVE PULMONARY TUBERCULOSIS ... ... ... ... ... ... 123
TUBERCULIN SENSITIVITY ... ... ... ... ... ... ... ... 179
NEWS AND NOTES
SEAL SALE COLLECTIONS ... ... ... ... ... ... ... ... ... 51
NINTH MEETING OF THE EASTERN REGION ... ... ... ... ... ... 51
REFRESHER COURSE ... ... ... ... ... ... ... ... ... 51
BOOKLET FOR GENERAL PRACTITIONERS ... ... ... ... ... ... ... 51
RESEARCH ... ... ... ... ... ... ... ... ... ... 51
CHEST & HEART ASSOCIATION FELLOWSHIP :.. ... ... ... ... ... ... 51
CHANCHAL SINGH MEMORIAL PRIZE ... ... ... ... ... ... ... 52
ESSAY COMPETITION—1974 ... .... ... ... ... ... ... ... 52
ANTI-TB SHIBIR ... ... ... ... ... ... ... ... ... ... 52
INTERNATIONAL CONFERENCE IN MEXICO ... ... ... ... ... ... ... 52
OBITUARY ... ... ... ... ... ... ... ... ... ... ... 52
ANNUAL MEETINGS ... ... ... ... ... ... ... ... ... 120
KUSHI RAM SHIELD ... ... ... ... ... ... ... ... ... 120
SEAL SALE AWARDS .,. ... ... ... ... ... ... ... ... 120
TWENTY-FIFTH Tb SEAL ... ... ... ... ... ... ... ... ... 120
HEALTH VISITOR’S COURSE ... ... ... ... ... ... ... ... 120
SEMINAR IN INDORE ... ... ... ... ... ... ... ... ... 120
ANTI-TB SHIBIRS ... ... ... ... ... ... ... ... ... ... 120
CHANCHAL SINGH MEMORIAL AWARD ... ... ... ... ... ... ... 121
EASTERN COMPETITION—1974 ... ... ... ... ... ... ... ... 121
EASTERN REGION CONEERENCE ... ... ... ... ... ... ... ... 121
BOGUS REGISTRATION BOARD ... ... ... ... ... ... ... ... 121
DR. R. VISWANATHAN ... ... ... ... ... ... ... ... ... 121
DR. B.C. ROY NATIONAL AWARD ... ... ... ... ... ... ... ... 121
OBITUARY ... ... ... ... ... ... ... ... ... ... ... 121
HEALTH VISITORS COURSE ... ... ... ... ... ... ... ... ... 17o
TWENTY-FIFTH T.B. SEAL ... ... ... ... ... ... ... ... ... 170
EASTERN REGION CONFERENCE ... ... ... ... ... ... ... ... 170
HAND BOOK ON TUBERCULOSIS ... ... ... ... ... ... ... ... 170
HARLEY WILLIAMS Is NO MORE ... ... ... ... ... ... ... ... 170
AWARDS BY THE ACADEMY OF MEDICAL RESEARCH ... ... ... ... ... ... 170
25th T.B. SEAL SALE CAMPAIGN ... ... ... ... ... ... ... ... 216
EASTERN REGION CONFERENCE ... ... ... ... ... ... ... ... 216
REFERESHER COURSE IN TUBERCULOSIS ... ... ... ... ... ... ... 216
SEMINAR AND SHIBIRS ... ... ... ... ... ... ... ... ... 216
HAND BOOK ON TUBERCULOSIS ... ... ... ... ... ... ... ... 216

INDEX
Abscess due to mycobacterium fortuitum 133
Amoebiasis, A clinico-pathological study of pleuropulmonary,
and its management 137
Annual meetings 120
Anti-TB Shibir 52, 120
Awards by academy of medical sciences 170
Bacteriological study of tuberculosis lymphadenitis 60
Bagga, A.S., et. al, Prevalence of tuberculosis disease
and infection in Kadambat__hur panchayat union,
Chingleput District, South India 6
Bagga, A.S., Histoplasmin sensitivity in South
India 129
Baily, G.V.J., et. al, BCG Vaccination induration size
as an indicator of infection with mycobacterium
tuberculosis 145
Baily, G.V.J. et.al., A concurrent comparison of an
unsupervised self-administered daily regimen and
a fully supervised twice-weekly regimen of chemotherapy
in a routine out-patient treatment programme
152
Balakrishna Sarma, V.N., et. al., Abscess due to
mycobacterium fortuitum 133
Banerjee, G.C., et. al., Interpretation of photofluorograms
of active pulmonary TB patients found in
epidemiological survey and their 5 year fate 90
Bogus Registration- Board 121
Booklet for General Practitioners 51
Bordia, N.L., Problem of the Sputum Negative
Patients 125
Broncho Pleura, management of spontaneous, fistula
in children — study of 30 cases 196
BCG Vaccination induration size as an indicator of
infection with mycobacterium tuberculosis 145
Chakraborty, A.K., et. al., Interpretation of photoflurograms
of active pulmonary TB patients found
in epidemiological survey and their five year
fate 90
Chanchal Singh Memorial Prize 52, 121
Chauhan, H.V.S., et. al., Tuberculosis in animals in
India 22
Chauhan, S.S., et.al., Tuberculosis in animals in
India 22
Chest and Heart Association Fellowship 51
Clinico-pathological, A, study of pleuro-pulmonary
amoebiasis and its management 137
Concurrent, A comparison of an unsupervised selfadministered
daily regimen and a fully supervised
twice weekly-regimen of chemotherapy in a routine
out-patient treatment programme 152
Cost of establishing and operating a Tuberculosis
Bacteriological Laboratory 181
Das Gupta, L.R., et. al., Abscess due to mycobacterium
fortuitum 133
Diabetes, Tuberculosis and 98
Dingley, H.B., The third pacific congress on diseases
of the Chest 46
Domiciliary treatment — A re-appraisal 1
Dwivedi, D.P., et al., Tuberculosis in animals in India —
A review 22
Eastern Region Conference 121, 170, 216
Electrophoretic pattern of serum proteins in childhood
tuberculosis 199
Epidermal, Toxic, necrolysis due to thiacetazone 36
Essay competition 1971 121
Fortuitum, Abscess due to Mycobacterium 133
Fluorescent, The role of Zichi-neelsen and, stains
in tissue sections in the diagnosis of tuberculosis 18
Gautam, K.D., et. al., A retrospective analysis of yield
of cases by two methods of sputum collectioa in
suspects of pulmonary tuberculosis amongst
symptomatics attending a TB Centre 191
Gothi, G.D., et. al., Interpretation of photoflurograms
of active pulmonary TB patients found in epidemiological
survey and their five year fate 90
Gothi, G.D., et. al., BCG Vaccination induration size
as an indicator of infection with mycobacterium
tuberculosis 145
Gowda, B.N. Appe, et. al., Histoplasmin sensitivity in
South India 129
Hand Book on TB 170, 216
Handa, F., et. al., Toxic epidermal necrolysis due
to thiacetazone 36
Harley Williams is no more 170
Health Visitors Course 120, 170
Histoplasmin sensitivity in South India 129
Hypogenesis of right lung associated with pulmonary
tuberculosis and corpulmonale 206
Infection, BCG vaccination induration size as an indicator
of, with mycobacterium tuberculosis 145
International, the 22nd, TB Conference 39
International Conference in Mexico 52
Interpretation of photoflurograms of active pulmonary
TB patients found in epidemiological survey
and their five year fate 90
Indian Council of Medical Research 216
Job, C.K., et. al., The role of Ziehl-neelsen and fluores
cent stains in tissue sections in the diagnosis of
tuberculosis 18
Kaira, D.S., et. al., Tuberculosis in animals in India —
a review. 22
Krishna Chari, A., et. al., Tubercular osteomyelitis of
skull bones 213
Krishna Murthy, M.S., et. al., Prevalence of Tuberculosis
diseases and infection in Kadambathur
Panchayat Union, Chingleput District, South
India. 6
Krishnaswami Hemalatha, et. al., The Role of
Ziehl-neelsen and fluorescent stains in tissue sections
in the diagnosis of tuberculosis 18
Krishna Murthy, M.S., et. al., Histoplasmin sensitivity
in South India 129
Kulkarni, K.G., Bacteriological study of Tuberculosis
Lymphadenitis 60
Kumar, Kamlesh, et. al., Toxic epidermal necrolysis
due to thiacetazone 36
Kul Bhushan, et. al., BCG Vaccination induration size
as an indicator of infection with mycobacterium
Tuberculosis 145
Kushi Ram Shield 120
Lahiri, D.E., et. al., Tuberculosis and diabetes 98
Letter to the Editor 212

IV
THE INDIAN JOURNAL OF TUBERCULOSIS
Loss of Tuberculin sensitivity in Tuberculous
peritonitis 209
Madras Conference, Summaries of papers presented
at,
Madras Conference
112
57
Management of spontaneous Broncho-pleural fistula
in children-study of 30 cases 196
Mathur, G.P., et. al., Relapse in pulmonary tubercu
losis after medical treatment 85
Mathur, G.P. et. al., A study to evaluate the contri
bution of an additional third drug as an initial
supplement in the treatment of pulmonary
tuberculosis 104
Mathur, K.C., et. al., Hypogenesis of right lung
associated with pulmonary tuberculosis and
corpulmonale 206
Mehrotra, M.L., et. al., A retrospective analysis of
yield of cases by two methods of sputum collection
in suspects of pulmonary tuberculosis amongst
symptomatics attending a TB Centre 191
Mirza, Tahir, Social and psychological aspects of
tuberculosis control programme 109
Misra, J.P. et.al., A retrospective analysis of yield
of cases by two methods of sputum collection in
suspects of pulmonary tuberculosis amongst
symptomatics attending a TB Centre 191
Mukhopadhya, C.C. et.al. ; Abscess due Mycobacterium
Fortuitum 133
Mycobacterium, Abscess due to, fortuitum 133
Mycobacterium, BCG Vaccination induration size as
an indicator of infection with, Tuberculosis 145
Naganathan, N., et. al., Cost of establishing and operating
a tuberculosis bacteriological laboratory 181
Nagaraj Rao, M., Electrophoretic pattern of serum
proteins in childhood tuberculosis 199
Nagpaul, D.R., et. al., A concurrent comparison of
an unsupervised self-administered daily regimen
and a fully supervised twice weekly-regimen of
chemotherapy in a routine out-patient treatment
programme 152
Nair, S.S., Significance of patients with X-ray evidence
of active tuberculosis not bacteriologically
confirmed 3
Nair S.S., et.al., B.C.G. Vaccination induration size
as an indicator of infection with Mycobacterium,
tuberculosis 145
Narasimhan, S.L. et. al., Abscess due to Myco
bacterium fortuitum 133
Necrolysis, Toxic epidermal due to thiacetazone 36
Ninth Meeting of the Eastern Region 51
Obiturary 170
Osteomyelitis, Tubercular of skull bones 213
Padmanabha Rao, K., et. al., Cost of establishing and
operating a Tuberculosis Bacteriological labora
tory 181
Pamra, S.P., The 22nd International Tuberculosis
Conference 39
Pamra, S.P., et. al., Relapse in pulmonary tuberculosis
after medical treatment 85
Pamra, S.P., et. al., A study to evaluate the contribution of
an additional third drug as an initial supplement in
the treatment of pulmonary tuberculosis 104
Pande, D.C., et. al., A retrospective analysis of yield of
cases by two methods of sputum collection in
suspects of pulmonary tuberculosis amongst
symptomatics attending a TB Centre 191
Patney, N.L., et. al., A clinico-pathological study of
pleuro-pulmonary amoebiasis and its manage
ment 137
Peritonitis, Loss of Tuberculin sensitivity in Tuberlous
209
Photoflurograms, interpretation of, of active pulmonary
TB patients found in epidemiological survey and
their five year fate 90
Prasad, Govind, et. al., Relapse in pulmonary tuberculo
sis after medical treatment 58
Prevalence of tuberculosis disease and infection in
Kadambathur Panchayat Union, Chingleput
District, South India 6
Problem of the sputum negative patients 125
Radha Rani, et. al., Toxic Epidermal necrolysis due to
thiacetazone 36
Rajalakshmi, R., et. al., Cost of establishing and
operating a Tuberculosis bacteriological labora
tory 181
Raja Reddy, D., et. al., Tubercular osteomyelitis of
skull bones 213
Rangaswamy, K.R., et. al., Prevalence of Tuberculosis
disease and infection in Kadamabathur Panchayat
Union, Chingleput District, South India. 6
Razdan, J.N., et. al., Hypogenesis of right lung
associated with pulmonary tuberculosis and
corpulmonale 206
Refresher Course in Tuberculosis 216
Relapse in pulmonary tuberculosis after medical
treatment 85
Retrospective, A, analysis of yield of cases by two
methods of sputum collection in suspects of
pulmonary tuberculosis amongst symptomatics
attending a TB Centre 191
Role of Ziehl-Neelsen and fluorescent stains in tissue
sections in the diagnosis of tuberculosis 18
Roy, Dr. B.C., National Award 126
Samuel, Rupert, et. al., BCG Vaccination induration
size as an indicator of infection with mycobacterium
tuberculosis 145
Samuel, Rupert, et. al., A concurrent comparison
of an unsupervised self-administered daily regimen
and a fully supervised twice weekly-regimen of
chemotherapy in a routine out-patient treatment
programme 152
Satyanarayana, K., et. al., Tubercular osteomyelitis of
skull bones 213
Seal Sale Collections 51
Seal Sale Awards 120
Seminar in Indore 120
Seminar and Shibirs 216
Sen, P.K. et.al. Tuberculosis and Diabetes 98
Serum proteins, Electrophoretic pattern of, in
childhood Tuberculosis 199
Shankar Rau, U., Loss of Tuberculin sensitivity in
Tuberculous peritonitis 209
Significance of patients with X-ray evidence of active
tuberculosis not bacteriologically confirmed 3

INDEX TO CONTENTS VOL. XXI
v
Social and psychological aspects of tuberculosis
control programme 109
Sputum negative pulmonary TB 123
Sputum, problem of the, negative patients 125
Sputum, A retrospestive analysis of yield of cases by
two mathods of, collection in suspects of pulmonary
Tuberculosis amongst symptomatics attending a
TB Centre 191
Srivastava, V.K., et. al., A Clinico-pathological study of
pleuropulmonaryamoebiasisand its management 137
State Conferences 51
Study, A, o evaluate the contribution of an additional
third drug as an initial supplement in the treatment
of pulmonary tuberculosis 104
Summaries of papers presented at Madras Conferences 112
Surpa, B.B., et. al., A study to evaluate the contribution
of an additional third drug as an initial supplement
in the treatment of pulmonary tuberculosis 104
TAI Gold Medal 59
Tandon, R K. et.al., A clinico-pathological study
of Pleuro-pulmonary amoebiasis and its
management 137
Tandon, R.K., Management of spontaneous broncho
pleura fistula in children — study of 30 cases 196
Tanwar, K.L., et. al., Hy pogenesis of right lung associated
with pulmonary tuberculosis and corpulmonale 206
The Role of Ziehl-Neelsen and fluorescent stains in
tissue sections in the diagnosis of Tuberculosis 18
The 22nd International TB Conference 39
The third pacific congress on Diseases of the Chest 46
Toxic Epidermal Necrolysis due to Thiacetazone 36
Tubercular Osteomyelitis of skull bones 213
Tuberculosis
Significance of patients with X-Ray evidence of
active, not bacteriologically confirmed 3
Prevalence of, diseases and infection in Kadambathur
Panchayat Union, Chingleput District,
South India. 6
The role of Ziehl-Neelsen and fluorescent stains
in tissue sections in the diagnosis of, 18
, in animals in India — A Review 22
The 22nd International, Conference 39
Bacteriological study of, lymphadenitis 60
Relapse in pulmonary, after medical treatment 85
, and diabetes 98
A study to evaluate the contribution of an additional
third drug as an initial supplement in the treatment
of pulmonary, 104
Social and psychological aspects of, control
programme 109
BCG vaccination induration size as an indicator of
infection with mycobacterium, 145
Cost of establishing and operating a, bacteriological
Laboratory 181
A restrospective analysis of yield of cases by two
methods of sputum collection in suspects of
pulmonary, amongst symptomatics attending a TB
Centre 191
Electrophoretic pattern of serum proteins in
childhood, 199
Hypogenesis of right lung associated with pulmonary,
and corpulmonale 206
Loss of, sensitivity in, peritonitis 209
Sputum negative pulmonary, 123
sensitivity 179
Refresher course in, 216
Twentyfifth TB Seal
120
Printed at Navchetan Press Private Limited (Lessees of Arjun Press) Naya Bazar, Delhi.

The
Indian Journal of Tuberculosis
Vol. XXI New Delhi, January 1974 No. 1
DOMICILIARY TREATMENT-A RE-APPRAISAL
Introduction of domiciliary treatment for tuberculosis in our country
dates back to 1940 when soon after the establishment of the Tuberculosis
Association of India, its experts advocated domiciliary treatment (or organised
home treatment as it was then called) since facilities for sanatorium treatment
were grossly inadequate. The field trial conducted by the New Delhi Tuberculosis
Centre showed the scheme to be feasible and acceptable. The results
of ambulatory collapse therapy conducted from the clinics were found to be
no worse than the results obtained in hospitals/sanatoria. When antimicrobial
drugs became available soon after, the domiciliary treatment became much
more effective. The world renowned Madras trial proved incontrovertibly
that domiciliary treatment is as effective and as safe as hospital treatment.
With this, domiciliary treatment which was originally recommended because
there was no other alternative, is now being advocated by choice not only in
developing countries like ours but all over the world.
Domiciliary chemotherapy today is the sheet anchor of tuberculosis
control. Although the available drugs are capable of giving, at least theoretically,
almost cent per cent sputum conversion, yet in actual practice in service
programmes conducted from majority of the clinics in the country, the results
fall short of the possible cent per cent. Obviously this is because the facilities
available from these service institutions do not measure up to the ideal conditions
under which research studies are conducted.
Experience has shown that the main reason for shortfall in results is
irregular and inadequate treatment by the patients. If drugs are not provided
free of cost to the patients, a large majority of whom are poor and if they have
to trek long distances to collect drugs month after month at timings which are
often not convenient to them and which clash with their normal working hours,
it is not surprising that many patients become irregular and/or give up treatment
prematurely. In other words, the patients’ default can many a time be
traced to organisational lacunae in the delivery of the services.
Another important reason is the early relief of symptoms with the help
of modern drugs, though drugs have to be continued regularly for about two
years. Many patients become irregular because to an ignorant and illiterate
mind symptoms are synonymous with disease, notwithstanding all motivation
to the contrary. This is essentially a psychological problem and it seems it will
be solved satisfactorily only when it is possible to reduce the duration of treatment
to a short period, say 4 to 6 months. Future research in chemotherapy
Ind. J. Tub., Vol. XXI, No. 1

2
would, thus, be more fruitful if it is directed not towards finding a drug combination
which further improves the percentage of sputum conversion but
which helps to reduce the duration of treatment. Even if the latter regimen
is more costly, it would still pay a bigger dividend in the long run by not only
cutting short the duration of treatment but, what is more, by reducing the
irregularity of the patients and thereby enabling many more of them to complete
treatment successfully. The results of the BMRC/East African trial in this
respect are promising. The Tuberculosis Association of India has planned a cooperative
study to test the efficiency of a few drug regimens in reducing the
duration of treatment. The results of this study will be eagerly looked forward
to.
Supervised treatment and hospitalization for 2 or 3 months at the start
of treatment are sometimes advocated to get over the problem of irregularity.
Supervised treatment creates difficulties which are almost insurmountable if
the patients are many and resources limited. Furthermore, supervised treatment
requires patients’ attendance at the treatment centre many more times
than unsupervised treatment with monthly attendance for drug collection.
This leads to increased opportunities for default. Supervised treatment, thus,
appears to offer no superiority over routine unsupervised treatment both in
relation to sputum conversion and irregularity. Similarly no study, to date,
has been able to prove that short-term hospitalization at start of treatment
makes patients take drugs more regularly during the subsequent and longer
domiciliary phase than those patients who were not hospitalized at all. Nor
is hospitalization of all patients feasible.
Drug resistant bacilli are also often blamed for failure of treatment.
Firstly this is not a problem of domiciliary treatment alone. Secondly, there
is enough evidence to show that initial drug resistance does not influence the
results so adversely as irregular treatment. And emergent drug resistance is
itself the result of injudicious, inadequate and irregular chemotherapy.
Domiciliary treatment has stood the test of time. There is no other
alternative, better yet practicable. To get the best possible results from domiciliary
treatment, it is imperative that free and regular supply of drugs should
be assured to all patients as long as indicated and as near the place of their
residence as possible. Social and economic impediments should be removed
as far as possible and above all, there should be a machinery to educate and
motivate the patients and to take prompt action to retrieve the defaulters.
Ind. J. Tub., Vol. XXI, No. 1

SIGNIFICANCE OF PATIENTS WITH X-RAY EVIDENCE OF ACTIVE
TUBERCULOSIS NOT BACTERIOLOGICALLY CONFIRMED
Patients who have shown radiological
evidence of tuberculosis without bacteriological
confirmation (suspect cases) have been considered
to be suffering from active pulmonary tuberculosis
without definite evidence and treated
with anti-tuberculosis drugs. This practice is
continued under the National Tuberculosis
Programme, though priority is given to treatment
of bacteriologically confirmed cases. There
has been no critical appraisal of continuing
this practice, on the basis of scientific investigations.
Efforts have not been made to understand
the nature of these patients. However,
some idea regarding the significance of such
suspect cases can be obtained from the available
data, from different situations.
Situation in general population
Raj Narain et al (1968) reported that only
7-10 percent of patients negative on direct
microscopy but showing radiological evidence
of disease, found in the first survey of a
longitudinal study were culture positive (Table
1). Even among those considered to be cavitary,
only about 18 to 25 percent were confirmed by
culture. A follow up of these abacillary suspect
cases, 18 months later, had shown that only
about 3 per cent of them became culture
positive in an area where organised treatment
facilities were not-available. Moreover,
radiological evidence persisted only in 25 to 36
percent of them.
Based on these findings, they had concluded
that most of those regarded as active cases of
pulmonary tuberculosis on the basis of single
X-ray examination alone are not likely to be
cases of tuberculosis. They had also estimated
S. S. NAIR
(From National Tuberculosis Institute, Bangalore)
microscopy negative suspect cases in longitudinal study
that probably only 12 per cent of them will
need treatment. They strongly supported the
statement of the WHO Expert Committee on
Tuberculosis (1964) that those in whom the
disease has not been confirmed bacteriologically
should be classified as suspect cases and should
remain so classified unless or until the presence
of tubercle bacilli or some other etiology was
established.
Suspect cases among symptomatics attending
health institutions
The findings from the longitudinal study
may not be relevant for symptomatic patients
seeking relief from health institutions. It is
believed that the percentage of true cases among
those with only radiological evidence of disease
may be much higher in this situation. In the
absence of any systematic study in which such
symptomatic patients have been followed up
without treatment, the actual position is not
clear. However, it will be interesting to review
the available data from State Tuberculosis
Demonstration and Training Centres and the
District Tuberculosis Programmes.
Situation in Tuberculosis Demonstration and
Training Centres
Annual reports of the New Delhi Tuberculosis
Centre (1970) show that only 27 per cent
of the microscopy negative suspect cases were
confirmed by culture in their Domicilliary
Treatment area. The corresponding figures for
Tuberculosis Demonstration and Training
Centres at Agra and Bangalore were 25 per cent
(Annual Report, 1969) and 20 per cent (unpublished
material) respectively. It may be
TABLE 1 Culture confirmation and Follow up results for
X-ray
reader
No.
Total patients
percent
confirmed
No.
Cavitary patients
percent
confirmed
Culture
negatives
followed
up
Percent
culture
positive
18 months
later
I 899 7.2 72 18.1 834 2.6
II 608 9.9 16 25.0 548 3.1
Ind. J. Tub., Vol. XXI, No. 1

4 S.S. NAIR
mentioned that such specialised centres have
larger number of staff, are better equipped and
have experienced X-ray readers. It would be
difficult to have such centres throughout the
country. Therefore, the standard of radiological
diagnosis may vary even more widely for
other tuberculosis centres and so also the
composition of their suspect cases.
Situation in District Tuberculosis Programme
Comparative figures are not directly available
for District Tuberculosis Programmes.
However, some idea could be obtained as
follows: Rao et al (1971) had reported that out
of 228 culture positives among symptomatics
seeking treatment in health institutions 141
(62 per cent) were diagnosed by direct microscopy
at these institutions. During the year
1970, about 560 cases were diagnosed in an
average district by direct microscopy (quarterly
reports from Director General of Health
Services, New Delhi). The total number of
culture positives in this group would have been
about 900 (i.e., 560/62 x 100). Thus the
number of cases missed from this group was
340 (i.e., 900—560). The average number of
microscopy negative X-ray cases (suspect cases)
per district in 1970 was about 1100. Even
assuming that all the culture positives missed by
direct microscopy made use of the X-ray
examination facility at DTC, only 340 cases
could have been included in the suspect cases.
In other words, among the 1100 suspect cases
there could have been at the most 340 true
cases of tuberculosis. This shows that not more
than 30 per cent of the microscopy negative
suspect cases diagnosed from symptomatics
attending health institutions could have been
cases of tuberculosis. The actual percentage
may be much less because only 15 per cent of
symptomatics who were willing to attend
District Tuberculosis Centre for X-ray actually
attended (Baily et al, 1967).
From the above data, it is difficult to conclude
what percentage of microscopy negative
suspect cases among symptomatics attending
health institutions are confirmed by culture.
But the upper limit is probably 30 per cent only.
Most of these missed cases are likely to again
seek relief and could be diagnosed then. This
could be better ensured by keeping the suspect
cases under observation.
In the absence of any systematic study in
which symptomatic culture negative suspect
cases have been followed up, it is not known
what proportion among them will develop
bacillary disease a year or two later. Data
presented earlier had shown that culture con-
firmation of microscopy negative suspect cases
among symptomatics was, at the most, only
about 3 times that among such cases in general
population. If this ratio could be any guide,
the proportion of culture negative symptomatics
who may develop disease later on is not likely
to exceed 10 per cent (3 times the rate of 3 per
cent in Table 1) even among symptomatics.
Even these may not all go undetected because
the symptomatic patients continue to take
action to get relief. Putting all suspects under
observation ensures that they are not missed
even if they do not take action on their own
accord.
Are cases radiologically diagnosed early cases ?
It is generally believed that X-ray diagnosis
would lead to detection of cases in the early
stage of disease who are more amenable to
treatment. This hypothesis could be examined
in the light of the above findings and the history
of treatment of tuberculosis cases. It is significant
that the above hypothesis was formulated
before the advent of effective chemotherapy.
When a group of 100 patients, of whom only
less than 30 per cent were cases of tuberculosis,
were put on treatment, it was natural to
consider that the vast majority of them got
cured as a result of the treatment given. As
against this, most of the real cases of tuberculosis
(those bacteriologically confirmed) could
not have been effectively treated in the absence
of effective drugs at that time. This might have
led to the formulation of the hypothesis that
X-ray diagnosis can discover cases in their
early stages who could be treated more effectively.
It is unfortunate that such a hypothesis,
formulated before effective chemotherapy
became available, has not been put to a
scientific test and even now the so called “cure”
rate among suspects (most of whom did not
suffer from tuberculosis) is considered as
evidence that they are early cases.
It is also relevant that though the difficulties
in interpretation of X-ray films had been
demonstrated by Yerushalmy in 1947 followed
by Groth-Peterson et al (1952) and Newell
et al (1954), it was only about 20 years later
that this idea gained International recognition
among research workers. IUAT (1965) reported
that large margin of difference can arise between
even experienced readers and that the greatest
dissensions concern the etiology (tuberculous or
non-tuberculous) and the clinical importance
(active or inactive) of the shadows. Still these
ideas are not yet acceptable to the bulk of those
in charge of treatment institutions but there is
hope that it will not take another 20 years for
this acceptance. It is also relevant that the
Ind. J. Tub., Vol. XXI, No. 1

PATIENTS WITH ACTIVE TUBERCULOSIS NOT BACTERIOLOGICALLY CONFIRMED 5
reported efficacy of treatment in different
institutions may also be affected by the proportion
of true and false cases which they put
under treatment, those with larger proportion
of the latter would naturally be considered as
more efficient.
Is anti-tuberculosis treatment of non-cases
harmless?
Another possible advantage of putting
suspect cases on treatment could be the prevention
of cases breaking down (chemoprophylaxis).
This possible advantage has to be weighed
against the practical difficulties of embarking
on such chemoprophylaxis and the possible
harmful effects to the treated non-cases. If the
available drugs in the country and the provision
of treatment facilities are not adequate to cope
up with the problem of treating infectious cases,
will it be proper to divert these scarce resources
for treatment of suspect cases ? Further, antituberculosis
treatment of patients not suffering
from tuberculosis has to be viewed with concern
because there are indications that some drugs
like isoniazid may do harm and even indirectly
increase general mortality (Editorial, 1966;
Yerushalmy, 1967: Yerushalmy, 1968). In view
of the above it seems that the treatment of
suspect cases on a large scale should be discouraged
or at least receive only a much lower
priority than at present. It would be better to
follow the recommendations of the WHO
Expert Committee (1964) and treat only those
suspect cases which later on show bacteriological
evidence of tuberculosis. In any case
systematic studies to obtain more scientific
information are long overdue and should be
conducted in different parts of the country. In
conclusion, the following points may be reemphasized
:
1. Among patients with X-ray evidence
of active tuberculosis but negative on
microscopy found during the longitudinal
study in the general population only
about 10 per cent were positive on
culture. Among the remaining culture
negatives followed up 18 months later
only about 3 per cent became culture
positive.
2. Making use of the reports of the
Tuberculosis Demonstration and
Training Centres, District Tuberculosis
Programmes (DTP) and the findings
of assessment of diagnosis by direct
microscopy in a DTP, it is estimated
that even among patients with X-ray
evidence of active tuberculosis but
negative on direct microscopy who had
chest symptoms and attended health
institutions for relief probably a maximum
of 30 per cent only were culture
positives.
3. The hypothesis that patients diagnosed
on X-ray alone are early cases and
hence can very easily benefit from
treatment is not valid becaue it has
been formulated on the basis of the so
called “cure” rates for such patients
(majority of whom do not suffer from
disease).
4. The possible advantage of considering
treatment of such cases as chemoprophylaxis
has to be weighed against
conservation of resources for treatment
of infectious cases and the possible
harmful effects to persons who are not
suffering from tuberculosis.
5. Systematic studies to obtain more
scientific information on suspect cases
are long overdue and should be conducted
in different parts of the
country.
REFERENCES
1. Editorial (1966). Lancet, ii, 1452.
2. Baily, GVJ, Savic, D., Gothi, G.D., Naidu V.B.,
and Nair, S.S. (1967). Bull. Wld. Hlth. Org., 37,
875-892.
3. Groth-Peterson, E., Lovgreen, A., and
Thillemann, J. (1952). Acta, Tuberc. Scand, 26,
13.
4. IUAT (1965). WAT Bulletin, 36, (1), 61-72.
5. Newell, R.R., Chamberlain, W.E. and Rigler, L.
(1954). Am. Rev. Tuberc., 69, 566-583.
6. Raj Narain, Nair, S.S., Naganna, K., Chandrasekhar,
P., Ramanatha Rao, G. and Pyare Lal
(1968). Bull. Wld. Hlth. Org., 39, 701-729.
7. Rao, K.P., Nair S.S., Naganathan, N. and
Rajalakshmi, R. (1971). Ind. J. Tub., 18, 10-21.
8. WHO Expert Committee on Tuberculosis (1964).
Wld. Hlth. Org. Tech. Rep. Ser., 290.
9. Yerushalmy (1947). United States of America—
Public Health Reports, 62, 1432.
10. Yerushalmy, J. (1967). Lancet, (letters to
Editor), 1,393, Feb. 18, 1967.
11. Yerushalmy, J. (1958). Journal of Pediatrics
(letters to Editor), 73 (2), 299-200.
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR
PANCHAYAT UNION,* CHINGLEPUT DISTRICT, SOUTH INDIA
A.S. BAGGA, M.S. KRISHNA MURTHY, K.R. RANGASWAMY AND M.S. KRISHNA MURTHY
(From Tuberculosis Prevention Trial, Bangalore).
Introduction
In connection with a controlled trial of the
protective effect of BCG vaccination, currently
under survey in a part of Chingleput District,
a base line survey was carried out, with two
skin tests to all (aged one year and above), X-
ray examination of all except children below 10
years, and sputum examination (smear and
culture) on the basis of the X-ray readings.
The earliest results are presented here as a contribution
to the knowledge about tuberculosis
prevalence in various parts of India. Several
prevalence surveys for tuberculous infection
and disease have been carried out in India.
National Sample Survey 1 revealed for the first
time the widespread nature of tuberculous
disease. Raj Narain et al 2 , Frimodt-Moller 3
and Sikand and Raj Narain 4 confirmed the
findings of National Sample Survey regarding
prevalence of disease. Edwards 5 , Palmer and
Edwards 6 , and Nyboe 7 observed that there is a
high degree of prevalence of non-specific sensitivity
in various parts of India. Two tuberculosis
prevalence surveys carried out in
Kancheepuram and in Ponneri Taluks of
Chingleput District also confirmed both these
findings.
As first shown by Palmer and Strange
Petersen 10 , some reactions to tuberculin are nonspecific,
that is, not caused by infection with
M. tuberculosis. Non-specific reactions tend
to be weaker than specific reactions. Nyboe 7
has shown that in temperate and subtropical
countries almost all tuberculin reactions are
either clearly positive or clearly negative
indicating that the test is highly efficient. In
tropical regions, on the other hand, a large
proportion of reactions are of intermediate size
and distinction between positive and negative
reactions is therefore difficult and a clear cut
distinction between tuberculous infected and uninfected
evidently cannot be made by means of
the present tuberculin test. He further
observed that it is not known whether strong
sensitivity to tuberculin can be carried by
agents other than the tubercle bacilli. It is
generally believed not to be the case, but the
possibility cannot be ruled out.
Palmer and Edwards 11 on the basis of
enormous experience in the laboratory and
among naval recruits recommended using a
sensitin prepared from an ‘atypical mycobacterium’,
in addition to the tuberculin in order
to distinguish human beings infected with
mycobacterium tuberculosis from those infected
with other mycobacteria. By the use of dual
test Edwards and co-workers 12 have shown
that the studies carried out in tuberculosis
patients using tuberculin and PPD-B (prepared
from the ‘Battey’ organism) were promising.
Almost all patients had more reactions to
tuberculin than to the other antigen given at the
same time.
False positive findings as shown by
Roelsgaard and Co-workers 13 in X-ray readings
and with regards to the examination of smears
by microscopy as shown by Raj Narain and coworkers
14 can also be a problem in prevalence
surveys.
Material and Methods :
The complete census of Kadambathur
Panchayat Union consisting of 42 panchayats
was taken (on pre-numbered cards) moving
from house-to-house. The total number of
persons registered was 71,685. A centre for
examinations was established in each village (a
group of villages makes a panchayat). Presence
or absence of old scare due to BCG was
recorded after verifying the identity of every
person. Persons with old scars have been
excluded from the analysis. Only the de jure
population have been included in the present
analysis.
Each person aged one year and more was
tested intradermally with 0.1 ml each of both
PPD-S (5 IU)* and PPD-B (10 Units)+ on the
* PPD-S is a batch of purified protein derivative
of Mammalian tuberculin prepared by Dr Florence
Seibert and Glenn 15 . A part of this batch is now the
international standard of PPD.
+ Palmer and Edwards 11 have shown that when both
PPD-S and PPD-B are used in equal concentrations (by
weight) the human tuberculin appears to be more
potent than PPD-B in persons who had tuberculous
infection and less potent in persons who have had nonspecific
type of reactions. The two preparations are
certainly not identical (qualitatively as well as quantitatively)
nor is the one merely more concentrated than
the other. Further they argue that when sensitising
agent is not known, its identity can only be inferred by
testing with qualitatively and quantitatively different
tuberculins.
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR PANCHAYAT UNION 7
upper dorsal surface of either forearm depending
upon the last digit of the individual
number, in order to avoid bias at reading. In
the event of last digit being an even number,
PPD-S was injected on the right fore-arm and
PPD-B on the left fore-arm but in case the last
digit was an odd number, the injections were
given in the reverse order. The reactions were
read on the third day moving from house-tohouse.
A clerk was provided to record the
reactions. (Whenever freeze dried PPD-S and
PPD-B were used, these were reconstituted with
normal saline). Every day syringes were sterilised
by autoclaving. Biologicals were stored
at refrigerator temperature until use. Ampoules
and vials once used on a working day and the
contents if any, left over after a day’s work,
were discarded.
All individuals aged 10 years and more were
X-rayed by mobile mass miniature radiography
on 70x70 roll films. The films were read
independently by two readers who had no
knowledge of the results of tuberculin testing
or the bacteriological examination.
The readers classified shadows indicating
lung pathology in order of ‘severity’ as ‘infiltrate
with cavity’, ‘infiltrate with doubtful
cavity’, ‘Infiltrate without cavity’, ‘Hydropneumothorax’,
‘Pleurisy with effusion’,
‘Glandular lesion in and around mediastinum’,
‘consolidations’, ‘fibrotic and calcified lesions’.
Cardiac, diaphragmatic and thoracic cage
abnormalities if present were also recorded.
The extent of the lesion and whether unilateral
or bilateral was also recorded using codes. The
readers also recorded their interpretation
according to the following categories in order
of severity:
D—Probably active tuberculosis
C—Possibly active tuberculosis
B—Inactive tuberculosis
A—Non-tuberculous.
Where more than one lesion was seen, the
classification was determined by the most severe
finding.
Persons with pulmonary or pleural lesions
irrespective of their interpretation by either
reader were eligible for sputum collection, the
exceptions being healed pleural scar, single
calcification in either lung less than 1.5 mm
and a pulmonary scar less than 1.5 mm only in
one lung (on the 70 mm film). In addition,
the persons who volunteered presence of
symptoms suggestive of tuberculosis and those
who had undergone treatment for tuberculosis
were also eligible for sputum collection. A
‘Spot’ and an ‘Overnight’ sputum samples were
collected by a house-to-house visit. Sputum
samples were sent to the Tuberculosis Research
Unit Laboratory at Madanapalle, where these
were examined independently by microscopy
and culture. Strains positive on culture were
examined for drug sensitivity. (The results of
drug sensitivity are not presented in this paper).
An attempt was made to classify the cultures
as typical or atypical for mycobacteria.
Results
Sensitivity to Tuberculin :
Tuberculin reactions to PPD-S in general
population in the age group 1—9 years,
were compared with those of contacts of
the same age of culture positive cases and
shown in Fig. 1. Distribution of reactions
among contacts was bimodal, one mode being
at 4-5 mm and another at 20-21 mm. On the
other hand in general population the distribution
has a pronounced mode at 4-5 mm.
Another mode of reactions on the right hand
which is just discernible corresponds closely in
position and shape with the right hand distribution
of reactions seen in the contacts of
culture positive cases. It seems reasonable to
assume that the child population contains a
small group whose tuberculin sensitivity closely
resembles that of the contacts.
The reactions to PPD-S in the general
population both in males and females in the
age group 10—19 years are shown in Fig. 2.
The reactions are of bimodal distribution both
in males and females. The distribution on the
left hand with a mode at 4-5 mm not only
contains negative reactors but fairly large
number of intermediate reactors. The right
hand distribution with a mode at 18-19 mm in
both males and females corresponds in its
position and shape to the distribution in the
culture positive cases shown later.
Tuberculin reactions to PPD-S in general
population in the age group 20—39 years and
in the age group 40 years and above both in
males and females along with the corresponding
reactions of the same sex and age group of
culture positive cases are shown in Fig. 3.
Reactions in general population in both the
age groups and in either sex are of bimodal
distribution. The reactions among culture
positive cases are of unimodal distribution, the
mode being at 20-21 mm in the males and at
22-23 mm in the females. Over 95 percent of
the culture positive cases, 20 years or more of
Ind. J. Tub., Vol. XXI, No. 1

8 A.S. BAGGA, M.S. KRISHNA MURTHY, K.R. RANGASWAMY AND M.S. KRISHNA MURTHY
FIG. 1
DISTRIBUTION OF REACTIONS TO PPD-S IN AGE GROUPCl-9) YEARS
BY SEX AMONG HOUSE-HOLD CONTACTS OF CULTURE POSITIVE
CASES AND IN GENERAL POPULATION
Frequency Polygon refers to General Population (G.P.)
Histogram refers to Contacts of Culture positive cases
age in both sexes had reactions more than 13
mm. The right hand distribution of the
frequency polygon corresponds to the reactions
among culture positive cases, and represent
specific reactions. The left hand distribution
with a mode at 6-7 mm consists as shown
previously not only of negative reactors, but
includes a fairly large number of intermediate
reactors. Based upon these findings it is not
unreasonable to assume that those having
reactions more than 13 mm to PPD-S were
infected with tubercle bacilli and that they
were showing specific reactions with a minimum
of overlapping.
Prevalence of Infection :
Prevalence of infection (reaction to PPD-S
more than 13 mm) in Kadambathur Panchayat
Union by age and sex is shown in Fig. 4. It
may be seen from this figure that the prevalence
rates rise sharply among younger age groups
and reach maximum by the age of 40 years
both in males and in females. In males almost
80 per cent and among females almost 65 per
cent were tuberculin reactors by that age.
Thereafter prevalence rates remain near the
peak level. There may be an additional number
of infected whose sensitivety has waned.
Panchayat wise prevalence of infection rates
in the age group 10—19 years (the age group
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR PANCHAYAT UNION 9
FIG. 3
DISTRIBUTION OF REACTIONS TO PPD-S BY SEX AND TWO AGE GROUPS
(20-39) AND (40 + YEARS) IN PATIENTS AND IN
GENERAL POPULATION
homogenous in order to demonstrate the prevalence
of infection rates) in both sexes were
studied. Infection rates (reaction size more
than or equal to 14 mm to PPD-S has been
used to distinguish between infected and uninfected)
range between 13 percent to 46 per
cent. The variation between panchayats was
highly significant statistically (P

10 A.S. BAGGA, M.S. KRISHNA MURTHY, K.R. RANGASWAMY AND M.S. KRISHNA MURTHY
F I G. 4
and PPD-B for the age group 10—14 years (the
age group was considered to be large enough
PREVALENCE OF INFECTION (REACTION as well as reasonably homogenous in order to
TO PPD-S >I4mm) BY AGE AND SEX demonstrate the presence of non-specific
sensitivity) is shown in Table I.
The reactions are distributed in an inverted-L
shaped pattern. The distribution of reactions to
PPD-B is unimodal with a mode 16-17 mm. The
distribution of reactions to PPD-S is unimodal,
one mode is at 4-5 mm and another mode at 18-
19 mm. The latter mode corresponds in its
position and shape to the mode observed in
culture positive cases.
Prevalence of Disease :
Definitions of some of the terms used in
this paper are listed below :
‘Smear Positive case’ : A person was
called a ‘Smear positive case’ if at least one
sputum smear was found to be positive for >4
tubercle bacilli. (Smears showing 1-3 bacilli
were not reported by the laboratory as those
were probably regarded as artefacts).
‘Culture Positive case’ :
A person was
TABLE 1
Correlation between reactions to PPD-S and to PPD-B in age group (10-14) years
Reaction to PPD-B (Induration in mm)
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR PANCHAYAT UNION 11
Fig. 5
MAP SHOWING PREVALENCE OF INFECTION 0 IN AGE GROUP(10-19) YEARS AND
PREVALENCE OF DISEASE 00 IN AGE GROUP (1O+) YEARS IN
EACH
PANCHAYAT
° Criterion for Infection: Reaction to PPD-S > 14mm Percentage to test read.
°° Disease: Culture positive: Per thousand X-Rayed persons
KADAMBATHUR
PANCHAYAT UNION
called a sputum ‘culture positive case’ if on at
least one sputum culture, colonies of mycobacterium
tuberculosis were grown.
‘Sputum Positive case’ : A person was
called a ‘sputum positive case’ if at least one
sputum specimen was found to be positive by
either smear or by culture.
‘X-ray case’ : A person was called a ‘X-ray
case’ if both X-ray readers classified his radiological
shadows as probably or possibly active
tuberculosis (X-ray alphabet codes C or D)
and whose sputum was negative.
The distribution of tuberculin reactions
among randomly selected controls from the
general population (matched for age and sex
with the X-ray cases), among the X-ray cases
and among culture positive cases were studied
separately for males and females and are shown
in Fig 7. Reactions to the tuberculin in the
controls are of bimodal distribution in males
as well as in females very similar to the pattern
Ind. J. Tub. Vol. XXI, No. 1

12 A.S. BAGGA, M.S. KRISHNA MURTHY, K.R. RANGASWAMY AND M.S. KRISHNA MURTHY
seen in the general population. The reactions
in the X-ray cases both in males and females
FIG.6
DISTRIBUTION OF MEAN REACTION TO PPD-B
FOR NEGATIVE REACTORS TO PPD-S
(PPD-S4 colonies of mycobacterium tuberculosis
were grown.
No statistically significant difference was
observed in the mean reactions in these two
sub-groups i.e. the mean reaction in terms of
level of tuberculin sensitivity.
It may be seen from the histogram in Fig. 7
that the culture positive cases displayed a
distinct pattern. The bimodal distribution seen
FIG. 7
DISTRIBUTION OF REACTIONS TO PPD-S AMONG CONTROLS TO X-RAY
CASES. X-RAY CASES AND CULTURE POSITIVE CASES
CONTROLS
CULTURE
POSITIVE
Reaction to PPD-S(in mm)
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR PANCHAYAT UNION 13
FIG.8
PREVALENCE OF CULTURE POSITIVES AND
X-RAY POSITIVES• BY AGE AND SEX IN
KADAMBATHUR PANCHAYAT UNION
in the X-ray cases may mean that active tuberculosis
was diagnosed by X-ray in some of the
sputum negative persons who were probably
not infected with mycobacteriom tuberculosis.
Scanty and highly positive cases on culture
were further studied regarding their X-ray
status. X-ray reading by two readers are shown
in Table II (a) and II (b) in terms of correlation
table between the two readings. Cases
scanty positive on culture were compared with
randomly selected controls from the general
population (matched for age and sex with
twice the number of cases scanty positive on
culture, excluding sputum positive cases and
also those with technically inadequate X-rays).
X-ray readings between two readers among
cases highly positive on culture were also
studied similarly and are shown in Table II (c).
It may be seen from Table II (b) that as few
as one third (35 per cent) were read as possibly
or probably active (X-ray alphabet codes C or
D) tuberculosis by both X-ray readers in cases
scanty positive on culture while as many as one
fourth (26 per cent) were missed by X-ray by
both X-ray readers.
• Reading of “POSSIBLY or PROBABLY
ACTIVE” Tuberculosis by at least
one of two X-Ray readers.
The correlation between smear and culture
results is shown in Table III. It may be seen
that as many as 129 (44 per cent) were culture
positive but negative on smear while only 166
(56 per cent) were positive on culture and were
also positive on smear.
TABLE II (a)
Correlation between two x-ray readings of controls* to culture scanty positives
I Reading
0** A B C D Others(i) Total
0** 100 5 2 — 1 1 109
A 6 — 2 — — — 8
II Reading
B 1 — 3 2 — — 6
C 1 — 2 2 — — 5
D — — — — — —
Others(i) 1 — 1 — — — 2
Total 109 5 10 4 1 1 130
* Matched for age (by 5 years age groups) and sex (excluding sputum positive cases and those with
technically inadequate X-rays) with twice the number of scanty positive cases.
** No abnormality.
(i) No code recorded.
Ind. J. Tub., Vol. XXI, No. 1

14 A.S. BAGGA, M.S. KRISHNA MURTHY, K.R. RANGASWAMY AND M.S. KRISHNA MURTHY
TABLE II (b)
Correlation between two x-ray readings of culture scanty positives
I Reading
0* A B C D Other** Total
0* — 2 7 1 1 — 11
II Reading
A 2 1 2 1 — — 6
B 3 — 2 11 — — 16
C 3 1 4 11 5 — 24
D — — 1 3 4 — 8
*No abnormality
** No code recorded
Others** — — — — — —
Total 8 4 16 27 10 65
TABLE II (c)
Correlation between two x-ray readings of cases highly positive on culture
I Reading
0* A B C D Other** Total
0* — 2 3 3 1 — 9
II Reading
A 3 — 1 2 2 — 8
B 1 2 4 15 1 — 23
C 1 2 6 35 28 — 72
D — — 1 21 95 — 117
Others** — 1 — — — — 1
* No abnormality
** No code recorded
Total 5 7 15 76 127 — 230
Smear Positive Cases :
16 cases were found to be positive on smear
only but were negative on culture. Could these
be atypical mycobacteria or dead bacilli in
recently treated cases or were they artefacts?
At 6-12 months follow-up, 2 of the 14 followed
up were found to be positive on culture and
remaining were found to be negative on smear
and also on culture. Sex and age distribution
of culture positive cases (in 5 years age groups)
was studied and is shown in Table IV. Only
over the age of 39 years, a significant difference
was seen between sexes, males having a higher
rate of highly positive cases on culture than
females (not shown in this table).
Prevalence of X-ray cases (>10 years) in
males was 2.1 per cent and in females was
1.1% per cent. The prevalence of culture positive
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN KADAMBATHUR PANCHAYAT UNION 15
TABLE III
Correlation between smear and culture results of sputum positive cases
Culture
Negative
(No bacilli)
(1-3)
colonies
4 or more
colonies
Total
Smear
Negative (No bacilli) — 63 66 129
4 or more bacilli 16 2 164 182
Total 16 65 230 311
TABLE IV
Age and sex distribution of sputum positive and x-ray cases in 5 year age groups
5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70+ Total
Sputum
Positive
Cases
Males — 2 3 7 12 19 37 41 30 25 29 19 13 8 245
Females — — 2 7 14 12 7 4 8 4 2 4 1 1 66
Both Sexes — 2 5 14 26 31 44 45 38 29 31 23 14 9 311
Males 4 16 6 7 30 19 50 47 50 46 52 46 31 42 446
X-ray Females 7 22 14 4 27 14 21 13 22 16 20 15 20 11 226
Cases Both Sexes 11 38 20 11 57 33 71 60 72 62 72 61 51 53 672
cases (> 10 years) in males was 10.9 per cent
and in females 2.8 per cent.
Prevalence of X-ray and sputum positive
cases by age and sex has been shown in Fig. 8.
(for absolute figures see Table IV). It may be
seen from Fig. 8 that the prevalence of X-ray
cases both in males and in females rises
gradually upto the age of 35 years and thereafter
it rises very sharply. On the other hand,
the prevalence of culture positive cases in
males rises gradually upto the age of 30 years.
The peak is reached by about 40 years of age
and thereafter it remains near the peak level.
However, in females no such phenomenon was
observed.
Discussion :
Many authors (BMRC trial 16 , Raj Narain
et al 2 , Edwards and Smith 17 , Hsu et al 18 ) in the past
have adopted different sizes of reaction to
tuberculin to classify reactors and non-reactors;
the chief aim in such a classification has been
to have a minimum of over lapping.
Edwards and Edwards 12 suggested that
tuberculin reactions above 12 mm only should
be considered without any doubt as due to
tuberculous origin while reactions between
6-12 mm are likely to be of non-specific
origin.
Based upon the material presented, a
reaction size to tuberculin of 14 mm or more
(irrespective of reaction size to PPD-B) was
considered as indicative of specific reaction.
Frimodt-Moller 3 has shown in South Indian
villages that beyond the age of 10 years, nonspecific
sensitivity reactions are almost universal.
Our findings are more or less similar
to those findings.
Palmer and Edwards 11 have demonstrated
among naval recruits by dual testing that those
infected with M. tuberculosis and those infected
with atypical mycobacteria run different kinds
of risks.
The controlled BCG trial population is
Ind. J. Tub., Vol. XXI, No. 1

16 A.S. BAGGA, M.S. KRISHNA MURTHY, K.R. RANGASWAMY AND M.S. KRISHNA MURTHY
TABLE V
Comparative prevalence of radiological and bacteriological disease in three surveys
Sex
Radiological
prevalence in
percentage (%)
Bacteriological
prevalence per
thousand (%)
* National Sample Survey
(Madanapalle Zone)
Males 2.2 8.5
Females 1.1 3.6
Both Sexes 1.6 6.1
Males 2.5 5.6
.
Tumkur Survey Females 1.2 2.5
Both Seves 1.9** 4.1**
Kadambathur Panchayat Union Males 2.1 10.9
Females 1.1 2.8
Both Sexes 1.6 6.9
* In the National Sample Survey the average for all the zones of radiological prevalence was 1.8 per cent
and the bacteriological prevalence was 4.0 per cent.
** For the villages the average radiological prevalence was 1.8 per cent and bacteriological prevalence
was 3.9 per cent
being followed now for many years and it
might become possible to arrive at an accurate
definition to distinguish infected and uninfected
and the risks involved.
Prevalence of Disease :
The comparative prevalence of radiological
and bacteriological disease observed in the
National Sample Survey, in the Madanapalle
zone of National Sample Survey, in the Tumkur
District Survey and in the Kadambathur
Panchayat Union are shown in Table V. The
Madanapalle zone in South India examined
during National Sample Survey lies not quite
far off from Kadambathur Panchayat Union.
The prevalences of radiological disease in
these areas do not differ much. The prevalences
of bacteriological disease in the National
Sample Survey and in the Tumkur district were
of the same order. Comparatively higher prevalences
were observed in the Madanapalle zone
of National Sample Survey and in the Kadambathur
Panchayat Union. However, the highest
prevalence was observed in the Kadambathur
Panchayat Union.
The prevalence of bacteriological disease in
the males was observed to be the highest in the
Kadambathur Panchayat Union.
ACKNOWLEDGEMENTS
The authors are grateful to Dr. Raj Narain,
Deputy Director General of Health Services,
Government of India, on deputation as Project
Director, Tuberculosis Prevention Trial,
Bangalore, for his constructive criticism.
The authors are also deeply indebted to
Dr. J. Guld, Medical Officer, Tuberculosis Unit
World Health Organisation, Geneva, for his
very useful suggestions and criticism.
Our thanks are also due to Dr S. Mayurnath,
Medical Officer, for his suggestions and to the
field teams, for their hard work.
We wish to thank Mr M. Haridas, Statistical
Assistant and the other staff of the
Statistical Section for their help in the analysis
and Mr P.R. Krishna Moorthy and Miss
Vaidehi for their Secretarial help.
Ind. J. Tub., Vol. XXI, No. 1

PREVALENCE OF TUBERCULOSIS DISEASE AND INFECTION IN K.ADAMBATHUR PANCHAYAT UNION 17
1. Indian Council of Medical Research (1959)
Tuberculosis in India. A sample survey 1955-57,
New Delhi (Special Report Series No. 34).
2. Raj Narain, Geser, A., Jambunathan, M.V.,
and Subramanian, M. (1963) Bull. Wld. Hlth.
Org. 29, 641-664.
3. Frimodt-Moller, J (1960) Bull. Wld. Hlth. Org.,
22, 61-170.
4. Sikand, B.K., and Raj Narain (1958) Radio
logical problems of tuberculosis as revealed by
the national survey. In : Tuberculosis Associa
tion of India, Proceedings of the 14th All India
Tuberculosis and Chest Diseases Workers’
Conference, held in Madras under the auspices
of Tuberculosis Association of India, pp. 75-84.
5. Edwards LB., Palmer, C.E., and Edwards,
P.Q., (1955) Bull. Wld. Hlth. Org. 12, 63-83.
6. Palmer, C.E., and Edwards, P.Q., (1955) Bull.
Wld. Hlth. Org. 12, 85-99.
7. Nyboe, J (1960) The Efficiency of the Tuber
culin Test, an Analysisbased on results from
33 countries. Bull. Wld. Hlth. Org. 22, 5.
8. Raj Narain, S. Mayurnath, A.S. Bagga, K.
Naganna, M.S, Subba Rao and K.R.
Rangaswamy (1969) Proceedings of the 24th
TB and Chest Diseases Workers’ Conference,
Trivandrum, January 1969.
9. Raj Narain, A.S. Bagga, S. Mayurnath, K.
Naganna, M.S. Subba Rao and K.R.
Rangaswamy (1969) Proceedings of the 24th
TB and Chest Diseases Workers’ Conference,
Trivandrum, January, 1969.
REFERENCES
10. Palmer, C.E., and Strange Peterson (1950). Pub.
Hlth. Rep. (Wash) 65, 1-32.
11. Palmer, C.E. and Edwards, L.B.. (1968) Identi
fying the Tuberculous infected. J. Amer. Med.
Ass. 205, 167.
12. Edwards, L.B., Edwards, P.Q., and Palmer,
C.E. (1959) Ada Tuber. Scand. Supplement, 47,
p. 77.
13. Roelsgaard, E , Iverson, E and Blocher, C (1964)
Bull. Wld. Hlth. Org. 30, 459-518.
14. Raj Narain, Subba Rao, M.S., Chandrasekhar,
P. and Pyarelal (1971) Microscopy Positive and
Microscopy Negative cases of Pulmonary Tuber
culosis, Amer. Rev. Resp. Dis. 103, 761-773.
15. Seibert, F.B., and Glenn, J.T., (1941) Tuber
culin purified Protein derivative: Preparation and
analysis of a large quantity for standard. Amer.
Rev. Tubcrc. 44, 9.
16. Medical Research Council, Tuberculosis
Vaccines Clinical Trial Committee (1959) II
Report, Brit. Med. J. 2, 379.
17. Edwards, L.B., and Smith, D.T. (1955) Amer.
Rev. Resp. Dis., 92,43.
18. Hsu, Katharine H.K., Fongee Jeu and Jenkins,
Daniel B.C., (1961) Amer. Rev. Resp. Dis.
90, 36.
Ind. J. Tub.. Vol. XXI, No. 1

THE ROLE OF ZIEHL-NEELSEN AND FLUORESCENT STAINS IN TISSUE
SECTIONS IN THE DIAGNOSIS OF TUBERCULOSIS
HEMALATHA KRISHNASWAMI AND C. K. JOB
(From Christian Medical College Hospital, Vellore)
Introduction
The histopathological appearance of tuberculosis
is so similar to other granulomatous
lesions that bacteriological studies are often
necessary to confirm the diagnosis. Although
culturing and isolation of M. tuberculosis is the
best way to confirm the diagnosis of tuberculosis,
often these facilities are not available.
Moreover culture for mycobacteria involve a
minimum period of 6-9 weeks. Hence the
study of tissue sections by staining with Ziehl-
Neelsen stain and fluorescent stain was considered
worthwhile in evaluating the comparative
merits of the staining techniques with culture
methods.
Material and methods
Two hundred and sixty five consecutive
lymph node biopsy specimens were studied over
a ten month period. One half of the lymph
node was kept in a sterile container for culture
studies and the other half was fixed in 10 per
cent formalin. Several 5 µ sections were made,
embedded in paraffin, stained using haematoxyling
and eosin stain and studied. All the
sections which were histologically diagnostic of
tuberculosis were stained for M. tuberculosis
by the Ziehl-Neelsen stain and Fluorescent
stain using auramine and rhodamine. Ziehl-
Neelsen stain was done on tissue sections
according to the method described in the Armed
Forces Institute of Pathology Manual of Histologic
and Special Staining Techniques (1937)
and acid fast bacilli were looked for by searching
the whole section under oil immersion lens
using a 10x objective.
The fluorescent staining was done by the
method of Matthaie as modified by Kuper and
May (1960) and Silver, Sonnenwirth and Alex
(1966) using auramine-rhodamine staining.
These sections were examined on the day of
staining using a 10x ocular and a low power
(10x) objective lens. Characteristic features
typical of M. tuberculosis were confirmed with
a higher power (45x) objective lens. Dark field
illumination was preferred as it was less
fatiguing and also in its fluorescence, the contrast
between organisms and the background
was more prominent. Control sections that
were known to contain organisms, were
prepared with each group of unknowns. An
additional negative control of 10 different
lymph node sections without granulomatous
lesions were stained with the fluorescent dye
and were found to be negative.
Results
Histopathologically 128 lymph nodes were
diagnostic of tuberculosis out of 265 lymph
nodes. M. tuberculosis was found in 91 specimens
(71.1 per cent) using Ziehl-Neelsen stain
and in 102 specimens (79.7 per cent) using
fluorescent stain. With fluorescent stain the
bacilli fluoresced a reddish golden yellow while
the tissue appeared a dark pale green and the
background appeared black. Artefacts tended
to appear hazy yellow or grey green and lacked
the reddish tinge and were poorly delineated.
Although the organisms tended to appear larger
than expected due to fluorescent glow, they
retained their slightly curved rod like structure.
Fig.
Lymph node showing morphologically typical
M. tuberculosis. Auramine-rhodamine
fluorescent stain, x 920.
Of interest was the fact that out of 265
lymph nodes subjected to culture for acid fast
bacilli, mycobacterium tuberculosis was grown
in 101 specimens (Krishnaswami and others,
1972). The correlation between culture method
and staining techniques for acid fast bacilli are
shown in the table below.
The table shows that of the 128 histopathologically
positive biopsies 101 were identified
by culture, 102 by fluorescent method and 91
by Ziehl-Neelsen staining method.
Ind. J. Tub., Vol. XXI, No. X

ROLE OF ZIEHL-NEELSEN AND FLUORESCENT STAINS IN TISSUE SECTIONS IN DIAGNOSIS
19
Correlation between culture and staining methods for acid fast bacilli
Ziehl-Neelsen
positive (91)
Ziehl-Neelsen
negative (37)
Total
Fluorescent
positive
Fluorescent
negative
Fluorescent
positive
Fluorescent
negative
Culture positive 73 5 11 12 101
Culture negative 11 2 7 7 27
Total 84 7 18 19 128
Discussion
Stains for acid fast bacilli were popularised
by the method of Ziehl-Neelsen in 1882 (Topley
and Wilson, 1966). Numerous other workers
have developed techniques for the demonstration
of acid fast bacilli. Many have described
staining methods using non-fluorescent stains
(Topley and Wilson, 1966). Among all the
methods Ziehl-Neelsen stain has been proved to
be most useful and most frequently used by
various workers (Braunstein and Adriano, 1961;
Korn and others, 1959, Mackellar, Hilton and
Masters, 1967; Reid and Wolinsky, 1969).
Fluorescent staining for acid fast bacilli was
first described by Hagemann in 1937 (cited by
Silver, Sonnenwirth and Alex, 1966),
While using Zieh-Neelsen technique for
demonstrating acid fast bacilli in sections, the
following points are to be borne in mind. In
tissue sections, fixed in formalin for a long
time, the bacilli often stain poorly with Ziehl-
Neelsen stain. According to Fielding, cited by
Topley and Wilson (1966), this is due to the
development of an acid reaction following
autolysis of the tissues and can be overcome by
fixing in a weakly alkaline solution of formol
or by staining with alkaline fuchsin. Also it
has been observed that in certain tissues like
specimens of cold abscess, granulomatous
lesions of lymph nodes, serous exudates and
some samples of sputum, acid fast bacilli
cannot be found even though such materials
produce tuberculosis into animals. In this
bacilli might be present in the form of non-acid
fast granules (Zinsser, 1968).
Many reports are available in literature
where the merits of using Ziehl-Neelsen and
fluorescent methods were investigated using
smears (Freiman and Mokotoff, 1943; Gilkerson
and Kanner, 1963; Koch and Kote, 1965: Lind
and Shaughnessy, 1941; Needham, 1957;
Traunt, Brett and Thomas, 1962; Weiser and
others, 1966), but there are only a few using
tissue sections (Braunstein and Adriano, 1961;
Koch and Cote, 1965; Tanner, 1941). Some
workers have claimed superiority of fluorescent
staining (Braunstein and Adriano, 1961;
Gilkerson and Kanner, 1963; Gray, 1959;
Koch and Cote, 1965; Lind and Shaughnessy,
1941; Tanner, 1941; Traunt, Brett and Thomas,
1962; Yamaguchi and Braunstein, 1965) whereas
others have claimed equivalent results (Freiman
and Mokotoff, 1943: Needham, 1957: Weiser
and others, 1966). In our study of the 128
lymph nodes with tuberculous histology. 91
(71.1 per cent) showed acid fast bacilli by Ziehl-
Neelsen method while 102 (79.7 per cent) were
positive by fluorescent method.
There are several advantages of fluorescent
staining (Kubica and Dye, 1967; Traunt, Brett
and Thomas, 1962; Weiser and others, 1966).
Smears may be scanned at a total magnification
of 100x as compared to approximately l000x for
Ziehl-Neelsen stain. The low magnification used
makes it possible to scan the entire section
rapidly. The dark field technique, used along
with the low magnification, enables easier
detection of mycobacteria as “glowing spots”
even if present in small numbers, thus making
it a more sensitive technique. Organisms
apparently dead, or non-cultivable due to
chemotherapy and ron-stainable by Ziehl-
Neelsen method may still be flourescent positive.
Fluorescent stained material may be
restained with Ziehl-Neelsen method but Ziehl-
Neelsen stained material cannot be effectively
decolorised and restained by fluorescent
method. However certain precautions have to
be kept in mind in view of the previous reports
of false positive results with this technique
(Freiman and Mokotoff, 1943). The stain has
to be mixed properly before use and experience
Ind. J. Tub., Vol. XXI, No. 1

20 HEMALATHA KRISHNASWAMI AND C. K. JOB
is necessary in deciding what is and what is
not an artefact and in identifying M. tuberculosis.
Of the 128 histopathologically tuberculous
lesions, 102 and 91 specimens were positive by
fluorescent and Ziehl-Neelsen’s method respectively.
In 101 mycobacteria were grown in
culture (Krishnaswami and others, 1972).
Hence it is reasonable to state that where
culture facilities are not available, the tissue
sections can be studied using the simple acid
fast staining method according to Ziehl-Neelsen,
yielding fairly comparable results. The fluorescent
stain has a definite advantage in speed in
identification of small numbers of mycobacteria
in tissues.
ACKNOWLEDGEMENTS
We acknowledge with gratitude the help
rendered by Mr. Jasper Daniels, Microbiologist
of the Microbiology Department and Mr.
Arthur John, Chief Technician of the Pathology
Department, Christian Medical College
Hospital, Vellore, and Mr. G.R. Vijayaraghavan
for secretarial assistance.
Summary
A prospective study to detect tuberculosis
was carried out on 265 consecutive lymph node
biopsies over a ten month period. Hlstopathological
evidence of tuberculosis was seen in 128
lymph nodes, while on culture pathogenic
mycobacteria were isolated in 101 specimens
(Krishnaswami and others, 1972). Of the 128
histologically tuberculous lymph node specimens,
mycobacteria were detected in 102 specimens
with fluorescent staining and in 91
specimens with Ziehl-Neelsen staining. While
fluorescent method for demonstrating M. tuberculosis
was found to be superior to Ziehl-
Neelsen technique, both are useful to confirm
the diagnosis of tuberculosis where culture
facilities are not available.
REFERENCES
Braunstein, H. and Adriano, S.M. (1961). Fluorescent
stain for tubercle bacilli in histologic sections. I:
Diagnostic efficiency in granulomathus lesions in
lymph nodes. American Journal of Clinical Pathology,
36, 37.
Freiman, D.G. and Mokotoff, G.F. (1943). Demonstration
of tubercle bacilli by fluorescence microscopy,
A comparative evaluation of the fluorescence and
Ziehl-Neelsen methods in the routine examination
of smears for acid fast bacilli. American Review of
Tuberculosis, 48, 435.
Gilkerson, S.W. and Kanner, O. (1963). Improved
technique for the detection of acid fast bacilli by
fluorescence. Journal of Bacteriology, 88, 890.
Ind. J. Tub., Vol. XXI, No. 1
Gray, D.F. (1953). Detection of small numbers of
mycobacteria in section by fluorescence microscopy.
American Review of Tuberculosis, 68, 82.
Koch, M.L. and Cote, R.A. (1965). Comparison of
fluorescence microscopy with Ziehl-Neelsen stain
for demonstration of Acid Fast Bacilli in smear
preparations and tissue sections. American Review
of Respiratory Diseases, 91, 283.
Korn, R.J., Kellow, W.F., Heller, P., Chomet, B. and
Zimmerman, H.J. (1959). Hepatic involvement in
extrapulmonary tuberculosis. American Journal of
Medicine, 27, 60.
Krishnaswami, H., Koshi, G., Kulkarni, K.G. and
Job, C.K. (in press). Tuberculous lymphadenitis in
South India—A histopathological and bacteriological
study.
Kubica, G.P. and Dye, W.E. (1967). Laboratory
methods for clinical and public health mycobacteriology.
Public Health Service Publication No. 1547,
Washington, D.C., p. 23.
Kuper, S.W.A. and May, J.R. (1960). Detection of
acid fast organisms in tissue sections by fluorescence
microscopy. Journal of Pathology and Bacteriology,
79,59.
Lind, H.E. and Shaughnessy, H.J. (1941). Fluorescent
staining technique for detection of acid fast bacilli.
Journal of Laboratory and Clinical Medicine, 27,
531..
Mackellar, A. Hilton, H.B. and Masters, P.L. (1967).
Mycobacterical lymphadenitis in childhood.
Archives of Diseases of Childhood, 42, 70.
Manual of Histologic and Special Staining Techniques,
Armed Forces Institute of Pathology, Washington,
p. 176, 1957.
McClure, D.M. (1954). The development of fluorescence
microscopy for tubercle bacilli and its use as an
adjunct to histological routine, Journal of Clinical
Pathology, 6, 273.
Needhan, G.M. (1957). Comparative efficiency of
direct microscopy (two methods) and culture in the
diagnosis of tuberculosis, Proceeding of Mayo
Clinic, 52, 1.
Reid, J.D. and Wolinsky, E, (1969). Histopathology of
lymphadenitis caused by atypical mycobacteria,
American Review of Respiratory Diseases, 99, 8.
Silver, H., Sonnenwirth, A.C. and Alex, N. (1966).
Modifications in the fluorescence microscopy
technique as applied to identification of acid fast
bacilli in tissue and bacteriological material, Journal
of Clinical Pathology, 19, 583.
Tanner, F.H. (1941). Fluorescence microscopy for
demonstration of mycobacterium tuberculosis in
tissue, Proceedings of Mayo Clinic, 16, 839.
Topley and Wilson’s Principles of Bacteriology and
Immunity, 5th Ed. Reprinted Vol. 1, p. 536, London.
Edward Arnold Ltd., 1966,

ROLE OF ZIEHL-NEELSEN AND FLUORESCENT STAINS IN TISSUE SECTIONS IN DIAGNOSIS 21
Traunt, J.P., Brett, W.A. and Thomas, W. (1962).
Florescence microscopy of tubercle bacilli stained
with auramine and rhodamine, Henry Ford Hospital
Bulletin, 10, 287.
Weiser, O.L., Sproat, E.F., Hakes, J.D. and Morse,
W.C. (1966.) Fluorochrome staining of mycobacteria,
American Journal of Clinical Pathology, 46,
587.
Yarnaguchi, B.T. and Bratinstein, H. (1965). Fluorescent
stain for tubercle bacilli in histological sections
II: Diagnostic efficiency in granulomatous lesions of
the liver, American Journal of Clinical Pathology,
43, 184.
Zinsser, H.Mycobacterium Tuberculosis and
Tuberculosis. In Zinsser’s microbiology. 14th Ed.
Appelton- New York, p. 533, 1968
Ind. J. Tub., Vol. XXI, No. 1

TUBERCULOSIS IN ANIMALS IN INDIA—A REVIEW
H.V.S. CHAUHAN, D., P. DWIVEDI, S.S. CHAUHAN AND D.S. KALRA
(From College of Veterinary Sciences, Haryana Agricultural University, Hissar)
Bovine Tuberculosis
Tuberculosis in animals in India was considered
to be a rare disease (Wilkinsen, 1914;
Smith, 1923). It is of historical interest to
mention the remarks of Professor Lingard
(cited by Guha and Sarkar, 1970) that he had
no knowledge of existence of tuberculosis in
cattle in India. This was contradicted by
Mitra (1910) who reported 45 cases of bovine
tuberculosis after 12 years of observations.
As a result of extensive investigation carried
out on tuberculosis in animals during the last
three or four decades, our concept about the
prevalence of animal tuberculosis has got
reoriented. Three cases were recorded in bullocks
in 1916 in Madras (Nagrajan, 1948-49),
and till the year 1917, Taylor and Oliver (cited
by Datta, 1934-35) found an incidence of
about 30 percent only, and mention of a case
of tuberculosis was seldom made in any of the
annual reports of Veterinary departments of the
States.
The first experimental investigation on
bovine tuberculosis may be said to have begun
with the work of Listen and Soparkar (1917).
The work was conducted primarily to obtain
explanation for the alleged rarity of the
disease and they attributed it to natural resistance
of Indian cattle. Later experiments of
Sheather (1920-21) appeared to show a relatively
low degree of virulence of organisms isolated
locally, but this rinding was challenged by other
workers (Soparkar, 1925: Sahai and Dhanda,
1941-42).
The subject of animal tuberculosis was next
discussed by the Board of Agriculture in its
meeting at Pusa in 1925. Later, the body
passed a resolution for conducting further
research on bovine tuberculosis and persuaded
Indian Research Fund Association to give
financial assistance. Research work was thus
started at the Indian Veterinary Research
Institute (I.V.R.I.) from 1925 onwards. The
experiments and experience of different workers
revealed that some indigenous cattle showed
less progressive or localised form of the disease
(Soparkar, 1925; Sahai and Dhandha, 1942-44:
Folding, 1945; Lall, 1955; Rajagopalan, 1949:
Lall and Singh, 1955; Sengupta, 1967). The
organisms isolated were, however, as virulent
as those obtained from other countries.
Soparkar (1924) indicated on the basis of his
experiments that buffaloes are much more resistant
than the calves and his later experiments
(1926) indicated that buffaloes are much more
susceptible than the cows.
Incidence
Our knowledge regarding the incidence of
tuberculosis in India has been largely built up
from two sources.
(a) Examination of carcases in the slaughter
houses.
(b) Mass tuberculin testing in cities, villages
and on various government, and organised
farms.
(a) Slaughter house examinations
In early phases of investigation, cattle and
buffaloes slaughtered at slaughter houses of
the various states were examined. The statistics
showed that percentage of infection in
certain states, like Punjab and Bombay, was
very high, whereas it was much less in Madras,
Mysore and Bengal. Cook (1902) examined
thousands of catties slaughtered in Madras
and Calcutta but failed to find even a single
case of tuberculosis although he has placed
on record 31 cases out of 4,155 cattle admitted
in Calcutta in Veterinary College Hospital,
during 1893 to 1902. Taylor (1917-18) found
gross lesions of tuberculosis in 3.5 per cent of
the cattle slaughtered at Ferozepur during 1915
to 1917. Later survey revealed that the incidence
rose to 17.54 per cent. Edwards (1927)
found 16 per cent incidence of tuberculosis in
cattle slaughtered at Ferozepur and Kanpur.
Out of 1116 slaughtered animals examined at
Lahore, 21.3 per cent cows, 23.6 per cent
buffaloes and 31.6 per cent bullocks showed
tuberculous lesions (Soparkar and Dhillon,
1931). Later on this type of survey was given
up with the idea that the animals slaughtered
were not truly representative of the animal
population.
(b) Tuberculin testing
The incidence revealed by tuberculin testing
was found to vary from herd to herd. In some
herds the incidence was negligible, while in
others 30 to 85 per cent (Abdul Salam and
Ind. J. Tub., Vol. XXI, No. 1

TUBERCULOSIS IN ANIMALS IN INDIA-A REVIEW 23
Shirlaw, 1939-41; Sahai, 1942; Sahai and
Dhanda, 1942-44; Mallick et al, 1942;
Rajagopalan et al, 1949; Saroop, 1952-53;
Taneja, 1955; Tulsaram, 1955: Lall and Singh,
1955; Dhanda and Lall, 1963; Lall, 1964).
Such tests, to begin with, were carried out in
big cities like Bangalore, Madras, Patna and
Lahore. Lahore and Ahmedabad represented
areas of high incidence while Madras and
Patna of low incidence (Rajagopalan, 1949;
Dhanda, 1951; Lall, 1952-55). The history at
Government Cattle Farm, Hissar, shows that
the incidence in 1940 was as high as 20.22 per
cent. The percentage was brought down by
Sahai and Dhanda (1944) to as low as 1 per
cent by March, 1944. The results of tuberculin
testing by various workers have been compiled
together and are presented in table 1.
Comparative incidence in cattle, buffaloes and
calves
In PEPSU, 152 animals were tuberculin
tested and the positive reaction was found to be
4.8 per cent in cows, 18.6 per cent in bulls and
bullocks and only 2.7 per cent in calves under
two years of age. The reactors in buffalo cows
and heifers were 12.5 per cent (Bhatia, 1960).
Lall (1964) and Lall et al, (1967) also found
the incidence to be higher in buffaloes (9.39
per cent) than in cattle (1.99 per cent). It can
also be seen from Table I that the incidence in
buffaloes, all over the country, is higher than
in the cattle. The incidence of disease was
higher in adult (3.59 per cent) than in young
stock (0.30 per cent). Kuppuswamy and Singh
(1968) found the incidence to be higher in
Tharparkar cattle.
Effect of environment on incidence
Purohit and Mehrotra (1969) found no
incidence of tuberculosis at Bikaner in cattle,
possibly because of the hot and dry climate
with poor rainfall and probably the Rathi
breeds of the area are comparatively more resistant
than Haryana and Gir breeds. There was
no significant difference in the incidence of the
disease in the animals kept in Indian cities and
villages (Lall et al, 1967).
Spread of the disease
Periodical tuberculin tests conducted on a
herd at Puri (from 1937 to 1942) amply demonstrated
that even under Indian conditions, the
spread occurs unchecked. In the herd tested,
it was shown that the incidence was 9.09 per
cent in 1973, 14.8 per cent in 1938, 50 per cent
in 1941 and 84.7 per cent in 1942 (Bhatia,
1960).
In-1924, a-small but severe outbreak occurred
in Victoria Gardens Bombay, amongst Llamas
obtained from Germany and from them
disease spread to several spotted deers and
blue bulls (Datta, 1934-35). This indicated
that wild animals can act as reservoirs and
spread the disease very fast.
Dissemination of tuberculosis through a
single breeding bull to cows can be a very
serious hazard. There appears to be only one
such case on record in which prostates and
testicles of a bull were involved (Bhambani,
1969). Tuberculin testing in Madhya Predesh
revealed 11 male cattle including 3 he-buffaloes
to be positive out of 43 tuberculin positive
cattle (1830 animals tested) in all the organised
farms in the state (Rawat and Kataria, 1971).
Singh et al., (1956) have described an
interesting case of tuberculous mastitis which
was later on shifted to goshalas (cow-sheds).
As a result many of the animals, particularly
calves, fed on pooled milk, became reactors to
tuberculin. Milk-borne infection to man is
also suggested by a case recorded by Mills
(1898-99).
Types of tubercle bacilli
Typing of the 60 stains of tubercle bacilli
from extrapulmonary tuberculosis in man by
Ukil (1933), 62 by Mallick et al. (1942) and 21
by Indrajit (1946) revealed all of them to be of
human type.
Further, during the period from 1942 to
1967, a total of 173 cultures of tubercle bacilli
isolated from cases of tuberculosis in man and
animals, have been typed at Indian Veterinary
Research Institute (I.V.R.I.), Izatnagar. The
type of isolates (Lall, 1969) alongwith the
work of others have been tabulated (Table 2).
It is noteworthy to mention that there is
only one case of bovine type of tuberculosis
recorded, in a girl in India (Soparkar, 1929)
and a suspected case in a child has been reported
by Mills (1898-99). This low incidence of
bovine tuberculosis in man, inspite of. high
incidence of tuberculosis in animals, could
possibly be explained either because of less
exhaustive surveys or to the universal practice
in India, of thorough boiling of milk and meat
(Myers and Steele, 1969). However, looking
to the high incidence of tuberculosis in animals,
airborne infection of farmers who live almost
together in Indian village houses, cannot be
ruled out.
The infection of large number of pigs, dogs
Ind. J. Tub., Vol. XXI, No, 1

24 H.V.S. CHAUHAN, D., P. DWIVEDI, S.S. CHAUHAN AND D.S. KALRA
Ind. J. Tub., Vol. XXI, No. 1

TUBERCULOSIS IN ANIMALS IN INDIA-A REVIEW 25
Ind. J. Tub., Vol. XXI, No. 1

26 H.V.S. CHAUHAN, D., P DWIVEDI, S.S. CHAUHAN AND D.S. KALRA
Source
TABLE 2**
Type of tubercle bacilli isolated from man and animals
Number of
cultures
Type of tubercle bacilli
Bovine Human Avian
Remarks
Human beings 71 + 1* 1* 71 — *Soparkar (1929)
Pigs 22+4* 4+3* 16+1* 2 *Bhattacharya et al. (1972)
Cattle & Buffaloes
(Mostly buffaloes)
40+1* 40 1* — *Chandrasekharan Nair and
Ram Krishnan (1969)
Camel 1 + 1* 1 + 1* — — *Ann. Rep. D.I.O. Camel,
Punjab (1960-67)
Giraffe 1 — — —
Sheep & Goats 5 5 — —
Dogs 6 — 6 —
Monkey 2 — 2 —
Chimpanzee 1 — 1 —
Deer 1* 1* — — *Ghoshal (1933-34)
Poultry
(Fowl, duck, goose,
24 — — 24
turkey, pigeons)
**Numbers without asteric marks have been typed at I.V.R.I. Izatnagar (Lall, 1969)
and primates by human type of tuberculosis
(Table 2) however, is explainable by close
association of these animals to human beings,
or feeding on leftovers of the human food etc.
Tuberculosis of cattle due to human type of
tubercle bacilli have also been recorded,
(Chandrasekhar and Ram Krishnan, 1969;
Chandrasekharan Nair and Ramkrishnan,
1969).
Cultural and staining methods
Most of the workers used Dorset egg
medium, glycerine potato, glycerine broth etc.
The earliest work was done by Nagrajan (1948-
49) to type out the tubercle bacilli responsible
for tuberculosis in cattle of Madras city, which
yielded bovine type of organisms, growing on
nonglycerinated Dorset’s egg medium. At
I.V.R.I. (1952-53) work was done, without
sucess, to use ammonium malate and ammonium
succinate in place of asparagin in Henley’s
and Dorset’s medium in order to evolve a
cheap medium for large scale cultivation of
organisms for tuberculin preparation. However,
similar work in 1942-43 indicated good
growth of avian strains on such media.
Matheson and Ayyer (1929-30) studied the
Ind. J. Tub., Vol. XXI, No. 1
efficacy of various staining methods such as
Zehl Neelsen’s, Spangler’s and ‘Alkali-fast’
method of Schulte-Tigger’s for staining of
acid-fast organisms in the tuberculous materials
from different animals and man. They found
Spangler’s method to be better giving, more
counts of bacteria in stained, tuberculous
material.
Pathology
The exact mode of infection, susceptibility,
the comparative incidence of parenchymatous,
lymphatic, intestinal or respiratory lesions in
cattle has not been well explored in India. It
was considered by most of the earlier workers
that bovine type of lesions in India are usually
minute and localized (non progressive lesions)
with only a few cases of generalization (Datta,
1934-35). However, at present it seems difficult
to give any clear cut explanation as to
why indigenous cattle show non-progressive type
of lesions as compared to those observed in
cattle of western countries (Dhanda and Lall,
1959).
Tulsaram and Sharma (1955) have reported
the following data on the basis of post mortem
examination of animals which died at the

Government Livestock Farm, Hissar. The
incidence of military tuberculosis was 15 per
cent. More than 80 per cent of the animals
showed lesions localized in mediastinal or
bronchial lymph nodes. Cases of generalized
tuberculosis did not exceed 5 per cent.
The incidence of pulmonary tuberculosis in
the buffaloes slaughtered in UP was 8.43 per
cent at Gorakhpur, 0.58 per cent at Mathura
and 0.44 per cent at Kanpur. The lesions were
distributed in all the lobes of both the lungs,
but more commonly in the diaphragmatic.
The lesions were usually typical, capsulated
nodules, 0.5 to 2 cm. in diameter, with calcification
in about 8 per cent cases. The adjoining
lung parenchyma revealed peribronchial fibrosis
and the atelectasis of alveoli. The mediastinal
and bronchial lymph nodes were involved in
50 per cent cases, with adhesions to pleura.
Histopathological examination of lungs of
buffaloes revealed the characteristic picture of
tuberculous nodules (Dwivedi and Singh, 1966;
Rathore and Singh, 1968). The bronchial
epithelium revealed papillomatous hyperplasia.
In some cases the caseous material rich in
tubercle bacilli were found to communicate
with the lumen of the bronchioles (Dwivedi and
Singh, 1966).
Pulmonary tuberculosis has been known to
occur as early as 2 months after congenital
infection in a calf (Singh and Singh, 1971).
Basu et al. (1967) reported tuberculosis in a
Jersey bull which had also concomitant infection
of brucellosis. Bronchial and mediastinal
lymph nodes with or without pulmonary tuberculosis
appear to be most frequently encountered
in Indian cattle, as revealed by post
mortem examination in Lahore (Singh, 1940),
Calcutta (Guha and Sarkar, 1970), and Bihar
(Singh and Prasad, 1969).
In the museum specimens (about 15 cases
of pulmonary tuberculosis) kept in the College
of Veterinary Sciences, Hissar, the authors have
found all the types of pulmonary tuberculosis
described in man, i.e., the miliary nodules, the
large encapsulated tuberculous nodules and
tuberculous bronchopneumonia with formation
of vomicae. There are about five specimens
of pleura and peritoneum showing typical
‘Pearl’ lesions of bovine tuberculosis, which
represent a cluster of typical closely placed
tuberculous nodules under the shining, smooth
serous surfaces. Tuberculous peritonitis has
also been described in buffaloes by Shukla and
Singh (1972).
Systematic examination of 224 cattle, which
died in the cattle ward of Bengal Veterinary
TUBERCULOSIS IN ANIMALS IN INLMA-A REVIEW 27
college, revealed 64 cases of tuberculosis having
the frequency of the lesions to be 100 per cent
in the lungs and mediastinal lymph nodes,
32.81 per cent in the mesenteric lymph nodes,
9.37 per cent in pleura, 6.25 per cent in retropharyngeal
lymph nodes, liver and pericardium,
4.68 per cent in intestines and udder, 3.12 per
cent in hepatic lymph nodes and myocardium
and 1.56 per cent in the uterus, illiac lymph
nodes and spleen (Guha & Sarkar, 1970). It
appears from these observations that the respiratory
tract is the route of infection as compared
to the infection through the digestive tract.
Kidneys affected with tuberculosis have been
observed in two cases, both in the bulls. One
bull had a primary infection in the lungs, and
secondary, bilateral, miliary tuberculosis in the
kidneys (Monanty, 1970). The second case,
involved kidneys with metastasis in prostrate
and testicle. In the kidneys, typical nodules
developed following arrest of the emboli in the
glomeruli (Bhambani, 1969).
Intestinal tuberculosis might possibly be
due to secondary infection through swallowing
of infective sputum by animals as seen in only
3 out of 64 tuberculous cattle examined by
Guha and Sarkar (1970). Chanderashekharan
Nair and Ramkrishnan (1969) found the
intestinal (jejunum and ileum) and hepatic
lesions in a calf, which were millet seed sized,
while the mesenteric lymph nodes were converted
into bags of caseous material. One case
was observed by the authors which revealed
nodules of about the size of pea in the intestines
while those in the mesenteric lymph nodes,
liver, lungs and spleen were one to several
centimeters in diameter. Histologically, the
intestinal lesions appeared similar to the regressing
intestinal lesions of tuberculosis describad
by Cohrs (1967).
Verma (1963) found two affected livers
from 340 cattle and buffaloes slaughtered in
Jabalpur city, while the lungs from 390 bovines
from the same source, revealed only
one case of tuberculosis which also secondarily
involved due to generalization (Gupta, 1965).
Genital tuberculosis
Aziz-ud-din (1948-49) studied 230 uteri
from slaughtered bovines. Two of these revealed
numerous pin-head to lentil sized nodules
in which acid fast bacilli identical to M. tuberculosis
could be demonstrated. One of these
two cases was very good example of descending
infection evidenced by the involvement of
peritoneum, broad ligaments, ovaries, fallopian
tubes and the horns of uterus. Deshpande et
al. (1966), however, found variable sized nodu-
Ind. J. Tub., Vol. XXI, No. 1

28 H.V.S. CHAUHAN, D., P. DWIVEDI, S.S. CHAUHAN AND D.S. KALRA
les with calcification in a case of tuberculous,
endometritis in a buffalo. Bhandari et al.
(1967) reported a single case of uterine tuberculosis
amongst 139 genitalia of buffaloes
examined by them. Guha and Sarkar (1970)
found uteri to be affected only in 1.56 per cent
of the 64 cases of tuberculosis examined by
them.
Sane et al. (1959) reported 8 cases of tuberculous
endomeritis and one of them was
accompanied by tuberculous salpingitis. In a
case of pulmonary tuberculosis, De and Basu
(1967) found miliary nodules in the uterine
mucosa of a pregnant cow, but none in the
placenta and foetus of 3-4 months gestation.
Ganapathy et al. (1968), however, found tuberculous
endometritis, in a case of generalized
tuberculosis, in a cow and its 6 months old calf.
Similar cases of congenital tuberculosis in
calves have been recorded by Singh and Singh
(1971).
A case of endometritis caused by atypical
M. tuberculosis of human type was recorded
by Chandrasekharan Nair and Ramkrishnan
(1969), which was accompanied by lesions in
lungs, liver, lymph nodes, intestines mesentery
generalized tuberculosis in its calf. Histopathologically,
there was proliferation of
endometrial stroma, atrophy of glands, infiltration
of plasma cells, lymphocytes, epitheliod
cells and giant cells in the nodules which
grossly varied from 0.5 to 2.0 cm, in diameter.
Tuberculous Mastitis
Mills (1898-99) recorded the first positive
case of tuberculous mastitis (tuberculin positive)
in a cow which later revealed typical tuberculous
lesions in the lungs and udder. Its milk
produced persistent diarrhoea in a European
child and its own calf which died later.
Presence of tubercle bacilli in milk sample was
investigated in Bombay city by Joshi (1914),
and out of 674 samples examined, he found
acid fast bacilli in 7.6 per cent (47) cases.
Gloster (1914), however, could not produce
tuberculosis in guinea pigs inoculated with
sediment from 101 milk samples. Examination
of fairly large number of milk samples from
tuberculin positive cows have been found to
be negative (Mallick et al, 1942; Sahai and
Dhanda, 1942-44; Folding, 1945; Rajagopalan,
1949). One case of tuberculous mastitis was
recorded by Naik (1932), two cases in military
dairy farms (Annual report, I.V.R.I. 1932-33,
1940-41) and one more is on record in the
Annual reports of I.C.A.R. (1941-42).
Singh et al. (1956) described a case of
tuberculous mastitis, caused by bovine type of
Ind. J. Tub., Vol. XXI, No. 1
organisms in a cow affecting one quarter which
was hypertrophied and indurated but without
heat or pain. The affected quarter weighed
10 Ibs and represented a case of diffuse caseous
type of mastitis. Teat canal contained nodules
of different sizes. Left lung, pleura, kidneys,
supra mammary, bronchial, mediastinal and
prescapular lymph nodes were also involved.
Many of the in-contact calves were shown to
become reactors to tuberculin.
A case of tuberculous mastitis with nodular
type of lesions in the left half of the gland and
supramammary lymph node with possible
infection through teat canal (since no lesions
were found else-where) was recorded by Prasad
et al. (1967). Two cases of proliferative type
of tuberculous mastitis were observed by the
authors out of autopsies conducted (1965 to
1972) at Veterinary College, Hissar. Tuberculous
mammary lesions were reported to be
quite common in Tharparkar cows in Bihar
(Singh and Prasad, 1969). In the autopsy
examination of 64 tuberculous cows the incidence
of mammary tuberculosis in Calcutta
was found to be as high at 4.64 per cent (Guha
and Sarkar, 1970).
Tuberculous mastitis in buffaloes seems to
still await investigation. Since there is only
one case on record, (Mandal and Iyer, 1969),
it can very well be deduced from the above
mentioned cases that tuberculous mastitis can
be a dangerous source of spread of the disease
to the animal attendants and children, besides
the suckling calves as also suggested by Singh
and Sengupta (1957).
Clinical pathology
Clinical pathological studies in cattle have
been confined mostly to haematology
(Ganpathy et al., 1968; Chandrasekharan Nair
and Ramkrishnan, 1969; Prasad and Singh,
1969; Singh and Prasad, 1969) found slight
neutropaenia and lymphocytosis, but no significant
change in E.S.R. value in cattle, reactors
to tuberculin. De and Basu (1967) found the
temperature varying between 101.6° to 102.8° F
in a case of pulmonary and genital tuberculosis
which died shortly thereafter.
In horses, certain haematological values in
reactors to tuberculin have been studied by
Singh and Prasad (1970); but these studies
require further work to draw any conclusive
results.
Diagnosis
(i) Subcutaneous test
According to the routine instructions laid

TUBERCULOSIS IN ANIMALS IN INDIA-A REVIEW 29
down (Annual Report. I.V.R.I. 1951-52) for
standardizing tuberculin for subcutaneous use
in cattle, each new brew has to be tested on
2 healthy and 2-3 sensitized bovines. Each
animal is infected with 3 ml. of new brew and
temperature reaction is observed at 9, 12, 15, 24
and 48 hours after injection. The brew is
passed if the healthy bovines do not show any
rise in temperature beyond 1°F (at the most)
and the sensitized bovines show a gradual rise
of temperature up to 2 °F or more.
It has been observed that the sensitized
bovines after a few tests become allergic and
fail to show thermal reactions, even with
standard brew. Secondly the sensitized bovines
are very expensive to maintain throughout
the year. So work was undertaken to see if
sensitized guinea pigs can be used for the
purpose or not. The results were favourable.
(2) Double intradermal (DID) test
Since there are considerable diurnal variation
of temperature in India, the double
intradermal test as recommended by British
Tuberculin Committee of Medical Research
Council (1925) has been adopted in preference
to subcutaneous test.
(3) Single intradermal test
Under field conditions in India it is very
difficult to collect the animals for second
injection, then again for final reading. With
this view, work was undertaken at I.V.R.I, to
see if the single intradermal (SID) test was
reliable or not. For this purpose, synthetic
heat concentrated tuberculin was used (Annual
Rep. I.V.R.I., 1953-54). A total of 20,197
cattle were tested both by SID and DID, for
this purpose. Analysis of the data showed that
single intradermal test was equally good but
the doubtful cases should be tested by DID
test.
DID test appears to be satisfactory for
diagnosis of tuberculosis in horses. There was
hot, painful swelling with an increase in the
thickness of skin 16.8mm (PCuppuswamy and
Singh, 1968). Swelling with avian tuberculin
in horses was less (6.9 mm) than with
mammalian tuberculin (Singh and Kuppuswamy,
1971).
(4) Indirect Haemagglutination (IHA) test
Recently, Shukla and Singh (1972) concluded
on the basis of tuberculin test, presence of
gross lesions of tuberculosis and indirect
haemagglutination (IHA) test, that IHA was
very sensitive and could detect early and
advanced tuberculosis in buffaloes where
tuberculin test failed.
Tuberculin for Diagnosis of Avian Tuberculosis
A brew of tuberculin prepared from avian
tubercle bacilli, recovered from birds other
than ducks, did not elicit a reaction in infected
ducks, at Military Poultry Farm, Nagpur,
where considerable mortality from tuberculosis
occurred (Annual Rep. I.V.R.I., 1942-48). For
intradermal test in birds various sites were
tried and neck was found to be the site of
choice (Annual Re. I.V.R.I., 1947-48).
No lesion Tuberculosis
Soparkar (1927) was able to isolate fully
virulent tubercle bacilli from material of a
reactor to subcutaneous tuberculin, although
no naked eye lesions were detected on slaughter
and a similar case has been encountered at
Mukteshwar (Datta, 1934-35).
Considerable amount of work has since
been done in this direction (Annual Rep.
I.V.R.I., 1951-52). In conducting tuberculin and
Johnin tests (Johne’s disease is a chronic granulomatous
enteritis of cattle and sheep caused by
acid fast bacilli-Mycobacteriumparatuberculosis)
it was believed that ingestion or wound infection
of saprophytic acid fast bacilli, such as
M. Phlei, or M. Smegmatis could give positive
tests. Two hill bulls and two goats negative
to mammalian and avian tuberculin, Johnin and
Phlein, were fed with M. Phlei on alternate
days in measured doses for 3 months, but no
allergen gave positive test and no gross lesions
were visible at post-mortem. Similarly, nine
guinea pigs negative to repeated tests with
mammalian and avian tuberculin, Johnin,
Phlein, Smegmatin and Stercusin, were injected
subcutaneously, in batches of three, with M.
Phlei, M. Smegmatis and M. Stercoris in doses
of 10 mg. in 0.5 ml. of olive oil and 50 mg. of
pumice stone. Ten weeks after inoculation,
these were again tested with different dilutions
of all the allergens. Typical reactions to
hemologous as well as saprophytic groups of
allergens were observed; but none showed any
reactions to mammalian and avian tuberculin
and Johnin.
Lall et al. (1969) also observed that guinea
pigs, goats experimentally infected with M.
Phlei, M. Smegmatis and M. Stercoris failed to
show cross-allergy to mammalian or avian
tuberculin on ingestion or inoculation.
Prevention
The calves vaccinated with B.C.G. are more
Ind. J. Tub., Vol. XXI, No. 1

30 H.V.S. CHAUHAN, D., P. DWIVEDI, S.S. CHAUHAN AND D.S. KALRA
resistant than non-vaccinated ones. Spahlihger’s
vaccine has also given encouraging results
in the initial trial, but little is known further
about it (Datta, 1934-35). Rajagopalan (1948)
suggested that the B.C.G. vaccination could be
useful only when the incidence of the disease
was low, whereas if it is extensive it will be
difficult to use the vaccine owing to its own
limitations under Indian conditions. Now
since the incidence of the disease, at least, in
the organized farms is fairly well known, and
the time, in our opinion, is ripe for adopting
vaccination where needed, as in the case of
human beings. It appears from the available
literature, that very little work has been done
in India in this direction.
Control and eradication
Finland was probably the first country to
eradicate the disease in animals in 1899. Some
countries followed the method of ‘test and
slaughter’. Such a plan is, however, not
practicable in India, (Lall et al., 1967). Moreover,
attempts to carry on control have been
stymied by the prohibition against slaughter of
cows. What to do with the tuberculin reactors
when they are identified, has not been resolved,
except to turn them out of the stable to become
wanderers, spread disease and die. The cost
of taking care of old and useless cows in India
has been estimated to be about one billion
rupees annually, which is being collected by the
holy men who maintain goshalas or cow sheds
(Myers and Steele, 1969).
Secondly, animals in India do not develop
progressive type of disease. Therefore the
best approach appeared to be ‘test and segregation’,
although the ‘test and slaughter’
method was sure, easy and quicker. Practicability
of the former method was demonstrated
by Sahai and Dhanda (1943-44), who successfully
controlled the tuberculosis at Government
Cattle Farm, Hissar. Dhanda and Lall (1959)
suggested to establish reactor farms, on coopetive
or Government level to segregate the
reactors. They were unaware of the usefulness
of the vaccine for eradication, as no such large
scale work was done in India. For eradication
of the tuberculosis, the following steps were
taken.
(1) Testing of entire stock at quarterly
intervals firstly, then at 6 monthly interval and
later, when incidence was low, at yearly
interval.
(2) Segregation of the tuberculin positive
cows and bullocks in a separate block, far
away from the clean (negative) herd. The
Ind. J. Tub., Vol. XXI, No. 1
progeny of the positive cows were allowed
suckling till 5 to 6 months of age, when they
were weaned and tested twice, at one month’s
interval. The reactors were retained at the
segregation block and the negative progeny
was immediately transferred to clean herd.
(3) The clinical cases were allowed to die
a natural death and not by slaughter.
(4) The bulls used for breeding were
either healthy tuberculin negative ones or in the
absence of these nonclinical but tuberculin
positive.
Tulsaram and Sharma (1955) found that
4.53 per cent of the calves born from tuberculin
reactors were tuberculin reactors as compared
to 3.15 per cent born from nontuberculin
reactor cows at the Government Livestock
Farm, Hissar.
Chemotherapy
Forty five chemotherapeutic substances
were tested at I.V.R.I. (Annual Rep. I.V.R.I.,
1955-56). Out of these N4-pheyal-L-Pyridil-paratolyl-amidine,
and N4 benzylla kinople-phenyle
were found to be comparable in their activity to
well known anti-tubercular compounds like
para aminosalicylic acid (PAS) and isonicotin
hydrazid. Cultures of mycobacte-rium were of
strain PN—a human virulent type maintained at
I.V.R.I, which was passaged occasionally
through guinea pigs to maintain virulence.
Results after one month’s incubation showed
that no organisms were viable.
In vitro studies with ‘Amritcos’, an indigenous
drug, revealed that the drug had no
inhibitory action on M. tuberculosis or therapeutic
effect on the diseased guinea pigs
either.
Tuberculosis in sheep and goats
Upto 1932, not a single case of caprine or
ovine tuberculosis was recorded, although
Royal Commission on Human and Animal
Tuberculosis (1907) has shown that goats are
very susceptible to bacilli of bovine type. Iyer
(1932) recorded 6 cases out of 943 goats examined
at post mortem (0.64 per cent). The
first authentic record of tuberculosis in a sheep
of Haryana State was made by Nanda and
Karnail Singh (1944). Nanda and Gopal
Singh (1943) reported five cases in caprines in
Haryana State. Radhey Mohan (1950-51), on
examination of 1602 carcasses, found lesions in
11 female and 3 male goats (0.87 per cent) in
Punjab. Tuberculin testing at two sheep farms

TUBERCULOSIS IN ANIMALS IN INDIA-A REVIEW 31
in Bombay state showed incidence of 3.7 per
cent and 6.3 per cent and tuberculin testing of
45 goats at Bombay and 133 goats at Mukteshwar
(U.P.) revealed 6.6 per cent and 13.5 per
cent goats to be positive and doubtful reactors
respectively (Singh, 1951). Lall (1964) found
0.39 per cent goats positive to tuberculin out
of 501 animals tested in the state of U.P.,
Kerala and Himachal Pradesh. Limited
number of tuberculin tests in goats and sheep
revealed 0 per cent incidence in Mysore (52
tested), 0 to 1.6 per cent in Punjab (690 tested),
1.1 to 2.3 per cent in Madras (223 tested) and
2.5 per cent in I.V.R.I. (81 tested).
The lesions were found mostly in the bronchial,
pharyngeal, mediastinal, mesenteric and
portal lymph nodes and in the lungs alone or
including mediastinal lymph nodes (Iyer 1932;
Radhey Mohan, 1950-51). The lesions varied
from the size of pin head to a tennis ball with
calcification in the older ones (Radhey Mohan,
1950-51).
Cultural examination on serum agar, glycerine
broth and glycerine potato after treatement
with antiformin showed scanty fine net like
growth after 4 weeks (Loc. cit). Iyer (1934)
found the biological tests positive in rabbits
(2 out of 6 cases) and negative in fowls. The
causal organisms responsible for the disease
appear to be of bovine type (Table 2). Radhey
Mohan (1950-51) demonstrated acid fast organisms
in the milk samples from 332 goats
(after treatment with antiformin).
Tuberculosis in dogs
Ajwani (1932-33) recorded tuberculosis
in dogs in Madras for the first time in India.
One dog revealed intestinal form and another
pulmonary form of tuberculosis. Out of 35
dogs tested at Bombay Veterinary College, 8
gave positive tuberculin test and one was a
doubtful reactor (Bhatia, 1960). Out of four
positive cases examined at post mortem, three
showed lesions in kidneys and liver from which
M. tuberculosis was isolated. The fourth dog
showed no lesions. The causal organisms
appear to be mostly of human type (Table 2).
Tuberculosis in pigs
Datta (1934-35) has described occurrence of
tuberculosis in 4 par cent pigs slaughtered in
Bandra, Bombay. Dhanda (1941-43) reported
porcine tuberculosis from the pigs slaughtered
in Bombay (17.7 per cent), Jullundur (0 per
cent) and Rawalpindi (7.4 per cent). The
results of 22 cultural isolates of mycobacteria
of porcine orgin (Table 2) have been stated by
Lall (1969).
Panduranga Rao and Venkata Narayan
(1965) observed two cases of tuberculous bronchopneumonia
even in 6 month old piglets in
Andhra Pradesh.
Sadana (1973) examined 2187 pig carcasses
in Delhi, Haryana and Punjab states, which
revealed tuberculosis in 11 cases. Three of
them revealed miliary lesions in the lungs and
lymph nodes while in the remaining only lymph
nodes (bronchial and mediastinal) were involved.
Bhattacharya et al. (1972) examined 100
pigs slaughtered for food in Calcutta, in which
tuberculous lesions were found in lymph nodes
(submaxillary, gastro-hepatic and cervical in
decreasing order) in 37 cases including one
having small foci in lungs and spleen. Eleven
of the affected pigs had given positive tuberculin
reaction prior to slaughter (8 for mammalian
and 3 for avian tuberculin). Results of
the cultural examination have been shown in
Table 3.
With reference to Table 2, it can be seen
that 17 out of 26 cultural isolates from pigs
were of human type, 7 of bovine and 2 of
avian types. The high rate of human tuberculosis
in pigs apparently is due to feeding of
garbage and human excreta. This needs more
attention from the point of view of zoonosis.
Tuberculosis in other animals
The evidence of tuberculosis in primates in
India was available as early as in the year 1906.
The disease was recorded in primates in Bombay
(Soparkar, 1924), Bengal Veterinary
College Zoological gardens, Calcutta, Madras
and Delhi (Malik, 1967). In Bombay, it was
alleged to be bovine type of tuberculosis transmitted
through Llamas imported from
Germany. In most of the cases human type
of tubercle bacilli were isolated. The disease
has also been recorded in deer (Ghoshal, 1933-
34), horses (Narayanan, 1925; Kuppuswamy
and Singh, 1968; Singh and Prasad, 1970),
elephants (Iyer, 1937), sambur, antelope,
nilgai, spotted deer, monkey, cat etc. (Datta,
(1934-35; Lall, 1969). A total of 178 camels
were tested in Haryana and Bikaner (from
1960-67), out of which 8 animals (4.5 per cent)
were found positive reactors (Final rep,, D.I.O.
camels, Punjab, 196-67). Kuppuswamy and
Singh (1968) found 9 horses to be positive out
of 160 animals tested by them. Singh and
Kuppuswamy (1971) further tested 87 horses
out of which 38 horses (34 to mammalian and
4 to mammalian and avian tuberculin) were
positive,
Ind, J. Tub., Vol. XXI, No. 1

32 H.V.S. CHAUHAN, D., P. DWIVEDI, S.S. CHAUHAN AND D.S. KALRA
TABLE 3*
Table showing the results of tuberculin sensitivity and the type of tubercle bacilli isolated from pigs.
Tuberculin
Test
Type of tuberculin
sensitivity
Presence or
absence of
lesions
Results of cultural examination
mycobacteria of type
Bovine Human Other Myco
bacteria
Positive
Mammalian
11 pigs (8 cases)
Negative
(89 pigs)
Avian
(3 cases)
*Taken from Bhattacharya et al. (1972)
Bopayya (1928-29) recorded tuberculosis in
two elephants belonging to Coorg Forest
Department. Director, I.V.R.I, and Principal,
Madras Veterinary College reported the sputum
smears from the elephant (32 year old) to be
positive for tuberculosis. Nodules with caseous
material were found in large intestine,
spleen, pleura and lungs (the elephant used to
suffer from spasmodic colic an year or two
before euthanasis).
Avian tuberculosis
In India the disease has been recorded in
parrots, pigeons, fowls and ducks. In the
parrots and pigeons, human type of bacilli have
been found to be responsible for the disease
(Datta, 1934-35). Cases of tuberculosis have
been recorded in a whistling swan (Iyer and
Nanda, 1966), a silver pheasant (Mohanty and
Patnaik, 1969), a crow in Kerala (Mariamma
et al., 1971) and in a Demoiselle crane (Damodaran
and Thanikachalam, 1972).
Bhasin (1961) recorded a case in deshi cock
in Jabalpur in which all the organs and bones
were involved. Bhatia (1960) found only two
affected birds out of 1022 birds examined by
him in Madras, Bombay, Kerala and PEPSU.
Early cases of tuberculosis in ducks were
Reactors
with
lesions-5
2 — —
No lesions
reactors-3
— — —
Reactors
with
lesions-1
— — 1
No lesions
reactors-2 — — —
Non-reactor
with lesions-31 1 1 3
Non-reactor
without
lesions-58
— — —
reported from Mysore State by Naidu (1943)
and Mohteda (1244), but the authentic report
was published by Zargar (1946). Gurumruti
(1962) conducted systematic studies on tuberculosis
of ducks in Andhra Pradesh where 139
ducks (out of 1212) died in a period of 8
months (11.4 per cent). The symptoms of
gradual emaciation, dullness and ruffled feathers
were observed. Singh et al. (1967) isolated a
virulent strain of M. avium from natural outbreak
of disease in ducks in Andhra Pradesh.
Mallick et al. (1970) observed a natural outbreak
on a farm in West Bengal with 6 per cent
mortality.
Gross lesions, observed in 437 ducks
(Gurumurty, 1962) were seen in liver (305),
lungs (708), spleen (60), mesentry and omentum
(58), bone marrow (47), kidney (15), ovary and
testes (13/3), intestines (8) and other organs (3).
The lesions started as greyish yellow irregular
foci which later became enlarged and nodular
(Gurumurti, 1962; Singh et al., 1967; Mallick
et al, 1970).
Microscopically, the lesions revealed calcification
only occasionally and giant cells in
avian lesions are reported to be very few
(Gurumurti, 1962). Kwatra (1967), however,
observed calcification in most of the lesions of
ducks.
Ind. J. Tub., Vol. XXI, No. 1

TUBERCULOSIS IN ANIMALS IN INDIA-A
REVIEW
33
For isolation of organisms, only Lowenstein
Jensen medium and glycerine egg yolk agar
were found satisfactory (Gurumurti 1962).
Gurumurti (1960) found that the subcutaneous
test was the only method available to
detect tuberculosis in ducks. The rapid plate
whole blood agglutination test was unsatisfactory
when tested in 100 ducks (Gurumurti,
1962).
Singh et al. (1967) considered intradermal,
subcutaneous tuberculin tests in the food web,
direct tube agglutination and rapid plate
agglutination test to be of no use in the
diagnosis. However, Kwatra et al. (1967)
found passive haemagglutination test (PHA),
using sheep red blood cells, sensitized with
protein purified derivative (PPD) of M. avium
origin to be very sensitive, even for early cases,
giving 1: 120 serum titre. Kwatra et al. (1972)
further reported that PPD derived from M.
tuberculosis (human), M. bovis (mammalian
tuberculin) and M. paratuberculosis (Johnin),
also gave equally sensitive results with passive
haemagglutination test.
Summary
A comprehensive review of work done on
tuberculosis of different species of animals,
including poultry, has been presented. The
review beginning from the earliest record of the
disease, in the first decade of this century, when
it was considered to be a rare, nonprogressive
type of disease, to the latest work done on the
incidence, typing of the organisms, pathology,
clinical pathology, diagnostic procedures,
chemotherapy, control and eradication etc.
has been compiled. Care has been taken to
mention the zoonotic aspects and the areas
where further work is needed.
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Ind. J..Tub., Vol. XXI, No. 1

CASE REPORT
TOXIC EPIDERMAL NECROLYSIS DUE TO THIACETAZONE
F. HANDA, KAMLESH KUMAR AND RADHA RANI
(From Govt. Medical College, Patiala)
In 1956, Alan Lyell 1 , reported four cases in
adults of a condition resembling widespread
scalding of skin. He suggested the appelation
“toxic epidermal necrolysis” (TEN) because he
considered that it was the result of necrosis of
the epidermis due to toxaemia. The disease
consists of a prodrome of malaise, lethargy
and fever followed by erythema and massive
flaccid bullae formation. Nikolsky’s sign is
usually positive. The mucous membranes
especially of the mouth are involved in almost
half of the cases and there may be an associated
bullous haemorragic ulcerative stomatitis and
conjuctivitis. Healing with little or no scarring
occurs in most of the patients, 10-14 days after
the bullae have formed. Death occurs in upto
30 per cent of the cases and apparently is the
result of toxaemia affecting various organs of the
body. Histopathologically, there is massive
epidermal necrosis and vesication at the dermoepidermal
junction but the dermis is relatively
normal.
Since the use of antimicrobial agents is
steadily increasing, it is not unexpected that
some patients occasionally experience unusual
and often severe or even fatal sensitivity
reaction of these agents. Despite a great
many case reports of TEN induced by various
drugs, 2 - 13 to our knowledge, there has been no
case documentation in the world literature due
to thiacetazone, which has led us to record
in this communication, two cases of this entity
due to thiacetazone sensitivity.
Case reports
Case I : A 35 year old labourer, with
pulmonary tuberculosis, was on parentral
streptomycin (1 G. daily) and oral I-sozone i.e.
combination of thiacetazone and isoniazid,
(2 tablets daily). About 1½ months later he
had fever, generalised intense erythema and
swelling followed by massive desquamation
of large sheets of the epidermis and
multiple flaccid bullae. He was hospitalised
in Skin inpatient department of Rajindra
Hospital, Patiala on 2. 12. 72. Past history
was noncontributory. His younger brother
too had pulmonary tuberculosis.
Clinical Evaluation; Patient appeared
acutely ill. He was obviously in pain with
slightest movement. Temperature—103° F
Pulse rate—120 minute, Blood pressure—125/80
mm Hg. Respirations 36/minute. The breath
was foul and medium to coarse crepitations
were audible in the lung bases. No cardiomegally
or sinus tachycardia. No neurological
deficit was found. Local examination revealed
an appearance simulating widespread burns.
Large flaccid bullae were present on the trunk
and extremities. Randomly placed were few ruptured
bullae with raw areas. Nikolsky’s sign was
positive and epidermis could be easily removed
in sheets. Face was crythematous, oedematous
with bilateral kerato-conjunctivitis and lid
injection. There were erosions on the buccal
mucosae, tongue, lip prepuce and glans penis.
Laboratory Investigations; Routine tests
were within normal limits. Blood urea, fasting
blood sugar, serum proteins (total and differentia!)
throat swab culture, and urine culture,
were normal. B.S.R. 48 mm Westergrens. X-ray
chest: Right lung showed cavitation with
interlobular infiltrations. Sputum for acid
fast bacilli prior to his hospitalisation was
positive. Tzanck test was negative. Skin
biopsy was non-contributory (most probably
because biopsy was done from a healed
pigmented patch, when the bullae had disappeared).
Basophil degranulation test (BDT)
for thiacetazone sensitivity was positive,
(4 + , Fig.l).
Administration of parentral Dexamethasone
2 mg. four times daily and tetracycline 100 mg.
three times daily was started immediately.
After 4-5 days, patient became afebrile, his
general condition improved immensely, and
bullae healed leaving pigmented spots. He was
again put on intramuscular streptomycin
(I G. daily), after a week isoniazid (300 mg.
daily) was also added. For kerato-conjunctivitis
atropine eye ointment 1 per cent and
soframyclne eye drops were also started.
Steroids were gradually tapered off and ultimately
arrested after two months. After the
start of streptomycin and isoniazid the
patient was observed for three months but
the lesions did not relapse. Hence, TEN was
suspected due to thiacetazone only which was
further corroborated by positive BDT for
thiacetazone.
Case II; A 10 year old girl was admitted
in Tuberculosis and Chest Diseases hospital,
Govt. Medical College, Patiala with pulmonary
Koch’s infection. She was started on Unithiben
i.e. combination of thiacetazone and isoniazid
Ind. J. Tub., Vol. XXI, No. 1

TOXIC EPIDERMAL NECROLYSIS DUE TO THIACETAZONE 37
mycin (Ig. daily) and isoniazid (300 mg, daily)
were started without any adverse sensitivity
reaction on observation for many months,
which led us to conclude that TEN was due to
thiacetazone only and it was further substantiated
by positive BDT for thiacetazone (3).
Fig. 1
Basophil cells are swollen. Cell walls are fuzzy.
Granules are streaming out of the ruptured cell
wall showing palisading.
(4 tablets daily). After 2 weeks, fever, painful
oedema and erythema of the face, bilateral
conjunctivitis, lip erosions ensued followed by
generalised erythema, multiple, flaccid bullae.
Rupture of the bullae was followed by
sloughing of large sheets of skin exposing an
intensely erythematous, moist, exuding base,
characteristic of TEN. Nikolsky’s sign was
produced with only slight pressure.
Laboratory Investigations: Routine tests
were normal. Urine culture, blood urea,
serum proteins (total and differential) were
also normal. X-ray chest favoured lesions of
pulmonary tuberculosis (bilateral infiltrations).
Sputum for acid fast-bacilli was positive.
However, skin biopsy could not be performed.
Patient was immediately started on oral
Prednisolone 30 mg daily, antihistaminics
(Pheniramine maleate, orally 25 mg four times
daily) and soframycine eye drops for conjuctivitis.
After 7-10 days, her general condition
bettered and discharge from the eyes ceased.
Cutaneous blisters also resolved. The prednisolone
was diminished gradually as the
condition improved. After 2 weeks, strepto-
Discussion
Toxic epidermal necrolysis is a cutaneous
reaction pattern of multiple causation. Various
etiologies have been proposed but the drugs
have been found to be the chief incriminating
agent. Lyell 15 (1967) defined four etiological
groups of TEN. The first group, the Ritter’s
type of TEN, is composed mainly of infants
and children, where infection with staphylococcus
aureus, group 2, phage type 71, seems
to be of etiological importance. The second
group was termed drug-produced TEN and
occurs primarily in adults. Drugs usually
incriminated in producing TEN, are penicillin 2 ,
sulphonamides 3 , phenyl butazone 2 3 4 5
phenolphthalein 3 and hydantion 6 . Other drugs
recorded are ipecac and opium powder 7 , oil of
chenopodium 8 , neomycin sulphate 9 , mesantion
10 , gold salts 11 , antipyrine 12 , acetazolamide 12 ,
barbiturates 13 , polio immunisation and diptheria
inoculation 7 and tetanus antitoxin 13 .
In the third group TEN was attributed to
a variety of underlying illnesses. The fourth
or idiopathic group was composed of children
whom Lyell 15 suspected as having undiagnosed
staphylococcal infection and elderly women
who were subject to repeated attacks of TEN.
According to the above criteria, both of our
patients belonged to Lyell’s second group.
Amazingly, no case of TEN due to thiacetazone
thus far has been reported in the world. In
both the cases (1 and 2) reported above,
occurrence of TEN about 6 weeks (case 1) and
2 weeks (case 2) after the commencement of
isozone and unithiben (both being combination
of thiacetazone and isoniazid) respectively,
recovery after its withdrawal, reinstitution of
rest of two drugs (streptomycin and isoniazid)
without any reaction and positive BDT for
thiacetazone, suggest that although thiacetazone
may not be the actual cause, it may be the
crucial precipitating allergic, factor in the
production of this syndrome. Hence one
should be mindful of the possibility of this
complication besides the other known toxic
reactions associated with thiacetazone administration.
The pathogenesis of TEN still remains
unclear. Rook 15 agreed with Lyell 1 that
epidermal necrolysis is a destructive reponse to
toxaemia of unknown nature. It may be a
Ind. J. Tub., Vol. XXI, No. 1

38 F. HANDA., KAMLESH KUMAR AND RADHA RANI
nonspecific reaction to more than one toxic
or infectious agents. Rowell and Thompson 1
believed it to be a toxic eruption due to
multiplicity of causes, including drugs,
infections (bacterial, viral or fungal) blood
diseases, reticulosis and metabolic disorders.
Walker 7 suggested that it is a rare and unusual
lytic manifestation of hypersensitivity and may
even be a transitory auto-immune disease.
Various other theories including an inborn
idiosyncrasy, a modified Sanarelli-Schwartzman
phenomenon have also been mentioned but
some workers believed that the most feasible
theory is that the disease represents an unusual
hypersensitivity state in some people 3 5 6
Beare 13 also reported in one out of his ten
cases drug sensitivity as the likely cause. Our
observations of probable thiacetazone allergy,
supported by positive basophil BDT, further
corroborates the theory of hyper-sensitivity in
the pathogenesis of TEN.
With the increasing use of thiacetazone, as
a replacement of PAS in the treatment of
tuberculosis, in a country like India, where
tuberculosis is still a very common disease, it
may well be that more cases of thiacetazone
induced TEN will be seen in the future.
Summary
Two cases of toxic epidermal necrolysis,
due to thiacetazone sensitivity are reported.
The hypersensitivity mechanism of thiacetazone
induced TEN was further supported by
positive basophil degranulation test in both
the cases.
REFERENCES
1. Lyell, A: Toxic Epidermal Necrolysis: An
eruption resembling scalding of the skin:
Br.J. Derm. 68: 355-361, 1956.
2. Zang, R. and Walker J: Toxic Epidermal
Necrolysis: Report of Four cases. S. Afr. Med.
J. 31: 713-716, 1957.
3. Browne, S.G. and Ridge E: Toxic Epidermal
Necrolysis. BR.Med.J. 1. 550-553, 1961
4. Rowell N. R. and Thompson H. : Toxic
Epidermal Necrolysis in patient with pulmonary
Aspergilosis; Br. J. Derm. 73: 278-283, 161.
5. Oyerton, J: Toxic Epidermal Necrolysis: Associated
with Phenylbutazoue Therapy, Br. J.
Derm. 74: 100-102, 1962.
6. Bailey G. Rosenbaum, J.M. and Anderson B:
Toxic Epidermal Necrolysis JAMA: 191: 107-
110, 1965.
7. Walker J.A. : Toxic Epidermal Necrolysis:
Theoretical considerations regarding its
Etiology and Pathogenesis, Med. Proc. 8: 208-
218, 1962.
8. Bush. R Park R, and Weston H. : Toxic
Epidermal Necrolysis, Report of Four Cases,
N. Zeal, Med. J. 62; 95-97, 1963.
9. Catto, J. V. F. : Toxic Epidermal Necrolysis
occurring in Child. Brit. Med. J. 2; 544-545,
1959.
10. Ruskin, D.B. Culminating Dermatitis Bullosa
Medicamentosa Due to Mesantoin. JAMA. 137:
1031-1035, 1948.
11. Jaerger, H. :Eruption Mortelle due aux selse d’or
erythematobulleuse pemphigoide a marche
rapide. Dermatologica 103: 280-283, 1951.
12. Kennedy, C.B. et al: Dermatitis medicamendsa
due to Antipyrine. A study of 28 cases in
Negroes following use of proprietary medi
cation (666 color preparution) Arch. Derm 75:
826-836: 1957.
13. Beare, J.M. Toxic: Epidermal Necrolysis. Arch.
Derm. 86: 638-653, 1962.
14. Rook, A : Toxic epidermal necrolysis (Lyell)
Arch Beiges dermat el syph 13: 391, 1957.
15. Lyell, A. : A review of toxic epidermal necro
lysis in Britain Br. J. Derm 79: 662-671,
1967
Ind. J. Tub., Vol. XXI, No. 1

REPORTS
THE 22ND INTERNATIONAL TUBERCULOSIS CONFERENCE
The 22nd International Tuberculosis Conference
was held in Tokyo from 24th to 28th
September, 1973. It was attended by nearly
2000 participants. There were nearly 600
delegates from the host country Japan, over
1000 delegates from 81 other countries and
about 400 accompanying persons. The Indian
delegation with accompanying persons consisted
of the following :—
Dr. and Mrs. M.S. Chadha
Mr. B.M. Cariappa
Dr. S.P. Tripathy
Dr. M L. Mehrotra
Dr. and Mrs. M.M. Singh
Dr. T. Manickam
Dr. Ramachandra Reddy
Dr. S.P. Pamra
A meeting of the Council of the International
Union against Tuberculosis was held on
the 23rd September, 1973. The main point
discussed in the meeting of the Council was
the dwindling reserves. The Executive Director
of the Union made a statement to the effect
that there had recently been a fall in the income
of the Union primarily due to arrears
in the contribution of some member
countries and lack of interest in tuberculosis
work in the developed countries which provided
most of the funds of the Union. In addition,
the expenditure of the Union had been consistently
going up owing to increase in staff
salaries and the cost of production of the
Union publications. Several suggestions for
balancing the budget and increasing the reserves
were discussed. The consensus was that
the quota of the constituent members be raised
and suspension of publication of T Bulletin be
looked into. Increased efforts are to be
made to get enhanced contribution from the
developed countries. It was also suggested to
change the name of the Association to “International
Union against Tuberculosis and
Respiratory Diseases” in order to create
interest in the activities of the Union amongst
the developed countries. Efforts are also to
be made to enrol more individual members of
the Union.
The revised constitution of the Union was
also discussed. The main features of ths
revision were that each constitutent country
will be allowed in future to have two Council
members only whereas the number of
Council members at present ranges from
S. P. PAMRA
one to five. The four regions of the Union
will have one representative each on all the
scientific committees of the International
Union.
It was also decided that the next International
Conference will be held in Mexico in
1975 and Prof. Jimenez of Mexico was elected
President of the International Union for the
next two years.
The inaugural session was held on 24th
September, 1973 at 11A.M. in the main
Banquet Hall of the Hotel Otani which was
tastefully decorated for the occasion. The
conference was inaugurated by Her Imperial
Highness Princess Chichibu, Patron of the
Japan Anti-Tuberculosis Association. Mr. T.
Shimazu presided. The inaugural session was
also addressed by the Minister of Health and
Welfare, Governor of Tokyo, President of
Japan Medical Association and Dr. K L. Hitze
on behalf of the W.H.O. Prof. E. Barnard,
Secretary-General of the Union, could not
attend the conference because of indisposition
and his message was read by Dr. D.R.
Thomson, Executive Director of the Association.
The inaugural session came to an end
with a short session of traditional Japanese
music.
The Japan Anti-TB Association was At
Home to the participants of the conference the
same day at 7 P.M. The Governor of Tokyo
gave another reception on 27th September. A
short entertainment programme consisting of
modern and classical Japanese dance and
music was also arranged for the participants of
the conference. All the three social functions
were well organised and the hospitality was
very lavish.
Scientific sessions started after lunch on the
24th of September, 1973. One hundred and
twenty four papers were presented in all during
the five days of conference. The general
pattern of the conference was that there were
one or two plenary sessions in the morning
and thereafter the conference met in two rooms
simultaneously for presentation of free communications
and symposia on important
subjects. The free communications sessions
on chemotherapy were the most popular and
26 out of the 124 papers were on chemotherapy.
In all there were 63 free communications. The
contribution from the Indian delegates consis-
Ind. J. Tub., Vol XXI, No; 1

40 S. P. PAMRA
ted of two papers by Dr. S.P. Tripathy and one
paper each by Dr. M.L. Mehrotra and Dr.
S.P. Pamra. As most of the time the conference
was meeting simultaneously in two
places, one had to pick and choose which
sessions to attend and many a time some
important papers had to be missed because
even more important papers were being simultaneously
presented in the other hall. A brief
account of some of the important sessions
attended by the reporter is as follows :—
1. General Health Programme in Japan
The state of health of the Japanese in
general has been consistently improving during
the last quarter of a century. The death rate
now is 6.5 per 1,000 and the birth rate only
19.3. In fact most of the younger Japanese
couples have only one child each and the
national average of children is less than 2 per
family. Life expectancy is rising steadily and
is, at present, 70.2 years for males and 75.6
years for females. The state of nutrition is
also considerably better than in 1946. In that
year the daily per capita protein consumption
was 59.2 grams, out of which animal protein
was 10.6 grams. In 1971 the per capita protein
consumption was 78.1 gram out of which
animal protein was 34.7. The average caloric
value of diet was 1,902 calories per capita in
1946 whereas now it is 2,286 calories. Low
birth and death rate and the increased expectancy
of life has changed the characteristic of
the population and the percentage of aged
people is rising considerably. The largest
number of deaths at present are due to cerebrovascular
and cardio-vascular disease and
cancer of the stomach.
The health of the community is looked after
by 839 health centres, each looking after a
population of approximately 100,000 population.
The health centres are responsible for all
clinical and preventive work and are very
adequately staffed and equipped. Some health
centres have now got mobile vans equipped
for diagnosis of gastrointestinal and cardiovascular
disease i.e. they are equipped with
x-ray apparatus for barium meal examination,
ECG, etc. Of all cancer cases, stomach is involved
the most (over 46 per cent in males and
over 37 per cent in females). The number of
beds for all diseases is 1,082,647 in the country
i.e. 1 per 100 population. The proportion of
doctors is 1.17 per 1000 population. The public
health nurses are still not enough (1 per 7000
population). 4 per cent of the total national
income is spent on health and 5 per cent of
the total health expenditure is in connection
with tuberculosis. 47 per cent of the cost of
Ind. J. Tub., Vol. XXI, No, 1
treatment is borne by the state, 45 per cent by
the Health Insurance Scheme and 8 per cent by
the patients themselves. Patients are free to
take treatment from private practitioners or at
health centres according to their choice.
2. Tuberculosis and its control in Japan
Dr. T. Iwasaki, Director of the Tuberculosis
Research Institute, Tokyo, gave a brief account
of the tuberculosis problem in Japan. Tuberculosis
mortality in 1972 had come down to
11.9 per 100,000 whereas it was 257 in 1918,
190 in 1935, 235 again in 1944 and 82 in 1952.
Whereas tuberculosis was the most common
cause of death unto 1950, it was 5th in 1955,
8th in 1970 and 10th in 1972. The number of
beds in tuberculosis institutions was 101,644 in
1950, reached the maximum of 263,235 in 1958
and has come down to 160,961 in 1972. Thus
there are 10 beds per annual death in Japan
at present. There is also a change in the type
of patients admitted and the duration of their
stay in the hospital. In 1950, 25 per cent of
the tuberculosis deaths took place in hospitals
and 75 per cent in the homes. To-day 75 per
cent of the deaths from tuberculosis take place
in hospitals and only 25 per cent of the patients
die in their home. Similarly the average stay
of a patient in the hospital is now 357 days.
In other words, incurable patients are kept in
the hospitals as long as they are alive and not
sent away to die at home. In all, only 21 per
cent of the patients are admitted in hospital at
all. Average interval between first diagnosis
and death is about 10 years.
BCG vaccination was made compulsory up
to the age of 30 years in 1948, with the result
that 70 per cent of the persons below the age
of 45 to-day are vaccinated. With declining
opportunities for infection, BCG vaccination
in new-borns is being abandoned and the
vaccination is usually at the school entry.
79.2 per cent of the population to-day consists
of reactors. The percentage of reactors is 25
per cent in 0 to 4 years age group, 65 per cent
in 5 to 9 years and 81 percent in 10 to 14
years. During the year 1971, a total of
147,941 cases were diagnosed giving an average
of 1.37 per 1,000; of these, infectious cases
were 0.34 per 1,000. Bacilli show primary
drug resistance in about 10 per cent of these.
Since only 40 per cent of new cases are discovered
through periodic compulsory mass
radiography and the remaining are found among
the symptomatics attending the health centres
spontaneously, mass case-finding is being
changed to casefinding amongst symptomatics
only. It has been estimated that 3 par cent of
the population has symptoms suggestive gf

THE 22ND INTERNATIONAL TUBERCULOSIS CONFERENCE 41
tuberculosis and 7 per cent of the symptomatics
have active disease. Amongst the non-symptomatics,
only 1.3 per cent have active disease
needing treatment. In this group are also
included cases who have inactive lesions more
than 2 cm in size but have never been treated
previously. The treatment in those cases is
really a chemoprophylaxis. 67 per cent of the
patients take treatment from private practitioners
and the remaining from chest centres.
Default rate is about 10 per cent.
In the longitudinal study of the Japan anti-
TB Association the rate ofbacillary disease
was 0.75 per cent in 1953, 0.55 per cent in 1958,
0.19 per cent in 1963 and 0.1 per cent in 1968.
During the same period the rate of abacillary
but active disease needing treatment has come
down from 2.7 percent to 1.4 per cent. 2.6
per cent of the population have inactive
lesions.
3. Tuberculosis programme as an integrated
part of Health Services
Dr. K.W. Newell of the W.H.O. read a
very interesting paper on this subject. He
pointed out that ordinarily 85 per cent of the
population who need primary health care are
not properly looked after whereas the remaining
15 per cent get much more than what they
should. Specialized care is usually utilized by
the self-selected minority of 15 per cent of the
population leaving very little money for primary
health care for the majority of the underprivileged
population. Even though basic
health care may be considered as a ‘disaster’
by the privileged few, he was of the opinion
that equitable health care distribution for the
entire community is more important than
specialized care demanded by the privileged
few. He emphasised the need for multipurpose
workers in peripheral health institutions
looking after the entire health needs of the
community. He was also of the opinion that
development of agriculture and food production
activities are more fruitful than food
distribution activities. Although health technology
is now well understood but this alone
will by itself not solve the health problem.
What is needed is a national will, a programme
compatible with resources, revolutionary
doctors and para-medical workers with honesty
of purpose and clarity of vision.
Prof. Ruderman of Canada brought out
the importance of integrated health services as
envisaged in the present tuberculosis control
programme of our country. Emphasis was
laid on the cost-benefit analysis according to
which priority in antituberculosis work in high
prevalence countries should be given to treatment
of infectious cases and BCG vaccination.
Dr. Thomson of the IUAT emphasised the
importance of a cafeteria approach to health
programmes. Instead of any standard
approach, there should be a variegated
approach taking into consideration the customs,
vocation and resources of the community.
4. Surveillance and evolution of tuberculosis
programmes
Drs. Styblo and Bass dealt with the indices
for planning surveillance and evolution of
tuberculosis programmes with the help of data
from the Tuberculosis Surveillance Research unit
(T.S.R.U.) of Netherlands. Notification rates
are not a good index of the tuberculosis problem
as these depend on case-finding activities,
measure only fresh cases and not relapses,
errors of diagnosis and assessment of activity
and hiding of diagnosis. Annual risk of
infection is, on the other hand, a very good
index. In low prevalence countries the risk of
infection to-day is below 1 per cent. In Netherlands
the risk was 5 per cent in 1925, 1 per
cent in 1940 and much less than that to-day.
On the other hand, there is very little decrease
in the infection rate in developing countries.
The TSRU has worked out a table according
to which if the risk of infection in a country is
1.5 per cent or more per year, then the rate of
bacillary TB in that country is likely to be 0.09
per cent and the infection rates at the age of
15 years would be 20 per cent and at the age
of 30 years 36 per cent. In low prevalence
countries if the risk of infection is 0.19 per
cent per year, then the rates will be 3 per cent
and 6 per cent at the age of 15 years and 30 years
respectively. TSRU expects the prevalence of
infection to be reduced by about 50 per cent
every 5 to 7 years in developed countries.
5. IUAT trial on preventive treatment in
persons with fibrotic lesions (high risk groups)
The results were presented by Mrs. S.
Ferebee Woolpert, Dr. Krebs, Dr. Dankova
and Dr. Vadasz. Nearly 28,000 patients with
fibrotic lesions were included in the trial from
7 countries. The duration of the treatment
was 12, 24 and 52 weeks in randomly selected
sub-groups. One fourth of the persons in each
group were on placebo and three-fourths were
given a daily dose of 300 mg of INH. Radiological
and bacteriological examinations were
carried out at 12, 24 and 52 weeks. 58 per
cent of the persons had no bacteriological
examination during the 3 years before the
trial. 52 per cent were males. More than 75
per cent were above 50 years. The size of the
Ind. J. Tub., Vol. XXI, No, 1

S. P. PAMRA
lesion was less than 2 sq. cm. in 60 per cent, 2
to 7 sq. cm in 30 per cent and more than 7 sq.
cm in the remaining. The rate and size of the
inactive lesions usually increased with age.
Pre-treatment culture was found positive
in 144 out of about 24,000. Bigger the size of
the lesion, the greater was the chance of a
positive culture initially. In 12 out of 118
positive cultures where sensitivity was tested,
12 were found resistant (4 to INH, 7 to Thiacetazone
and 1 to Thiacetazone and Ethambutol).
Eleven out of these 12 were in the INH group
and one only in the placebo group. Over 80
per cent of those found positive initially bscame
negative in the treated and 90 per cent in
the placebo group. Five cases out of those
who had a sensitive culture previously showed
evidence of resistance.
88% of the treated and 90% of the placebo
group completed the scheduled treatment. 75%
had a regularity of 100%. The non-cooperators
were 3.6% in the treated group. The toxic
reactions were significantly more in persons in
the higher age group and increased with the
duration of treatment. Gastro-intestinal
disturbances were 1.3% and liver toxicity
0.4%.
X-ray deterioration was seen in 1.7 per
1,000 in the placebo group and 0.7 per 1,000,
0.2 per 1,000 and 0.4 per 1,000 in those
treated for 12, 24 and 52 weeks respectively.
Bacteriological deterioration was noted in 4.4
per 1,000 in the placebo group and 1.1 per
1,000, 0.2 per 1,000 and 0.2 per 1,000 in 12,
24 and 52 weeks groups respectively. Thus
INH reduced the rate of breakdown by 75%
in the 12 weeks’ group and 96% in the 24 and
52 weeks’ group. Seven of the 8 positive
cultures in INH group had sensitive bacilli
whereas in the placebo group all patients had
sensitive bacilli. The breakdown rate did
not differ in relation to the time that the
lesions were known. However, the bigger the
lesion the greater was the breakdown rate.
Taking radiology and bacteriology together,
INH protected 65% in the 12 weeks, 91% in
24 weeks and 88% in 52 weeks.
6. Endogenous versus exogenous re-infection
Five papers were presented on this important
subject and all of them favoured endogenous
re-infection as the commoner of the two
methods. This conclusion was based by and
large on indirect evidence. Prof. W.W. Stead
based his remarks on a number of observations
including phage typing of bacilli
recovered from more than one organ in the
Ind. J. Tub., Vol. XXI, No. 1
same person. Dr. Chiba of Japan had kept
70,000 workers under surveillance for nearly
30 years. He found that the history of
contact was present more often in primary
disease but not so in the re-infection
type of disease. Furthermore, contact history
was similar in patients and matched pairs of
non-patients. Dr. Komanko deputizing for
Prof. Kotechnova of Moscow found that reinfection
type of disease was 40 times more
common in those with residual primary lesion
than in those without such residual lesions.
87% of x-ray negatives give 21.5% new cases
whereas 7.8% of those with some residual
lesions are responsible for 52.1% of the cases.
0.4% of the population with history of contact
gave only 1.3% of the cases. Dr. T. Shimao
gave the results of follow up of 625 persons
working in tuberculosis hospitals and sanatoria
in Japan. He found that incidence of fresh
disease amongst these persons is on the decline
inspite of the fact that the risk of infection has
not changed at all. This would tend to prove
that the cause of fresh disease is endogenous
rather than exogenous re-infection.
7. Epidemiological trends in low prevalence
countries
Four papers were presented from Netherlands,
France, Rumania and Germany. In
Netherlands reduction in the annual risk of
infection is of the order of 40%. In 1920 to
1948, the risk of infection was 2.8% in Prague,
2.2% in Vienna and 0.5% in Netherlands and in
West Germany the risk of infection has fallen
from 0.3% to 0.03% from 1955 to 1971 and in
Saskatchewan from 0.3% to 0.04%. The
prevalence of infection in schools in these
countries now is usually less than 3% and the
rates are falling at the rate of 10% every year.
In France the risk of infection is 0.005%
at present, the rate being somewhat higher in
Paris than in the rest of the country. Dr.
Mori presented some figures from Okinawa.
The risk of infection was 0.1 % in 1940 and
had come down to 0.01 in 1970.
8. BCG Vaccination policies
Dr. Rouillon of the IUAT and Mr. Waaler
presented an interesting study on cost-benefit
analysis of BCG vaccination. The cost of
BCG vaccination and the cost of treatment of
its complications etc. were matched against the
cost of treatment of disease amongst persons
who are likely to have been prevented from
developing disease as a result of BCG under
various epidemiological situations. The
analysis is naturally subject to various assumptions
in relation to acceptability of BCG,

THE 22ND INTERNATIONAL TUBERCULOSIS CONFERENCE 43
extent of coverage and efficacy of BCG. The
authors came to the conclusion that in low
prevalence countries, the value of BCG vaccination
in new-borns is marginal but if vaccination
is limited to the school leaving age, the
cost-benefit analysis is favourable under any
et up of factors. BCG vaccination should be
dcommended in infants if the annual inciscnce
of infection is 0.3% or more
9. Chemotherapy
As already mentioned there were 26 papers
on chemotherapy and most of the papers dealt
with controlled trials using Rifampicin and
Ethambutol with other standard drugs daily
or intermittently. The important conclusions
of almost all these studies were that by using
Rifampicin, nearly 100% sputum conversion
is possible and the results in respect of sputum
conversion are better with intermittent regimens
of Rifampicin rather than daily regimens.
However, the hyper-sensitivity reactions of
intermittent Rifampicin regimens are rather
serious whereas these reactions are, by and
large, absent in regimens based on daily
administration of Rifampicin. Sister Aquinas
reported a study from Hong Kong showing
that if Rifampicin in a dose of 75 mg once
daily is given in addition to the usual intermittent
dose of Rifampicin (900 to 1200 mg),
adverse reactions are considerably reduced.
Several authors referred to the existence of
Rifampicin—dependent circulating antibodies
which were responsible for adverse reactions
in intermittent regimens of Rifampicin. There
was a significant correlation between the
existence of these anti-bodies and hypersensitivity
reactions usually described as ‘Flu’
syndrome, comprising high fever, pain in the
joints and severe prostration. Some of the
important controlled trials reported at the
conference are summarised below.
Dr. Karuga from Kenya reported a cooperative
trial based on 1,137 patients from 27
centres in 3 countries carried out in 1971. The
trial regimens consisted of Streptomycin, INH,
Rifampicin, PZA and THC in various combinations
for 6 months and the results were
compared with the conventional 18 months’
treatment with Streptomycin, INH and THC
for 2 months followed by INH and THC for
the following 16 months. It was found that
the sputum conversion in all regimens was 95
per cent to 97 per cent. Relapse rates were 2
per cent in Streptomycin + INH + Rifampicin
regimen, 10 per cent in Streptomycin + INH
+ PZA, 22 per cent in Streptomycin + INH
+ Thiacetazone and 27 per cent in Streptomycin
+ INH for 6 months and 3 per cent in the
conventional 18 months’ treatment regimen.
Maximum relapses occurred 7 to 9 months
after stopping the 6 months regimens. Single
isolated culture (not relapse) was obtained in
12 to 22 per cent in various drug regimens.
Prof. Brouet presented the results of 243
patients treated with Streptomycin, INH,
Rifampicin and Ethambutol. Streptomycin
and Ethambutol were given only for the first
3 months. Thereafter the patients were divided
into 3 groups which were given INH and
Rifampicin for 6, 9 and 12 months. There
were no significant differences in the fall out
rate, sputum conversion, radiological change
or relapse during the first 18 months of follow
up in any of the groups.
Dr. Figuerredo of Brazil presented the
results of two groups each of 75 patients. One
group was given supervised treatment in
hospital for 6 months and the other group was
given hospital treatment for 2 months followed
by 4 months of domiciliary treatment. The
drug regimen was the same in all patients viz.
Rifampicin, INH and Ethambutol daily.
Eleven patients did not complete the treatment.
The sputum coversion rate was 100 per cent in
both groups amongst patients who completed
the treatment. There were 5 relapses in a
follow up of 24 months, all but one within 6
months after completion of treatment, the last
one being 23 months after the end of chemotherapy.
There was no case of major toxicity.
Dr. Bignall reported the results of a controlled
trial carried out in 8 countries from
1969 to 1972 with a view to find out if 12
months’ supervised intermittent treatment with
Streptomycin and INH can be improved by the
addition of Thiacetazone or PAS. The patients,
775 in all, were divided into a number of subgroups
and the main conclusion was that the
addition of Thiacetazone or PAS did not make
any significant difference in the rate or speed
of sputum conversion. Unfavourable results
in each group varied from 7 per cent to 12 per
cent. The unfavourable results were about 4
per cent in regular patients, and 18 per cent in
those who missed more than 2 months’ treatment.
This difference was statistically significant.
The results were appreciably better in
those with sensitive bacilli initially (85 percent)
as against those whose bacilli were initially
resistant (47 per cent). Whether bacilli were
resistant to INH or Streptomycin did not seem
to make much difference in the results. The
toxic reactions were more in patients given
Thiacetazone as the additional drug but the
difference was not significant.
Ind. J, Tub, Vol. XXI, No. 1

44 S. P. PAMRA
Dr. Tripathy presented the results of a
controlled clinical trial comparing 4 regimens,
using Streptomycin, Ethambutol and INH. All
the 431 patients included in the trial were given
Streptomycin, Ethambutol and INH daily for
4 weeks. Thereafter, 3 groups of patients were
administered under supervision (a) Ethambutol
plus INH twice a week, (b) Ethambutol plus
INH once a week and (c) Ethambutol once a
week plus INH twice a week. The fourth
group received Ethambutol plus INH daily,
unsupervised. Only 4 patients were grossly
irregular. There were no significant differences
in the radiological clearing or cavity closure
rates in all groups. When Ethambutol plus
INH were given daily, 96 per cent of the
patients had a sputum conversion. Correspondingly
88 per cent had a sputum conversion
with Ethambutol plus INH twice a week.
The results were poorest (75 per cent conversion),
if INH and Ethambutol were given onceweekly.
If INH was given twice a week and
Ethambutol once a week, the sputum conversion
rate was 93 per cent. The difference between
93 per cent and 75 per cent conversion
is significant. Similarly, relapse rates were the
lowest (9 per cent in the first 6-12 months of
follow up) in the regimen with best sputum
conversion and significantly higher (35%) in the
Ethambutol plus INH once a week regimen.
Most of the relapses occurred in the first 3
months after stopping chemotherapy. There
was no difference between rapid and slow
inactivators on the daily regimen; there was a
small difference between the two groups in the
Ethambutol plus INH twice-weekly series, but
when Ethambutol plus INH were given once a
week, the results were significantly inferior in
the rapid inactivators. The author’s conclusions
were :
1. When one moves from daily to onceweekly
regimens, the efficiency of INH
decreases but that of Ethambutol
increases.
2. Ethambutol is probably a bacteriostatic
drug, which cannot fully compensate
for the deficiency of INH in the rapid
inactivators.
In another paper, Dr. Tripathy reported the
results of investigations to determine the optimum
dosage of a slow-release preparation of
INH. Investigations suggested that onceweekly
administration of 40 mg/kg slow-release
INH may be therapeutically effective in rapid
inactivators of INH. However with this dose,
exposure to INH in slow inactivators was more
than double the exposure with 15 mg/kg and
ordinary INH, thus distinctly increasing the
Ind. J. Tub., Vol. XXI, No. 1
possibility of toxic reactions in slow inactivators
of INH.
Prof. Polansky presented the results of
various daily and intermittent regimens using
Streptomycin, INH and PAS in hospitalized
and non-hospitalized patients. Nearly 100 per
cent sputum conversion was obtained in all
patients. There was no difference in hospitalized
and non-hospitalized patients.
Dr. Yamamoto compared the results of
daily Rifampicin and Ethambutol with intermittent
regimen using these two drugs along
with INH in one study and INH and PZA in
another study. 900 mg of Rifampicin twice
weekly gave better results than the 450 mg
Rifampicin daily. PZA did not improve the
results significantly. Side effects of Rifampicin
were more in intermittent regimen than in the
daily regimen.
Dr. Horsfall and Dr. Girling presented
results of the Hong Kong trial of 575 patients,
all of whom were excreting bacilli resistant to
one or more first line drugs. The average age
of the patients was 44 years; two-thirds were
far advanced and only 14 per cent had no
cavities. They were all given Ethambutol and
Rifampicin daily or intermittently. The treatment
was supervised for the first 6 months and
unsupervised for the subsequent 6 months.
Admission in hospital varied from 3 to 6
months. The conversion rate after 12 months
treatment varied from 80 per cent to 90 per
cent. Majority of the unpleasant reactions
were in the first 3 months of treatment and
very few in the last quarter of treatment.
Majority of the adverse reactions (22 per cent)
were what has been described as ‘Flu’ syndrome.
Next in frequency were the gastrointestinal
disturbances in 11 per cent of the
cases. ‘Flu’ syndrome was more common in
intermittent Rifampicin regimen.
Dr. Reagan compared the results of treatment
in Detroit in 1965 when all patients were
hospitalized at the start of treatment and in
1971 when only 40 per cent of the patients
were admitted for an average of 90 days and
thereafter the treatment was from the outpatient
department. No difference was found
in the results of treatment obtained in the two
series, even though drug default was more in
the 1971 series during out-patient treatment.
Dr. Mehrotra’s paper on compatibility of
oral contraceptives with anti-tuberculous drugs
showed that the oral contraceptives were fully
compatible with anti-tuberculous drugs and
furthermore overall progress of patients on

THE 22ND INTERNATIONAL TUBERCULOSIS CONFERENCE 45
contraceptives was faster and they had a
greater sense of well being.
Prof. Anastasatu reported the results of
967 resistant cases with five Rifampicin containing
regimens. Rifampicin 900 mg. plus
Ethambutol 50 mg/kg twice weekly in outpatients
gave the maximum results (96 per cent
sputum conversion). The additional advantages
were its comparatively lower cost and better
acceptability by the patients. No relapses
were noticed in the 12 months following
stoppage of chemotherapy.
Dr. Sanz reported the results of 142
patients treated daily and intensively for the
first 3 months followed by once weekly and
twice weekly Rifampicin with other drugs later
on. Failure of sputum conversion was more
frequent in daily Rifampicin but adverse reactions
were more in the intermittent regimen.
Two cases of thrombo-cytopaenia were noticed
in intermittent regimen.
Prof. Zierski reported the results of 247
resistant patients given Rifampicin and Ethambutol
daily for 12 weeks followed by one or
twice weekly regimens for the subsequent 40
weeks. Sputum conversion was 98 per cent in
all regimens. 93 per cent of the patients took
the drugs with 100 per cent regularity.
Dr. S.P. Pamra reported the results of a cooperative
study based on 525 patients. All
patients were given Streptomycin, INH and
Thiacetazone for 8 weeks followed by INH and
Thiacetazone (unsupervised treatment) in one
group and intermittent Streptomycin and INH
(supervised treatment) in another group for 44
weeks. There was no significant difference in
the results of sputum conversion and cavity
closure in the supervised and unsupervised
regimens though overt irregularity was significantly
more in the supervised regimen.
Further, the latter regimen is more costly and
difficult to organise in a situation where a large
number of patients have to be treated with
meagre resources.
S. P. PAMRA
Ind. J. Tub., Vol. XXI, No. 1

THE THIRD ASIA PACIFIC CONGRESS ON DISEASES OF THE CHEST
H. B. DlNGLEY
The Third Asia Pacific Congress on the
Diseases of Chest was held in Bangkok, Thailand
from Nov. 1—4, 1973. Nearly 300, delegates
from 15 countries namely, Australia, Republic
of China, Germany, Hong Kong, India,
Indonesia, Italy, Japan, Korea, Macao,
Philippines, Singapore, South Vietnam. U.S.A.
and the host country Thailand participated.
Dr. Viswanathan and the author participated
on behalf of our country.
The Inaugural Session was held in Napalai
Ballroom, Dusit Thani Hotel and the Conference
was inaugurated by His Excellency the Health
Minister of Thailand.
This was followed by six international
seminars simultaneously. The subjects covered
were Lung Cancer, Bronchial Asthma, Tuberculosis
(Preventive aspect), Tuberculosis
(Treatment), Problems of Cardiac Surgery in
the orient and Problems of Non-Tuberculous
infection and surgery in the orient.
The scientific sessions were held in the
Faculty Auditorium, Chulalongkorn University
Hospital. The symposia were held simultaneously
in three separate halls.
The subjects covered were Lung Cancer,
Bronchial Asthma and Pulmonary Tuberculosis.
The gist of presentation on Pulmonary
Tuberculosis is as follows:
Tuberculosis ; Investigation and Diagnosis
1. Fluorescence microscopy for detection
of A.F.B. in clinical specimens:— Chaivej
Nuchprayoon et al (Thailand):
A double blind study was done on 982
consecutive sputum specimens from tuberculosis
patients. Duplicate smears were prepared
from each specimen, one was stained by
Ziehl-Neelsen method and examined under
light microscope, the other by Auramine-0 stain
and examined under fluorescence microscope.
Of the 239 culture positive specimens,
Ind. J. Tub., Vol. XXI, No. 1
60.8 percent were positive by Ziehl-Neelsen
method and 55.6 percent were positive by
fluorescence method.
Among 743 culture negative specimens, 2.2
percent were falsely positive by Ziehl-Neelsen
and 1.8 percent were falsely positive by
fluorescence. Differences of the two methods
were not statistically significant (P>0.05).
It is concluded that fluorescence microscopy
offers no better results than Ziehl-Neelsen
method for the detection of tubercle bacilli in
clinical specimens.
2. Serum immunoglobulins in pulmonary
tuberculosis patients:—Prasert Thongcharoen et
al (Thialand).
Serum immunoglobulins (IgG, IgA and IgH)
were determined by radical immunodiffusion on
fifty samples of sera obtained from 50 pulmonary
tuberculosis patients with positive sputum.
The mean concentration of Igs were higher
than normal levels. The mean concentration
values of IgG IgA and IgM in pulmonary
tuberculosis patients were 2214 mg/100 ml,
371 mgm/100 inland 116/100 ml respectively
(the corresponding levels in the normals were
1701 mgm/100 ml, 274 mgm/100 ml and 99
mgm/100 ml).
These findings arc compatible with the
levels of serum Igs concentration in leprosy
patients. It is evident that the humoral antibody
in tuberculous patients increased as in other
chronic infections.
3. Bacteriological and clinical studies on
atypical mycobacteria in Korea:—Tae Kyungchoi
(Korea).
Ten percent of the atypical mycobacteria
isolated from 627 tuberculosis patients, none
of the photochromogens (group 1) was
isolated, schoto-cliromogens from 49.0 percent
and rapid growers from 8.5 percent of the
total isolation of mycobacteria.
4. Mycoplasmal Pneumonia in patients
,

THE 22ND INTERNATIONAL TUBERCULOSIS CONFERRENCE 45
Contraceptives was faster and they had a greater
sense of well being.
Prof. Anastasatu reported the results of
967 resistant cases with five Rifampicin containing
regimens. Rifampicin 900 mg. plus
Ethambutol 50 mg/kg twice weekly in outpatients
gave the maximum results (96 per cent
sputum conversion). The additional advantages
were its comparatively lower cost and better
acceptability by the patients. No relapses
were noticed in the 12 months following
stoppage of chemotherapy.
Dr. Sanz reported the results of 142
patients treated daily and intensively for the
first 3 months followed by once weekly and
twice weekly Rifampicin with other drugs later
on. Failure of sputum conversions was more
frequent in daily Rifampicin with other drugs
later on. Failure of sputum conversion was
more frequent in daily Rifampicin but adverse
reac-tions were more in the intermittent
regimen Two cases of thrombo-cytopaenia were
noticed in intermittent regimen.
Prof. Zierski reported the results of 247
resistant patients given Rifampicin and Ethambutol
daily for 12 weeks followed by one or
twice weekly regimens for the subsequent 40
weeks. Sputum conversion was 98 percent in all
regimens. 93 per cent of the patients took the
drugs with 100 per cent regularity.
Dr . S.P. Pamra reported the results of a
co-operative study based on 525 patients. All
patients were given Streptomycin, INH and
Thiacetazone for 8 weeks followed by INH and
Thiacetazone (unsupervised treatment) in one
group and intermittent Streptomycin and INH
(supervised treatment ) in another group for 44
weeks. There was no significant difference in
the results of sputum conversion and cavity
closeure in the supervised and unsupervised
regimens though overt irregularity was significantly
more in the supervised regimen.
Further, the latter regimen is more costly and
difficult to organize in a situation where a large
number of patients have to be treated with
meager resources.
S.P. PAMRA

THE THIRD ASIA PACIFIC CONGRESS ON DISEASES OF THE CHEST 47
with pulmonary tuberculosis:—Osamu Kitamoto
(Japan) reviewed 11 cases of mycoplasmal
pneumonia confirmed by culture and/or serum
reactions in patients with active or inactive
pulmonary tuberculosis. In patients with
pulmonary tuberculosis, who develop new
shadows with X-ray, it is important to determine
the nature of the shadow.
5. Aspergillosis in Post Tuberculous Cavity
oftheLung:-Sango Hamano (Japan)
The incidence of aspsrgillosis in post tuberculous
cavity is rapidly increasing in frequency
in Japan.
Radiologically there is thickening of the
cavity wall, which indicated primary stage of
fungus infection with the thickening of the
wall of these walled cavities, there is shrinkage
of the cavity, which is gradually occupied by
the fungus ball. But if the cavity is present in
widely adherent surroundings neither the cavity
shrinkage nor the fungus ball formation was
observed.
Regarding the sputum examination, as
aspergillus is a common contaminant of normal
sputum, quantitative evaluation for the aspergillus
is very important. Presence of more
than ten colonies in the culture of one ml
sputum had a direct co-relation between
bacteriological and roentgenographic findings.
In conclusion combination of roentgenological
and bacteriological examination is of
great value for the early diagnosis of pulmonary
aspergillosis in post tuberculous cavities.
6. Systemic chemotherapy in mice ex
perimentally infected with mycobacterium
marinum:—Seitsu Hokama (Japan).
Female mice were injected intravenously
with bacterial suspension at the rate of 0.1
ml per each 4 gm body weight of mouse. To
evaluate the effectiveness of rifampicin and
other antituberculosis drugs improvement in
peripheral lesions and daily survival rate of the
mice in each group were compared at the end
of the treatment according to their degrees and
extensions.
Rifampicin and clofazimine, used as
monotherapy were eflective drugs showing
better survival rate. Peripheral lesion showed
maximum improvement treated with rifampicin.
In regard to the combination effect of
rifampicin with other drugs RAMP + B663
and RAMP + ETH gave better results than
their monotherapy effects.
Tuberculosis Treatment-I
Treatment of pulmonary tuberculosis
I. Initial intensive chemotherapy in tuberculosis:—Banyat
Priyanoda-et-al (Thailand).
A controlled study of two-phase chemotherapy
in pulmonary tuberculosis showed
favourable results in the group of patients who
were given daily streptomycin, isoniazid and
PAS for six months followed by isoniazid alone
for six months. The other group who were given
daily streptomycin, ethambutol plus PAS for
six months followed by isoniazid alone for
six months showed poorer results.
2. A clinical study of the effectiveness of
secondary ant i-tuberculosis drugs in the treatment
of pulmonary tuberculosis:—J.Y. Haw (Korea)
272 active pulmonary tuberculosis patients
bacteriologically and clinically resistant to
primary and secondary drugs were treated for
more than 12 months and divided into five
groups:
Group-I 51 patients were given with a second
line drug either (INH+TH) or (INH-f-EM).
Group-II Of 91 patients were treated with two
second line drugs (INH+TH+PZA) or
(INH+TH+CS).
Group-III Of 86 patients treated with two
second line drugs either (INH+EM+TH) or
(INH+EM+PZA) or INH+EM and two
other second line drugs)
Group IV:- Of 27 patients treated with three
second line drugs (INH+EM and two other
second line drugs).
Group VI:- Of 17 patients treated with
Rifampicin.
Sputum conversion after 2, 6 and 12 months
of chemotherapy were:
Group I:-56.9, 49.0 and 31.4 percent
Group II:-46.2, 48.4 and 48.4 ” ” ”
Group III.--51.2 70.9 and 77.9 ” ” ”
Group 1V:-63.0, 77.8 and 81.5 ” ” ”
Group V:-70.6, Si.5 and 88.2 ” ” ”
Ind. J. Tub., Vol. XXI, No. 1

48 H. B. DINGLEY
The X-ray improvement at 6 and 12 months
were:
Group I:-47.1 and 43.1 percent
Group II :-53.8 and 54.9 ” ”
Group III:-60.4 and 64.0 ” “
Group IV:-74.1 aad 74.1 ” ”
Group V:-76.6 and 82.4 ” ”
Conclusions:-Results of treatment were
best in Group V, followed by group IV, III, II
and I respectively. Group IV (triple second line
drugs including EM) was not better than
group III (two second line drugs including EM).
Since Group I (INH+single second line
drug) showed very poor results, such a regimen
does not seem to be desirable for retreatment
of tuberculous patients.
3, Experiences with
Aquinas (Hong Kong).
Rifampicin-.-Mary
Results of two studies were presented. In
the first study in 40 Chinese patients treated
with Rifampicin/Ethambutol for 2 years along
with Capreomycin for the first 6 months.
In the second study in 300 Chinese with
first line drug failure patients, with Rifampicin
-f EM daily, once weekly, twice weekly and
daily for 2 months followed by once weekly.
One of the main points was use of Rifampicin
on intermittent basis.
Therapeutically there was little difference
between the various regimens but there was
marked difference in the incidence of adverse
reaction, which were associated with the
intermittent use of Rifampicin.
4. Ambulatory intermittent Rifampicin and
Ethambutol in the retreatment of pulmonary
tuberculosis:- Nadda Syriyabhaya-et-al
(Thailand)
A comparative trial of two regimens of
rifampicin in combination with ethambutol in
75 patients with positive sputum after long
term treatment with standard drugs showed
that in the group with daily rifampicin and
ethambutol for an initial period of 6 weeks
followed by thrice weekly regimen the sputum
conversion during the first six months was
93.9 percent in whom the two drugs were given
thrice weekly from the start. At the end of
12 months, overall results were the same in
the two groups. Toxic reactions were observed
in five patients in both the groups.
5. Management of Treatment Failure cases
of Pulmonary Tuberculosis in Southern Aboriginal
Communities in Jo/wan :-Chen-chi Chang
(Republic of China)
For the treatment failure patients, two or
more second line anti TB drugs were distributed
and supervised for one year through
local health workers, hospitalization. Surgical
intervention was done for those needing it.
Necessary financial relief to the families of
those who were not in job was provided.
Tuberculosis Treatment-H
1. A Study of Tuberculosis Beginning with
Psychoneurotic Symptoms: Yun Kyu Park
(Korea)
In the presence of emotional stress or other
factors, the adrenal cortex excretes excess
corticoid harmones. This phenomenon results
in disharmony, brings various symptoms.
Infection from tubercle bacilli may be one
factor of stress causing hyper-function of
adrenal glands.
Diagnosis of early tuberculosis beginning
with neurotic symptoms before showing
abnormalities on chest X-ray or sputum examination
should be done. According to the
author modern method of diagnosis of tuberculosis
such as chest X-ray and sputum examination
are not satisfactory to find out the so
called camouflaged tuberculosis.
Examination of eye fundus to find chronic
retro bulbar optic neuritis is more significant.
Regarding treatment there is not much
difference between tuberculosis and so-called
camouflaged tuberculosis. Satisfactory results
in this treatment of so-called camouflaged
tuberculosis were obtained with anti-tuberculous
drugs
2. Treatment of pulmonary tuberculosis
in children—A controlled study:-H.E. Dingley
(India).
Results of co-ordinated study carried out in
a group of 280 hospitalized child patients
suffering from pulmonary tuberculosis allocated
at random to four groups with isoniazid as
common drug to Ethambutol, Thiacetazone,
PAS and Streptomycin were reviewed. The
treatment was continued for six months.
Bacteriological conversion was quicker and
100 percent with Ethambutol and cavity closer
were more i.e. nearly 45 percent. There were
no side effects. Both drugs were given in
Ind. J. Tub., Vol. XXI, No. 1

THE THIRD ASIA PACIFIC CONGRESS ON DISEASES OF THE CHEST 49
syrup form and this drug combination was
more acceptable.
3. Some aspects of bacteriological effect of
Rifampicin in vitro and clinical evaluation of
daily and intermittent Rifampicin and its toxicity,
A Cooperative Study: -Fumiyuki Kuza (Japan).
Ninety patients who received both first and
second line drugs were treated for six months
with daily or intermittent rifampicin.
The daily rifampicin regimen appeared
superior than intermittent rifampicin.
77 percent in daily rifampicin 450 mgm in a
single dose, 55 percent in 600 mgm twice weekly
and 60 percent in 600 mgm thrice weekly
rifampicin after six months of treatment
became culture negative.
Of all the 97 patients, rifampicin was
abandoned in 2 because of gastro-intestinal
intolerance, in 3 because of liver function
abnormality and in 3 rifampicin was discontinued
because of low platelet count, symptomless
thrombocytopaenia.
4. Rifampicin and Ethambutol in daily and
intermittent regimens in pulmonary tuberculo
sis .--Results of a controlled study in Hong Kong:-
Peter A.L. Horsfall (Hong Kong).
Five hundred and forty five patients were
allocated at random to one of the five regimens
viz. rifampicin and ethambutol daily (ER7)
twice weekly, (ER2) weekly, (ER1) daily for
two months followed by twice weekly (ER7-
ER1). The control regimen being ethionamide,
pyrazinamide and cycloserine (EL-Z-C-EIZ).
The treatment was continued for 12
months or 18 months. The results were best
after daily administration of ethambutol and
rifampicin.
5. Drug Resistant Pulmonary Tuberculo
sis:- Result of retreatment:-Songkram Supchareon
et al (Thailand)
Three hundred and sixty five cases of
pulmonary tuberculosis resistant to standard
drugs were given second line drugs for
6 months unsupervised. Of these, results of
285 patients treated with ethionamide, pyrazinamide,
d-cycloserine, kanamycin, viomycin,
ethambutol and rifampicin after 12 months
treatment were presented.
6. In vitro and in vivo activity of nitroxiline
against tubercle bacili:-Tanzil et al (Indonesia).
The International Standard Strain myco-
bacterium tuberculosis H 37 RV was found to
be susceptible to nitroxpline in Lowenstein
Jensen medium as well as in guinea pigs injected
with H 37 RV strain of mycobacterium tuberculosis.
Tuberculosis Treatment-Ill
1. Therapeutic effects of Lividomycin, a
new antituberculosis drug, on the already treated
pulmonary tuberculosis patients: -Masakiko
Yamamoto (Japan).
Lividomycin produced by streptomyces
Lividus was administered twice a week in a
group of 41 patients in dosages of 1.5 to 2 msg.
depending upon the weight. In 15 patients it
was given along with other drugs while in
26 patients only Lividomycin was used.
Regarding the adverse effects of LVM, the
bearing activity at 8000 C/S in audiogram
was disturbed in 26.3 percent of the patients
during 6 months administration.
2. The rise and fall (Evolution) of surgical
treatment of Pulmonary Tuberculosis :-Otto C.
Brontigon (U.S.A.)
The author reviewed the history of surgical
treatment of Pulmonary Tuberculosis both in
the pre and post chemotherapeutic era.
3. Surgical Treatment for pulmonary
tuberculosis Today when chemotherapy made
great advancemenf.-Chuzo Nagaishi and Takashi
Teramatsu (Japan)
Surgical treatment should be performed
when no other treatment is effective or patient
needs to be back to the social life as soon as
possible. Once surgical treatment is decided
as most suitable for the case, the method of
operation has to be selected after a thorough
investigation.
It is necessary to keep the post-operative
respiratory insufficiency and the deformity
of the thorax to minimum and shorten the
terms of medical treatment as much as possible
with the aid of chemotherapy.
In conclusion operative methods such as
pneumonectomy and thoracoplasty have to be
avoided and taking into consideration the
indication of each case, lobectomy or a local
surgical treatment with small operative invasion
into the region, which is resistant to chemotherapy
has to be revaluated.
Ind, J, Tub., Vol. XXI, No. 1

50 H. B. DINGLEY
Cavernoplasty was considered as one of the
most important routine surgical methods.
5. Pulmonary resection with simultaneou
thoracoplasty :-Arak Porapukkham (Thailand).
The combined procedure was done in 67
patients to prevent reactivation of the residual
lesions in the remaining lung and to reduce
the incidence of post operative empyema and
bronchopleural fistula. Post operative complications
developed in 6 patients (9%) and
mortality occurred in 2 patients (3%).
6. Long term results of surgical treatment
for far advanced cases of Pulmonary Tuberculosis
:-Masayoshi Orimoto (Japan).
Follow up of 847 advanced surgically operated
patients of tuberculosis, out of total 5259
patients with surgical treatment were presented.
Advanced tuberculosis patients were those
with severely reduced VC (less than percent of
the predicted normal value) and a severely
reduced FEV percent in 1 Sec (less than 50 percent.
H.B. DINGLEY
Ind. J. Tub., Vol. XXI, No. 1

NEWS & NOTES
SEAL SALE COLLECTIONS
A sum of Rs. 11,20.903.78 has been collected
by State TB Associations in respect of 23rd
Seal Sale Campaign. Andhra Pradesh, Assam,
Bihar, Gujarat, Kerala, Madhya Pradesh,
Orissa, Pondicherry, Himachal Pradesh and
Tripura have yet to finalise their accounts of
the campaign. The total collections reported
by State TB Associations in respect of 22nd
Campaign amounted to Rs. 14,21,346.
NINTH MEETING OF THE EASTERN
REGION
The IXth Eastern Region Conference of the
International Union Against Tuberculosis will
be held in New Delhi from 3rd to 8th November,
1974. The Conference will be organised
by the Tuberculosis Association of India with
the cooperation of the Government of India.
The Delhi TB Association and other Associations
affiliated to the TAI will be active
participants in organising the conference.
The tentative subjects for discussion at the
conference will be: TB Control Programme in
the countries of the Region; Role of voluntary
organisations with special reference to Tuberculosis
Association of India; Chemotherapy;
Education and Training of Medical and paramedical
personnel; Fungus diseases of the
chest; Review of epidemiological situations in
the various countries of the region; BCG
vaccination programme in the countries of the
region; BCG vaccination programme in the
countries of the Region and Non-Pulmonary
tuberculosis. The twenty-ninth National
Conference on Tuberculosis and Chest Diseases
will also be held in conjuction with the IXth
Eastern Region Conference.
REFRESHER COURSE
A refresher cum re-orientation course for
general practitioners was held from 12th to
17th November, 1973 in the New Delhi Tuberculosis
Centre under the auspices of the Tuberculosis
Association of India and the I.M.A.
College of General Practitioners.
Eleven general practitioners from the States
of Delhi, Bihar, Uttar Pradesh and West Bengal
attended the course. The course was inaugurated
by Sri S. Ranganathan, President of the
Tuberculosis Association of India. The course
included lectures and demonstrations on pathogenesis,
diagnosis, laboratory procedures,
treatment, prevention and the national control
programme of tuberculosis.
STATE CONFERENCES
The 2nd Gujarat State TB Workers Conference
was held on 2nd December, 1973 at
Ahmedabad. The Conference was inaugurated
by Shri Chimanbhai Patel, Chief Minister,
Gujarat. Dr. M.D. Deshmukh who was the
guest speaker at the Conference inaugurated
the scientific session and the discussions
included: ‘Modern trends in management of
Tuberculosis’ and ‘Can we control Tuberculosis?’
The 3rd West Bengal State Conference
organised by the Ranaghat Sub-divisional TB
Association will be held on 20th January at
Ranaghat under the auspices of the Bengal TB
Association.
BOOKLET FOR GENERAL
PRACTITIONERS
Tuberculosis Association of India has
published a booklet entitled ‘Diagnosis, treatment
and prevention of Tuberculosis for
General Practitioners’ by courtesy Unichem
Laboratories Limited, Bombay.
RESEARCH
The Research Committee of the Tuberculosis
Association of India has decided to undertake
a study to find out if the period of treatment
of tuberculosis can be shortened with
some of the latest anti-TB drugs. It is proposed
to take 150 patients and conduct the study
with Streptomycin, INH, Pyrazinamide,
Ethambutol and Refampicin. The study will
cover a period of 18 months and will be supervised
by a Special Committee. The Amar Singh
Chanchal Singh Charitable Trust, Delhi, has
donated 60,000 tablets of Themibutol for this
purpose. Messrs Pharmed Private Limited,
Bombay, have agreed to obtain free of cost
40,000 tablets of Pyrazinamide through Messrs
Bracco Industria Clinica, Italy (Milano).
Messrs Grupp Lepetit Limited, Milano, have
agreed to supply free of cost 21,000 capsules
of Refampicin. The study will be undertaken
in Delhi in the New Delhi TB Centre, Lala
Ram Sarup TB Hospital and Rajen Babu
Memorial Hospital.
CHEST AND HEART ASSOCIATION
FELLOWSHIP
Dr. Harley Willams, Director-General, Chest
Ind. J. Tub., Vol. XXI, No. 1

52 NEWS & NOTES
and Heart Association, London, has offered
two fellowships to the Tuberculosis Association
of India of the value of £.600 each for 1974.
The TAI invites applications from State
Associations and those interested in availing
the fellowships. Selected candidates or sponsoring
authorities will have to meet their travel
expenses to and from U.K.
CHANCHAL SINGH MEMORIAL PRIZE
The Tuberculosis Association of India will
award a cash prize of Rs. 500/- to a Tuberculosis
worker, below 45 years of age, for an
original article not exceeding 30 double-spaced
fullscape typed pages (approximately 6,000
words) excluding charts and diagrams on a
subject relating to tuberculosis. Papers may be
sent in quadruplicate to reach the Tuberculosis
Association of India Office on or before 31st
August, 1974.
ESSAY COMPETITION—1974
The Tuberculosis Association of India will
award in 1974 a cash prize of Rs. 300/- to a
final year medical student in India for an
original essay on Tuberculosis, adjudged best
by a special committee of this Association. The
subject selected for the 1974 competition is
“Prevention of Tuberculosis”.
The essay should be in English, typed in
fullscape size, double-spaced and should not
exceed 15 pages (approximately 3,000 words)
excluding tablets, diagrams, etc., if any Four
copies of the manuscript should reach the
Secretary-General, Tuberculosis Association of
India, 3, Red Cross Road, New Delhi-110001,
not later tean 31st August, 1974 and should be
forwarded through the Dean or Principal of
the College/University.
ANTI-TB SHIBIR
The fifty-first Anti-TB Shibir of the
Maharashtra State Anti-TB Association was
held at Ashagad, Dahanu Taluka, Thana
District on Sunday the 16th December, 1973.
The Shibir was arranged in collaboration with
the Grail Mobile Extension Training Unit,
Bombay, and was sponsored by Biological
Evans Limited. A team of specialists and
technicians led by Dr. M.D. Deshmukh
examined 58 persons and vaccinated 847
children with BCG. 9 cases of TB were
detected in this shibir and TB germ was found
in sputum specimen of 3 of these 9 patients.
INTERNATIONAL CONFERENCE IN
MEXICO
The twenty-third International Conference
on Tuberculosis will be held under the auspices
of the International Union Against Tuberculosis,
in Mexico from 22nd to 26th September,
1975. Prof. M. Jimenez will be the president
of the conference.
OBITUARY
The Association regrets to announce that
Lala Ram Sarup Khanna whose donation of
his Estate ‘Mod Bhavan’ and Rs. 25,000
formed the nucleus for the establishment of
the LRS Hospital, Mehrauli, passed away on
3rd November, 1973.
Ind. J. Tub., Vol. XXI. No. 1

The Indian Journal of Tuberculosis
ABSTRACTS
Vol. XXI January 1974 Abst. No. 1
The risk of tuberculous infection in Uganda,
derived from the findings of National
Tuberculosis Surveys in 1958 and 1970
H. Stott, Anil Patel, Ian Sutherland, 1. Thorup,
P.O. Smith. P.W. Kent and Y.P. Rykushin.
Tub, 1973, 54, 1.
For studying the changes in the prevalence
of tuberculous infection, test results were
available for 5719 subjects in 1958 and for 6875
subjects, (258 of whom were tuberculin negative
and had been given BCG vaccine at the 1958
survey) living in the identical geographical areas
in 1970-71.
Based on the findings upto the age 30 years,
the annual risk of infection (at age 10) was 2.8
per cent in 1940, 2.6 per cent in 1950, 2.4 per
cent in 1960, and 2.3 per cent in 1970. The
slight decrease (amounting each year to less
than 1 per cent of the risk) is not statistically
significant. There does however appear to be
a definite increase in the risk with age. The
estimates of the risk at ages 5, 10 and 15 years
in 1970 were 1.9, 2.3 and 2.8 per cent (amounting
to a rise of 4 per cent of the risk with each
year of age).
It is concluded that the tuberculosis situation
in Uganda has shown little improvement during
the 12½ years between the two surveys, and
there is still a substantial risk of tuberculous
infection there. There is thus considerable
scope in Uganda for benefit from BCG
vaccination and other modern methods of
tuberculous control which include simplified
case finding and chemotherapy.
H.B.D.
A controlled comparison of two fully supervised
once weekly regimen in the treatment of
newly diagnosed pulmonary tuberculosis
Tuberculosis Chemotherapy Centre,
Tub. (1973) 54,23.
Madras.
Four hundred and fifteen patients with
pulmonary tuberculosis were admitted to a
controlled study of a year’s treatment on an
out patient basis, with one of the following
two fully supervised regimens.
SHI SHOW: Streptomycin 1 g. or 0.75 g.
plus Isoniazid 400 mgms. administered daily
for the first four weeks, followed by Streptomycin
in the same dosage plus Isoniazid 13
mgm/kg. or 17 mgm/kg. body weight,
administered once a week for the rest of the
year. Pyridoxine 6 mgm was incorporated in
every dosage of Isoniazid.
SPH/SPHOW: Streptomycin, Isoniazid
and Pyridoxine in the same dosage as in the
SH/SHOW regimen plus Sodium PAS 6 gm.
throughout the year. All the drugs being
administered daily for the first four weeks and
once a week for the rest of the year. The
regimen, the Streptomycin dosage and the
once weekly isoniazid dosage were allocated
at random for each patient.
Of the 359 newly diagnosed patients with
cultures sensitive to Isoniazid and Streptomycin,
181 were allocated to SH/SHOW and the 178
to SPH/SPHOW regimen. About 90 per cent
of the patients had cavitated disease and 40
per cent were rapid inactivators of Isoniazid.
Two patients (both SH/SHOW) died of
tuberculosis and four (all SH/SHOW) had their
chemotherapy changed on account of radiographic
or clinical deterioration in the presence
of positive sputum.
At one year 85 per cent of the SH/SHOW
and 87 per cent of the SPH/SPHOW patients
were classified as having a favourable response,
mainly on the basis of culture results at 10, 11
and 12 months.
Among those who had unfavourable
response, approximately half had responded
well initially but had a bacteriological relapse
by one year. Considerable or exceptional
radiographic improvement was shown by about
three fourths of the patients in each series and
cavitation had disappeared in about half.
Ind. J. Tub., Vol. XXI, No. 1

54 ABSTRACTS
Resistance to Isoniazid was observed at one
year in 8 per cent of the SH/SHOW and 5
per cent of the SPH/SPHOW patients and
resistance to Streptomycin in 8 per cent and 2
per cent respectively. It is concluded that the
addition of PAS to SH/SHOW regimen did not
have any appreciable benefit. Slow inactivators
of Isoniazid responded better than rapid
inactivators, the proportion with favourable
response at one year being 93 per cent and 72
per cent respectively in SH/SHOW and 95 per
cent and 76 per cent respectively in the SPH/
SPHOW series.
The duration of coverage with a bacteriostatic
concentration of Isoniazid (0-2 mg/ml)
following a once weekly dose and the total
exposure to Isoniazid (expressed as the area
under the time concentration curve) were higher
in the slow inactivators (30-34 hours, 85-111
units) than in the rapid inactivators (14-15
hours, 3-51 units). The peak concentration in
the former, however, was only 22 per cent
higher than that in the later, the difference
being of the same order as that between SPH/
SPHOW and SH/SHOW patients and Isoniazid
high dosage (17 mgm/kg) and low dosage
(13 mgm/kg) patients. These findings suggest
that response to once weekly chemotherapy
with Isoniazid is largely determined by the
duration of coverage and the total exposure to
Isoniazid. Streptomycin 0.75 gm (approximately
20 mgm/kg body weight) was therapeutically
effective as 1 gm and less toxic. The
Isoniazid dosage of 17 mgm/kg in the once
weekly phase appeared to be slightly more
effective than dosage of 13 mgm/kg, but only
in rapid inactivators.
H.B.D.
Etharabutol in the initial treatment of pulmonary
tuberculosis
Bernice Doster, Francis J. Murray, Rae Newman
and Shirley F. Woolpert. Amer. Rev. Resp.
Dis.; 1973, 107, 177.
Four chemotherapy trials were carried out
by the US Public Health Service to study the
efficiency of ethambutol (EMB) as a substitute
for PAS and pyrazinamide (PZA) in previously
untreated patients. In the first two trials,
patients with less than far advanced cavitary
disease were included. In the third and the
fourth trials, the patients were far advanced.
In the first trial, 232 patients were treated with
INH and PAS and 221 patients with INH and
EMB 6 mg per kg. body weight. In the second
trial, 198 patients were treated with INH and
PAS and 209 patients were given INH and
Ind. J. Tub., Vol. XXI, No. 1
EMB 15 mg per kg. body weight. In the third
trial. 351 patients were given streptomycin
(SM) and PZA for 4 weeks then INH and PAS
for 4 weeks. 357 patients were given SM and
PZA alternating with INH and EMB 6 mg per
kg. body weight. 271 patients were given SM,
INH and PAS. In the fourth trial 326 patients
were given SM and EMB 15 mg per kg. body
weight alternating every 4 weeks with INH and
PAS. 351 patients were given SM and PZA
alternating every 4 weeks with INH and EMB
15 mg per kg. body weight. 311 patients
were given SM, INH and EMB 15 mg per kg.
body weight. Total duration of treatment was
20 weeks.
In the first trial 3.3 per cent in INH/PAS
regimen and 12.1 per cent in INH and 6 EMB
regimen remained unconverted. In the second
trial the unconverted were 5.4 per cent and
7.9 per cent in INH/PAS and INH 15 EMB
regimen respectively. In the third trial the
percentage of unconverted ranged from 1.0 per
cent to 3.5 per cent and in the fourth trial,
from 4.1 per cent to 7.7 per cent. The difference
in the second, third and the fourth trial were
not significant, proving that EMB in a dosage
of 15 mg per kg. body weight is an effective
substitute for PAS and PZA and virtually nontoxic.
The frequency and degree of changes
in visual acuity were equal with EMB and non-
EMB regimens.
The radiological changes followed more or
less the same course as bacteriological changes.
Major toxic reactions were less than 1 per cent
in the two drug regimens and varied from
5.5 per cent to 8 7 per cent in the alternating
or three drug regimens. Minor reactions however
were nearly 14 per cent in regimens containing
PAS and less than 6 per cent in all
other regimens.
S.P.P.
Isoniazid plus Ethambutol in the initial treatment
of Pulmonary Tuberculosis
G.B. Marshall Clarke, James Cuthbert, R.J.
Cuthbert and A.W. Lees. Brit. J. Dis. Chest;
1972, 66, 272.
One hundred and thirty nine previously
untreated patients of pulmonary tuberculosis
with bacilli sensitive to INH and Ethambutol
initially were put on 300 mg of INH and
Ethambutol 25 mg/kg daily. After 2 months
the dose of Ethambutol was reduced to 15 mg/
kg daily. Bacteriological conversion was
achieved in 134 out of 139 in 6 months. Three
more were converted after completing 7 months

ABSTRACTS 55
treatment and 1 more after 9 months treatment.
In one patient which remained unconverted,
bacilli resistant to INH but sensitive to Ethambutol
emerged after 7 months treatment. Only
1 patient developed evidence of reversable
optic neuritis after 5 months treatment.
Isoniazid plus Rifampicin in the initial treatment
of Pulmonary Tuberculosis
G.B. Marshall Clarke, James Cuthbert, R.J.
Cuthbert & A.W. Lees. Brit. J. Dis. Chest:
1972, 66, 268.
A combination of 300 mg INH daily with
600 mg Rifampicin daily was used in 134
previously untreated patients of pulmonary
tuberculosis with bacilli sensitive to both drugs
initially. One hundred and thirty two of these
became bacillary negative after 6 months treatment
and the remaining 2 after 8 months’
treatment. Some disturbance of liver function
was noted in 26.6 per cent but in 16 per cent it
consisted merely in elevation of transaminase
levels which returned to normal without stopping
the treatment. In the other 106 per cent
serum bilirubin was also elevated above 1 mg/
100 ml in addition to transaminase increase.
There was however no constitutional disturbance
and both bilirubin and transaminase
returned to normal levels in 6 patients without
stopping the treatment. In the remaining 5
there was a speedy return to normal after
temporary stopping of drugs. In 3 of these
there was no further trouble with resumption
of treatment but in the other two, bilirubin
rose again after resumption of treatment and
the patients had, therefore, to be withdrawn
from the trial.
INH and Rifampicin is a very satisfactory
combination but liver function is to be carefully
monitored in the early weeks of treatment,
especially in patients with pre-existing liver
disease.
S.P.P.
Relapse in Tuberculosis
A report from the Research Committee of the
South-East Metropolitan Regional Thoracic
Society. Brit. J. Dis. Chest; 1973, 67, 33.
An attempt has been made to discover
whether certain groups of patients are more
liable to relapse than others. The chest clinics
in South-East England were asked to report
during a period of 12 months (May, 1964 to
April, 1965) all patients with bacteriological
evidence of re-activation of pulmonary tuberculosis
after not less than 2 years of quiescence.
The relapses reported were 158, constituting
0.5 per cent of the tuberculous patients known
to the clinics during that period.
These patients were compared with 244
controls drawn at random from tuberculosis
register of the same clinics in respect of sex,
age, previous treatment and radiological
features. Among the relapses there was a
significant excess of males, specially in older
age groups, and a significantly higher proportion
of patients who had received insufficient
chemotherapy. Amongst the 89 positive
sputum cultures there were 10 strains resistant
to streptomycin, INH or PAS. There was
little difference between the relapse and control
groups in respect of the number of patients
treated by surgery. The radiological extent of
original disease and the extent just before
relapse was similar in the two groups. Persistent
cavitation and presence of caseous nodules were
not found to carry increased risk of relapse.
Future policy in keeping tuberculosis patients
on long continued observation at chest clinics
is discussed.
Insufficiency of primary treatment of pulmonary
tuberculosis in relation to marriage and
abuse of alcohol
Axel Kok-Jensen. Scand. J. Resp. Dis ; 1972, 53,
274.
Drug default in 1064 patients of pulmonary
tuberculosis in Copenhagen was investigated
in relation to marital status and alcoholism.
40 per cent of the men and 3 per cent of the
women were chronic alcoholics. 56 per cent of
the men and 51 per cent of the women were not
married. Single men and women and alcoholics
had a greater tendency to default. Women on the
whole were more co-operative than men. Age
and severity of the disease did not seem to
have any effect on the default rate.
Isoniazid-Associated Hepatitis
SP.P.
Jerold D. Mose, James E. Lewis and C.
Michael Knauer. Amer. Rev. Resp. Dis.; 1972,
106, 849.
Five cases of hepatitis arising amongst a
group of patients on chemoprophylaxis with
INH have been reported. The patients were
in the age group 40 to 60 years in which age
viral hepatitis is uncommon. Untowards
symptoms appeared after 3 weeks to 3 months
of the start of INH. Two were males and 3
females. In none of the 5, hepatitis-associated
(Australian) antigen (HAA) was demonstrated
Ind. J. Tub., Vol. XXI, No.1

56 ABSTRACTS
in the serum. Four of the 5 patients were
receiving other drugs in addition to INH.
However none of these drugs is known to
produce liver damage and furthermore these
drugs were re-star ted without clinical exacerbation
after discontinuation of INH. The
patients however were not re-challenged with
INH. The historical feature of liver biopsy
specimens varied and included the picture of
classic viral hepatitis, portal inflammation and
portal granuloma. Unlike allergic or toxic
reaction, INH-associated hepatitis is apparently
idiosyncratic and not related to dose size. The
severity varied from transient serum transaminase
elevation to fulminant hepatitis. The
SGOT and SGPT values varied from 340 to
1430 units.
Isoniazid-Associated Hepatitis
Richard A. Garibaldi et al.
Dis.i 1972, 106, 357.
S.P.P.
Amer. Rev. Resp.
Two thousand three hundred and twenty
one adults who were reactors to tuberculin
were given INH chemoprophylaxis in February,
1970 in Washington, USA. During the
following 9 months, 19 of them manifested
clinical signs of liver disease. In 9 of the 19,
symptoms appeared within the first 60 days
of starting INH and in the remaining 10 during
the next 6 months. Symptoms consisted of
fatigue, anorexia, fever and gastro-intestinal
distress. Thirteen out of the 19 had jaundice
and 2 of these died. Ten of the 19 were
women and 9 men; their mean age was 49.4
years. In a matched controlled group of nonreactors
to tuberculin who were not given INH,
hepatitis developed only in one person during
the same 9 months period and in none of the
260 tuberculin reactors who refused
chemoprophylaxis.
Isoniazid toxicity in Chemoprophylaxis
S.P.P.
Richard B. Byrd. Transactions of the 31st VA—
Armed Force Pulmonary Diseaee
Conference; 1972, 31.
Research
232 adults of both sexes referred to the
tuberculosis control units of 3 military thoracic
diseases centres in USA were included in the
study. They comprised personnel on active
duty, retired military personnel and their
dependents. All of them were tuberculin
positive and had no evidence of active pulmonary
tuberculosis. There was no history of
alcoholism and SGOT was below 40 units in
all. Out of 232, only 160 persons who took
INH prophylaxis for one year or more are
included in the analysis. Ninety two of these
were males with a mean age of 39 years, range
being 19 to 63 years. The mean age of females
was 38 years with a range of 20 to 78. In 16
out of these 160 persons the drug had to be
discontinued because of symptoms suggesting
reaction or because of abnormal liver function
result. Twelve of these had symptoms of
intolerance, usually low grade fever, myalgia,
arthralgia and nausea with or without anorexia.
Urticaria, poly neuritis and paraesthesia were
noticed each in one person, Many persons
complained of lethargy and dizziness. Two
persons complained of alcohol intolerance
which is being reported as a side effect of INH
therapy. All these 12 persons became asymtomatic
within 2 weeks of stopping the drug.
No instance of clinical jaundice occurred
although in 9 of the 72 patients with clinical
symptoms, SGOT level was 50 units or greater,
ranging from 50 to 1400 units. The incidence
of elevated SGOT in asymptomatic patients
was also appreciable, 33 showing more than
50 units at least once. However only 7 had
values exceeding 100 units. Twenty eight
asymptomatic patients with SGOT elevation
not exceeding 100 units continued their
medication without interruption and liver
function eventually resolved either during the
course of study or after completing 12 months
treatment. On the basis of available data,
the author concludes that it is reasonable to
continue medication in such individuals as
long as they are asymptomatic and the SGOT
remains below 100.
S.P.P.
Ind. J. Tub., Vol. XXI, No. 1