The Indian Journal of Tuberculosis - LRS Institute of Tuberculosis ...

The 

Indian Journal of Tuberculosis 

Vol. 39 New Delhi, January 1992 No. 1 

SURAJKUND DELIBERATIONS 

The recent government effort to thoroughly review the NTP in respect of its overall achievements as 

well as shortfalls from expectations is both timely and commendable. At Surajkund (Haryana) gathered 

35 senior, experienced tuberculosis workers and public health administrators from all over India at a 

“Think-tank” workshop organised by the Directorate General of Health Services (DGHS) for this 

purpose on llth & 12th September, 1991. The publication in the pages of this Journal, in late 1990, of a 

comprehensive review of NTP by Dr. Wallace Fox, the eminent British scientist quite familiar with the 

Indian scene and the proposed initiative in that direction by the Tuberculosis Association of India, 

perhaps, led to the deliberations. The wider circulation of the recommendations of the workshop is 

being eagerly awaited by all concerned. 

At the “Surajkund Conclave” were present representatives of the Ministry of Health and Family 

Welfare, Directorate General of Health Services, W.H.O., UNICEF, Tuberculosis Association of India 

and some of its state affiliates, Planning Commission and Indian Council of Medical Research. The 

broad coverage and course of their discussions are discussed here to promote formation of a national 

consensus, necessary to prepare the ground for later effective implementation of the recommendations. 

The near unanimous view was to persevere with the present technical, organisational, operational 

and administrative set up of NTP, in view of the modest but definite successes achieved and the 

increasingly widespread acceptability of the fact that there really is no alternative to having the NTP 

integrated with the general health services. 

The foremost need was to accord NTP its due priority among the various other health programmes 

being implemented at the peripheral level. At present, NTP was receiving a low priority, leading to a 

comparative neglect of its various activities, and the resulting all round below-the-expectation 

performance. 

The distinct improvement, from a low level of performance in respect of case-finding, since 1981 with 

the setting up of yearly targets for sputa to be examined and new cases found - despite some misgivings 

regarding over-reporting and false reporting from some centres-was reviewed with satisfaction. It was 

the general opinion that the system should not only be continued but further improved. The premature 

discontinuation in some states of the participation of male multipurpose health workers (MPW) in casefinding 

was seen with concern in view of the very favourable results shown by operational studies, done 

by the National Tuberculosis Institute, Bangalore. The consensus, therefore, was in favour of 

redeployment of MPWs to improve rural case-finding, from the present 50% contribution to the overall 

case-finding achievement, to the expected 80% level. In cities and metropolises, however, the focus 

should be on slums, bustees and newly-come-up colonies where the health services' presence was 

minimal. Here, non governmental organisations (NGOs) could contribute a lot. The modus operandi of 

this supplemental effort would need to be evolved, separately in each city, through mutual discussion 

between the most active area NGO and the District Tuberculosis/City Tuberculosis Officer concerned. 

Strengthening of the laboratory component of peripheral health institutions (PHI) was considered 

essential for improving rural case-finding. Some measures, envisaging international assistance were

2 EDITORIAL 

suggested so that both quantitative and qualitative dividends could be expected by NTP as well as 

general health services. 

A growing tendency in some quarters to view case-finding and case-holding as separate entities for 

the purpose of laying emphasis was noted with great concern. Greater efficiency of one compared to the 

other was likely to prove more frustrating than rewarding and needed to be avoided. 

The crucial importance of ensuring timely, adequate and regular supplies of anti-tuberculosis drugs 

to obtain better treatment completion and fewer defaults was underlined unanimously. Besides, it was 

thought essential to reduce to a minimum number (one or two) the drug regimens made available under 

the national chemotherapy policy, in order to remove confusion, especially among the PHI medical 

officers and treatment organisers. 

The government plan to introduce short course chemotherapy in all the district tuberculosis 

programmes in a phased manner was welcomed. However, it was strongly felt that the case-holding 

capability must also be considerably strengthened and the staff given intensive training (especially in 

PHIs) in order to avoid the stark possibility of an inappropriate usage of powerful anti-tuberculosis 

drugs like Rifampicin and Pyrazinamide, leading to large-scale emergence of resistance to these drugs. 

Innovative approaches in drug distribution/defaulter action taking and operational studies to suggest 

steps were considered essential to achieve better treatment compliance. Also, it was felt that NGOs 

could play a crucial role in improving case-holding and treatment completion to a minimum of 70%. 

The importance of supervision and monitoring of NTP activities, at all levels, was supported by all. 

Health education, in which DTO must play a key role, was considered equally important. Nonetheless, 

the pre-eminent role of the Tuberculosis Association of India, its state affiliates and other NGOs in 

health education was accepted without question. 

It was also strongly felt that the time had come for NGOs to step forward to assist NTP reaching its 

expectations by graduating from their past “complementing/supplementing of the activities” role to 

partnership with the Government in making NTP a greater success. 

Important though the deliberations of this eminent group are and little doubt though there is that 

their recommendations would receive very favourable consideration from the Government, where is the 

mechanism to ensure that these recommendations would indeed be implemented effectively, within a 

suitable time frame? This aspect, perhaps the most important of all the considerations, must 

presumably have been placed by the Government under its own purview, since it was not discussed. 

However, tuberculosis workers would like to be assured that this crucial aspect is not lost sight of. 

Earlier, we had recommended the setting up of a “Task Force” with proper terms of reference and a 

suitable budget to oversee that the recommendations are implemented, as well as the necessary 

corrective actions are taken, till the time of the next review. It should be logical to associate State 

Governments and representatives of the Tuberculosis Association of India and its state affiliates in this 

joint effort. The composition of and the name given to such a body falls entirely within the purview of 

the Government. This is as it should be, because the primary responsibility for the success of NTP is 

that of the Government. We can render service by offering our full assistance in this endeavour. 

D.R. NAGPAUL

Leading Article Ind. J. Tub., 2992, 39, 3 

HIV AND TUBERCULOSIS 

An unusual pattern of opportunistic diseases 

in predominantly young homosexual men was 

notified to the Centers for Disease Control 

(CDC) in Atlanta, U.SA. by physicians in New 

York city, Los Angeles and San Francisco in late 

1980 and early 1981. These notifications were the 

first cases of Acquired Immunodeficiency 

Syndrome (AIDS) representing the severe end of 

the clinical spectrum that follows infection with a 

retro virus, the human immunodeficiency virus 

(HIV), formerly called the human T Lymphotrophic 

virus type III/Lymphadenopathy associated 

virus (HTLV-III/LAV), by scientists at the 

Pasteur Institute 1 and the National Institute of 

Health 2 . 

The biological characteristic of AIDS is a 

major deficiency in cellular immunity that occurs 

with destruction of a substantial amount of T 4 or 

T helper lymphocytes. The deficient cellular 

immunity leads to frequent occurrence of 

infections which is normally controlled by cellular 

immunity. Tuberculosis is a classic example of a 

disease, resistance to which is mediated by 

cellular immunity. As such, tuberculosis is 

prominent among the diseases that affect patients 

with AIDS. 

Etiological Aspects 

The HIV infection, transmitted essentially 

through blood or sexual intercourse is generally 

asymptomatic. The clinical profile caused by HIV 

infection results from the virus infecting the CD 4 

(T 4 ) lymphocytes which may be destroyed or have 

their normal function impaired. 

Nearly all the cases of tuberculosis occur as a 

result of infection acquired via the lungs through 

the inhalation of infectious aerosol droplets 

containing viable M. tuberculosis. Following 

primary infection with Koch's bacilli, the strain 

can survive in the host (even a non-HIV-infected 

host) for years and decades without causing any 

pathological manifestation. This is due to the 

balance that is reached between the 

aggressiveness of the pathogen and host's defence 

mechanisms, drawn mainly from cellular 

immunity 3 . Murray and Mills 4 have noted that 

lungs may be more predisposed to opportunistic 

complications because their immunological 

capabilities may be more suppressed than those 

of other organs. It is not clear whether the 

vulnerability of lungs to infections is merely the 

regional manifestation of the systemic 

abnormality or additional HIV induced factors 

affect the lungs' own complex local defense 

mechanisms. 

Epidemiological Aspects 

(a) 

North America 

In the United States, the trend of tuberculosis 

is known since 1953 when national reporting was 

started. There has been an average decline of 

about 5% per year in the tuberculosis case rate 

upto the year 1984. In 1985, the rate of decline 

lessened to 0.2% and in 1986, for the first time in 

33 years, there was an increase of 2.6% in the 

number of reported cases 5 . Pitchenick et al 6 have 

reported that tuberculosis occurred in 61.4% of 

Haitians with AIDS (27/44) compared with 2.7% 

of non-Haitians (1/37) with the syndrome. Louis 

et al 7 reported that 24 of 280 (8.6%) patients with 

AIDS had tuberculosis while Chaisson et al 8 

found in a San Francisco population based study 

that of the 287 cases of tuberculosis in non Asian 

males, 15 to 60 years of age, 35 (12%) had AIDS, 

including 23 America born whites. 

(b) 

African Countries 

In sub-Sahara Africa, there is a high 

prevalence of HIV infection in many countries 

that also have an extremely high prevalence of 

tuberculosis. In urban centres of this region, 5% 

to 20% of the sexually active population are 

infected with HIV 9 Although data from Tanzania 

and Burundi show an increase in the number of 

tuberculosis cases after 1983, yet the increase 

could either be due to HIV infection or to an 

improved utilisation of health services 10.

4 V. SIVARAMAN ETAL 

(c) India 

The Indian Council of Medical Research 

(ICMR) in collaboration with the Directorate 

General of Health Services has built up a network 

of 43 surveillance and 5 reference centres to carry 

out a serosurveillance of HIV infection in the 

country. Of the 580,824 high-risk group persons 

screened during October 1985 to October 1990, 

4,082 (7.0 per 1000) were found to be HIV 

positive, including 57 AIDS patients 11 - Extensive 

disseminated tuberculosis was seen only in 2 

patients 113 

Our group in Pondicherry screened 225 

tuberculosis patients admitted in TB Sanatorium, 

and the method outlined by Murray 13 , a 

computerised mathematical model has been 

developed to estimate the impact of HIV 

infection on tuberculosis epidemiology within a 

wide range of assumptions : 

(1) Seroprevalance of HIV in general 

population varies from 0.07 to 1.75 per 1000 (i.e. 

1 to 25% of the general population is at risk and 7 

per 1000 among them develop HIV infection). 

(2) Seroprevalence of HIV among TB 

patients varies from 1% to 6% (corresponding to 

95% confidence limits of our Pondicherry 

patients). 

Figure 2 shows the estimated impact of coinfection 

with HIV on the incidence of TB 

Fig. 1. Conceptual mode] of inter relationship of HIV infection and tuberculosis 

Pondicherry and suspected to be harbouring HIV 

infection and found 6 to be seropositives 12 . 

Applying the 95% confidence limits to this selective 

study, we can assume that roughly between 

1% to 6% of the tuberculous patients might be 

HIV seropositive in this area. The assumption, 

based on so limited and selective data has been 

made in order to understand the relationship 

between HIV infection and tuberculosis, 

A conceptual model of the inter relationship 

between HIV and tuberculosis is shown in figure 

1, along with the flow rates applicable to the 

Indian epidemiological conditions. Based on this 

disease. For a given Seroprevalance, the incidence 

among TB population shows very little variation 

when the seroprevalence in the community varies. 

Figure 3 shows time trend of the prevalence of 

TB under Indian conditions, with 3 different 

seroprevalence of HIV infection. The HIV 

related increase in the prevalence of tuberculosis 

may be considerable (The graph is computer 

generated from the model described by 

Sivaraman et al 14 The input parameters are the 

same as the program A but the incidence rate is 

higher and is derived by the method described by 

Murray 13 ).

Fig. 2. Estimated impact of HIV infection on TB incidence 

Note: The TB incidence per 100,000 may vary from 293.4 to 293.9, 299.5 to 300 and 309.0 to 309.6 when the 

seroprevalence of HIV among TB patients is 1%, 3%, 6% respectively (indicated below the curves). 

2,55-1 

2,30 

Years (since 1987) 

Fig. 3. Impact of HIV infection on time trend of TB 

Note: NOHJV: A downward trend in prevalence of TB will be noted when there is no HIV infection in the 

community: It will decline from 2.52 per 1,000 to 2.36 per 1,000 over nine years. 

EHW: The estimated seroprevalence of HIV among tuberculosis patients is 2.7% from our observations in 

Pondicherry. The decline in the prevalence of TB will be from 2.52 per 1,000 to 2.41 per 1,000. 

HIH1V: If the highest limit of seroprevalence of HIV among TB patients i.e. 6% is assumed, the decline in 

prevalence of TB per thousand will be negligible and will be from 2.52 to 2.50 per 1,000.


Clinical Aspects 

Pitchenick and Rubinson 15 have made the 

following detailed observations on 23 adult 

patients who had culture proved tuberculosis and 

acquired immuno-deficiency syndrome: 

(1) Chest radiographs resemble frequently 

the pattern of primary tuberculosis, i.e. hilar or 

mediastinal adenopathy with or without 

cavitation; pulmonary infiltrates are located with 

approximately equal frequency in the upper and 

lower lung fields; sputum cultures for M. 

tuberculosis are frequently positive; pleural 

effusions are infrequent and small while 

extrathoracic (especially lymphatic) tuberculosis 

is very common, probably part of a generalised 

lymphatic tuberculosis. 

(2) Patients may present with or develop 

miliary TB while under observation. 

(3) Other concurrent pulmonary infections 

(e.g. Pneumocystis carinii pneumonia) are 

common and confound the radiographic 

diagnosis of pulmonary tuberculosis. In this 

situation, rapidly changing pulmonary infiltrates 

suggest a non tuberculous infection and hilar or 

mediastinal adenopathy may serve as a clue to the 

co-existence of tuberculosis. 

(4) Patients may have positive sputum 

cultures for M. tuberculosis or active extra 

thoracic or disseminated tuberculosis even 

though the chest radiographs are normal. 

(5) Despite the immuno-suppressed state, 

the chest radiographic abnormalities clear within 

months of starting anti-tuberculosis drug therapy. 

(6) Patients with AIDS and mycobacterial 

disease, frequently, do not show the typical 

granulomatous tissue reaction. This may explain 

the absence of pulmonary cavitation and rapid 

radiographic clearing of tuberculous infiltrates 

after drug therapy without evidence of scaring. 

The presence of tissue granulomas may denote a 

better state of body immune defences. 

Two closely related non-chromogenic 

mycobacteria (Runyon's group III)-M. avium 

and M intracellulare grouped together as 

Mycobacterium avium complex (MAC) have been 

isolated from patients with HIV infection in the 

United States and other developed countries, 

more often than other mycobacteria including the 

more virulent M. tuberculosis, although the 

reverse is true in Central Africa and other 

developing countries 4 ' However, the clinical 

significance of the recovery of these mycobacteria 

from the lungs alone remains uncertain, while the 

identification of these organisms in lymphnodes, 

bone marrow or blood is persuasive evidence of 

the presence of disseminated disease. But the 

clinical relevance of disseminated disease with M 

avium complex in patients with AIDS is not clear. 

The currently available anti-mycobacterial agents 

do not, usually, produce clinical improvement or 

microbiologic cure. 

Therapeutic Aspects 

The standard anti-tuberculosis drugs are 

extremely effective in TB patients with HIV 

infection. The recommended regimen for treating 

tuberculosis in HIV infected adult patients is 

Isoniazid, Rifampicin and Pyrazinamide but 

Ethambutol may also be used if Isoniazid 

resistance is suspected. The CDC and the 

American Thoracic Society have recommended 

that treatment be given for at least six months 

beyond the conversion of sputum culture to 

negative in patients with HIV infection and 

pulmonary tuberculosis 16 

Adverse reactions to anti-tuberculosis 

medicaments necessitating a change in therapy 

occurred in 25% of Chaisson's patients 8 . 

Mortality in patients with tuberculosis and 

AIDS is high in the different reported series : the 

median survival from the time of tuberculosis 

diagnosis was 7.4 months and from the time of 

AIDS diagnosis 8.1 months in Chaisson's series. 

The cause of death was almost always AIDS, not 

tuberculosis. 

Efforts to treat HIV infection and AIDS have 

been directed towards inhibition of virus 

replication and restoration or stimulation of the 

impaired immune function 17 - Restoration of 

immunity has been attempted by bone marrow 

transplantation or lymphocyte transfusion and by 

lymphokine administration. Immune-stimulatory 

drug therapy has also been proposed for 

increasing immune functions in HIV infected 

persons. Preliminary reports on isoprinosine in 

patients with generalised lymphadenopathy or the 

AIDS related complex have shown a transient 

improvement in the natural killer cell functions 18

HIV AND TUBERCULOSIS 7 

without consistent clinical alleviation. Further, 

the use of cyclosporin, despite its obvious 

potential hazards, and intravenous gammaglobulin 

has also been tried. Further trials of 

antibody preparations may be expected 19 

The Effect of HIV Infection on Tuberculosis 

Programmes 

Besides the possible increase in the number of 

tuberculosis patients, to receive services, 

important qualitative changes in the tuberculosis 

services can be anticipated in the HIV/AIDS era. 

The new problems to be tackled include the 

following 10 : 

1. HIV positive persons are frequently 

tuberculin negative, lowering the sensitivity of this 

tool. 

2.. The clinical and radiographic pictures of 

tuberculosis are different from what is normally 

seen. 

3. There are reports of more frequent 

relapses with the use of conventional 

chemotherapy and CDC has made different 

recommendations for effective treatment. 

4. The concern about the use of BCG, 

following reports of severe local reactions and 

possible dissemination has led to a modification 

in the WHO EPI recommendation favouring its 

exclusion in symptomatic HIV infected children. 

5. The transmission of HIV may occur 

among TB patients through the use of 

inadequately sterilized syringes for Streptomycin 

injections. The joint WHO/IUATLD working 

group on HIV infection and tuberculosis 20 has 

recommended that when sterility of needles and 

syringes cannot be ensured, an entirely oral 

regimen should be used. The working group has 

further recommended that in countries where the 

national TB programme strategies include 

chemoprophylaxis, dual infection with HIV and 

M. tuberculosis should be considered as an 

indication for chemoprophylaxis. 

So far as India is concerned, pessimism on 

account of AIDS may not be warranted as the 

seroprevalence rate even in high risk groups is 

comparatively low. Nevertheless, vigilance and 

prompt action by clinicians and programme 

planners is called for. 

Acknowledgement 

We are grateful to Director, JIPMER and 

Director, Health and Family Welfare Services, 

Government of Pondicherry for permission to 

publish this paper. Shri Ram Mohan's assistance 

in getting the computer print outs is also 

acknowledged. 

References 

1. Barre, Sinoussi F., Chermann J.C, Rey F et al. 

Isolation of a T lymphotropic retrovirus from a 

patient at risk for acquired immuno deficiency 

syndrome (AIDS), Science; 1983, 220, 868. 

2. Popovi C.M, Sarangadharan M.D,, Read E, 

Gallo R.C. Detection, isolation and continuous 

production of cytopathic retroviruses (HTLV- 

III) from patients with AIDS and pre AIDS. 

Science, 1984, 224 ? 497. 

3. Prignot J, and Sonnet. AIDS, Tuberculosis and 

mycobacteriosis. Bull. IUATLD; 1987, 62, 7. 

4. Murray J.F and Mills J. Pulmonary infectious 

complications of Human immuno deficiency 

virus infection; Am. Rev. Respir. Dis., 1990,141, 

1356, 

5. Centers for Disease Control—Tuberculosis final 

data-United States 1986 MMWR 1988, 36, 817. 

6. Pitchenick A.E., Cole C, Russel B. 5 Fischl, 

M.S., Spira J and Snider D,E, Jr. Tuberculosis, 

atypical mycobacteriosis and the acquired 

immunodeficiency syndrome among Haitian 

and non Haitian patients in South Florida. Ann. 

Intern. Med., 1984, 101, 641. 

7. Louis E.E., Ricel B. ; and Hizman R.S. 

Tuberculosis in non Haitian patients with 

acquired immuno deficiency syndrome. Chest; 

1986, 90, 542. 

8. Chaisson R.E., Sheeter G.E., Thever C.P., 

Rutherford G.W., Echenberg D.F., and 

Hopeweil P.C. Tuberculosis in patients with the 

acquired immuno deficiency syndrome, clinical 

features, responses to therapy and survival. Am. 

Rev. Respir. Dis.; 1986, 136, 570. 

9. Mann J.M. Chin J, Piot P., Quinn T. The 

international epidemiology of AIDS Sci. Am. 

1988, 8, 82. 

10. Slutkin G. Leowski J and Mann J. The effects of 

the AIDS epidemic on the tuberculosis 

problems and tuberculosis programmes. Bull. 

IUATLTD; 1988, 63, 21.


11. ICMR HIV infection—On going studies and 

future research plans. ICMR Bull; 1990, 20, 

120. 

lla. 

ICMR HIV infection—On going studies and 

future research plans ICMR Bull.; 1989,19,115. 

12. Sivaraman V. Fernandez G and Sambasiva Rao 

R. HIV infection and pulmonary tuberculosis 

Report of 6 cases. Ind. J. Tub. (see pages 35-39.) 

13. Murray J.F. The Burns Amberson lecture. The 

White Plague : Down and out or up and 

coming? Am. Rev. Respir. Dis., 1989,140,1788. 

14. Sivaram V. Balu V. and Flora V. Alternative 

tuberculosis control strategies and their 

potential impact. Ind. J. Tub., 1988, 35, 117. 

15. Pitchenick A.E.C. and Rubinson H.A. The 

radiographic appearance of tuberculosis in 

patients with the acquired immuno deficiency 

syndrome (AIDS) and pre AIDS : Am. Rev. 

Respir. Dis., 1985, 131, 393. 

16. Centres for Disease Control : Diagnosis and 

management of mycobacterial infection and 

disease in patients with human T lymphotropic 

virus type III/ lymphadenopathy associated 

virus infections. MMWR, 1986, 35, 448. 

17. Mitsuya H. Broder S. Strategies for antiviral 

therapy in AIDS. Nature; 1987, 325, 773. 

18. Wallace J. Bekesi J.G. : A double blind clinical 

trial of the effects of inosine pranoblex in 

patients with prolonged generalized 

lymphadenopathy. Clin. Immunol Immunopathol, 

1986, 39,179. 

19. Selgmam M, Pinching R.J, Rosen F.S., Fahey 

J.L, Khartov R.M., Klatzman Detal : 

Immunology of Human immunodeficiency 

virus infection and the acquired immuno 

deficiency syndrome. Ann. Interm. Med., 1987, 

107, 234. 

20. WHO/IUATLD: Tuberculosis and AIDS 

Statement on AIDS and Tuberculosis. BULL. 

Int. Union Tuberc. Lung Dis.; If 89, 64, 8. 

Dr. V. Sivaraman and Dr. Gilbert Fernandez 

TB Sanatorum, Gorimedu, Pondicherry 

Dr. R. Sambasiva Rao 

AIDS Surveillance Centre, JIPMER, Pondicherry

Original Article Ind. J. Tub., 1992, 39, 9 

SHORT COURSE CHEMOTHERAPY AND EFFICIENCY VARIABLES IN 

NATIONAL TUBERCULOSIS PROGRAMME : A MODEL 

A.K. Chakraborty 1 , V.H. Balasangameshwara 2 , P. Jagota 3 , T.R. Sreenivas 4 , and K. Chaudhuri 5 

(Original received on 19.2.91; Revised version received on 4.9.91; Accepted on 8.11.91) 

Summary. The mathematical model presented here 

brings out the role of various levels of efficiency in 

the performance of key tuberculosis control 

activities in the light of the introduction of short 

course chemotherapy (SGG) under the District 

Tuberculsosis Programme (DTP) in India. It shows 

that the potential of DTP could be realised only 

when all the Various activities are performed with 

a high degree of efficiency; And that SCC alone 

cannot appreciably alter the DTP Efficiency 

expectations. For example, DTP efficiency with 

SCC, even when 100% of patients take more than 

80% of the prescribed drugs increases only to 29% 

with SCC, over 24% with standard chemotherapy 

(SR), if case-finding efficiency (CF efficiency) 

remains unchanged at 33%, Which is its current 

level. A “critical DTP efficiency” i.e., the efficiency of 

the various DTP activities that could lead to 

sputum conversion of 85% of the cases diagnosed 

requires the performance of key activities at a 

high level namely, CF efficiency of 100%, cases put 

on SCC 100% a rid the compliance structure of 70% 

iii level four and 20% in level three. Thus, DTP 

shall have to be geared to meet high performance 

requirements to achieve its avowed objectives. 

The model gives various levels of expectations 

as the outcome of DTP, relating to changes in 

efficiency estimates of the key DTP activities. 

Introduction 

The introduction in District Tuberculosis 

Programme (DTP) of short course chemotherapy 

regimens (SCC) which have achieved nearly one 

hundred percent treatment efficacy in clinical 

trials has generated a high degree of expectation 

among the planners and programme officers 

regarding the role of SCC in tuberculosis control. 

The faith in SCC as a tool of tuberculosis control. 

however, needs to be viewed in the light of the 

earlier hypothesis in respect of standard regimens 

(SR) 1,2,3. Thus, in a misplaced perception of 

priorities, one may overlook the earlier inference 

that was derived from the then mathematical 

projection, showing that the overall success in 

DTP depended more on increasing the efficiency 

of case-finding than that of treatment, per se. 

It may be argued, that mathematical 

projection of some likely situations (effectvariables) 

on the basis of some data on the 

simultaneous interaction of multiple variables 

may, after all, lead to a thin approximation to the 

actual situations because the quantification of 

interactions is obtained from separate studies. 

Moreover, many variables of unknown magnitude 

may be left out on account of failure to conceive 

them theoretically and prepare a suitable 

hypothesis. Further, confidence intervals of the 

effect-variables are difficult to work out, 

rendering the task of calculating a curve of 

mathematical fit a distinct hazard 4 - There is no 

denying the difficulty in the case of chronic 

illnesses in obtaining inferences from 

observational studies with multiple cross 

classifications. It is also realised that this becomes 

almost impracticable in the face of increasing 

number of variables. However, mathematical 

models may be helpful, in this context, in getting 

a torrent of data arranged and processed 

systematically 5 ’ even though the indiscriminate 

inclusion of multiple variables may become 

complex and create problems about the 

credibility of the inferences. Many scientists, 

engaged in the study of the so called “soft 

sciences”, including medical sciences like to 

construct models, if only to serve as qualitative 

1. Additional Director; 2. Bacteriologist; 3. Chief Medical Officer; 4. Statistician; 5. Director, National 

Tuberculosis Institute, 8, Bellary Road, Bangalore-560 003. 

Correspondence : The Director, National Tuberculosis Institute, 8, Bellary Road, Bangalore-560 003..

10 A.K. CHAKRABORTYET AL 

statements on the nature of working systems, 

without resorting to the rigors of obtaining 

statistical support from co-efficients of the effectvariables. 

Others like to limit the number of 

variables to be studied, or further verify whether 

the nature of the findings generated by the model 

are in consonance with a prior hypothesis. In 

other words, the bounds of direct observation are 

sought to be extended through constructing 

models. The present study is an attempt on 

similar lines. Its aim is to present the decision 

makers a choice in selecting one among the 

several alternative courses, worked out by an 

interplay of several sets of variables that could 

not have been practicably obtained from 

observational studies. 

The data from several relevant operational 

studies have been used by us in seeking to 

investigate the role of case-finding and treatment 

under DTP, at various efficiency levels in the 

context of tuberculosis control, consequent to the 

introduction of SCC. The model thus constructed 

could also be used to compute expectations, 

based on the performance of some of the key 

activities in tuberculosis control at some 

hypothetically imputed levels, based on user 

response and service efficiency. These 

expectations, on the other hand, could also set the 

process of matching the current as well as future 

performance of DTP, subject to input variations 

from time to time. 

Material and Methods 

The model was constructed on a Personal 

Computer (PC-XT, ET&T), using LOTUS 1-2-3 

software package. The operational flow chart 

considered for the preparation of the model is 

given in the Figure (P. 11). The definitions used 

and the ratios and assumptions governing the 

flow of events in the model, along with the 

computed absolute numbers constituting the flow 

are as follows : 

Prevalence of cases in an average district: (A in 

Fig.) The population size of an average Indian 

district is taken as 1.5 million. The prevalence of 

sputum culture positive cases among those aged 

= >5 years in an average district works out to 

5,000, at nearly 4/1,000 (Ref. 6). Case load for 

an average DTP : (B in Fig.) The 

case load in an average DTP is the number of 

previously undiagnosed symptomatics reporting 

to DTP units and diagnosed as cases. It is 

calculated to be approximately 2,500 cases i.e., 

50% of the prevalence in the district 7 

Potential of case-finding : (C in Fig.) It is the 

number of cases, diagnosable by Ziehl-Neelsen 

microscopy 8 , being 80% of 2,500 culture positive 

case load i.e., 2,000 cases. These cases are taken 

to be smear as well culture positive. 

Efficiency of case-finding : (CF efficiency-D in 

Fig.) It is the number or proportion of cases that 

could be diagnosed out of previously undiagnosed 

sputum smear positive cases presenting 

themselves for diagnosis in a DTP. [At the 

average level of efficiency of 33%, as estimated by 

the Monitoring Section of National Tuberculosis 

Institute, Bangalore 9 (NTI), about 660 cases]. 

Levels of compliance : These are the proportions 

of doses taken (collected doses are presumed to 

have been consumed) out of the total due by the 

cases put on treatment. The levels of compliance 

for INH-Thiacetazone regimen for standard 

chemotherapy 10 (SR) and fully self administered 

2ERH/4H2R2 SCC regimen 11 have been 

considered for developing the model. These 

regimens were selected because valid data on 

compliance levels could be computed from them. 

The levels of compliance for treatment are 

defined as follows: 

In respect of SR—expressed as percent of 

collections made out of due in one year : 

Level 1-up to 25; Levels 2-from 26 to 50; 

Levels 3-from 51 to 75; Level 4-from 76 to 100. 

In respect of SCO-expressed as percent of 

drug collections during the first two months of 

intensive and the following four months of 

continuation phase: 

Level 1-less than 80 in both intensive and 

continuation phase; Level 2- less than 80 in 

intensive phase and more than 80 in continuation 

phase; Level 3-more than 80 in intensive phase 

and less than 80 in continuation phase; Level 4- 

more than 80 in both the phases. Rate of 

Compliance: It is the proportion of cases who 

take treatment at a given level of compliance 

(Tables 1 and 2). These proportions are taken 

from some operational studies and then rounded 

off to the nearest digit in Tables 5 & 6 10 ' 11

SCC AND EFFICIENCY VARIABLES IN DISTRICT TB PROGRAMME 11 

Flow Chart showing interventions in tuberculosis problem through DTP at various performance levels 

Prevalence cases in Community (5,000) A 

Symptomatics 

OPD Case Load Cases Reporting to 

PHIs and DTC B 

(50% x A = 2,500) I 

Notes :OPD-Out Patients Department; PHI-Peripheral Health institution; DTC-District Tuberculosis Centre; SR- 

Standard Regimen in DTP; DTP-District Tuberculosis programme; SCC-Short Course Chemotherapy 

regimen in DTP; Compliance levels (1 through 4) see text. Figure based on hypothetical population of an 

average district as 1.5 million. 

H

12 A.K. CHAKRABORTY ETAL 

The distribution of cases at the different levels 

of compliance is termed “compliance structure''. 

Sputum Conversion by levels of compliance : The 

proportion of cases becoming sputum negative at 

the end of the prescribed period of 

chemotherapy, by the various rates of 

Mix of regimens : In those districts which have 

implemented SCC, not all the cases are put on 

SCC. The proportions put on SR and SCC would 

vary from DTP to DTP, ranging between two 

hypothetical extremes of 100% on SR with 0% on 

SCC at one end and 0% on SR with 100% on 

SCC at the other end. The situation of mix of 

Table 1. Compliance and sputum conversion among 660 cases put on SR 

Compliance Structure @ 

Sputum Negative 

Level Rate (%) Number** Rate (%) Number** 

1 

2 

37.0 

9.6 

244 

63 

21.7 - 

47.6 

53 

30 

3 7.9 52 47.6 25 

4 45.5 300 73.3 220 

Total 100.0 660 49.7* 328 

@ Compliance structure-see text; * Treatment efficiency with 100% SR = (328/660) x 100 = 49.7%; ** For value 

of cases, decimal points omitted 

Table 2. Compliance and sputum conversion among 660 cases put on SCC 

Compliance Structure @ 


Level Rate (%) Number** Rate (%) Number** 

1 20.3 134 56.3 75 

2 4.1 27 66.7 18 

3 19.6 129 79.2 102 

4 56.0 370 87.8 325 

Total 100.0 660 78.9* 520 

@ Compliance structure-see text; * Treatment efficiency with 100% SCC = (520/660) x 100 = 78.86%; ** For 

values of cases, decimal points omitted 

compliance, out of those actually put on 

treatment as observed in operational studies is 

computed in Tables 1 & 2 columns 4 & 5. The 

computation is based on the observation that 

some proportions of cases become sputum 

negative in 1st, 2nd and 3rd levels of compliance 

and remain so even at the end of the stipulated 

period of treatment, inspite of not having 

consumed the prescribed number of doses of 

drugs 10,11. 

regimens has been denoted in Roman numericals 

from I to XI in Table 3 & Figure. 

Treatment efficiency : (E,F,G in Fig.) It is the 

proportion of cases estimated to be sputum 

negative at the end of the treatment period out of 

those put on treatment (i.e. the number 

converted out of 660 cases in district of average 

performance). Sputum conversions have been 

calculated taking into consideration the sum-total


Table 3. Sputum conversion among cases diagnosed in DTP on various mixes of SR & SCC regimens 

(taking the rate of compliance as in Table 1) 

Situation 

of regimen mix 

Proportion of Cases 

on(%) 


(Number)* 

Efficiency 

(%) 

SR On SR On SCC Total Trt Eff DTP Eff 

(a) (b) 

SCC 

I 100 0 328 0 328 49.71 16.40 

II 90 10 295 52 347 52.63 17.37 

III 80 20 263 104 367 55.54 18.33 

IV 70 30 230 156 386 58.46 19.29 

V 60 40 197 208 405 61.37 20.25 

VI 50 50 164 260 424 64.28 21.21 

VII 40 60 132 312 444 67.20 22.18 

VIII 30 70 98 365 463 70.11 23.14 

IX 20 80 66 416 482 73.03 24.10 

X 10 90 33 468 501 75.94 25.06 

XI 0 100 0 520 520 78.86 26.02 

Case-finding potential - 2,000 : Case-finding efficiency (33% of 2,000) - 660; (a) Trt, eff= (Treatment 

efficiency) = ((value in column 6)/660) x 100; (b) DTP. Eff-(DTP efficiency) - ((value in column 6)/2,000) x 100; 

* For values of cases, decimal points omitted, being number of cases 

of conversions achieved at varying compliance 

structures, either under SR, SCC, or the various 

mixes of SR and SCC (Tables 1,2 and column 7 of 

Table 3). 

DTP efficiency : (H in Fig.) It is the proportion of 

cases estimated to be sputum negative out of the 

total diagnosable cases m the DTP i.e., casefinding 

potential of 2,000. The sputum 

conversions are computed as under treatment 

efficiency. It needs to be underlined that the 

denominator includes the number of smear 

positive cases who report themselves for 

diagnosis to the participating centres of the DTP 

but are not diagnosed. As a manifestation of 

shortfall in the efficiency of DTP, a proportion of 

cases are thus denied treatment and possible 

conversion which should have occurred if all the 

cases had been diagnosed. 

The formula used in estimating DTP efficiency 

is H-D X G(G- E x proportion of SR in the 

mix) + (F X proportion of SCC in the mix). 

Results 

Mix of Regimens 

Table 3 computes the various mixes of the 

proportion of cases likely to be on SR and SGC in 

the DTPs where SCC is implemented, as 

situations I to XL At one extreme could be placed 

the DTPs where SCC is not implemented at all 

(situation I with 100% SR and 0% SCC) and on 

the other the presently hypothetical and 

unrealistic situation where all the diagnosed 

sputum positive cases are on SCC (situation XI). 

In between the two extremes, one may expect 

DTPs where SCC is implemented to the extent of 

10% to 90% of cases on SCC with corresponding 

decrease in the proportion of cases on SR. 

Expectations of sputum conversions, as a 

proportion of the estimated number of diagnosed 

cases relative to the various mixes detailed as 

above, are also given in the Table. 

Treatment efficiency under mixes 

The treatment efficiency in a district with no

14 A.K. CHAKRABORTY ETAL 

SCC would be 49.7% (situation I). The 

corresponding efficiency for a DTP where all the 

cases are put on SCC would work out to be 78.9% 

(situation XI). For situations II to X, the expected 

sputum conversion could be calculated to be 

anywhere between 52.6% and 75.9%. 

DTP efficiency under mixes 

After bringing in the additional factor of 

efficiency of case-finding, the estimated 

proportions of cases converted out of the 

potentially diagnosable cases (DTP efficiency) 

are presented in Col. 8 of Table 3. The DTP 

efficiency ranges from 16.4% to 26.0%. 

Compliance & treatment efficiency 

The above computations made respective to 

the rates of compliance, in cases put on SR and 

SCC at compliance levels of 1 to 4 are given in 

Tables 1 and 2 respectively. Estimates of 

treatment efficiency with hypothetically imposed 

improvements in the rate of compliance are given 

in Tables 4 & 5. Assuming that all the cases are 

put on 100% SR or 100% SCC at level 4, (i.e., 

with 80% or more of drug consumption), the 

treatment efficiency would be 73.3% & 87.8% 

respectively (not on Table). However, 

considering it to be an unrealistic situation, four 

different assumptions on compliance structure 

are worked out, with upto 70% of cases being 

compliant at level 4 (Table 4). In this exercise, the 

rates of compliance are gradually decreased at 

the lower levels of compliance with proportionate 

increase of the rates at the higher levels. Sputum 

conversion under the varying proportions of 

mixes with SR and SCC are then worked out, 

Table 4. Treatment efficiency* by varying proportional distribution of cases on SR 

& SCC at different compliance levels 

Proportion of Cases complying at (%) (a) 

On SR 

Levels Current (:) 

compliance 

Compliance hypothetically varied 

1 

37 10 10 5 5 

2 10 20 10 10 10 

3 8 20 20 20 15 

4 45 50 60 65 70 

Overall 100 100 100 100 100 

(49.71) (57.86) (60.43) (63.01) (64.30) 

(Overall percentage of cases sputum negative in brackets) 

(b) On SCC 

1 20 10 5 5 5 

2 4 10 10 5 5 

3 20 20 20 25 20 

4 56 60 65 65 70 

Overall 100 100 

(78.86) (80.81) 

(Overall percentage of cases sputum negative in brackets) 

100 

(82.39) 

100 

(83.01) 

100 

(83.44) 

(:) Observed from recent operational studies (Ref 10,11). See Tables 1 & 2; * Treatment efficiency-negative status 

of cases at the end of treatment among cases diagnosed in DTP, computed on the basis of respective sputum 

conversion rates for compliance given in columns 2 to 6 of parts a & b


Situation of 

Regimen 

Mix 

Table 5. Treatment efficiency* by varying compliance structure and regimen mix (SR +SCC) 

Proportion of 

Patients(%) SR 

SCC 

Current (:) 

Compliance 

Sputum negative (%)* At 

Compliance Hypothetically Varied® 

1 2 3 4 5 6 7 8 

I 100 0 49.71 57.86 60.43 63.01 64.30 

II 90 10 52.63 60.15 62.63 65.01 66.21 

III 80 20 55.54 62.45 64.82 67.01 68.12 

IV 70 30 58.46 64.74 67.02 69.01 70.04 

V 60 40 61.37 67.04 69.21 71.01 71.95 

VI 50 50 64.28 69.33 71.41 73.01 73.8 

VII 40 60 67.20 71.63 73.60 75.01 75.78 

VIII 30 70 70.11 73.92 75.80 77.01 77.70 

IX 20 80 73.03 76.22 77.99 79.01 79.61 

X 10 90 75.94 78.51 80.19 81.01 81.53 

XI 0 100 78.86 80.81 82.39 83,01 83.44 

(:) Observed from recent operational studies (Ref 10,11). See Tables 1 & 2; * Treatment efficiency-negative status 

of cases at the end of treatment among cases diagnosed in DTP, computed on the basis of respective sputum 

conversion rates for compliance given in columns 2 to 6 of parts a & b of Table 4; @ column 5,6,7,8 correspond to 

the variables given in columns 3,4,5,6 of Table 4 respectively 

respective to each compliance structure (Table 

5). For example, in Table 4 the column 2 under 

SR gives the currently observed compliance rates 

at the respective levels observed in operational 

studies (same as in Table 1). In column 3, a 

hypothetically improved situation of compliance 

is depicted, wherein only 10% of the cases are at 

level 1, 20% each at levels 2 & 3 and 50% at level 

4. Assuming a still further improvement, a 

situation is constructed (in column 6) where 70% 

of the cases complete treatment at level 4 and 

only 5% at level 1. Similar variations for SCC are 

shown in Table 4 Part (b) (SCC). Table 5 gives 

the treatment efficiency of various mixes, 

computed by mixing respective sputum 

conversion rates, by varying both the proportions 

of cases on SR or SCC as well as the compliance 

structure, as per columns 3 to 6 of Parts a & b of 

Table 4. For example, in the. situation IIP of 

regimen mix given in Table 5 (i.e., 80% of cases 

on SR and 20% on SCC), as per compliance by 

levels given in column 2 of a & b in Table 4, 

55.54% of the cases would turn sputum negative 

(Table 5). However, when compliance rates as 

per column 6 of a & b (Table 4) are applied to 

the same mix (situation III), 68.1% of the cases 

get converted (column 8 situation III in Table 5). 

Sputum conversions at other hypothetical 

compliance structures by various mixes could be 

worked out from Table 5. 

Compliance & DTP efficiency 

Tables 6 and 7 show the computations of DTP 

efficiencies when the rates of compliance are 

gradually improved from the current rates to a 

hypothetical situation of all the cases complying 

at level 4 and, at the same time, the efficiency of 

case-finding is increased from the current 33% to 

40% and applying thereafter an incremental value 

of 10% in CF efficiency till 100% efficiency is 

reached. For example, the DTP efficiency of SR 

would then increase from 16.4% at the current 

rates (shown in column 2 of Table 6) to 24.2%, 

when all the cases comply at level 4 (column 8, 

Table 6) with CF efficiency remaining at 33%. 

The DTP efficiency would be three times the 

above figure (49.7% for the current compliance 

structure and 73.3% when all the cases comply at 

level 4) if the CF efficiency is 100% (last row of 

Table 6, Part a). 

The estimates are similar when DTP efficiency

16 A.K. CHAKRABORTYCTAL ETAL 

CF 

efficiency 

% 

Current# 

compliance 

Table 6. DTP efficiency by varying proportional distribution of patients at 

different compliance levels & case-finding efficiency 

Sputum negative (%)* At 

Compliance Hypothetically Varied** 

1 2 3 4 5 6 7 8 

(a)SR 

33 16.40 19.09 19.94 20.79 21.64 22.07 24.19 

40 19.88 23.14 24.17 25.20 26.24 26.75 29.32 

50 24.86 28.93 30.22 31.51 32.80 33.44 36.65 

60 29.83 34.72 36.26 37.81 39.35 40.12 43.98 

70 34.80 40.50 42.30 44.11 45.91 46.81 51.31 

80 39.77 46.29 48.34 50.41 52.47 53.50 58.64 

90 44.74 52.07 54.39 56.71 59.03 60.19 65.97 

100 49.71 57.86 60.43 63.01 65.59 66.88 73.30 

(b) SCC 

33 26.02 26.67 27.19 27.39 27.91 28.26 28.98 

40 31.54 32.32 32.95 33.20 33.84 34.26 35.12 

50 39.43 40.40 41.19 41.51 42.29 42.82 43.90 

60 47.32 48.48 49.43 49.81 50.75 51.39 52.68 

70 55.20 56.57 57.67 58.11 59.21 59.95 61.46 

80 63.09 64.65 65.91 66.41 67.67 68.52 70.24 

90 70.97 72.73 74.15 74.71 76.13 77.08 79.02 

100 78.86 80.81 82.39 83.01 84.59 85.65 87.80 

*DTP efficiency-negative status of cases at the end of treatment out of potential (2,000) computed on the basis of 

respective sputum conversion rates for compliance structure given in columns 2 to 8 given in Appendix Table.; 

** Structure of compliance:-please see Appendix Table 

with SCC is calculated, except that improvement 

with SCC over SR, when rates of compliance are 

increased to 100% at level 4, increases only from 

24% to 29% at CF efficiency of 33% (row 1 of 

Table 6 Part b). The DTP efficiency at 100% CF 

efficiency improves to nearly three times (78.9%) 

the value attainable for CF efficiency at 33%, at 

the current rates of compliance (column 2, last 

rowofTable6b). 

Compliance, regimen mixes, CF efficiency and 

DTP efficiency 

Another factor that could be studied through 

the model is the effect of varying the mixes of 

relative proportions of cases on SR and SCC. The 

DTP efficiency at varying efficiencies of casefinding, 

computed by varying hypothetically the 

proportions of regimen mixes and compliance 

structure by levels is given in Table 7. Only a few 

compliance structures are shown, with one 

currently seen in an operational study and 

another with all the cases complying at 100% at 

level 4, and two others with arbitrarily imputed 

values, in order to illustrate the dynamics. One of 

the latter two alternatives (structure 'b' in Table 

7) is a close approximation of the situation in a 

DTP with the best treatment compliance 9 . The 

DTP efficiency increases by about 10%, if all the 

cases are put on SCC instead of SR, at the current


Table 7. DTP efficiency* by varying CF efficiency

A.K. CHAKRABORTY ETAL 

5% in level 2 & 20% in level 3 will increase DTP 

efficiency to 83.44% (column 8, second row from 

bottom in Table 7). Other alternative 

combinations are also shown in the Table. 

Discussion 

Introduction of SCC regimens of high efficacy 

in DTP in 1983 could be viewed as a measure for 

increasing DTP efficiency through improving the 

treatment efficiency, DTP efficiency, however, is 

not only related to treatment efficiency but to 

other variables as well, e.g., case-finding 

efficiency (CF efficiency), efficiency of 

implementing the SCC regimen policy and, 

finally, to regimen acceptance & conformity by 

patients (compliance). Through this model, an 

attempt is made to demonstrate the role of. some 

of these key variables in determining the likely 

output from the policy of augmenting treatment 

efficiency with SCC, as a lone measure of 

increasing DTP efficiency. 

DTP efficiency/CF efficiency under SCC . 

The model confirms the hypothesis made by 

the earlier workers 1,2,3 that given the resources 

made available for NTP, improvement in CF 

efficiency is a more crucial corrective variable 

than trying to change only treatment efficiency 

through selective augmented inputs. At the lower 

levels of CF efficiency (say 33%), the additional 

benefit accruing from SCC over SR is not 

appreciable, being below 10% in terms of the 

gain in DTP efficiency. Even this extent of 

improvement with SCC could result with 100% of 

the cases diagnosed in DTP being so treated 

which, in any case, may not be. possible in the 

foreseeable future. It would require a 

substantially higher CF efficiency to obtain still 

better results (say 70% CF efficiency will gain 

about 15% greater DTP efficiency) with patient 

compliance remaining at the currently observed 

level (columnV, row one from top and fourth row 

from bottom in Table 7). In the unlikely situation 

of 100% CF efficiency and 100% cases put on 

SCC, the likely DTP efficiency could be 78.9%, 

which is the maximum possible under DTP when 

the patient compliance remains unchanged. This 

could, of course, be compared with the situation 

in which 100% CF efficiency and 100% cases 

being placed on SR will give DTP efficiency of 

49.7 (Table 7), highlighting the benefit from SCC. 

Compliance structure and DTP efficiency 

The model has shown that treatment efficiency 

and DTP efficiency are also directly proportional 

to changes in compliance structure i.e., 

proportional distribution of patients complying in 

varying proportions at different levels of 

compliance. The rates of compliance, no doubt, 

are also dependent on the treatment regimen : 

The current rates of compliance at levels 1 & 2, 

are high both for SR and SCC. In the model 

developed by Radhakrishna 2 , compliance at 

level 4 has been taken as the overall extent of 

case-holding efficiency, ignoring the rates of 

compliance at other levels. Under the 

circumstances, the resultant DTP efficiency of 

8%, worked out by him may not represent the 

actual DTP efficiency because some cases in 

levels 1, 2 and 3 do convert to a stable smear 

negativity 1,12 . This has been demonstrated by the 

model developed by Srikantaramu et al 1 , still later 

by Radhakrishna 3 and now through the use of the 

factor of compliance structure. 

Apart form chemotherapy, another factor 

utilised in the model constructed by Srikantaramu 

et ai ] contributing to sputum conversion was the 

phenomenon of “self-cure”. The annual 

proportion of self-cures occurring naturally has 

been estimated to be 20% of the total cases in the 

community, in an epidemiological survey 13 and, 

understandably, the information on self cures 

amongst tuberculosis cases attending clinics is not 

known. If “self cure” is applied to cases in the 

lower levels of compliance (levels 1, 2 and 3), 

then sputum conversion should be in excess of 

20%, even in level 1. The observed sputum 

conversion of about 22% in level 1 under SR, 

therefore, could possible represent “self cure” 

(Table 1, column 4). 

It is interesting to study the effect of different 

regimen mixes varying with compliance structure 

(Table 5). At the regimen mix of situation II, with 

90% SR & 10% SCC, raising the current 

compliance (column 4) to a very high level 

(column 8) would result in an increase in 

treatment efficiency of 13.58%. On the other 

hand, in situation X, with 10% SR & 90% SCC, a 

similar improvement in compliance would give a 

5.58% improvement in treatment efficiency.


Appendix Table. Percentage of cases on SR & SCC complying under varying compliance structures* 

At current 

Level compliance# At compliance hypothetically varied® 

1 

(a)SR 

1 37 10 10 5 0 0 0 

2 10 20 10 10 5 0 0 

3 8 20 20 20 25 25 0 

4 46 50 60 65 70 75 100 

(b) SCC 

1 20 10 5 5 0 0 0 

2 4 10 10 5 5. 0 0 

3 20 20 20 25 25 25 0 

4 56 60 65 65 70 75 100 

# Observed from recent operational studies, see Tables 1 & 2; 

refer to Table 6 

) variations presented, only illustrative; * Please 

Hence, at regimen mixes with a higher proportion 

of patients on SCC, an increase in compliance 

may give a diminishing return in treatment 

efficiency. 

Critical DTP efficiency 

Considering that the DTP at its full potential 

should be able to diagnose and convert nearly a 

third of the prevalence of cases at a point of time 

i.e., equivalent to the annual incidence, the DTP 

efficiency levels through which some dent in the 

problem of tuberculosis can be made remain to 

be ascertained. In order to achieve that, a DTP 

efficiency of 85% (85% of 2,000 - 1,700), termed 

the critical DTP efficiency would be needed 

which can only be possible through the 

implementation of SCC having a high treatment 

efficiency. It has been observed that acceptability 

of SCC varies between 60% n and 40% 12 . Under a 

comparatively low acceptability of SCC and 

assuming that rest of the patients will be on SR, a 

50%-50% SCC-SR mix should be the most likely 

regimen mix. Then, even if DTP has a CF 

efficiency of 100%, the maximum DTP efficiency 

obtainable would not be more than 65% (Table 

7) at the current rates of compliance, thus falling 

short of the critical DTP efficiency of 85%. 

Hence, corrective actions towards increasing the 

rates of compliance in level 4 are necessary. For 

example, if an optimal hypothetical compliance 

structure is ensured to be 5%, 5%, 20% and 70% 

of patients at levels 1,2,3 and 4 respectively, with 

100% SCC, then DTP efficiency of 83% can be 

achieved only with 100% CF efficiency (Table 7). 

Limitations of the model 

Some of the limitations of a model of this kind 

have to be underlined. For example, the variables 

are assumed to be deterministic. In reality, they 

could be stochastic and error estimates in making 

prediction can not be made. The extent to which 

the levels used in the model are assumed to have 

discriminatory value has not been established by 

the studies that are used in constructing the 

model. Only a few compliance structures have 

been used for reasons explained already but 

changes in compliance are possible due to socioeconomic 

changes or an improvement in CF 

efficiency. Alternative situations whose nature 

and magnitude are presently unknown might, 

therefore, be expected. Paucity of data to form 

viable hypothesis prevents further development of 

the model, incorporating more alternatives than 

used now, thereby excluding biases of unknown 

magnitude in the estimation of effect variables.

20 A.K. CHAKRABORTYCTAL ETAL 

Use of the model 

The critical evaluation of DTP efficiency 

through the conscious selection of very high CF 

efficiency, compliance, and SCC coverages, as 

inputs, is certainly an optimistic projection. No 

doubt, with the present levels of efficiency inputs 

in case-finding, case-holding and treatment, it 

may appear impossible to postulate an annual 

reduction of cases equivalent to or more than the 

annual incidence. Hopefully,however, one could 

still expect a dent in the problem of tuberculosis, 

if only in a long time-frame. With that end in 

view, a model is separately being constructed to 

estimate the time frame required to observe a 

downward trend in the problem of tuberculosis 

under some of the alternative efficiency situations 

given above. 

Apart from the use of the present model in 

constructing the long term epidemiological time 

trend of tuberculosis, following programme 

interventions, realistic estimates of expectations 

given in this paper could be used to demonstrate 

the gains that could accrue by improving the 

efficiency of various programme activities. 

Programme planners and administrators could 

make conscious selection of some of the 

alternatives, of input-combinations given in Table 

7 in context of resources available, and expect 

commensurate results by matching with outputs 

given in the paper. 

References 

1. Srikantaramu, N., Baily, G.V.J., Nair, S.S. : An 

operational model of the District Tuberculosis 

Programme; Ind. J. Pub. Health.; 1976, 20, 3. 

2. Radhakrishna, S. : National Tuberculosis 

Programme - Relative merits of enhancing the 

operational efficiency of different components of 

the treatment programme; Ind. J. Tub.; 1983, 30, 

3. 

3. Radhakrishna, S. : Direct impact of treatment 

programme on totality of tuberculosis patients in 

the community; Ind. J. Tub.; 1988, 35,110. 

4. Vandenbroucke, J.P. : Should we abandon 

statistical modelling altogether?; Am. J. 

Epidemiol; 1987, 126, 10. 

5. King, M.E., Soskolne, C.L. : Use of modelling in 

infectious disease epidemiology; Am. J. 

Epidemiol.; 1988,128, 949. 

6. Nagpaul, D.R. : District Tuberculosis Control 

Programme in concept and outline; Ind. J. Tub.; 

1967, 14, 186. 

7. Banerji, D., Anderson, S. : A sociological survey 

of awareness of symptoms suggestive of 

pulmonary tuberculosis; Bull. Wld. Hlth. Org.; 

1963, 29, 665. 

8. Rao, K.P., Nair, S.S., Naganathan, N., Rajalaxmi, 

R.: Assessment of diagnosis of pulmonary 

tuberculosis by sputum microscopy in a district 

tuberculosis programme. Ind. J. Tub.; 1971, 18, 

10. 

9. Report on National Tuberculosis Programme. 

Period : Quarter July to September 1989. 

National Tuberculosis Institute, Bangalore- 

560003. 

10. Baily, G.V.J., Samuel, G.E.R., Nagpaul, D.R.: 

Concurrent comparison of an unsupervised selfadministered 

daily regimen and a fully supervised 

twice weekly regimen of chemotherapy in a 

routine out patient treatment programme; Ind. J. 

Tub; 1974, 21, 152. 

11. Jagota, P., Gupta, E.V.V., Parimala, N., 

Shrinivas, T.R., Chaudhuri, K.: Operational 

feasibility of an unsupervised intermittent short 

course chemotherapy regimen in District 

Tuberculosis Centre; Ind. J. Tub. : 1991, 38, 55. 

12. Jagota, P., Sudha, X., Parimila, N., Chaudhuri, 

K.: A study of operational factors influencing the 

applicability of two regimens of Short Course 

Chemotherapy under conditions of an urban 

tuberculosis programme; Ind. J. Tub.: 1989, 36, 

.213. 

13. National Tuberculosis Institute : Tuberculosis in 

rural population of south India : a five year 

epidemiological study; Bull. W.H.O.; 1974, 51, 

473.


EFFECT OF ADMINISTRATION OF RIFAMPICIN ON THE 

ADRENOCORTICAL FUNCTION IN PATIENTS WITH 

PULMONARY TUBERCULOSIS 

G. Raghupati Sarma 1 , Chandra Immanuel 2 , P.V. Krishnamurthy 3 , Rani Balasubramanian 3 , 

Geetha Ramachandrari 4 and R. Prabhakar 5 


Summary. Adrenocortical function was studied on 

admission and during treatment in 57 newlydiagnosed 

patients with pulmonary tuberculosis 

16 of whom were treated with a daily regimen 

containing Rifampicin (R-7), 22 with a twice 

weekly regimen containing; the same drug (11-2) 

and 19 with a daily regimen that did not contain 

Rifampicin (NR-7). In patients on daily treatment 

(R-7 and NR-7), there was a slight increase in 

plasma cortisol at 1 week followed by a decline; 

while the mean level at 4 weeks was similar to that 

on admission in[the R-7 patients, that in the NR-7 

patients was significantly lower ( P < 0.01). No 

change was observed in the R-2 patients. A 

positive response to tetracbsactrin was observed in 

the 7 R-7, 14 R-2 and 7 NR-7 patients on 

admission and in 6, 14 and 14, respectively at 4 

weeks/The increase in the proportion of positive 

responders in the NR-7 patients was significant 

(P == 0.05). On admission, the diurnal rhythm of 

the release of cortisol, as assessed by changes in 

salivary cortisol* was disturbed in the patients 

With an evening rise in the cortisol levels; it had, 

however, reverted to a near-normal pattern after 2 

months of treatment in all 3 groups of patients. 

Introduction 

Tuberculosis is believed to be one of the 

important causes of adrenal insufficiency in man. 

Investigations undertaken recently in patients 

with pulmonary tuberculosis at Tuberculosis 

Research Centre, Madras, had shown that the 

plasma cortisol concentrations were high and 

nearly 50% of the patients had a negative 

response to tetracosactrin, suggesting a lack of 

adrenal reserve (or functional adrenocortical 

insufficiency) in these patients 1 - Further, the 

diurnal rhythm of cortisol release was disturbed 

in these patients, with an evening rise in cortisol 

levels; the pattern of changes observed in saliva 

was similar to that observed in plasma 

(unpublished findings), though the concentrations 

were much lower. Rifampicin is a known inducer 

of the hepatic microsomal enzyme system and has 

been shown to cause an enhanced clearance of 

endogenous cortisol 2 and also of exogenously 

administered corticosteroids 3 ' 4 ' 5 ' 6 The occurrence of 

acute adrenal crisis in patients on treatment with 

drug regimens containing Rifampicin has also 

been reported 7 - 8 - We, therefore, undertook an 

investigation to study the effect of two 

different rhythms of administration of Rifampicin 

(daily and twice-weekly) on the response to 

tetracosactrin (given on admission and after 4 

weeks of treatment) and compared the findings 

with those observed in patients who received a 

daily regimen that did not contain the drug. The 

diurnal rhythm of the release of cortisol, as 

assessed by cortisol levels in saliva, was also 

examined on admission and after 2 months of 

treatment in all the 3 groups of patients. This 

report presents the findings. 


Patients and treatment regimens: Sputum smearpositive 

patients with pulmonary tuberculosis 

were randomly allocated to one of the following 

1. Deputy Director; 2. Research officer; 3. Assistant Director; 4. Research Assistant; 5. Director, Tuberculosis 

Research Centre (Indian Council of Medical Research), Madras. 

Correspondence: Dr. G. Raghupati Sarma, Deputy Director, Tuberculosis Research Centre, Chetput, 

Madras-600 031.

22 G. RAGHUPATI SARMA ETAL 

regimens (during the initial intensive phase of 2 

months) : 

R-7: Rifampicin 450 mg plus Ethambutol 800 mg 

plus Isoniazid 300 mg plus Pyrazinamide 1.5 g 

daily. 

R-2: Rifampicin 450 mg plus Ethambutol 1.6 g 

plus isoniazid 600 mg plus Pyrazinamide 2.0 g 

twice-weekly. 

NR-7: Same as R-7 above, but without 

Rifampicin. 

None of the patients was diabetic or pregnant 

or on any form of steroid treatment at the time of 

the investigation. 

Plasma cortisol and tetracosactrin stimulation test: 

Blood was collected between 08:00 and 08:30 

hours on admission and at 1, 2 and 4 weeks after 

the start of treatment, and plasma cortisol 

determined. The tetracosactrin stimulation test 

was performed on admission and at 4 weeks. On 

both occasions, blood was collected for the 

determination of the basal plasma cortisol and at 

l /2 hour and 1 hour after intramuscular 

administration of 0.25 mg (about 24 units) of 

tetracosactrin (kindly donated by Hindustan Ciba 

Geigy Ltd). Plasma was separated and stored at - 

20°C till assay. 

The patients were classified as positive or 

negative responders to tetracosactrin, the 

criterion for a positive response being an increase 

in plasma cortisol of 200 nmol/1 or more at 1 /2 

hour and 1 hour over the respective basal level 1 

Diurnal variation of cortisol level : This was 

studied from changes in salivary cortisol on 

admission and at 2 months after the start of 

treatment. Saliva was collected at 08:00 hour and 

then at 2-hourly intervals up to 20:00 hour. The 

saliva specimens were frozen (kept at -20°C) 

overnight. They were then thawed and 

centrifuged; the residue containing mucoproteins 

was discarded and the clear supernatant stored at 

-20°C till assay. 

Plasma cortisol was determined by a standard 

RIA technique employing commercially available 

cortisol assay kit (Amersham International pic, 

England), and salivary cortisol was estimated 

according to a method, adapting these kits, 

standardized at our Centre (unpublished). 

Student's t-test (paired and unpaired) was 

employed for testing the difference between the 

mean cortisol levels, the chi-square test with 

Yates' correction for continuity to test the 

differences between the proportions in the 

different treatment groups, and McNemar's test 

for testing the differences between the 

proportions within the same group at different 

time-points. 

Results 

A total of 61 patients (54 male, 7 female) was 

admitted to the study; of these, 17 were allocated 

to the R-7 regimen, 23 to the R-2 regimen and 21 

to the NR-7 regimen. Four patients (1 R-7,1 R-2, 

2 NR-7) were excluded from the analysis due to 

culture negativity on admission, inadequate (< 

80%) chemotherapy or failure to attend on one 

or more of the designated test-days. The analysis 

is therefore based on 57 patients (16 R-7, 22 R-2, 

19 NR-7). The culture grading for M. tuberculosis 

on admission was 3 + (confluent growth) in 35 

patients, 2 + (> 100 colonies) in 19, 1 + (20-100 

colonies) in 2 and less than 20 colonies in 1 

patient. 

Plasma cortisol levels : The mean basal plasma 

cortisol levels (08:00 hour) in the 3 groups, on 

admission and at 1, 2 and 4 weeks after the start 

of treatment are presented in Table 1 and Figure 

1. The mean values were similar in the 3 groups 

on admission. In the R-7 patients, the mean 

plasma cortisol at 1 week was about 24% higher 

(P = 0.06) than on admission. Further treatment 

caused a decrease in the levels and the mean 

value at 4 weeks was about 14% less than that at 1 

week, and similar to that on admission. In the 

NR-7 patients too, the mean value at 1 week was 

about 11% higher (P - 0.06) than that on 

admission and further treatment caused a 

decrease and the mean value at 4 weeks was 

about 21% less than that at 1 week (P < 0.01); 

the difference between the mean values on 

admission and at 4 weeks (12%) was also 

significant (P < 0.01). There was practically no 

change in the mean basal plasma cortisol values 

at different weeks in the R-2 patients. 

At 1 and 2 weeks, only the mean value in the 

R-7 patients was significantly higher than that in 

the R-2 patients (P = 0.01 and 0.04, respectively), 

and at 4 weeks,, only the mean value in the R-7

RIFAMPICIN AND ADRENOCORTICAL FUNCTION 23 

Fig. 1. Mean plasma cortisol levels (nmol/1) on 

admission (0 week) and at 1, 2 and 4 weeks 

after the start of treatment in R-7 (• -----•), 

R-2 (| -----J|) and NR-7 patients (O -----O). 

Vertical bars indicate the standard error of the 

mean. 

patients was higher than that in the NR-7 patients 

(P = 0.05). 

Response to tetracosactrin : The response of 

patients to tetracosactrin on admission and at 4 

weeks after the start of treatment is given in 

Table 2. On admission, 7 of 16 R-7, 14 of 22 R-2 

and 7 of 19 NR-7 patients had a positive response 

to tetracosactrin, the total number of patients 

with a positive response being 28 (49%) of 57 

patients. The proportion of positive responders 

among the R-2 patients was higher than those in 

the other two groups, the differences not being 

significant. Among the R-7 patients, 4 were 

positive and 7 negative responders both on 

admission and at 4 weeks; 3 patients who had a 

positive response initially became negative 

responders and 2 who were negative responders 

initially had a positive response at 4 weeks. 

Among the R-2 patients, the classification did not 

alter in 14 patients; of the remaining 8 patients, 4 

who had a positive response initially became 

negative responders and 4 who were negative 

initially had a positive response at 4 weeks. 

Among the NR-7 patients, the classification was 

the same on admission and at 4 weeks in 10 

patients; 8 patients who were initially negative 

became positive responders, and 1 patient who 

was initially positive became a negative responder 

at the end of 4 weeks. The proportions of patients 

with a positive response to tetracosactrin at 4 

weeks were 6 of 16 R-7,14 of 22 R-2 and 14 of 19 

NR-7 patients. The increase in the proportion of 

positive responders at 4 weeks over that on 

admission was significant in the NR-7 patients (P 

= 0.05), and there was a suggestion that this 

proportion was higher than that in the R-7 

patients at 4 weeks (P = 0.07). 

The association between sputum culture 

grading for M. tuberculosis and plasma cortisol or 

positive response to tetracosactrin on admission 

in the 57 patients is presented in Table 3. The 

mean plasma cortisol value in patients with a 3 + 

grading was significantly higher than that in 

patients with a grading of 2 + or less (P = 0.01). 

The difference between the proportions of 

positive responders among patients with a 

grading of 3 + and 2 + or less was not significant. 

Sputum became negative for M. tuberculosis in 5 

of 16 R-7, 3 of 22 R-2 and 5 of 19 NR-7 patients 

by 1 months. No significant associations were 

observed between the bacteriological status at 1 

months and plasma cortisol or the proportion of 

positive responders to tetracosactrin at 4 weeks 

(data not presented). 

Diurnal variation of salivary cortisol: The mean 

salivary cortisol levels being similar in the R-7, 

R-2 and NR-7 patients on admission and at 2 

months were, therefore, amalgamated for further 

analysis. The mean salivary cortisol levels at the 

different time-points during the 12-hour period of 

collection on admission and at 2 months, together

24 G. RAGHUPATI SARMAETAL 

Table. 2. Response to tetracosactrin on admission and after 4 weeks of treatment with daily (R-7) and twice-weekly 

(R-2) regimens of Rifampicin and a daily regimen not containing the drug (NR-7) 

Table. 3. Mean plasma cortisol and number of patients 

with positive response to tetracosactrin 

according to sputum culture grading for 

M. tuberculosis on admission 

with the distribution curve for health subjects 

from an earlier study are presented in Table 4 

and Figure 2. On admission, there was a decline 

in salivary cortisol between 08:00 and 18:00 hours 

(P < 0.001) followed by an increase, and the 

mean value at 20:00 hour was significantly higher 

than that at 18:00 hour (P = 0.03). After 2 

months of treatment, the mean cortisol levels at 

the different time-points were significantly lower 

than the corresponding values on admission 

(P< 0.02). Further, there was a decrease in the 

cortisol levels beyond 18:00 hour, and the mean 

value at 20:00 hour was significantly lower than 

those at 18:00 hour and 08:00 hour (P < 0.001 for 

both). The pattern of change in salivary cortisol in 

the patients at 2 months was fairly similar to that 

observed in the healthy subjects.


Fig. 2. Diurnal variation, of salivary cortisol on 

admission (O----- O) and at 2 months after the 

start of treatment (• ----- •) in patients with 

pulmonary tuberculosis, and in healthy subjects 

from an earlier study (n---- a). Vertical bars 

indicate the standard error of the mean. 

Discussion 

Adrenocortical function appears to be 

compromised in patients with pulmonary 

tuberculosis. Despite high plasma levels of 

cortisol, nearly 50% of the patients are negative 

responders to tetracosactrin, suggesting a lack of 

adrenal reserve (or functional adrenocortical 

insufficiency). This inadequate response is not 

due to the high basal levels, as the association 

between the base-line levels and the increase at Vi 

hour and 1 hour was weak, the correlation coefficients 

being -0.64 at 1 A hour and -0.45 at 1 

hour. Further, the diurnal rhythm of cortisol 

secretion is disturbed in these patients with an 

evening rise in cortisol levels. These Findings are 

in close agreement with those reported earlier 

from this Centre 1 

Maximal induction of the hepatic microsomal 

enzyme system is known to occur after about a 

week of treatment with daily regimens containing 

Rifampicin 9 ' 10 Hence, the systemic clearance of 

cortisol would also be expected to be high at this 

time. Our findings, however, show that there is a 

slight increase in plasma cortisol at 1 week in 

both the groups of patients who received daily 

treatment (R-7 and NR-7). Wilkins et al 8 have 

observed that there is a swelling of the adrenals 

soon after start of treatment, probably similar to 

the paradoxical enlargement of tuberculous 

lymph nodes and cerebral tuberculomas with the 

initiation of chemotherapy 11 ' 12 ' 13 ' 14 - It is not known 

whether this enlargement of the adrenals is 

accompanied with an increase in the activity of 

the glands, and whether this is responsible for the 

initial increase in plasma cortisol observed in our 

study. 

Plasma cortisol and adrenal function in 

tuberculous patients are governed by the stress 

due to the disease, and a possible damage to the 

adrenals due to the tuberculous process. Hence, 

treatment with effective anti-tuberculosis drugs 

should result in a decrease in the circulating 

plasma cortisol level and an increase in the 

proportion of patient*; with a 

positive response to tetracosactrin. Both 

these effects were seen in patients who did not 

receive Rifampicin (NR-7); however, in patients 

who received this drug (R-7 and R-2), the plasma 

cortisol levels at 4 weeks after the start of 

treatment were similar to those on admission and 

no increase was observed in the number of 

positive responclers to telracosactrin. On the 

contrary, 7 of 21 patients (in both the R-7 and R- 

2 groups), who had a positive response initially, 

became negative responders at 4 weeks as 

against 1 of 7 patients in the NR-7 group. 

Response to tetracosactrin, on admission and 

during treatment in patients with tuberculosis has 

been studied by 3 other groups of investigators. 

Ellis and Tayoub 15 observed that 55% of 41 

African Zulu patients had a sub-normal response 

to tetracosactrin and that the improvement in the 

response after 15 days of treatment was inferior 

in patients who received Rifampicin as one of the 

drugs than in those who did not. These authors 

did not report on plasma cortisol levels. In a 

recent report, Scott et al u observed a negative 

response to tetracosactrin in 4 of 18 British 

patients on admission. All the patients were 

treated with a daily regimen containing 

Rifampicin, Isoniazid and Ethambutol and these 

authors have reported that the expected decrease 

in plasma cortisol during treatment was not seen, 

an observation similar to our study; of the 4 

patients with a sub-normal response, 1 died 

unexpectedly, 2 received steroids and 1 patient 

had a persistent sub-normal response to 

tetracosactrin. In a study by Barnes et al 11 in 

Melanesian patients, the proportion of those with 

a sub-normal response to tetracosactrin (8% of 

90 patients with pulmonary, miliary or

26 G. RAGHUPATI SARMA ETAL 

extrapulmonary tuberculosis) was much less than 

that in our series, and this is most probably due to 

difference in the definition employed to classify 

the patients as positive or negative responders to 

tetracosactrin 1 Further, they observed a 

significant decrease in plasma cortisol, 3-4 weeks 

after the start of treatment with a regimen 

containing daily Rifampicin in addition to 

Isoniazid, Pyrazinamide and Streptomycin, 

findings contrary to those reported in our study 

and by Scott et al 16 The daily regimen employed 

by us (R-7) was similar to that used by Barnes et 

al 17 , except that Streptomycin was replaced by 

Ethambutol, and it seems unlikely that this single 

change could be responsible for the different 

findings. 

Findings in this paper suggest that 

Rifampicin, whether administered daily or twiceweekly 

exerts a deleterious effect on the 

adrenocortical function, in patients with 

pulmonary tuberculosis. The mechanism of 

action is not clear; the sustained high plasma 

cortisol concentrations, even up to 4 weeks in 

patients receiving Rifampicin, appear to go 

against a mechanism involving a more rapid 

systemic clearance of this hormone induced by 

the drug. Earlier investigations had shown that 

dexamethasone causes an appreciable 

suppression of cortisol levels in patients with 

pulmonary tuberculosis 1 And this suggests that 

the HPA axis is intact in these patients. As such, a 

decrease in plasma cortisol caused by an increase 

in its clearance would trigger the release of 

ACTH by the pituitary resulting in an increase in 

the secretion of cortisol by the adrenal cortex. 

Whether formation of antibodies to Rifampicin 

or other immunological reactions such as the 

formation of immune complexes involving 

mycobacterial antigens precipitated by the rapid 

killing of the bacteria or the induction of autoimmune 

antibodies against adrenocortical cells 

are responsible, is a matter of conjecture. Several 

drugs such as procainamide, hydrallazine, 

methyldopa and pencillamine have been shown to 

induce auto-immune disorders such as systemic 

lupus erythematosis, myasthenia gravis, 

haemolysis and hepatitis 18 ' and Rifampicin has 

been implicated in evoking pemphigus, an autoimmune 

disease of the skin 19 

The diurnal rhythm of cortisol secretion was 

disturbed in the patients with an evening rise in 

cortisol levels before the start of treatment. The 

immune system is known to modulate adrenal 

production of glucocorticoids and cortisol, in 

turn, has been shown to regulate certain immune 

responses. Monokines, particularly interleukin-1, 

released by activated monocytes, are known to 

stimulate the hypothalamus, the pituitary and the 

adrenal cortex 20 ' 21 ' 22 Stimulation of hypothalamus 

would not only cause an increase in the release of 

CRF, which would ultimately lead to an increase 

in the cortisol production, but also of certain 

other factors such as PGE 2 which cause an 

elevation in body-temperature 23 ' An evening rise 

in body-temperature is well-established in 

patients with tuberculosis, but the association 

between the two phenomena pre-supposes a 

circadian rhythm in the release of monokines 

also. The existence of such a rhythm of several 

immune responses is now well-recognised. Thus, 

cytolytic activity of natural killer cells 24 , mitogenic 

and antigenic responses 25 ' 26 ' 27 ' 28 , the counts of 

eosinophils and neutrophils 28 and of T and B cell 

populations of human lymphocytes 2930 have been 

shown to exhibit a circadian rhythm. The maximal 

levels of T and B cells were attained at midnight 

followed by a depression during the day, and Abo 

et a I 29 have shown that variations in the cell 

counts were inversely related with plasma cortisol 

levels in healthy subjects. 

The diurnal rhythm of cortisol secretion had 

reverted to a near-normal pattern after 2 months 

of treatment in all the 3 groups of patients. 

Response to tetracosactrin was not examined at 

this time and whether this also returns to normal 

in a majority of the patients with continued 

treatment with regimens containing Rifampicin 

remains to be investigated. 

Acknowledgements 

We are grateful to Hindustan Ciba Geigy 

Limited, Bombay, for their kind gift of synacthen. 

We wish to thank Mr. K. Jayasankar for technical 

assistance and the Clinic and Nursing Staff for 

organising the blood and saliva collections. 

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Adrenal function in patients with active 

tuberculosis. Thorax; 1989, 44, 422. 

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Chronobiologia; 1979, 6, 172 (Abstract). 

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618.


LOWER LUNG FIELD TUBERCULOSIS - A TROHOC ANALYSIS 

P. Ravindran 1 , M. Joshi 2 , P. Sundaram 2 , R. Jose Raj 3 and K. Parameswaran 4 

(Received on 15.5.90; Accepted on 5.6.91) 

Summary. Pulmonary Tuberculosis occasionally 

presents with atypical features, lower lung field 

tuberculosis being one among them At trohoc 

analysis of all tuberculosis admissions done 

during a period of 5 years-from 1985 to 1989-ibiind 

20 cases (2.4%) of lower lung field tuberculosis. 

Lower lung field tuberculosis was more common in 

diabetic (13.8%) than in n6n-diabetic tuberculosis 

patients (1.4%) , the difference being statistically 

significant (P< 0.005). It was also observed that 

diagnosis of pulmonary tuberculosis on 

radiological evidence alone was made more often 

(40%) in diabetes msellitus than in patients 

without diabetes (12.1%). 

Introduction 

It is well known that diabetics have a higher 

chance of developing pulmonary tuberculosis, 

among whom the disease has quite often an 

atypical presentation. Lower lung field 

tuberculosis is one such presentation. 


This study examines the proportion of those 

with diabetes mellitus among hospitalized 

patients of pulmonary tuberculosis, and the 

extent of lower lung field tuberculosis in them. 

The study design adopted was a Trohoc Analysis' 

(retrospective cohort) whereby patients with 

pulmonary tuberculosis were retrospectively 

analyzed with respect to age, sex, clinical, 

laboratory and roentgenographic features, 

associated disorders and response to treatment. 

A trohoc analysis lacks the accuracy and 

credibility of a prospective cohort study but is less 

time consuming, easier to perform and yields 

almost comparable results. 

A total of 843 patients with pulmonary 

tuberculosis who were admitted in the wards of 

the Department of Respiratory Medicine at the 

Medical College, Trivandrum over a period of 5 

years-1985 to 1989-formed the subject of this 

study. 

Results 

Among the 843 admissions, a total of 20 

patients (2.4%) had roentgenographic evidence 

of lower lung field tuberculosis (lesions below the 

hilum) : 15 were males and 5 females; 8 patients 

(40%) belonged to 50-70 age group; the 

commonest presenting complaint was cough with 

expectoration (65%); 8 patients had cavitary and 

12 (60%) non-cavitary lesions. As regards 

location, 11 cases had right lung lesions while 9 

had left lower lung disease (Table 1). 

In all, 723 of the 843 admissions were sputum 

positive (85.8%). The total comprised 65 cases 

who had diabetes mellitus with 39 (60.0%) being 

sputum positive and 778 non-diabetics with 684 

(87.9%) being sputum positive (Table 2) 

Sputum was positive for AFB in 14 patients 

(70%) out of 20 with lower lung field 

Table. I. Distribution of lower lung field tuberculosis 

according to right or left lung and nature of 

lesion as seen in x-ray 

Nature of lesion 

Rt. 

Side of lesion 

Lt. Both Total 

1. Director and Professor; 2. Associate Professor; 3. Assistant Professor; 4. Post Graduate Student 

From the Department of Respiratory Medicine, Medical College, Trivandrum. 

Correspondence : Dr. P. Ravindran, Head, Department of Respiratory Medicine, Medical College, Trivandrum.

30 P. RAVINDRANETAL 

Table. 2. Sputum smear positivity among cases of 

pulmonary tuberculosis separately for 

diabetics and non-diabetics 

No. of 

cases 

Sputum 

positive 

Sputum 

negative 

No. % No. % 

With diabetes 65 39 60.0 20 40.0 

Without diabetes 778 684 87.9 94 12.1 

All cases 843 723 85.8 120 14.2 

tuberculosis. Among the eight patients with 

cavitary lesions, six were sputum positive whereas 

eight patients were sputum positive among the 12 

non-cavitary cases. Of the 20 patients, nine had 

diabetes mellitus. Among the 11 non-diabetic 

patients with lower lung field tuberculosis, four 

had liver disease (recent hepatitis-1, alcoholic 

liver disease-3), and two had Hansen's disease. 

The proportion of those with diabetes among 

the total admissions was 7.71% (65/843) whereas 

proportion of those with lower lung field 

tuberculosis was 2.4% (20/843). The proportion 

of lower lung field tuberculosis among the 

diabetic tuberculosis patients was 13.81% (9/65) 

whereas it was only 1.41% (11/778) among nondiabetic 

tuberculosis patients. (Table 3). 

The response to antituberculosis chemotherapy 

of the twenty cases with lower lung field 

tuberculosis was as remarkable as in any other 

patient of pulmonary tuberculosis. There were no 

relapses with follow up ranging from 9 months to 

3 years. 

Discussion 

It is well known that post primary pulmonary 

tuberculosis usually occurs in the upper lung 

lobes. Tuberculosis involves the lower lobes 

usually by bronchogenic spread from upper lobe 

cavities. The apical segment of the lower lobe 

may occasionally be the first site of the disease 

and the upper and the posterior parts of the lower 

lobe are second in vulnerability to the apical 

segment. 

Earlier, the term 'basal tuberculosis' was 

employed for the disease in lower lung lobes but 

with the common usage of lateral skiagrams, the 

terms lower lung field tuberculosis”, “hilar” and 

“parahilar” tuberculosis have come into vogue. 

Studies analyzing the associated features of lower 

lung field tuberculosis have been made by several 

authors 1 - 23 . 

The proportion with lower lung field 

tuberculosis in this series of 843 cases of 

pulmonary tuberculosis is 2.4% compared with 

3.4% reported by Parmar 2 . According to 

Romendick 4 the proportion with lower lobe 

disease may vary from 0.003% to 183%. It has 

been observed that the right lung is more 

frequently involved with mainly cavitary lesions 

(78% in the study by Parmar 2 ) while in the 

present series only 40% of the patients had 

cavitary lesions, although right side was more 

frequently involved. Bilateral lower lung field 

tuberculosis was not observed (Table 1). 

Sputum examination is essential to confirm the 

diagnosis of pulmonary tuberculosis. However, 

when sputum result is negative, one has to make a 

Year 

Table. 3. Number of cases with diabetes among total admissions and in those with lower 

lung field tuberculosis (LLFT) during 1985-1989 

Total admissions 

No. with 

No. with LLFT 

with tuberculosis diabetes Diabetics Others Total 

1985 202 11 - - - 

1986 194 17 3 5 8 

1987 161 13 3 2 5 

1988 96 9 - 2 2 

1989 190 15 3 2 5 

Total 843 65 11 20

LOWER LUNG FIELD TUBERCULOSIS 31 

diagnosis on radiological finding if there are 

other unmistakable clinical features of pulmonary 

tuberculosis. It was found that in diabetes 

mellitus, diagnosis on skiagram findings alone 

was made more often (40%) than in patients 

without diabetes (12.1%). The difference was 

statistically significant (P < 0,005). It is inferred 

that in diabetic patients, diagnosis of tuberculosis 

is often made before there are enough bacilli in 

the sputum for detection. The diabetics, being 

immunosuppressed manifest the disease earlier. 

Statistical significance was also examined for 

coming across lower lung field tuberculosis in 

diabetics compared with non diabetics (13.8% 

and 1.4% respectively). The p-value was less than 

0.005 confirming more frequent lower lung field 

tuberculosis in diabetics. A depression of 

immune status of the body in diabetes mellitus is 

evidenced by a lowered opsonization index, defect 

in cell mediated immunity and in vitro lymphocyte 

transformation, but why the lower lobes should 

be more involved in diabetes is open for 

investigation. 

Acknowledgements 

We are grateful to the Principal, Medical 

College, Trivandrum, for allowing us to publish 

this study. We are al' thankful to the 

department of Medical Illustrations for providing 

us with the prints of the skiagrams. 

References 

1. Berger H.W. and Granada M.G. Lower lung 

field tuberculosis. Chest; 1974, 65, 522. 

2. Parmar M.S. Lower lung field tuberculosis. Am. 

Rev. Resp. Dis.; 1967,96, 310. 

3. Segarra F., Sherman D.S. and Rodriguez 

Aguero J. Lower lung field tuberculosis. Am. 

Rev. Resp. Dis.; 1963, 87, 37.


FIBREOPTIC BRONCHOSCOPY IN PATIENTS HAVING 

IDIOPATHIC HAEMOPTYSIS 

B.K Khanna and S.K. Sharma 


Then, fibreoptic bronchoscopy was done in 

each case under local anaesthesia. Bronchial 

biopsy was done in those patients having visible 

growth. In all the cases, bronchial aspirate was 

collected under aseptic conditions and sent for 

microbiological and pathological examination. 

Introduction 

Haemoptysis is a common symptom in 

diseases of respiratory system. It is all the more 

common in this country where tuberculosis is still 

rampant. The aetiological diagnosis can be 

established in not more 66% of the cases with 

non-invasive techniques 1 The problem, indeed, 

becomes challenging when this symptom occurs 

in an asymptomatic case presenting with a 

'normal' chest X-ray (“idiopathic” haemoptysis). 

In our department, we have performed 

fibreoptic bronchoscopy (bronchial aspirate and 

bronchial biopsy, where indicated) in 28 such 

cases. The analysis of the findings in these cases is 

presented. 


In all 28 cases with a 'normal' chest X-ray and 

history of having had haemoptysis (moderate 

degree : more than 10 ml. but less than 100 ml) 

were admitted to Kasturba TB Hospital for 

investigation during the calender years 1987-1989. 

Of these, 20 cases were male and 8 female; their 

mean age was 26.2 years and history of previous 

respiratory and or cardiac illness was absent. 

None were smokers or ex-smokers. 

Repeat chest X-ray (P.A. and the relevant 

lateral view) was taken in each case and labelled 

as normal only when two physicians of the 

department concurred. 

Results 

The final diagnosis arising out of fibreoptic 

bronchoscopy is shown below : 

Total cases examined Tracheo-bronchitis 

Pulmonary tuberculosis Bronchogenic 

carcinoma (adeno-carcinoma) No finding 

Discussion 

28 

6 

Fibreoptic bronchoscopy is a valuable 

diagnostic tool and its indications are well 

defined 1 Haemoptysis of unknown origin is a 

recognised clinical entity despite repeated efforts 

at establishing the aetiology of haemoptysis, 

which do not succeed beyond 33% 2 - The diseases 

commonly responsible for idiopathic haemoptysis 

include bronchogenic carcinoma, chronic 

bronchitis, pulmonary tuberculosis and 

endobronchial granuloma. In Jackson's series of 

48 cases 2 ' only in 4 cases could the cause of 

haemoptysis be established by fibreoptic 

bronchoscopy. The frequency and nature of 

diseases underlying idiopathic haemoptysis vary 

with age of the patient, amount of apparent 

haemoptysis and prevalence of various 

respiratory diseases in that country. However, we 

2 

1 

Department of Tuberculosis & Respiratory Diseases, K.G.'s Medical College, Lucknow. 

Correspondence : Dr. B.K. Khanna, Professor and Head of Department of TB and Resspiratory Diseases, K.G.'s 

Medical. College, Lucknow-226 003.

B.K KHANNA AND S.K. SHARMA 

also succeeded in establishing the correct 

diagnosis by fibreoptic bronchoscopy in 32.8% (9 

out of 28 cases) which is comparable to the other 

studies conducted elsewhere 3 ' 455 

With the advent of newer techniques, 

especially CAT Scan of thorax, the diagnostic 

success of non-invasive procedures is bound to 

increase. However, these procedures being very 

costly may not be within the reach of all the cases 

in developing countries. For all unlabelled cases, 

periodic follow up is the only available 

alternative, the duration of follow up varying with 

the circumstances 5 

References 

1. Seaton, A., Seaton, D. and Leitch, A.G.: Crofton 

and Douglas's Respiratory Diseases, 4th Edition 

1989, Oxford University Press, Delhi. 

2. Jackson, C.V., Savage, P.J. and Quinn, D.L. ; 

Role of fibreoptic bronchoscopy in patients with 

haemoptysis and a normal chest roentgenogram, 

Chest; 1985, 87, 142. 

3. Somner, A.R., Hillis, B.R,, Douglas, A.C., 

Marks, B.L. and Grant, I.W. Value of 

Bronchoscopy in clinical practice. : Brit. Med Jl.; 

1958, 2: 1079. 

4. Johnson, R.N., Lockhart, W., Ritchie, R.T. and 

Smith, D.H. : Haemoptysis, Brit. Med. JL; 1960, 

1, 592. 

5. Crofton, J. and Douglas, A. : Respiratory 

Diseases, 1983, 3rd Edition, Blackwell Scientific 

Publications London.

Case Report Ind. J. Tub., 1992, 39, 35 

HIV INFECTION AND PULMONARY TUBERCULOSIS : 

REPORT ON 6 CASES 

V. Sivaraman 1 , Gilbert Fernandez 2 and R. Sambasiva Rao 3 


Summary. During a 3 month period, 225 patients 

with pu1monary tuberculosis admitted to TB 

Sanatorium, Pondicherry were screened for HIV 

infection. Six were found ELISA positive : all were 

smearpositive for AFB. Their clinacal 

presentation, investigation results and 

management while in hospital are described. 

Introduction 

There is an increasing awareness of the 

problem of acquired immunodeficiency syndrome 

(AIDS) caused by the human immunodeficiency 

retrovirus (HIV) in different parts of the world. 

Observations on the association of 

tuberculosis with HIV infection have been 

published abroad. As far as we are aware no such 

reports are available in the Indian literature. 

Hence, the experience with 6 cases of co-existing 

HIV infection and tuberculosis, in TB 

Sanatorium, Pondicherry, would be of interest. 

During the period 31.1.1990 to 31.4.1991, the 

following types of admissions into the TB 

Sanatorium, Pondicherry, were screened for 

AIDS : 

Patients with atypical radiographic pattern. 

Patients harbouring multi-drug resistant 

bacilli. 

Patients with fairly limited radiological 

lesions whose general condition showed 

unexplained deterioration. 

It would have been desirable to test all the 

admissions but due to resources constraint a 

selection had to be made. 

Routine history, clinical examination, skiagram 

of chest, sputum smear and culture examination 

for AFB, urine, blood and stool examinations, 

and liver function tests, whenever indicated, were 

undertaken for all the selected cases. 

For immunological examination, blood was 

collected by venepuncture with aseptic 

precautions. Serum was separated and stored at 

20°C till needed. For the test, serum was diluted 

1:100 and tested for anti-HIV antibodies by 

ELISA technique as per the manufacturer's 

instructions (Vironstika, Organon). In respect of 

those found reactive by ELISA, the test was 

repeated before it was considered positive. The 

ELISA positive specimens were subjected to 

Western Blot confirmatory test (HIV Reference 

Centre, CMC, Vellore). The presence of 

antibodies to antigen p24 was considered positive 

in Western Blot test. 

During the period in question. 225 patients 

were so selected for testing of which six were 

found positive and are reported hereunder : 

Case Reports 

Case 1 

Mr. D., Hindu male aged 39 years, a textile 

mill worker was admitted on 20.4.1990 for cough 

with expectoration of 2 months, chest pain one 

month, fever 3 days and blood stained sputum. 

Skiagram of the chest showed a cavity with fluid 

level in left upper zone suggestive of lung abscess 

(Fig. 1). Sputum smear was repeatedly negative 

for AFB. The patient was put on Ampicillin. 

Flexible fiberoptic bronchoscopy did not reveal 

any significant finding. Bronchoscopy secretions 

1. Medical Superintendent; 2. Assistant Surgeon, TB Sanatorium, Gorimedu, Pondicherry; 3. Chief Investigator, 

AIDS Surveillance Centre (ICMR), Department of Microbiology, JIPMER, Pondicherry.. 

Correspondence : Dr. V. Sivaraman, Medical Superintendent, TB Sanatorium, Gorimedu, Pondicherrv-605 006.

Fig. 1. Skiagram of chest showing consolidation in left 

upper zone with cavity having fluid level in the centre 

were sent for cytology, fungus and pyogenic 

culture. Light growth of Pseudomonas aeroginosa 

was obtained but other examinations were 

negative. The patient improved and was 

discharged but had to be readmitted on 4.6.1990 

with recurrence of cough. Chest skiagram showed 

a cavity in left lung and infiltrations both sides. 

Sputum smear was now positive for AFB. 

Treatment was started with Streptomycin, INH, 

Rifampicin and Pyrazinamide. Since the patient 

developed arthralgia, Pyrazinamide had to be 

stopped because concomitant administration of 

aspirin was ruled out as the patient had gastritis. 

There was clinical improvement and sputum 

conversion was obtained. 

The T cell typing employing Dako monoclonal 

and immuno-histochemical technique showed low 

T4/T8 ratio due to increase in T8 cells and no 

decrease in T4 cells. 

Case 2 

A Hindu male aged 30 years was admitted on 

22.9.1990 with cough, expectoration, loss of 

weight and blood stained sputum. The clinical 

Fig. 2. Skiagram of chest showing left hilar adenopathy 

examinations revealed a thin built, pedal edema 

and scattered coarse crackles over both the lungs. 

X-ray chest showed left hilar adenopathy (Fig. 2). 

Sputum smear was positive for AFB. A daily 

regimen of Ethambutol, INH, Rifampicin and 

Pyrazinamide was given along with steroids and 

diuretic. There was first deterioration in the 

general condition and patient went into shock. 

However, managed with I.V. fluids, the patient 

apparently recovered sufficiently to be put on oral 

fluids. There was worsening again along with 

shock and he did not respond to therapy (I.V. 

fluids and steroids) and died on the seventh day 

of admission. The positive results of ELISA and 

Western blot tests became available only after his 

death. 

The results of T cell typing employing Dako 

technique in cases 1 and 2 are shown in Table 1. 

Case 3 

A Tibetan male refugee aged 26 years was 

admitted on 31.3.1990 with cough and 

expectoration for 6 months. General condition 

was poor on admission. Skiagram chest showed

HIV INFECTION AND PULMONARY TUBERCULOSIS 37 

Table 1. Report on T cell typing employing Dako* 

monoclonals and immunohistochemical 

technique (in cases 1 & 2) 

Cell Case 1 

type 

Case 2 

Laboratory 

controls 

Lymphocytes/cmm 6588 682 more than 1500 

CD4-T cells 1449 191 622-3510 

CD8-T cells 4282 109 277-1728 

CD4:CD8 Ratio 0.388 1.752 1.023-2.695 

Note 1: In case 1 there is no decrease in T4 cells, but 

CD4/CD8 ratio is decreased because of 

increased cytotoxic T cells. 2: In case 2 there 

is decrease in T4 and T8 cells 

and the ratio CD4/CD8 is within normal 

limits. 

* Performed at the immunology laboratory of 

Christian Medical College and Hospital, Vellore. 

Fig. 3. Skiagram of chest showing bilateral diffuse 

fibrocaseous infiltrations 

bilateral diffuse infiltrates (Fig. 3). Sputum smear 

was positive for AFB. 

As the patient had prior chemotherapy for 

about 2 years, with regimens containing 

Streptomycin, INH, Rifampicin and 

Pyrazinamide, he was put on Kanamycin, 

Ethionamide, Cycloserine, and INH (high dose). 

The sensitivity results obtained later showed 

strains resistant to Streptomycin, INH and 

Rifampicin. Patient developed an erythematous 

rash while on treatment which was treated first as 

non specific dermatitis but showed only partial 

clearing. After 6 weeks, the same rash was 

diagnosed as tinea infestation and treated with 

whitefield ointment with complete clearing. Antituberculosis 

treatment had been temporarily 

stopped after the appearance of rash. When it 

was restarted, one drug at a time, it was found 

that the patient did not tolerate Kanamycin, 

which was discontinued. The patient developed 

Herpes Zoster over the right back, localized to 

T8 and T9, later spreading to LI and L2 as well. 

This prompted us to look for HIV infection. With 

topical creams and steroids, it responded slowly 

to treatment. After four months of 

chemotherapy, there was some radiological 

improvement but the sputum smear remained 

positive. He was discharged with advice to 

continue drugs on domiciliary basis. When the 

HIV result became available, the patient was 

readmitted on 9.1.1991. He was found smear 

positive even alter 6 months of chemotherapy, 

although he was clinically better, 

On readmission, he was put on Ethambutol, 

Ethionamide, INH, Oflaxacin and Trimethoprim 

Sulpha combination. The patient developed 

vomiting, off and on, and drugs had to be stopped 

for brief periods. The patient had urticarial rash, 

due to intolerance to Trimethoprim-Sulpha 

combination and haemop-tysis for which styptics 

were given. He developed Tinea corporis again. 

This did not respond to Whitefield ointment for 

which reason Ketoconazole was given with 

remarkable improvement. On 5.5.1991, the 

patient complained of chest pain and 

breathlessness due to a left sided pneumothorax, 

which was managed by intercostal tube drainage. 

Later, the patient complained of throat pain and 

began bringing out cartilage like material in 

sputum. The E.N.T. specialist diagnosed it as 

pharyngitis sica. The patient had a bout of 

haemoptysis on 17.5.1991, followed by sudden 

dyspnea and cardiorespiratory arrest. All 

measures of resuscitation failed and the patient 

expired.


Table 2. Some peculiar radiographic features of tuberculosis among patients with AIDS 

Presence of 

cavitation 

Hilar 

adenopathy 

Diffuse/ 

miliary 

Pleural 

effusions 

Chaisson et al 1 1 (35) 4 (35) 12 (35) 4 (35) 

Pitchenik and Rubinson 2 0 (17) 10 (17) 1 (17) 2 (17) 

Modilevsky et al 3 3 (29) 10 (34) 2 (17) 8 (28) 

Present series 3 (6) 2 (6) 2 (6) 0 (6) 

Numbers within brackets indicate the total number of cases in the series. 

Case 4 

An unmarried female aged 21 years was 

admitted on 23.1.1991 with cough and 

expectoration of 1 month duration and fever off 

and on. On examination, the patient was febrile 

(38°C). Auscultation of the lungs revealed 

scattered crackles but, otherwise, the physical 

examination was non-contributory. The 

roentgenogram of the chest showed a well 

demarcated oval shadow in left upper zone. The 

sputum smear was positive for AFB. Casoni's test 

was negative. ELISA was positive and Western 

Blot result is awaited. No history of sexual 

promiscuity or blood transfusion could be elicited 

despite repeated questioning. 

The patient was put on Ethambutol, INH, 

Rifampicin and Pyrazinamide on 1.2.1991. 

Treatment had to be stopped on 12.3.1991 due to 

petechial and ecchymotic lesions over both the 

feet and ankles : the lesions were symmetrical 

with excoriation marks and mild edema over and 

about the lesions. The movement of both the 

ankle joints was painful and the lesion blanched 

on diascopy. There were no purpuric spots on the 

palate, suggesting that the lesions were on 

account of allergic vasculitis due to drugs. The 

skin lesions responded to topical application of 

calamine lotion and oral antihistaminics. The 

total/differential leukocyte and platelet counts, 

liver function tests, blood urea, serum creatinine, 

and urine examination were all within normal 

limits. Anti-tuberculosis treatment with INH and 

Ethambutol was restarted after desensitisation 

for INH. The general condition improved and the 

patient was discharged on 15.5.1991 to continue 

ambulatory treatment. She is being followed up, 

Case 5 

A male aged 48 years, rickshaw puller and a 

known alcoholic was admitted on 16.1.1991 with 

cough and expetoration of one month and itchy 

skin lesions of 2 weeks' duration. On 

examination, the general condition was fair. 

There were extensive infected scabies lesions 

involving face and both the palms. There were 

coarse crackles over both the lungs. 

Roentgenogram of the chest showed diffuse 

bilateral infiltrations with multiple small cavities. 

Sputum smear was positive for AFB; ELISA test 

was positive and Western Blot result is awaited. 

Since the serum bilirubin was found raised on 

admission, a relatively non hepatotoxic regimen 

of Streptomycin and Ethambutol was given till 

the return of liver function to normal. Thereafter, 

a regimen of Ethambutol, INH, Rifampicin and 

Pyrazinamide was given on alternative days for 1 

month, till sputum conversion was obtained. The 

infected scabies was treated with antibiotics and 

thrice weekly 25% benzylbenzoate applications 

till complete clearing was obtained. The patient is 

continuing INH and Ethambutol daily on an 

ambulatory basis. 

Case 6 

A female patient aged 24 years was admitted 

on 23.1.1991 with cough and expectoration, loss 

of weight, loss of appetite and chest pain. On 

examination, the general condition was fair, there 

were crackles over the right interscapular lung 

area, sputum smear was positive for AFB and 

roentgenogram of chest showed multiple cavities 

and patchy pneumonitis over the right upper 

zone. Both ELISA and Western Blot tests were 

positive. 

A regimen of Ethambutol, INH and 

Rifampicin was started. The course of the disease 

during the hospital stay was uneventful except for 

the appearance of cervical adenitis. The nodes

HIV INFECTION AND PULMONARY TUBERCULOSIS 39 

were small, non tender and responsive to antituberculosis 

treatment. She was discharged on 

16.4.1991 and is being followed up. 

Discussion 

Reports from various parts of the world 

indicate that the frequency of infection with the 

human immunodeficiency virus is increasing 

every year, at least among the high risk groups. 

Due to an interrelation between tuberculosis and 

AIDS, evidently depending on the level of 

infection by these respective pathogens in the 

same population, the problem of tuberculosis is 

assuming greater importance in every country. It 

is known that the prevalence of infection with M 

tuberculosis in India is 30.4% (It ranges from 

35.7% in the age group 20-24 to 65.9% in the age 

group 45-48 years). The dimension of the 

problem of tuberculosis might, therefore, 

increase with the coming in of AIDS. 

Table 2 shows the peculiar radiographic 

features of tuberculosis among patients with 

AIDS reported in literature and our own 

experience of tuberculosis patients co-infected 

with HIV. 

Our series had a strikingly higher incidence of 

poor tolerance to anti-tuberculosis chemotherapy 

(4 out of 6) compared to experience of other 

authors. The case fatality rate among those 

having AIDS and tuberculosis is very high (76%). 

The cause of death is almost always AIDS, not 

tuberculosis. We came across 2 deaths out of 6 

persons with HIV infection and TB disease. 

Except case 6, with extra pulmonary 

manifestation, our cases did not satisfy the 

Centers for Disease Control, Atlanta 4 criteria for 

being labelled as full-blown cases of AIDS. The T 

cell typing employing Dako Technique showed a 

low T4/T8 ratio on account of an increase in T8 

cells.This might be because the patient had not 

yet reached the stage of immunosuppression. As 

has been pointed out by Pitchenick et al (loc cit) 

M. tuberculosis being a more virulent organism 

would be expected to cause disease at an earlier 

stage of immuno-suppression among tuberculosis 

infected patients who have or are developing the 

syndrome. It is quite possible that some of our 

cases contracted HIV infection after developing 

pulmonary tuberculosis. The response to 

chemotherapy was good in 4 out of our 6 cases. 

The knowledge of the clinical profile and 

evolution of disease under Indian conditions 

might be of help in evolving strategies of control 

and case management. 

Acknowledgement 

We are grateful to Dr. Jacob John, Professor 

& Head of Dept. Microbiology, CMC, Vellore 

for carrying out the tests, the Director, JIPMER 

and Director, Health and Family Welfare 

Services, Government of Pondicherry for 

permission to publish this paper. The secretarial 

assistance rendered by Smt. Krishnakumari is 

also acknowledged. 

References 

1. Chaisson, R.E., Shecter, G.E., Thever C.C.P., 

Rutherford G.W., Echenbergg D.F. and 

Hopewell, P.C. : Tuberculosis in patients with 

the acquired immunodeficiency syndrome. 

Clinical features, response to therapy and 

survival. Am. Rev. Respir. Dis.; 1986, 136, 570. 

2. Pitchenik A.E. and Rubinson H.A. : The 

Radiographic appearance of tuberculosis in 

patients with the acquired immunodeficiency 

syndrome (AIDS) and pre-AIDS. Am. Rev. 

Respir. Dis.; 1985,131, 393. 

3. Modilevsky, Sattler F.R. and Barnes P.P. : 

Mycobacterial disease in patients with human 

immunodeficiency virus infection. Arch. Intern. 

Med.; 1989, 149, 2201.

Case Report Ind. L Tub., 1992, 39, 41 

UNUSUAL PRESENTATION OF TUBERCULOUS BRAIN ABSCESS 

S.C. Tandon 1 , S. Asthana 2 and S. Mohanty 3 


Introduction 

Tuberculous brain abscess is a somewhat rare 

manifestation of intracranial tuberculosis, the 

usual presentations being tuberculous meningitis 

and tuberculoma. Not more than 30 cases of 

tuberculous brain abscesses have been reported. 

Similar is the situation in India where 

tuberculosis is more common 1 ' 2 ' 3 ' 4 ' 5 ' 6 . We are 

reporting two such cases, who also had an 

unusual presentation. 

Case Reports 

Case No. 1 

A 6 year old male child presented with 4 

months' history of headache, vomiting off and on, 

high grade fever and progressive loss of weight. 

He also had gradually increasing weakness in 

right upper and lower limbs for one month. A soft 

swelling which had appeared over the top of head 

was gradually increasing in size for one month. 

He was thin built, had enlarged but discrete 

and non-tender bilateral cervical lymph nodes, 

and his fundus showed bilateral papilloedema. 

Power was Gr. I/II in the right upper and lower 

limbs. There was a 5 cm X 10 cm soft, cystic, non 

tender, fluctuating swelling over left parieto- 

occipital region. ESR was raised. X-ray chest was 

normal. CT scan showed a huge hypodense lesion 

involving a major portion of left cerebral 

hemisphere, with a smooth enhancing wall, 

communicating with a large subperiosteal abscess 

through the eroded left parietal bone (Fig. 1). 

Aspiration of the brain abscess was done through 

a drill hole while the scalp abscess was aspirated 

seperately. Pus was sterile on culture but acid fast 

bacilli were seen in smear examination. Patient 

was treated with repeated aspirations and antituberculosis 

drugs (Streptomycin, Rifampicin, 

Isoniazid and Ethambutol). There was a 

remarkable improvement in the clinical condition 

and CT Scan done six months later showed 

complete disappearance of the lesion (Fig. 2). 

The patient is completely asymptomatic now. 

Case No. 2 

A 22 year old male presented with symptoms 

of raised intracranial pressure (ICP) for one 

Fig. 1. CT scan of Case no.l showing large 

intracerebral abscess, adjacent osteomyelitis 

and a large scalp abscess 

1. Reader; 2. Senior Resident; 3. Professor and Head, Section of Nurosurgery, Department of Surgery, Institute 

of Medical Sciences, Banaras Hindu University, Varansai-221 005. 

Correspondence: Dr. S. Mohanty, Department of Surgery, Institute of Medical Sciences, Banaras Hindu 

University, Varanasi-221 005.

42 S.C.TANDON£T/1L 

Fig. 4. CT Scan of Case No. 2 showing recurrence of 

abscess 15 days after trephine craniotomy and excision 

Fig. 3. 

CT Scan of Case No. 2 showing large 

multilocular abscess in left frontal region 

month, without any history of focal infection in 

the body. On examination, no neurological deficit 

was present except for bilateral gross 

papilloedema. X-ray chest was normal. CT Scan 

showed multilocular brain abscess with one large 

loculus in left frontal region (Fig. 3). Urgent 

aspiration was done to relieve raised ICP. Pus 

was thick, white-creamy and sterile on culture. 

AFB were demonstrated in smear examination. 

Aspiration was followed by excision through left 

frontal trephine craniotomy. Two weeks later, he 

had a recurrence of the symptoms and repeat CT 

scan revealed a single large abscess (Fig. 4). The 

abscess was excised through the same trephine 

craniotomy. Surgery was followed by antituberculosis 

chemotherapy. Histopathology of the 

abscess wall confirmed tubercular nature of the 

lesion. At 3 months' follow up, the patient was 

completely normal. 

Discussion 

According to Whitner 7 , tubercular infection of 

the CNS is hematogenous. The host which has 

developed hypersensitivity responds to 

inoculation of a large number of tubercle bacilli 

by exaggerated exudation with massive caseation. 

Softening of the caseation is accompanied by 

influx of polymorphonuclear leucocytes leading to 

true pus formation. Tandon et al 8 have 

experimentally produced tuberculous brain 

abscess by intracerebral injection of M. 

tuberculosis in BCG vaccinated monkeys 

protected with chemotherapy. They attributed the 

histological difference between abscess and the 

usual tuberculoma formation to host resistance,

UNUSUAL PRESENTATION OF TUBERCULOUS BRAIN ABSCESS 43 

degree of tuberculin sensitivity, bacillary dose and 

route of infection. 

Clinical diagnosis of tuberculous brain abscess 

may be missed due to its rarity 1 ' 4 ' 6 . It is only when 

the pus or excised abscess capsule is examined 

that a definitive diagnosis is made 7 ' 9 . The CT 

picture of capsular enhancement and central low 

density, however, are not sufficient for making a 

pre-operative diagnosis of tuberculous abscess 7 . 

However, if there is an associated chronic cranial 

osteomyelitis, sub-periosteal cold abscess or a 

recurrent multilocular brain abscess not 

responding to excision and antipyretic treatment, 

tubercular origin of the brain abscess should be 

strongly suspected. To achieve cure, surgery 

(aspiration/excision) followed by antituberculosis 

treatment are necessary. 

The unique presentation, of the first case, 

having extensive tuberculous osteomyelitis of left 

parietal bone, producing a massive underlying 

brain abscess and an equally large communicating 

subperiosteal cold abscess, like a dumbell 

cold abscess, has not been described in literature. 

References 

1. Chandramukhi A., Rao T.V., and Rao A.N.S. 

Tuberculous brain abscess. Report of two cases. 

Neurology India; 1981, 29, 38. 

2. Devadiga K.V., Date A., Mathai K.V. and 

Chandy J. Tuberculous abscess of the brain. 

Neurology India; 1969,17, 35. 

3. Dinaker I., and Rao S.B. Tuberculous abscess of 

cerebellum. International Surgery; 1971, 52, 277. 

4. Kumar S, Malhotra V., Brahm Prakash, Singh 

A.K., Sharma A.K. and Puri V. Tubercular brain 

abscess with computed tomography 

appearance—a case report. Neurology India; 

1987, 35,103. 

5. Mohanty S. and Rao C.J. Tuberculous abscess 

of the brain. Journal of Postgraduate Medicine; 

1978, 54, 678. 

6. Ramamurthi B., Vasudevan M.G., and 

Thamburaj A.V. Tuberculous brain abscess. 

Neurology India; 1981, 29, 35. 

7. Whitner D.R. Tuberculous brain abscess. 

Report of a case and review of literature. 

Archives of Neurology; 1976, 35, 148. 

8. Tandon P.N., Singh B., Mahapatra L.N., Kumar 

M. and Das S. Experimental tuberculosis of the 

central nervous systems. Neurology India, 1970, 

18, 81. 

9. Rab S.M., Bhatti I.H., Ghani A. and Khan A. 

Tuberculous brain abscess. Neurology India; 

1981, 29, 35.


TUBERCULOSIS OF THE TONGUE A CASE REPORT 

A. Chakravarti 1 , VJN. Chaturvedi 2 , N. Samal 3 and P. Narang 4 


Introduction 

By 1937, three hundred fifty seven cases of 

lingual tuberculosis had been reported 1 

Following the introduction of Streptomycin and 

other potent antituberculosis drugs, the 

proportion of oral lesions is reported to have 

been reduced to just 1% in patients with 

pulmonary tuberculosis 2 In a review of 834 

patients with tuberculosis, 16 were found to have 

upper respiratory tract tuberculosis but only two 

had involvement of the tongue 3 and only a few 

cases of ulcerative lesion of the tongue as 

presenting feature of pulmonary tuberculosis 

have been reported 4,5 in recent years. The rare 

occurrence of tuberculous ulcerative lesion of the 

tongue, as a presenting feature of pulmonary 

tuberculosis has induced us to report this case. 

Case Report 

A 51 year old male presented at the ENT 

services of the Mahatma Gandhi Institute of 

Medical Sciences, Sevagram, on 1st February, 

1990 with multiple painful ulcers over the ventral 

surface of the tongue, lip, buccal mucosa. of three 

months' duration. He had been treated by a 

private practitioner but the lesions had continued 

to progress and, therefore, he was referred to the 

hospital. Examination of the tongue revealed 2 

ulcers measuring 1.5 to 2 cm each with an 

intervening normal area (Fig. 1). Buccal mucosa 

on the left inner aspect of lower lip also revealed 

similar ulcers (Fig. 2). The ulcers were irregular, 

superficial, indurated, covered with dirty yellow 

slough and painful on palpation. The regional 

lymph nodes, specifically submandibular, were 

not palpable. Routine laboratory investigations, 

were normal except ESR which was 100 mm 1st 

hour (Westergren). VDRL was non-reactive. 

Smear from ulcerative lesion revealed acid fast 

bacilli (AFB++). Sputum examination also 

revealed acid fast bacilli. Biopsy taken from the 

tongue ulcer under local anaesthesia showed 

granulomatous process with tuberculoid reaction, 

Langhan's giant cells and epitheloid cells. There 

was no evidence of malignancy (Fig. 3). 

Skiagram of the chest revealed reticulonodular 

infiltration in both upper and mid zone of 

left lung suggestive of pulmonary tuberculosis. 

The patient was put on antituberculosis 

treatment, and the lesions regressed within 5 

months. 

Discussion 

The upper respiratory tract is generally 

considered resistant to tuberculosis 6 Moreover, 

unusual forms like tongue tuberculosis are likely 

to be missed. The points which suggest 

tuberculous involvement of the tongue are 

superficial nature of the ulcers, presence of 

multiple foci and dirty yellow slough 7 - These 

ulcers are to be differentiated from chronic 

infective granulomatous lesions such as syphilis, 

and lupus. Syphilitic ulcers are deep and punched 

out. Lupoid lesions have superficial ulceration 

associated with healing and cicatrization. 

Histopathological study is necessary to confirm 

the diagnosis of tuberculosis and also to exclude 

carcinomatous changes. 

1. Registrar; 2. Professor and Head, Department of Dtolaryngology; 3. Professor and Head, Department of 

Pathology; 4. Professor and Head, Department of Microbiology, Mahatma Gandhi Institute of Medical 

Sciences, Sevagram, Wardha-442 102. 

Correspondence: Dr. V. N. Chaturvedi, Prof. & Head, Deptt. of Otolaryngology, M. G. Institute of Medical 

Sciences, P.O. Sevagram-442 102.

A. CHAKRAVARTIETAL 

Fig. 2. Ulcer on the lower lip 

2. Komet, H., Scheffer, R.F. and McHoney, P.L. : 

Bilateral tuberculous granulomas of the tongue. 

Arch Otolaryngology; 1965, 82, 649. 

3. Rohwedder, J.J. : Upper respiratory tract 

tuberculosis, Ann. Intern. Med.; 1974, 80, 708. 

4. Weaver, R.A.: Tuberculosis of the tongue; Jour, 

of American Med. Association; 1976, 235, 2418. 

5. Verma, A., Mann, S.B.S. and Radotra, B. 

:Primary Tuberculosis of Tongue; Ear Nose 

Throat Journal; 1989, 68 No. 9, 718. 

6. Neumann, J.L. : Retropharyngeal abscess in 

spinal tuberculosis, Am. Rev Respir Dis; 1974, 

110, 508. 

7. Soni, N.K., Chaterjee, P. Chhimpa, I. : Lingual 

tuberculosis; Ind. Jour, of Otolaryngology; 1979. 

31, 92.


SPREAD OF PULMONARY TUBERCULOSIS 

FOLLOWING BRONCHOSCOPY 

R.L. Agrawal 1 , Manju Agrawal 2 and D.K. Agrawal 3 


Summary. Fibreoptic bronchoscopy was performed 

in a suspected case of pulmonary tuberculosis. 

Radiological dissemination and sputum positivity 

for acid fast bacilli followed after two days of the 

procedure. 

Introduction 

Diagnosis of pulmonary tuberculosis is 

confirmed after sputum is found positive for acid 

fast bacilli either by direct smear or culture 

examination. Any pulmonary tuberculosis patient 

suspected on clinical and radiological grounds 

whose sputum is negative for acid fast bacilli, on 

repeated smear examination, poses a diagnostic 

problem, specially in an emergency situation. 

Fibreoptic bronchoscopy and bronchial washings 

are, then, very useful in making the diagnosis in 

such cases 1 ' 2 - 

Case Report 

J.S., 22 year old Indian male, presented in 

S.R.N. Hospital, Allahabad with recurrent 

1. Assistant Professor, Tuberculosis and Respiratory Diseases; 2. Assistant Professor, Anaesthesiology; 

3. Lecturer, Cardiology 

From M.L.N. Medical College, Allahabad. 

Correspondence: Dr. R.L. Agrawal, 27, Chah Chand, Allahabad-211. 003.

R.L. AGRAWAL ETAL 48 

episodes of hemoptysis for two months. Clinical 

examination of chest revealed no abnormality. 

Haemogram was within normal limits except for 

raised ESR (47 mm); Mantoux test induration 

was 12 mm and sputum was repeatedly negative 

for acid fast bacilli on 3 direct smear and culture 

examinations. Skiagram chest showed no other 

abnormality except a small cavity in left middle 

zone (Fig. 1). 

Bronchial washing of the left upper lobe was 

done using 30 ml normal saline without wedging 

of instrument. The aspirated fluid was positive for 

acid fast bacilli by floatation smear method and 

culture. Post bronchoscopy, sputum smear was 

positive for acid fast bacilli. On the third day of 

bronchoscopy, patient had fever with chill and 

dyspnoea. On auscultation, there were rales in 

left lower chest. No organism could be isolated 

on smear and culture examination of blood. 

Skiagram chest showed multiple small nodular 

shadows in left middle and lower zone (Fig. 2). 

Patient showed good response with 

chemotherapy (Rifampicin, Isoniazid and 

Ethambutol) and skiagram chest after nine 

months showed closure of the cavity with residual 

fibrosis. 

Discussion 

In suspected patients of pulmonary 

tuberculosis where demonstration of acid fast 

bacilli by sputum smear and culture is not 

possible, bronchoscopy along with bronchial 

washing, tissue histology and post-bronchoscopy 

sputum smear examinations are important tools 

for confirmatory diagnosis 23 

Complications following fibreoptic 

bronchoscopic procedure are relatively 

uncommon 4 ' 5 However, no significant spread of 

tuberculosis after this procedure has been 

reported 1 ' 2 - 6 In our patient, there was spread of 

pulmonary tuberculosis which became evident 

both on clinical and radiological examinations. 

Three such similar cases have been reported in 

the available literature 7 ' 8 - Reactivation of a 

tuberculous lesion following bronchography has 

also been described 9 - 

Spread of tuberculosis after bronchoscopy can 

be explained by (1) spillage of contaminated 

washing fluid from bronchoscope, (2) entrance of 

contaminated bronchoscope into a normal site, 

and (3) opening of bronchi adjacent to cavity 

lesion due to raised intrabronchial pressure 

leading to leakage of contents of the cavity. It is 

difficult to say which of the above factors 

contributed to the spread in our case. 

References 

1. Sarkar, S.K., Shaarma C.S., Gupta, P.R. and 

Sharma, R.K. : Fibreoptic bronchoscopy in the 

diagnosis of pulmonary tuberculosis. Tubercle; 

1980, 61, 97. 

2. SO, S.Y, Lam, W.K. and Yu, D.Y.C. : Rapid 

diagnosis of suspected pulmonary tuberculosis by 

fibreoptic bronchoscopy. Tubercle; 1982, 63,195. 

3. Wallace, J.M, Deutsch, A.L., Harrell, J.H. and 

Moser, K.M. : Bronchoscopy and transbronchial 

biopsies for evaluation of patients with suspected 

active tuberculosis. Am. J. Med.; 1981, 70,1189. 

4. Credle, W.F, Smidd, J.F. and Elliot, R.C. : 

Complications of fibreoptic bronchoscopy. Am. 

Rev. Respir. Dis.; 1974, 109, 67. 

5. Pereira, W., Kornat, D.M. and Snider, G.L.: A 

prospective study of complications following 

flexible fibreoptic bronchoscopy. Chest; 1978, 73, 

813. 

6. Jaiswal, A.K., Kulpati, D.D.S., Jain, J.K. and 

Singh M.M. : Role of bronchoscopy in the early 

diagnosis of suspected smear negative cases of 

pulmonary tuberculosis. Ind. J. Tub.; 1989, 36, 

233. 

7. Rimmer, J., Gibson, P. and Bryant, D.H. : 

Extension of pulmonary tuberculosis after 

fibreoptic bronchoscopy. Tubercle; 1988, 69, 57. 

8. Sesma, P., Sanchez, E., Deben, F.M. and 

Sambade, D.S. : Tuberculous pneumonia, a 

complication of bronchoscopy. Rev. Clin. Espan.; 

1984, 173, 185. 

9. Jain, S.K. and Agarwal, R.L. : Reactivation of a 

tuberculous lesion following bronchoscopy. 

Tubercle; 1980, 61, 105.

Case Report Ind. J. Tub., 1992, 39, 49 

ACUTE MASSIVE ATELECTASIS IN PULMONARY TUBERCULOSIS 

R.P. Singh 1 , and S.K. Katiyar 2 


Introduction 

Atelectasis of the Jung in pulmonary 

tuberculosis is fairly common. However, it is 

usually not an acute and massive occurrence. Two 

episodes of acute and massive atelectasis, of left 

lung, occurring in cases of pulmonary 

tuberculosis and both resolving with conservative 

management are reported. 

Clinical Reports 

Case No. 1. N.D., a 42 year old female was 

admitted for cough with mucoid sputum, pyrexia 

and weight loss, of three months' duration. She 

had developed heaviness in left chest and 

breathlessness three days earlier. She was from 

low socio-economic group and had not taken 

anti-tuberculosis drugs before. 

On examination, she was in unsatisfactory 

health condition with gross weight loss, body 

temperature 100° to 104°F, dyspnoeic, anaemic 

and dehydrated. There was no cyanosis clubbing. 

J.V.P. was not raised. Chest examination revealed 

flattening and reduced movement with 

mediastinal shift to left side. Percussion note was 

dull on left side, breath sounds were absent on 

the left side, except upper part and bilateral 

rhonchi were audible. Cardio-vascular system was 

normal. 

Skiagram chest (Fig. 1) showed a dense 

homogenous opacity occupying practically the 

whole left hemithorax. Mediastinum was shifted 

to the left side with contraction of the left 

hemithorax. Blood test was within normal limits, 

except ESR 56 mm/ first hour and Hb. 10gm%. 

Sputum smear was positive for AFB. Culture of 

sputum showed mixed organisms with 

streptococci pneumoniae, strept. Viridans and 

Neisseria Cattarhalis. She was put on 

Streptomycin, Isoniazid, Rifampicin along with 

Dexamethasone and Serratiopeptidase (Bidanzen 

forte). Supportive treatment e.g. antibiotics, 

bronchodilators, oxygen inhalation, cough 

expectorant and I.V. fluid, was also given. 

Bronchoscopy could not be done as patient 

refused permission. The patient showed 

significant clinical improvement after 72 hours. 

The X-ray chest after 7 days showed partial lung 

expansion and after three weeks complete 

expansion (Fig. 2). The patient- is progressing 

well, 

Case No. 2. N.V., a 45 year old female school 

teacher was admitted in a serious condition with 

complaints of severe dyspnoea, cough with mucopurulent 

sputum, high grade fever and heaviness 

in left chest for two days. She had cough with 

expectoration, frequent mild pyrexia, weight loss 

and weakness for the last two months, for which 

she took symptomatic treatment. 

On examination, she was found to be acutely 

ill with marked dyspnoea, cyanosis, body 

temperature 103° to 104°F, pulse 120/minute, 

B.P. 106/88 mm Hg. and dehydration. J.V.P. was 

not raised and clubbing was absent. Chest 

examination showed flattening and decreased 

movement of left hemithorax with marked 

mediastinal shift to left side. Dull note on 

percussion and absent breath sounds with fine 

crepitations were met with on left side. Bilateral 

rhonchi were also heard. Other systems were 

normal. 

1, Reader; 2. Professor, Department of Tuberculosis and Chest Diseases, G.S.V.M. Medical College, 

Kanpur-208 002. 

Correspondence : Dr. R.P. Singh, D-25, Medical College, Kanpur-208 002.

50 R..P. SINGH AND S.K. KATIYAR 

Fig, 1. X-ray chest showing dense homogenous 

opacity occupying left hemithorax except 

upper part. Mediastinum is shifted to left side 

with contraction of left hemithorax 

Skiagram chest (Fig. 3) revealed a dense 

homogenous opacity occupying the left 

hemithorax, with shrinkage in volume and 

mediastinum markedly shifted to the left. Right 

chest showed compensatory emphysema. There 

was leucocytosis, ESR 64 mm/hour and Hb. 

llgm%. Sputum smear revealed AFB. E.C.G. 

was normal. Bronchoscopy could not be done due 

to serious condition of the patient. 

She was put on anti-tuberculosis treatment 

along with dexamethasone and serratiopeptidase. 

Supportive treatment e.g. broad spectrum 

antibiotic, bronchodialator, oxygen inhalation, 

cough expectorants and i.v. infusion, was also 

given. Postural drainage with percussion over 

affected side was done to facilitate expectoration. 

The patient started showing clinical improvement 

after 48 hours. X-ray chest after 5 days revealed 

partial and after three weeks, complete expansion 

of the left lung (Fig. 4). The patient was 

discharged after six weeks to continue O.P.D. 

treatment. 

Discussion 

The collapse of a whole lung is usually seen in 

carcinoma of bronchus, post-operatively, after 

Fig. 2. X-ray chest after three weeks showing complete 

expansion of left lung 

inhalation of foreign body, as a result of chest 

trauma, enlarged lymph node pressing the 

bronchus, in reticulosis and tuberculosis. 

In tuberculosis, atelectatic collapse may occur 

due to an enlarged lymph node pressing over 

bronchus: A lymph node may become adherent 

to the main bronchus, erode its wall, produce 

intense oedema of the bronchial mucosa leading 

to complete bronchial obstruction. Alternatively, 

lymph node caseous material may be discharged 

through the eroded bronchial wall into the 

bronchus leading to obstruction. These may 

happen in primary tuberculosis in children in 

whom the lymph node component is more 

prominent. In adults, the pulmonary parenchymal 

component is more dominant. Therefore, 

collapse due to pressure from lymph gland is 

uncommon 1 

Instead, the spread of tuberculous granulation 

tissue into the bronchus, with resultant bronchial 

stenosis, or tuberculous iracheo-bronchitis may 

cause obstruction of main or peripheral bronchus 

due to spasm of bronchial muscle and oedema of 

bronchial mucosa 2 Incomplete bronchial 

obstruction may becpme total due to thick, 

tenacious mucous. Super added infection in the 

above mentioned situation may also lead to

Fig. 3 X-ray chest showing complete atelectasis of left 

lung with marked mediastinal shift to left 

complete obstruction. The super added 

conditions, if promptly controlled, may lead to 

removal of the obstruction and reversal of the 

collapse 3 

The two cases reported here were fresh cases 

of tuberculosis. While collapse in tuberculosis, 

usually lobar or segmental, may occur, an acute 

Unilateral whole lung collapse in tuberculosis is 

rather uncommon. Unfortunately, bronchoscopy 

could not be done in both the cases. In this 

situation, the management of the two cases was 

based on treating the tuberculosis granulation 

tissue in bronchus plus super added acute 

respiratory infection leading to complete 

obstruction of bronchial lumen. The left bronchus 

Fig. 4 X-ray chest after three weeks showing near 

total expansion of left lung. Both upper zones 

reveal few tubercular lesions 

being long, narrow and oblique is perhaps more 

vulnerable to obstruction. 

References 

1. Seaton, A., Seaton, D. & Gordon Leitchv A. : 

Crofton and Douglas's Respiratory Diseases. 

Fourth Edition, Oxford University Press, Delhi, 

1989, pp. 396 

2. Perry, K.M.A. and Sellers, T.H: Chest Diseases, 

Vol. 2, Butterworth and Co. London. 1963, pp. 

507. 

3. Fraser, R.G., Pare, J.A.P., Pare, P.D. 

Fraser, R.S. and Genereux, G.P: Diagnosis of 

Diseases of the Chest. 3rd Edition W.B. 

Saunders, Company, Philadelphia, 1988, 

pp. 473.

Continuing Medical Education Ind. L Tub., 1992, 39, 53 

TUBERCULIN SKIN TEST* 

A.N. Sashidhara 1 and K. Chaudhuri 2 

Introduction 

The tuberculin skin test has a 100 year old 

chequered history. Its use and validity were very 

different at the start compared with what they are 

today. 

After the discovery of the tubercle bacillus in 

1882, Robert Koch began experimenting with its 

growth on culture media in the laboratory. By 

1890, he had developed a brownish, transparent, 

broth culture filtrate which he named “tuberculin”. 

Soon followed his announcement that tuberculin 

“protected against tuberculosis in guinea 

pigs, and had a specific healing effect on tuberculosis 

processes of all kinds in human beings”, 

which claim proved to be baseless. However, his 

observation that the “subcutaneous inoculation of 

tuberculin in a tuberculous patient led to a rise in 

temperature and local reaction at the inoculation 

site, whereas it had no such effect on the non-tuberculous” 

laid the foundation at that time, for its 

use in the diagnosis of tuberculosis. However, 

neither a standard tuberculin preparation nor a 

uniform technique for testing was developed. 

In 1907, Von Pirquet demonstrated that on 

skin “a tiny scratch made through a little quantity 

of tuberculin.... produced evidence of tuberculin 

sensitivity”, which observation was the next step 

in the long journey towards the present day tuberculin 

test. In 1908, Charles Mantoux used a syringe 

to administer a measured quantity of tuberculin, 

at a desired depth in the skin (Mantoux 

test), which has since become the standard procedure 

for doing the tuberculin skin test. No doubt, 

several other methods for doing the test have 

been developed but none can be standardized, 

qualitatively and quantitatively, as is possible with 

the Mantoux test. 

In order that the test could be used, by clinicians 

to identify persons at a higher risk of developing 

tuberculosis and epidemiologists to meas- 

ure the extent of tuberculosis infection in the 

community, Carrol E. Palmer and his co-workers 

identified, around 1950, most of the shortcomings 

of the tuberculin skin test, and developed ways to 

overcome them. Their monumental researches 

led to the desired standardization of the test, thus 

retaining its value as a reference test for other 

competing tuberculin tests. They showed that a 

significant reaction (say > 10 mm) merely indicated 

infection with M. tuberculosis, and the person 

being at a higher risk of developing the disease. 

The isolation of tubercle bacillus, from a 

specimen obtained from a person and/or detection 

of characteristic tissue changes in a biopsy 

specimen was essential to establish the definitive 

diagnosis. In other words, even the currently used 

standard tuberculin skin test has shortcomings, 

which are being overcome by a very careful interpretation 

of the results, making it a very valuable 

epidemiological tool, but hardly a-diagnostic test. 

Tuberculins 

Currently, two main tuberculin preparations 

are in use: 

Old Tuberculin (OT) which is a M tuberculosis 

broth culture, containing soluble portions 

of the used culture medium and lysis 

products of one or more strains of the bacillus, 

filtered and concentrated to a desired 

volume; and 

Purified Protein Derivative (PPD) which is 

a pure mixture of protein polysaccharides 

derived from the bacillus by a process 

developed by Seibert et al. 

The OT is a crude product containing many 

extraneous agents that produce cross reactions to 

many mycobacteria of non-tuberculosis type. The 

composition and quantities of the active principles 

in different preparations of OT are never 

* Abridged and condensed from : The Tuberculin Skin Test - Emerging 100 years since its first use\ NTI Newsletter 

(1990), 26, 1 & 2, Supplement. 

1. Investigator; 2. Director, National Tuberculosis Institute, 8, Bellary Road, Bangalore- 560 003.

54 A.N. SASHIDHARA AND K. CHAUDHURI 

the same. Its standard dose is 1:100 (1 mg in 0.1 

ml). OT is now rarely used, except for multipuncture 

tuberculin tests. 

The PPD is a highly specific, potent, stable and 

constant strength tuberculin. It is always prepared 

and diluted according to a standard procedure. 

Nonetheless, the mixture of polysaccharides varies 

in composition and strength from batch to 

batch. Besides, on storage, the active principles 

get adsorbed to varying extent to the glass/plastic 

vial walls. Polysorbate (Tween 80) has been 

found to minimise such adsorption, but its addition 

leads to comparatively smaller and softer reactions 

which are more difficult to read correctly, 

and their distributions tend to take a shape different 

from those from tuberculin without Tween 

80. 

There is great merit in using a standard tuberculin, 

of pre-determined strength, proved stability 

and specificity. The search for a better, purer and 

monospecific tuberculin than PPD has been 

going on for a long time, without much success so 

far. 

The attempt to reduce the noted shortcomings 

of PPD led to the preparation of very large 

batches of PPD, field tested before use to determine 

its potency and preserved in deep freeze for 

worldwide use for a long time. One large batch 

(lot 496.8) was prepared by Seibert et al in 1941, 

and was labelled as PPD-S. It was made the international 

standard and the United States standard 

for calibrating other tuberculins in 1952. The 

standard (first) dose of PPD-S is 5 TU (Tuberculin 

units), defined as the delayed skin test activity 

elicited by 0.0001 mg of PPD-S in 0.1 ml dose. 

Another large batch was prepared for WHO in 

1952, labelled as RT-23. Its standard dose for a 

single or first test (1 TU) is equal to 0.00002 mg 

of PPD-S + 0.000008 mg of buffer salts and 

0.005% Tween 80. In India, RT-23 is preserved 

and diluted for general use by the BCG Vaccine 

Laboratory, Guindy (Madras). Most of the research 

studies reported from India, therefore, are 

with RT-23 with Tween 80 and comparable with 

studies reported from elsewhere using the same 

tuberculin. 

Tuberculin Supplies 

The ready-for-use tuberculin is supplied by the 

BCG Vaccine Laboratory in amber colour, stop- 

pered 100 ml vials; 0.1 ml of the solution contains 

1 TU of RT-23. Exposure to light, heat and storage 

leads to denaturing and deterioration in the 

strength of tuberculin. Therefore, the vials must 

be stored in a refrigerator (4°c) and used up, after 

shaking, within the recommended time. Unless 

these precautions are taken, the results of the 

test will not be reliable. However, cooling is not 

essential, for short duration, during actual testing; 

the vial then needs to be protected against light 

only. 

The dose related rationale of the test is complex. 

The reaction to a particular dose (tuberculin 

sensitivity) varies with the biological species, and 

in a species, individually as well as with the quality 

of the antigen used. Therefore, the dose to be 

used for testing is decided on the basis of sensitivity 

and specificity of the test. Sensitivity (the condition 

being present, what is the probability that 

the test will be positive) measures the capability 

of the test to correctly pick up truly infected person. 

Specificity denotes the error of wrongly labelling 

people as being infected (the condition 

not being present, what is the probability of the 

test response being negative). The epidemiological 

situation also influences both these parameters. 

Scientific studies done with the standard tuberculin 

test have indicated the following : 

1. Almost anyone, even infants less than 6 

months in age, would react to tuberculin if a 

sufficiently high dose is used for testing. 

2. Most, but not all, patients of tuberculosis 

react to a relatively low dose of tuberculin. 

3. Most persons who have no history of tuber 

culosis or a known contact with a case of 

tuberculosis react to higher doses of tuber 

culin. 

4. With higher doses, the frequency of reac 

tions due most probably to infection with 

non-tuberculosis mycobacteria increases. 

5. Taking > 6 mm reaction size as indicative 

of tuberculous infection, a dose of 0.00001 

mg of PPD would elicit 85% response 

among patients and none at all in children 

with no history of contact. However, with 

the dose increased to ten times, 99.7% 

among the patients would react and 0.9% 

among children with no history of contact. 

As a rule, the first or single dose of tuberculin 

is selected on the basis of field trials. Higher

TUBERCULIN SKIN TEST 55 

doses than the first dose e.g. 2 TU or 20 TU are 

used on a very selective basis considering the 

circumstances and the need. 

The Test 

The Mantoux technique is preferred over all 

other methods e.g. patch test, scarification test, a 

variety of multiple puncture tests, etc. The test is 

performed by injecting 0.1 ml of PPD dilution 

into the upper folds of the skin, at a pre-determined 

site, with a non-leaking, special 1 ml tuberculin 

syringe fitted with a short 26 or 27 gauge 

needle. The injection is made slowly, with the 

needle bevel facing upwards, the skin stretched 

slightly in the opposite direction by finger. The 

syringe is held by the rubber ring attached to the 

barrel and the plunger is not touched until the 

needle eye is properly in place. After 0.1 ml has 

been precisely injected, the finger is removed 

from the plunger and the needle is withdrawn. A 

satisfactory test ought to raise a pale weal, 6-9 

mm in diameter, with visible hair follicles. The 

preferred site is either dorsal or volar surface of 

the forearm. Previous test sites are carefully 

avoided for reasons of unreliability and the increased 

frequency of stronger, bullous reactions. 

Care is taken to draw just enough tuberculin 

into the syringe for immediate use; after standing 

in the syringe for an hour, the left over solution 

must be discarded. The test must be performed 

by a trained person. The test is read on the 3rd or 

4th day of the injection, when maximum size of 

induration at the test site is attained. Reading 

comprises careful measurement of the largest 

palpable transverse diameter of induration by using 

a transparent, mm plastic scale. Reading is 

made in good light, with the forearm flexed at the 

elbow. And margins of the induration are determined 

by sight and gentle stroking of the induration 

with finger. 

Repeat Test 

The tuberculin test is not advised to be done 

as a routine clinical procedure. It is indicated only 

when the determination of tuberculin sensitivity 

status is considered necessary; therefore, the 

need for repetition of the test seldom arises, especially 

if the test has been performed precisely 

and correctly in the first instance. However, the 

test may be repeated if technical flaws in its performance 

have been noted and the result has 

been read as insignificant; or under some special 

circumstances, such as a scientific study. 

BCG Test 

The use of BCG vaccine as an antigen instead 

of standard tuberculin has been advocated by 

some when a child is clinically suspected to be 

suffering from tuberculosis, often of a severe 

type, yet the tuberculin test is negative. In contrast 

to healthy children, such children produce 

an induration of 5 mm and above in 24-48 hours 

at the vaccine site, a pustule by the 5th day, leading 

to a scab by the 10-15th day. This reaction, 

due not to delayed hypersensitivity but to an accelerated 

response is measured between 24-48 

hours. The demonstration of this new type of allergy 

(called infra-tuberculin allergy) was first described 

by A. de Assis. 

Since 0.1 ml of BCG vaccine given intradermally 

may cause intense local reaction and itching, 

many modifications of BCG test have also 

been practiced. However, as a diagnostic tool, 

neither is the BCG test recommended nor is it 

widely used. 

Interpretation of Tuberculin Skin Test 

When a measured dose of tuberculin is injected 

in an already sensitised person, a reaction 

occurs at the test site due to the delayed type of 

hypersensitivity (DTH). The quantitative measurement 

of the induration permits of a meaningful 

interpretation of the test. This DTH, which 

develops coincidently with tuberculosis infection 

has been found to be the cause of caseation and 

tissue destruction, as disease manifestations, related 

to the concentration of tubercle bacilli (bacillary 

antigen) in the tissues of the host. Non-tuberculosis 

mycobacteria also produce DTH, 

which even reacts with tuberculin test and produces 

problems in its interpretation. 

The direct effect of the entry of tubercle bacilli 

into the host tissue is the development of acquired 

immunity, through the activation of thymus 

dependent lymphocytes (Tcells). When 

stimulated, the T cells in the presence of their 

lymphokines activate macrophages which then 

destroy intra-cellular bacilli. This cell mediated 

immunity (CMI) co-exists with DTH in the body,

56 A.N. SASHIDHARA AND K. CHAUDHURI 

but their precise relationship is not yet fully understood. 

The duration of their co-existence is 

also not known, but the immunologically committed 

lymphocytes are long lived and respond 

quickly to specific antigenic stimuli. It is, therefore, 

possible to have a fully immune host not 

showing hypersensitivity to the first test but 

quickly recalling it after stimulation by showing 

significant reaction. 

Once acquired, tuberculin sensitivity tends to 

persist. One reason for that, apparently, is that a 

few bacilli keep getting released from the inapparent 

caseous foci in the host boosting up the tuberculin 

sensitivity, which otherwise has a tendency 

to wane with time. Longitudinal surveys 

have shown that persons retested in the subsequent 

surveys show, each time, a larger reaction; 

a smaller proportion among such persons show a 

much larger reaction, which is probably due to 

exogenous re-infection. Tuberculin sensitivity induced 

by the non-specific mycobacteria also 

wanes with time. It also contributes to the boosting 

effect but transiently. 

The aim of the tuberculin skin test is to classify 

people, on the basis of the size of skin induration, 

into those infected with M. tuberculosis (significant 

reactors) and the non-infected (non-significant 

reactors). Since not all persons react in the 

same manner to any particular dose of tuberculin 

(antigen), no unambiguous size can be designated 

for the purpose of this classification. 

As discussed earlier, many determinants influence 

the interpretation of test results, besides the 

necessary bias of different view points (clinician's 

vs. epidemiologist's) and purposes (between first 

infection and reinfection). Therefore, it becomes 

incumbent for interpretation to prepare a distribution 

of the test results and then decide on the 

“cut-off point for the purpose of classification, 

keeping in view the epidemiological situation and 

the probability that the test results should be reproducible 

under a similar situation. Indeed, any 

cut-off point, say, 5, 10, 14 or 16 mm will always 

include/exclude some infected/non-infected individuals. 

One has to opt for the cut-off level which 

is perhaps nearest to the actual reality. Fortunately, 

enough work has been done with the standard 

tuberculin test so that most of the factors 

which lead to errors in classification are fairly 

well understood. On the basis of numerous distributions 

(histograms) that have been interpreted, 

it can be stated that induration sizes upto 5 mm 

size are mostly due to the trauma of the test and 

not indicative of tuberculosis infection; the intermediate 

size reaction i.e. between 6 mm and 10 to 

14 mm are due mostly to infection with non-tuberculosis 

mycobadteria, but include a sizable 

proportion of the truly infected and non-infected 

persons and induration size above 15 mm are 

mostly due to the specific infection. Therefore, 

decisions with regard to cut-off point in the intermediate 

size group are often determined by the 

purpose in view, such as clinical (lowering of the 

cut-off point in order not to miss a false negative 

reactor) or for BCG vaccination (raising the cutoff 

point to give the benefit of protection to the 

maximum numbers) or selection for chemoprophylaxis, 

etc. For making such decisions meaningful, 

it becomes imperative that the test is performed 

with a low dose of the satisfactorily preserved 

tuberculin, by a trained person, meticulously, 

and expressed in mm of the reaction induration 

and not as a positive or negative result. 

With the present day tuberculin, PPD rather 

than OT, the tuberculin skin test in the hands of 

properly trained persons in a valuable tool of epidemiology 

but not so much a means for making 

the diagnosis of tuberculosis.

Ind. J. Tub., 1992, 39, 57 

FORUM 

Sir, 

During yesteryears, we rightly involved 

ourselves in operational studies, at times cooperatively. 

The same problem was studied in 

different centres under the same protocol and 

central supervision; as for example, the national 

survey of the prevalence of drug resistant bacilli 

under domiciliary chemotherapy, by ICMR. 

Many studies done by individuals and 

institutions have also contributed in respect of 

other operational problems to serve tuberculosis 

control, namely: The Research Centre, Calcutta; 

the New Delhi Tuberculosis Centre and, 

specially, our Tuberculosis Research Centre, 

Madras and N.T.I., Bangalore. 

I had got closely associated in the planning and 

execution of many co-operative studies, and had 

strongly advocated it in my presidential address, 

at the National Tuberculosis Conference, in 1960. 

A lot of water, both good and bad, has passed 

under the bridge by this time. Today, I am 

thinking of another policy, not new but not yet 

well planned and supported by the TAI or even 

the ICMR, for which I propose the name 

“Collaborative Research”. 

Though Robert Koch discovered the cause of 

tuberculosis, through his great research and 

technical abilities, we have still many problems to 

solve concerning the evolution of tuberculous 

infection to disease, due to the different Man & 

Microbic reactions and other basic problems. 

Each one of you has seen, like me, the worst 

environmental conditions of Calcutta Bustees : 

children sleeping under the same cover with 

mothers spitting innumerable bacilli around. 

Among hundreds of such heavily infected 

children, only a few develop disease. There 

cannot be any accountable reason for this, based 

either on the massiveness of infection or the 

bacillary strain. 

Research on such basic aspects may be 

academic, and not useful at present, but such 

knowledge is most valuable for tuberculosis 

control, and even its eradication. 

I think our own research discipline, alone, is 

neither competent enough nor adequate for 

undertaking such studies. They require not only 

expert advice but active participation by others, 

through multi-disciplinary experiments carried 

out with necessary instruments in their Institutes. 

This means a “Team Study-Group” along with 

other faculties like Microbiology, Immunology, 

Bio-engineering, etc. 

How best to develop such a team may be 

discussed by the Standing Technical Committee 

of TAI, who may also take steps to implement the 

recommendations. I am placing this plea in the 

Journal so that the Technical Committee may at 

least give due recognition- to papers attempting 

such studies, and help their authors to forge 

ahead. 

I know that many of my young colleagues have 

the research talent of acute observation and 

deductive imagination in search of the cause, but 

they do not have a leading path, nor a carriage, 

like the Prince of Serindip of Aesop's Fables had, 

which can drive them to the destination, turning 

Fantasy into Fact. 

I believe such collaboration is likely to be 

accepted by life minded Institutions and other 

Faculties, if the approach is made to selected 

workers with practical protocols, showing the 

share of work for each Faculty. Why riot try this 

step forward? It may give great dividends. 

Sir, 

Prof. P.K. Sen 

Calcutta 

I wish to offer the following suggestions : 

1. The contents including the titles, names of 

authors and page numbers should appear on the 

front cover instead of the back cover, as well as 

on the page before the editorial. This will be 

convenient to those who have to review previous 

issues for reference, research and training 

purposes. 

2. The frequency of the Journal's publication 

should be increased from quarterly to once in two 

months.

58 FORUM 

3. The blank left hand pages, which number from 

three to ten in any issue, and half blank pages 

must be utilised for advertisements. 

4. There should be a new column “TEMPLE OF 

SERVICE” to briefly describe the objectives, 

activities and distinguished services rendered by 

important institutions such as NTI, Bangalore; 

TRC, Madras; BCG Laboratory, Guindy; V.P. 

Chest Institute, Delhi; State TB Demonstration 

& Training Centres and Chest Institutes, 

Tuberculosis and Chest Hospitals, Sanatoria and 

voluntary organizations, etc. 

5. A separate feature should give the tuberculosis 

control services and management structures 

available at central and state levels. The feature 

could comprehensively cover one state in an 

issue. 

Dr. V.K. Tiwari 

Agra 

Sir, 

Apropos the recent Editorial on “Editorial 

Process” (IJT, 1991, 38, 117), I wish to share 

some experiences with the readers. Although the 

purpose of publication of papers in medical 

journals is to share knowledge/experience, yet 

some see it as a “status symbol”. It is all the more 

sad that such an attitude is more prevalent in 

academic institutions. Towards that end, Heads 

of Departments do not mind sharing the work of 

their juniors in order to show off their research 

leadership, even though little leadership is 

provided. The craze to publish may even lead 

to less attention being given to patient care and 

more to publishing as many articles possible, 

and including as many departmental staff as 

possible in authorship in order to ensure timely 

promotion for all. Lastly, in this game creep in ills 

like favouritism in selection of papers for 

publication, or misuse of submitted material into 

an Editorial, or the like, after rejection of the 

paper on some ground or other. I am, therefore, 

strongly in favour of peer review of each paper as 

proposed by you. The referees should clearly 

point out the flaws in each paper at the time of 

rejection and give suggestions on how to improve 

the study design or the writing of the text, etc. 

Dr. Rajinder Singh Bhatia 

Ludhiana 

Sir, 

Infection with the human immunodeficiency 

retro virus (HIV) leading to an impairment or 

profound reduction in the cell mediated immunity 

(CMI) in the body has become a special focus of 

professional interest of late. For the last few 

years, information is being collected regarding 

the prevalence of HIV seropositivity and the 

associated opportunistic infections, including 

tuberculosis, in India. Screening for HIV 

seropositivity in India has been mainly possible so 

far in the high risk groups. It is also of interest to 

know how many of the tuberculous patients under 

the care of our tuberculosis services are HIV 

positive, since the state of immunodeficiency in 

them may have led to the breakdown of their 

latent tubercular infection into frank disease. 

We studied 200 newly diagnosed male patients 

of pulmonary tuberculosis at the TB and Chest 

Clinic of SVRR Hospital, Tirupati. Properly 

collected serum specimens from these patients, 

without any selection, were tested for the 

presence of HIV antibodies by the enzyme linked 

immunosorbent assay (ELISA) using the 

Wellcozyme kits. The positive sera among the 

specimens were sent to Christian Medical 

College, Vellore for confirmation by the Western 

Blot test. 

Out of the 200 patients tested, only 3 (1.5%) 

were found HIV positive. Simultaneously, 50 

healthy individuals had been tested in order to 

exercise a check on the technique but without 

anyone being positive. Earlier, we had found HIV 

seropositivity of 0.25% among blood donors, 

0.5% in women under antenatal care and 0.58% 

among patients attending a sexually transmitted 

disease (STD) clinic compared with 25.9% 

among prostitutes. However, none among these 

seropositive individuals was found to have 

tuberculosis. 

. 

The above findings are reported as a brief 

communication in order to stimulate interest in 

the setting up of appropriate but wider facilities 

for ELISA testing and medical as well as public 

health interventions, as early as possible. 

(Smt) N. Lakshmi and Gururaj Kumar, 

Tirupati.

Ind. J Tub., 1992, 39, 59 

NEWS AND NOTES 

FORTYSIXTH NATIONAL CONFERENCE 

The 46th National Conference on TB & Chest 

Diseases, organised by the Delhi TB Association 

under the auspices of the Tuberculosis 

Association of India, was held in New Delhi from 

22nd to 24th of November, 1991. The Conference 

was inaugurated by Dr. M.S. Chadha, President, 

Tuberculosis Association of India. Dr. S.B. 

Trivedi, Director, TB Research Centre, 

Amargadh & Vice-Chairman, Gujarat State TB 

Association, presided over the Conference. The 

Programme Committee of the Conference had 

selected 52 papers for presentation at the 

Conference, out of which 47 papers were 

presented. During the inaugural function, Dr. 

M.S. Chadha, presented the 'Lupin-TAI Oration 

Award' to Dr. G.P. Talwar; 'Ranbaxy-Robert 

Koch Oration Award' to Dr. S. Radhakrishna; 

'Charu Chandra Das Memorial Award' to Dr. 

S.M. Govil; 'Dr. R. Krishna Memorial Cash 

Prize' to Dr. Manjula Datta and 'R.C. Garg 

Memorial Award' to Dr. Prema Gurumurthy. 

Two panel discussions, one on 'National TB 

Programme' and the other on 'Case-Finding' 

were held. These were moderated by Dr. D.R. 

Nagpaul and Dr. I. Ranga Rao respectively. Dr. 

G.P. Talwar, Director, Institute of Immunology, 

New Delhi, delivered the 'Lupin-TAI Oration' on 

'Continuing challenges in tuberculosis research' 

and Dr. S. Radhakrishna, Director, Institute for 

Research in Medical Statistics, Madras, delivered 

the 'Ranbaxy-Robert Koch Oration' on 

'Statistical Methodology and tuberculosis-A 

fruitful association'. The Delhi TB Association 

organised a cultural programme on the evening 

of 22nd November. In all, about 600 delegates 

attended the Conference. 

42ND TB SEAL CAMPAIGN 

The 42nd TB Seal Campaign organised by the 

Tuberculosis Association of India and its affiliates 

in the States was inaugurated on 2nd of October, 

1991, by the Hon'ble Shri R. Venkataraman, 

President of India and Patron, Tuberculosis 

Association of India, at Rashtrapati Bhavan, New 

Delhi, when the 42nd TB Seals were presented to 

Rashtrapatiji for release. Rashtrapatiji 

complimented the Tuberculosis Association of 

India for the excellent work being done by it. Dr. 

D.R. Nagpaul, Vice-Chairman of the Association, 

proposed the Vote of Thanks. The function was 

widely covered by Doordarshan, All India Radio 

and newspapers. Representatives of the 

Tuberculosis Association of India, the Delhi TB 

Association and some special invitees, attended. 

On this occasion, the Association also brought 

out, for distribution to the public, a tastefully 

printed and informative Special Souvenir carrying 

meaningful, educative articles on various aspects 

of tuberculosis by eminent TB workers. 

HEALTH VISITORS' COURSE 

The 1992-93 TB Health Visitors' Course will 

commence in July, 1992. The Course will be of 

nine months' duration and will be held at the New 

Delhi TB Centre. The minimum qualification for 

admission to this course is 10 + 2 with Science 

and/or Hygiene subjects in Matriculation 

(equivalent to 10th standard). Application forms 

for admission to the course can be had from the 

Secretary-General, Tuberculosis Association of 

India, 3, Red Cross Road, New Delhi-110 001. 

The last date for receipt of applications is 30th 

April, 1992. 

CHANCHAL SINGH MEMORIAL 

AWARD-1992 

The Tuberculosis Association of India awards 

a cash prize of Rs. 1,000/- to a medical graduate 

(non-medical scientists working as bacteriologist, 

biochemists, etc. in the field of tuberculosis are 

also eligible) below 45 years of age and working 

in tuberculosis, for an original article not 

exceeding 30 double spaced foolscap typed pages 

(approximately 6,000 words excluding charts and 

diagrams) on a subject relating to TB. Articles or 

papers already published or based on work of 

more than one author will not be considered for 

this award. Papers may be sent, in quadruplicate,

60 NEWS AND NOTES 

to reach the Secretary-General, Tuberculosis 

Association of India, 3, Red Cross Road, New 

Delhi-110 001, before the 31st of July, 1992. 

ESSAY COMPETITION-1992 

The Tuberculosis Association of India awards 

every year a cash prize of Rs. 500/- to a final year 

medical student in India for an original essay on 

tuberculosis, adjudged best by a special 

committee of the Association. The subject 

selected for the 1992 competition is “National TB 

Control Programme: Present Status”. The essay 

should be written in English, typed in foolscap 

size, double spaced and should not exceed 15 

pages (approximately, 3,000 words including 

tables, diagrams, etc.). Four copies of the 

typescript should be forwarded through the Dean 

or Principal of College/University to reach the 

Secretary-General, Tuberculosis Association of 

India, 3, Red Cross Road, New Delhi-110 001, 

before the 31st of July, 1992, with the certificate 

that the student is in final year. 

A.P. TB & CHEST DISEASES WORKERS' 

CONFERENCE 

The 18th Andhra Pradesh TB & Chest 

Diseases Workers' Conference was held on 13th 

and 14th July, 1991, at the Indian Medical 

Association Hall, Hyderabad. The Conference 

was inaugurated by Dr. (Mrs.) G. 

Kuthuhalamma, Minister for Medical & Health 

and presided over by Dr. O.A. Sarma. The theme 

of the Conference was “Is Tuberculosis 

Conquered?''. About 200 delegates attended the 

Conference. 

CASE-FINDING CAMPS 

A Health Check-up Camp was held on 

21.7.1991 at B.H.E.L., International Club, 

Ramachandrapuram, to detect cancer and TB 

among the staff of B.H.E^L. Shri G.K. Rao, 

General Manager of B.H.E.L was the chief guest 

and Dr. K.L. Naidu, Medical Officer, B.H.E.L 

Hospital, was the president of the Camp. In all 52 

patients examined of which one was found to be 

suffering from cancer of the breast. Forty persons 

with symptoms of cough and expectoration were 

subjected to sputum and blood examination. 

None of them was found to be sputum positive. 

Another General Health Check-up camp was 

held on 7th July, 1991 at Mandal Praja Parishad 

Officer, Hayathanagar, Ranga Reddy Dist. under 

the auspices of Sri Satya Sai Seva Samithi, 

Hyderabad. About 30 doctors participated in the 

Camp. In all 11,578 people attended the Camp. 

About 45 patients having symptoms like cough, 

fever and expectoration were referred to the 

Chest Department out of which one was found to 

be positive. 

CONTINUING MEDICAL EDUCATION (TB) 

The Divisional Railway Tuberculosis 

Association, Ratlani, organised a CME 

Programme on tuberculosis on llth August, 

1991, at the Railway Officers' Club, Ratlam. The 

session was inaugurated by Dr. K.P. Pathak, 

Chief Medical Officer, Western Railway and 

chaired by Shri R.K. Goel. 

The main objectives of the CME Programme 

were to (i) update the knowledge of Doctors on 

recent advances in tuberculosis, (ii) to detect 

defaulters and improve case-holding during 

treatment and (iii) to spread awareness about TB 

in Railway population specially those working on 

wayside stations, with the help of railway officers, 

supervisors and trade union workers. 

THE 1991 ANNUAL MEETING OF THE 

IUATLD 

The annual meetings of the IUATLD were 

held in the Headquarters office of the IUATLD, 

from llth to 15th November, 1991. These 

comprised meetings of the Governing body, 

various advisory bodies, Councils, Scientific 

Committees and a Session on 'HIV Infection and 

Tuberculosis'. From India, Dr. S.P. Pamra, Dr. 

D.R. Nagpaul and Dr. P.M. Udani attended the 

meetings. 

Among the highlights were retirement of Dr. 

Annik Rouillon from the office of Executive 

Director of IUATLD, nomination of Dr. Billo of 

Switzerland to succeed Dr. Rouillon, Dr. Murray 

to succeed Dr. Kilpatric as Chairman of the six 

Scientific Committees and merger of Tubercle 

with the Bulletin of the IUATLD, the new 

publication to appear six times a year under a 

new Editorial Committee.

NEWS AND NOTES 61 

It was also decided that the next Annual 

Meetings be held either in Paris or along with the 

African Regional Conference to be held in Cairo 

in 1992; the Eastern Region Conference to be 

held in Thailand in 1993 and the World 

Tuberculosis and Chest Diseases Conference to 

be held in Mainz (Germany) in 1994. 

DR. S.C. KAPOOR 

Dr. S.C. Kapoor, Chest Physician £ TB 

Specialist, formerly the Chief Medical Officer of 

the Indian Railways has been appointed as the 

Associate Editor of the Indian Journal of 

Tuberculosis. 

OBITUARY 

Prof. K.V. Krishnaswami, a senior tuberculosis 

worker, passed away on 17th November, 1991 at 

Madras. He was the Director of Institute of TB & 

Chest Diseases (now Institute of Thoracic Medicine) 

for over eleven years. Prof. Krishnaswami 

was a member of the Central, Executive and 

Standing Technical Committees of the Tuberculosis 

Association of India. He was the President 

of the 32nd National Conference on TB & Chest 

Diseases held at Trivandrum in November 1977 

and also the Chairman of the Standing Technical 

Committee—1977. He was also a member of the 

Editorial Board of the Indian Journal of Tuberculosis. 

He was the recipient of Dr. B.C. Roy Award 

in 1979, the T.A.I. Gold Medal in 1983 and was 

awarded the 'Wander-TAI Oration' in 1974. 

Prof. Krishnaswami, sudden demise is a great 

loss to the Tuberculosis Association of India, 

Anti-TB Association of Tamil Nadu and the TB 

workers in the country, which would be very 

difficult, if not impossible to make up. Our 

heartfelt condolences are extended to the family 

of late Prof. K.V. Krishnaswami. 

NEW OFFICIAL JOURNAL OF IUATLD 

In February 1992, a new scientific journal will 

replace the IUATLD Bulletin as the official 

journal of the IUATLD. It will be formed by 

merging the two existing journals, Tubercle and 

the Bulletin, and will be published by Churchill 

Livingstone under the title Tubercle and Lung 

Disease. 

It will publish original primary articles and 

commissioned reviews on both research and 

clinical work in tuberculosis and all other lung 

diseases with particular emphasis on community 

health, elaboration, implementation and 

assessment of field projects and action 

programmes against tuberculosis and lung 

diseases. 

The new scientific journal will have six issues 

per year, compared with the four issues of the 

present Bulletin, containing articles principally in 

English but also orginal articles submitted in 

French and Spanish. Each article will be 

preceded by an abstract translated into the two 

other languages. 

SUBSCRIPTION INFORMATION 1992 

Ordinary membership fee of the IUATLD, 

Paris, for the year 1992 is FF 575 (equivalent to 

Rs. 2,800/-). By virtue of this membership the 

members will be eligible to receive from the 

Union the new scientific journal and Newsletter 

and just for the membership and the Newsletter, 

the subscription is FF 200 (equivalent to Rs. 950). 

Subscription for the new scientific journal for 

non-IUATLD members is SB 66.26. For 

subscribing, kindly contact the Secretary-General, 

Tuberculosis Association of India, 3, Red Cross 

Road, New Delhi-110 001, before 28th February, 

1992.

Ind. J. Tub., 1992, 39, 62 

Indian Journal of Tuberculosis 

. 

ABSTRACTS 

Vol. 39 January 1992 

EVALUATION OF A POLYMERASE CHAIN 

REACTION FOR THE DIAGNOSIS OF TU- 

BERCULOSIS 

N. MANJUNATH ET AL\ TUBERCLE; 1991, 

72, 21. 

The limitations of the conventional methods in 

detecting infectious cases early enough is one of 

the reasons for the failure of tuberculosis control 

programmes in developing countries. A polymerase 

chain reaction (PCR) for the specific detection 

of M. tuberculosis which can detect 10 organisms 

is reported. 

The samples studied included both pulmonary 

(48) and extra-pulmonary cases (69) received at 

the Tuberculosis Diagnostic Service of the All 

India Institute of Medical Services, New Delhi. 

Out of the total of 117 specimens in the test 

group, 19 were culture positive for mycobacteria 

and 17 of these isolates were identified as M, tuberculosis. 

All the specimens from which M. tuberculosis 

was grown were also PCR positive, 

while the remaining two isolates identified as 

mycobacteria other than tuberculosis were PCR 

negative. Fourteen specimens which were culture 

negative were also found to be positive by PCR, 

thus yielding an overall positivity rate of 26.5% 

(31/117) compared to 14.5% (17/117) by culture. 

On the other hand, none of the specimens in the 

control group was positive by PCR. The increased 

sensitivity and specificity is due to the DNA segment 

chosen for amplification. The authors derived 

from MPB 64 protein coding gene because 

this protein has been extensively characterized 

and shown to be highly specific to species within 

the M. tuberculosis complex. 

SHORT COURSE CHEMOTHERAPY FOR 

PULMONARY TUBERCULOSIS UNDER 

ROUTINE PROGRAMME CONDITIONS: A 

COMPARISON OF REGIMENS OF 28 AND 36 

WEEKS DURATION IN ALGERIA 

ALGERIAN WORKING GROUP/BRITISH 

MEDICAL RESEARCH COUNCIL COOP- 

ERATIVE STUDY; TUBERCLE; 1991, 72, 88. 

Two short course chemotherapy regimens (of 

28 weeks' and 36 weeks' duration respectively) 

were compared in previously untreated pulmonary 

TB patients in Algeria. The regimens were 

8 SHRZ/20 HR and 8 SHRZ/8 HR/2 OH. 

Whole districts were allocated to one or the other 

regimen. Results were assessed at the end of 2 

years irrespective of departures from protocol. 

Also, 25% of the patients in the first group and 

29% in the second could not be assessed and 

another 5% and 4% respectively died. Of initially 

drug sensitive patients who completed treatment 

and could be assessed, 97% in both groups had a 

favourable status. Of those INH resistant at start, 

none of the 19 in the 28 weeks' group and 5 of the 

26 in the 36 weeks' group had an unfavourable 

outcome suggesting that the duration of Rifampicin 

may have been important in this group. 

Default rate was nearly the same in both groups 

(6.7% and 9.3%) and adverse reactions, though 

uncommon, were slightly more frequent in the 28 

weeks' group (6%) than in the 36 weeks' group 

(2%). 

SUSTAINED RELEASE OF ISONIAZID IN 

VIVO FROM A SINGLE IMPLANT OF A BIO- 

DEGRADABLE POLYMER 

P.RJ. GANGADHARAM ET AL\ TU- 

BERCLE; 1991,72,115 

The problem of poor patient compliance in 

completing treatment for the prescribed period 

continues to be a big limitation in mass chemotherapy 

programmes, even after the introduction 

of short course chemotherapy. Supervised intermittent 

administration of drugs has been suggested 

as an alternative but in many parts of the 

world this can be practical only if the interval between 

two doses is fairly long. The authors describe 

an animal experiment where with a single

INDIAN JOURNAL OF TUBERCULOSIS 63 

dose of INH incorporated in a biodegradable 

polymer, the levels of the free durg and its major 

metabolites, 6 weeks after a single implant, were 

similar to those obtained with daily oral administration 

of the same dose. Homogenates of liver 

and lungs from animals killed after 6 weeks 

showed high antimycobacterial activity against M. 

Tuberculosis. There were no significant differences 

in renal, hepatic and haematological parameters 

when sera were tested. Implants did not 

cause any local or systemic toxicity. 

ASSOCIATION OF PULMONARY TUBERCU- 

LOSIS AND HLA IN SOUTH INDIA 

V. BRAHMAJOTHI ET AL; TUBERCLE; 

1991, 72,123. 

Since many of us are exposed to mycobacterial 

infection which does not result into disease, it is 

suggested that hereditary predisposition may be 

responsible for the oncet of disease. To find out 

the relationship between disease and genetic factors, 

204 patients with smear positive pulmonary 

tuberculosis and 404 healthy controls were studied. 

It was found that HLA-A10, B8 and DR2 

were more frequent among patients than in 404 

control subject (p = 0.01). A primary association 

of HLA-DR2 in radiologically for advanced, 

smear-positive patients has also been identified 

(p = 0.001). Thus, HLA-DR2 not only predisposed 

for smear-positive disease but also for far 

advanced lung lesions. In 152 patients with 

smear-negative pulmonary tuberculosis, the frequencies 

of HLA-A10 and B8, but not of DR2, 

were greater in the control subjects. The study 

further revealed other HLA associations (A3, 

B12 and DR4) in genetically disparate populations 

(caste) unique to them suggesting that genes 

linked with the HLA complex might also be significant 

in the pathogenesis of tuberculosis. This 

study, along with others which have revealed a 

HLA-DR2 association in tuberculosis and leprosy, 

suggests that the mechanism of immunogenetic 

predisposition to these mycobacterial diseases 

may be the same. 

SUPERVISED OUT-PATIENT TERATMENT 

OF TUBERCULOSIS: EVALUATION OF A 

SOUTH AFRICAN RURAL PROGRAMME 

M.S. WESTAWAY ET AL; TUBERCLE; 1991. 

72140. 

The paper reports on a supervised out-patient 

treatment programme in a predominantly rural 

area of South Africa for black TB patients. A 3- 

year study covering 454 patients showed treatment 

completion rates improving from 88% in 

the first year to 94% in the third year. The rate of 

default was reduced from 8.5% to 3% over the 

same period. The remaining 3% to 4% of the patients 

died during the course of treatment. Treatment 

supervision, after an initial period of hospitalisation 

was for the vast majority of patients, 

entrusted to voluntary health workers. The rindings 

suggest that supervised out-patient treatment 

with community involvement and responsible 

participation was successful in achieving the aim 

viz. holding and curing TB patients. 

DIFFERENTIATION OF MYCOBACTERIUM 

TUBERCULOSIS STRAINS BY USE A NON- 

RADIO ACTIVE SOUTHERN BLOT HYBRIDI- 

ZATION METHOD 

BRUCE C. ROSS ET AL; JOURNAL OF IN- 

FECTIOUS DISEASES; 1991,163, 904. 

Currently, the only means of distinguishing M. 

tuberculosis isolates is by phage typing, which is 

impractical for most laboratories. Attempts to 

develop an alternative approach based on defining 

differences in DNA by detecting restriction 

fragment length polymorphisms (RFLP) have not 

yielded satisfactory results. Moreover, the earlier 

attempts used a costly and health hazard radiosotope. 

The authors have developed a. non-radioactive 

RFLP technique which also differs by using 

enzymes that have four base recognition sites 

rather than six. Various restriction enzymes such 

as Alul, Ddel, Himl, Ndell, Rsal and TaqI were 

used to digest genomic DNA. The high molecular 

weight fragments were visualized after Southern 

blotting with digoxigenin-labelled M. tuberculosis 

DNA. Among all the enzymes used, AluI showed 

the greatest potential by distinguishing all eight 

M. tuberculosis isolates and three type strains 

from tuberculosis complex, while enzyme Ndell 

distinguished all but two strains. The other enzymes 

used in this study were of little help. Thus, 

this method is particularly useful where there is a 

small amount of species diversity and where the 

identity or location of variable regions within the 

genome are not known.

THE INDIAN JOURNAL OF TUBERCULOSIS 

Published quarterly by the Tuberculosis Association of India 

Reproduction of any article, or part thereof, published in the Indian Journal of Tuberculosis without 

prior permission of the Tuberculosis Association of India is prohibited. 

The views expressed in the various articles are those of the authors and not necessarily of the 

Tuberculosis Association of India or the Editors of the Journal. 

Published on behalf of the Tuberculosis Association of India, New Delhi, by the Secretary-General and printed by Cambridge 

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The Indian Journal of Tuberculosis - LRS Institute of Tuberculosis ...

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