Practical Approach to Tuberculosis Management VK Arora, Raksha Arora
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1Epidemiology of Tuberculosis2

History of Tuberculosis in India1

B Mahadev,
Prahlad Kumar
 
 
Historical Perspective
Tuberculosis (TB) is one of the most ancient disease known to mankind which was traced and documented from Ancient Ayurvedic System practiced by Sushrutha, Charaka and others around 2500 BC. The literature reveals that the disease process results from imbalance in the homeostasis. It has also been documented in the Vedas and Ayurvedic Samhitas as early as 2000 BC. Dating back to 1000 BC, archaeological evidences of spinal TB in the Egyptian mummies were also available.
The landmark discovery of the causative organism of TB by Sir Robert Koch was announced on 24th March 1882.12 In the later part of the 18th century, in Europe and America, TB cases were picked up based on their history and clinical examination. The burden of TB referred to as consumption in those days was high and the only available mode of treatment was providing good food, ventilation and isolation. Where ever it struck there was total devastation. The scenario continue to be the same till the discovery of anti-TB drugs in 1940s. However, Robert Koch's discovery set the wheel in motion for further research in prevention and control of the disease.
 
Portal of Entry of TB Disease
History also reveals that TB disease entered India through the European migrants who came in search of greener pastures following the industrial revolution in Europe 1 and 3.
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Fig. 1.1: Dr Robert Koch
TB was not a major problem in the Indian subcontinent in the early part of 19 th century. According to Young (in the Transactions of Calcutta Medical Society; 1823, IV, 36) and Murray (Trans, Bombay Med.Soc.1838, II, 45), TB was extremely rare in the upper plateau of the Western Ghats, Nilgiri hills and on the northern and southern slopes of the Himalayas. The disease was however known as Kshaya or Yakshma by its symptoms. It can be presumed that the TB disease at that time was considered as one of the low profile disease. During the British rule, Dr A Lankaster for the first time, conducted a Tuberculin survey in 1921 and the results revealed high incidence of TB infection among the study population.
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Fig. 1.2: Lady Linlithgow
Towards the end of 19th century, TB had penetrated the Indian population and had become quite common.
The government suggested India to associate itself as a member of the International Union against TB in 1929. Due to the financial crunch prevailing at that point of time Her excellency Lady Linlithgow through a public appeal raised funds to the tune of one crore on behalf of the government which was named as King George V thanksgiving fund for anti-TB activities. The credit of starting the first TB Association as early as 1929 in the country goes to Bengal. On the advice of this association TB was declared as a notifiable disease by the government in 1936. Using the King Goeroge V thanksgiving fund, the TB Association of India (TAI) was started in 1939. The provinces and states later on started TB associations in their respective areas.45
 
Birth of Sanatoria
With the industrialization taking the forefront, the country witnessed migration of population from rural to the urban areas resulting in congestion of big cities and towns. The infrastructure development was not commensurate with the population growth. This became a fertile ground for the spread of infectious diseases among the population. The first TB Sanitarium was opened in Tilaunia near Ajmer of Rajasthan in the year 1906. It was intended mainly for admitting the girls from mission schools and orphanages in North India who were suffering from TB. In 1908 a sanatorium at Almora in the foothills of the Himalayas was started. Christian missionaries pioneered the starting of the sanatorium for isolation of TB patients. The Indian Philanthropists took a lead in 1909 by opening a sanitarium at Dharampore in Simla Hills under the management of Consumptives’ Homes Society of Bombay. This resulted in encouraging the governmental agency to open King Edward Sanatorium at Bhowali in1912. In the same year, as a private initiative, Dr RB Billimoria opened the first sanatorium in Pune, which was later shifted to Panchagani in Maharashtra.4 This was followed by opening up sanatoria in different parts of the country. These institutions provided supervised bed rest, nutritious food, fresh air, exercise, sun-bathing, etc. to the individual cases.
Dr C Frimodt Moller worked as the superintendent of Union Mission Tuberculosis Sanatorium (UMTS), Arogyavaram, South India in 1915. A number of field studies were under taken to estimate the average annual number of deaths from tuberculosis and the number of infectious cases existing in the community. The estimates from these studies brought out that existing facilities to treat TB patients was meager which provoked the experts in the field to think of providing alternate avenues.
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Fig. 1.3: TB association of India
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Fig. 1.4: Dr C Frimodt Moller
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Fig. 1.5: TB Dispensaries and clinics, New Delhi TB centre
With passage of time and influx of patients to the Sanatoria, it was realized that that the available beds in these institutions were grossly inadequate to meet the requirements. In order to overcome this crunch, It was deemed fit to open TB dispensaries and TB clinics to supplement the activities carried out by the Sanatoria. In India, the first TB dispensary was established in 1917 at Bombay followed by another two dispensaries, one at Madras and the other at Calcutta, in 1929. The first free TB clinic in the country was started by Ramakrishna mission at Delhi in 1933. Another landmark in this venture was setting up of New Delhi TB Clinic in 1940 which was later named as New Delhi TB Centre (NDTC).
Following this, similar clinics were opened in other parts of the country. The experiences gained by running the TB dispensaries were utilized for initiating a systematic campaign, providing health education to the public and drawing their attention to the hazards of the diseases, possible treatment, precaution and preventive measures against infection.
 
Report of Health Survey and Development
However, it was evident that the Sanatoria, TB dispensaries / clinics could tackle only the fringe of the problem and public opinion began to build up slowly for active intervention of the government to tackle the situation. The government formed a committee under the chairmanship of Sir Joseph Bhore for assessing the magnitude of the problem and suggest remedial measures to tackle the situation. The report submitted by the Bhore Committee in 1946 estimated that about 2.5 million TB patients require treatment but the availability of the beds in the TB hospitals were grossly inadequate.6 In order to bridge the gap, the committee recommended establishment of organized domicilery services by setting up TB clinics at the districts and mobile TB clinics for rural areas.
 
Concept of Home Treatment
Drs C Frimodt Moller and BK Sikand were the first to advocate the concept of home treatment. This was a complementary scheme to take care of the waitlisted patients attending the sanatorium, TB clinics and dispensaries. This was found viable on a limited scale for handling individual cases.7
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Fig. 1.6: Dr BK Sikand
 
National Sample Survey on TB
6For a large country like India, a much more comprehensive information on the magnitude and extent of the disease in the various cross sections of the population was required. Considering the size and topography of India, estimating the disease burden by carrying out disease surveys was not an easy task. Apart from resources, the necessary equipment and trained medical and Para medical personnel to man the various health institutions conducting large-scale surveys were not readily available. Dr P V Benjamin encouraged Medical Colleges to start TB departments and also opened up avenues for training of para medical workers like viz.. Laboratory Technicians, X-ray technicians and Health visitors to meet the Human Resource requirements of the country. He was also a guiding source for several university to start post graduate education in TB.
As Dr PV Benjamin was also a member of the health planning in the planning commission, he was instrumental in coaxing Indian Council of Medical Research (ICMR) to undertake National Sample Survey (NSS) survey on TB. To oversee these activities, TB Division was set up under the Directorate General of Health Services (DGHS), New Delhi headed by Dr PV Benjamin in the year 1946. The NSS survey was carried out between 1955-58 in order to obtain reliable information on the disease situation expeditiously and rationally. The survey revealed that the problem of TB was uniformly distributed both in urban and rural population of the country.8 On an average the bacillary cases were 4/1000 and X-ray active cases 16/1000.
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Fig. 1.7: Dr PV Benjamin
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Fig. 1.8: Dr Pamra
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Fig. 1.9: Dr Sen
 
Introduction of Anti-TB Drugs in India
The development of anti-TB drugs was sporadic over a period of two decades starting from 1940s. Streptomycin (1944), Para-Amino Salicylic Acid (1946) followed by Thioacetazone (1950) and Isonicotinic Acid Hydrazide (1952) were first introduced in western countries. Till the late fifties, there were no specific drugs for treatment of TB in our country. However, with the availability anti-TB drugs in the late fifties, only a few elite group of patients could be treated and it was still not within the reach of 7common man. These drugs were tried on a limited number of patients in India by Dr Sikand from New Delhi TB Centre9 and Dr Sen from Calcutta in 1952 and Dr Sikand and Dr Pamra from Delhi10 in 1956.
 
EVOLUTION OF DIAGNOSTIC TOOL
 
X-ray
Following the discovery of X-rays by Wilhelm Konrad Roentgen in 1895 and further innovations and refinement of procedure in chest radiology, physicians were equipped with one more tool for diagnosing TB cases. X-ray became the cornerstone for TB diagnosis. India did not lag behind in utilizing this facility and they were made available in the sanatoria as well as TB clinic in the later half of the 19th century. However limitations observed were that it was expensive, difficult to interpret, lack of training for accurate diagnosis and indiscriminate use of chest X-ray and Mobile Mass Radiography (MMR) in the general population posing serious problems in classifying the disease.
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Fig. 1.10: Dr Rajnarain
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Fig. 1.11: Dr Bordia
On one hand large number of non TB cases were being diagnosed as TB and put on treatment and on the other hand inter reader variation was observed in the interpretation of MMR films. It is worth recollecting the names of the personalities like Drs. F Moller, BK Sikand, Raj Narain, NL Bordia, TJ Joseph who ventured to find solutions to some of the vexing issues.
 
Sputum Smear Microscopy
With the discovery and demonstration of tubercle bacilli by Dr Robert Koch using microscope followed by the technological upgradation of microscope as well as the staining techniques over a period, smear microscopy by Ziehl-Neelsen and the Fluorescence technique became the standard technique for diagnosing TB cases. It was found that this tool can be applied on a wide scale as it happen to be cost effective, quite sensitive and specific. In order to minimize the disadvantages of the X-ray as a tool, sputum smear microscopy as a tool for diagnosis was found to be more effective and feasible. This was further validated by the experiences gained at the NDTC, NTI, UMTS and TRC by the use of smear microscopy, which was unambiguous to diagnose patients. No doubt X-ray active cases needed to be picked up and treated effectively, but from the point of view of TB control strategy, smear positive patients would form the priority group as they are the primary source of infection.
 
BCG Vaccination as Preventive Tool
One of the milestone in prevention of the TB was the discovery of BCG vaccine in the year 1908. BCG was the only avenue available at that time for prevention against TB and was extensively used in most of the European countries during 1920s1 In India, Dr C Frimodt Moller was the first to introduce BCG vaccination in the year 1948. BCG vaccination programe was pilot tested in Madanapalle of Andhra 8Pradesh before mass BCG campaign was launched in the country in early 50s. BCG vaccine production centre was also established in Guindy of Madras with the assistance of WHO and UNICEF around the same time. Mass BCG vaccination program got the international recognition as one of the biggest and most successful operation carried out by any country. For the next two decades BCG program was in vogue. Scientific evidences of varied protective effect of BCG started accumulating from various countries and it was in the range of 0 to 80 percent. With this disturbing trend, the scientific community thought it fit to carry out an immaculate study and this challenge was taken by the Indian scientists.
A planned and impeccable double blind BCG vaccination trial was conducted in Chingleput district, Tamil Nadu. The Trial was spearheaded by Drs Raj Narain, CE Palmer, HT Mahler, J Holms and J Guld under the technical guidance of WHO team. After 12 years of follow-up it was astonishining to the scientific community, that BCG did not provide any protection against the bacillary forms of TB. At this juncture, mass BCG campaign was in full swing. In the light of the results of the chingleput trial, the planners had to make an indepth review on the role of BCG vaccination result resulting in inclusion of BCG vaccination under the Expanded Programe of Immunization as it afforded protection against childhood forms of TB.1113
 
ESTABLISHMENT OF INSTITUTIONS OF NATIONAL REPUTE
 
Tuberculosis Research Center (TRC)
Under the dynamic leadership of Dr PV Benjamin, Tuberculosis Chemotherapy Centre (TCC) was established in 1956, later known as TRC in Madras (now Chennai) under ICMR. We will be failing in our duty if we do not mention the names of the stalwarts like Wallace Fox, DA Mitchison, lan Sutherland, S  Radhakrishna, PRJ Ganghadharam, V Ramakrishna, J Firmodt Moller, SP Tripathy, NK Menon and others who had immensely contributed for the epoch making study on domiciliary vs Sanatorium treatment, which demonstrated that the key to success of treatment rests on adequate chemotherapy at home and not on hospitalization with adequate bed rest in a well ventilated area and balanced diet.
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Fig. 1.12: Tuberculosis Research Center
It also demonstrated that there was no significant difference in the risk of contracting TB among the close family contacts of patients treated at home as well as at sanatorium.14
 
National Tuberculosis Institute (NTI)
With the path-breaking findings of the studies carried by the TCC and also the information available from the NSS carried out by ICMR, Dr PV Benjamin was instrumental in establishing NTI at Bangalore in the year 1959 with the primary objective of formulating a Nationally applicable TB Control programme.15
 
Formulation of National TB Program (NTP)
After a series of breakthrough studies, NTP was formulated in 1962. Several important studies on different aspects of TB disease, viz. Epidemiological, Operational, Sociological and Bacteriological conducted by NTI was found useful in improving the TB control strategies. Of the several breakthrough studies carried out during this period, the following needs a special mention as they laid foundation for the program:
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Fig. 1.13:
  • The sociological study of awareness of symptoms suggestive of pulmonary TB study by Dr D Banerji et al.16
  • Tuberculosis in a rural population of South India: A five-year Epidemiological study by NTI, Bangalore.17
    It will be befitting to mention the name of Dr DR Nagpaul who was the former Director of NTI. During his tenure the District TB Program was established in most of the Districts of the country. NTI also took the onus of training a large number of key personnel, viz. Medical officers and paramedical TB workers under the programme besides engaging itself in monitoring the TB control program to provide feedback from time to time both to the central and state authorities.
 
Implementation of NTP
NTP was pilot tested in Ananthpur district of Andhra Pradesh in 1961 and followed by launching of the programme in a phased manner throughout the country by creation of a good infrastructure within the limited resources available. With this theera of Conventional Chemotherapy took its roots in our country Standard drug regimens were formulated using the information obtained from the studies on chemotherapy conducted by NTI and TRC.
The programme was expanded to 364 districts using R1 to R5 regimen. District TB Centre (DTC) formed the hub from where the programme was implemented and supervised. Initially, monitoring was taken up on a regional basis. Thereafter NTI had to shouldered monitoring of the programme for the entire country.18
 
State TB Demonstration Center (STDC)
TB Demonstration and training centres (TDTC) came into existence following the successful study on domicilary versus sanitarium treatment carried out by TRC. These centres were established with the aim of demonstrating the practicability of treating TB patients on ambulatory basis from TB clinics as effectively as in patient in any TB hospitals or sanatoria. The TDTCs were upgraded and strengthened under NTP. It was redesignated as STDC with responsibility of training health workers in the state on the policy issues and running model DTP units as demonstration sites. How ever these centres fell short of meeting the objectives for which they were started.
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Fig. 1.14: Dr DR Nagpaul
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Fig. 1.15: Dr Wallace Fox
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Table 1.1   Standard drug regimens in NTP
Code no
Drug and dosage
Mode and rhythm of administration
R1
Isoniazi 300 mg + Thioacetazone 150 mg.
Both drugs in a single dose or in two divided doses orally, daily.
R2
Bi-weekly regimen
Inj. Sterptomycin 0.75 g / 1 g. +
Isoniazid 600 to 700 mg, Pyrodoxine 10 mg.
Intramuscularly Orally
R3
Isoniazid 300 mg + PAS 10 g.
In a single dose. In two divided doses. Both drugs orally, daily
R4
Isoniazid 300 mg + Ethambutol 800 mg
Both drugs in a single dose, daily, orally
R5
Bi-phasic regimen
Intensive phase
Inj. Streptomycin (Sm) 0.75 g / 1 g. + Isoniazid 300 mg + Thioacetazone 150 mg or Ethambutol 800 mg. or PAS 10 g. Followed by
Continuation phase
10-16 months duration.
First two months
Sm Intramuscularly, daily single dose orally, daily, (Thioacetazone and PAS given in two divided doses if not tolerated)
Total duration of treatment = 12 to 18 months
Table 1.2   Short course chemotherapy regimens in NTP
Code
Drug regimen with dosage
Mode and rhythm of administration
RA
2 EHRZ/6TH
a. Intensive Phase EHRZ (2 Months)
b. Continuation Phase HT (6 months)
E = 800 mg H = 300 mg, R = 450 mg
Z = 1500 mg and T = 150 mg
All drugs in a single dose or in two divided doses orally, daily.
RB
2 SHRZ / 4S2H2R2
a. Intensive Phase(2 months)
S = 0.75g, H = 300 mg, R = 450 mg and Z=1.5 g
b. Continuation Phase (4 months)
S = 0.75 g, H = 600 mg and R = 600
All drugs in a single dose or in two divided doses orally, daily. For two months followed by twice weekly intermittent treatment for four months Streptomycin in the form of injection
 
Introduction of Short Course Chemotherapy (SCC)
From the findings of a number of related studies and on analysis of reports, it was evident that under field situation, compliance of anti-TB treatment for 12 to 18 months was a major problem. In the meanwhile, there was major breakthrough with the discovery of rifampicin in 1966 and re-introduction of pyrazinamide. Rifampicin in combination with other anti-TB drugs proved to be an arsenal to combat TB.
The results of the various clinical trials carried out in the west and our country by NTI and TRC were quite encouraging. Dr Wallace Fox has done a pioneering work in the field of TB through British Medical Research Council units in East Africa, India, Hong-kong and Singapore and handed over the greatest gift to the world in the form of SCC.
Dr Wallace Fox is considered as the father of clinical trials for chemotherapy of TB. This was a very important milestone in the fight against TB on a global scale which brought enormous hope of early TB control. These findings enabled to reduce the duration of treatment to 6 to 8 months. In 1983, TRC, Madras, pilot tested SCC in 18 districts of the 11country to assess the feasibility of its implementation on a larger scale. Government of India started implementation of SCC in 1986, and scaled up the coverage to cover 252 districts 13 with the following regimens:
 
SHORT COURSE CHEMOTHERAPY REGIMENS IN NTP
Inspite of the introduction of SCC, monitoring report as well as findings of some studies continued to show high rate of default and the disturbing trend of low compliance in SCC districts.1922 In light of these findings, two programme reviews by ICMR and Institute of Communication, Banglore were carried out in India.2324 However, there was no concrete follow-up actions on the recommendations of these committees.
Following the global review of the programme25 WHO declared TB as global emergency in 1993: and government of India adopted Revised National Tuberculosis Control Programme (RNTCP) with the Directly Observed Treatment Short (DOTS) course as the main strategy, our country has gains considerable experience in running the (RNTCP) for more than a decade. The programme now covers more than 947 million population in 543 districts of the country. It is also making an all out effort to involve key health care providers in the private sectors with the goal of controlling TB in India.26
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