Historical Background / Periodical Development

The Early Days

TB is one of the most ancient diseases. It has been referred to in the Vedas and Ayurvedic Samhitas.

A TB Division in the Directorate General of Health Services (DGHS), was established in New Delhi in 1946, with an Adviser in TB as its head. TB was also given a prominent place in the planning. Since the government was not only concerned with TB but with other diseases and health infrastructure, it constituted a committee under the chairmanship of Sir Joseph Bhore. Its secretary was Rao Bahadur KCKE Raja, who as the Director General of Health Services (DGHS) played a dominant role in the TB field during his tenure. The Bhore Committee, which published its report in 1946, placed organized domiciliary service at the forefront of the programme. It recommended setting up of a clinic for each district and the use of mobile clinics for rural areas. 

BCG vaccine, named after the two scientists who developed it, stands for Bacillus Calmette Guerín. BCG work started in India as a pilot project in two centers in 1948. In 1949, it was extended to schools in almost all states of India. Under the aegis of the International Tuberculosis Campaign, which had considerable experience in BCG work in many countries, it was introduced in India on a small scale in Madanapalle with Dr Frimodt Moller in the lead. India started a mass BCG Campaign in 1951. A BCG Vaccine Production Center in Guindy, Madras was set up in 1948. WHO and UNICEF provided support. 

The very notion that there could be effective drugs against the tubercle bacilli was so revolutionary that researchers began to experiment on the effective dosages and combinations of drugs to be used. The issue of affordability was also considered. In the 1949 Annual TB Workers' Conference, several papers were presented on the effects of PAS and SM on the patients and on the distribution of SM in India. In 1952 Drs Robitzek and Selikoff revealed that INH is a miracle drug against TB and it continues as such till date. 
In 1953, Frimodt Moller reported remarkable results with the regimen SM and INH, single and combined, in the treatment of pulmonary TB in Indian patients. In 1956, Drs Sikand and Pamra presented a paper on the "effect of Streptomycin(SM),Para amino Salicylic Acid (PAS) and Isoniazid (INH) in 703 cases of pulmonary TB, diagnosed and treated during 1951-53". They found that the results of domiciliary treatment were encouraging enough to warrant a shift of emphasis from hospitals and sanatoria to clinics without waiting for any further trials. 

These studies would, in time, revolutionize the management of TB all over the world. However, it soon became apparent that the tubercle bacilli could not be destroyed easily even with drugs. The tubercle bacilli had powerful survival techniques, besides developing resistance to drugs. Trials indicated that the newly available drugs, when used singly, were effective only for short periods. To be effective, conventional treatment had to be continued for at least 12-18 months. This brought with it several problems. How many patients would continue to take medicines for such a long duration? How to keep track? Further research was, therefore, needed to harness the potential of these newly discovered drugs. 

In the mean time, the government in 1956 had established the Tuberculosis Chemotherapy Center, later known as Tuberculosis Research Center (TRC) in Madras (Chennai), under the auspices of the ICMR, Government of Madras, WHO, and the British Medical Research Council (BMRC). This Center was to provide information on the mass domiciliary application of chemotherapy in the treatment of pulmonary TB. It demonstrated that the time-honoured virtues of sanatorium treatment such as bed rest, well-balanced diet and good accommodation were remarkably unimportant provided adequate chemotherapy was prescribed and taken.

Further, there was no evidence that close family contacts of patients treated at home incurred an increased risk of contracting TB. Therefore, it would be appropriate to treat infectious patients in their own homes. This finding revolutionized TB treatment the world over. 

National Tuberculosis Institute (NTI) was established in 1959 to evolve through research a practicable TB programme that could be applied in all parts of the country. This Institute would train medical and para-medical workers to efficiently apply proven methods in rural as well as urban areas. 

In 1950, Dr P V Benjamin reported that tuberculosis infection is so widespread that no part of the country is free from it. The subsequent BCG campaigns revealed similar findings. However, this needed to be checked by scientifically conducted surveys. 

For a country as large as India, the sample of one area was inadequate. Reliable information on the magnitude and extent of the disease in the various cross sections of the population was required. This was not an easy task. Apart from resources, trained personnel to conduct large- scale surveys was not readily available. A special committee of the ICMR was set up to address the issue of obtaining this information expeditiously and rationally. It decided that a systematic survey on a countrywide basis should be undertaken.

District TB Programme

Based on the findings of the operational studies conducted, a draft recommendation for the District Tuberculosis Programme was prepared in 1961, keeping in mind an average Indian district, its population and health facilities available. 
The national programme policy as enunciated in the introduction manual of DTP comprised: 

	Domiciliary treatment
	Use of a standard drug regimen of 12-18 months duration
	Treatment free of cost
	Priority to newly diagnosed patients, over previously treated patients
	Treatment organization fully decentralized
	Treatment organization fully decentralized
	Efficient defaulter system/mostly self-administered regimen
	Timely follow up
	Chemoprophylaxis not recommended as it is impractical on mass basis.

Social sciences were consciously included as hard evidence and peoples' voices were placed on par with science, technology and administration. The National Programme was fully integrated with the government health services of the country, thus extending the scope of TB work to be available through its vast reaches.

Controlled clinical trial for efficacy of BCG vaccine
NTI was also concerned with the efficacy of the BCG vaccine itself. BCG vaccination was the only available protective measure against TB. Different trials had not revealed credible proof of its efficacy. Many, including late Sri C Rajagopalachari, even thought that its efficacy was not fully proven and strongly advocated against its continued large-scale use. It would be in the interest of the country to undertake a well designed trial to seek clear answers to the major issues confronting it.
Therefore, the NTI had been vigorously planning to conduct a major BCG trial and had even reserved certain areas in the country as vaccination-free zones. It was in touch with the international scientific community, various vaccine production centres and in the field.
In January 1964, it initiated intensive discussions with the WHO experts and representatives from United States Public Health Service (USPHS). It was agreed that any trial undertaken must not interfere with the progress of NTI and NTP; and because such a trial was expensive and prolonged, it would have to be designed with utmost care and efficiency. 

Ultimately, the project named Feasibility Study for TB Prevention Trials became part of the ICMR and moved out of the campus to its own building. In time, its studies showed that the major BCG trial would be best if conducted in Chingleput district of Tamil Nadu than in other areas reserved for the purpose.
Field work began and the office was moved to Madras. In spite of shifting of the project camp to Madras, NTI continued to assist the BCG Trial by providing technical guidance and replacement of staff. When Dr Raj Narain, Epidemiologist of NTI retired, Dr Baily, TB Specialist of NTI joined as the Director of this study and continued to serve till the first report was published. 

The BCG trial was completed as scheduled. After a period of twelve and a half years, it brought out a revolutionary report. It showed that BCG vaccination did not offer significant protection against TB of the lung. Several expert committees appointed both by the authorities in India and by the WHO examined all the procedures followed up in the study and came to the conclusion that the study had been meticulously carried out and vaccine used in the trial were the best available ones. The implications of this study was: Should BCG vaccination be given up in India? Another committee appointed jointly by ICMR and the WHO went into the epidemiological aspects of the causation of TB under Indian conditions. It concluded that though BCG may not protect against TB of lung which occurs mostly in adults, it could provide substantial protection against childhood forms of TB such as tubercular meningitis, miliary TB. The protective effect of BCG against these forms of TB was not studied in Chingleput Trial. In India BCG vaccination policy was revised and it was recommended to be given at an early age preferably before the end of the first year after birth by integrating under UIP. BCG vaccination policies in many other countries were also revised as a consequence of the Chingleput study findings.

Era of short course chemotherapy

Chemotherapy of TB underwent revolutionary changes in the seventies owing to the availability of two well-tolerated and highly effective drugs - rifampicin and pyrazinamide. These drugs allowed short course chemotherapy (SCC) and made it possible to simplify treatment and reduce its duration. Discovery of rifampicin in 1967 is considered as one of the greatest achievements in the history of development of anti-TB drugs. After its discovery no new drug has been found. 
Monitoring of the programme 
It is not possible to measure disease burden accurately through monitoring. However, it is an important tool to evaluate the performance of the units of the DTPs in an ongoing manner and take corrective action simultaneously. This would improve the programme efficiency on a regular basis. Till 1978 monitoring of the programme was done by northern and southern regional centres and from then by NTI only. 

The evaluation of the NTP 

The NTI had believed in assessment and evaluation as an ongoing process. It welcomed the idea of periodic assessment, especially from experts, on scientific lines as they are vital to the growth and improvement in the programme. 

The NTP was evaluated by three agencies, ICMR, Institute of Communication, Operations Research and Community Involvement (ICORCI) and WHO. 

In 1992, the Government of India, together with the World Health Organization (WHO) and Swedish International Development Agency (SIDA), reviewed the national programme and concluded that it suffered from managerial weakness, inadequate funding, over-reliance on x-ray, non-standard treatment regimens, low rates of treatment completion, and lack of systematic information on treatment outcomes. As a result, a Revised National Tuberculosis Control Programme (RNTCP) was designed.

Formulation of the RNTCP

In the light of the recommendations and concerns expressed by the Central Health Council, steps were taken since 1993 to implement the Revised National TB Control Programme (RNTCP) in selected areas with World Bank assistance. 

The RNTCP builds on the very substantial strengths and accomplishments of the National Tuberculosis Programme (NTP). 

The RNTCP strengthens the existing NTP infrastructure by creating a sub-district-level supervisory team (known as the TB Unit), consisting of a treatment supervisor (Senior Treatment Supervisor, STS) and a laboratory supervisor (Senior TB Laboratory Supervisor, STLS). These are new posts. In addition, a medical officer from the general health system serves as Medical Officer-TB Control at sub-district level who is specifically allocated TB control duties in addition to his other duties. These 3 individuals constitute the management unit, which is responsible for overseeing operations in approximately a 5 lakh population including, on average, 5 designated microscopy centers. All these three staff have been made mobile by giving vehicle/POL inputs. At each microscopy centre, a state-of-the art binocular microscope, good quality reagents and new recording and reporting proformae are available. More importantly, intensive modular training, supervision, and cross-checking of the work of the laboratory technician should ensure that reliable results are obtained. 

The goal of RNTCP is to cure at least 85% of new smear-positive cases of tuberculosis and to detect at least 70% of such patients, after the desired cure rate has been achieved. Clearly, both good outcomes and high case detection rates are essential. But it is essential that the system is geared up to reliably cure patients, before any attempts are made at expanding case detection. In fact, experience clearly shows that reliably curing patients results in a "recruitment effect" - wherever effective services are offered, case detection rates steadily increase. Cured patients act as one of the best motivators promoting case detection and patient adherence to treatment.

The basic principles of the RNTCP are: 

	Political commitment to ensure adequate funds, staff, and other key inputs
	Diagnosis primarily by microscopy of patients presenting to health facilities
	Regular and uninterrupted supply of anti-TB medications including the use of a patient-wise box which contains the entire course of treatment for an individual patient so that no patient should ever stop treatment for lack of medicines
	Direct observation of every dose of treatment in the intensive phase and at least the first dose in the continuation phase of treatment

Systematic monitoring, supervision and cohort analysis; one Senior Treatment Supervisor for organization of uninterrupted treatment and one Senior Tuberculosis Laboratory Supervisor for ensuring quality laboratory service for every 5 lakh population. Additional staff are provided for difficult hilly, tribal, and some urban areas. 

If 3 AFB smears are negative and there is no response to 1-2 weeks of antibiotics, X-ray is taken, and, if consistent with TB, the patient is treated for smear-negative TB. If only one of three specimens is positive, an x-ray is taken and the patient is evaluated. All treatment is given thrice weekly on alternate days. During the intensive phase, every dose is directly observed; medications for the continuation phase are packaged into a weekly blister pack, at least the first dose of which is directly observed. 

Policy direction, supervision, drugs and microscopes are provided by the central government. Modular training has been used for all staff from medical officers to health workers. Multi-purpose workers are responsible for treatment observation; where they are not available, treatment observation is done by community volunteers including Anganwadi workers, traditional dais, and community and religious leaders. Observation by a family member is not acceptable in the programme. In some larger cities with limited health infrastructure, the RNTCP has funded specialized, full-time staff for microscopy and for treatment observation.
Maharashtra is second largest populous state in the country, but also first largest state to cover the entire population under RNTCP in India. Revised National Tuberculosis Control Programme (RNTCP) has been expanded rapidly in the past four years in Maharashtra without compromising quality of services. The state was covering only 20% of population till 1999. Now the RNTCP program has covered entire population in the state. 

To implement this programme effectively State TB Society and 48 Districts/City TB Societies have been established. Detailed planning for implementation of the programme is done at State and District levels.

Phasewise implementation of RNTCP