Tuberculosis Epidemiology in IndiaCHAPTER 1

Each year, in India, an estimated 28 lacs people develop tuberculosis (TB) disease and approximately 4.8 lacs people die from TB— World Health Organization's (WHO's) Global Report 2017.

The private sector holds a factual predominance of healthcare service delivery in India. There is very little information about TB patients from the private sector which is available to the program and little is known about their quality of treatment, including treatment outcomes.

The RNTCP works at five levels: national level, state level, district level, subdistrict level, and peripheral health institution level.

At the central level, the RNTCP is managed by the Central TB Division (CTD) under Ministry of Health and Family Welfare (MoHFW). Joint Secretary of Health from the administrative arm of the MoHFW and a national program manager—Deputy Director General-TB (DDG-TB), is in-charge of RNTCP.^2,3 The CTD is assisted by six national level institutes, namely the National Tuberculosis Institute (NTI) in Bengaluru, the National Institute for Research in Tuberculosis (NIRT) in Chennai, the National Institute of TB and Respiratory Diseases (NITRD) in New Delhi, National Japanese Leprosy Mission for Asia (JALMA), Institute of Leprosy and other Mycobacterial Diseases in Agra, Bhopal Memorial Hospital and Research Centre (BMHRC) in Bhopal, and Regional Medical Research Centre (RMRC) in Bhubaneswar.

At the state level, the state TB officer (STO) does the planning, training, supervising, and monitoring of the program in their respective states. The STO, based at the state TB cell, is answerable to their respective state governments, whilst implementing the technical policies and guidelines issued by the CTD. The state TB cells (STC) have been provided with equipment, infrastructure, and RNTCP contractual staff to carry out its functions. The State TB Training and Demonstration Centre (STDC) has three units: A training unit, supervision, and monitoring unit and an intermediate reference laboratory (IRL). There is state drug store (SDS) for the effective management of anti-TB drug logistics. One SDS per 50 million populations is established in all larger states.

The District TB Centre (DTC) is the nodal point for all TB control activities in the district. In RNTCP, the primary role of the DTC has shifted from clinical to managerial functions. The district TB officer (DTO) at the DTC has the overall responsibility of management of RNTCP at the district level as per the program guidelines and the guidance of the District Health Society.

The tuberculosis unit consists of a designated Medical Officer-Tuberculosis Control (MO-TC) who does RNTCP work in addition to other responsibilities. There are two full-time RNTCP contractual supervisory staff exclusively for TB work: A Senior TB Treatment Supervisor (STS) and a Senior TB Laboratory Supervisor (STLS). These tuberculosis units cover a population of approximately 200,000–250,000.5

For the purpose of RNTCP, a peripheral health institution (PHI) is a health facility which is manned by at least a medical officer.

The RNTCP has developed clear definitions for pulmonary TB cases that allow clinicians to categorize patients in terms of their diagnostic status and outcomes of treatment.

Presumptive case: A patient with symptoms and signs of EPTB who needs investigation

Bacteriologically confirmed case: A patient with microbiological diagnosis of EPTB, based on positive microscopy, culture or a validated PCR (polymerase chain reaction)-based test.

Clinically diagnosed case: A patient with negative microbiological tests for TB (microscopy, culture and validated PCR-based tests), but with strong clinical suspicion and other evidence of EPTB, such as compatible imaging findings, histological findings, ancillary diagnostic tests or response to anti-TB treatment. A presumptive case started on antitubercular therapy (ATT) empirically, without microbiological testing, should also be considered a clinically diagnosed case (empirically treated). A clinically diagnosed case subsequently found to be bacteriologically positive (before or after starting treatment) should be reclassified as bacteriologically confirmed.

Non-EPTB case: A patient who has been investigated for EPTB and has been diagnosed with a different condition, with no microbiological evidence of EPTB found.

Presumptive relapse: A patient who was declared successfully treated and now presents again with symptoms and signs of any form of TB.

Bacteriologically confirmed relapse: A patient with presumptive relapse who has microbiological evidence of persisting M. tuberculosis infection on subsequent diagnostic sampling.7

Clinically diagnosed relapse: A patient with presumptive relapse who does not have microbiological evidence of persisting M. tuberculosis infection on repeat diagnostic sampling.

A patient with presumptive relapse who is started on ATT empirically without repeat microbiological tests should also be considered a clinically diagnosed relapse (empirically treated). A clinically diagnosed relapse subsequently found to be bacteriologically positive (before or after starting treatment) should be reclassified as bacteriologically confirmed relapse.

Ancillary diagnostic tests refer to organ system-specific tests such as pleural fluid adenosine deaminase activity (ADA) in pleural TB, or cerebrospinal fluid (CSF) biochemistry and differential cell count in TB meningitis.

Successfully treated: A TB patient who has clinical and radiological evidence of resolution of active TB at the end of ATT. Some people have residual tissue damage that causes ongoing symptoms or radiological change (sequelae) despite resolution of TB infection.

Completed treatment: A TB patient who completed treatment without clinical evidence of failure but with no record to show complete resolution by radiological or bacteriological evidence of persisting infection by the last month of treatment because tests were not done.

Presumptive treatment failure: A patient who has no satisfactory clinical or imaging response to treatment after completing 3–6 months ATT.

Bacteriologically confirmed treatment failure: A patient with presumptive treatment failure who has microbiological evidence of persisting M. tuberculosis infection on repeat diagnostic sampling.

Clinically diagnosed treatment failure: A presumptive treatment failure case who does not have microbiological evidence of persisting M. tuberculosis infection on repeat diagnostic sampling and has no evidence of another disease process, but has strong clinical suspicion of treatment failure and other evidence of active TB, such as imaging findings.

The difficulty in defining treatment end-points in EPTB is due to the development of sequelae as a result of the inflammation and subsequent fibrosis.⁴ Patients with sequelae though may have complete microbiological cure, but continue to have symptoms. In EPTB at times, sequelae can mimic the signs and symptoms of active TB infection, and to declare the patient successfully treated difficult.

Early accurate diagnosis of TB and enhancing case finding efficiency, identification of presumptive TB cases and avail the best available diagnostic tests are of paramount importance to interrupt the transmission of TB disease. RNTCP screens around 20 million TB symptomatic by microscopy and initiates around 1.5 million cases of TB on treatment annually since 2007–2008. Rapid molecular diagnostics and line probe assay and cartridge based-nucleic acid amplification test (CBNAAT) testing is available throughout 8the country. In 2016, 520,000 patients have been tested and 35,000 rifampicin resistant (RR)/MDR-TB patients are diagnosed using these tests. Second-line drug susceptibility testing (DST) using liquid culture systems are available in the entire country. RNTCP has a three-tier laboratory network system. The National Reference Laboratory (NRL), IRL, DMCs, and all the laboratories under RNTCP follow the quality assurance (QA) protocol for all technologies as per the WHO guidelines.

Strengthening of these patient-centered treatment services in RNTCP with enhanced capacity to rapidly accommodate new drugs and treatment modalities will be the cornerstone of the current NSP.

The World Health Organization's Global TB Report 2015 estimates approximately 71,000 cases of MDR-TB that emerge annually from the notified cases of pulmonary TB in India. Based on subnational drug resistance surveys carried out in three states of India, ~3% among new TB cases and 12–17% among previously-treated TB cases have MDR-TB.

Decentralized diagnosis with with specimen transported to laboratory in cold chain. Rapid molecular DST [CBNAAT or line probe assay (LPA)] is the first choice of DST. All failures of first-line regimen, contacts of known MDR-TB case, all retreatment cases at diagnosis, any patient with smear positive follow up results, and all TB-HIV cases are offered DST.

Treatment is based on DR or DST results. Initial hospitalization is done at DR-TB center followed by ambulatory care. A standardized treatment regimen is used for MDR-TB—daily DOT that consists of 6–9 months of kanamycin; levofloxacin; cycloserine; ethionamide; pyrazinamide; ethambutol or 18 months of levofloxacin; cycloserine; ethionamide; ethambutol. Para-aminosalicylic acid (PAS) is used as a substitute drug in case of intolerance.

Tuberculosis is commonest opportunistic infection in HIV-infected individuals and HIV-infection is an important risk factor for acquiring TB infection and its progression to active TB. About 120,000 HIV-associated TB patients are emerging annually in India and accounts for about 10% of the global burden of HIV-associated TB. The mortality in among TB/HIV coinfected patients is 38,000 people every year.10

In 2014, 74% TB patients knew their HIV status and 44,067 were diagnosed as HIV positive. The 93% HIV-TB patients were provided co-trimoxazole preventive therapy (CPT) and 91% coinfected patients are put on ART.

The increasing co-occurrence of TB with tobacco consumption and diabetes mellitus (DM) is well evident. Smoking is three times more prevalent in TB patients and is strongly associated with increased rates of TB infection. Similarly, the prevalence of DM is as high as 13% and the prevalence even goes higher in MDR-TB cases. Patients with TB may have lung damage that is aggravated by continued tobacco use.

As per the Global Report on TB 2014, there were an estimated 550,000 TB cases among children (under 15 years of age) and 80,000 TB deaths (among HIV-negative children) in 2013 (6% and 8% of the global totals, respectively). It is one of the top 10 causes of childhood mortality.

In India, the private sector is the first point of care in many episodes of ill health. While most TB cases are ultimately treated by the RNTCP, most patients by then have already approached the private sector for TB diagnosis and treatment.

Advocacy communication and social mobilization (ACSM) is an inbuilt component of RNTCP and is recognized as an important element.

In addition to better diagnostic tool and treatment regimens, other patient supportive initiatives including better nutrition, counseling and financial support are equally essential. WHO's “End TB strategy” has this important target of “no affected family face catastrophic costs due to TB”.

Acute respiratory infections (ARIs) are the leading cause of morbidity and mortality affecting the youngest and oldest people in low- and middle-income nations. These infections, typically caused by viruses or mixed viral–bacterial infections, can be contagious and spread rapidly. Although knowledge of transmission modes is ever-evolving, current evidence indicates that the primary mode of transmission of most acute respiratory diseases is through droplets, but transmission through contact (including hand contamination followed by self-inoculation) or infectious respiratory aerosols at short range can also happen for some pathogens in particular circumstances.

In RNTCP, contact screening has been a clinical function and the end result expected is that most TB patients will have their contacts screened, with secondary cases detected and treated.

Tuberculosis infection is the seedbed for developing TB disease and continued transmission. The lifetime risk of reactivation of latent tuberculosis infection (LTBI) in healthy HIV-uninfected individuals is 10%, with 5% developing TB disease during the first 2–5 years after infection. The risk of reactivation is greatly increased in the context of immunosuppression, primarily due to HIV infection. Child contacts living in TB-affected households are particularly vulnerable populations for progression to TB and severe disease forms such as disseminated and meningeal TB. WHO has included scaling up TB preventive therapy for persons at high risk of developing TB in its End TB strategy and increasing coverage of contact investigations and TB preventive therapy for people living with HIV (PLHIV) and child contacts are important strategies. Scaling up TB preventive therapy is therefore important to meet the goals of ending TB in India.13

Children <6 years of age, who are close contacts of a TB patient, will be evaluated for active TB by a medical officer/pediatrician. After excluding active TB, he/she will be given INH preventive therapy irrespective of their Bacillus Calmette–Guérin (BCG) vaccine or nutritional status. The dose of INH for preventive therapy is 10 mg/kg body weight daily for 6 months be collected on monthly basis. INH preventive therapy: