The Indian Tuberculosis Scenario An Updated Insight
by Dr. Thirupathi K
The Indian Tuberculosis Scenario An Updated Insight by Dr. Thirupathi K
The latest surveillance and surveys shows that the Tuberculosis (TB) epidemic in India is larger than previously estimated. As per WHO Global TB report 2016, India has 2.8 million people diagnosed with tuberculosis. It is nearly one third of Global TB burden. Deaths due to TB have doubled in the country from 2.2 lakh in 2014 to 4.8 lakh in 2015. India has more patients living with drug-resistant TB than any other country in the world, with an estimated 79,000 persons becoming sick with this disease each year. India must do whatever it can to stop the transmission of TB both within and beyond its borders and this can best be accomplished with early diagnosis and effective treatment.
In order to manage the TB crisis in India, we need to diagnose the disease at the earliest using newer techniques currently available and manage the disease with proper regimens, and most importantly, we have to ensure that the patients are completing the full course of treatment.
The primary method for TB diagnosis in low and middle-income countries is the detection of Acid-Fast Bacilli (AFB) using smear microscopy, namely ZN stain. It is simple, affordable, quick and also provides results within hours. Fluorescence microscopy with fluorochrome staining and light emitting diode technology improves the sensitivity of TB detection. Still the gold standard for diagnosis of TB is isolating M.tuberculosis in culture. Solid culture (LJ medium) takes longer time to grow. Liquid culture media using automated systems, such as BACTEC radiometric method and mycobacterial growth indicator tube (MGIT) are even more sensitive and can detect growth in 1–3 weeks. Currently, we prefer to use liquid culture media for respiratory and extra pulmonary samples in view of faster results.
Molecular Methods such as Gene Xpert MTB and Line Probe Assay are available for clinical use in India both in government as well as private sectors. The introduction Nucleic Acid Amplification Tests has been one of the major developments in the diagnosis of M. tuberculosis. WHO has advocated universal use of Xpert MTB/RIF for the diagnosis of TB. Xpert MTB/RIF is a commercially available diagnostic test to test specimens for genetic material specific to Mycobacterium tuberculosis and simultaneously detects a gene which confers resistance to rifampicin, rpoB. Unlike other commercial PCR-based tests, it is a fully automated test. Results will be usually within 2 hours. Line Probe assay is another Nucleic Acid Amplification Test, which detects resistance to Rifampicin and INH in addition to detecting M.tuberculosis. It is not useful in testing extra pulmonary samples where the bacillary load is less.
Diagnosis Challenges
Extra-pulmonary tuberculosis (EPTB) accounts for about one fifth of all cases of tuberculosis and a major health burden in many forms of extrapulmonary TB (EPTB) are paucibacillary and the diagnosis of EPTB is therefore challenging. Acid-fast bacilli (AFB) smear of biological specimens is often negative. A high level of suspicion is important in evaluating a patient with presence of risk factors. The firm diagnosis of TB requires culturing of Mycobacterium tuberculosis and it is important for drug-susceptibility testing. Appropriate specimens are obtained and tested microbiologically and histologically. Chest x-ray should be part of the basic initial workup and may show evidence of active or old TB. Testing of extra pulmonary samples with Gene Xpert MTB is currently recommended for lymph node samples and CSF samples.
IGRA assays namely Quantiferon Gold TB and T spot ELISA are used for detecting latent TB infection. As they eliminate false positive results due to BCG vaccination and NTM infection, they are more specific than the conventional tuberculin tests. But at the same time, they are expensive, not standardized and they are also not useful in diagnosing active disease.
RNTCP India has come out with a new recommendation to use daily ATT in treatment of drug sensitive tuberculosis. The initial phase should consist of two months of Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E). The continuation phase should consist of three drugs, Isoniazid (H), Rifampicin (R) and Ethambutol (E) given for at least four months.
Bedaquiline, known as the ‘miracle drug’, is the first TB drug to be approved by Food and Drug Administration (FDA) in over 40 years. The treatment has been rolled out under the Revised National Tuberculosis Control Programme for treatment of MDR TB patients. The drug is made available in six public hospitals in Delhi, Mumbai, Chennai, Guwahati and Ahmedabad.
HIV & TB, the Deadliest Duo
HIV and TB are, in fact, partners in crime, and the world’s deadliest duo. In India, people living with HIV accounted for 1.2 million of all new TB cases. HIV poses several challenges to TB control. Tackling the problem of HIV and TB co infection presents both diagnostic and therapeutic challenges. It results in more risk of infection, disease, drug resistance, adverse drug reaction and paradoxical reaction. Tuberculosis is the most important cause of death in patients with HIV-AIDS. It is very important to diagnose tuberculosis at the earliest and screen all TB patients for HIV to address these issues.
Paradoxical reactions and IRIS (Immune Restitution Inflammatory Syndrome) in TB infection has long been observed in both HIV-positive and HIV-negative TB patients. Multiple definitions of paradoxical reaction exist in the literature, but essentially this term refers to the phenomenon of clinical (or radiological) deterioration of TB lesions or the development of new lesions in a patient with TB, who has initially improved on ATT occurring in the early phase of treatment (during the first 3 months). Paradoxical reactions manifest in a wide variety of ways and can sometimes be life threatening or lead to increased disability in EPTB survivors. Both paradoxical reaction and IRIS pose significant challenges to physicians treating TB patients in India.
The TB-Diabetes Nexus
In India since 2011, there were 61.3 million people living with Diabetes and the incidence keep on rising to epidemic levels. If we do not seriously think about the link between TB and Diabetes, it may begin to derail some of the good advances made in TB control especially in India. The link between TB and Diabetes mellitus has established what is needed now in good quality implementation of knowledge to screen for both diseases and monitor this dual burden of disease. It will be a meaningful strategy to screen diabetic patients for the symptoms or signs of TB and submit them for necessary investigations to make early diagnosis of tuberculosis. Not only that, but it is also important to screen for Diabetes or Impaired Glucose Tolerance in TB patients as maintaining good glycemic control is important for faster cure of TB.
The Importance of Follow up
A significant proportion of tuberculosis cases were being treated by private practitioners in India. There was no mechanism to follow the patients treated by them, which results in poor clinical outcomes. Finally, this situation affected the cure rates and development of drug resistant TB. If the TB patients diagnosed and treated under private sector are reported to public health authorities, the mechanisms available under the programme can be extended to these patients also to ensure treatment adherence and completion. The impending epidemic of M/XDR TB can only be prevented to a large extent by this intervention.
To address this situation, Government of India declared Tuberculosis as a notifiable disease where in, all TB cases diagnosed are to be reported mandatorily to the public health authorities in a specified format. With increasing number of health facilities, registered notification of TB cases also increased many folds.
To conclude, early diagnosis of TB using the available tests and appropriate molecular and culture methods is very important to cut the chain of transmission of TB. By ensuring that the patients are completing treatment, drug-resistant TB will be definitely reduced. Notification of tuberculosis patients will be an important step in ensuring follow-up. Effective management of various immunosuppressive disorders like diabetes, HIV and organ transplant recipients is essential in handling various infectious diseases and reducing the communicable nature of those infections.