World Tuberculosis Day: Present Scenario and Future Prospects

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. It usually affects the lungs (pulmonary TB), but can affect other sites as well (extra-pulmonary TB). The disease usually spreads through air, for example by coughing. Overall, a relatively small proportion (5–15%) of the people infected with M. tuberculosis will develop TB disease during their lifetime.

World TB Day is celebrated every year on March 24 to commemorate Dr. Robert Koch, who announced his discovery of M. tuberculosis, on the same date in the year 1882

Incidence:

• There were an estimated 9.6 million incident cases of TB globally, equivalent to 133 cases per 100,000 populations in the year 2014.
• India, Indonesia, and China had the largest number of cases: 23%, 10% and 10% of the total cases, respectively.
• An estimated 480,000 people developed multidrug-resistant TB (MDR-TB) globally in 2014.
• The absolute number of incident cases has fallen over last few years; an average rate of reduction was 1.5% per year between 2000 and 2014, and 2.1% between the year 2013 and 2014. The cumulative reduction in the TB incidence rate from 2000 to 2014 was 18%.

Co-epidemics of TB and HIV

• The probability of developing TB is much higher among people infected with human immune-deficiency virus (HIV).
• Out of 9.6 million incident TB cases in 2014, there were approximately 1.1–1.3 million (11–13%) people living with HIV.
• Almost three-quarters of these cases were noted in the African Region.

Mortality:

• In the absence of treatment, the death rate of TB is very high.
• There were an estimated 1.5 million TB deaths in 2014, including 0.4 million among people who were HIV-positive.

Treatment:

• Effective drug molecules for TB were first developed in the 1940s. The most effective first-line anti-TB drug, rifampicin, became available in the 1960s.
• The currently recommended treatment for new cases of drug-susceptible TB is a six-month regimen of four first-line drugs: isoniazid, rifampicin, ethambutol, and pyrazinamide.
• MDR-TB, defined as resistance to isoniazid and rifampicin (the two most powerful anti-TB drugs), requires more expensive and more toxic drugs such as kanamycin, levofloxacin, cycloserine etc.
• The duration of the current regimen recommended by World Health Organization (WHO) for MDR-TB is 20 months; however, treatment success rate is much lower for most patients with MDR-TB.

In 2014, the cost per patient treated for drug-susceptible TB ranged from US$ 100−500 in most countries with a high burden of TB. The cost per patient treated for MDR-TB was typically US$ 5000−10,000.

Between 2000 and 2014, TB treatment alone saved an estimated 35 million lives among HIV-negative people. Among HIV-positive people, TB treatment supported by anti-retroviral therapy (ART) saved an additional 8.4 million lives.

Research Pipeline

• WHO has issued an interim guidance on the use of bedaquiline (in 2013) and delamanid (in 2014), two new drugs that have recently been recommended for the treatment of MDR-TB under specific conditions.
• Additionally, eight new or re-purposed anti-TB drugs are in advanced phases of clinical development; some new chemical entities are discussed below:
  • For the first time in six years, an anti-TB drug candidate (TBA-354) was in Phase I testing. However, on 11 March 2016, TB Alliance announced discontinuation of the clinical development program of TBA-354 based on its safety and pharmacokinetic data.
  • PA-824 (pretomanid), currently in Phase II, is a potential cornerstone of future TB and drug-resistant TB treatment regimens.
  • Sutezolid (PNU-100480) and SQ109 are under development for the treatment of both drug-resistant and sensitive tuberculosis, and are currently in early Phase II testing.
• Recent observational studies of the effectiveness of short-term regimens for MDR-TB in Niger and Cameroon found that a 12-month regimen (instead of current 20 months) was effective and well-tolerated in patients not previously exposed to second-line drugs.
• Currently, there are 15 vaccines in Phase I or Phase II trials. However, for the time being, a vaccine that is effective in preventing TB in adults remains elusive.

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