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After a less than significant effect in curbing MDR TB by the drug delamanid, WHO is revising its advice on the drug.

Details

• Delamanid drug, approved for use in multidrug-resistant tuberculosis (MDR-TB) patients by the World Health Organisation in October 2014, did not show any statistically significant difference in successfully curing the disease or reducing the mortality rates compared with a dummy in a Phase III human clinical trial, WHO’s position statement issued on January 15 says. However, the drug was found to be safe unlike many of the other second-line medicines used for MDR-TB treatment.
• Though the trial did not confirm the efficacy findings of earlier studies, delamanid should be retained in country guidelines, national essential medicine lists and procurement options. But the MDR-TB treatment algorithms “may need adjustment” in view of the Phase III trial results.
• The 2014 interim guidance issued by the WHO on the use of the drug for treating MDR-TB patients was based on Phase IIb trial results and subject to review once Phase III trial results become available. A person is said to have MDR-TB when there is drug resistance to at least isoniazid and rifampicin, the two main first-line TB drugs.
• In addition to optimised MDR-TB regimen, participants in the trial received either delamanid or a dummy for six months. At the end of 30 months of follow-up, 77.1% of MDR-TB patients who received delamanid drug were cured compared with 77.6% of those who received a placebo (dummy), and mortality was 5.3% in the delamanid group and 4.7% in the placebo group.
• As a result, the WHO has advised all national TB programmes to include delamanid to longer MDR-TB regimen only when patients cannot tolerate or show resistance to certain second-line TB drugs.
• The conditions for using delamanid drug in patients remain the same — careful selection of patients who are likely to benefit, designing a longer MDR-TB regimen as receommended by the WHO, close monitoring of treatment response, and active TB drug-safety monitoring and management.

About MDR TB

• Multi-drug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs), isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).
• Tuberculosis is caused by infection with the bacteria Mycobacterium tuberculosis. Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the person’s immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone).
• However, beginning with the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see mechanisms.) Currently the majority of multidrug-resistant cases of TB are due to one strain of TB bacteria called the Beijing lineage. This process accelerates if incorrect or inadequate treatments are used, leading to the development and spread of multidrug-resistant TB (MDR-TB). Incorrect or inadequate treatment may be due to use of the wrong medications, use of only one medication (standard treatment is at least two drugs), not taking medication consistently or for the full treatment period (treatment is required for several months).
• Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs. Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over $100,000 USD.
• If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB.
• Almost one in four people in the world are infected with TB bacteria.
• MDR-TB caused an estimated 480,000 new TB cases and 250,000 deaths in 2015. MDR-TB accounts for 3.3% of all new TB cases worldwide. Resistant forms of TB bacteria, either MDR-TB or rifampin-resistant TB, cause 3.9% of new TB cases and 21% of previously treated TB cases.
• Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.
• Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected. Under ideal program conditions, MDR-TB cure rates can approach 70%.

Source

The Hindu