Ethics, human rights and programmatic management of drug-resistant tuberculosis.

Sir,

Programmatic Management of Drug-Resistant Tuberculosis (PMDT) is being implemented in a phased manner in India since 2007. Three hundred and thirty-one million people in 150 districts across 15 states in the country are covered under DOTS Plus. So far, 4217 multi-drug resistant tuberculosis (MDR TB) patients are on treatment under this program in India.[1] MDR TB suspects from Revised National Tuberculosis Control Program (RNTCP) i.e., Category 2 failures, Category 1 failures and contacts of MDR TB patients are being subjected to sputum AFB culture and drug susceptibility test (DST) at the Intermediate Reference Laboratories (IRLs) and some accredited private labs. Under the DOTS Plus strategy, a standard treatment regimen (STR) is being followed. The regimen includes injection Kanamycin (K), Ofloxacin (OFL), Ethionamide (ETA), Cycloserine (CLY), Pyrazinamide (Z) and Ethambutol (E). PAS is available in cases where the oral medications are not tolerated. A detailed protocol for follow up and monitoring the treatment efficacy and adherence is in place. Results from DOTS Plus pilot sites have shown good treatment success rates.[2]

Pattern of DST differs among individuals depending on prior drug history and strains of M. tuberculosis in the region. A comprehensive individualized therapy is therefore necessary to control MDR TB.[3] Inadequate treatment of MDR TB can lead to poor outcomes and are a risk for extensively drug resistant tuberculosis (XDR TB).[4] Results from Peru, which was one of the first high burden countries to have piloted and implemented PMDT, have shown that individualized treatment regimen (ITR) after drug susceptibility testing is cost-effective as compared to STR and likely to be true for other high burden resource limited countries such as ours.[5] This strategy of ITR is based on WHO principles of management of MDR TB i.e., introducing three new drugs which have not been used in past and which bear no cross-resistance to the previously prescribed regimen.

The Mumbai PMDT is being implemented in three zones since July 2010 and is privileged to have the DST reports to four first line medicines Streptomycin (S), Isoniazid (H), Rifampicin (R) and Ethambutol (E) from the accredited private laboratory - Hinduja Hospital which does not test for PZA for RNTCP patients. Around 200 patients have been initiated on second-line treatment under the STR till date in Mumbai. It has been observed that at one of the peripheral public health centers in Mumbai, of the 21 MDR suspects referred for investigations: 6 (28.5%) were negative on culture, 15 (72.5%) were positive for M. Tuberculosis by culture. Two of the fifteen (13.3%) were fully sensitive to all four drugs; 11 out of the fifteen (73.3%) culture positives were resistant to all four first line drugs viz SHRE; 1/15 (6.6%) was resistant to SandH and one result is pending. In a study conducted by The Foundation for Medical Research, where patients from the above center were included, the proportion of resistance to three or more drugs including (HR+E/Z/EZ) (24%) was greater than that of resistance to HR (4%) only.[6]

In this situation following the STR using Ethambutol, with documented drug resistance, poses a danger of amplifying resistance[7] toward XDR TB; especially when the status of susceptibility to Pyrazinamide is not known. The program has an alternative drug available in the form of PAS which can be used in such instances (guidelines state that PAS can be used if other oral drugs are not tolerated or have adverse drug reactions but are silent about its use in case of resistance to any other drug in the regimen). By continuing use of a drug with documented resistance, we are placing patient's lives at risk and also may be inadvertently fueling an XDR TB epidemic.[8] Medical ethics demands that patients be provided the best care available. Also, by denying our patients the opportunity to be effectively treated[7] and cured and alleviated of the disease we are violating the basic human right of an individual.

It is time that we rise above protocols and put the health of patients and community on our priority and not wait till another epidemic to overwhelm us.