Published Date: 2012-01-19 14:44:31
Subject: PRO/EDR> Tuberculosis, TDR - India (04): (MH) fatal
Archive Number: 20120119.1015543
TUBERCULOSIS, TDR - INDIA (04): (MAHARASHTRA) FATAL
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Tue 17 Jan 2012
Source: UN Integrated Regional Information Networks (IRIN) News [edited]
The "totally drug-resistant" tuberculosis (TDR-TB) reportedly emerging in India is actually an advanced stage of drug-resistant TB, which researchers called totally drug-resistant for lack of a better term.
"Whilst waiting for the WHO [World Health Organization] to define this advanced stage of resistance, TDR is a good descriptor," Zarir Udwadia, a doctor from PD Hinduja National Hospital and Medical Research Centre in Mumbai, India, told IRIN.
Udwadia and colleagues reported in late December  on the 1st cases of what they called TDR-TB in 4 patients who did not respond to 12 drugs used to treat TB, based on lab tests.
Drug-resistant TB develops when patients do not complete the recommended 6-month antibiotic treatment correctly or take sub-standard drugs, which then increases treatment time and costs. 3 of the 4 patients in Mumbai studied had "received erratic, unsupervised 2nd-line drugs, added individually and in incorrect doses" from multiple doctors trying to cure their multidrug resistance, noted the researchers.
WHO recognizes 2 groups of drug-resistant TB: multidrug-resistant (MDR-TB) occurs when patients do not respond to the 2 most effective anti-TB drugs. In the case of extensively drug-resistant TB, (XDR-TB), fluoroquinolone and anti-TB injectable drugs also fail.
"In reality it is not clear what 'total' really means -- hardly ever do labs test against all drugs," Paul Nunn, a TB expert with WHO's TB control department, who has led the agency's global response to XDR-TB since 2006, told IRIN. WHO has issued treatment guidelines for 14 drugs -- 6 that were not tested by the Indian labs -- for TB cases that do not respond to the 4 "1st-line" drugs [http://whqlibdoc.who.int/publications/2008/9789241547581_eng.pdf].
In a 13 Jan 2012 briefing note, WHO explained how the lack of international standards on lab testing to determine sensitivity to some anti-TB drugs made it difficult to rule out a cure [http://www.who.int/tb/challenges/mdr/tdrfaqs/en/index.html]. While a strain of TB may not respond to a drug in a lab, it may be do so in an infected person, said Nunn. In addition, as new anti-TB drugs are still under development, their effectiveness against the reportedly totally drug-resistant strains cannot yet be proven, said WHO.
WHO is convening a meeting of TB experts in March 2012 to consider whether a new TB definition is needed. "If 'totally drug-resistant' TB defines a subset of XDR-TB with different characteristics to other XDR-TB cases, particularly with respect to the outcome of such cases, then an internationally recognized definition may be needed," noted WHO in its recent post. "We must at least concede that this is a much more difficult-to-treat form than XDR where some SLD [2nd-line drug] options exist," said Udwadia.
Medical literature has recorded 21 cases labelled TDR-TB in Germany, Italy, Iran, and now India. "It is very likely that many countries will have a handful of [such] cases -- in eastern Europe probably even more," said Nunn. By the end of 2010, 69 countries reported to WHO at least one case of XDR-TB, with China and India accounting for almost half the world's estimated number of MDR-TB cases. In 2010, 16 of the 36 countries with a high burden of TB or MDR-TB did not have at least one laboratory capable of performing TB culture and drug susceptibility testing per 5 million people.
ProMED-mail rapporteur Mary Marshall
[It is important that WHO is addressing the situation of "totally drug resistant tuberculosis" or TDR-TB. TDR-TB may, indeed, not be exactly totally drug resistant. The TDR-TB strains from India were reported resistant to all 1st-line (isoniazid, rifampin, ethambutol, pyrazinamide, and streptomycin) and the 2nd-line (ofloxacin, moxifloxacin, kanamycin, amikacin, capreomycin, para-aminosalicylic acid, and ethionamide) drugs tested. No mention was made of the activity of so-called 3rd-line anti-TB drugs, such as the macrolides (for example, clarithromycin), clofazimine, amoxicillin/clavulanic acid, linezolid, imipenem, or high-dose isoniazid, and several new investigational drugs against these strains. The in vitro drug susceptibility testing, however, for some anti-TB drugs remains problematic. According to the January 2012 WHO document (http://www.who.int/tb/challenges/mdr/tdrfaqs/en/index.html):
"The term "totally drug resistant" has not been clearly defined for tuberculosis. While the concept of "total drug resistance" is easily understood in general terms, in practice, in vitro drug susceptibility testing (DST) is technically challenging and limitations on the use of results remain: conventional DST for the drugs that define MDR and XDR-TB [isoniazid, rifampin, the fluoroquinolones, kanamycin, amikacin, and capreomycin] has been thoroughly studied and consensus reached on appropriate methods, critical drug concentrations that define resistance, and reliability and reproducibility of testing. Data on the reproducibility and reliability of DST for the remaining SLDs [2nd-line drugs] are either much more limited or have not been established, or the methodology for testing does not exist. Most importantly, correlation of DST results with clinical response to treatment has not yet been adequately established. Thus, a strain of TB with in vitro DST results showing resistance could in fact, in the patient, be susceptible to these drugs. The prognostic relevance of in vitro resistance to drugs without an internationally accepted and standardised drug susceptibility test therefore remains unclear and current WHO recommendations advise against the use of these results to guide treatment.
"Lastly, new drugs are under development, and their effectiveness against these "totally drug resistant" strains has not yet been reported.
"For these reasons, the term "totally drug resistant" tuberculosis is not yet recognised by the WHO. For now these cases are defined as extensively drug resistant tuberculosis (XDR-TB), according to WHO definitions."
A map of the states of India can be accessed at http://www.globalsecurity.org/military/world/india/images/IndiaMap_tourism.gif. The HealthMap/ProMED-mail interactive map of India can be accessed at http://healthmap.org/r/1pr7. - Mod.ML]