Totally Drug-Resistant TB may be a Misnomer

The world’s press earlier this week announced the news that a strain of tuberculosis known as TDR-TB has emerged in India that is resistant to all drugs, raising the specter of rising numbers of TB deaths. However, say researchers, it is actually an advanced stage of drug-resistant TB, which was called totally drug-resistant only for lack of a better term.

"While waiting for the 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 first cases of what they called TDR-TB in four 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 six-month antibiotics treatment correctly or take sub-standard drugs, which then increases resistance, treatment time and costs.

Three of the four patients in Mumbai studied had "received erratic, unsupervised second-line drugs, added individually and in incorrect doses" from multiple doctors trying to cure their multidrug resistance, noted the researchers.

Definitions

The World Health Organization recognizes two groups of drug-resistant TB. Multidrug-resistant (MDR-TB) occurs when patients do not respond to the two 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," said Paul Nunn, a TB expert with WHO's TB control department, who has led the agency's global response to XDR-TB since 2006.

The WHO has issued treatment guidelines for 14 drugs - six that were not tested by the Indian labs - for TB cases that do not respond to the four "first-line" drugs. In a 13 January briefing note, the 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.

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. The organization is convening a meeting of TB experts in March 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 second-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 five million people.

(IRIN is a service of the United Nations Office for the Coordination of Humanitarian Affairs. This report does not necessarily reflect the views of the United Nations.)