Anti-tuberculosis program in South Africa may have inadvertently helped create new strain of XDR TB

In South Africa, the 2001 implementation of the World Health Organization's anti-tuberculosis program may have inadvertently helped to create a new strain of extensively drug-resistant tuberculosis (XDR TB).

In a new study published in the December 1 issue of Clinical Infectious Diseases, currently available online, researchers tracked the developing drug resistance of one particular strain of Mycobacterium tuberculosis over 12 years. They found that at the time of the 2001 adoption of the DOT+ strategy for multi-drug resistant strains, the strain was already resistant to one or more of the drugs mandated by that strategy, thus allowing the strain to survive and develop resistance to additional drugs.

“The spread of a highly transmissible strain of drug-resistant tuberculosis has been facilitated by applying standard treatment regimens for susceptible and multi-drug resistant tuberculosis in the absence of drug resistance surveillance,” said one of the authors, A. Willem Sturm, MD, of the University of KwaZulu-Natal's Nelson R. Mandela School of Medicine in South Africa. “Public health programs for the treatment and control of infectious diseases need to be supported by drug resistance surveillance programs.”

Like all bacteria, M. tuberculosis can evolve and develop resistance to the drugs that have historically killed them. The strategy that has been used to limit the development of drug-resistant TB is to treat the patient with multiple drugs so that if one drug is ineffective, then the others will ensure the elimination of the bacteria.

Drug-resistant M. tuberculosis develops when tuberculosis patients cannot or do not comply with the medication regimen. A second line of drugs has been used to treat those infected with drug-resistant TB. This second-line medication regimen was adopted in South Africa in 2001 to treat drug-resistant TB.

Unfortunately, at least one strain of M. tuberculosis in South Africa had already developed resistance to one or more of these second-line drugs by the time they were introduced. Drug susceptibility tests would have warned doctors that the standard second-line regimen was unlikely to help the patient but was likely to lead to additional drug-resistance, but these tests were not performed or were not available. Indeed, the reduced efficacy of the regimen allowed the strain to survive and, over time, develop resistances to other drugs.

The authors recorded the development of resistance to seven drugs in just over a decade in one strain of M. tuberculosis. There are very few treatment options for patients infected with XDR TB. For the most part, patients are given drugs that had been used to treat tuberculosis but which were abandoned when today's first-line drugs became available. The older drugs were abandoned because they were less effective or more toxic.

The authors call for an increased use of drug resistance surveillance programs to help forestall the development of drug-resistance in M. tuberculosis.