Public Release: 

XDR TB in South Africa traced to lack of drug susceptibility testing

Infectious Diseases Society of America

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.

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It has come to the attention of IDSA and CID that some media coverage of the above article has suggested that the World Health Organization's TB control program is responsible for the development of extensively drug-resistant tuberculosis (XDR TB) in South Africa. The article in question traces the development of XDR TB during the implementation of a tuberculosis control program. In their conclusion, the authors state, "It is postulated that the introduction of these programs in the absence of susceptibility testing or drug resistance surveillance has been instrumental in the development of XDR in this highly transmissible...strain."

Founded in 1979, Clinical Infectious Diseases publishes clinical articles twice monthly in a variety of areas of infectious disease, and is one of the most highly regarded journals in this specialty. It is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Arlington, Virginia, IDSA is a professional society representing more than 8,300 physicians and scientists who specialize in infectious diseases. Nested within the IDSA, the HIV Medicine Association (HIVMA) is the professional home for more than 3,500 physicians, scientists and other health care professionals dedicated to the field of HIV/AIDS. HIVMA promotes quality in HIV care and advocates policies that ensure a comprehensive and humane response to the AIDS pandemic informed by science and social justice. For more information, visit www.idsociety.org and www.hivma.org.

This article is part of the contribution by Clinical Infectious Diseases to the Global Theme Issue on Poverty and Human Development, as organized by the Council of Science Editors. Clinical Infectious Diseases is one of more than 230 journals throughout the world participating. On October 22, 2007, these journals, from developed and developing countries, will simultaneously publish papers on topics of worldwide interest to raise awareness, generate interest, and stimulate research into poverty and human development. For more information, visit http://www.councilscienceeditors.org/globalthemeissue.cfm.

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