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Outbreak of Highly Lethal, Extensive Drug Resistant Tuberculosis in South Africa

By Eric Toner, M.D., September 6, 2006

On September 5, 2006, the World Health Organization (WHO) posted information on an outbreak of highly lethal “Extensive (or Extreme) Drug Resistant TB (XDR-TB)” in South Africa [1]. “XDR-TB” refers to strains of Mycobacterium tuberculosis that are resistant to the two first line antimicrobials, isoniazid and rifampin, and are also resistant to at least 3 of 6 of the second line drugs (i.e. amikacin or kanamycin [aminoglycosides], capreomycin, ciprofloxacin or ofloxacin [quinolones], ethionamide, cycloserine, and para-aminosalicylic acid). In contrast, multi-drug resistant TB, or MDR-TB, is characterized by resistance to isoniazid and rifampin, but not by resistance to the second line drugs as well. This new descriptor was coined earlier this year by WHO and CDC following a global survey of TB resistance, which was conducted from 2000 to 2004. According to that WHO survey, XRD-TB was found in small numbers throughout the world (347 of 17,690 isolates) and accounted for 10% of MDR isolates. It was most common in South Korea (200 cases) and the former Soviet Union (55 cases) [2].

The outbreak in South Africa came to light as a result of a survey of MDR-TB prevalence among patients suspected to have TB who were hospitalized in rural areas of the KwaZulu-Natal region. The survey was conducted during the 14 month period between January 2005 and March 2006. Results were reported by N.R. Gandi, who delivered an abstract at the XVI International AIDS Conference in Toronto in mid-August [3].

Gandi and colleagues collected sputum from 1540 patients. Analysis indicated that: 

  • 536 (35%) patients had sputum specimens that resulted in a positive culture for M. tuberculosis

  • 221 (41% of the specimens) had MDR-TB

  • 53 (24% of MDR isolates, 10% of all positive cultures) had XDR-TB*

  • 52 of those patients have died (median survival after sputum collection was 25 days; range: 11–136 days.)

  • All 47 of the XDR-TB patients whose HIV status was known were HIV infected.

*The drugs tested were isoniazid, rifampin, ethambutol, streptomycin, ciprofloxacin and kanamycin

Spoligotyping, which is a polymerase chain reaction–based method used for the simultaneous detection and typing of M. tuberculosis strains, revealed that 90% of XDR-TB patients were infected with a genetically similar strain. Since the majority of these patients were not receiving treatment, and 34% had never been treated, the authors concluded that these cases represent transmission of XDR-TB rather than development during therapy, which may occur in patients who are receiving suboptimal drug regimens or who fail to complete chemotherapy with the appropriate combination of drugs. The authors also concluded that nosocomial transmission was likely in the 64% of the patients who had previously been hospitalized and in 6 healthcare workers who died of proven or suspected XDR-TB. In the 36% of patients who had not been previously hospitalized, community transmission was presumed.

This outbreak of XRD-TB is of concern because it accounts for 13% of all known cases of XDR-TB (53/400), and it appears to be both highly and rapidly lethal: 52 of the 53 patients (98%) are known to have died, most within just a few weeks, compared with the 3% mortality rate uncovered by the WHO’s global survey. According to Paul Nunn, coordinator of the WHO's drug-resistance unit, “This new strain leaves us facing a nightmare. It is resistant to nearly every drug in our arsenal. We are now on the threshold of the appearance of a strain of TB that is resistant to every medicine known to science.”[4]

The World Health Organization (WHO), the Centers for Disease Control (CDC), and the South African Research Council will convene an Expert Consultation meeting in Johannesburg on September 7 and 8 to address the situation and will hold a press conference on September 7.

Community and nosocomial transmission of this highly lethal strain of XDR-TB appears to present a serious threat to the large number of poor and HIV-infected people in this rural area. Vigorous intervention is needed. This means effective contact tracing, isolation of suspected cases with active infection, prompt diagnosis and treatment. It is essential to perform drug-susceptibility testing and to optimize treatment of drug-resistant disease. On a policy level, this means more resources for global TB and HIV control. 

References

  1. Emergence of XDR-TB World Health Organization. Available at: http://www.who.int/mediacentre/news/notes/2006/np23/en/index.html. Accessed September 5, 2006.

  2. Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs --- Worldwide, 2000—2004. MMWR. March 24, 2006 / 55(11);301-305. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5511a2.htm. Accessed September 5, 2006.

  3. Gandi N R et al. High prevalence and mortality from extensively-drug resistant (XDR) TB in TB/HIV coinfected patients in rural South Africa. Abstact presented at XVI International AIDS Conference. August, 2006. Available at: http://www.aids2006.org/PAG/Abstracts.aspx?AID=51350. Accessed September 5, 2006.

  4. McKie R. Fears of 'extreme' TB strain, The Observer, Guardian Unlimited. Available at http://observer.guardian.co.uk/world/story/0,,1863850,00.html. Accessed September 5, 2006.