High Mortality in a South African XDR TB Outbreak

Salim S. Abdool Karim, MD, PhD

AIDS Clinical Care 


Researchers found alarmingly high prevalences of both multidrug-resistant and extensively drug-resistant TB among HIV-coinfected people in rural South Africa.

This study was conducted in a rural subdistrict of KwaZulu-Natal,South Africa, where the local hospital has an established DOTS (Directly Observed Treatment, Short Course) program for TB treatment. In this hospital, 40% of inpatient beds are occupied by HIV-infected individuals.

From January 2005 through March 2006, sputum samples were collected for mycobacterial culture from 1539 patients. Cultures from 542 patients (35%) were positive for Mycobacterium tuberculosis. Multidrug-resistant (MDR) TB was identified in 221 of the culture-positive patients (41%), including 53 with extensively drug-resistant (XDR) TB (here defined as resistant to isoniazid, rifampin, ethambutol, streptomycin, aminoglycosides, and fluoroquinolones).

Genotyping studies, completed on isolates from 46 patients with XDR TB, revealed that 85% (95% confidence interval, 74%–95%) of patients with XDR TB were infected with a genetically similar strain, unique to KwaZulu-Natal. All 44 XDR TB patients with known HIV status were HIV-infected. Fifty-two of the 53 XDR TB patients died (median survival from the time of specimen collection, 16 days). Notably, 55% of the patients with XDR TB had never been treated for TB, and 30% had documented cure or completion of their previous TB treatment course.


To standardize the identification of XDR TB, CDC and WHO have jointly released a revised definition of XDR TB (MMWR 2006; 55:1176). The new definition stipulates resistance to isoniazid and rifampicin, as well as to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

In the current study, which was presented at the 2006 XVI International AIDS Conference (see ACC Sep 18 2006), prevalences of MDR TB and XDR TB were substantially higher than those previously reported. (Only 347 cases of XDR TB were identified worldwide from 2000 though 2004.) Furthermore, XDR TB was rapidly — and almost uniformly — fatal. The convergence of the HIV and TB epidemics is placing great strain on healthcare services in resource-poor settings and threatens to overturn the survival gains achieved by DOTS for TB and by antiretroviral therapy for HIV infection. These findings highlight the importance of active surveillance for MDR and XDR TB, as well as the need for improved TB-treatment adherence, better diagnostic tools, and new therapeutic drugs.

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