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@NEJM Ask the Authors & Experts: Transmission of Extensively Drug-resistant Tuberculosis in South Africa

Drug-resistant tuberculosis (TB) threatens gains in TB and HIV treatment worldwide. South Africa is experiencing a widespread epidemic of extensively drug-resistant (XDR) TB, including a ten-fold increase in cases since 2002. Factors driving this rapid rise have not been fully elucidated, but are needed to guide public health interventions. 

We conducted a prospective study of XDR-TB patients from KwaZulu-Natal, South Africa, from 2011–2014. Interviews and medical record reviews elicited previous TB and HIV history, hospitalizations and social networks. M. tuberculosis isolates underwent IS6110 RFLP, targeted gene sequencing and whole genome sequencing. We calculated the proportion of XDR-TB cases from inadequate treatment of multidrug-resistant (MDR) TB (i.e., acquired resistance) versus transmission, using clinical and genotypic case definitions. We used social network analysis to identify community and hospital locations of transmission.

We enrolled 404 XDR-TB patients from throughout KwaZulu-Natal province, of whom 311 (77%) were HIV-infected; median CD4 count was 340 cells/mm3 (IQR 117–431). Two hundred eighty (69%) had never been treated for MDR-TB. Genotypic analysis revealed that 84% (323 of 386) belonged to one of 31 clusters. Clusters ranged from 2–14 participants, except one large cluster (LAM4/KZN strain) with 212 (55%) participants. Person-to-person or hospital-based epidemiologic links were found for 123 (30%) participants.

The majority of XDR-TB cases in this high-TB burden setting in KwaZulu-Natal, South Africa likely occurred due to transmission, rather than inadequate treatment of MDR-TB. These data suggest that control of the drug-resistant TB epidemic requires greater focus on interrupting transmission.

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