Transmission of Extensively Drug-Resistant Tuberculosis in South Africa
- 19 January 2017
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 376 (3), 243-253
- https://doi.org/10.1056/nejmoa1604544
Abstract
Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants’ history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment–length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission. (Funded by the National Institute of Allergy and Infectious Diseases and others.)Keywords
This publication has 39 references indexed in Scilit:
- Inferring patient to patient transmission of Mycobacterium tuberculosisfrom whole genome sequencing dataBMC Infectious Diseases, 2013
- Nosocomial Transmission of Extensively Drug-Resistant Tuberculosis in a Rural Hospital in South AfricaThe Journal of Infectious Diseases, 2012
- Molecular Characterization and Second-Line Antituberculosis Drug Resistance Patterns of Multidrug-Resistant Mycobacterium tuberculosis Isolates from the Northern Region of South AfricaJournal of Clinical Microbiology, 2012
- National Survey of Drug-Resistant Tuberculosis in ChinaThe New England Journal of Medicine, 2012
- Characteristics and Treatment Outcomes of Patients with MDR and XDR Tuberculosis in a TB Referral Hospital in Beijing: A 13-Year ExperiencePLOS ONE, 2011
- Clusters of Multidrug-ResistantMycobacterium tuberculosisCases, EuropeEmerging Infectious Diseases, 2009
- Extensively Drug-Resistant Tuberculosis in the United States, 1993-2007JAMA, 2008
- Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistanceBulletin of the World Health Organization, 2007
- Worldwide Emergence of Extensively Drug-resistant TuberculosisEmerging Infectious Diseases, 2007
- Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South AfricaThe Lancet, 2006