Nosocomial Transmission of Extensively Drug-Resistant Tuberculosis in a Rural Hospital in South Africa

• Published in: The Journal of infectious diseases 2013-01, Vol.207 (1), p.9-17
• Main Authors: Gandhi, Neel R., Weissman, Darren, Moodley, Prashini, Ramathal, Melissa, Elson, Inga, Kreiswirth, Barry N., Mathema, Barun, Shashkina, Elena, Rothenberg, Richard, Moll, Anthony P., Friedland, Gerald, Sturm, A. Willem, Shah, N. Sarita
• Format: Article
• Language: English
• Subjects: Adult; Antitubercular Agents - therapeutic use; BACTERIA; Biological and medical sciences; Cluster Analysis; Cross Infection - complications; Cross Infection - epidemiology; Cross Infection - microbiology; Cross Infection - transmission; Data transmission; Disease transmission; Drug Therapy, Combination; Epidemics; Ethambutol - therapeutic use; Extensively Drug-Resistant Tuberculosis - complications; Extensively Drug-Resistant Tuberculosis - epidemiology; Extensively Drug-Resistant Tuberculosis - microbiology; Extensively Drug-Resistant Tuberculosis - transmission; Female; Ferries; Fundamental and applied biological sciences. Psychology; Genotype; HIV; HIV Infections - complications; HIV Infections - virology; Hospital admissions; Hospitals, Rural; Humans; Infection control; Infectious diseases; Isoniazid - therapeutic use; Major and Brief Reports; Male; Medical sciences; Microbiology; Multidrug resistant tuberculosis; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Polymorphism, Restriction Fragment Length; Prevalence; Pyrazinamide - therapeutic use; Retrospective Studies; Rifampin - therapeutic use; Sequence Analysis, DNA; South Africa - epidemiology; Tuberculosis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis631

Background. Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a global public health threat, but few data exist elucidating factors driving this epidemic. The initial XDR-tuberculosis report from South Africa suggested transmission is an important factor, but detailed epidemiologic and molecular analyses were not available for further characterization. Methods. We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links. We used spoligotyping, IS6110-based restriction fragment-length polymorphism analysis, and sequencing of resistance-determining regions to identify clusters. Social network analysis was used to construct transmission networks among genotypically clustered patients. Results. Among 148 XDR-tuberculosis patients, 98% were infected with human immunodeficiency virus (HIV), and 59% had smear-positive tuberculosis. Nearly all (93%) were hospitalized while infectious with XDR-tuberculosis (median duration, 15 days; interquartile range: 10-25 days). Genotyping identified a predominant cluster comprising 96% of isolates. Epidemiologic links were identified for 82% of patients; social network analysis demonstrated multiple generations of transmission across a highly interconnected network. Conclusions. The XDR-tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal. However, the epidemic is not the result of a point-source outbreak; rather, a high degree of interconnectedness allowed multiple generations of nosocomial transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the 1990s, poor infection control, delayed diagnosis, and a high HIV prevalence facilitated transmission. Important lessons from those outbreaks must be applied to stem further expansion of this epidemic.