title: Nosocomial transmission of extensively drug-resistant tuberculosis in a rural hospital in South Africa.
abstract: 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.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA. neelgandhi@alumni.williams.edu
authors.forename: Neel R
authors.initials: NR
authors.lastname: Gandhi
authors.forename: Darren
authors.initials: D
authors.lastname: Weissman
authors.forename: Prashini
authors.initials: P
authors.lastname: Moodley
authors.forename: Melissa
authors.initials: M
authors.lastname: Ramathal
authors.forename: Inga
authors.initials: I
authors.lastname: Elson
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.forename: Elena
authors.initials: E
authors.lastname: Shashkina
authors.forename: Richard
authors.initials: R
authors.lastname: Rothenberg
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Moll
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedland
authors.forename: A Willem
authors.initials: AW
authors.lastname: Sturm
authors.forename: N Sarita
authors.initials: NS
authors.lastname: Shah
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D016000:Cluster Analysis; D003428:Cross Infection / Q000150:complications / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D054908:Extensively Drug-Resistant Tuberculosis / Q000150:complications / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006780:Hospitals, Rural; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D011718:Pyrazinamide / Q000627:therapeutic use; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D013019:South Africa / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin