title: Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa.
abstract: BACKGROUND
  The epidemics of HIV-1 and tuberculosis in South Africa are closely related. High mortality rates in co-infected patients have improved with antiretroviral therapy, but drug-resistant tuberculosis has emerged as a major cause of death. We assessed the prevalence and consequences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in a rural area in KwaZulu Natal, South Africa.
  
  
  METHODS
  We undertook enhanced surveillance for drug-resistant tuberculosis with sputum culture and drug susceptibility testing in patients with known or suspected tuberculosis. Genotyping was done for isolates resistant to first-line and second-line drugs.
  
  
  RESULTS
  From January, 2005, to March, 2006, sputum was obtained from 1539 patients. We detected MDR tuberculosis in 221 patients, of whom 53 had XDR tuberculosis. Prevalence among 475 patients with culture-confirmed tuberculosis was 39% (185 patients) for MDR and 6% (30) for XDR tuberculosis. Only 55% (26 of 47) of patients with XDR tuberculosis had never been previously treated for tuberculosis; 67% (28 of 42) had a recent hospital admission. All 44 patients with XDR tuberculosis who were tested for HIV were co-infected. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis (IQR 6-37) among the 42 patients with confirmed dates of death. Genotyping of isolates showed that 39 of 46 (85%, 95% CI 74-95) patients with XDR tuberculosis had similar strains.
  
  
  CONCLUSIONS
  MDR tuberculosis is more prevalent than previously realised in this setting. XDR tuberculosis has been transmitted to HIV co-infected patients and is associated with high mortality. These observations warrant urgent intervention and threaten the success of treatment programmes for tuberculosis and HIV.
authors.affiliation: AIDS Program, Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. negandhi@montefiore.org
authors.forename: Neel R
authors.initials: NR
authors.lastname: Gandhi
authors.forename: Anthony
authors.initials: A
authors.lastname: Moll
authors.forename: A Willem
authors.initials: AW
authors.lastname: Sturm
authors.forename: Robert
authors.initials: R
authors.lastname: Pawinski
authors.forename: Thiloshini
authors.initials: T
authors.lastname: Govender
authors.forename: Umesh
authors.initials: U
authors.lastname: Lalloo
authors.forename: Kimberly
authors.initials: K
authors.lastname: Zeller
authors.forename: Jason
authors.initials: J
authors.lastname: Andrews
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedland
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D011159:Population Surveillance / Q000379:methods*; D015995:Prevalence; D012423:Rural Health; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents