title: Tuberculosis burden in households of patients with multidrug-resistant and extensively drug-resistant tuberculosis: a retrospective cohort study.
abstract: BACKGROUND
  Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have emerged as major global health threats. WHO recommends contact investigation in close contacts of patients with MDR and XDR tuberculosis. We aimed to assess the burden of tuberculosis disease in household contacts of such patients.
  
  
  METHODS
  We undertook a retrospective cohort study of household contacts of patients treated for MDR or XDR tuberculosis in Lima, Peru, in 1996-2003. The primary outcome was active tuberculosis in household contacts at the time the index patient began MDR tuberculosis treatment and during the 4-year follow-up. We examined whether the occurrence of active tuberculosis in the household contacts differed by resistance pattern of the index patient: either MDR or XDR tuberculosis.
  
  
  RESULTS
  693 households of index patients with MDR tuberculosis were enrolled in the study. In 48 households, the Mycobacterium tuberculosis isolate from the index patient was XDR. Of the 4503 household contacts, 117 (2·60%) had active tuberculosis at the time the index patient began MDR tuberculosis treatment-there was no difference in prevalence between XDR and MDR tuberculosis households. During the 4-year follow-up, 242 contacts developed active tuberculosis-the frequency of active tuberculosis was nearly two times higher in contacts of patients with XDR tuberculosis than it was in contacts of patients with MDR tuberculosis (hazard ratio 1·88, 95% CI 1·10-3·21). In the 359 contacts with active tuberculosis, 142 (40%) had had isolates tested for resistance against first-line drugs, of whom 129 (90·9%, 95% CI 85·0-94·6) had MDR tuberculosis.
  
  
  CONCLUSIONS
  In view of the high risk of disease recorded in household contacts of patients with MDR or XDR tuberculosis, tuberculosis programmes should implement systematic household contact investigations for all patients identified as having MDR or XDR tuberculosis. If shown to have active tuberculosis, these household contacts should be suspected as having MDR tuberculosis until proven otherwise.
  
  
  BACKGROUND
  The Charles H Hood Foundation, the David Rockefeller Center for Latin American Studies at Harvard University, and the Bill & Melinda Gates Foundation.
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA 02115, USA. mbecerra@post.harvard.edu
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.forename: Sasha C
authors.initials: SC
authors.lastname: Appleton
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.forename: Katiuska
authors.initials: K
authors.lastname: Chalco
authors.forename: Fernando
authors.initials: F
authors.lastname: Arteaga
authors.forename: Jaime
authors.initials: J
authors.lastname: Bayona
authors.forename: Megan
authors.initials: M
authors.lastname: Murray
authors.forename: Sidney S
authors.initials: SS
authors.lastname: Atwood
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D016358:Contact Tracing; D017281:Cost of Illness; D054908:Extensively Drug-Resistant Tuberculosis / Q000453:epidemiology; D005191:Family Characteristics; D005260:Female; D006801:Humans; D017053:Infection Control / Q000379:methods; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D010568:Peru / Q000453:epidemiology; D011159:Population Surveillance / Q000379:methods; D015995:Prevalence; D012189:Retrospective Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology*; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents