title: Identifying Hotspots of Multidrug-Resistant Tuberculosis Transmission Using Spatial and Molecular Genetic Data.
abstract: BACKGROUND
  We aimed to identify and determine the etiology of "hotspots" of concentrated multidrug-resistant tuberculosis (MDR-tuberculosis) risk in Lima, Peru.
  
  
  METHODS
  From 2009 to 2012, we conducted a prospective cohort study among households of tuberculosis cases from 106 health center (HC) areas in Lima, Peru. All notified tuberculosis cases and their household contacts were followed for 1 year. Symptomatic individuals were screened by microscopy and culture; positive cultures were tested for drug susceptibility (DST) and genotyped by 24-loci mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR).
  
  
  RESULTS
  3286 individuals with culture-confirmed disease, DST, and 24-loci MIRU-VNTR were included in our analysis. Our analysis reveals: (1) heterogeneity in annual per-capita incidence of tuberculosis and MDR-tuberculosis by HC, with a rate of MDR-tuberculosis 89 times greater (95% confidence interval [CI], 54,185) in the most-affected versus the least-affected HC; (2) high risk for MDR-tuberculosis in a region spanning several HCs (odds ratio = 3.19, 95% CI, 2.33, 4.36); and (3) spatial aggregation of MDR-tuberculosis genotypes, suggesting localized transmission.
  
  
  CONCLUSIONS
  These findings reveal that localized transmission is an important driver of the epidemic of MDR-tuberculosis in Lima. Efforts to interrupt transmission may be most effective if targeted to this area of the city.
authors.affiliation: Robert Wood Johnson Foundation Health and Society Scholars Program, Interdisciplinary Center for Innovative Theory and Empirics (INCITE) & Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Zelner
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Department of Epidemiology, Harvard School of Public Health.
authors.forename: Megan B
authors.initials: MB
authors.lastname: Murray
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.affiliation: Socios En Salud, Lima, Peru.
authors.forename: Jerome
authors.initials: J
authors.lastname: Galea
authors.affiliation: Socios En Salud, Lima, Peru.
authors.forename: Leonid
authors.initials: L
authors.lastname: Lecca
authors.affiliation: Socios En Salud, Lima, Peru.
authors.forename: Roger
authors.initials: R
authors.lastname: Calderon
authors.affiliation: Socios En Salud, Lima, Peru.
authors.forename: Rosa
authors.initials: R
authors.lastname: Yataco
authors.affiliation: Socios En Salud, Lima, Peru.
authors.forename: Carmen
authors.initials: C
authors.lastname: Contreras
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital.
authors.forename: Zibiao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Health Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts.
authors.forename: Justin
authors.initials: J
authors.lastname: Manjourides
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, New Jersey Fogarty International Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Grenfell
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D015994:Incidence; D017720:Molecular Epidemiology / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D010568:Peru / Q000453:epidemiology; D011446:Prospective Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000635:transmission*
chemical_list: D000995:Antitubercular Agents
keywords: MDR-tuberculosis; drug resistance; spatial analysis; tuberculosis