title: Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households: A Prospective Cohort Study.
abstract: BACKGROUND
  The "fitness" of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients.
  
  
  RESULTS
  This 3-y (2010-2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases. A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34-0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting.
  
  
  CONCLUSIONS
  The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.
authors.affiliation: Wellcome Centre for Clinical Tropical Medicine, Imperial College London, London, United Kingdom; Universidad Peruana Cayetano Heredia, Lima, Peru; TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Louis
authors.initials: L
authors.lastname: Grandjean
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru; Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Laura
authors.initials: L
authors.lastname: Martin
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Esther
authors.initials: E
authors.lastname: Soto
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castro
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lopez
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.affiliation: Laboratorio de Mycobacteriologia, Dirección Regional de Salud-Región Callao, Lima, Peru.
authors.forename: Edith
authors.initials: E
authors.lastname: Castillo
authors.affiliation: Unidad Técnica de TB-MDR, Ministerio de Salud, Lima, Peru.
authors.forename: Valentina
authors.initials: V
authors.lastname: Alarcon
authors.affiliation: Estrategia Sanitaria Nacional de Prevención y Control de la Tuberculosis and Laboratorio de Mycobacteriologia, Dirección de Salud II-Lima Sur, Lima, Peru.
authors.forename: Virginia
authors.initials: V
authors.lastname: Lopez
authors.affiliation: Estrategia Sanitaria Nacional de Prevención y Control de la Tuberculosis and Laboratorio de Mycobacteriologia, Dirección de Salud II-Lima Sur, Lima, Peru.
authors.forename: Angela
authors.initials: A
authors.lastname: San Miguel
authors.affiliation: Instituto Nacional de Salud, Lima, Peru.
authors.forename: Neyda
authors.initials: N
authors.lastname: Quispe
authors.affiliation: Instituto Nacional de Salud, Lima, Peru.
authors.forename: Luis
authors.initials: L
authors.lastname: Asencios
authors.affiliation: Office for HIV/AIDS, Malaria, Tuberculosis and Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dye
authors.affiliation: Universidad Peruana Cayetano Heredia, Lima, Peru; TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D005191:Family Characteristics; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D010568:Peru / Q000453:epidemiology; D011446:Prospective Studies; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission*
chemical_list: D000995:Antitubercular Agents