title: The incubation period distribution of tuberculosis estimated with a molecular epidemiological approach.
abstract: BACKGROUND
  There is limited information on the distribution of incubation periods of tuberculosis (TB).
  
  
  METHODS
  In The Netherlands, patients whose Mycobacterium tuberculosis isolates have identical DNA fingerprints in the period 1993-2007 were interviewed to identify epidemiological links between cases. We determined the incubation period distribution in secondary cases. Survival analysis techniques were used to include secondary cases not yet symptomatic at diagnosis with weighting to adjust for lower capture probabilities of couples with longer time intervals between their diagnoses. In order to deal with missing data, we used multiple imputations.
  
  
  RESULTS
  We identified 1095 epidemiologically linked secondary cases, attributed to 688 source cases with pulmonary TB. Of those developing disease within 15 years, the Kaplan-Meier probability to fall ill within 1 year was 45%, within 2 years 62% and within 5 years 83%. The incubation time was shorter in secondary cases who were men, young, those with extra-pulmonary TB and those not reporting previous TB or previous preventive therapy.
  
  
  CONCLUSIONS
  Molecular epidemiological analysis has allowed a more precise description of the incubation period of TB than was possible in previous studies, including the identification of risk factors for shorter incubation periods.
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. mborgdorff@ggd.amsterdam.nl
authors: Martien W
authors: MW
authors: Borgdorff
authors: Maruschka
authors: M
authors: Sebek
authors: Ronald B
authors: RB
authors: Geskus
authors: Kristin
authors: K
authors: Kremer
authors: Nico
authors: N
authors: Kalisvaart
authors: Dick
authors: D
authors: van Soolingen
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D005260:Female; D006801:Humans; D055256:Infectious Disease Incubation Period; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D012042:Registries; D012307:Risk Factors; D016019:Survival Analysis; D014376:Tuberculosis / Q000453:epidemiology*; D055815:Young Adult