title: Use of multiple markers in population-based molecular epidemiologic studies of tuberculosis.
abstract: METHODS
  Many epidemiologic studies of tuberculosis are being conducted worldwide. Fingerprinting with a secondary marker in strains with fewer than six IS6110-hybridizing bands enhances the tracking of strains, but its impact on population-level inferences has not been well studied.
  
  
  OBJECTIVE
  To investigate the effects of secondary genotyping for low-copy Mycobacterium tuberculosis isolates with polymorphic guanine-cytosine-rich repetitive sequence (PGRS) on epidemiologic inferences in population-based research settings.
  
  
  METHODS
  For San Francisco tuberculosis cases (1991-1996), clusters were defined by IS6110 alone and by PGRS/IS6110 to 1) estimate recent transmission, 2) evaluate the theoretical influence of bacterial population parameters on these estimates, and 3) assess risk factors for recent transmission.
  
  
  RESULTS
  Secondary typing on low-copy strains (20.3% of all isolates) decreased the estimate of recent transmission from 29.1% to 25.3% (P = 0.03). The most influential parameters in determining whether supplemental genotyping results in different estimates were the proportion of low-copy strains and the amount of clustering. Risk factors for recent transmission were identical for both definitions of clustering.
  
  
  CONCLUSIONS
  The statistical and inferred effects of secondary genotyping of M. tuberculosis seem to depend on the proportion of low-copy strains in the population. When this proportion is low or when few secondary patterns match, supplemental genotyping may yield minimal insight into population-level investigations.
authors.affiliation: Department of Health Research and Policy, Stanford University School of Medicine, California, USA. jeanne@molepi.stanford.edu
authors.forename: J T
authors.initials: JT
authors.lastname: Rhee
authors.forename: M M
authors.initials: MM
authors.lastname: Tanaka
authors.forename: M A
authors.initials: MA
authors.lastname: Behr
authors.forename: C B
authors.initials: CB
authors.lastname: Agasino
authors.forename: E A
authors.initials: EA
authors.lastname: Paz
authors.forename: P C
authors.initials: PC
authors.lastname: Hopewell
authors.forename: P M
authors.initials: PM
authors.lastname: Small
mesh_terms: D000328:Adult; D015373:Bacterial Typing Techniques / Q000379:methods*; D016172:DNA Fingerprinting / Q000379:methods*; D005819:Genetic Markers; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000145:classification*; D016017:Odds Ratio; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D012495:San Francisco / Q000453:epidemiology; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*
chemical_list: D005819:Genetic Markers