Use of multiple markers in population-based molecular epidemiologic studies of tuberculosis

Int J Tuberc Lung Dis. 2000 Dec;4(12):1111-9.


Setting: 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.

Design: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bacterial Typing Techniques / methods*
  • DNA Fingerprinting / methods*
  • Genetic Markers*
  • Humans
  • Logistic Models
  • Middle Aged
  • Multivariate Analysis
  • Mycobacterium tuberculosis / classification*
  • Odds Ratio
  • Repetitive Sequences, Nucleic Acid
  • Risk Factors
  • San Francisco / epidemiology
  • Tuberculosis / epidemiology
  • Tuberculosis / microbiology
  • Tuberculosis / transmission*


  • Genetic Markers