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Use of multiple markers in population-based molecular epidemiologic studies of tuberculosis
J T Rhee1, M M Tanaka, M A Behr
1Department of Health Research and Policy, Stanford University School of Medicine, California, USA. jeanne@molepi.stanford.edu
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.