Use of multiple markers in population-based molecular epidemiologic studies of tuberculosis
Abstract: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.
Document Type: Regular Paper
Affiliations: 1: Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, USA 2: Department of Biological Sciences, Stanford University, Stanford, California, USA 3: Division of Infectious Diseases and Microbiology, Montreal General Hospital, Montreal, Canada 4: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA 5: Department of Public Health, Division of Tuberculosis Control, City and County of San Francisco, San Francisco, California, USA; and Francis J. Curry National Tuberculosis Center, San Francisco, California, USA
Publication date: December 1, 2000
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