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

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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.
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Keywords: IS6110; PGRS; molecular epidemiology; tuberculosis

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: 2000-12-01

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

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