How Close Is Close Enough? Exploring Matching Criteria in the Estimation of Recent Transmission of Tuberculosis

摘要

If Mycobacterium tuberculosis isolates from 2 people have the same genotype, transmission may have occurrednbetween them. Genotyping based on the insertion sequence IS6110 uses identical restriction fragment lengthnpolymorphisms (‘‘fingerprints’’) to infer transmission. However, once transmission has occurred, the genotypesnmay mutate, resulting in divergent fingerprints. Estimation of the proportion of tuberculosis (TB) cases due to recentntransmission includes 3 approaches to determine if genotypes match: exact matching (assumes no fingerprintnchange); band-addition, band-loss, band-shift matching (ad hoc attempt to account for fingerprint changes); andngenetic distance (directly accounts for fingerprint changes). Via simulation study, the authors varied the fingerprintnchange rate, level of recent transmission, and background genetic heterogeneity and estimated sensitivity, spec-nificity, and bias of the recent transmission index by matching method. For exact matching, specificity was alwaysnhigh, but sensitivity decreased as the change rate increased. For band-addition, band-loss, band-shift matching,nspecificity decreased as genetic diversity decreased, and sensitivity remained high as the change rate increased.nGenetic distance offered a compromise between the 2. Results from this study suggest that interpretation of thenrecent transmission index and the resulting necessary public health interventions will vary according to hownresearchers account for spontaneous mutation when estimating transmission from genotyping data.