Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
Am J Epidemiol. 2010 Aug 1;172(3):318-26. doi: 10.1093/aje/kwq124. Epub 2010 Jun 24.
If Mycobacterium tuberculosis isolates from 2 people have the same genotype, transmission may have occurred between them. Genotyping based on the insertion sequence IS6110 uses identical restriction fragment length polymorphisms ("fingerprints") to infer transmission. However, once transmission has occurred, the genotypes may mutate, resulting in divergent fingerprints. Estimation of the proportion of tuberculosis (TB) cases due to recent transmission includes 3 approaches to determine if genotypes match: exact matching (assumes no fingerprint change); band-addition, band-loss, band-shift matching (ad hoc attempt to account for fingerprint changes); and genetic distance (directly accounts for fingerprint changes). Via simulation study, the authors varied the fingerprint change rate, level of recent transmission, and background genetic heterogeneity and estimated sensitivity, specificity, and bias of the recent transmission index by matching method. For exact matching, specificity was always high, but sensitivity decreased as the change rate increased. For band-addition, band-loss, band-shift matching, specificity decreased as genetic diversity decreased, and sensitivity remained high as the change rate increased. Genetic distance offered a compromise between the 2. Results from this study suggest that interpretation of the recent transmission index and the resulting necessary public health interventions will vary according to how researchers account for spontaneous mutation when estimating transmission from genotyping data.
如果来自两个人的结核分枝杆菌分离株具有相同的基因型，则可能在他们之间发生了传播。基于插入序列 IS6110 的基因分型使用相同的限制性片段长度多态性（“指纹”）来推断传播。然而，一旦发生传播，基因型可能会发生突变，导致指纹出现分歧。估计由于近期传播导致的结核病（TB）病例比例包括确定基因型是否匹配的 3 种方法：完全匹配（假设指纹没有变化）；带添加、带丢失、带移位匹配（专门尝试解释指纹变化）；和遗传距离（直接解释指纹变化）。通过模拟研究，作者改变了指纹变化率、近期传播水平和背景遗传异质性，并按匹配方法估计了近期传播指数的敏感性、特异性和偏差。对于完全匹配，特异性始终很高，但随着变化率的增加，敏感性降低。对于带添加、带丢失、带移位匹配，特异性随着遗传多样性的降低而降低，而敏感性随着变化率的增加而保持较高水平。遗传距离在两者之间提供了一个折衷方案。这项研究的结果表明，解释近期传播指数以及由此产生的必要公共卫生干预措施将根据研究人员在从基因分型数据估计传播时如何解释自发突变而有所不同。
