Data from: Transmission of multidrug-resistant and drug-susceptible tuberculosis within households: a prospective cohort study

Background: The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients. Methods and Findings: This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases. A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting. Conclusions: The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult.背景：传染性病原体的适应性（fitness）被定义为该病原体存活、繁殖、传播以及引发疾病的能力。耐多药结核病（multidrug-resistant tuberculosis, MDRTB）相对于药物敏感结核病的适应性，被认为是影响耐多药结核病传播规模与流行程度的最重要决定因素之一。为估算耐药结核病病例的相对适应性，本研究对比了耐多药结核病索引病例的家庭接触者与药物敏感结核病索引病例的家庭接触者的结核病发病情况。 方法与结果：本研究于秘鲁利马南部与卡亚俄开展，为一项为期3年（2010—2013年）的前瞻性队列家庭追踪研究，共纳入213例耐多药结核病索引病例的1055名家庭接触者，以及487例药物敏感结核病索引病例的2362名家庭接触者，对两组人群的结核病发病率进行了测定。结果显示，213例耐多药结核病索引病例的家庭接触者中，共有35/1055（3.3%）发生结核病；而487例药物敏感结核病索引病例的家庭接触者中，共有114/2362（4.8%）发生结核病。药物敏感结核病接触组的总随访时长为2620人年，耐多药结核病接触组的总随访时长为1425人年。通过多因素Cox回归校正接触者HIV感染状态、年龄、社会经济地位以及索引病例痰涂片分级等混杂变量后发现，耐多药结核病家庭接触者的结核病发病风险比为药物敏感接触组的一半（风险比0.56，95%置信区间0.34—0.90，P=0.017）。本研究的传播推断受到局限，原因在于缺乏家庭接触者的基因分型数据。此外，仅对家庭接触者的发病情况进行随访，也限制了本研究结果向社区场景的外推。 结论：本研究估算得到的耐多药结核病较低相对适应性，提升了耐药结核病的防控可行性。然而，随着时间推移出现的适应性更强的耐多药菌株，可能会使防控工作愈发困难。