Fennelly Kevin P
Pulmonary Clinical Medicine Section, Cardiovascular Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA.
Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S51. doi: 10.1016/j.ijmyco.2016.10.037. Epub 2016 Nov 25.
OBJECTIVE/BACKGROUND: The aims of this talk are to: (a) provide an overview of our method of collecting, quantifying, and sizing infectious aerosols of Mycobacterium tuberculosis; and (b) to review data indicating that cough aerosol cultures of M. tuberculosis are the best predictors of infection and incident disease among household contacts of persons with active tuberculosis (TB). New infection was defined as tuberculin skin test conversion.
We developed a cough aerosol sampling system by placing two Andersen cascade impactor viability samplers inside a cylinder into which patients cough via connector tubing. We recruited sputum acid fast bacilli (AFB) smear-positive patients from the tuberculosis clinic and wards at Mulago Hospital in Kampala, Uganda. Patients were asked to cough as strongly and frequently as they comfortably could for two 5-min sessions of coughing.
In a cohort of 96 sputum culture positive index TB cases, 43 (45%) produced culture-positive cough aerosols. Household contacts of TB patients who produced high aerosols (⩾10colony forming units (CFU)) were more likely to have a new infection compared with contacts with low aerosol CFU (1-9CFU) and aerosol-negative cases (69%, 25%, and 30%, respectively, p=0.009). In adjusted multivariate analyses, high cough aerosols were the only predictor of new TB infection (odds ratio [OR] 4.81; 1.20-19.23). In a follow-up (median 3.9years) of this cohort, 369 (84%) of the contacts could be traced; eight (2%) had developed TB disease. Incident TB disease was associated with larger bacillary load in sputum measured by days to positive in liquid culture (OR 7.9; 0.7-70.5), exposure to a high-aerosol TB case patient (OR 6.0, 1.4-25.2) and marginally to HIV infection in the contact (OR 7.2; 0.7-70.5). Cough aerosol studies of TB patients in Brazil and South Africa are ongoing and appear to be finding similar proportions of cough aerosol cultures among TB patients (personal communication).
Cough aerosol cultures of M. tuberculosis are the best predictors of infectiousness and predict incident TB disease among sputum smear-positive patients in Uganda. We propose that cough aerosol cultures are a better surrogate of inhaled dose than sputum smear.
目的/背景：本次演讲的目的是：（a）概述我们收集、量化和测定结核分枝杆菌感染性气溶胶的方法；（b）回顾数据，表明结核分枝杆菌咳嗽气溶胶培养是活动性结核病（TB）患者家庭接触者中感染和发病的最佳预测指标。新感染定义为结核菌素皮肤试验阳转。
我们开发了一种咳嗽气溶胶采样系统，将两个安德森级联撞击式活菌采样器置于一个圆筒内，患者通过连接管向筒内咳嗽。我们从乌干达坎帕拉穆拉戈医院的结核病门诊和病房招募痰涂片抗酸杆菌（AFB）阳性患者。要求患者尽可能舒适地用力且频繁咳嗽，分两个5分钟时段进行咳嗽。
在96例痰培养阳性的结核病例队列中，43例（45%）产生了培养阳性的咳嗽气溶胶。与气溶胶CFU较低（1 - 9CFU）和无气溶胶的病例相比，产生高气溶胶（⩾10菌落形成单位（CFU））的结核病患者家庭接触者更易发生新感染（分别为69%、25%和30%，p = 0.009）。在多变量校正分析中，高咳嗽气溶胶是新结核感染的唯一预测指标（比值比[OR] 4.81；1.20 - 19.23）。对该队列进行随访（中位时间3.9年），369例（84%）接触者可被追踪；8例（2%）发生了结核病。结核病发病与液体培养阳性天数所测量的痰中杆菌载量较大有关（OR 7.9；0.7 - 70.5），与接触高气溶胶结核病例患者有关（OR 6.0，1.4 - 25.2），与接触者中的HIV感染有微弱关联（OR 7.2；0.7 - 70.5）。巴西和南非正在对结核病患者进行咳嗽气溶胶研究，似乎在结核病患者中发现了相似比例的咳嗽气溶胶培养阳性情况（个人交流）。
结核分枝杆菌咳嗽气溶胶培养是乌干达痰涂片阳性患者传染性的最佳预测指标，并可预测结核病发病。我们认为咳嗽气溶胶培养比痰涂片更能替代吸入剂量。
