Department of Clinical Research, National Institute for Research in Tuberculosis, Chennai, India.
Johns Hopkins University School of Medicine, Baltimore, United States of America.
PLoS One. 2018 Aug 1;13(8):e0199360. doi: 10.1371/journal.pone.0199360. eCollection 2018.
World Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.
A prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.
Of 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15-40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.
Prevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.
世界卫生组织（WHO）建议对高危人群（包括成人肺结核（TB）患者的家庭接触者（HHCs））进行系统筛查，作为消除结核病的关键策略。QuantiFERON-TB Gold In-Tube（QFT-GIT）检测和结核菌素皮肤试验（TST）是两种常用于检测潜伏性结核感染（LTBI）的常用工具，但可能会产生不同的结果，影响到结核病预防性治疗的资格。
在印度的浦那和钦奈两个城市，对成年肺结核患者及其 HHCs 进行了前瞻性队列研究。HHCs 接受了 QFT-GIT（QIAGEN）和 TST（PPD SPAN 2TU/5TU）检测。QFT-GIT 检测阳性定义为值≥0.35IU/ml，TST 检测阳性定义为硬结≥5mm。还探索了 TST 硬结≥10mm 的次要结局。计算了两种或两种以上检测方法的阳性率、阳性和阴性的不一致率；使用百分比一致性和 Kappa 统计评估了检测的一致性；并使用逻辑回归评估了包括年龄类别在内的一致性和不一致性的相关因素。使用潜在类别模型估计了敏感性和特异性。
在纳入的 1048 名 HHCs 中，869 名[中位数（IQR）年龄：27 岁（15-40）]同时具有 TST 和 QFT-GIT 结果，QFT-GIT 检测 LTBI 的患病率为 54%[95%CI（51,57）]，TST 检测的患病率为 55%[95%CI（52,58）]，两种检测方法的患病率均为 74%[95%CI（71,77）]，两种检测方法的患病率均为 35%[95%CI（31,38）]。TST+/QFT-GIT-的不一致率为 21%，而 TST-/QFT-GIT+的不一致率为 26%。使用 TST 5mm 或 10mm 截断值时，一致性较差（60%和 61%的一致性，kappa 值分别为 0.20 和 0.25）。检测一致性因年龄、TST 强度和硬结截断值而异。在多变量分析中，SPAN PPD 是 QFT-GIT+和 TST-的危险因素，而 BCG 疤痕缺失是 TST+和 QFT-GIT-的危险因素。有工作和接触家庭外的结核病病例与两种检测方法的阳性结果相关。TST 和 QFT-GIT 检测 LTBI 的敏感性分别为 77%和 69%。当两种检测均为阳性时，LTBI 的可能性>90%，无论暴露梯度如何。
印度成年肺结核患者的 HHCs 中 LTBI 的患病率非常高，且因检测类型、年龄和暴露梯度而异。在我们结核病负担高的环境中，应在未来的预防性治疗和疫苗研究中评估治疗所有 HHCs 或使用暴露指数的针对性策略，因为 HHCs 有几个因素使他们处于结核病发病的高风险中。
