Mendelsohn Simon C, Mulenga Humphrey, Tameris Michele, Moloantoa Tumelo, Malherbe Stephanus T, Katona Austin, Maruri Fernanda, Noor Firdows, Panchia Ravindre, Hlongwane Khuthadzo, Stanley Kim, van der Heijden Yuri F, Hadley Katie, Ariefdien Dominique T, Chegou Novel N, Walzl Gerhard, Scriba Thomas J, Sterling Timothy R, Hatherill Mark
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Lancet Glob Health. 2025 Nov;13(11):e1869-e1879. doi: 10.1016/S2214-109X(25)00276-1.
More than half of tuberculosis cases detected by community prevalence surveys are classified as asymptomatic. We evaluated yield of symptom and chest radiograph screening of tuberculosis-exposed household contacts in South Africa.
For this prospective observational cohort study, adult volunteers (aged ≥18 years) with household exposure within the past 6 months to patients with untreated or partially treated pulmonary tuberculosis, identified through local health services, were enrolled at three sites in South Africa (Worcester and Ravensmead, Western Cape Province, and Soweto, Gauteng Province). Household contacts were excluded if they were unlikely to attend study visits, or had conditions interfering with consent or study participation, including psychiatric illness, substance dependence, or incarceration. Systematic screening of tuberculosis symptoms (any duration), chest radiograph (any abnormality indicative of active tuberculosis), and sputum microscopy, Xpert Ultra, and liquid culture were performed. Serum C-reactive protein (CRP) was measured by multiplex bead array. Prevalent tuberculosis was microbiologically confirmed (Xpert Ultra or culture). Symptomatic and asymptomatic tuberculosis were defined as prevalent tuberculosis with and without reported symptoms compatible with tuberculosis. The primary outcome was the diagnostic yield (sensitivity) of microbiologically confirmed pulmonary tuberculosis.
Between April 22, 2021 and Sept 22, 2022, 979 household contacts were enrolled, 345 (35·2%) male and 634 (64·8%) female, 185 (18·9%) living with HIV and 187 (19·1%) with previous tuberculosis. Prevalent tuberculosis occurred in 51 (5·2%) and was asymptomatic in 42 (82·4%) of 51. Only 13 (31·0%) of 42 asymptomatic people with tuberculosis were sputum-smear positive; eight (61·5%) of these 13 had a low bacillary burden, with smear grades scanty or 1+ (1-99 acid-fast bacilli per 100 fields). CRP did not discriminate healthy household contacts from those with asymptomatic tuberculosis (area under the curve 0·60, 95% CI 0·47-0·73). An abnormal chest radiograph suggestive of tuberculosis was observed in 23 of 41 asymptomatic (sensitivity 56·1%, 95% CI 41·0-70·1) versus eight of nine symptomatic (sensitivity 88·9%, 56·5-98·0) people with tuberculosis. Sensitivity of chest radiograph in combination with symptom screening was 32 (64·0%) of 50 (50·1-75·9) for all prevalent tuberculosis.
More than 80% of confirmed people with tuberculosis among household contacts were asymptomatic; chest radiograph screening missed more than 40% of these. Community prevalence surveys reliant on symptom-based and chest radiograph-based approaches might substantially underestimate the prevalence of asymptomatic tuberculosis in endemic countries.
Regional Prospective Observational Research for Tuberculosis South Africa through funding from the US National Institutes of Health, the Civilian Research and Development Foundation, and the South African Medical Research Council.
社区患病率调查发现的结核病病例中，超过一半被归类为无症状。我们评估了南非结核病暴露家庭接触者症状和胸部X光筛查的检出率。
在这项前瞻性观察队列研究中，通过当地卫生服务机构确定的在过去6个月内有家庭接触未治疗或部分治疗的肺结核患者史的成年志愿者（年龄≥18岁），在南非的三个地点（西开普省的伍斯特和雷文斯米德，豪登省的索韦托）入组。如果家庭接触者不太可能参加研究访视，或有影响同意或参与研究的情况，包括精神疾病、药物依赖或监禁，则将其排除。对结核病症状（任何持续时间）、胸部X光（任何提示活动性结核病的异常）以及痰涂片镜检、Xpert Ultra和液体培养进行系统筛查。通过多重珠阵列测量血清C反应蛋白（CRP）。确诊结核病通过微生物学方法（Xpert Ultra或培养）。有症状和无症状结核病分别定义为有和无与结核病相符的报告症状的确诊结核病。主要结局是微生物学确诊的肺结核的诊断检出率（敏感性）。
2021年4月22日至2022年9月22日期间，979名家庭接触者入组，男性345名（35.2%），女性634名（64.8%），185名（18.9%）感染艾滋病毒，187名（19.1%）既往有结核病。确诊结核病51例（5.2%），其中42例（82.4%）无症状。42例无症状结核病患者中仅13例（31.0%）痰涂片阳性；这13例中的8例（61.5%）细菌载量低，涂片分级为少量或1+（每100视野1 - 99条抗酸杆菌）。CRP无法区分健康家庭接触者和无症状结核病患者（曲线下面积0.60，95%置信区间0.47 - 0.73）。41例无症状结核病患者中有23例胸部X光有提示结核病的异常（敏感性56.1%，95%置信区间41.0 - 70.1），而9例有症状结核病患者中有8例（敏感性88.9%，56.5 - 98.0）。胸部X光与症状筛查联合的敏感性为50例确诊结核病中的32例（64.0%）（50.1 - 75.9）。
家庭接触者中超过80%确诊的结核病患者无症状；胸部X光筛查漏诊了其中超过40%的患者。依赖基于症状和胸部X光方法的社区患病率调查可能会大幅低估流行国家无症状结核病的患病率。
通过美国国立卫生研究院、民用研究与发展基金会和南非医学研究理事会的资助开展的南非结核病区域前瞻性观察研究。
