Mendelsohn Simon C, Andrade Bruno B, Mbandi Stanley Kimbung, Andrade Alice M S, Muwanga Vanessa M, Figueiredo Marina C, Erasmus Mzwandile, Rolla Valeria C, Thami Prisca K, Cordeiro-Santos Marcelo, Penn-Nicholson Adam, Kritski Afranio L, Hatherill Mark, Sterling Timothy R, Scriba Thomas J
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.
Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
J Infect Dis. 2024 Dec 16;230(6):e1355-e1365. doi: 10.1093/infdis/jiae237.
Approximately 5% of people infected with Mycobacterium tuberculosis progress to tuberculosis (TB) disease without preventive therapy. There is a need for a prognostic test to identify those at highest risk of incident TB so that therapy can be targeted. We evaluated host blood transcriptomic signatures for progression to TB disease.
Close contacts (≥4 hours of exposure per week) of adult patients with culture-confirmed pulmonary TB were enrolled in Brazil. Investigation for incident, microbiologically confirmed, or clinically diagnosed pulmonary or extrapulmonary TB disease through 24 months of follow-up was symptom triggered. Twenty previously validated blood TB transcriptomic signatures were measured at baseline by real-time quantitative polymerase chain reaction. Prognostic performance for incident TB was tested by receiver operating characteristic curve analysis at 6, 9, 12, and 24 months of follow-up.
Between June 2015 and June 2019, 1854 close contacts were enrolled. Twenty-five progressed to incident TB, of whom 13 had microbiologically confirmed disease. Baseline transcriptomic signature scores were measured in 1789 close contacts. Prognostic performance for all signatures was best within 6 months of diagnosis. Seven signatures (Gliddon4, Suliman4, Roe3, Roe1, Penn-Nicholson6, Francisco2, and Rajan5) met the minimum World Health Organization target product profile for a prognostic test through 6 months and 3 signatures (Gliddon4, Rajan5, and Duffy9) through 9 months. None met the target product profile threshold through ≥12 months of follow-up.
Blood transcriptomic signatures may be useful for predicting TB risk within 9 months of measurement among TB-exposed contacts to target preventive therapy administration.
约5%的结核分枝杆菌感染者在未接受预防性治疗的情况下会进展为结核病。需要一种预后测试来识别发生结核病风险最高的人群，以便进行有针对性的治疗。我们评估了宿主血液转录组特征与结核病进展的关系。
在巴西招募了成年肺结核确诊患者的密切接触者（每周接触≥4小时）。通过24个月的随访，根据症状触发情况对新发、微生物学确诊或临床诊断的肺结核或肺外结核进行调查。在基线时通过实时定量聚合酶链反应测量20个先前验证的血液结核转录组特征。在随访的6、9、12和24个月时，通过受试者工作特征曲线分析测试新发结核病的预后性能。
2015年6月至2019年6月，共招募了1854名密切接触者。25人进展为新发结核病，其中13人有微生物学确诊的疾病。在1789名密切接触者中测量了基线转录组特征分数。所有特征的预后性能在诊断后6个月内最佳。7个特征（Gliddon4、Suliman4、Roe3、Roe1、Penn-Nicholson6、Francisco2和Rajan5）在6个月内达到了世界卫生组织预后测试的最低目标产品轮廓要求，3个特征（Gliddon4、Rajan5和Duffy9）在9个月内达到要求。在随访≥12个月时，没有一个特征达到目标产品轮廓阈值。
血液转录组特征可能有助于在结核病暴露接触者测量后的9个月内预测结核病风险，以指导预防性治疗的实施。
