Paradkar Mandar, Padmapriyadarsini Chandrasekaran, Jain Divyashri, Shivakumar Shri Vijay Bala Yogendra, Thiruvengadam Kannan, Gupte Akshay N, Thomas Beena, Kinikar Aarti, Sekar Krithika, Bharadwaj Renu, Dolla Chandra Kumar, Gaikwad Sanjay, Elilarasi S, Lokhande Rahul, Reddy Devarajulu, Murali Lakshmi, Kulkarni Vandana, Pradhan Neeta, Hanna Luke Elizabeth, Pattabiraman Sathyamurthi, Kohli Rewa, S Rani, Suryavanshi Nishi, B M Shrinivasa, Cox Samyra R, Selvaraju Sriram, Gupte Nikhil, Mave Vidya, Gupta Amita, Bollinger Robert C
Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, Maharashtra, India.
Johns Hopkins University Center for Clinical Global Health Education, Pune, Maharashtra, India.
PLoS One. 2020 Jul 29;15(7):e0236743. doi: 10.1371/journal.pone.0236743. eCollection 2020.
The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.
世界卫生组织（WHO）最近更改了其针对结核病（TB）预防性治疗（TPT）的指导意见，建议对所有与肺结核（PTB）患者有接触的家庭接触者（HHC）进行TPT，以预防新发结核病（iTBD），无论其结核感染（TBI）状态如何。然而，这一建议是有条件的，因为证据力度不强。我们评估了印度近期接触过结核病的成人和儿童HHC发生iTBD的风险因素，以确定哪些HHC亚组可能从TPT中获益最大。我们前瞻性地招募了印度浦那和金奈成年PTB患者的同意参与研究的HHC。他们在入组时、4 - 6个月、12个月和24个月接受了结核病（TBD）和TBI的临床、微生物学和放射学筛查。TBI检测通过结核菌素皮肤试验（TST）和全血γ干扰素释放试验（QGIT）进行。对无基线TBD的HHC随访观察iTBI和iTBD的发生情况。我们使用混合效应泊松回归，评估包括TBI状态在内的基线特征以及使用多种TST和/或QGIT临界值的新发TBI（iTBI），作为iTBD的潜在风险因素。在招募的1051名HHC中，42名（4%）有基线TBD，12名（1%）未进行基线TBI检测，被排除。在其余997名HHC中，707名（71%）有基线TBI（TST≥5 mm或QGIT≥0.35 IU/ml）。总体而言，20名HHC（2%）发生了iTBD（12例/1000人年，95%CI：8 - 19）。HIV感染（调整后发病率比[aIRR]=29.08，95%CI：2.38 - 355.77，p = 0.01）和营养不良（aIRR = 6.16，95%CI：1.89 - 20.03，p = 0.003）与iTBD独立相关。iTBD与年龄、糖尿病、吸烟、饮酒以及基线TBI或iTBI无关，无论TST（≥5 mm、≥10 mm、增加≥6 mm）或QGIT（≥0.35 IU/ml、≥0.7 IU/ml）临界值如何。鉴于近期接触的HHC中iTBD总体风险较高，且TBI状态与iTBD之间缺乏关联，我们的研究结果支持WHO的新建议，即向居住在印度等结核病高负担国家的PTB患者的所有HHC提供TPT，并且不表明在基线或随访期间进行TBI检测对近期接触的HHC进行TPT风险分层有任何益处。
