The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis
Journal
The Lancet
Journal Volume
395
Journal Issue
10228
Date Issued
2020-03-21
Author(s)
Cords, Olivia
Horsburgh, C. Robert
Andrews, Jason R.
Acuna-Villaorduna, Carlos
Desai Ahuja, Shama
Altet, Neus
Augusto, Orvalho
Baliashvili, Davit
Basu, Sanjay
Becerra, Mercedes
Bonnet, Maryline
Henry Boom, W.
Borgdorff, Martien
Boulahbal, Fadila
Carvalho, Anna Cristina C.
Cayla, Joan A.
Chakhaia, Tsira
Chan, Pei Chun
Cohen, Ted
Croda, Julio
Datta, Sumona
del Corral, Helena
Denholm, Justin T.
Dietze, Reynaldo
Dobler, Claudia C.
Donkor, Simon
Egere, Uzochukwu
Ellner, Jerrold J.
Espinal, Marcos
Evans, Carlton A.
CHI-TAI FANG
Fielding, Katherine
Fox, Greg J.
García, Luis F.
García-Basteiro, Alberto L.
Geis, Steffen
Graham, Stephen M.
Grandjean, Louis
Hannoun, Djohar
Hatherill, Mark
Hauri, Anja M.
Hesseling, Anneke C.
Hill, Philip C.
Huerga, Helena
Hussain, Rabia
Jarlsberg, Leah
Jones-López, Edward C.
Kato, Seiya
Kato-Maeda, Midori
Kampmann, Beate
Kirchner, H. Lester
Kritski, Afrânio
Lange, Christoph
Lee, Chih Hsin
Lemos, Antonio Carlos
Lienhardt, Christian
Ling, Du Lin
Liu, Qiao
Lo, Nathan C.
Long, Richard
Lopez-Varela, Elisa
Lu, Peng
Magee, Matthew
Malone, La Shaunda L.
Mandalakas, Anna M.
Martinson, Neil A.
Mazahir, Rufaida
Murray, Megan B.
Netto, Eduardo Martins
Otero, Larissa
Parsonnet, Julie
Reingold, Arthur
Schaaf, H. Simon
Seddon, James A.
Sharma, Surendra
Singh, Jitendra
Singh, Sarman
Sloot, Rosa
Sotgiu, Giovanni
Stein, Catherine M.
Iqbal, Najeeha Talat
Triasih, Rina
Trieu, Lisa
van der Loeff, Maarten F.Schim
Van der Stuyft, Patrick
van Schalkwyk, Cari
Vashishtha, Richa
Verhagen, Lilly M.
Villalba, Julian A.
Whalen, Christopher C.
Yoshiyama, Takashi
Zar, Heather J.
Zellweger, Jean Pierre
Zhu, Limei
Pediatric TB Contact Studies Consortium
Abstract
© 2020 Elsevier Ltd Background: Tens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood. Methods: In this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protocol is registered with PROSPERO (CRD42018087022). Findings: In total, study groups from 46 cohort studies in 34 countries—29 (63%) prospective studies and 17 (37%) retrospective—agreed to share their data and were included in the final analysis. 137 647 tuberculosis-exposed children were evaluated at baseline and 130 512 children were followed for 429 538 person-years, during which 1299 prevalent and 999 incident tuberculosis cases were diagnosed. Children not receiving preventive therapy with a positive result for tuberculosis infection had significantly higher 2-year cumulative tuberculosis incidence than children with a negative result for tuberculosis infection, and this incidence was greatest among children below 5 years of age (19·0% [95% CI 8·4–37·4]). The effectiveness of preventive therapy was 63% (adjusted HR 0·37 [95% CI 0·30–0·47]) among all exposed children, and 91% (adjusted HR 0·09 [0·05–0·15]) among those with a positive result for tuberculosis infection. Among all children <5 years of age who developed tuberculosis, 83% were diagnosed within 90 days of the baseline visit. Interpretation: The risk of developing tuberculosis among exposed infants and young children is very high. Most cases occurred within weeks of contact investigation initiation and might not be preventable through prophylaxis. This suggests that alternative strategies for prevention are needed, such as earlier initiation of preventive therapy through rapid diagnosis of adult cases or community-wide screening approaches. Funding: National Institutes of Health.
SDGs
Type
journal article