학술논문

The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis
Document Type
article
Author
Martinez, LeonardoCords, OliviaHorsburgh, C RobertAndrews, Jason RConsortium, Pediatric TB Contact StudiesAcuna-Villaorduna, CarlosAhuja, Shama DesaiAltet, NeusAugusto, OrvalhoBaliashvili, DavitBasu, SanjayBecerra, MercedesBonnet, MarylineBoom, W HenryBorgdorff, MartienBoulahbal, FadilaCarvalho, Anna Cristina CCayla, Joan AChakhaia, TsiraChan, Pei-ChunCohen, TedCroda, JulioDatta, Sumonadel Corral, HelenaDenholm, Justin TDietze, ReynaldoDobler, Claudia CDonkor, SimonEgere, UzochukwuEllner, Jerrold JEspinal, MarcosEvans, Carlton AFang, Chi-TaiFielding, KatherineFox, Greg JGarcía, Luis FGarcía-Basteiro, Alberto LGeis, SteffenGraham, Stephen MGrandjean, LouisHannoun, DjoharHatherill, MarkHauri, Anja MHesseling, Anneke CHill, Philip CHuang, Li-MinHuerga, HelenaHussain, RabiaJarlsberg, LeahJones-López, Edward CKato, SeiyaKato-Maeda, MidoriKampmann, BeateKirchner, H LesterKritski, AfrânioLange, ChristophLee, Chih-HsinLee, Li-NaLee, Meng-RuiLemos, Antonio CarlosLienhardt, ChristianLing, Du-LinLiu, QiaoLo, Nathan CLong, RichardLopez-Varela, ElisaLu, PengMagee, MatthewMalone, LaShaunda LMandalakas, Anna MMartinson, Neil AMazahir, RufaidaMurray, Megan BNetto, Eduardo MartinsOtero, LarissaParsonnet, JulieReingold, ArthurSchaaf, H SimonSeddon, James ASharma, SurendraSingh, JitendraSingh, SarmanSloot, RosaSotgiu, GiovanniStein, Catherine MIqbal, Najeeha TalatTriasih, RinaTrieu, Lisavan der Loeff, Maarten F SchimVan der Stuyft, Patrickvan Schalkwyk, CariVashishtha, RichaVerhagen, Lilly MVillalba, Julian AWang, Jann-YuanWhalen, Christopher CYoshiyama, TakashiZar, Heather JZellweger, Jean-PierreZhu, Limei
Source
The Lancet. 395(10228)
Subject
Clinical Research
Pediatric
Infectious Diseases
Prevention
Tuberculosis
HIV/AIDS
Rare Diseases
Health Services
Emerging Infectious Diseases
Infection
Good Health and Well Being
Adolescent
Age Factors
Child
Child
Preschool
Contact Tracing
Disease Transmission
Infectious
Family Characteristics
Female
Global Health
Humans
Incidence
Male
Mycobacterium tuberculosis
Risk Assessment
Sex Factors
Tuberculosis
Pulmonary
Pediatric TB Contact Studies Consortium
Medical and Health Sciences
General & Internal Medicine
Language
Abstract
BackgroundTens 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.MethodsIn 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).FindingsIn 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