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) followup 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 mixedeffects 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 9...

Dams have long been associated with elevated burdens of human schistosomiasis, but how dams increase disease is not always clear, in part because dams have many ecological and socio-economic effects. A recent hypothesis argues that dams block reproduction of the migratory river prawns that eat the snail hosts of schistosomiasis. In the Senegal River Basin, there is evidence that prawn populations declined and schistosomiasis increased after completion of the Diama Dam. Restoring prawns to a water-access site upstream of the dam reduced snail density and reinfection rates in people. However, whether a similar cascade of effects (from dams to prawns to snails to human schistosomiasis) occurs elsewhere is unknown. Here, we examine large dams worldwide and identify where their catchments intersect with endemic schistosomiasis and the historical habitat ranges of large, migratory Macrobrachium spp. prawns. River prawn habitats are widespread, and we estimate that 277–385 million people live within schistosomiasis-endemic regions where river prawns are or were present (out of the 800 million people who are at risk of schistosomiasis). Using a published repository of schistosomiasis studies in sub-Saharan Africa, we compared infection before and after the construction of 14 large dams for people living in: (i) upstream catchments within historical habitats of native prawns, (ii) comparable undammed watersheds, and (iii) dammed catchments beyond the historical reach of migratory prawns. Damming was followed by greater increases in schistosomiasis within prawn habitats than outside prawn habitats. We estimate that one third to one half of the global population-at-risk of schistosomiasis could benefit from restoration of native prawns. Because dams block prawn migrations, our results suggest that prawn extirpation contributes to the sharp increase of schistosomiasis after damming, and points to prawn restoration as an ecological solution for reducing human disease.This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’.

Summary Background Prisons are recognised as high-risk environments for tuberculosis, but there has been little systematic investigation of the global and regional incidence and prevalence of tuberculosis, and its determinants, in prisons. We did a systematic review and meta-analysis to assess the incidence and prevalence of tuberculosis in incarcerated populations by geographical region. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Knowledge, and the LILACS electronic database from Jan 1, 1980, to Nov 15, 2020, for cross-sectional and cohort studies reporting the incidence of Mycobacterium tuberculosis infection, incidence of tuberculosis, or prevalence of tuberculosis among incarcerated individuals in all geographical regions. We extracted data from individual studies, and calculated pooled estimates of incidence and prevalence through hierarchical Bayesian meta-regression modelling. We also did subgroup analyses by region. Incidence rate ratios between prisons and the general population were calculated by dividing the incidence of tuberculosis in prisons by WHO estimates of the national population-level incidence. Findings We identified 159 relevant studies; 11 investigated the incidence of M tuberculosis infection (n=16 318), 51 investigated the incidence of tuberculosis (n=1 858 323), and 106 investigated the prevalence of tuberculosis (n=6 727 513) in incarcerated populations. The overall pooled incidence of M tuberculosis infection among prisoners was 15·0 (95% credible interval [CrI] 3·8–41·6) per 100 person-years. The incidence of tuberculosis (per 100 000 person-years) among prisoners was highest in studies from the WHO African (2190 [95% CrI 810–4840] cases) and South-East Asia (1550 [240–5300] cases) regions and in South America (970 [460–1860] cases), and lowest in North America (30 [20–50] cases) and the WHO Eastern Mediterranean region (270 [50–880] cases). The prevalence of tuberculosis was greater than 1000 per 100 000 prisoners in all global regions except for North America and the Western Pacific, and highest in the WHO South-East Asia region (1810 [95% CrI 670–4000] cases per 100 000 prisoners). The incidence rate ratio between prisons and the general population was much higher in South America (26·9; 95% CrI 17·1–40·1) than in other regions, but was nevertheless higher than ten in the WHO African (12·6; 6·2–22·3), Eastern Mediterranean (15·6; 6·5–32·5), and South-East Asia (11·7; 4·1–27·1) regions. Interpretation Globally, people in prison are at high risk of contracting M tuberculosis infection and developing tuberculosis, with consistent disparities between prisons and the general population across regions. Tuberculosis control programmes should prioritise preventive interventions among incarcerated populations. ...

Tuberculosis is a major cause of death and disability among children globally, yet children have been neglected in global tuberculosis control efforts. Historically, tuberculosis in children has been thought of as a family disease, and because of this, household contact tracing of children after identification of an adult tuberculosis case has been emphasised as the principal public health intervention. However, the population-level effect of household contact tracing is predicated on the assumption that most paediatric tuberculosis infections are acquired within the household. In this Personal View, we focus on accumulating scientific evidence indicating that the majority of