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...

Background The aim of this study is to quantify the effects of the SARS-CoV-2 pandemic on health services utilization in China using over four years of routine health information system data. Methods We conducted a retrospective observational cohort study of health services utilization from health facilities at all levels in all provinces of mainland China. We analyzed monthly all-cause health facility visits and inpatient volume in health facilities before and during the SARS-CoV-2 outbreak using nationwide routine health information system data from January 2016 to June 2020. We used interrupted time series analyses and segmented negative binomial regression to examine changes in healthcare utilization attributable to the pandemic. Stratified analyses by facility type and by provincial Human Development Index (HDI) – an area-level measure of socioeconomic status – were conducted to assess potential heterogeneity in effects. Findings In the months before the SARS-CoV-2 outbreak, a positive secular trend in patterns of healthcare utilization was observed. After the SARS-CoV-2 outbreak, we noted statistically significant decreases in all indicators, with all indicators achieving their nadir in February 2020. The magnitude of decline in February ranged from 63% (95% CI 61–65%; p <0•0001) in all-cause visits at hospitals in regions with high HDI and 71% (95% CI 70–72%; p <0•0001) in all-cause visits at primary care clinics to 33% (95% CI 24–42%; p <0•0001) in inpatient volume and 10% (95% CI 3–17%; p = 0•0076) in all-cause visits at township health centers (THC) in regions with low HDI. The reduction in health facility visits was greater than that in the number of outpatients discharged (51% versus 48%; p <0•0079). The reductions in both health facility visits and inpatient volume were greater in hospitals than in primary health care facilities ( p <0•0001) and greater in developed regions than in underdeveloped regions ( p <0•0001). Following the nadir of health services utilization in February 2020, all indicators showed statistically significant increases. However, even by June 2020, nearly all indicators except outpatient and inpatient volume in regions with low HDI and inpatient volume in private hospitals had not achieved their pre-SARS-COV-2 forecasted levels. In total, we estimated cumulative losses of 1020.5 (95% CI 951.2- 1089.4; P <0.0001) million or 23.9% (95% CI 22.5–25.2%; P <0.0001) health facility visits, and 28.9 (95% CI 26.1–31.6; P <0.0001) million or 21.6% (95% CI 19.7–23.4%; P <0.0001) inpatients as of June 2020. Interpretation Inpatient and outpatient health services utilization in China declined sig...

The Manhiça Health Research Centre, established in 1996 in a rural area of southern Mozambique, currently follows around 92 000 individuals living in approximately 20 000 enumerated and geo-positioned households. Its main strength is the possibility of linking demographic data and clinical data to promote and conduct biomedical research in priority health areas. Socio-demographic data are updated twice a year and clinical data are collected on a daily basis. The data collected in Manhiça HDSS comprises household and individual characteristics, household socio-economic assets, vital data, migration, individual health history and cause of death, among others. Studies conducted in this HDSS contributed to guide the health authorities and decision-making bodies to define or adjust health policies such as the introduction of Mozambique's expanded programme of immunization with different vaccines (Haemophilus influenzae type b, Pneumococcus) or the development of the concept of Intermittent Preventive Treatment for Infants (IPTi) that led to the World Health Organization recommendation of this method as best practice for the control of malaria among infants. Manhiça's data can be accessed through a formal request to Diana Quelhas (diana.quelhas@manhica.net) accompanied by a proposal that will be analysed by the Manhiça HDSS internal scientific and ethics committees.