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BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included "mycobacterium tuberculosis", "TB", "tuberculosis", and "contact". We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health.

Background In areas where Plasmodium falciparum malaria is seasonal, a dry season reservoir of blood-stage infection is essential for initiating transmission during the following wet season. Methods In The Gambia, a cohort of 42 individuals with quantitative polymerase chain reaction-positive P falciparum infections at the end of the transmission season (December) were followed monthly until the end of the dry season (May) to evaluate infection persistence. The influence of human host and parasitological factors was investigated. Results A large proportion of individuals infected at the end of the wet season had detectable infections until the end of the dry season (40.0%; 16 of 40). At the start of the dry season, the majority of these persistent infections (82%) had parasite densities >10 p/µL compared to only 5.9% of short-lived infections. Persistent infections (59%) were also more likely to be multiclonal than short-lived infections (5.9%) and were associated with individuals having higher levels of P falciparum-specific antibodies (P = .02). Conclusions Asymptomatic persistent infections were multiclonal with higher parasite densities at the beginning of the dry season. Screening and treating asymptomatic infections during the dry season may reduce the human reservoir of malaria responsible for initiating transmission in the wet season.

Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we identify genome-wide statistically significant genotype-phenotype associations in surface-exposed choline-binding (P = 5.00 × 10−08) and helicase proteins (P = 1.32 × 10−06) important for invasion, immune evasion and pneumococcal tropism to CNS. The small effect sizes and negligible heritability indicated that causation of CNS infection requires multiple genetic and other factors reflecting a complex and polygenic aetiology. Our findings suggest that certain pathogen genetic variation modulate pneumococcal survival and tropism to CNS tissue, and therefore, virulence for meningitis., Using a genome-wide association study approach, Chaguza et al. identify significant genotype-phenotype associations relevant to Streptococcus pneumoniae infection. These findings indicate genetic variations in the pathogen attributed to pneumococcal tropism to central nervous system tissues, with implications for meningitis virulence.

International audience; BackgroundNipah virus is a highly virulent zoonotic pathogen that can be transmitted between humans. Understanding the dynamics of person-to-person transmission is key to designing effective interventions.MethodsWe used data from all Nipah virus cases identified during outbreak investigations in Bangladesh from April 2001 through April 2014 to investigate case-patient characteristics associated with onward transmission and factors associated with the risk of infection among patient contacts.ResultsOf 248 Nipah virus cases identified, 82 were caused by person-to-person transmission, corresponding to a reproduction number (i.e., the average number of secondary cases per case patient) of 0.33 (95% confidence interval [CI], 0.19 to 0.59). The predicted reproduction number increased with the case patient’s age and was highest among patients 45 years of age or older who had difficulty breathing (1.1; 95% CI, 0.4 to 3.2). Case patients who did not have difficulty breathing infected 0.05 times as many contacts (95% CI, 0.01 to 0.3) as other case patients did. Serologic testing of 1863 asymptomatic contacts revealed no infections. Spouses of case patients were more often infected (8 of 56 [14%]) than other close family members (7 of 547 [1.3%]) or other contacts (18 of 1996 [0.9%]). The risk of infection increased with increased duration of exposure of the contacts (adjusted odds ratio for exposure of >48 hours vs. ≤1 hour, 13; 95% CI, 2.6 to 62) and with exposure to body fluids (adjusted odds ratio, 4.3; 95% CI, 1.6 to 11).ConclusionsIncreasing age and respiratory symptoms were indicators of infectivity of Nipah virus. Interventions to control person-to-person transmission should aim to reduce exposure to body fluids. (Funded by the National Institutes of Health and others.)

Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a collection of 48 sub-Saharan African groups. We show that coastal populations experienced an influx of Eurasian haplotypes over the last 7000 years, and that Eastern and Southern Niger-Congo speaking groups share ancestry with Central West Africans as a result of recent population expansions. In fact, most sub-Saharan populations share ancestry with groups from outside of their current geographic region as a result of gene-flow within the last 4000 years. Our in-depth analysis provides insight into haplotype sharing across different ethno-linguistic groups and the recent movement of alleles into new environments, both of which are relevant to studies of genetic epidemiology. DOI: http://dx.doi.org/10.7554/eLife.15266.001, eLife digest Our genomes contain a record of historical events. This is because when groups of people are separated for generations, the DNA sequence in the two groups’ genomes will change in different ways. Looking at the differences in the genomes of people from the same population can help researchers to understand and reconstruct the historical interactions that brought their ancestors together. The mixing of two populations that were previously separate is known as admixture. Africa as a continent has few written records of its history. This means that it is somewhat unknown which important movements of people in the past generated the populations found in modern-day Africa. Busby et al. have now attempted to use DNA to look into this and reconstruct the last 4000 years of genetic history in African populations. As has been shown in other regions of the world, the new analysis showed that all African populations are the result of historical admixture events. However, Busby et al. could characterize these events to unprecedented level of detail. For example, multiple ethnic groups from The Gambia and Mali all show signs of sharing the same set of ancestors from West Africa, Europe and Asia who mixed around 2000 years ago. Evidence of a migration of people from Central West Africa, known as the Bantu expansion, could also be detected, and was shown to carry genes to the south and east. An important next step will be to now look at the consequences of the observed gene-flow, and ask if it has contributed to spreading beneficial, or detrimental, mutations around Africa. DOI: http://dx.doi.org/10.7554/eLife.15266.002

Erratum in :Correction to Lancet Glob Health 2016; 4: e568-78.Lancet Glob Health. 2016 Nov;4(11):e794. doi: 10.1016/S2214-109X(16)30272-8. PMID: 27765292; International audience; Background: Despite the high burden of hepatitis B virus (HBV) infection in sub-Saharan Africa, absence of widespread screening and poor access to treatment leads to most people remaining undiagnosed until later stages of disease when prognosis is poor and treatment options are limited. We examined the cost-effectiveness of community-based screening and early treatment with antiviral therapy for HBV in The Gambia.Methods: In this economic evaluation, we combined a decision tree with a Markov state transition model to compare a screen and treat intervention consisting of adult community-based screening using a hepatitis B surface antigen (HBsAg) rapid test and subsequent HBV antiviral therapy versus current practice, in which there is an absence of publicly provided screening or treatment for HBV. We used data from the PROLIFICA study to parameterise epidemiological, primary screening, and cost information, and other model parameter inputs were obtained from a literature search. Outcome measures were cost per disability-adjusted life-year (DALY) averted; cost per life-year saved; and cost per quality-adjusted life-year (QALY) gained. We calculated the incremental cost-effectiveness ratios (ICERs) between current practice and the screen and treat intervention. Costs were assessed from a health provider perspective. Costs (expressed in 2013 US$) and health outcomes were discounted at 3% per year.Findings: In The Gambia, where the prevalence of HBsAg is 8·8% in people older than 30 years, adult screening and treatment for HBV has an incremental cost-effectiveness ratio (ICER) of $540 per DALY averted, $645 per life-year saved, and $511 per QALY gained, compared with current practice. These ICERs are in line with willingness-to-pay levels of one times the country's gross domestic product per capita ($487) per DALY averted, and remain robust over a wide range of epidemiological and cost parameter inputs.Interpretation: Adult community-based screening and treatment for HBV in The Gambia is likely to be a cost-effective intervention. Higher cost-effectiveness might be achievable with targeted facility-based screening, price reductions of drugs and diagnostics, and integration of HBV screening with other public health interventions.Funding: European Commission.

International audience; The Gambia National Cancer Registry (GNCR) is one of the few nationwide population-based cancer registries in sub-Saharan Africa. Most registries in sub-Saharan Africa are limited to cities; therefore, the GNCR is important in providing estimates of cancer incidence in rural Africa. Our study assesses the quality of its data. The methods proposed by Bray and Parkin, and Parkin and Bray (Eur J Cancer 2009;45:747-64) were applied to the registry data from 1990 to 2009 to assess comparability, validity and completeness. The system used for classification and coding of neoplasms followed international standards. The percentage of cases morphologically verified was 18.1% for men and 33.1% for women, and that of death certificate only cases was 6.6 and 3.6%, respectively. Incidence rates in rural regions were lower than in the urban part of the country, except amongst young male adults. Comparison with other West African registries showed that the incidences of liver and uterine cervical cancer were comparable, but those of prostate and breast in The Gambia were relatively low. The overall completeness was estimated at 50.3% using the capture-recapture method. The GNCR applies international standard practices to data collection and handling, providing valuable data on cancer incidence in sub-Saharan Africa. However, the data are incomplete in the rural and elderly populations probably because of health care access and use.

We read with great interest the letter from Stockdale et al 1 in which they concluded that the gamma-glutamyl transpeptidase to platelet ratio (GPR) and aspartate transaminase (AST)-to-platelet ratio index (APRI) would not be ideal for the diagnosis of liver fibrosis in patients with HIV–HBV coinfection from West Africa. In a relatively small cohort of HIV–HBV coinfected subjects (n=100) from Ghana, the authors reported poor sensitivity (57%–67%) and specificity (63%–79%) of GRP and APRI in diagnosing advanced fibrosis (≥F3) and cirrhosis (F4). These findings are interesting, but should be interpreted with caution with regards to the internal validity of using transient elastography as the reference, the study population itself and the cut-offs generated as a result. The GPR was originally developed for the assessment of liver fibrosis in HBV mono-infected individuals in a West African setting.2 It has been recently applied to patients predominately treated for HIV–HBV coinfection by a French team, reporting good diagnostic performance to diagnose cirrhosis (sensitivity 77%, specificity 87%).3 In both studies, the accuracy of GPR was assessed …