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BackgroundThe natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia.MethodsBetween 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012–2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease.Results405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012–2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy.ConclusionsThe incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.

Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. Bill & Melinda Gates Foundation.

Background Early age at infection with hepatitis B virus (HBV) increases the risk of chronic HBV infection. In addition early age at infection may further increase the risk of persistent viral replication beyond its effect on chronicity. The effects of perinatal and early postnatal transmission on the risk of prolonged hepatitis B e antigenaemia in children with chronic HBV infection are not well documented in Africa. We examine these associations using maternal HBV sero-status and the number of HBV-positive older siblings as proxy measures for perinatal and early postnatal transmission, respectively. Methods Hepatitis B e antigen (HBeAg)-positive mothers were identified in six population-based HBV sero-surveys conducted in The Gambia between 1986 and 1990. For every HBeAg-positive mother, a hepatitis B surface antigen (HBsAg)-positive HBeAg-negative mother and HBsAg-negative mother were randomly selected from the population surveyed. These mothers and their family members were tested for HBV sero-markers in a subsequent survey conducted between 1991 and 1993. Results Thirty-eight HBeAg positive mothers and the same number of HBsAg-positive HBeAg-negative mothers and HBsAg-negative mothers participated in the study. Sixty-nine percent of their children also participated. There was a non-significant positive association between HBeAg prevalence in children and the number of HBeAg-positive older siblings (64.1%, 69.2% and 83.3% in children with 0, 1 and ≥2 HBeAg-positive older siblings, respectively). After adjusting for confounders, having an HBeAg-positive mother was a risk factor for HBeAg positivity in children carrying HBsAg (adjusted OR 4.5, 95% CI: 1.0-19.5, p = 0.04), whilst the number of HBeAg-positive older siblings was not. Conclusions Maternal HBeAg was associated with positive HBeAg in children with chronic HBV infection. This suggests that interrupting mother-to-infant transmission in sub-Saharan Africa might help reduce the burden of liver disease. A timely dose of HBV vaccine within 24 hours of birth, as recommended by WHO, should be implemented in sub-Saharan Africa.

Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as 'Good', scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07-1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.

Gay, bisexual, and other men who have sex with men (MSM) continue to have disproportionately high burdens of HIV infection in countries of low, middle, and high income in 2016. 4 years after publication of a Lancet Series on MSM and HIV, progress on reducing HIV incidence, expanding sustained access to treatment, and realising human rights gains for MSM remains markedly uneven and fraught with challenges. Incidence densities in MSM are unacceptably high in countries as diverse as China, Kenya, Thailand, the UK, and the USA, with substantial disparities observed in specific communities of MSM including young and minority populations. Although some settings have achieved sufficient coverage of treatment, pre-exposure prophylaxis (PrEP), and human rights protections for sexual and gender minorities to change the trajectory of the HIV epidemic in MSM, these are exceptions. The roll-out of PrEP has been notably slow and coverage nowhere near what will be required for full use of this new preventive approach. Despite progress on issues such as marriage equality and decriminalisation of same-sex behaviour in some countries, there has been a marked increase in anti-gay legislation in many countries, including Nigeria, Russia, and The Gambia. The global epidemic of HIV in MSM is ongoing, and global efforts to address it remain insufficient. This must change if we are ever to truly achieve an AIDS-free generation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.

In sub-Saharan Africa, hypertension prevalence is usually estimated from participant recall. We assessed the accuracy of self-reported hypertension in women of reproductive age. In PRECISE (PREgnancy Care Integrating translational Science, Everywhere), an observational prospective cohort study, we recruited 1825 non-pregnant women of reproductive age, 610 in the Gambia, 609 in Kenya and 606 in Mozambique. We compared self-reported and measured hypertension (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg). We adjusted hypertension prevalence for age, body mass index, education, parity, and antihypertensive medicine and oral contraceptive use. PRECISE was conducted in both urban and rural hospitals or clinics. The women were generally in their late twenties and parous. Adjusted measured hypertension prevalence was higher in Mozambique (10.4%; 95% confidence interval, CI: 7.9-12.7) and the Gambia (9.3%; 95% CI: 6.6-12.6) than in Kenya (4.6%; 95% CI: 3.0-6.6). Self-reported hypertension prevalence was highest in the Gambia (12.9%; 95% CI: 10.2-15.9) versus Mozambique (4.2%; 95% CI: 2.8-5.7) or Kenya (6.7%; 95% CI: 5.0-8.6). Sensitivity of self-reported (versus measured) hypertension was less than 45% in all countries, with specificities more than 89%. Positive likelihood ratios were fair in the Gambia (3.70; 95% CI: 2.47-5.54), and good in Kenya (5.79; 95% CI: 3.36-9.98) and Mozambique (5.18; 95% CI: 2.56-10.46). All negative likelihood ratios were poor (≥ 0.20). Self-reported hypertension is unsuitable for population hypertension estimates among women of reproductive age in these countries.

Host genetic factors can confer resistance against malaria 1 , raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum . We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member 2 – 4 PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations. A strong association has been found between three regions of the Plasmodium falciparum genome and sickle haemoglobin in children with severe malaria, suggesting parasites have adapted to overcome natural host immunity.

In a phase 3 noninferiority trial, one dose of a new meningococcal vaccine (NmCV-5) elicited immune responses similar to those of MenACWY-D for the four serotypes in common and additional immune responses for serogroup X.