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Summary Background Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov , NCT02509494 . Findings From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. Funding Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.

Hospital admissions and their clinical outcomes can reflect the disease burden in a population and can be utilised as effective surveillance and impact monitoring tools. Inadequate documentation of admissions and their outcomes have contributed to the poor quality of paediatric care in many health care settings in sub-Saharan Africa. We have developed and piloted a simple tool for documentation of basic, standardised patient-level information on causes of admissions, diagnoses, treatments and outcomes in patients admitted to the paediatric ward of a district hospital in a rural community in Sierra Leone.From 1 August 2019 to 31 July 2021, we used this tool to document the admissions, treatments and clinical outcomes of 1,663 children admitted to this hospital. The majority of the children (1015, 62%) were aged between 12-59 months, were boys (942, 57%), were wasted (516, 31%), stunted (238 14%) or underweight (537, 32%). More than half of the children lived more than 1 km distance from the hospital (876/1410, 62%). Most were admitted before 4pm (1171/1626, 72%) and during weekdays (1231/1662, 74%). The highest number of paediatric admissions occurred in November 2019 and the lowest in April 2020. Severe malaria was the leading cause of admission. More than 80% of the children were successfully treated and discharged home (1356/1663, 81.5%) while 122/1663 (7.3%) died. Children aged under-five years who were underweight, and those who presented with danger signs (e.g. signs of breathing difficulty, dehydration, head injury or severe infections) had a higher risk of death than children without these features (pLack of systematic documentation of medical histories and poor record keeping of hospital admissions and outcomes can be overcome by using a simple tool. Continuous use of the tool with regular audits could improve delivery of paediatric care in resource-limited settings.

Introduction: The EBOVAC-Salone trial of a candidate Ebola two-dose vaccine regimen (Ad.ZEBOV/MVA-BN-Filo) was conducted in a research-naïve setting in rural northern Sierra Leone, where no local laboratory reference values (LRV) had been established. In the first stage (n = 43) of the trial, laboratory screening was based on internationally-derived protocol LRV (PLRV). For postrecruitment participant care, LRV derived from a West African population (WALRV) were used. We assessed what difference using WALRV rather than PLRV for screening might have made to the eligibility of volunteers. METHODS: We reviewed the laboratory screening results of study volunteers. Red blood cells (RBC), white blood cells (WBC), platelets (PTT), haemoglobin, haematocrit, creatinine, and alanine (ALT) and aspartate (AST) transaminases were measured. Overall and for each parameter, we compared the actually eligible proportion of volunteers using PLRV with the potentially eligible proportion using WALRV. Results: Of 102 (82 males, 20 females) volunteers, overall 55 (53.9% males) met PLRV eligibility criteria for inclusion, compared with 91 (89.2% males) who were within WALRV normal limits (p < 0.0001). Thus, 36 volunteers who failed laboratory screening using PLRV (76.6% of screening failures) might have been eligible if WALRV had been applied. Parameters with significant effect were haemoglobin (33 ineligible by PLRV, vs. 2 ineligible by WALRV; p < 0.0001); RBC (27 vs. 1; p < 0.0001); and PTT (18 vs. 6; p = 0.0093). Levels of creatinine and ALT did not present any differences. Discussion: Use of WALRV in eligibility assessment would potentially have led to considerable differences in the baseline laboratory characteristics of enrolled volunteers. Clinical trials are increasingly common and crucial in emerging infectious disease research. Our findings underscore the importance of locally-derived LRV in clinical trials in sub-Saharan Africa, to avoid excluding potentially eligible study volunteers, and to better support routine clinical care and safety assessments. Appropriately designed studies are needed in each region to establish local LRV.

OBJECTIVE: African men who have sex with men often sell sex to men and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). DESIGN: Descriptive behavioural study METHODS: : A novel validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. RESULTS: Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence were more likely to only report insertive anal sex roles and reported lower frequencies of condomless receptive anal sex than exclusive MSW. CONCLUSION: Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.

Endemic Burkitt's lymphoma (eBL) has been linked to Epstein-Barr virus and holoendemic Plasmodium falciparum malaria. These co-infections, however, are insufficient to explain the non-random occurrence of Endemic Burkitt's lymphoma within Equatorial Africa. To explore whether this distribution could be explained by household characteristics and family environment, we conducted a case-control study using 41 hospitalized incident endemic Burkitt's lymphoma cases and 91 healthy controls identified through a population-based multistage cluster-sampling scheme in Nyanza Province, Kenya. In a multivariate analysis, odds ratios associated with having one, two, and three or more younger siblings compared with none were 0.28 (90% CI: 0.09, 0.83), 0.59 (90% CI: 0.16, 2.23) and 0.15 (90% CI: 0.03, 0.67) respectively, suggesting that children with endemic Burkitt's lymphoma were more likely than controls to be last-born. Children with endemic Burkitt's lymphoma were also more likely to live in non-monogamous families (OR=3.12, 90% CI:1.19, 8.17) and to have at least one deceased parent (OR=3.38, 90% CI: 1.18, 9.64). Household characteristics, especially sibship relationships, may contribute to endemic Burkitt's lymphoma and therefore warrant further study.

Endemic Burkitt's lymphoma (eBL) has been linked to Epstein-Barr virus and holoendemic Plasmodium falciparum malaria. These co-infections, however, are insufficient to explain the non-random occurrence of Endemic Burkitt's lymphoma within Equatorial Africa. To explore whether this distribution could be explained by household characteristics and family environment, we conducted a case-control study using 41 hospitalized incident endemic Burkitt's lymphoma cases and 91 healthy controls identified through a population-based multistage cluster-sampling scheme in Nyanza Province, Kenya. In a multivariate analysis, odds ratios associated with having one, two, and three or more younger siblings compared with none were 0.28 (90% CI: 0.09, 0.83), 0.59 (90% CI: 0.16, 2.23) and 0.15 (90% CI: 0.03, 0.67) respectively, suggesting that children with endemic Burkitt's lymphoma were more likely than controls to be last-born. Children with endemic Burkitt's lymphoma were also more likely to live in non-monogamous families (OR=3.12, 90% CI:1.19, 8.17) and to have at least one deceased parent (OR=3.38, 90% CI: 1.18, 9.64). Household characteristics, especially sibship relationships, may contribute to endemic Burkitt's lymphoma and therefore warrant further study.

Background Malaria epidemics in highland areas of East Africa have caused considerable morbidity and mortality in the past two decades. Knowledge of "hotspot" areas of high malaria incidence would allow for focused preventive interventions in resource-poor areas, particularly if the hotspot areas can be discerned during non-epidemic periods and predicted by ecological factors. Methods To address this issue, spatial distribution of malaria incidence and the relationship of ecological factors to malaria incidence were assessed in the highland area of Kipsamoite, Kenya, from 2001–2004. Results Clustering of disease in a single geographic "hotspot" area occurred in epidemic and non-epidemic years, with a 2.6 to 3.2-fold increased risk of malaria inside the hotspot, as compared to outside the area (P < 0.001, all 4 years). Altitude and proximity to the forest were independently associated with increased malaria risk in all years, including epidemic and non-epidemic years. Conclusion In this highland area, areas of high malaria risk are consistent in epidemic and non-epidemic years and are associated with specific ecological risk factors. Ongoing interventions in areas of ecological risk factors could be a cost-effective method of significantly reducing malaria incidence and blunting or preventing epidemics, even in the absence of malaria early warning systems. Further studies should be conducted to see if these findings hold true in varied highland settings.