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 vectorbased 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. 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. 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]). 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. Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.

Vaccination has been shown to reduce mortality and morbidity due to vaccine-preventable diseases. However, these diseases are still responsible for majority of childhood deaths worldwide especially in the developing countries. This may be due to low vaccine coverage or delay in receipt of age-appropriate vaccines. We studied the timeliness of routine vaccinations among children aged 12–59 months attending infant welfare clinics in semi-urban areas of The Gambia, a country with high vaccine coverage. A cross-sectional survey was conducted in four health centres in the Western Region of the Gambia. Vaccination dates were obtained from health cards and timeliness assessed based on the recommended age ranges for BCG (birth–8 weeks), Diphtheria-Pertussis–Tetanus (6 weeks–4 months; 10 weeks–5 months; 14 weeks–6 months) and measles vaccines (38 weeks–12 months). Risk factors for delay in age-appropriate vaccinations were determined using logistic regression. Analysis was limited to BCG, third dose of Diphtheria-Pertussis -Tetanus (DPT3) and measles vaccines. Vaccination records of 1154 children were studied. Overall, 63.3 % (95 % CI 60.6–66.1 %) of the children had a delay in the recommended time to receiving at least one of the studied vaccines. The proportion of children with delayed vaccinations increased from BCG [5.8 % (95 % CI 4.5–7.0 %)] to DPT3 [60.4 % (95 % CI 57.9 %-63.0 %)] but was comparatively low for the measles vaccine [10.8 % (95 % CI 9.1 %–12.5 %)]. Mothers of affected children gave reasons for the delay, and their profile correlated with type of occupation, place of birth and mode of transportation to the health facilities. Despite high vaccination coverage reported in The Gambia, a significant proportion of the children’s vaccines were delayed for reasons related to health services as well as profile of mothers. These findings are likely to obtain in several countries and should be addressed by programme managers in order to improve and optimize the impact of the immunization coverage rates.

Background: Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries.Methodology/Principal findings: We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in endemic countries. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane’s Q and evaluated the severity of heterogeneity using I²statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger’s test (bias if p<0.1).Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence ofPlasmodium-helminth co-infections of 17.7% (95% CI 12.7–23.2%). Summary estimates from 14 studies showed a lower odds ofP.falciparuminfection in children co-infected withSchistosoma spp(OR: 0.65; 95%CI: 0.37–1.16). Similar lower odds ofP.falciparuminfection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28–0.64).When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk ofP.falciparuminfection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03–1.65).A subset of 16 studies showed that the odds of anaemia were higher in children co-infected withPlasmodiumand STH than in children withPlasmodiuminfection alone (OR = 1.20; 95% CI: 0.59–2.45), and were almost equal in children co-infected withPlasmodium-Schistosoma spporPlasmodiuminfection alone (OR = 0.97, 95% CI: 0.30–3.14).Conclusions/Significance: The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.

Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI). We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns. ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC). ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted. Pactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430

To induce a deployable level of efficacy, a successful malaria vaccine would likely benefit from both potent cellular and humoral immunity. These requirements are met by a heterologous prime-boost immunization strategy employing a chimpanzee adenovirus vector followed by modified vaccinia Ankara (MVA), both encoding the pre-erythrocytic malaria antigen ME-thrombospondin-related adhesive protein (TRAP), with high immunogenicity and significant efficacy in UK adults. We undertook two phase 1b open-label studies in adults in Kenya and The Gambia in areas of similar seasonal malaria transmission dynamics and have previously reported safety and basic immunogenicity data. We now report flow cytometry and additional interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) data characterizing pre-existing and induced cellular immunity as well as anti-TRAP IgG responses. T-cell responses induced by vaccination averaged 1,254 spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) across both trials and flow cytometry revealed cytokine production from both CD4⁺ and CD8⁺ T cells with the frequency of CD8⁺ IFN-γ-secreting monofunctional T cells (previously shown to associate with vaccine efficacy) particularly high in Kenyan adults. Immunization with ChAd63 and MVA ME-TRAP induced strong cellular and humoral immune responses in adults living in two malaria-endemic regions of Africa. This prime-boost approach targeting the pre-erythrocytic stage of the malaria life-cycle is now being assessed for efficacy in a target population.