2 research outputs found
Effectiveness of the RTS,S/AS01E malaria vaccine in a real-world setting over 1 year of follow-up after the three-dose primary schedule: an interim analysis of a phase 4 study in Ghana, Kenya, and Malawi.
No full textBACKGROUND: RTS,S/AS01E was first introduced within the Malaria Vaccine Implementation Programme in selected areas in Ghana, Kenya, and Malawi. A series of post-introduction observational studies were initiated in these areas to assess RTS,S/AS01E safety and effectiveness in real-world settings. Here, we report the results of the interim analysis of the EPI-MAL-003 study secondary objectives related to vaccine effectiveness. METHODS: EPI-MAL-003 was a phase 4, disease surveillance study with prospective cohort event monitoring. The study was performed in routine medical practice settings at 12 sites (four per country) in Ghana, Kenya, and Malawi. Children younger than 18 months were enrolled in exposed clusters (sites where RTS,S/AS01E was introduced) and unexposed clusters; data were collected via active surveillance. In an interim analysis, we estimated the effect of vaccination on the incidence of malaria, all-cause hospitalisations, and malaria-related hospitalisations, the prevalence of anaemia among hospitalised children, and mortality over 1 year of follow-up after primary vaccination with three RTS,S/AS01E doses. These endpoints were analysed in the effectiveness analysis set. The primary endpoints are reported elsewhere, together with secondary safety endpoints. This study is registered with ClinicalTrials.gov, NCT03855995, and is completed. FINDINGS: The first child was enrolled on March 21, 2019, and the cutoff date for the current analysis was Nov 2, 2023. 45 000 children were enrolled (22 426 [49·8%] were female and 22 574 [50·25%] were male). 39 463 children were included in the analyses. When comparing vaccinated children from exposed clusters with unvaccinated children from unexposed clusters, country-adjusted incidence rate ratios were 0·70 (95% CI 0·67-0·73; p<0·001) for any malaria, 0·42 (0·30-0·60; p<0·001) for severe malaria, 0·64 (0·56-0·72; p<0·001) for malaria-related hospitalisations, 0·79 (0·74-0·84; p<0·001) for all-cause hospitalisations, and 0·83 (0·64-1·09; p=0·18) for all-cause mortality. The adjusted odds ratio for the prevalence of anaemia among children who were hospitalised (vaccinated children from exposed clusters vs unvaccinated children from unexposed clusters) was 0·81 (95% CI 0·73-0·90; p<0·001). Similar trends were observed in a before-after comparison with unvaccinated children enrolled in the EPI-MAL-002 study conducted before the RTS,S/AS01E introduction. INTERPRETATION: Over 1 year of follow-up after the third vaccine dose, vaccination with RTS,S/AS01E in real-world settings showed significant reductions in malaria burden. These findings reinforce the continued use of RTS,S/AS01E vaccination in children as an effective public health measure to reduce malaria-related illness and mortality in endemic regions, and highlight its relevance for future malaria control strategies. FUNDING: GSK
Safety of RTS,S/AS01E malaria vaccine up to 1 year after the third dose in Ghana, Kenya, and Malawi (EPI-MAL-003): a phase 4 cohort event monitoring study
No full textBackground: RTS,S/AS01E has been successfully administered to over two million children since 2019 through the Malaria Vaccine Implementation Programme (MVIP). In this Article, we report the safety results of a study evaluating RTS,S/AS01E safety and effectiveness in real-world settings. Methods: EPI-MAL-003 is an ongoing phase 4 disease surveillance study with prospective cohort event monitoring and hospital-based surveillance, done in the setting of routine health-care practice in Ghana, Kenya, and Malawi and fully embedded in the MVIP. The study design was dependent on the cluster-randomised vaccine implementation. In active surveillance, we enrolled children younger than 18 months from exposed (where RTS,S/AS01E was offered) and unexposed clusters. The coprimary endpoints were the occurrence of predefined adverse events of special interest and aetiology-confirmed meningitis. We report primary and secondary safety results up to 1 year after the primary vaccine schedule (three doses). The study is registered with ClinicalTrials.gov, NCT03855995. Findings: The first participant was enrolled on March 21, 2019. The cutoff date for the current analysis was 1 year after the third RTS,S/AS01E dose for each participant. In total, 44 912 children (19 993 in Ghana, 11 990 in Kenya, and 12 929 in Malawi) were included in the analysis set for the cluster-randomised comparison: 22 508 from exposed clusters and 22 404 from unexposed clusters. Incidence rates (expressed per 100 000 person-years) for generalised convulsive seizures and intussusception were similar between vaccinated and unvaccinated children. Aetiology-confirmed meningitis was reported in two children: one case of bacterial meningitis due to Streptococcus pneumoniae in an RTS,S/AS01E-vaccinated child in the exposed clusters, and one case of viral meningitis due to human herpesvirus 6 in an unvaccinated child in the unexposed clusters. Both cases occurred within 12 months after vaccination in children in the cluster-design analysis set, leading to incidence rates of 4·1 (95% CI 0·1–23·0) per 100 000 person-years in RTS,S/AS01E-vaccinated children and 4·0 (0·1–22·6) per 100 000 person-years in unvaccinated children, and a country-adjusted incidence rate ratio (IRR) of 0·96 (95% CI 0·06–15·34; p=0·98). Cerebral malaria cases were reported for four (E-vaccinated children in the exposed clusters and two (E-vaccinated children and unvaccinated children, respectively (IRR 1·43, 95% CI 0·24–8·58, p=0·70). Incidence rates for all-cause mortality were 659·7 (95% CI 561·5–770·3) in vaccinated children versus 724·5 (622·3–838·8) in unvaccinated children, with similar incidence rates for boys and girls. Interpretation: We found no evidence of vaccination being associated with an increased risk of meningitis, cerebral malaria, or mortality among vaccinated children, and no new safety risks were identified. Funding: GSK
