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Background In 2019, the RTS,S/AS01 E malaria vaccine was introduced on a pilot basis in six regions of Ghana by the Ministry of Health/Ghana Health Service as part of the WHO-coordinated Malaria Vaccine Implementation Programme (MVIP). This is the first time a malaria vaccination programme has been implemented in any country. This paper describes the challenges faced, and lessons learned, during the planning and early implementation of the RTS,S/AS01 E vaccine in three out of the six regions that implemented the programme in Ghana. Methods Twenty-one in-depth interviews were conducted with regional and district health service managers and frontline health workers three months after the start of MVIP in May 2019. Data were coded using NVivo software version 12 and a coding framework was developed to support thematic analysis to identify the challenges and lessons learned during the RTS,S/AS01 E implementation pilot, which were also categorized into the Consolidated Framework for Implementation Research (CFIR). Results Participants reported challenges related to the characteristics of the intervention, such as issues with the vaccine schedule and eligibility criteria, and challenges related to how it was implemented as a pilot programme. Additionally, major challenges were faced due to the spread of rumours leading to vaccine refusals; thus, the outer setting of the CFIR was adapted to accommodate rumours within the community context. Health service managers and frontline health workers also experienced challenges with the process of implementing RTS,S/AS01 E , including inadequate sensitization and training, as well as issues with the timeline. They also experienced challenges associated with the features of the systems within which the vaccine was being implemented, including inadequate resources for cold-chain at the health facility level and transportation at the district and health facility levels. This study identified the need for a longer, more intensive and sustained delivery of contextually-appropriate sensitization prior to implementation of a programme such as MVIP. Conclusions This study identified 12 main challenges and lessons learned by health service managers and health workers during the planning and early implementation phases of the RTS,S/AS01 E pilot introduction in Ghana. These findings are highly relevant to the likely scale-up of RTS,S/AS01 E within Ghana and possible implementation in other African countries, as well as to other future introductions of novel vaccines.

The RTS,S/AS01 malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use. In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission. By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury). In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S. Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Anaemia in young sub-Saharan African children may be due to the double burden of malaria and iron deficiency. Primary analysis of a double-blind, cluster randomized trial of iron containing micronutrient powder supplementation in Ghanaian children aged 6 to 35 months found no difference in malaria risk between intervention and placebo groups. Here, we performed a secondary analysis of the trial data to assess the impact of long-term prophylactic iron fortificant on the risk of iron deficiency and anaemia in trial subjects. This population-based randomized-cluster trial involved 1958 children aged between 6 to 35 months, identified at home and able to eat semi-solid foods. The intervention group (n = 967) received a daily dose containing 12.5 mg elemental iron (as ferrous fumarate), vitamin A (400 μg), ascorbic acid (30 mg) and zinc (5 mg). The placebo group (n = 991) received a similar micronutrient powder but without iron. Micronutrient powder was provided daily to both groups for 5 months. At baseline and endline, health assessment questionnaires were administered and blood samples collected for analysis. The two groups had similar baseline anthropometry, anaemia, iron status, demographic characteristics, and dietary intakes (p > 0.05). Of the 1904 (97.2%) children who remained at the end of the intervention, the intervention group had significantly higher haemoglobin (p = 0.0001) and serum ferritin (p = 0.0002) levels than the placebo group. Soluble transferrin receptor levels were more saturated among children from the iron group compared to non-iron group (p = 0.012). Anaemia status in the iron group improved compared to the placebo group (p = 0.03). Continued long-term routine use of micronutrient powder containing prophylactic iron reduced anaemia, iron deficiency and iron deficiency anaemia among pre-school children living in rural Ghana’s malaria endemic area.

Iron fortification and micronutrient initiatives, specifically, vitamin A, and zinc supplementation are the most cost-effective developmental strategies against malnutrition and health emergencies in pre-school children. Iron-deficiency among pre-school children have been documented, however, studies evaluating the impact of immunoglobulin G (IgG) isotype responses among iron-fortified pre-school children in malaria endemic communities has not been assessed. We evaluated the impact of iron fortification on the IgG responses to GLURP R0, GLURP R2 and MSP3 FVO malaria-specific antigens among pre-school children in malaria endemic areas. This community-based, placebo-controlled, double-blinded, cluster-randomized trial study was conducted in Wenchi Municipal and Tain District of Bono Region. The trial was registered at ClinicalTrials.gov-registered trial (Identifier: NCT01001871). Ethical approval was obtained and informed consent were sought from each participant parents/guardian. For the current objective, 871 children aged 6-35 months were screened, from which 435 children received semi-liquid home-made meals mixed with 12.5 mg of iron daily (intervention group), and 436 received micronutrient powder without iron (placebo group) for 5 months. Standardized clinical and epidemiological questionnaires were administered and blood samples taken to measure IgG responses to GLURP R0, GLURP R2 and MSP3 FVO recombinant antigens using the Afro Immunoassay (AIA) protocol. Baseline anthropometry, malaria diagnosis, anaemia and iron status, demographic features and dietary intake were identical among the groups (p > 0.05). After the intervention, there was no significant difference in the IgG response against GLUP R0, GLUP R2 and MSP3 FVO between the iron-containing micronutrient and placebo groups (p > 0.05). The iron-containing micronutrient powder group who were iron-sufficient or iron replete had significantly higher IgG response to GLURP R0 and GLURP R2 compared to iron-deficient and iron-deficiency anaemia in the same group (p < 0.05). The IgG responses to all the three malaria specific antigens were low among children without malaria episode but high among those with two and four episodes due to exposure differences. Iron fortification did not influence antibody response against endogenous malaria specific antigens among pre-school children in malaria endemic areas, however, IgG response to malaria specific antigens were high among children with sufficient iron status.

In 2009, on the basis of promising evidence from trials in south Asia, WHO and UNICEF issued a joint statement about home visits as a strategy to improve newborn survival. In the Newhints trial, we aimed to test this home-visits strategy in sub-Saharan Africa by assessing the effect on all-cause neonatal mortality rate (NMR) and essential newborn-care practices. The Newhints cluster randomised trial was undertaken in 98 zones in seven districts in the Brong Ahafo Region, Ghana. 49 zones were randomly assigned to the Newhints intervention and 49 to the control intervention by use of restricted randomisation with stratification to ensure comparability between interventions. Community-based surveillance volunteers (CBSVs) in Newhints zones were trained to identify pregnant women in their community and to make two home visits during pregnancy and three in the first week of life to promote essential newborn-care practices, weigh and assess babies for danger signs, and refer as necessary. Primary outcomes were NMR and coverage of key essential newborn-care practices. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00623337. 16 168 (99%) of 16 329 deliveries between November, 2008, and December, 2009, were livebirths; the status at 1 month was known for 15 619 (97%) livebirths. 482 neonatal deaths were recorded. Coverage data were available from 6029 women in Newhints zones; of these 4358 (72%) reported having CBSV visits during pregnancy and 3815 (63%) reported having postnatal visits. This coverage increased substantially from June, 2009, after the introduction of new implementation strategies and reached almost 90% for pregnancy visits by the end of the trial and 75% for postnatal visits. The Newhints intervention significantly increased coverage of key essential newborn-care behaviours, except for four or more antenatal-care visits (5975 [76%] of 7859 vs 5988 [74%] of 8121, respectively; relative risk 1·02, 95% CI 0·96–1·09; p=0·52) and baby delivered in a facility (5373 [68%] vs 5539 [68%], respectively; 0·97, 0·81–1·14; p=0·69). The largest increase was for care-seeking, with 102 (77%) of 132 sick babies in Newhints zones taken to a hospital or clinic compared with 77 (55%) of 139 in control zones (1·43, 1·17–1·76; p=0·001). Increases were also noted in bednet use during pregnancy (5398 [69%] of 7859 vs 5135 [63%] of 8121, respectively; 1·12, 1·03–1·21; p=0·005), money saved for delivery or emergency (5730 [86%] of 6681 vs 5525 [80%] of 6941, respectively; 1·09, 1·05–1·12; p<0·0001), transport arranged in advance for facility (2496 [37%] vs 2061 [30%], respectively; 1·30, 1·12–1·49; p=0·0004), birth assistant for home delivery washed hands with soap (1853 [93%] of 1992 vs 1817 [87%] of 2091, respectively; 1·05, 1·02–1·09; p=0·001), initiation of breastfeeding in less than 1 h of birth (3743 [49%] of 7673 vs 3280 [41%] of 7921, respectively; 1·22, 1·07–1·40; p=0·004), skin to skin contact (3355 [44%] vs 1931 [24%], respectively; 2·30, 1·85–2·87; p=0·0002), first bath delayed for longer than 6 h (3131 [41%] vs 2269 [29%], respectively; 1·65, 1·27–2·13; p<0·0001), exclusive breastfeeding for 26–32 days (1217 [86%] of 1414 vs 1091 [80%] of 1371; 1·10, 1·04–1·16; p=0·001), and baby sleeping under bednet for 8–56 days (4548 [79%] of 5756 vs 4291 [73%] of 5846; 1·09, 1·03–1·15; p=0·002). There were 230 neonatal deaths in the Newhints zones compared with 252 in the control zones. The overall NMRs per 1000 livebirths were 29·8 and 31·9, respectively (0·92, 0·75–1·12; p=0·405). The reduction in NMR with Newhints is consistent with the reductions achieved in three trials undertaken in programme settings in south Asia. Because there is no suggestion of any heterogeneity (p=0·850) between these trials and Newhints, the meta-analysis summary estimate of a reduction of 12% (95% CI 5–18) provides the best evidence for the likely effect of the home-visits strategy delivered within programmes in sub-Saharan Africa and in south Asia. Improvements in the quality of delivery and neonatal care in health facilities and development of innovative, effective strategies to increase coverage of home visits on the day of birth could lead to the achievement of more substantial reductions. WHO, Bill & Melinda Gates Foundation, and UK Department for International Development.

High rates of childhood vaccination defaulting remain a significant barrier to achieving full vaccination coverage in sub-Saharan Africa, contributing to preventable morbidity and mortality. This study evaluated the utility of machine learning algorithms for predicting childhood vaccination defaulters in Ghana, addressing the limitations of traditional statistical methods when handling complex, high-dimensional health data. Using a merged dataset from two malaria vaccine pilot surveys, we engineered novel temporal features, including vaccination timing windows and birth seasonality. Six algorithms, namely logistic regression, support vector machine, random forest, gradient boosting machine, extreme gradient boosting, and artificial neural networks, were compared. Models were trained and validated on both original and synthetically balanced and augmented data. The results showed higher performance across the ensemble tree classifiers. The random forest and extreme gradient boosting models reported the highest F1 scores (0.92) and AUCs (0.95) on augmented unseen data. The key predictors identified include timely receipt of birth and week six vaccines, the child’s age, household wealth index, and maternal education. The findings demonstrate that robust machine learning frameworks, combined with temporal and contextual feature engineering, can improve defaulter risk prediction accuracy. Integrating such models into routine immunization programs could enable data-driven targeting of high-risk groups, supporting policymakers in strategies to close vaccination coverage gaps.

Background The Expanded Programme on Immunization (EPI) is the most successful global childhood programme in reducing mortality and morbidity from vaccine-preventable diseases. Introducing the RTS, S/AS01 malaria vaccine into the routine health system added additional vaccination visits at 24 months. This study determined the factors contributing to compliance with EPI, including RTS, S/AS01 malaria vaccine schedules in the Central Tongu District of Ghana. Methods A matched case–control study (1:1) was undertaken between December 2021 and February 2022 among caregivers of children aged 24 to 40 months. Mantel-Haenzel odds ratio and conditional logistic regression analysis were used to determine the strength of association between the level of compliance and independent variables. Results Of the 220 caregivers,110 were cases, and 110 were controls. Good knowledge about vaccines and vaccination schedules among caregivers was 62% (n = 139). Caregivers who earned income 46% (OR MH 0.54, 95% CI 0.29–1.00, p = 0.047); had immunization information 98% (OR MH 0.02, 95% CI 0.00–0.12, p = 0.001); with no obstacles accessing immunization services 98% (OR MH 0.02, 95% CI 0.00–0.12, p < 0.001) and had good knowledge about immunization schedules 70% (OR MH 0.30, 95% CI 0.15–0.61, p < 0.001) were more likely to comply with childhood vaccination. Knowledge of (EPI) services, including RTS, S/AS01 malaria vaccine, was associated with high compliance to overall immunization services and schedules 78% (AOR 0.22, 95% CI 0.06–0.78, p = 0.019). Conclusion Non-compliance with recommended EPI vaccinations, including RTS,S/AS01 , was largely due to socio-economic factors, having information and knowledge about vaccines, immunization schedules, and access to immunization services. Healthcare providers can improve immunization coverage by emphasizing education on vaccines and vaccine schedules, using technologies and making services accessible in Ghana.

Introduction Africa has a higher burden of malaria-related cases and deaths globally. Children under five accounted for over two-thirds of all malaria deaths in sub-Saharan Africa (SSA). This scoping review aims to map evidence of the prevalence, contextual factors and health education interventions of malaria amongst children under 5 years (UN5) in SSA. Method Four main databases (PubMed, Central, Dimensions and JSTOR) produced 27,841 records of literature. Additional searches in Google, Google Scholar and institutional repositories produced 37 records. Finally, 255 full-text records were further screened, and 100 records were used for this review. Results Low or no formal education, poverty or low income and rural areas are risk factors for malaria amongst UN5. Evidence on age and malnutrition as risk factors for malaria in UN5 is inconsistent and inconclusive. Furthermore, the poor housing system in SSA and the unavailability of electricity in rural areas and unclean water make UN5 more susceptible to malaria. Health education and promotion interventions have significantly reduced the malaria burden on UN5 in SSA. Conclusion Well-planned and resourced health education and promotion interventions that focus on prevention, testing and treatment of malaria could reduce malaria burden amongst UN5 in SSA.

Results of randomised controlled trials of newborn (age 1–3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana. This study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50 000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055. We assessed 26 414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22 955 newborn infants, with 11 474 randomly assigned to receive vitamin A and 11 481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22 698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95–1·33; p=0·183) and risk difference (RD) 2·66 (95% CI −1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94–1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88–2·62, p=0·130). The results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana. Bill & Melinda Gates Foundation grant to the WHO.

Background In 2019, the RTS,S/AS01 E malaria vaccine (RTS,S) was introduced into Ghana’s routine health system as part of the Malaria Vaccine Implementation Programme (MVIP). Household surveys were conducted prior to vaccine introduction and approximately 18 and 30 months post-introduction. We present a description of the area in Ghana based on the baseline household survey including malaria prevalence, malnutrition, wealth, insecticide-treated net (ITN) coverage, other health interventions (deworming, Vitamin A supplementation (VAS)), coverage of Expanded Programme on Immunization (EPI) vaccines, and health-seeking behaviour for febrile children. Methods The baseline household survey was conducted between 25 February and 18 March 2019 in a representative sample of 6778 households across 66 districts (33 in each of the implementing and comparator areas) in Ghana. Caregivers of children aged 5–48 months were interviewed. For each child, vaccination details were transcribed from the maternal and child health record book, and we measured the mid-upper arm circumference and obtained a malaria Rapid Diagnostic Test (RDT). Survey-weighted coverage estimates were obtained using standard survey methods. Survey Poisson regression was used to estimate prevalence ratios. Results Overall, 7768 children were included in the study, and 21% (95% CI 18–23) tested positive for malaria parasitemia by RDT. About 87%, 95%CI (85–89) of all households owned at least one ITN, and 62%, 95%CI (59–64) of children aged 5–48 months slept under an insecticide-treated net (ITN) the night before the survey. Additionally, 22%, 95%CI (21–24) of children reported having fever in the two weeks preceding the survey; among those with reported fever, 72%, 95%CI (69–74) sought advice or treatment, 40%, 95%CI (37–44) were tested for malaria, and 42%, 95%CI (39–46) of those with fever took an antimalarial drug. Additionally, 17%, 95%CI (16–19) had a mid-upper arm circumference (MUAC) ≤ 13.5 cm, and 1%, 95%CI (0–1) had a (MUAC) ≤ 11.5 cm. The uptake of vitamin A VAS in the 6 months prior to the survey was 36%, based on routine delivery through EPI, and deworming coverage was 29%. Coverage of EPI vaccines was > 90%. Indicators in comparison and implementation areas were comparable. Conclusions The pilot implementation and evaluation of the RTS,S malaria vaccine in Ghana was conducted in an area with substantial malaria transmission and illness, modest health-seeking behaviour and ITN use, and good EPI vaccine coverage. This study has established the baseline comparability between implementation and comparator areas, which serves as the foundation for future feasibility assessments.