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Abstract Background Vulnerable children, including those with neuro-developmental delays and disabilities, often face barriers in accessing early primary education, thus hindering progress toward Sustainable Development Goal 4.2. Evidence-based interventions are essential to enhancing inclusivity and establishing sustainable implementation strategies to address this challenge. This study, Every Newborn—Reach up Early Education Intervention for All Children (EN-REACH), builds on the previous Every Newborn- Simplified Measurement Integrating Longitudinal Neurodevelopmental and Growth (EN-SMILING) observational cohort study. This paper provides the protocol for a cluster randomized controlled trial (cRCT) to evaluate the effectiveness of a parenting group intervention program for enhancing school readiness in Bangladesh, Nepal, and Tanzania, and an embedded process evaluation to inform scalability and feasibility. Methods EN-REACH is a cRCT with at least 150 clusters to evaluate the impact of a parent training program led by trained parent-teacher facilitator pairs, focusing on children aged 4 ~ 6 years preparing for preschool. Approximately 500 participants from the EN-SMILING cohort at each site have been identified. A geographic information system will define ~ 50 clusters in each of the three countries, each with approximately ten parent–child dyads. Half the clusters will be randomly assigned to intervention and control groups. The primary outcome is “school readiness”, assessed using the Measuring Early Learning Quality and Outcomes tool. Secondary outcomes include Intelligence Quotient, child functioning, growth, visual, and hearing assessments. Data will be collected at baseline, and post-intervention data following implementation of the parent group intervention sessions over approximately 5 months. Quantitative data on coverage and quality care, combined with qualitative insights from children, caregivers, facilitators, and stakeholders’ perspectives, will be used to conduct a process evaluation applying the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Discussion This protocol details a trial focused on enhancing school readiness and cognitive abilities in young children, inclusive of those with disabilities, aiming to bridge gap from home to early primary education. EN-REACH aims to provide insights into the effectiveness and acceptability of a co-designed disability-inclusive school readiness program in three countries, potentially impacting national and global policies for all children, including those with disabilities. Trial registration The trial was retrospectively registered on clinicaltrials.gov on 29 February 2024 (NCT06334627).

BackgroundParasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome.MethodsA matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community.ResultsIn simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia.ConclusionThe findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.

Objectives: Malaria is still one of the main reasons for hospitalization in children living in sub-Saharan Africa. Rapid risk stratification at admission is essential for optimal medical care and improved prognosis. Whereas coma, deep breathing, and, to a lesser degree, severe anemia are established predictors of malaria-related death, the value of assessing prostration for risk stratification is less certain. Methods: Here we used a retrospective multi-center analysis comprising over 33,000 hospitalized children from four large studies, including two observational studies from the Severe Malaria in African Children network, a randomized controlled treatment study, and the phase-3-clinical RTS,S-malaria vaccine trial, to evaluate known risk factors of mortality and with a specific emphasis on the role of prostration. Results: Despite comparable age profiles of the participants, we found significant inter- and intra-study variation in the incidence of fatal malaria as well as in the derived risk ratios associated with the four risk factors: coma, deep breathing, anemia, and prostration. Despite pronounced variations, prostration was significantly associated with an increased risk of mortality (P

A phase III, double-blind, randomized, controlled trial (NCT00866619) in sub-Saharan Africa showed RTS,S/AS01 vaccine efficacy against malaria. We now present in-depth safety results from this study. 8922 children (enrolled at 5–17 months) and 6537 infants (enrolled at 6–12 weeks) were 1:1:1-randomized to receive 4 doses of RTS,S/AS01 (R3R) or non-malaria control vaccine (C3C), or 3 RTS,S/AS01 doses plus control (R3C). Aggregate safety data were reviewed by a multi-functional team. Severe malaria with Blantyre Coma Score ≤2 (cerebral malaria [CM]) and gender-specific mortality were assessed post-hoc. Serious adverse event (SAE) and fatal SAE incidences throughout the study were 24.2%–28.4% and 1.5%–2.5%, respectively across groups; 0.0%–0.3% of participants reported vaccination-related SAEs. The incidence of febrile convulsions in children was higher during the first 2–3 days post-vaccination with RTS,S/AS01 than with control vaccine, consistent with the time window of post-vaccination febrile reactions in this study (mostly the day after vaccination). A statistically significant numerical imbalance was observed for meningitis cases in children (R3R: 11, R3C: 10, C3C: 1) but not in infants. CM cases were more frequent in RTS,S/AS01-vaccinated children (R3R: 19, R3C: 24, C3C: 10) but not in infants. All-cause mortality was higher in RTS,S/AS01-vaccinated versus control girls (2.4% vs 1.3%, all ages) in our setting with low overall mortality. The observed meningitis and CM signals are considered likely chance findings, that – given their severity – warrant further evaluation in phase IV studies and WHO-led pilot implementation programs to establish the RTS,S/AS01 benefit-risk profile in real-life settings.

BackgroundFebrile illness is the commonest cause of hospitalization in children four million genomes/μL) of P. falciparum in plasma. Overall, in-hospital death was 4% (89/2,146), and it was higher in children with bacteraemia (8%, 18/227) than malaria (2%, 4/194, p = 0.007). Risk factors for death were bacteraemia (p = 0.03), unconsciousness at admission (p < 0.001), and admission at a tertiary hospital (p = 0.003).ConclusionCompared to previous studies in this region, our study showed a reduction in malaria prevalence, a decrease in in-hospital mortality, and an increase in antimicrobial resistance (AMR) including ESBLs and multidrug resistance. An increase of AMR highlights the importance of continued strengthening of diagnostic capability and antimicrobial stewardship programs. We also found malaria and bacteraemia contributed equally in causing febrile illness, but bacteraemia caused higher in-hospital death. The most severe form of clinical malaria was associated with P. falciparum parasitaemia.