Pregnant women, particularly those in the first trimester, have been historically excluded from clinical trials, resulting in substantial evidence gaps for the prevention and treatment of malaria in early pregnancy. Despite increasing calls from global health and regulatory bodies to include pregnant women in research, ethical, socio-cultural, and contextual challenges continue to impede their meaningful participation. Formative research is essential to understanding these challenges and informing trial procedures that are ethically robust and contextually appropriate. This study aims to explore stakeholder perceptions, beliefs, and decision-making processes related to early pregnancy and participation in clinical trials, to inform the development of culturally sensitive recruitment, retention, and community engagement strategies for the multi-country SAFIRE clinical trial on the safety and efficacy of artemisinin-combination therapies. Qualitative methods include in-depth interviews and focus group discussions with purposively sampled women of childbearing age, pregnant women, health providers and managers, community leaders, and other key health decision-makers. Data will be collected across five malaria-endemic countries in sub-Saharan Africa. A reflexive thematic analysis approach will be used, combining inductive and deductive coding within a collaboratively developed coding framework. Analysis will be informed by a Theory of Change to examine how identified barriers and facilitators may influence pathways to successful recruitment and retention. This protocol demonstrates how formative research can be systematically integrated into clinical trials to support the ethical inclusion of pregnant women.

Background:It is unknown whether the choice of malaria treatment for uncomplicated malaria affects coronavirus disease 2019 (COVID-19) severity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, or duration of viral shedding. Several antimalarials exhibit antiviral activity against SARS-CoV-2 in vitro and have been suggested as potential therapeutic candidates for COVID-19, particularly pyronaridine-artesunate (PA), despite disappointing clinical results with chloroquine and hydroxychloroquine. Methods:We conducted an open-label randomised trial comparing standard 3-day treatment with PA and artemether-lumefantrine (AL) in newly diagnosed SARS-CoV-2 infected patients aged ≥6 months with rapid diagnostic test or microscopy-confirmed non-severe malaria in Kenya and Burkina Faso. SARS-CoV-2 was assessed by RT-PCR on days 3, 7, 14, and 28, and symptom resolution was assessed daily for 14 days using FLU-PRO Plus. The primary endpoint was the proportion of participants with SARS-CoV-2 clearance by day 7. Secondary endpoints included SARS-CoV-2 clearance by days 14, 21, and 28, time to SARS-CoV-2 clearance over 28 days, median viral load on day 7, and time to symptom resolution. Complete case analysis was conducted using log-binomial regression for binary outcomes, Cox-regression for time-to-event outcomes, and negative binomial regression for count outcomes, all adjusted for disease severity and viral load at enrolment. The trial is registered with ClinicalTrials.gov NCT04695197. Findings:From January 2021 to January 2022, 143 participants were randomised (PA = 69, AL = 74, intention-to-treat [ITT] population), including 117 with reverse transcription polymerase chain reaction (RT-PCR) confirmed (PA = 58, AL = 59, modified intention-to-treat [mITT] population) and 26 with rapid-antigen test confirmed SARS-CoV-2 infection. The median age was 19 years (interquartile range [IQR] 13-38), 66% were aged ≥15 years. Baseline characteristics were comparable. SARS-CoV-2 clearance by day 7 (primary endpoint) was 41% (22/54) with PA versus 58% (33/57) with AL (adjusted risk ratio [aRR] = 0.78, 95% confidence interval [CI] 0.45-1.35, p = 0.37); by day-14: PA = 80% (44/55) versus AL = 96% (55/57) (aRR = 0.86, 0.58-1.29, p = 0.47). Median (IQR) viral load on day 7 was higher with PA (855 [30-2883] versus AL:81 [12-209] copies/mL, p = 0.023). Time to SARS-CoV-2 clearance over 28 days was slower with PA (adjusted hazard ratio [aHR]: 0.55, 0.37-0.83, p = 0.004). Time to symptom clearance between treatments was similar (aHR = 1.01, 0.91-1.13, p = 0.79). Parasitological cure rates by day 42 were PA = 100% and AL = 99%. Five serious adverse events occurred (PA = 2, AL = 3) in three participants (PA = 1, AL = 2), including three hospitalisations (PA = 1, AL = 2), resulting in two deaths, both from respiratory failure (PA = 1, AL = 1). No serious adverse events (SAEs) were considered treatment-related. Interpretation:Pyronaridine-artesunate in COVID-19 patients co-infected with malaria was associated with slower viral clearance than standard treatment with artemether-lumefantrine but similar symptom resolution. Both treatments were highly effective as antimalarials and should continue to be considered first- or second-line treatment options for uncomplicated malaria in patients with mild to moderate COVID-19. Funding:Gates Foundation.

Given limited data on SARS‑CoV‑2 transmission and immunity in rural, low‑vaccine‑coverage settings, we evaluated infection rates and population‑level neutralizing antibody increase in a rural community in western Kenya. The study was conducted at the KEMRI/WRAIR-Africa Health Demographic Surveillance System that has a population of 160,000. Clusters of households that had representative demographics were identified and individuals invited to participate in six cross-sectional surveys that targeted 234 participants at each survey, two months apart, conducted between April 2021 and March 2022, during which time, the Alpha, Delta and Omicron waves dominated. At each survey, participants provided naso-pharyngeal samples for SARS-CoV-2 detection and serum for measuring neutralizing antibodies (NAbs) using surrogate virus neutralizing test which assessed inhibition of RBD-ACE2 binding. 69% (917/1329) of the participants were females. By RT-qPCR, SARS-CoV-2 increased from 3% (7/224) at survey one (April 2021) to 24% (55/229) by survey two (June 2021), and thereafter decreased to zero, only to rise to 10% (23/234) during the January 2022 Omicron wave. NAbs increased from 18% (40/224) at survey one to 86% (202/234) by end of the study. The quantity of NAbs rose from geometric mean of 0.42 U/mL at survey one to 9.4 U/mL by survey six. Females had higher NAbs (3.73U/mL, 95% CI), compared to 1.98 U/mL, 95% CI (p = 0.0146) for males. NAbs quantities increased with age: 2.1 U/mL for <9 years, 2.6 U/mL for 10 - 19 years, 3.4 U/mL for 20 - 39 years, 3.8 U/mL for 40 - 59 years and 4.9 U/mL for >60 years. The increase in population-level NAbs is consistent with widespread exposure to the virus during the study period. As caveat, causality of NAbs for the decline in SARS‑CoV‑2 infections cannot be inferred with confidence, because other factors such as the use of non‑pharmaceutical interventions and other individual-level variables were not measured.

Background: Malaria is resurging in sub-Saharan Africa due to climate change, emerging drug and diagnostics resistance, new vectors and reduced international funding. These challenges highlight the need to expand access to malaria diagnosis and surveillance beyond the public sector. A large share of care seeking occurs in the private sector. Hence, strengthening connections with private providers has the potential to improve diagnostic coverage and close surveillance gaps. In Kenya ~ 40% of malaria cases are managed in the private sector, however data regarding the quality of care provided and malaria cases in this context remain largely unlinked to routine public malaria surveillance systems. Here we describe a digital mobile engagement of private community-based providers to expand malaria case detection and improve quality of care and completeness of surveillance data. Methods: A cross-sectional study was conducted in Kisumu County, Kenya engaging five private health facilities, 25 private chemists, and 50 community health promoters. Providers were digitally supported to perform and report malaria rapid diagnostic tests using an AI-enabled mobile application that captured photographic images of test outcomes and transmitted them to County surveillance dashboards. Analyses examined malaria positivity by provider type, demographic patterns of infection, and distribution of test outcomes across commonly used malaria test brands. Differences were assessed for statistical significance using chi-square tests. Results: Between July 2024 and June 2025, 26,090 malaria tests were recorded through an AI-supported digital surveillance system across private health facilities, private chemists, and community health promoters. Overall, 25,993/26,090 (99.6%) test records were valid; 7,035/25,993 (27.1%) were positive. Malaria positivity differed significantly by provider type: 1,523/3,930 (38.8%) among community health promoters, 3,260/9,364 (34.8%) among chemists, and 2,252/12,699 (17.7%) among private health facilities (p < 0.001). Positivity was highest among children. WHO prequalified malaria rapid diagnostic test brands showed significant heterogeneous positivity across provider types (all p < 0.001). Conclusions: Digitally integrating private and community-based providers into malaria surveillance substantially increases the capture of malaria cases into formal surveillance systems and provides important information for targeted quality improvement of the private sector diagnostic performance.

BACKGROUND:Malaria remains a major cause of mortality globally, especially among young children in sub-Saharan Africa. The long-acting monoclonal antibody L9LS has shown high efficacy in preventing malaria in children aged 6-10 years exposed to seasonal transmission but remains untested in perennial transmission settings and younger children. We assessed the safety, tolerability, and efficacy of L9LS in infants and children in a high perennial malaria transmission setting. METHODS:This double-blind, two-part, randomised, placebo-controlled, phase 2 trial was done in Siaya county in western Kenya. In parts 1a and 1b, we tested the safety and tolerability of L9LS using an age de-escalation and dose escalation approach and randomly assigned (3:1) cohorts of healthy children (three cohorts aged 5-10 years, three cohorts aged 5-59 months, and two cohorts aged 5-71 months) to L9LS at doses of 5, 10, 20, 30, or 40 mg/kg subcutaneously or to placebo (normal saline). In part 2, healthy children aged 5-59 months were randomly assigned (1:1:1) by use of centralised computer-generated lists to receive two doses of L9LS at 10-20 mg/kg at baseline and month 6, one dose of L9LS at baseline and placebo at month 6, or placebo at both timepoints. Children were followed up for 12 months with monthly clinic visits and blood smear collections. Primary safety outcomes were incidence and severity of local and systemic solicited adverse events within 7 days of dosing and serious adverse events throughout follow-up. The primary efficacy endpoint was Plasmodium falciparum infection detected by blood smear over 12 months. Primary analyses were done in the modified intention-to-treat population, consisting of all randomly assigned participants who received the study intervention. This trial is registered with ClinicalTrials.gov (NCT05400655) and is complete. FINDINGS:In parts 1a and 1b, 96 children were enrolled and randomly assigned between Oct 1, 2022, and Jan 16, 2024; 72 participants were assigned to L9LS and 24 were assigned to placebo. In part 2, 324 children aged 5-59 months were enrolled and randomly assigned between Jan 26 and June 2, 2023; 108 children were assigned to one-dose L9LS, 106 to two-dose L9LS, and 110 to placebo. Across all study parts, grade 3 or worse treatment-related adverse events occurred after four (1%) of 384 L9LS injections and two (1%) of 338 placebo injections; these events all resolved by study end. The proportion of solicited and unsolicited adverse events was similar across all L9LS dose groups. There were no serious adverse events related to the trial. In part 2, 70 (66%) of 106 children in the two-dose L9LS group had at least one P falciparum infection during the 12-month follow-up versus 91 (83%) of 110 children in the placebo group (protective efficacy 42·7%, 95% CI 22·5-57·7; p=0·0003). INTERPRETATION:L9LS was protective against malaria in young children in western Kenya without evident safety concerns over 6-12 months. A higher dose of L9LS might be needed to achieve high-level efficacy against malaria in young children exposed to intense perennial P falciparum transmission. FUNDING:Gates Foundation.

Abstract Malaria remains a major health challenge in western Kenya, where transmission persists despite decades of control efforts. Community health volunteers (CHVs) are increasingly engaged in community case management (CCM) to expand timely malaria care, but quantitative evidence of their contributions is limited. This analysis evaluated the effectiveness of CHVs in malaria case management and their impact on healthcare access in Siaya County. Data from 1.4 million encounters recorded by 936 CHVs and 86 health facilities (HFs) across 713 villages (2021–2023) were analyzed. The outcomes included coverage, testing practices, test positivity rates (TPRs), malaria incidence, and adherence to treatment guidelines. CHV coverage was defined as adequate at one CHV per ≤ 500 people; HF access was estimated via the two-step floating catchment area (2SFCA) method, incorporating proximity and utilization, with access scores classified as adequate or inadequate. CHV coverage was adequate for 82.5% of the villages vs. 30% for HFs. CHVs managed 28.1% of all encounters, including 12.1% of suspected malaria cases and 15.6% of rapid diagnostic test–positive cases. A greater proportion of CHV-suspected patients reported fever (77.0% vs. 53.1%). HFs more suspected and febrile cases, but afebrile testing was similar. CHVs recorded higher TPRs than HFs did (82.0% vs. 64.3%). Nearly all confirmed malaria cases received antimalarials. Incorporating CHV data increased malaria incidence estimates by 18% (467 vs. 549 per 1,000 population). CHVs extend access to malaria diagnosis and treatment, particularly in areas with limited HF coverage. Their practices align with national guidelines, and program expansion with adequate support could enhance malaria control in resource-limited settings.

Malaria continues to cause over 600,000 deaths annually in sub-Saharan Africa, disproportionately affecting children under five. Despite sustained control efforts, transmission remains highly sensitive to local environmental and climatic variability, underscoring the need for physically grounded models capable of capturing these dynamics. To address this challenge, we developed a high-resolution hybrid modeling framework linking WRF/WRF-Hydro and VECTRI. The framework integrates atmospheric, hydrological, ecological, and intervention processes at 1 km and 50 m resolutions and includes a new compartment for insecticide-treated net (ITN) coverage. Using data from 2007–2022 in western Kenya, a period of large-scale ITN deployment, the model reproduced observed malaria trends with a mean monthly deviation of ±100–150 cases. Simulations showed that ITN coverage reduced the entomological inoculation rate and malaria incidence by 58

Environmental enteric dysfunction, universal in young children exposed to poor sanitation and hygiene, impairs growth and development through malabsorption and as a driver of chronic systemic inflammation (CSI). In an open-label, randomized, four-arm, phase II clinical trial, infants with birthweight ≥2000 g in Homa Bay County, western Kenya receive live, multi-strain Bifidobacterium spp. and Lactobacillaceae pro/synbiotics from 0 to 6 months. CSI (plasma α1-acid glycoprotein >1 g/L) at age 6 months (primary outcome) occurs in 60/138 (43%) controls versus 4/144 (3%; risk ratio [RR], 0.06; 95% confidence interval [CI], 0.02-0.17) infants in the Labinic synbiotic arm, 3/132 (2%; RR = 0.05; 95% CI, 0.02-0.16) in the Lab4b synbiotic arm, and 3/141 (2%; RR, 0.05; 95% CI, 0.02-0.15) in the Lab4b probiotic arm. Biomarkers of gut health and growth hormones also improve, and no serious adverse events are attributed to the interventions. Pro/synbiotics safely and markedly reduce CSI in a highly disadvantaged population, warranting further investigation of health impacts. The trial is registered at https://pactr.samrc.ac.za; identifier: PACTR202003893276712.

BACKGROUND:Quantifying the impact of malaria vaccines on outpatient malaria burden in children is of interest to many countries introducing either of the World Health Organization (WHO)-recommended vaccines (RTS,S/AS01 [RTS,S] or R21/Matrix-M [R21]). The cluster randomized implementation of RTS,S by the Kenya Ministry of Health during the Malaria Vaccine Implementation Programme (MVIP) provided a unique opportunity to measure the impact of RTS,S on uncomplicated malaria cases reported through routine malaria case surveillance data in western Kenya. METHODS:From 23 implementing and 23 comparison subcounties in western Kenya, monthly numbers of confirmed uncomplicated malaria cases among individuals under 5 years of age (< 5y) and 5 years of age and older (≥ 5y) were extracted from the Kenya Health Management Information System, stored in a DHIS2 instance. Facilities that reported data ≥ 11 months per year from January 2015 through December 2022 (132 implementing, 139 comparison) were included in the analysis. Prevaccination data (January 2015-December 2019) were used to predict counterfactual case counts during the evaluation period (January 2020-December 2022), beginning when the first children vaccinated under MVIP became age-eligible for the third dose. Models of < 5y malaria cases included a covariate for ≥ 5y malaria cases to control for non-RTS,S malaria control measures. The impact was estimated as the difference between predicted and observed cases across implementing and comparison areas. RESULTS:The proportion of vaccine eligible children (RTS,S doses at 6, 7, 9, and 24 months) among all children < 5y was small at the start of MVIP but was estimated to reach 60% by December 2022. During the 3-year evaluation period following dose-3 age-eligibility, < 5y malaria cases were 2.3% lower than predicted in non-implementing facilities and 13.8% lower in implementing facilities, a reduction of 11.6%. The reduction was 5.6% during the first year of follow-up, increasing to 8.2% after two years. CONCLUSION:This analysis revealed that routine health data, although age-aggregated to both vaccine eligible and noneligible children < 5 years, demonstrated a reduction in malaria cases throughout the evaluation period. A further reduction in cases was observed as more vaccine-eligible children comprised the under 5 population. High quality routine data can be used to monitor vaccine impact on clinical malaria.

BACKGROUND:The relationship between malaria and COVID-19 varies across different clinical scenarios; historical malaria exposure might protect against severe COVID-19, whereas co-infection in hospitalised patients with severe disease might increase mortality. Interactions between non-severe malaria and COVID-19 remain poorly understood. We conducted a cohort study among COVID-19 patients of all ages in western Kenya and Burkina Faso to assess the effects of acute, uncomplicated Plasmodium falciparum malaria co-infection on COVID-19 outcomes in ambulatory patients. METHODS:Participants with laboratory-confirmed SARS-CoV-2 infection (positive rapid antigen test or reverse transcription quantitative real-time PCR [RT-qPCR]) were tested for malaria by rapid antigen tests with confirmatory microscopy. Patients with COVID-19 and malaria co-infection received artemether-lumefantrine or pyronaridine-artesunate. COVID-19 symptom course was assessed daily using FLU-PRO Plus (a validated patient-reported outcome instrument) until day 14. Viral load was measured by RT-qPCR on days 0, 3, 7, 14, and 28. The primary endpoint was time to symptom resolution on the FLU-PRO Plus. Analyses were adjusted for country, age, disease severity, and viral load. FINDINGS:Between Jan 8, 2021 and Jan 24, 2022, we screened 5161 participants and recruited 756 with COVID-19. 742 participants with valid malaria tests were enrolled, of which 151 (20%) had malaria co-infection and the remaining 591 (80%) did not have malaria. Patients with malaria were younger (49 [32%] aged <15 years) than those without malaria (35 [6%]; p<0·0001). Time to symptom resolution was similar between those with malaria (median 9 days [IQR 5-13]) and those without (10 days [IQR 6-13]; adjusted hazard ratio [aHR] 1·14 [95% CI 0·91-1·42]; p=0·26). Three (2%) patients with malaria and nine (2%) without malaria were hospitalised; two (1%) with malaria and three (1%) without malaria died, four from acute respiratory distress syndrome and one (in the no malaria group) from perforated peptic ulcer complicated by anaemia. Participants with malaria more frequently reported moderate-to-severe symptoms at enrolment (68% vs 60%; p=0·074), but overall symptom duration was similar (adjusted incidence rate ratio 0·95 [95% CI 0·86-1·05]; p=0·31). Previous malaria exposure significantly modified outcomes, with patients with malaria co-infection and previous exposure having faster symptom clearance than those without previous exposure (pinteraction=0·042). SARS-CoV-2 clearance was slower in the malaria group by day 7 (aHR 0·69 [95% CI 0·51-0·94]; p=0·017) but was similar between groups by day 28 (adjusted risk ratio 0·99 [95% CI 0·79-1·24]; p=0·95). INTERPRETATION:This study shows that acute uncomplicated malaria co-infection does not adversely affect COVID-19 progression when appropriately treated. Moreover, serological evidence confirms that previous lifelong malaria exposure might provide some protection, with exposed individuals having faster symptom resolution. FUNDING:Gates Foundation. TRANSLATION:For the French translation of the abstract see Supplementary Materials section.

BACKGROUND:Malaria vaccines have been added to immunisation schedules in 25 sub-Saharan African countries, with the expectation that deaths in young children would be prevented. The introduction of the RTS,S/AS01E malaria vaccine (RTS,S) in Ghana, Kenya, and Malawi in 2019 was evaluated over 4 years to show the impact on mortality in young children and to monitor severe malaria admissions, vaccine uptake, and safety. Favourable evidence on safety and impact on severe malaria admissions during the first 2 years contributed to WHO's recommendations on malaria vaccines. Here, we report the primary analysis of the impact on mortality at 46 months. METHODS:Clusters of administrative units (districts in Ghana, subcounties in Kenya, and groups of immunisation clinics in Malawi), each with an estimated annual birth cohort of about 4000 children, were randomly assigned 1:1 to introduce the RTS,S malaria vaccine in 2019 (implementation areas), or to implement later (comparison areas). RTS,S was delivered in a four-dose schedule, at age 6, 7, 9, and 24 months in Ghana and Kenya, and at age 5, 6, 7, and 22 months in Malawi. Surveillance for post-neonatal mortality in children younger than 5 years was established throughout by a network of 26 000 local reporters who notified deaths in their community. The families were then visited at home by study staff to confirm details and complete a verbal autopsy. Surveillance for severe malaria and other conditions was strengthened in 18 sentinel hospitals serving part of the study area and maintained for 46 months. Uptake of RTS,S and other vaccines was monitored by the Expanded Programme on Immunisation in each country and independently through three household coverage surveys, at baseline, and at about 18 months and 30 months after introduction of RTS,S. The primary outcome of this impact evaluation was mortality due to any cause, except injury, in children eligible to receive three doses of RTS,S. Mortality rate ratios were estimated by comparing the ratio of deaths among vaccine-eligible age groups to deaths in non-eligible age groups between implementation and comparison areas. This evaluation is registered on ClinicalTrials.gov (NCT03806465) and is complete. FINDINGS:158 clusters (66 in Ghana, 46 in Kenya, and 46 in Malawi) were selected and randomly assigned; 79 areas served as implementation areas and 79 as comparison areas. By the end of the 46-month evaluation period, 1 289 504 children had received the first dose of RTS,S, 1 158 850 had received the second dose, 1 068 039 had received a third dose, and 436 527 had received a fourth dose. Coverage assessed in 2022 was 82·8% (95% CI 80·7-84·9) for the first dose, 71·1% (68·8-73·5) for the third dose, and 39·9% (36·9-42·9) for the fourth dose. Excluding deaths due to injury, there were 5576 deaths in implementation areas versus 6152 in comparison areas in children eligible to have received the third dose of RTS,S, and 7534 versus 7044 deaths among non-eligible children. The mortality rate ratio was 0·87 (95% CI 0·77-0·97; p=0·016). INTERPRETATION:Introduction of the RTS,S malaria vaccine in routine immunisation programmes was associated with a significant reduction in mortality in young children, averting about one in eight deaths, in areas with moderate coverage of three doses of the vaccine and low uptake of the fourth dose. These results highlight the urgency to accelerate the deployment of malaria vaccines in areas of Africa where malaria continues to be a leading cause of child mortality. FUNDING:WHO; Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid. TRANSLATIONS:For the French translation of the abstract see Supplementary Materials section.

Abstract Background In September 2019, Kenya began pilot introduction of the RTS,S/AS01E (RTS,S) malaria vaccine through the World Health Organization (WHO)-coordinated Malaria Vaccine Implementation Programme (MVIP). The pilot, conducted in 46 sub-counties in western Kenya with moderate-to-high perennial malaria transmission, aimed to assess feasibility of delivering the 4-dose schedule through routine immunization services, vaccine safety, and impact on mortality and severe malaria admissions. This paper presents findings from the baseline household survey conducted prior to vaccine introduction to characterize malaria burden, coverage of malaria control interventions, health-seeking behaviors, immunization coverage, and caregiver perceptions of RTS,S. Methods A cross-sectional, population-representative household survey was conducted from July to October 2019 in all 46 MVIP sub-counties. Using two-stage cluster sampling, 4065 households were enrolled, including 4948 children aged 5–48 months. Structured questionnaires captured data on insecticide-treated net (ITN) ownership and use, vaccination status, recent febrile illness and care-seeking, and vaccine acceptability. Malaria rapid diagnostic tests were performed to estimate malaria prevalence. Analyses accounted for cluster design and sampling weights. Results Overall P. falciparum malaria prevalence was 22% (95% CI 19–26), with substantial sub-county variation (1–71%). Prevalence was higher in rural areas, among older children, in lower wealth households, and in areas randomized to vaccine introduction vs. comparison areas, indicating baseline imbalance between the arms. ITN ownership and use were high (93% and 87%). Thirty-eight percent of children had fever in the prior two weeks; 70% sought care, 39% of whom received antimalarials, nearly all artemisinin-combined therapies. Availability of home-based vaccination records declined with age (93% among 5–11 months vs. 63% among 36–48 months). Coverage exceeded 85% for first-year-of-life vaccines, but was lower for measles dose 2 (49%). Vitamin A supplementation (46%) and deworming (50%) coverage were also suboptimal. Before introduction, only 36% of caregivers had heard of the malaria vaccine, yet willingness to vaccinate exceeded 98%. Conclusions High malaria burden, strong coverage of core interventions, and strong caregiver support provided a favorable context for RTS,S introduction. However, gaps in second-year-of-life services and suboptimal vaccination records retention may challenge delivery and monitoring of the 4th RTS,S dose. These findings establish a benchmark for evaluating RTS,S rollout and integration into routine child health services. Trial registration number NCT03806465.

Background Accurate gestational age (GA) estimation is fundamental for perinatal research and pharmacovigilance but remains challenging in low-resource settings where routine pregnancy records are inconsistent, early ultrasound is limited, and multiple GA estimates often conflict. This challenge is most acute in large-scale observational studies and pharmacovigilance registries, where the data quality controls available in clinical trials are rarely feasible. Methods This study implemented a two-stage approach to derive more reliable pregnancy conception dates using routine pregnancy data from 42 healthcare facilities in Western Kenya. We first applied Isolation Forest to identify and exclude implausible GA estimates, then used a linear mixed-effects model to synthesise the remaining measurements into a single calibrated “best” estimate, accounting for systematic biases and pregnancy-level variation. The model pools information across all pregnancies to generate a calibrated conception date for each individual woman, even when her own measurements are limited. Results Integrating multi-modal inputs in each pregnancy synthesised a unified GA estimate, providing a robust dating consensus even in the absence of early ultrasound and variation across dating methods. Anomaly detection revealed data quality was unevenly distributed, with anomaly rates higher among pregnancy complications: 0.5% in term live births versus 5.1% in miscarriages. These discrepancies were primarily driven by data entry errors in antenatal clinic records (46.8%) and last menstrual period (LMP) date recall. The mixed effects model identified varying precision among dating methods. Using early ultrasound as the gold standard (mean gestation: 278.6 days), later ultrasound scans showed progressive bias, increasing from 3.15 days in the second trimester to 6.41 days in the third trimester, but retained high precision (SD: 7.5–8.9 days). Despite this drift, ultrasound markers remained more precise than other methods, such as LMP, Ballard score, foot length and fundal height, which had wider uncertainty spreads (>35 days). Conclusion Routine care datasets have the potential to yield reliable GA estimates in the absence of widespread early ultrasound through rigorous data cleaning and statistical modelling. However, translating this approach into real-time clinical practice will require embedding these algorithms into interoperable electronic medical records.

Abstract In sub-Saharan Africa, continental-scale genomic surveillance of Plasmodium falciparum malaria is needed to track the spread of drug and diagnostic resistance, as well as monitor parasite evolutionary responses to vaccine rollout. Yet continental-scale implementation is hindered by a lack of genomic approaches suitable for local laboratories, and the vastness of the continent. Here, we initiate a decentralised scale-up of P. falciparum genomic surveillance by locally sequencing and analysing 1065 samples across six African countries in one year. We achieve this with a novel nanopore sequencing protocol that is rapid (~5 hr) and cost-effective (<$25 USD/sample), providing surveillance of antimalarial drug resistance genes, hrp2/3 deletions, the vaccine target csp, and the polymorphic gene ama1. We couple this to a laptop-based bioinformatics dashboard that runs offline and displays mapping and variant calling results in real-time. We demonstrate robust sequencing coverage across parasitemia levels and laboratories, accurate identification of antimalarial resistance markers and hrp2/3 deletions; and, with a novel variant caller, sensitive detection of mutations carried by minor clones. Our approach will accelerate genomic surveillance of P. falciparum malaria across sub-Saharan Africa at a time of urgent need.

BACKGROUND:One in ten newborns in sub-Saharan Africa weigh <2500 g (i.e. low birthweight [LBW]). Breastfeeding difficulties from birth are common among LBW infants. This study explored the use of trained peer mothers to deliver breastfeeding support to mothers of LBW infants in healthcare facilities in rural Kenya. METHODS:Five trained peer mothers provided breastfeeding support to 23 mothers of LBW infants across eight healthcare facilities in Homa Bay County. Qualitative, semi-structured interviews were conducted with 11 mothers, 10 healthcare providers and 5 peer mothers prior to and during the breastfeeding support intervention. Inductive thematic analysis was used. RESULTS:Three key themes were discovered: mothers valued the confidence the peer mothers gave them to breastfeed their LBW infants, peer mothers found that the training and their previous experience caring for LBW infants enabled them to work collaboratively with mothers and healthcare providers and healthcare providers valued the additional time that the peer mothers were able to spend providing breastfeeding support. CONCLUSIONS:Facility-based breastfeeding peer support for mothers with LBW infants was acceptable among mothers and healthcare providers in the context of resource constraints, potentially improving uptake of appropriate breastfeeding practices among vulnerable mother-infant pairs. This strategy warrants more robust evaluation.

Despite intensive malaria control efforts, the lowlands of western Kenya continue to experience high malaria transmission. Spatial and temporal variations in climatic factors, interventions, parasite dispersal, and human travel, influence malaria incidence in moderate-to-high transmission areas. Additionally, population movement facilitates the importation of parasites from endemic to non-endemic areas, sustaining infections where local transmission would otherwise be unsustainable. The aim of this work was to develop a process-based stochastic metapopulation transmission model that accounts for key mechanisms of malaria dynamics, such as immunity, infectivity, and migration, while considering both the host and vector mobility. The model also incorporates and quantifies the effects of malaria interventions and climate variability at the local scale. Unlike existing models that often consider these drivers in isolation, our framework captures their joint influence within a single, mechanistic system. We show that, between 2008 and 2019, the developed metapopulation model accurately captured the effects of small-scale heterogeneity at the subpopulation level in western Kenya. Although demonstrated in a Kenyan context, the model is generalisable to other endemic regions and can support localized forecasting and intervention planning under future climate scenarios. Finaly, we assess its potential to forecast malaria incidence at the spatial-unit level, by integrating future climatic conditions with intervention scenarios.

Abstract Background Quantifying the impact of malaria vaccines on outpatient malaria burden in children is of interest to many countries introducing either of the World Health Organization (WHO)-recommended vaccines (RTS,S/AS01 [RTS,S] or R21/Matrix-M [R21]). The cluster randomized implementation of RTS,S by the Kenya Ministry of Health during the Malaria Vaccine Implementation Programme (MVIP) provided a unique opportunity to measure the impact of RTS,S on uncomplicated malaria cases reported through routine malaria case surveillance data in western Kenya. Methods From 23 implementing and 23 comparison subcounties in western Kenya, monthly numbers of confirmed uncomplicated malaria cases among individuals under 5 years of age (< 5y) and 5 years of age and older (≥ 5y) were extracted from the Kenya Health Management Information System, stored in a DHIS2 instance. Facilities that reported data ≥ 11 months per year from January 2015 through December 2022 (132 implementing, 139 comparison) were included in the analysis. Prevaccination data (January 2015–December 2019) were used to predict counterfactual case counts during the evaluation period (January 2020–December 2022), beginning when the first children vaccinated under MVIP became age-eligible for the third dose. Models of < 5y malaria cases included a covariate for ≥ 5y malaria cases to control for non-RTS,S malaria control measures. The impact was estimated as the difference between predicted and observed cases across implementing and comparison areas. Results The proportion of vaccine eligible children (RTS,S doses at 6, 7, 9, and 24 months) among all children < 5y was small at the start of MVIP but was estimated to reach 60% by December 2022. During the 3-year evaluation period following dose-3 age-eligibility, < 5y malaria cases were 2.3% lower than predicted in non-implementing facilities and 13.8% lower in implementing facilities, a reduction of 11.6%. The reduction was 5.6% during the first year of follow-up, increasing to 8.2% after two years. Conclusion This analysis revealed that routine health data, although age-aggregated to both vaccine eligible and noneligible children < 5 years, demonstrated a reduction in malaria cases throughout the evaluation period. A further reduction in cases was observed as more vaccine-eligible children comprised the under 5 population. High quality routine data can be used to monitor vaccine impact on clinical malaria.

Kenya has made notable progress in reducing malaria prevalence and improving child survival, yet the lake-endemic region continues to face high transmission and substantial malaria-related illness and death. To strengthen prevention, the RTS,S/AS01 malaria vaccine was introduced in 2019 through Kenya’s Expanded Programme on Immunization (EPI), leveraging a robust platform with decades of experience in rolling out new vaccines. This situational analysis provides a comprehensive description of the demographic, epidemiologic, and health system context in Kenya, with particular attention to the eight high-burden counties where the Malaria Vaccine Implementation Programme (MVIP) was launched. It highlights the organization of the health system, the burden of malaria, ongoing control strategies, and the strength of Kenya’s immunization infrastructure as the backbone for vaccine introduction. By documenting the epidemiologic, health system, and immunization context, this paper provides the foundation for interpreting RTS,S/AS01 malaria vaccine implementation and evaluation findings and offers lessons for vaccine introduction in other malaria-endemic settings.

Abstract Background Although rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, they have notable limitations. Blood smear (BS) microscopy remains the gold standard, yet its reliability in public health facilities (HFs) across malaria-endemic regions of Kenya can be compromised by limited infrastructure, technical capacity, and quality assurance. Methods We assessed the quality of malaria microscopy in 29 HFs in Siaya County, western Kenya, from January–July 2024 by evaluating the concordance of routine HF BS results with expert microscopy. We evaluated the availability and quality of reagents, standard operating procedures, and infrastructure using the National Malaria Control Program (NMCP) technical supervision checklist which follows WHO-certified microscopy standards. Up to 60 participant slides were randomly selected over three visits and two slides were prepared for each participant. Slide 1 was prepared and read on-site as per routine HF practice, then re-examined by an expert microscopist using the HF microscope and again at the Kenya Medical Research Institute (KEMRI). Slide 2 was stained and read at KEMRI, serving as the gold standard. We evaluated factors and characteristics associated with accurate diagnosis using logistic regression. Results Of the 1,494 blood smears examined, 501 (34%) were positive. Concordance between routine microscopy and expert re-reading was 91% (1,289/1,414), ranging from 55% (6/11) to 100% (60/60) across health facilities. Percent agreement between HF slide 1 and slide 2 was 86% (1,276/1,485), with a range from 55% (6/11) to 98% (39/40) by HF. Compared to slide 2, sensitivity and specificity of HF results was 76% and 92%, respectively, resulting in undertreatment of 24% and overtreatment of 8% of patients. Those with parasitemia 1–100 p/μL had lower odds of accurate diagnosis (OR = 0.12; 95% CI: 0.05–0.29; p < 0.001) while specimens with parasite densities > 10,000 p/μL had higher odds of accurate diagnosis (OR = 6.08; 95% CI: 2.22–25.1; p = 0.002), indicating a positive association between parasite density and diagnostic accuracy. Six (21%) of HFs had poor quality BS with debris or contamination. Conclusions While overall concordance was high, the variability in results by HF, limited accuracy at low parasite densities, and challenges with required infrastructure highlight the need for ongoing malaria microscopy quality assurance to ensure proper case management.

Malaria in pregnancy is a major but poorly quantified contributor to maternal anaemia in sub-Saharan Africa. We combined individual-level data on haemoglobin (Hb), gravidity, gestational age and PCR-confirmed Plasmodium falciparum infection from 12,608 pregnancies in 7 African countries with a gravidity-specific model of malaria exposure and immunity linked to contemporary maps of transmission and fertility. For 2023, we estimate that 13.1 million pregnancies in malaria-endemic African regions were exposed to P. falciparum. In the absence of preventive measures, this exposure would have resulted in 2.41 million (95% credible interval 1.98-3.04 million) cases of moderate or severe anaemia (Hb < 9 g dl-1), including 600,000 (408,000-906,000) severe cases (Hb < 7 g dl-1). A counterfactual scenario using 2,000 transmission levels suggests that a 32% reduction in exposure during pregnancy translated into only a 22% decline in intrinsic anaemia burden, reflecting a shift from a concentration of risk in primigravidae to a more even distribution across gravidities as multigravid women acquire less pregnancy-specific immunity. Calibrating our model to randomized trials, we estimate that under current coverage, intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine averted around 1.10 million (0.72-1.61 million) cases of moderate or severe anaemia and 330,000 (225,000-523,000) severe cases in 2023. These findings show that although burden has declined substantially, malaria remains a major driver of maternal anaemia risk. Meanwhile, lower immunity across multigravidae means any interruption to intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine, or other population-based malaria control efforts, risks rapid resurgence of severe maternal anaemia, with substantial consequences for maternal and neonatal health.