Malaria Journal

Malaria remains a major global health challenge, with over 263 million cases and nearly 600,000 deaths reported in 2023, the majority in sub-Saharan Africa. While conventional interventions such as insecticide-treated nets, indoor residual spraying and antimalarial drugs have reduced transmission, progress has stalled due to the limitations of these interventions and the emergence of resistance. Gene drive-modified mosquitoes represent a promising, potentially transformative vector control strategy, capable of spreading malaria-refractory traits or suppressing mosquito populations. Successful field deployment will depend upon monitoring systems to track the presence and frequency of gene drive constructs as they spread and persist. Current molecular surveillance techniques, though effective, are resource-intensive and reliant on laboratory infrastructure and technical competencies. Here, we make the case for a near-universal and low-cost rapid diagnostic test (RDT) designed to detect gene drive mosquitoes in the field, to complement existing surveillance infrastructure. Two use cases are outlined: i) to detect the presence of the drive construct in a new population, and ii) to provide an estimate of drive frequency prior to more accurate laboratory-based measurements. We provide a target product profile for the RDT outlining minimally essential and ideal characteristics, including test procedures, sensitivity, specificity, usability by a range of stakeholders in field settings, and compatibility with pooled testing of mosquito samples. An RDT for gene drive construct detection would support community access and participation in monitoring, enhance regulatory oversight, and promote transparency in field trials, thereby facilitating responsible deployment of gene drive-based malaria interventions.

BackgroundMalaria constitutes a major public health burden in sub-Saharan Africa. It remains a key health concern and the leading cause of death in children under five years of age in Benin. Since October 2021, the World Health Organization has recommended the use of malaria vaccines for the prevention of Plasmodium falciparum malaria in children living in malaria endemic areas, prioritizing areas of moderate and high transmission in sub-Saharan Africa. However, with the exception of Ghana, there is a scarcity of studies modelling the potential impact of the RTS,S/AS01 vaccine in the context of West Africa. This study addresses a gap in research by modelling the impact of malaria childhood vaccination on Plasmodium falciparum malaria transmission in Benin. MethodsA compartmental mathematical model has been developed to estimate clinical and severe malaria cases averted in children under the age of five with the primary series (3 doses) of the RTS,S/AS01 malaria vaccine in Benin. Over a period of 10 years, scenarios including vaccine introduction at different coverage levels to supplement the use of long-lasting insecticidal nets to assess the impact of the RTS,S/AS01 vaccine on malaria transmission in Benin are modelled. ResultsThe model projected malaria burden alleviation by malaria vaccination in Benin. The combination of childhood malaria vaccination at a coverage equivalent to the national DTP3 coverage and the current use of long-lasting insecticidal nets is projected to result in 40% reduction in malaria clinical cases and deaths among children under five years old compared to using nets alone, from 2025 to 2034. However, if the introduction of a malaria vaccine has the unintended consequence of decreased net use, cumulative benefits may be offset. A 1.5-fold decrease in the use of long-lasting insecticidal nets is projected to result in an increase in malaria burden, surpassing baseline levels despite the introduction of the vaccine. ConclusionThis modelling exercise concludes that childhood vaccination is expected to avert clinical and severe cases of malaria and is an additional tool to advance malaria control efforts in Benin but potential unintended consequences of a reduction in net usage may reduce these gains.

As reductions in malaria transmission in sub-Saharan Africa stagnate, gene drive-modified mosquitoes represent one of the most promising novel tools for continued disease control. In order to advance from the laboratory to the field, gene drives will be assessed against target product profiles, planning tools that list minimum criteria products should satisfy as they progress through the development pipeline. Here, we use an eco-epidemiological model to investigate parameter values for population modification gene drives that satisfy two previously-discussed target outcomes: a 50% reduction in clinical malaria incidence for a duration (window-of-protection) of at least three years, and a time-to-impact of less than one year. We consider two African settings, Burkina Faso and Kenya, where gene drive mosquitoes are currently being researched, and consider three transmission intensities at each. For the gene drive product, we explore rates of homing and resistance allele generation, fitness costs associated with gene drive and non-functional resistance alleles, and the efficacy of the effector gene(s) at reducing mosquito-to-human transmission. We find that when the window-of-protection criterion is satisfied, the time-to-impact criterion also is. Target outcomes are most influenced by the fitness cost associated with the gene drive allele and effector gene efficacy. Resistance allele parameters are also highly influential on target outcomes, and determine how long the gene drive allele persists in the population after most available wild-type alleles have been cleaved. Low rates of functional resistance allele generation are preferred, while costly non-functional resistance alleles will allow the drive allele to outcompete them. Homing rates already achieved for Anopheles gene drives do not need to be improved upon. A conundrum exists whereby the most important product parameters for predicting field efficacy are those that can only be reliably measured in the field, which presents a challenge for assessment of product readiness.

The World Health Organizations recommendations regarding the use of antimalarials for the prevention of malaria in endemic areas have greatly expanded, allowing more flexibility in the demographic groups and regions where chemoprevention and mass treatment are acceptable. An overlooked aspect of expanding human population-level drug exposure is the downstream impact of ingested drug on the mosquito vector. Data suggest both infected and uninfected Anopheles mosquitoes re-feed often with [≥]4 blood meals during their lifespan. This provides repeated opportunities for mosquitoes to ingest drug via bloodmeals taken from people with antimalarials in the bloodstream and raises questions as to whether exposure may impact the mosquito itself, and/or parasites developing within the infected mosquito. We investigated the impact of exposure to physiologic levels of commonly used long-acting human antimalarials in the Anopheles mosquito via drug-spiked blood feeds. We did not observe any significant differences in mosquito feeding, behavior, fertility, or viability after ingestion of amodiaquine, desethylamodiaquine, piperaquine, and sulfadoxine-pyrimethamine in either lab-reared An. gambiae or field-derived An. coluzzii mosquitoes. Interrogating drug distribution within mosquitoes utilizing LC-MS/MS, desethylamodiaquine, the longer-acting active metabolite of amodiaquine, was fed at 2 concentrations (1/2X and 2X Cmax) with drug subsequently detected in a dose-dependent manner in pooled whole mosquitoes, midguts and hemolymph. This was significant for whole mosquitoes harvested at 24hrs and 120hrs, and midguts harvested at 24hrs. Between 24 to 120 hrs, drug decreased in midguts but increased in hemolymph. Our results show biochemical evidence of antimalarial absorption into Anopheles hemolymph following bloodmeal ingestion. These studies lay the foundation for future work to assess the impact of vector-stage antimalarial drug exposure on parasite progression throughout development in the mosquito, which could in turn have important implications for transmission dynamics and drug resistance spread. Author summaryDrug resistance to first-line antimalarials has emerged in multiple African countries. A better understanding of antimalarial drug resistance emergence and spread is critical in preventing further morbidity and mortality. Millions regularly receive antimalarials for prophylaxis and mass treatment that are purposefully long-acting. Anopheles mosquitoes re-feed frequently, and these malaria vectors (both infected and uninfected) routinely feed on people whose blood contains these long-acting antimalarials. Parasites take approximately 10 days to develop within the mosquito. There is published precedent that several antimalarials can act upon vector-stage parasites, yet any potential impact of antimalarials on mosquitoes and/or parasites developing within has been largely overlooked. We questioned whether antimalarials ingested in mosquito bloodmeals could influence parasite development and drug resistance selection. As initial investigations, we exposed uninfected Anopheles mosquitoes to commonly used long-acting antimalarials via drug-spiked bloodmeals, mimicking predicted physiologic drug exposure. Investigated drugs did not impact mosquito viability. However, mass spectrometry confirmed drug absorption in whole mosquitoes, as well as within midguts and circulatory fluid, several days after feeding, demonstrating that mosquitoes can ingest key drugs without suffering fitness costs, and these drugs can persist in mosquitoes. This highlights the potential for antimalarials to impact parasite development and drug resistance selection within the mosquito.

BackgroundMalaria during pregnancy contributes to maternal anemia and adverse birth outcomes in sub-Saharan Africa. This study assessed seasonal malaria burden among pregnant women in Cape Coast, Ghana, during 2019-2021. MethodsRetrospective surveillance analysis of pregnant women attending Cape Coast Teaching Hospital. Malaria was diagnosed by microscopy, and hemoglobin levels were measured. Seasonal trends and demographic characteristics were analyzed using descriptive statistics and chi-square tests. ResultsAmong 334 pregnant women, 294 (88.0%) were tested for malaria. Overall prevalence was 2.04% (6/294; 95% CI: 0.75-4.41%), exclusively Plasmodium falciparum. Prevalence was higher in the dry season (2.26%) than wet season (1.27%), with 67% of cases in Q4 2021. Mean age was 35.0 {+/-} 5.1 years, and 79.4% presented in third trimester. Anemia (Hb <11 g/dL) affected 41.3% of participants despite low malaria prevalence. Sensitivity analyses confirmed robust estimates across analytical approaches. ConclusionsLow malaria prevalence reflects progress toward Ghanas elimination goals, though the unexpected dry season pattern warrants investigation. High anemia burden despite low malaria indicates non-malarial causes require attention. Year-round screening and comprehensive antenatal care remain essential as Ghana transitions toward elimination.

Severe malaria disproportionately affects children during their earliest Plasmodium falciparum infections, when immunopathology rather than parasite burden often drives clinical deterioration. Because direct investigation of host-parasite interactions during severe disease is ethically impossible, we developed a two-dimensional ex vivo co-culture system that recapitulates key physiological features of malaria pathogenesis. Using PBMCs from malaria-naive and malaria-exposed adults co-cultured with a freshly adapted P. falciparum isolate, we modelled the combined effects of febrile temperature, pipecolic acid (PA), and lysophosphatidylcholine (LPC) depletion on IL-6 secretion. We also integrated clinical data from children with severe malaria in Anambra State, Nigeria. Across conditions, IL-6 output was not driven by temperature alone but by a metabolically gated interaction: febrile temperature amplified IL-6 only when PA was present, and LPC was not limiting. LPC depletion suppressed IL-6 to near-baseline levels regardless of temperature or PA, indicating that lipid availability constrains inflammatory signalling. Clinical data showed that adverse outcomes clustered with markers of multi-organ dysfunction. Together, these findings support a model in which IL-6 is a context-dependent mediator - participating in inflammatory pathways but not acting as a singular causal driver - and in which metabolic stress, febrile cues, and host tolerance mechanisms jointly shape cytokine production. Ongoing bioinformatics analysis will define the transcriptional responses of both parasite and host cells under these malaria-relevant conditions.

Introduction: Malaria during pregnancy is a major risk factor for low birth weight (LBW) in newborns, which in turn negatively affects the growth and development of the child. The World Health Organization (WHO) recommended interventions for pregnant women living in malaria endemic countries that include the use of intermittent preventive treatment in pregnancy (IPTp). However, WHO asserts that the coverage of pregnant women taking the recommended doses of IPTp are still very low. The primary goal of this study was to estimate the effects of increasing the coverage of doses of IPTp and to assess the effect of pregnancy timing in relation to seasonal transmission on malaria infections during pregnancy and neonates with LBW. We explored these effects in moderate and high transmission settings. Methods and Findings: A compartmental mathematical model depicting malaria during pregnancy with IPTp doses was formulated to analyze the effects of IPTp, insecticide treated net (ITN) use and seasonal variations in moderate and high malaria transmission settings. Our simulation findings suggest that increasing both ITN use and IPTp dose coverages to high levels, prevents 90% and 84% clinical cases for pregnancies starting in August in moderate and high transmission, respectively. Our model predicts that increasing the coverage of the first dose of IPTp to 90%, while lowering subsequent doses, averts 44% and 37% LBW cases for the August cohort in moderate and high transmission settings, respectively. Unprotected pregnancies overlapping the January peak in rainfall and malaria incidence during the third trimester experience the highest LBW burden. Conclusions: The highest IPTp coverage prevents the highest number of LBWs providing evidence of the benefits of scaling up IPTp. Overall, our results demonstrate that increasing ITN use has a substantial impact in reducing clinical malaria cases during pregnancy and improves birth outcomes. This highlights its importance as a key intervention, and the health benefits it would provide for malaria control goals for pregnant women. Pregnancies that overlap with the epidemic peaks in later trimesters lead to a rise in LBWs, indicating the necessity of protecting pregnant women at risk of malaria infection till delivery.

BackgroundInsecticide treated nets (ITNs) represent a key tool in reducing human vector contact for malaria control. However, increasing insecticide resistance of malaria vectors threatens the effectiveness of pyrethroid-only nets in reducing malaria risk. Next- generation nets, such as those with dual active ingredients, have been recommended for use in areas with high malaria burden and confirmed pyrethroid resistance. Here, we assessed the impact of the distribution of Interceptor(R) G2 (IG2) ITNs on malaria cases in the Western North region of Ghana distributed in 2021. MethodsWe analysed monthly numbers of confirmed malaria cases reported by health facilities in the Western North Region from 2018 to 2023. To control for possible confounding effects of climatic conditions, monthly mean values of both modelled vector habitat suitability and temperature suitability for the periods were included. Bayesian Poisson regression time series models were developed to assess the immediate and sustained impact of IG2 ITNs on malaria case trends. ResultsMalaria cases reduced by 30% [odds ratio: 0.70, 95% CrI (0.624, 0.778)] immediately after the distribution of IG2 ITNs in the Western North region. This effect was sustained at six months up to 30 months post-intervention, where cases were reduced by 26% [odds ratio: 0.74, (0.65, 0.75) and 40% [odds ratio: 0.598 (0.495, 0.722)], respectively. The intervention was also strongly associated with reductions in malaria cases in seven of the nine districts in the region, after controlling for climatic factors. ConclusionThis study demonstrates the effectiveness of dual active Interceptor(R) G2 ITNs in the Western North region, an area with confirmed pyrethroid resistance. These findings support the scale-up of these next-generation nets by National Malaria Programs and highlight the need for further research to explore the utility of these nets in other high- burden malaria areas with region-specific insecticide resistance profiles. Key messagesMalaria prevalence and incidence both decreased after deployment of IG2 ITNs in the Western North region of Ghana. Distribution of IG2 ITNs caused immediate and sustained impact on malaria case reduction. Dual-active ingredient insecticide-treated nets are effective in field settings and could be deployed at a large-scale.

Background Seasonal malaria chemoprevention (SMC) is a malaria intervention in which antimalarial drugs are administered monthly to children under 5 years of age during the high-transmission season. In the district of Moissala in southern Chad, SMC has been implemented since 2013, with an interruption in 2019, resumption in 2020, and expansion to five rounds of treatment in 2021. Recent World Health Organization (WHO) guidelines allow countries to adapt the timing and number of SMC rounds to local transmission patterns, creating a need to identify optimal strategies for each setting. In this study, we used mathematical modeling for three primary purposes: 1) to estimate the effectiveness of SMC in Moissala from 2018 to 2023, 2) to assess the impact of changes to SMC strategies since 2018, and 3) to determine the optimal SMC strategy in Moissala. Methods and findings We adapted a compartmental, climate-informed malaria transmission model to represent malaria dynamics in the presence of SMC. The model incorporates temperature and rainfall data to capture how climate variability influences malaria transmission over time. It was calibrated to routine surveillance data on malaria cases in children under five years old from 2018 to 2023. Using the calibrated model, we simulated malaria cases under alternative scenarios, including the absence of SMC and variations in the number and timing of SMC rounds. These simulations were then used to estimate the overall effectiveness of SMC, assess the impact of past changes in SMC strategies, and identify the optimal strategy in Moissala. Between 2018 and 2023, SMC reduced malaria cases in children under five by 26% (95% credible interval: 21%, 31%) relative to a scenario without SMC, corresponding to an average of approximately 14400 cases averted each year. The interruption of SMC in 2019 led to an estimated increase of 13600 cases (95% credible interval: 11200, 15800), representing a 31% rise during the high-transmission season. Expanding from four to five SMC rounds in 2021 reduced cases by 7% relative to a four-round schedule, while starting the five-round schedule earlier in June rather than July led to an additional 5% reduction. Overall, the most effective strategy from 2018 to 2023 was a five-round schedule beginning in mid-June. Conclusions Seasonal malaria chemoprevention has substantially reduced malaria incidence among children under five in Moissala. The currently implemented strategy of five rounds of SMC starting in June was estimated to achieve the greatest reduction in cases over the study period. Climate-informed modelling and open-source software can support timely decision-making across settings under changing climate and transmission conditions.

Vaccines, monoclonal antibodies, and long-acting injectables are being developed to prevent Plasmodium falciparum malaria. These therapeutics may target multiple stages of the parasite life cycle; evidence is needed to articulate their benefits with chemoprevention and prioritise candidates for clinical development. We used an individual-based malaria transmission model to estimate the health impact of combining new therapeutics with seasonal malaria chemoprevention (SMC). Our modelling framework used emulator-based methods with models of pre-liver and blood stage therapeutic dynamics. We evaluated the benefit of combining therapeutics with SMC in children under five by estimating reductions in the cumulative incidence of uncomplicated and severe malaria, relative to SMC or the new therapeutic alone, during and five years after deployment. New therapeutics may require extended pre-liver stage duration or multi-stage activity to combine with SMC. For three SMC cycles in a high transmission setting, a pre-liver stage therapeutic with partial initial efficacy (>50%) required a protection half-life >230 days to reduce cumulative severe cases by >5% five years after deployment stopped (>23% during interventions). Longer protection was needed when combined with four or five SMC cycles. Combining SMC with a multi-stage therapeutic increased public health impact both during and after deployment. Combining SMC with malaria therapeutics active against multiple stages of the parasite life cycle can improve the effectiveness of SMC, highlighting the need to prioritise the clinical development of these therapeutics for combination with malaria chemoprevention.

IntroductionMalaria remains a critical health challenge in Kenya, particularly among children under five years who are highly vulnerable to its complications. Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria. However, their uptake varies due to socio-economic inequalities, geographic disparities, and the influence of social networks. Understanding how social interactions, particularly those mediated by religious affiliations, impact ACT uptake can inform strategies to improve malaria treatment outcomes in malaria-prone regions. MethodsThis study utilized data from the Kenya Malaria Indicator Survey (KMIS) 2020, employing a cross-sectional design and stratified two-stage cluster sampling. Data on malaria prevalence, treatment-seeking behavior, and ACT usage were analyzed using descriptive statistics and logistic regression. The analysis focused on socio-demographic factors, geographic differences, and the role of social networks mediated through religious affiliations. ResultsACT uptake among children under five was 52%. Male children were less likely to receive ACTs, with probabilities 6.3% lower in rural areas and 3.1% lower in urban areas. Younger children in rural areas, particularly those aged one, had a 5.7% higher likelihood of ACT usage, while uptake declined with age. Caregivers education significantly enhanced ACT uptake in rural areas, increasing the likelihood by 25%. Rural Muslim households were 17.2% more likely to use ACTs, while urban Christian households showed modest improvements. Wealth disparities also affected uptake, with wealthier urban households less likely to use ACTs. ConclusionThe study highlights the critical role of social networks, particularly religious affiliations, in shaping ACT uptake in malaria-prone zones of Kenya. Addressing barriers to access through these networks offers a promising avenue for increasing ACT utilization and improving health outcomes. Leveraging community-driven approaches and religious institutions could enhance equitable malaria treatment coverage across vulnerable populations.

Plasmodium falciparum is the most virulent and widespread of the human malaria parasite species. This parasite has a complex life cycle that involves sexual replication in a mosquito vector and asexual replication in a human host. During the 48-hour intraerythrocytic developmental cycle (IDC), parasites develop and multiply through the morphologically distinct ring, trophozoite and schizont stages. Stage-specific transcriptomic approaches have shown gene expression profiles continually change throughout the IDC. Cultures of tightly synchronized parasites are required to capture the transcriptome specific to a developmental stage. However, the most commonly used synchronization methods require lysis of late stages, potentially perturbing transcription, and often do not result in tightly synchronized cultures. To produce complete transcriptome profiles of the IDC a synchronous culture requires frequent sampling over a 48-hour period, this is both time consuming and labor intensive. Here we develop a method to sample the IDC densely by isolating parasites from an asynchronous culture with fluorescence activated cell sorting (FACS). We sort parasites in tight windows of IDC progression based on their DNA/RNA abundance. We confirmed the tight synchronization and stage specificity by light microscopy and RNAseq profiling. We optimized our protocol for low numbers of sorted cells allowing us to rapidly capture transcriptome profiles across the entire IDC from a single culture flask. This methodology will allow malaria stage-specific studies to perform experiments directly from asynchronous cultures with high accuracy and without the need for labor-intensive time-course experiments.

Andrade et al have reported that P. falciparum parasitised erythrocytes circulate for longer in persistent asymptomatic infections than in symptomatic malaria. This radical suggestion, attributed to in-vivo adaptation by the parasite population to reduced cytoadherence, is based largely on in-vivo transcriptomic data from 24 Malian children: 12 with acute falciparum malaria and 12 with asymptomatic parasitaemia. We show that the reported analysis generated erroneous results because of data formatting issues. We also show that the algorithm used to estimate the average asexual parasite developmental stage (hours post-invasion) from in-vivo transcriptomic data breaks down when applied to asynchronous infections. We argue that comparisons between asymptomatic and symptomatic malaria of asexual parasite developmental stage distributions are confounded by differences in synchronicity and gametocytaemia, and also by selection bias (because schizogony often precipitates clinical presentation). There is no convincing evidence of an adaptive delayed cytoadherence phenotype in chronic P. falciparum infections.

BackgroundMalaria in urban areas is a growing concern in most sub-Saharan African countries. The growing threats of Anopheles stephensi and insecticide resistance magnify this concern and hamper elimination efforts. It is therefore imperative to identify areas, within urban settings, of high-risk of malaria to help better target interventions. MethodsIn this study, we combined a set of environmental, climatic, and urban covariates with observed data from a malaria prevalence study and used geospatial methods to predict malaria risk in the Greater Accra Region of Ghana. Georeferenced data from 12,371 surveyed children aged between 6 months and 10 years were included in the analysis. ResultsPredicted malaria prevalence in this age group ranged from 0 to 52%. Satellite-driven data on tasselled cap brightness, enhanced vegetation index and a combination of urban covariates were predictive of malaria prevalence in the study region. We produced a map that quantified the probability of malaria prevalence exceeding 10%. ConclusionsThis map revealed areas within the districts earmarked for malaria elimination that have high malaria risk. This work is providing evidence for use by the National Malaria Elimination Program and District Health Managers in planning and deploying appropriate malaria control strategies. Summary boxO_ST_ABSWhat is already known?C_ST_ABSReduction in malaria incidence globally has stalled in the past few years. Malaria endemic countries are being encouraged to use local data to inform appropriate malaria control strategies. Malaria prevalence studies seldomly provide estimates below regional administrative levels. The availability of environmental, climatic, and socioeconomic factors as well as computational methods has enhanced predictive methods that quantifies the disproportionate variation of malaria risk between and within urban areas. What are the new findings?Predictive maps of malaria at high spatial resolutions such as 100m allows for visualizing fine-scale heterogeneity of malaria in neighbourhoods. Inclusion of urban covariates in models predicting malaria risk in urbanized communities helps to account for socioeconomic disparities and their effect on malaria risk. What do the new findings imply?Malaria control efforts needs to be guided by highly granular data. Systems to generate granular data on a continuous basis needs to be strengthen in malaria endemic countries, especially, to better inform deployment of appropriate interventions in resource constraint settings. This type of analysis provide information on which intervention is appropriate in a specified geographical area.

BackgrounMalaria transmission is primarily limited to tropical regions where environmental conditions are conducive for the survival of Plasmodium parasites and Anopheles mosquitoes. Adequate rainfall provides breeding sites, while suitable temperatures facilitate vector mosquito life-cycles and parasite development. Evaluating the efficacy of vector control interventions is crucial to determine their effectiveness in reducing malaria transmission. The aim of this study was to explore how these factors affect transmission dynamics at varying levels of vector control efficacy. MethodsWe developed a vector-host compartmental mathematical model to compare three published approaches to incorporating weather influences on malaria transmission. The first approach examines mosquito biting behaviour and mortality rates in larval and adult stages. The second focuses on temperature effects on mosquito life-cycle characteristics throughout the aquatic and adult stages. The third considers how temperature and rainfall influence adult mosquito behaviour, environmental carrying capacity, and survival during the aquatic stages. Model simulations were conducted at different annual vector control coverage levels, to identify variations in transmission patterns and seasonal variability in daily and annual incidence across three climate regions. ResultsThe first approach indicates sustained seasonal transmission, with lower cases per 1,000 in tropical regions compared to semi-arid and sub-tropical regions, even with enhanced vector control reducing cases. The second approach projects extended seasonal peaks in malaria transmission in tropical and semiarid regions, driven by prolonged warm periods, while sub-tropical regions show lower incidence due to cooler temperatures limiting mosquito survival. In contrast, the third approach projects multiple irregular peaks, with transmission ceasing in winter across all regions. ConclusionsSimulations indicate that climatic events like heatwaves or flooding, can trigger mosquito population surges and malaria outbreaks, even in areas previously free of malaria, despite strong vector control efforts. However, the results demonstrate that sustained and effective vector control, particularly in regions with moderate temperatures, can substantially reduce malaria incidence. Effective malaria control requires incorporating weather predictions into intervention plans, and enhancing current vector control strategies with supplementary measures like larval source management. Accurate timing and targeting of these interventions, based on transmission season projections, are crucial for maintaining robust control as weather conditions evolve and to prepare for future challenges.

Growing insecticide resistance and other causes of residual transmission of malaria parasites have led to a global stagnation in progress in malaria control, despite widespread deployment of insecticide-treated bed nets (ITNs). New bed net technologies including dual active ingredient (AI) and piperonyl butoxide plus pyrethroid (PBO + P) nets have been developed to address these problems and be more effective malaria prevention tools. Two types of dual-AI ITNs and PBO + P ITNs were evaluated across five countries in pilot studies coupled with economic evaluations. Chlorfenapyr + pyrethroid (C + P) ITNs showed the best overall performance in terms of incidence rate reduction (Incidence rate ratio 0.62 vs. standard ITN) and generally in terms of incremental cost-effectiveness ratio, but using any dual-AI or PBO + P ITN was favored over standard pyrethroid-only ITNs alone. There was significant overlap between the recommended strategy in any given study location due to high uncertainty in cases averted and relatively similar product costs. While the addition of indoor residual spraying (IRS) to standard ITNs was a more effective strategy than dual-AI or PBO + P ITNs, this evidence was based on only one study site and the incremental cost for the addition of IRS was substantially greater than the incremental cost of dual-AI or PBO ITNs compared to standard ITNs (ICER 18.59 USD per case averted vs. 1.51 USD per case averted for C + P ITN in this settings). The switch from standard ITNs to dual-AI or PBO ITNs is recommended in most African settings, with the chlorfenapyr + pyrethroid (C + P) nets being the broadly favored choice. Ultimately programs will need to incorporate local information on the malaria burden and up to date product price information to determine the most efficient malaria prevention strategy in the settings in which they serve.

Characterising connectivity between geographically separated biological populations is a common goal in many fields. Recent approaches to understanding connectivity between malaria parasite populations, with implications for disease control efforts, have used estimates of relatedness based on identity-by-descent (IBD). However, uncertainty around estimated relatedness has not been accounted for to date. IBD-based relatedness estimates with uncertainty were computed for pairs of monoclonal Plasmodium falciparum samples collected from five cities on the Colombian-Pacific coast where long-term clonal propagation of P. falciparum is frequent. The cities include two official ports, Buenaventura and Tumaco, that are separated geographically but connected by frequent marine traffic. The fraction of highly-related sample pairs (whose classification accounts for uncertainty) was greater within cities versus between. However, based on both the fraction of highly-related sample pairs and on a threshold-free approach (Wasserstein distances between parasite populations) connectivity between Buenaventura and Tumaco was disproportionally high. Buenaventura-Tumaco connectivity was consistent with three separate transmission events involving parasites from five different clonal components (groups of statistically indistinguishable parasites identified under a graph theoretic framework). To conclude, P. falciparum population connectivity on the Colombian-Pacific coast abides by accessibility not isolation-by-distance, potentially implicating marine traffic in malaria transmission with opportunities for targeted intervention. Further investigations are required to test this and alternative hypotheses. For the first time in malaria epidemiology, we account for uncertainty around estimated relatedness (an important consideration for future studies that plan to use genotype versus whole genome sequence data to estimate IBD-based relatedness); we also use a threshold-free approach to compare parasite populations, and identify clonal components in a statistically principled manner. The approaches we employ could be adapted to other recombining organisms with mixed mating systems, thus have broad relevance.

Sickle cell trait is the quintessential example of the human response to malaria, providing protection against severe disease, but leading to sickle cell disease (SCD) in the homozygous state. Fetal Hemoglobin (HbF) reduces the pathology of SCD and several mutations lead to the prolonged production of HbF into childhood and adult life. HbF has been suggested to contribute to protection against malaria. Two long-term cohorts were genotyped for three quantitative trait loci associated with HbF production and analyzed for HbF titers, malaria clinical episodes and the production of parasite stages infectious to mosquitoes, gametocytes in asymptomatic infections. Plasmodium falciparum parasites were also grown in vitro in HbSS cells with measured levels of HbF. The genetic determinants of prolonged HbF production were associated with increased HbF titers and that increased HbF afforded protection from malaria disease but increased the production of gametocytes. The presence of HbF in sickled red cells was also shown in in vitro culture to enable parasite persistence in conditions otherwise deleterious for the parasite and enabled complete maturation of gametocytes. The beneficial personal effect of HbF, whether through protection against malaria or alleviating effects of SCD, is offset by increased parasite transmissibility and disease burden for the community. These individuals represent an important reservoir of infection and need to be targeted in elimination strategies. Key pointsO_LIIndividuals with mutations associated with fetal hemoglobin production had fewer clinical episodes but produced more gametocytes. C_LIO_LIHbF in red blood cells enables gametocyte production at tissue level oxygen partial pressures at which normally parasite lysis would occur. C_LI

Background: Malaria remains a major cause of morbidity and mortality among children under five years in Ghana. This study examined household, maternal, and child characteristics associated with malaria prevalence. Methods: Data were drawn from the 2019 Ghana Malaria Indicator Survey. The analytic sample comprised 2,867 children with valid malaria rapid diagnostic test results. Analyses accounted for the survey's multistage cluster design, including primary sampling units, strata, and sampling weights. Survey-weighted descriptive statistics, Rao-Scott corrected chi-square tests, and survey-weighted logistic regression with a quasibinomial link were used. Results: Overall, 22.9% of children tested positive for malaria. At the bivariate level, child age, number of children under five, household wealth, residence, region, household net usage, electricity, television ownership, maternal education, household size, and anaemia level were significantly associated with malaria status (p < 0.05). In the fully adjusted model, children in the poorest and poorer households had higher odds of testing positive than those in the richest households (AOR = 4.13 and 3.13, respectively). Rural children had higher odds than urban children (AOR = 2.36). The highest regional odds were observed in the Eastern Region (AOR = 15.3) compared with Greater Accra. Older children and those with severe anaemia had higher odds of testing positive (AOR = 4.17 and 24.5, respectively). Maternal education significantly interacted with household wealth and household net usage. Conclusion: Household wealth, region, residence, maternal education, child age, and anaemia level were important correlates of malaria prevalence. Findings support interventions addressing socioeconomic and regional inequalities in childhood malaria.

BackgroundPlasmodium vivax (P. vivax) has emerged as the primary cause of malaria in Cambodia. Achieving malaria elimination and securing malaria-free certification requires a focused effort on addressing P. vivax malaria. This is essential because the elimination of P. vivax often lags behind that of Plasmodium falciparum, making it a critical component in the overall strategy. This study assesses the feasibility of the Mass Drug Administration (MDA) and P. vivax Serological Testing and Treatment (PvSeroTAT) integrated with Reactive Case Detection (RACD) in two of the highest malaria burden operational districts of Cambodia and examines the potential for integrating these two approaches with existing malaria elimination efforts. MethodsThis study employs an observational, prospective cohort design. MDA with chloroquine (CQ) will be conducted in Stung Treng through four monthly rounds, while RACD with PvSeroTAT will be implemented in Sen Monorom, targeting households near confirmed P. vivax cases. Data on coverage, compliance, cost, and stakeholder perceptions will be collected through surveys, interviews, and malaria case monitoring. A Composite Feasibility Index will integrate quantitative and qualitative indicators. Cost and budget impact analyses will assess scalability for malaria-endemic districts. DiscussionInnovative and targeted public health approaches and tools are necessary to ensure the elimination of the malaria parasite reservoir, including the hidden hypnozoites. While MDA with CQ clears active blood-stage infections leading to immediate reductions in malaria prevalence, PvSeroTAT can detect past exposure to P. vivax by using serological markers allowing for targeted treatment of individuals at risk of developing relapsing infections with an 8-aminoquinoline. This helps reduce the parasite reservoir more efficiently. This study will provide insight into operational feasibility, implementation costs, community acceptance, and long-term sustainability. The findings will guide Cambodias malaria elimination efforts through improved surveillance and targeted interventions. Trial RegistrationOSF Preregistration: https://doi.org/10.17605/OSF.IO/5KZH7, retrospectively registered 15 October 2025.