Background:Plasmodium falciparum and Plasmodium vivax cause most malaria cases worldwide and are co-endemic in many countries, yet differ substantially in biology and in their responses to common interventions. As programmes drive down P. falciparum, P. vivax is a growing challenge for elimination, but most modelling tools assess the species separately, limiting coordinated policy. We aimed to build a unified malaria transmission modelling framework for co-endemic settings and assess how well it reflects global prevalence. Methods:We integrated an established P. vivax model into a flexible P. falciparum modelling platform, enabling parallel simulation of both species within a shared biological, demographic, and intervention environment. Modelled equilibrium prevalences, matched by mosquito density, were compared with 19,225 yearly co-prevalence estimates from the Malaria Atlas Project (769 sub-national regions, 33 co-endemic countries, 2000-2024); uncertainty was represented by 95% quantile-based regions from 50 parameter draws. We assessed how this fit was modified by biological factors and simulated interventions. Results:Here we show that the framework captures 51% of co-prevalence estimates within its uncertainty regions, rising to 65.5% when country-specific P. vivax relapse rates and human Duffy negativity are included. P. falciparum predominates where mosquito densities are high, whereas P. vivax is relatively more prevalent at lower densities. Simulated interventions produce larger relative reductions in P. falciparum prevalence, while P. vivax shows greater rebounds after intervention withdrawal, particularly at low mosquito densities. Conclusions:This unified framework provides a quantitative tool to support coordinated, species-specific intervention strategies in co-endemic settings, a step toward sustainable malaria elimination.

Abstract Background The malaria vaccine R21/Matrix-M is recommended for young children in malaria-endemic regions. However, the small vaccine-eligible population and waning vaccine efficacy mean that routine vaccination is unlikely to prevent severe cases in older children who experience significant malaria burden. As R21/Matrix-M vaccination expands, targeting older age groups may be warranted, depending on funding. Methods Using a stochastic, individual-based Plasmodium falciparum malaria transmission model, we estimate the impact of (1) one-off catch-up campaigns with R21/Matrix-M to previously unvaccinated age groups between age 6 months and 14 years, and/or (2) extra boosters at 2, 5, and/or 10 years after the primary series in low, moderate, and high transmission settings. We assume that vaccine immunogenicity in older children is equivalent to that of the standard target age group, though clinical trials have shown lower immunogenicity in older children. Results Catch-up campaigns in moderate-to-high transmission settings targeting younger children averted the most uncomplicated cases per 1000 additional doses (358 (95% credible interval (CI) 113–570) in children aged 6 months–2 years at 45% PfPR2-10), compared with targeting older children. In low transmission settings, the impact was similar across age groups, with a slightly higher impact when targeting school-aged children (373 (95% CrI 240–518) in children aged 5–9 years at 5% PfPR2-10). Across extra booster strategies, an extra booster 10 years post- primary series averted the most severe cases per 1000 additional doses at low transmission (12 (95% CrI 6–18) at 5% PfPR2-10), but the least at high transmission (− 4 (95% CrI − 11–3) at 45% PfPR2-10). Expanding the vaccine-eligible population in areas of moderate-to-high transmission often had higher incremental efficiency than routine age-based vaccination at low transmission. For example, an extra booster 5 years post-primary series averted 835 (95% CrI 605-1274) clinical cases per 1000 additional doses in a 45% PfPR2-10 perennial setting versus 247 (95% CrI 177-345) clinical cases per 1000 doses with routine vaccination in a 5% PfPR2-10 perennial setting. Sensitivity analyses assuming lower immunogenicity in older children modestly reduced the per-dose impact, but overall conclusions remained unchanged. Conclusions Catch-up campaigns or extra booster doses of R21/Matrix-M can provide benefits beyond routine administration, with the per-additional-dose value approaching that of routine vaccination, but this varies by transmission and seasonality setting. Further empirical studies, particularly on vaccine efficacy in older children, are warranted to inform policy guidance for malaria vaccination implementation.

Global climate models (GCMs) are essential tools for understanding the climate system and projecting its evolution under different scenarios. However, differences in model construction introduce uncertainties, and GCMs have coarse resolution and inherent biases, limiting their effectiveness for informing local or regional adaptation and mitigation planning. We apply the statistical Double Bias-Corrected Constructed Analogues (DBCCA) method to generate bias-corrected and downscaled climate projections at daily and 0.1° spatial resolution for 1985–2100, with a specific focus on supporting tropical health-related impact research. Our quasi-global, high-resolution projections are based on six GCMs from Phase 6 of the Coupled Model Intercomparison Project (CMIP6) under two emission scenarios (SSP2-4.5 and SSP5-8.5), covering 12 land-only domains between 60°N and 60°S. Moreover, many impact researchers rely on accessible data aggregated to administrative units, often weighted by population, rather than gridded data, as these align more directly with policy- and decision-making. Based on our projections, we also provide user-ready (population-weighted) spatially aggregated climate variables at administrative unit levels (0–2) for 104 countries prioritized for tropical disease research.

The use of advanced analytics in public health policy remains hindered by a disconnect between researchers, policymakers and technical experts. Bridging this gap requires intentional knowledge translation strategies that facilitate interdisciplinary collaboration and real-world application of research findings. Hackathons, which bring together diverse stakeholders in a time-bound, solution-oriented format, offer an approach to address this challenge. In January 2025, the MRC Centre for Global Infectious Disease Analysis and the Centre for Epidemiological Modelling and Analysis at the University of Nairobi organised the Bridging the Gap Hackathon, designed to strengthen collaboration between academia, policy and public health practitioners in Kenya. The hackathon convened researchers, software engineers and policymakers to co-develop data-driven tools to tackle public health challenges identified by Kenya's Ministry of Health and the Directorate of Veterinary Services. Over five days and using a structured multi-stage process, six interdisciplinary teams developed prototype solutions to improve outbreak surveillance, vaccine deployment, data quality monitoring and health workforce estimation. This paper reflects on the hackathon's structure, participant experiences and project outcomes, highlighting key lessons for future knowledge translation initiatives. Our findings suggest that hackathons can serve as effective platforms for accelerating interdisciplinary research impact, fostering engagement between policymakers and researchers and promoting the development of solutions to public health issues.

BACKGROUND:Global investments to combat HIV, tuberculosis, and malaria (HTM) have delivered substantial health gains and may have reduced the burden placed by these diseases on the routine health system. We estimated the reduction in primary healthcare (PHC) utilization resulting from the scale-up of HTM services over 2000-2023 in 108 low- and middle-income countries. METHODS AND FINDINGS:For each disease, we applied established mathematical models to quantify PHC utilization (outpatient visits and inpatient bed-days provided outside of HTM programs) by individuals with symptomatic HIV, tuberculosis, or malaria unable to access HTM-specific services. For each country, we estimated averted PHC utilization by comparing a scenario describing the actual scale-up of HTM services to a counterfactual scenario holding HTM service coverage constant at year 2000 levels. We applied published unit costs to estimate the averted costs resulting from reduced PHC utilization. Over 2000-2023, scale-up of HTM services averted an estimated 6.9 (95% uncertainty interval (UI) [4.4, 10.5]) billion outpatient PHC visits and 3.9 (95% UI [2.5, 5.9]) billion inpatient bed-days, representing US$135 (95% UI [71, 250]) billion in averted costs. These reductions were greatest in sub-Saharan Africa and East Asia and Pacific regions. Across study countries, these reductions represented a median of 4.4% of hospital bed capacity and 1.6% of government health spending in 2023. These percentages were 22.9% and 5.1%, respectively, for low-income countries. Our analysis did not consider changes in PHC services beyond utilization. Also, several inputs were missing in some countries, with missing values estimated using regression imputation. CONCLUSIONS:Over recent decades, sustained investments in HTM services in high-burden settings have averted substantial PHC utilization and associated costs. These benefits should be considered when assessing investment impact.

BackgroundThe availability of many tools for malaria control leads to complex decisions regarding the most cost-effective intervention package based on local epidemiology. Mosquito characteristics influence the impact of vector control, but entomological surveillance is often limited due to a lack of resources in national malaria programmes.MethodsThis study quantified the monetary value of information provided by entomological data collection for programmatic decision-making using a mathematical model of Plasmodium falciparum transmission. The 3-year impact and cost of various intervention packages was simulated in different sub-Saharan African settings, including combinations of scaling-up insecticide-treated nets (ITN), switching to next-generation ITNs, and a treatment and prevention package. The DALYs averted and their net monetary benefit were compared at different cost-effectiveness thresholds and the value of resolving uncertainty in entomological model parameters was calculated.ResultsAcross transmission settings and at cost-effectiveness thresholds over US$170 per DALY averted, the most cost-effective intervention package was switching to and scaling up pyrethroid-pyrrole ITNs combined with the treatment and prevention package. The median expected value of perfect information on the entomological indicators was US$0.05 (range 0.02-0.23) and US$0.17 (range 0.09-1.43) per person at risk at thresholds of US$75 and US$1000 per DALY averted, respectively. This represented less than 2% of the net monetary benefit of implementing the most cost-effective intervention package. Value of information estimates at cost-effectiveness thresholds over US$250 were higher than current investments into entomological monitoring by the US President's Malaria Initiative.ConclusionsThese results suggest that entomological data collection should not delay implementation of interventions with demonstrated efficacy in most settings, but that sustained investments into and use of entomological surveillance are nevertheless worthwhile and have broad value to national malaria programmes.

Background: Investments to combat HIV, tuberculosis, and malaria (HTM) have delivered substantial health gains in high-burden settings. There is limited evidence on how this has affected primary health care (PHC). We estimated the changes in PHC utilization and associated cost savings resulting from scale-up of HTM interventions in 108 low- and middle-income countries over 2000-2023. Methods: For each disease, we applied validated mathematical models quantifying the incremental differences in PHC outpatient visits and inpatient bed-days by individuals with untreated symptomatic HIV, tuberculosis, or malaria. By country and year, we compared the actual scale-up of HTM services scenario against a counterfactual scenario holding HTM intervention coverage constant at year 2000 levels. We estimated the cost savings associated with these utilization reductions, and compared results to national hospital capacity and health expenditure. Findings: Over 2000-2023, scale-up of HTM services averted an estimated 6.9 (95% interval: 4.4-10.4) billion PHC outpatient visits and 3.9 (2.5-6.1) billion inpatient bed-days, equivalent to US$135 (77-225) billions in total cost savings. Reductions in utilization and cost savings were greatest in the Sub-Saharan Africa and East Asia and Pacific regions. For 2023, a median of 4.4% of hospital bed capacity and 1.6% of government health expenditures were freed-up across study countries. These percentages were 22.9% and 5.1% respectively for low-income countries. Interpretation: Sustained investments in HTM services in high-burden settings generated substantial cost savings over recent decades through reduced PHC utilization. These benefits should be considered when assessing investment impact. Funding: The Global Fund. ### Competing Interest Statement Funding for this study was provided by the Global Fund. PW acknowledges support from the Bill & Melinda Gates Foundation (INV-043624). TBH and PW acknowledge funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/X020258/1), funded by the UK Medical Research Council (MRC). This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking. NAM acknowledges support from the US National Institutes for Health, US Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, and the European Commission. ### Funding Statement NM, TBH, CP, JS, and PW acknowledge support from the Global Fund to Fight AIDS, TB, and Malaria. PW acknowledges support from the Bill & Melinda Gates Foundation (INV-043624). TBH and PW acknowledge funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/X020258/1), funded by the UK Medical Research Council (MRC). This UK funded award is carried out in the frame of the Global Health EDCTP3 Joint Undertaking. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Objective:To estimate the outcome of programmes on human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis and malaria in Malawi across multiple health domains. Methods:We used an integrated epidemiological and health system model to estimate the impact of HIV/AIDS, tuberculosis and malaria programmes in Malawi from 2010 to 2019. We incorporated interacting disease dynamics, intervention effects and health system use in the model. We examined four scenarios, comparing actual programme delivery with hypothetical scenarios excluding the health programmes individually and collectively. Findings:From 2010 to 2019, an estimated 1.08 million deaths and 74.89 million disability-adjusted life years were prevented by the HIV/AIDS, tuberculosis and malaria programmes. An additional 15 600 deaths from other causes were also prevented. Life expectancy increased by 13.0 years for males and 16.9 years for females. The programmes accounted for 18.5% (95% uncertainty interval, UI: 18.2 to 18.6) of all health system interactions, including 157.0 million screening and diagnostic tests and 23.2 million treatment appointments. Only 41.5 million additional health worker hours (17.1%; 95% UI: 15.9 to 17.4%) of total health worker time) were needed to achieve these gains. The HIV/AIDS, tuberculosis and malaria programmes required an additional 120.7 million outpatient appointments, which were offset by a net decrease in inpatient care (9.4 million bed-days) that would have been necessary in their absence. Conclusion:HIV/AIDS, tuberculosis and malaria programmes have greatly increased life expectancy and provided direct and spill-over effects on health in Malawi. These investments reduced the burden on inpatient and emergency care, which requires more intensive health worker involvement.

Malaria vector control tools currently focus on insecticide treated nets (ITNs) and indoor residual spraying in malaria-endemic locations, but additional preventative strategies are needed to address protection gaps. Larval source management (LSM) includes larvicide application to aquatic habitat and an array of alternative forms of environmental efforts. An individual-based transmission model for falciparum malaria is used to demonstrate the theoretical benefit of suppressing malaria adult mosquito vector densities through LSM. The model simulates results of epidemiological trials from Western Kenya (a hilly area with papyrus swamps adjacent to human settlements and moderate to high perennial malaria transmission) and Côte d'Ivoire (an area with Sudanese climate, reducing vegetation cover and high transmission) that applied larvicide alongside ITNs, and investigates whether estimated changes in adult density can be used to project changes in human malaria. In the Western Kenya setting generalised linear models estimate 82% (90% credible intervals: 64% - 92%) and 88% (79% - 94%) reductions in the proportion of adult Anopheles funestus and Anopheles gambiae complex mosquitoes respectively as measured by CDC light traps. In Côte d'Ivoire, an 82% (56% - 93%) reduction of the dominant An. gambiae vector was estimated using standard window trap and pyrethrum spray catch. Both studies had variable village-level impacts. The transmission dynamics model predicted that these entomological impacts would result in a reduction in malaria prevalence in children of 6-months to 10-years of age of 48 - 72% in Kenya, and a 11 - 78% reduction in all-age clinical incidence across villages in Côte d'Ivoire, which are broadly consistent with the empirically observed outcomes. High heterogeneity between villages within the same study indicate that the relative or absolute reductions in mosquito adult density observed in these trials cannot be simply extrapolated to other regions. The LSM strategy adopted, unit area covered, and multiple environmental covariates all contribute to differences in indicators that could be used to assess entomological impacts and the corresponding epidemiological outcomes. This important malaria control tool was impactful across all sites examined, though further work is needed to understand how best to use this tool in the fight against malaria.

BACKGROUND:The Sustainable Development Goals (SDGs) include ending the epidemics of HIV, tuberculosis, and malaria by 2030. With 5 years remaining to meet this goal, and with the Global Fund to Fight AIDS, Tuberculosis and Malaria seeking funding for programmes in 2027-29, establishing what can be achieved through continued investment in combatting these diseases is crucial. We aimed to estimate the potential for impact by analysing the funding landscape and epidemiological situations of these three diseases, the costs of key programmes, and the extent of possible future progress in the countries eligible for Global Fund support. METHOD:In this modelling study, we developed estimates of the financial resources needed in Global Fund-supported countries to combat HIV, tuberculosis, and malaria from the global plans produced by UNAIDS, the Stop TB Partnership, and WHO. Estimates of available resources in the coming years were obtained by assuming that national expenditure on the three diseases would grow in line with general governmental expenditures, that the Global Fund would contribute an additional $18·0 billion, and that other developmental assistance would be at the same level in real terms as the average in the period 2020-22. Epidemiological and costing models for each of the three diseases were used to quantify the possible impact in Global Fund-eligible countries (including on aggregated mortality and incidence rates). The return on investment (ROI) was computed considering both the intrinsic value of health and the direct economic benefits of the reduced risk of morbidity and premature mortality. The analysis was completed at the end of 2024 with the latest available data, which pertained to the year 2023. The focus of the projection period was 2027-29, a period for which scale-up plans and funding have not yet been committed and the period when most of the resources raised by the eighth replenishment of the Global Fund would be used. FINDINGS:The total resource needs for the three diseases were estimated to be US$140·6 billion in 2027-29. We calculated that $111·3 billion (79%) of this need could be met from domestic financing ($69·7 billion), the Global Fund ($18·0 billion), and other external donors ($23·6 billion). Optimal use of these available resources could save 23 million lives and avert 400 million cases and new infections during 2027-29. The trajectory of the combined mortality rate for all diseases was projected to approach that needed to reach the SDG for 2030 (with a difference between the target in 2030 and the projection at the end of 2029 of between 1·5% and 15·5% of the normalised aggregated mortality rate), inequality in life expectancy between countries would be 7% lower by 2029, and 189 million fewer hospital days and 572 million fewer outpatient visits would be needed in 2027-29, saving $1·1 billion. For every $1·00 invested, there could be up to $19·00 in intrinsic health value created or $3·50 in direct economic benefits. INTERPRETATION:Continued investments to combat HIV, tuberculosis, and malaria could yield enormous health gains and a high return on investment. Realising these benefits will require continued growth in national expenditure and a broad maintenance of external financing for these diseases, including a successful replenishment of the Global Fund in 2025. FUNDING:The Global Fund.

COVID-19 has underscored the need for more timely access to vaccines during future pandemics. This has motivated development of broad-spectrum vaccines providing protection against entire viral families, which could be stockpiled and deployed rapidly following detection. Using mathematical modelling, we assess the utility of a broadly protective sarbecovirus vaccine during a hypothetical SARS-X outbreak, for a range of implementation strategies including ring-vaccination, spatial-targeting and mass vaccination of high-risk groups. Broadly protective sarbecovirus vaccine ring- or spatial strategies alone are insufficient to contain epidemics driven by a SARS-CoV-2-like virus, but when paired with rapid isolation and quarantine, can achieve containment of a SARS-CoV-1-like virus. Where suppression fails, broadly protective sarbecovirus vaccine utilisation still reduces the effective reproduction number and slows epidemic growth - buying valuable time for health-system response and virus-specific vaccine development. Vaccination of high-risk populations with the broadly protective sarbecovirus vaccine ahead of virus-specific vaccine availability could reduce mortality and enable shorter and less stringent non-pharmaceutical interventions to be imposed; results are sensitive to vaccine properties (e.g., efficacy), health system capabilities (e.g. rollout speed) and timeline to virus-specific vaccine availability. Our modelling suggests that broadly protective sarbecovirus vaccine delivery to those aged 60+ years could have averted 21-78 % of COVID-19 deaths during the pandemic's first year, depending on the size of the stockpile. Realising this potential impact will require investment in manufacturing, delivery capacity and equitable access ahead of future pandemics.

Large reductions in the global malaria burden have been achieved, but plateauing funding poses a challenge for progressing towards the ultimate goal of malaria eradication. Using previously published mathematical models of Plasmodium falciparum and Plasmodium vivax transmission incorporating insecticide-treated nets (ITNs) as an illustrative intervention, we sought to identify the global funding allocation that maximized impact under defined objectives and across a range of global funding budgets. The optimal strategy for case reduction mirrored an allocation framework that prioritizes funding for high-transmission settings, resulting in total case reductions of 76% and 66% at intermediate budget levels, respectively. Allocation strategies that had the greatest impact on case reductions were associated with lesser near-term impacts on the global population at risk. The optimal funding distribution prioritized high ITN coverage in high-transmission settings endemic for P. falciparum only, while maintaining lower levels in low-transmission settings. However, at high budgets, 62% of funding was targeted to low-transmission settings co-endemic for P. falciparum and P. vivax. These results support current global strategies to prioritize funding to high-burden P. falciparum-endemic settings in sub-Saharan Africa to minimize clinical malaria burden and progress towards elimination, but highlight a trade-off with ‘shrinking the map’ through a focus on near-elimination settings and addressing the burden of P. vivax.

AbstractGene drives are a promising means of malaria control with the potential to cause sustained reductions in transmission. In real environments, however, their impacts will depend on local ecological and epidemiological factors. We develop a data-driven model to investigate the impacts of gene drives that causes vector population suppression. We simulate gene drive releases in sixteen ~ 12,000 km2 areas of west Africa that span variation in vector ecology and malaria prevalence, and estimate reductions in vector abundance, malaria prevalence and clinical cases. Average reductions in vector abundance ranged from 71.6–98.4% across areas, while impacts on malaria depended strongly on which vector species were targeted. When other new interventions including RTS,S vaccination and pyrethroid-PBO bednets were in place, at least 60% more clinical cases were averted when gene drives were added, demonstrating the benefits of integrated interventions. Our results show that different strategies for gene drive implementation may be required across different African settings.

AbstractObjectiveHuge investments in HIV, TB, and malaria (HTM) control in Malawi have greatly reduced disease burden. However, the joint impact of these services across multiple health domains and the health system resources required to deliver them are not fully understood.MethodsAn integrated epidemiological and health system model was used to assess the impact of HTM programmes in Malawi from 2010 to 2019, incorporating interacting disease dynamics, intervention effects, and health system usage. Four scenarios were examined, comparing actual programme delivery with hypothetical scenarios excluding programmes individually and collectively.FindingsFrom 2010-2019, HTM programmes were estimated to have prevented 1.08 million deaths and 74.89 million DALYs. An additional 15,600 deaths from other causes were also prevented. Life expectancy increased by 13.0 years for males and 16.9 years for females.The HTM programmes accounted for 24.2% of all health system interactions, including 157.0 million screening/diagnostic tests and 23.2 million treatment appointments. Accounting for the anticipated health deterioration without HTM services, only 41.55 million additional healthcare worker hours were required (17.1% of total healthcare worker time) to achieve these gains. The HTM programme eliminated the need for 123 million primary care appointments, offset by a net increase in inpatient care demand (9.4 million bed-days) that would have been necessary in its absence.ConclusionsHTM programmes have greatly increased life expectancy, providing direct and spillover effects on health. These investments have alleviated the burden on inpatient and emergency care, which requires more intensive healthcare provider involvement.

The introduction of artemisinin combination therapies (ACTs) has significantly reduced the burden of Plasmodium falciparum malaria, yet the emergence of artemisinin partial resistance (ART-R) as well as partner drug resistance threatens these gains. Recent confirmations of prevalent de novo ART-R mutations in Africa, in particular in Rwanda, Uganda and Ethiopia, underscore the urgency of addressing this issue in Africa. Our objective is to characterise this evolving resistance landscape in Africa and understand the speed with which ART-R will continue to spread. We produce estimates of both ART-R and partner drug resistance by bringing together WHO, WWARN and MalariaGen Pf7k data on antimalarial resistance in combination with a literature review. We integrate these estimates within a mathematical modelling approach, aincorporating to estimate parameters known to impact the selection of ART-R for each malaria-endemic country and explore scenarios of ART-R spread and establishment. We identify 16 malaria-endemic countries in Africa to prioritise for surveillance and future deployment of alternative antimalarial strategies, based on ART-R reaching greater than 10% prevalence by 2040 under current malaria burden and effective-treatment coverage. If resistance continues to spread at current rates with no change in drug policy, we predict that partner drug resistance will emerge and the mean percentage of treatment failure across Africa will reach 30.74% by 2060 (parameter uncertainty range: 24.98% - 34.54%). This translates to an alarming number of treatment failures, with 52,980,600 absolute cases of treatment failure predicted in 2060 in Africa (parameter uncertainty range: 26,374,200 - 93,672,400) based on current effective treatment coverage. Our results provide a refined and updated prediction model for the emergence of ART-R to help guide antimalarial policy and prioritise future surveillance efforts and innovation in Africa. These results put into stark context the speed with which antimalarial resistance may spread in Africa if left unchecked, confirming the need for swift and decisive action in formulating antimalarial treatment policies focused on furthering malaria control and containing antimalarial resistance in Africa. The rise of artemisinin partial resistance (ART-R) and increasing partner drug tolerance by Plasmodium falciparum malaria in Africa threatens to undo malaria control efforts. Recent confirmations of de novo ART-R markers in Rwanda, Uganda, and Ethiopia highlight the urgent need to address this threat in Africa, where the vast majority of cases and deaths occur. This study characterises the resistance landscape and predicts the spread of antimalarial resistance across Africa. We estimate and map the current levels of resistance markers related to artemisinin and its partner drugs using WHO, WWARN, and MalariaGen Pf7k data. We combine these estimates with current malaria transmission and treatment data and use an established individual-based model of malaria resistance to simulate future resistance spread. We identify 16 African countries at highest risk of ART-R for prioritisation of enhanced surveillance and alternative antimalarial strategies. We project that, without policy changes, ART-R will exceed 10% in these regions by 2040. By 2060, if resistance spreads unchecked, we predict mean treatment failure rates will reach 30.74% (parameter uncertainty range: 24.98% - 34.54%) across Africa. This alarming spread of resistance is predicted to cause 52.98 million treatment failures (uncertainty range: 26.37 million - 93.67 million) in 2060. The impact of antimalarial resistance in Africa, if left unchecked, would hugely damage efforts to reduce malaria burden. Our results underscore the critical need for swift policy action to contain resistance and guide future surveillance and intervention efforts.

BACKGROUND:The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS:We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS:Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION:Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING:The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.