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Background: The 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., Methods: This 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., Results: Across 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., Conclusions: These 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., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Insecticide treated nets (ITNs) are the most important malaria prevention tool in Africa but the rise of pyrethroid resistance in mosquitoes is likely impeding control. WHO has recommended a novel pyrethroid-pyrrole ITN following evidence of epidemiological benefit in two cluster-randomised, controlled trials (CRTs). It remains unclear how effective more costly pyrethroid-pyrrole ITNs are compared with other tools, or whether they should be deployed when budgets are limited. We aimed to compare the epidemiological impact and cost-effectiveness of the mass distribution of pyrethroid-pyrrole ITNs relative to other ITNs over 3 years in different African settings., Methods: In this individual-based malaria transmission dynamics modelling study we characterise the entomological impact of ITNs using data from a systematic review of experimental hut trials from across Africa. This African entomological data was used to inform an individual-based malaria transmission dynamics model, which was validated against CRT results from Benin and Tanzania. The full impact of new ITNs was quantified for trial sites and simulation was used to project impact in different settings which were included within an accessible interface (the Malaria Intervention Tool) to support National Malaria Programmes to explore how vector control tools and budgets could be allocated across regions to avert the most cases., Findings: The model projects that distributing pyrethroid-pyrrole ITNs averted 65% (95% credible interval 48-74) of cases over 3 years in Tanzania, and 75% (28-93) in Benin. The model indicates that trials might have underestimated the benefits of switching ITNs by 12-16% over 3 years because participants stopped using trial-allocated nets. In moderate endemicity non-trial settings, pyrethroid-pyrrole ITNs are projected to reduce malaria prevalence by 25-60% and switching from pyrethroid-only ITNs is probably highly cost-effective in most locations given current prices, averting an additional 10-30% of cases., Interpretation: The benefit of pyrethroid-pyrrole ITNs varies by setting but is generally the most cost-effective indoor vector control intervention in Africa. National Malaria Programmes can strategise deployment to maximise impact. Entomological data could broadly predict epidemiological impact, although there are some inconsistencies, illustrating the challenge in capturing the dynamics across diverse settings., Funding: Unitaid, Bill & Melinda Gates Foundation, the UK Medical Research Council, Wellcome Trust, and the UK Foreign, Commonwealth & Development Office., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has underscored the beneficial impact of vaccines. It also highlighted the need for future investments to expedite an equitable vaccine distribution. The 100 Days Mission aims to develop and make available a new vaccine against a future pathogen with pandemic potential within 100 days of that pathogen threat being recognised. We assessed the value of this mission by estimating the impact that it could have had on the COVID-19 pandemic., Methods: Using a previously published model of SARS-CoV-2 transmission dynamics fitted to excess mortality during the COVID-19 pandemic, we projected scenarios for three different investment strategies: rapid development and manufacture of a vaccine, increasing manufacturing capacity to eliminate supply constraints, and strengthening health systems to enable faster vaccine roll-outs and global equity. Each scenario was compared against the observed COVID-19 pandemic to estimate the public health and health-economic impacts of each scenario., Findings: If countries implemented non-pharmaceutical interventions (NPIs) as they did historically, the 100 Days Mission could have averted an estimated 8·33 million deaths (95% credible interval [CrI] 7·70-8·68) globally, mostly in lower-middle income countries. This corresponds to a monetary saving of US$14·35 trillion (95% CrI 12·96-17·87) based on the value of statistical life-years saved. Investment in manufacturing and health systems further increases deaths averted to 11·01 million (95% CrI 10·60-11·49). Under an alternative scenario whereby NPIs are lifted earlier on the basis of vaccine coverage, the 100 Days Mission alone could have reduced restrictions by 12 600 days (95% CrI 12 300-13 100) globally while still averting 5·76 million deaths (95% CrI 4·91-6·81)., Interpretation: Our findings show the value of the 100 Days Mission and how these can be amplified through improvements in manufacturing and health systems equity. However, these investments must be enhanced by prioritising a more equitable global vaccine distribution., Funding: Schmidt Science Fellowship in partnership with the Rhodes Trust, WHO, UK Medical Research Council, Coalition for Epidemic Preparedness Innovations., Competing Interests: Declaration of interests The Coalition for Epidemic Preparedness Innovations (CEPI) funded the investigation into the impact of the 100 Days Mission. The authors maintained full freedom when designing the study and deciding on additional scenarios to explore. ACG has received personal consultancy fees from HSBC, GlaxoSmithKline, Sanofi, and WHO related to COVID-19 epidemiology and from The Global Fund to Fight AIDS, Tuberculosis and Malaria for work unrelated to COVID-19. ACG was previously a non-remunerated member of a scientific advisory board for Moderna and is a non-remunerated member of the scientific advisory board for the Coalition for Epidemic Preparedness; has received personal consultancy fees from WHO for work related to malaria. OJW also received personal consultancy fees from WHO and the Clinton Health Access Initiative for work related to malaria. ABH has received personal consultancy fees from WHO for work related to COVID-19, and grant funding for COVID-19 work from WHO and NSW Ministry of Health, Australia; and is a member of the WHO Immunization and Vaccines Related Implementation Research Advisory Committee. AAT developed the allocation algorithm in collaboration with COVAX through funding from the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Interests OJW received personal consultancy fees from Clinton Health Access Initiative related to artemisinin resistance modelling.

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 (PfPR 2-10 ) and ranges from 3% to 65% PfPR 2-10 ., 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 PfPR 2-10 ., 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., Competing Interests: Declaration of interests AVSH and KJE are named as co-inventors on patent applications related to R21 and are entitled to a royalty share on any future income in conformity with the University of Oxford's policy. KJE was an employee of the University of Oxford at the time of the work and is now an employee of GSK. KJE holds restricted shares in the GSK group of companies. The University of Oxford has received funding from the Serum Institute of India to support funding of several African trials including the ongoing phase 3 trial of R21/Matrix-M. AVSH is chief investigator of these trials. PW has received funding from Gavi and the Wellcome Trust in the past 36 months. ACG has received funding from Gavi and NIH and consulting fees from the Global Fund in the past 36 months and is a trustee at Malaria No More UK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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 ., Competing Interests: NS, HT, MP, GC, PW, MW, KH, AG No competing interests declared, (© 2023, Schmit, Topazian, Pianella et al.)

Background: Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity., Methods and Findings: We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus., Conclusions: Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality., Competing Interests: ACG was previously a non-renumerated member of a scientific advisory board for Moderna, has received consultancy funding from GSK and Sanofi related to COVID-19 vaccination, and is a member of the CEPI scientific advisory board. She has received grant funding from Gavi for COVID-19 related work. ABH, PW and ACG have previously received consultancy payments from WHO for COVID-19 related work. ABH provides COVID-19 modelling advice to the New South Wales Ministry of Health, Australia. ABH was previously engaged by Pfizer Inc to advise on modelling RSV vaccination strategies for which she received no financial compensation. EMR is a non-remunerated member of the UK Vaccines Network, the UKRI COVID-19 taskforce and the British Society for Immunology Covid-19 taskforce. SLW is currently employed by Merck (USA/CAN), MSD (outside USA/CAN). None of this work was done while the author was an employee and none of his work for Merck is related in any way to the contents of this paper. NMF declares grants from UK MRC, UK NIHR, Bill and Melinda Gates Foundation, Gavi, Wellcome Trust. NMF is Member of UK government and WHO advisory committees., (Copyright: © 2023 Hogan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Increasing vaccine hesitancy and refusal poses a challenge to public health as even small reductions in vaccine uptake can result in large outbreaks of infectious diseases. Here we estimate the societal costs of vaccine refusal using measles as a case study., Methods: We developed a compartmental metapopulation model of measles transmission to explore how the changes in the size and level of social mixing between populations that are "pro-vaccination", and "anti-vaccination" impacts the burden of measles. Using the projected cases and deaths, we calculated the health, healthcare, direct medical costs, and productivity loss associated with vaccine refusal. Using measles in England as a case study, we quantified the societal costs that each vaccine refusal imposes on society., Findings: When there is a high level of mixing between the pro- and anti-vaccination populations, those that refuse to be vaccinated benefit from the herd immunity afforded by the pro-vaccination population. At the same time, their refusal to be vaccinated increases the burden in those that are vaccinated due to imperfect vaccines, and in those that are not able to be vaccinated due to other underlying health conditions. Using England as a case study, we estimate that this translates to a societal loss of GBP 292 million and disease burden of 17 630 quality-adjusted-life-years (sensitivity range 10 594-50 379) over a 20-year time horizon. Of these costs, 26 % are attributable to healthcare costs and 74 % to productivity losses for patients and their carers. This translates to a societal loss per vaccine refusal of GBP 162.21 and 0.01 (0.006-0.03) quality-adjusted-life-years., Interpretation: Our findings demonstrate that even low levels of vaccine refusal can have a substantial and measurable societal burden on the population. These estimates can support the value of investment in interventions that address vaccine hesitancy and vaccine refusal, providing not only improved public health but also potential economic benefits to society., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The World Health Organization has recommended a 4-dose schedule of the RTS,S/AS01 (RTS,S) vaccine for children in regions of moderate to high P. falciparum transmission. Faced with limited supply and finite resources, global funders and domestic malaria control programs will need to examine the relative cost-effectiveness of RTS,S and identify target areas for vaccine implementation relative to scale-up of existing interventions., Methods: Using an individual-based mathematical model of P. falciparum, we modelled the cost-effectiveness of RTS,S across a range of settings in sub-Saharan Africa, incorporating various rainfall patterns, insecticide-treated net (ITN) use, treatment coverage, and parasite prevalence bands. We compare age-based and seasonal RTS,S administration to increasing ITN usage, switching to next generation ITNs in settings experiencing insecticide-resistance, and introduction of seasonal malaria chemoprevention (SMC) in areas of seasonal transmission., Results: For RTS,S to be the most cost-effective intervention option considered, the maximum cost per dose was less than $9.30 USD in 90.9% of scenarios. Nearly all (89.8%) values at or above $9.30 USD per dose were in settings with 60% established bed net use and / or with established SMC, and 76.3% were in the highest PfPR 2-10 band modelled (40%). Addition of RTS,S to strategies involving 60% ITN use, increased ITN usage or a switch to PBO nets, and SMC, if eligible, still led to significant marginal case reductions, with a median of 2,653 (IQR: 1,741 to 3,966) cases averted per 100,000 people annually, and 82,270 (IQR: 54,034 to 123,105) cases averted per 100,000 fully vaccinated children (receiving at least three doses)., Conclusions: Use of RTS,S results in reductions in malaria cases and deaths even when layered upon existing interventions. When comparing relative cost-effectiveness, scale up of ITNs, introduction of SMC, and switching to new technology nets should be prioritized in eligible settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)