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Journal articleWatson OJ, Tran TN-A, Zupko RJ, et al., 2025,
Global risk of selection and spread of <i>Plasmodium falciparum</i> histidine-rich protein 2 and 3 gene deletions
, NATURE MEDICINE, Vol: 31, ISSN: 1078-8956 -
Journal articleDjègbè NDC, Da DF, Somé BM, et al., 2025,
Exploring near-infrared spectroscopy ability to predict the age and species of Anopheles gambiae sensu lato mosquitoes from different environmental conditions in Burkina Faso
, Malaria Journal, Vol: 24, ISSN: 1475-2875BackgroundNear infrared spectroscopy (NIRS) has shown ability in previous studies to predict age and species of laboratory-reared and wild mosquitoes with moderate to high accuracy. To validate the technique as a routine tool, it is necessary to assess NIRS accuracy on these variables under different environmental conditions susceptible to affect the mosquito cuticle and interfere with the machine accuracy. This study investigated the influence of environmental conditions on NIRS accuracy to determine the age and species of Anopheles gambiae sensu lato (s.l.).MethodsEnvironmental conditions of three important seasonal periods in Burkina Faso covering the onset, the peak and the end of the rainy season were mimicked in the laboratory using incubators. Emerged An. gambiae s.s. and An. coluzzii from laboratory colonies were reared in each period using temperature and relative humidity for predicting mosquito species by NIRS. Wild An. gambiae s.l. (n = 3788) were caught during the 3 different periods described above and analysed by NIRS to predict Anopheles species. Furthermore, first generation of wild Anopheles (n = 1014) was used to assess NIRS ability to classify mosquito age in each environmental condition. All data analysis were performed using a binomial logistic regression model.ResultsNIRS discriminated between laboratory-reared Anopheles with 83% of accuracy independently of any environmental condition. Similar trend was found in wild-caught Anopheles. NIRS accuracies varied slightly in laboratory Anopheles (77–85%) and more strongly in their field counterparts (67–84%). In both cases, models developed from the season of interest were more accurate than models trained with insectary conditions or from a different period of the year, indicating temperature and humidity can impact NIRS accuracy. Models derived from laboratory-mosquitoes reared under fluctuating environmental conditions predicted field-derived mosquito spec
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Journal articleStopard IJ, Sherrard-Smith E, Ranson H, et al., 2025,
Modelling the effects of adult emergence on the surveillance and age distribution of medically important mosquitoes
, PLoS Computational Biology, Vol: 21, ISSN: 1553-734XEntomological surveillance is an important component of mosquito-borne disease control. Mosquito abundance, infection prevalence and the entomological inoculation rate are the most widely reported entomological metrics, although these data are notoriously noisy and difficult to interpret. For many infections, only older mosquitoes are infectious, which is why, in part, vector control tools that reduce mosquito life expectancy have been so successful. The age structure of wild mosquitoes has been proposed as a metric to assess the effectiveness of interventions that kill adult mosquitoes, and age grading tools are becoming increasingly advanced. Mosquito populations show seasonal dynamics with temporal fluctuations. How seasonal changes in adult mosquito emergence and vector control could affect the mosquito age distribution or other important metrics is unclear. We develop stochastic mathematical models of mosquito population dynamics to show how variability in mosquito emergence causes substantial heterogeneity in the mosquito age distribution, with low frequency, positively autocorrelated changes in emergence being the most important driver of this variability. Fitting a population model to mosquito abundance data collected in experimental hut trials indicates these dynamics are likely to exist in wild Anopheles gambiae populations. Incorporating age structuring into an established compartmental model of mosquito dynamics and vector control, indicates that the use of mosquito age as a metric to assess the efficacy of vector-control tools will require an understanding of underlying variability in mosquito ages, with the mean age and other entomological metrics affected by short-term and seasonal fluctuations in mosquito emergence.
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Journal articleSherrard-Smith E, Fillinger U, Tia J-PB, et al., 2025,
Heterogeneous impacts for malaria control from larviciding across villages and considerations for monitoring and evaluation
, PLoS Pathogens, Vol: 21, ISSN: 1553-7366Malaria 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 th
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Journal articleBiggs J, Challenger J, Dee DP, et al., 2025,
Characterisation of between-cluster heterogeneity in malaria cluster randomised trials to inform future sample size calculations
, Nature Communications, Vol: 16, ISSN: 2041-1723Cluster randomised trials (CRTs) are important tools for evaluating the community-wide effect of malaria interventions. During the design stage, CRT sample sizes need to be inflated to account for the cluster heterogeneity in measured outcomes. The coefficient of variation (k), a measure of such heterogeneity, is typically used in malaria CRTs yet is often predicted without prior data. Underestimation of k decreases study power, thus increases the probability of generating null results. In this meta-analysis of cluster-summary data from 24 malaria CRTs, we calculate true prevalence and incidence k values using methods-of-moments and regression modelling approaches. Using random effects regression modelling, we investigate the impact of empirical k values on original trial power and explore factors associated with elevated k. Results show empirical estimates of k often exceed those used in sample size calculations, which reduces study power and effect size precision. Elevated k values are associated with incidence outcomes (compared to prevalence), lower endemicity settings, and uneven intervention coverage across clusters. Study findings can enhance the robustness of future malaria CRT sample size calculations by providing informed k estimates based on expected prevalence or incidence, in the absence of cluster-level data.
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Journal articleMousa A, Cuomo-Dannenburg G, Thompson H, et al., 2025,
Impact of dhps mutations on sulfadoxine pyrimethamine protective efficacy and implications for malaria chemoprevention
, Nature Communications, Vol: 16, ISSN: 2041-1723Sulfadoxine-pyrimethamine (SP) is recommended for perennial malaria chemoprevention in young children in high burden areas across Africa. Mutations in the dihydropteroate synthase (dhps) gene (437 G/540E/581 G) associated with sulfadoxine resistance vary regionally, but their effect on SP protective efficacy is unclear. We retrospectively analyse time to microscopy and PCR-confirmed re-infection in seven efficacy trials including 1639 participants in 12 sites across Africa. We estimate the duration of SP protection against parasites with different genotypes using a Bayesian mathematical model that accounts for variation in transmission intensity and genotype frequencies. The longest duration of SP protection is >42 days against dhps sulfadoxine-susceptible parasites and 30.3 days (95%Credible Interval (CrI):17.1-45.1) against the West-African genotype dhps GKA (437G-K540-A581). A shorter duration of protection is estimated against parasites with additional mutations in the dhps gene, with 16.5 days (95%CrI:11.2-37.4) protection against parasites with the east-African genotype dhps GEA (437G-540E-A581) and 11.7 days (95%CrI:8.0-21.9) against highly resistant parasites carrying the dhps GEG (437G-540E−581G) genotype. Using these estimates and modelled genotype frequencies we map SP protection across Africa. This approach and our estimated parameters can be directly applied to any setting using local genomic surveillance data to inform decision-making on where to scale-up SP-based chemoprevention or consider alternatives.
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Journal articleStopard I, Sanou A, Suh E, et al., 2025,
Modelling the effects of diurnal temperature variation on malaria infection dynamics in mosquitoes
, Communications Biology, Vol: 8, ISSN: 2399-3642Mosquito infection experiments that characterise how sporogony changes with temperature are increasingly being used to parameterise malaria transmission models. In these experiments, mosquitoes are exposed to a range of temperatures, with each group experiencing a single temperature. Diurnal temperature variation can, however, affect the sporogonic cycle of Plasmodium parasites. Mosquito dissection data is not available for all temperature profiles, so we investigate whether mathematical models of mosquito infection parameterised with constant temperature thermal performance curves can predict the effects of diurnal temperature variation. We use this model to predict two key parameters governing disease transmission: the human-to-mosquito transmission probability and extrinsic incubation period – and, embed this model into a malaria transmission model to simulate sporozoite prevalence with and without the effects of diurnal and seasonal temperature variation for a single site in Burkina Faso. Simulations incorporating diurnal temperature variation better predict changes in sporogony in laboratory mosquitoes, indicating that constant temperature experiments can be used to predict the effects of fluctuating temperatures. Including the effects of diurnal temperature variation, however, did not substantially improve the predictive ability of the transmission model to predict changes in sporozoite prevalence in wild mosquitoes, indicating further research is needed in more settings.
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Journal articleMeier-Scherling CPG, Watson OJ, Asua V, et al., 2025,
Selection of Plasmodium falciparum kelch13 mutations in Uganda in comparison with southeast Asia: a modelling study
, The Lancet Microbe, ISSN: 2666-5247BackgroundArtemisinin partial resistance, mediated by mutations in the Plasmodium falciparum kelch13 gene (k13), rapidly spread in southeast Asia, undermining the antimalarial effectiveness of artemisinin-based combination therapies. k13 mutations have also arisen in Africa, but their rates of increase are not well characterised. We aimed to quantify the selection of k13 mutations in Africa and compare the selection with that in southeast Asia.MethodsIn this modelling study, we investigated k13 mutation allele frequency at 16 sites in Uganda (2016–22) and five sites in southeast Asia (in Cambodia, Thailand, and Viet Nam; 2003–14). The Ugandan data were obtained from annual clinical surveillance studies and the southeast Asian data were obtained from the MalariaGEN Pf7 dataset. We investigated five validated and candidate k13 mutations: Pro441Leu, Cys469Phe, Cys469Tyr, Arg561His, and Ala675Val. We calculated annual selection coefficients using Bayesian mixed-effect linear models. We then tested whether the k13 mutation allele frequency in southeast Asia could have been forecast accurately using up to the first 5 years of available data and forecast future k13 mutation allele frequency in Uganda.FindingsWe used data from 7564 samples from Uganda and 6568 samples from southeast Asia. The annual selection coefficient of evaluable k13 mutations (Pro441Leu, Cys469Phe/Tyr, Arg561His, and Ala675Val) across all sites was estimated at 0·381 (95% credible interval 0·298 to 0·472) per year, a 38% increase in relative allele frequency. Selection coefficients across Uganda were 0·494 (−0·462 to 1·410) for Pro441Leu, 0·324 (−0·629 to 1·150) for Cys469Phe, 0·383 (0·207 to 0·591) for Cys469Tyr, and 0·237 (0·087 to 0·403) for Ala675Val. In southeast Asia, the selection coefficients were 0·627 (−0·088 to 1·312) for Cys580Tyr, 0&mid
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ReportWinskill P, Haile L, Ruybal-Pesántez S, et al., 2025,
Rapid response modelled estimates of the effect of the US global aid freeze on President’s Malaria Initiative impact in sub-Saharan Africa
The current freeze on US global aid has the potential to disrupt critical live-saving activities of the President’s Malaria Initiative (PMI). Disruptions or cessation of planned PMI activities in 2025, with no mitigation, could result in an estimated additional 84,200 (95% CI: 69,300, 98,100) malaria deaths in sub-Saharan Africa over the course of 2025. Empirical observations and modelled scenarios highlight the speed at which malaria can resurge following the cessation of core interventions.
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Journal articleDjaafara B, Sherrard-Smith E, Churcher T, et al., 2025,
Spatiotemporal heterogeneity in malaria transmission across Indonesia: analysis of routine surveillance data 2010-2019
, BMC Medicine, Vol: 23, ISSN: 1741-7015BackgroundIndonesia faces challenges in achieving its goal of eliminating malaria by 2030, with cases stagnating between 2015 and 2019. This study analysed regional epidemiological trends and demographic changes in malaria cases from 2010 to 2019, considering differences in surveillance across the country.MethodsWe analysed national and sub-national malaria routine surveillance data using generalised additive and generalised linear models to assess temporal trends in case reporting, test positivity, demographics, and parasite species distribution while accounting for surveillance variations.ResultsAfter adjusting for increased testing from 2015 onwards, we estimated declining malaria incidence in six of seven Indonesian regions. These regions showed a demographic shift toward older, predominantly male cases, suggesting a transition from household to occupational transmission. In contrast, Papua maintained high transmission with cases concentrated in children. Despite comprising only 2% of Indonesia’s population, Papua’s contribution to national malaria cases rose from 40 to 90% (2010–2019).ConclusionWhile most Indonesian regions progress toward elimination by addressing mobile and migrant populations and P. vivax transmission, Papua shows different patterns with persistently high transmission among children. Achieving nationwide elimination requires enhanced control measures, improved healthcare access, and strengthened multisectoral collaboration to address these region-specific challenges.
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Journal articleSchmit N, Topazian H, Pianella M, et al., 2025,
Quantifying the potential value of entomological data collection for programmatic decision-making on malaria control in sub-Saharan African settings
, Malaria Journal, Vol: 24, ISSN: 1475-2875Background: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 investme
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Journal articleMoghaddas NR, Traore MM, Wagman J, et al., 2025,
Exploring the epidemiological impact of attractive targeted sugar bait against malaria in combination with standard malaria control
, Current Research in Parasitology and Vector-Borne Diseases, Vol: 7, ISSN: 2667-114XAttractive targeted sugar bait (ATSB) is a potential new vector control tool that exploits the sugar-feeding behaviour of mosquitoes. Little is known about the factors which drive ATSB efficacy, either as a standalone vector control tool or in combination with existing intervention strategies. It has been suggested that the percentage of wild mosquitoes caught fed on dye-containing sugar baits without the toxin could provide an entomological correlate of the potential epidemiological benefit of ATSB. A transmission dynamics mathematical model is combined with data from wild mosquitoes to investigate the relationship between the mosquito dyed fraction, bait-feeding rate and the potential epidemiological impact of ATSB in the presence of standard malaria control. The dyed fraction in Mali varies substantially in space and time (mean 0.34, standard deviation 0.15), causing estimates of the bait-feeding rate to be highly uncertain, especially in areas with existing vector control tools. The model indicates the dyed fractions observed in field experiments were broadly predictive of the reductions in mosquitoes caught when ATSB stations were deployed at scale in Mali (R2 = 0.90). Model projections suggest that if these bait-feeding rates were observed in all mosquitoes, then the widespread use of ATSB could substantially reduce malaria burden alone or in combinations with standard malaria control, though epidemiological impact is likely to vary substantially in different areas. For example, observing a dyed fraction of 5% would indicate a daily bait-feeding rate of 0.024 (range 0.008–0.049) which is projected to result in 0.13 clinical cases averted per person-year (range 0.051–0.22), a 39% efficacy (range 12–66%) in this particular site. Nevertheless, the uncertainty in the relationship between the observed dyed fraction and the true bait-feeding rate, and the underlying biology of mosquito sugar-feeding means that the epidemiological benefit of this ne
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Journal articlePagabeleguem S, Da DF, Some BM, et al., 2025,
Near-infrared spectroscopy discriminates mass-reared sterile and wild tsetse flies
, PLoS Neglected Tropical Diseases, Vol: 19, ISSN: 1935-2727BackgroundMonitoring the efficacy of the sterile insect technique (SIT) programs, it is desirable to discriminate between wild and sterile tsetse males captured in monitoring traps. Currently, this is primarily achieved by marking sterile males with fluorescent dye powder before release, and identifying them using a fluorescence camera and/or microscope. However, the accuracy of this method is limited due to defective marking and wild flies contaminated with a few dye particles in the monitoring traps. Molecular techniques have been developed to discriminate doubtful flies, but they are expensive for endemic countries.Methodology/Principal findingsHere, we investigate the ability of a new generation monitoring tool, Near-Infrared Spectroscopy (NIRS), to discriminate between laboratory-reared Glossina palpalis gambiensis males and their field counterparts. NIRS was able to discriminate wild males from laboratory-reared males with 86% accuracy. Notably, the prediction accuracy improved to 88% when the laboratory-reared flies had been irradiated.Conclusions/SignificanceThese findings suggest that NIRS can successfully identify tsetse flies even when UV camera identification is inconclusive. However, further studies are needed to expand the training dataset and include additional environmental variables before validating NIRS as a complementary method for future tsetse eradication programs.
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Journal articleAgbevo A, Syme T, Fagbohoun J, et al., 2024,
The experimental hut efficacy of next-generation insecticide-treated nets against pyrethroid-resistant malaria vectors after 12, 24 and 36 months of household use in Benin
, Malaria Journal, Vol: 23, ISSN: 1475-2875BackgroundCluster-randomized controlled trials (cluster-RCTs) have demonstrated variation in the epidemiological efficacy of different next-generation insecticide-treated net (ITN) types, with some providing shorter-lived impact than others. Further studies are needed to assess changes in the insecticidal durability of these ITNs over time to complement cluster-RCT results.MethodsA series of experimental hut trials were performed to evaluate the bioefficacy of new and field-aged next-generation ITNs (PermaNet® 3.0, Royal Guard®, Interceptor® G2) compared to a pyrethroid-only net (Interceptor®) against pyrethroid-resistant malaria vectors in Covè, southern Benin. Field-aged nets were withdrawn from households at 12, 24 and 36 months. Net pieces cut from whole ITNs were analysed for chemical content, and susceptibility bioassays were performed during each trial to assess changes in insecticide resistance in the Covè vector population.ResultsInterceptor® G2 induced superior mosquito mortality than the other ITNs across all time points. The improved mortality with Interceptor® G2 compared to Interceptor® was evident across all time points but was greater with new nets (odds ratio (OR) = 8.6, 95% CI [7.4, 10.1]) than field-aged nets (OR = 2.5, 95% CI [1.8, 3.5] at 12 months, OR = 2.4, 95% CI [1.6, 3.7] at 24 months and OR = 2.9, 95% CI [1.6, 5.1] at 36 months). New Royal Guard® reduced mosquito fertility compared to the other ITNs, but this improvement fell after field-ageing, particularly at 24 months when it was similar to Interceptor® (11% vs 3%, p = 0.08). When new, mortality was significantly higher with PermaNet® 3.0 compared to Interceptor® (OR = 3.6, 95% CI [3.0, 4.2]); however, this benefit was lost with field-aged nets at 12 months (OR = 1.1, 95% CI [0.8, 1.5]) and 24 months (OR = 0.6, 95% CI [
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Journal articleChurcher TS, Stopard IJ, Hamlet A, et al., 2024,
The epidemiological benefit of pyrethroid–pyrrole insecticide treated nets against malaria: an individual-based malaria transmission dynamics modelling study
, The Lancet Global Health, Vol: 12, Pages: e1973-e1983, ISSN: 2214-109XBackgroundInsecticide 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.MethodsIn 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.FindingsThe 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
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