There is concern that increases in temperature due to climate change could lead to shifts in the dynamics and distribution of mosquito vectors. Many current models assume there are average thermal performance curves for a given vector species transmission. However, this one-size-fits-all assumption ignores the potential for local adaptation to create population-specific differences in thermal performance. In this study, we explored thermal performance of five independent field populations of Ae. aegypti from Mexico, together with a standard laboratory strain. We reared these six populations at temperatures between 13°C- 37°C to generate thermal performance curves for a suite of life-history traits. Composite models integrating these traits revealed the effects of temperature on population growth rates and dengue virus transmission potential. The results provide strong evidence for the potential for local adaptation in Ae. aegypti populations, challenging applicability of one-size-fits-all thermal performance models to assess climate impact on mosquito-borne diseases. ### Competing Interest Statement The authors have declared no competing interest.

The distribution and abundance of ectothermic mosquitoes are strongly affected by temperature, but mechanisms remain unexplored. We describe the effect of temperature on the transcriptome of Anopheles stephensi, an invasive vector of human malaria. Adult females were maintained across a range of mean temperatures (20 °C, 24 °C and 28 °C), with daily fluctuations of +5 °C and −4 °C at each mean temperature. Transcriptomes were described up to 19 days post-blood meal. Of the >3100 differentially expressed genes, we observed shared temporal expression profiles across all temperatures, suggesting their indispensability to mosquito life history. Tolerance to 20 and 28 ( + 5°C/−4°C) was associated with larger and more diverse transcriptomes compared to 24 ( + 5 °C/−4 °C). Finally, we identified two distinct trends in gene expression in response to blood meal ingestion, oxidative stress, and reproduction. Our work has implications for mosquitoes’ response to thermal variation, mosquito immune-physiology, mosquito-malaria interactions and the development of vector control tools. Effect of thermal variation and a blood meal on the size, composition and dynamics of the transcriptome of the ectotherm and major malaria vector, Anopheles stephensi

There is concern that increases in temperature due to climate change could lead to shifts in the transmission dynamics and distribution of mosquito vectors. Many current models assume there are 'average' thermal performance curves for a given vector species' life-history traits. However, this 'one-size-fits-all' assumption ignores the potential for standing phenotypic variation in life-history traits to create population-specific differences in thermal performance. In this study, we explored thermal performance of five independent field populations of Ae. aegypti from Mexico, together with a standard laboratory strain. We reared these six populations at temperatures between 13°C- 37°C to generate thermal performance curves for a suite of life-history traits. Composite models integrating these traits revealed the effects of temperature on population growth rates and dengue virus transmission potential. The results provide strong evidence for the potential for local adaptation in Ae. aegypti populations, challenging the applicability of 'one-size-fits-all' thermal performance models to assess climate impact on mosquito-borne diseases.

Mosquito 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.

Most models exploring the effects of climate change on mosquito-borne disease ignore thermal adaptation. However, if local adaptation leads to changes in mosquito thermal responses, “one size fits all” models could fail to capture current variation between populations and future adaptive responses to changes in temperature. Here, we assess phenotypic adaptation to temperature in Aedes aegypti , the primary vector of dengue, Zika, and chikungunya viruses. First, to explore whether there is any difference in existing thermal response of mosquitoes between populations, we used a thermal knockdown assay to examine five populations of Ae. aegypti collected from climatically diverse locations in Mexico, together with a long-standing laboratory strain. We identified significant phenotypic variation in thermal tolerance between populations. Next, to explore whether such variation can be generated by differences in temperature, we conducted an experimental passage study by establishing six replicate lines from a single field-derived population of Ae. aegypti from Mexico, maintaining half at 27°C and the other half at 31°C. After 10 generations, we found a significant difference in mosquito performance, with the lines maintained under elevated temperatures showing greater thermal tolerance. Moreover, these differences in thermal tolerance translated to shifts in the thermal performance curves for multiple life-history traits, leading to differences in overall fitness. Together, these novel findings provide compelling evidence that Ae. aegypti populations can and do differ in thermal response, suggesting that simplified thermal performance models might be insufficient for predicting the effects of climate on vector-borne disease transmission.

Despite concern that climate change could increase the human risk to malaria in certain areas, the temperature dependency of malaria transmission is poorly characterized. Here, we use a mechanistic model fitted to experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae , is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, parasite development rate, and overall vector competence. We use these data, together with estimates of the survival of infected blood-fed mosquitoes, to explore the theoretical influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted.

Biological control has been effectively exploited by mankind since 300 CE. By promoting the natural regulation of pests, weeds, and diseases, it produces societal benefits at the food-environment-health nexus. Here we scrutinize biological control endeavours and their social-ecological outcomes through a holistic ‘One-Health’ lens, recognizing that the health of humans, animals, plants, and the wider environment are linked and interdependent. Evidence shows that biological control generates desirable outcomes within all One Health dimensions, mitigating global change issues such as chemical pollution, biocide resistance, biodiversity loss, and habitat destruction. Yet, its cross-disciplinary achievements remain underappreciated. To remedy this, we advocate a systems-level, integrated approach to biological control research, policy, and practice. Framing biological control in a One Health context helps to unite medical and veterinary personnel, ecologists, conservationists and agricultural professionals in a joint quest for solutions to some of the most pressing issues in planetary health.

Climate warming is considered to be among the most serious of anthropogenic stresses to the environment, because it not only has direct effects on biodiversity, but it also exacerbates the harmful effects of other human-mediated threats. The associated consequences are potentially severe, particularly in terms of threats to species preservation, as well as in the preservation of an array of ecosystem services provided by biodiversity. Among the most affected groups of animals are insects-central components of many ecosystems-for which climate change has pervasive effects from individuals to communities. In this contribution to the scientists' warning series, we summarize the effect of the gradual global surface temperature increase on insects, in terms of physiology, behavior, phenology, distribution, and species interactions, as well as the effect of increased frequency and duration of extreme events such as hot and cold spells, fires, droughts, and floods on these parameters. We warn that, if no action is taken to better understand and reduce the action of climate change on insects, we will drastically reduce our ability to build a sustainable future based on healthy, functional ecosystems. We discuss perspectives on relevant ways to conserve insects in the face of climate change, and we offer several key recommendations on management approaches that can be adopted, on policies that should be pursued, and on the involvement of the general public in the protection effort.

Background In recent years, the downward trajectory of malaria transmission has slowed and, in some places, reversed. New tools are needed to further reduce malaria transmission. One approach that has received recent attention is a novel house-based intervention comprising window screening (S) and general house repairs to make the house more mosquito proof, together with EaveTubes (ET) that provide an innovative way of targeting mosquitoes with insecticides as they search for human hosts at night. The combined approach of Screening + EaveTubes (SET) essentially turns the house into a ‘lure and kill’ device. Methods This study evaluated the impact of SET on malaria infection prevalence in Côte d’Ivoire and compares the result in the primary outcome, malaria case incidence. Malaria infection prevalence was measured in a cross-sectional survey in 40 villages, as part of a cluster-randomised trial evaluating the impact of SET on malaria case incidence. Results Infection prevalence, measured by rapid diagnostic test (RDT), was 50.4% and 36.7% in the control arm and intervention arm, respectively, corresponding to an odds ratio of 0.57 (0.45–0.71), p < 0.0001). There was moderate agreement between RDT and microscopy results, with a reduction in odds of infection of 36% recorded when infection was measured by microscopy. Prevalence measured by RDT correlated strongly with incidence at a cluster level. Conclusions In addition to reducing malaria case incidence, house screening and EaveTubes substantially reduced malaria infection prevalence 18 months after installation. Infection prevalence may be a good metric to use for evaluating malaria interventions in areas of similar transmission levels to this setting. Trial registration ISRCTN18145556, registered 1 February 2017.

Background Attractive targeted sugar bait (ATSB) is a novel approach to vector control, offering an alternative mode of insecticide delivery via the insect alimentary canal, with potential to deliver a variety of compounds new to medical entomology and malaria control. Its potential to control mosquitoes was recently demonstrated in major field trials in Africa. The pyrrole chlorfenapyr is an insecticide new to malaria vector control, and through its unique mode of action—disruption of ATP mediated energy transfer in mitochondria—it may have direct action on energy transfer in the flight muscle cells of mosquitoes. It may also have potential to disrupt mitochondrial function in malarial parasites co-existing within the infected mosquito. However, little is known about the impact of such compounds on vector competence in mosquitoes responsible for malaria transmission. Methods In this study, ATSBs containing chlorfenapyr insecticide and, as a positive control, the anti-malarial drugs artemether/lumefantrine (A/L) were compared for their effect on Plasmodium falciparum development in wild pyrethroid-resistant Anopheles gambiae sensu stricto (s.s.) and for their capacity to reduce vector competence. Female mosquitoes were exposed to ATSB containing either sublethal dose of chlorfenapyr (CFP: 0.025%) or concentrations of A/L ranging from 0.4/2.4 mg/ml to 2.4/14.4 mg/ml, either shortly before or after taking infective blood meals. The impact of their component compounds on the prevalence and intensity of P. falciparum infection were compared between treatments. Results Both the prevalence and intensity of infection were significantly reduced in mosquitoes exposed to either A/L or chlorfenapyr, compared to unexposed negative control mosquitoes. The A/L dose (2.4/14.4 mg/ml) totally erased P. falciparum parasites: 0% prevalence of infection in female mosquitoes exposed compared to 62% of infection in negative controls (df = 1, χ 2 = 31.23 p < 0.001). The dose of chlorfenapyr (0.025%) that killed < 20% females in ATSB showed a reduction in oocyte density of 95% per midgut (0.18/3.43 per midgut). Conclusion These results are evidence that chlorfenapyr, in addition to its direct killing effect on the vector, has the capacity to block Plasmodium transmission by interfering with oocyte development inside pyrethroid-resistant mosquitoes, and through this dual action may potentiate its impact under field conditions.

The In2Care EaveTube is a house modification designed to block and kill malaria mosquitoes using an electrostatic netting treated with insecticide powder. A previous study demonstrated prolonged duration of effective action of insecticide-treated electrostatic netting in a semi-field setting. As part of a cluster randomized controlled trial (CRT) of the EaveTube intervention in Côte d’Ivoire, we investigated the residual efficacy of a pyrethroid insecticide deployed in EaveTubes under village conditions of use. We also explored the scope of using existing malaria control technologies including LLINs and IRS as alternative methods to deliver insecticides in the lethal house lure. The efficacy of beta-cyfluthrin was monitored over time using the “eave tube bioassay” method. Mortality of beta-cyfluthrin exposed pyrethroid resistant Anopheles gambiae mosquitoes was > 80% after 4 months. The impact (mosquito mortality) of PVC tubes coated with pirimiphos methyl was similar to that of beta-cyfluthrin treated insert (66.8 vs. 62.8%) in release-recapture experiments in experimental huts. Efficacy was significantly lower with all the LLINs tested; however, the roof of PermaNet 3.0 induced significantly higher mosquito mortality (50.4%) compared to Olyset Plus (25.9%) and Interceptor G2 (21.6%) LLINs. The efficacy of the alternative delivery methods was short-lived with mortality decreasing below 50% within 2 months in residual activity bioassays. None of the products tested appeared superior to the powder treatments. Further research is therefore required to identify suitable insecticide delivery options in EaveTube for malaria vector control.

Malaria is a life-threatening disease caused by Plasmodium parasites transmitted by Anopheles mosquitoes. In 2021, more than 247 million cases of malaria were reported worldwide, with an estimated 619,000 deaths. While malaria incidence has decreased globally in recent decades, some public health gains have plateaued, and many endemic hotspots still face high transmission rates. Understanding local drivers of malaria transmission is crucial but challenging due to the complex interactions between climate, entomological and human variables, and land use. This study focuses on highly climatically suitable and endemic areas in Côte d'Ivoire to assess the explanatory power of coarse climatic predictors of malaria transmission at a fine scale. Using data from 40 villages participating in a randomized controlled trial of a household malaria intervention, the study examines the effects of climate variation over time on malaria transmission. Through panel regressions and statistical modeling, the study investigates which variable (temperature, precipitation, or entomological inoculation rate) and its form (linear or unimodal) best explains seasonal malaria transmission and the factors predicting spatial variation in transmission. The results highlight the importance of temperature and rainfall, with quadratic temperature and all precipitation models performing well, but the causal influence of each driver remains unclear due to their strong correlation. Further, an independent, mechanistic temperature-dependent R 0 model based on laboratory data aligns well with observed malaria incidence rates, emphasizing the significance and predictability of temperature suitability across scales. By contrast, entomological variables, such as entomological inoculation rate, were not strong predictors of human incidence in this context. Finally, the study explores the predictors of spatial variation in malaria, considering land use, intervention, and entomological variables. The findings contribute to a better understanding of malaria transmission dynamics at local scales, aiding in the development of effective control strategies in endemic regions.

Background A better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d’Ivoire. Methods From May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region. Results Overall, Anopheles gambiae , Anopheles funestus , and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222–298], 43.5 [35.8–51.29] and 3.02 [1.96–4] infected bites per year from An. gambiae, An. funestus and An. nili , respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations. Conclusion These results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease.

Malaria transmission is strongly influenced by traits such as mosquito life expectancy, vector competence, and the Extrinsic Incubation Period (EIP, which is the development time of the parasite inside the mosquito). Even though these traits are known to be shaped by environmental temperature and there is considerable concern that climate change could increase disease risk in certain areas, surprisingly, these temperature dependencies are poorly characterized. Here, we use a mechanistic model fitted to novel experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae, is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, EIP and overall competence. We use these data, together with novel estimates of the survival of infected blood-fed mosquitoes, to explore the potential influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission efficiency due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted.

Background Eave tube technology is a novel method of insecticide application that uses an electrostatic coating system to boost insecticide efficacy against resistant mosquitoes. A series of previous experiments showed encouraging insecticidal effects against malaria vectors. This study was undertaken to assess the effects of the eave tube approach on other Culicidae , in particular Culex quinquefasciatus , under laboratory and semi-field conditions. Methods Larvae of Cx. quinquefasciatus from Bouaké were collected and reared to adult stage, and World Health Organization (WHO) cylinder tests were performed to determine their resistance status. WHO standard 3-min cone bioassays were conducted using PermaNet 2.0 netting versus eave tube-treated inserts. To assess the transient exposure effect on Cx. quinquefasciatus , eave tube assay utilizing smelly socks as attractant was performed with exposure time of 30 s, 1 min, and 2 min on 10% beta-cyfluthrin-treated inserts. Residual activity of these treated inserts was then monitored over 9 months. Field tests involving release–recapture of Cx. quinquefasciatus within enclosures around experimental huts fitted with windows and untreated or insecticide-treated eave tubes were conducted to determine house entry preference and the impact of tubes on the survival of this species. Results Bouaké Cx. quinquefasciatus displayed high resistance to three out of four classes of insecticides currently used in public health. After 3 min of exposure in cone tests, 10% beta-cyfluthrin-treated inserts induced 100% mortality in Cx. quinquefasciatus , whereas the long-lasting insecticidal net (LLIN) only killed 4.5%. With reduced exposure time on the eave tube insert, mortality was still 100% after 2 min, 88% after 1 min, and 44% after 30 s. Mortality following 1 h exposure on 10% beta-cyfluthrin-treated insert was > 80% continuously up to 7 months post-treatment. Data suggest that Cx. quinquefasciatus have a stronger preference for entering a house through the eaves than through windows. Beta-cyfluthrin-treated inserts were able to kill 51% of resistant Cx. quinquefasciatus released within the enclosure. Conclusions Eave tubes are a novel method for delivery of insecticide to the house. They attract nuisance host-seeking Cx. quinquefasciatus mosquitoes and are as effective in controlling them as they are against pyrethroid-resistant Anopheles gambiae , despite the high level of resistance Cx. quinquefasciatus have developed. Graphical Abstract

Increased rate of aerobic glycolysis in idiopathic pulmonary fibrosis (IPF) is associated with pathological cellular phenotypes like epithelial barrier dysfunction, pro-fibrotic secretions and myofibroblast activation. Expression of lactate dehydrogenase (LDH), an enzyme involved in the final step of glycolysis and responsible for interconversion of pyruvate and lactate, is increased in IPF and the mouse bleomycin model lung tissue. Importantly, it has been shown that inhibition of glycolysis in bleomycin-induced lung fibrosis in mice led to a decreased collagen deposition and overall improve of the architecture of the lung. Here we investigate the potential of LDH inhibition in attenuating fibrosis-related features in human systems. To this end we pre-treated human small airway epithelial cells (SAEC) in air-liquid-interface setting with an LDH inhibitor and exposed them to TNFα to induce injury. LDH inhibition reduced the increased epithelial permeability, a hallmark of chronic lung diseases, in a dose-dependent manner. We further assessed the impact of prophylactic LDH inhibition on fibroblasts activation in a scar-in-a-jar model using primary material. Inhibition of LDH decreased Collagen I deposition and fiber formation in a dose-dependent manner. Additionally, inhibition of LDH in human monocyte-derived macrophages reduced the secretion of MMP9, a metalloprotease elevated in IPF and associated with aberrant lung remodeling, upon inflammatory and pro-fibrotic stimuli. Collectively, we show that inhibiting LDH and reducing lactate acidosis attenuates fibrosis-related features. Whether targeting LDH represents a new therapeutic concept for IPF will require assessment in in vivo preclinical models but recent data already provide a link between LDH5 and human fibrotic diseases.

Abstract Background A study was conducted prior to implementing a cluster-randomized controlled trial (CRT) of a lethal house lure strategy in central Côte d’Ivoire to provide baseline information on malaria indicators in 40 villages across five health districts. Methods Human landing catches (HLC) were performed between November and December 2016, capturing mosquitoes indoors and outdoors between 18.00 and 08.00 h. Mosquitoes were processed for entomological indicators of malaria transmission (human biting, parity, sporozoite, and entomological inoculation rates (EIR)). Species composition and allelic frequencies of kdr-w and ace-1 R mutations were also investigated within the Anopheles gambiae complex. Results Overall, 15,632 mosquitoes were captured. Anopheles gambiae sensu lato (s.l.) and Anopheles funestus were the two malaria vectors found during the survey period, with predominance for An. gambiae (66.2%) compared to An. funestus (10.3%). The mean biting rate for An. gambiae was almost five times higher than that for An. funestus (19.8 bites per person per night for An. gambiae vs 4.3 bites per person per night for An. funestus) and this was evident indoors and outdoors. Anopheles funestus was more competent to transmit malaria parasites in the study area, despite relatively lower number tested for sporozoite index (4.14% (63/1521) for An. gambiae vs 8.01% (59/736) for An. funestus; χ2 = 12.216; P < 0.0001). There were no significant differences between the proportions infected outdoors and indoors for An. gambiae (4.03 vs 4.13%; χ2 = 0.011; P = 0.9197) and for An. funestus (7.89 vs 8.16%; χ2 = 2.58e−29; P = 1). The majority of both infected vectors with malaria parasites harboured Plasmodium falciparum (93.65% for An. gambiae and 98. 31% for An. funestus). Overall, the EIR range for both species in the different districts appeared to be high (0.35–2.20 infected bites per human per night) with the highest value observed in the district of North-Eastern-Bouaké. There were no significant differences between transmission occurring outdoor and indoor for both species. Of the An. gambiae s.l. analysed, only An. gambiae sensu stricto (14.1%) and Anopheles coluzzii (85.9%) were found. The allelic frequencies of kdr and ace-1 R were higher in An. gambiae (0.97 for kdr and 0.19 for ace-1 R ) than in An. coluzzii (0.86 for kdr and 0.10 for ace-1 R ) (P < 0.001). Conclusion Despite universal coverage with long-lasting insecticidal nets (LLINs) in the area, there was an abundance of the malaria vectors (An. gambiae and An. funestus) in the study area in central Côte d’Ivoire. Consistent with high insecticide resistance intensity previously detected in these districts, the current study detected high kdr frequency (> 85%), coupled with high malaria transmission pattern, which could guide the use of Eave tubes in the study areas.

[This corrects the article DOI: 10.1371/journal.pntd.0005568.].

There is a pressing need to improve understanding of how insecticide resistance affects the functional performance of insecticide-treated nets (ITNs). Standard WHO insecticide resistance monitoring assays are designed for resistance surveillance and do not necessarily provide insight into how different frequencies, mechanisms or intensities of resistance affect the ability of ITNs to reduce malaria transmission. The current study presents some novel laboratory-based assays that attempt to better simulate realistic exposure of mosquitoes to ITNs and to quantify impact of exposure not only on instantaneous mortality, but also on blood-feeding and longevity, two traits that are central to transmission. The assays evaluated the performance of a standard ITN (Permanet® 2.0; Vestergaard Frandsen), a ‘next generation’ combination ITN with a resistance-breaking synergist (Permanet® 3.0) and an untreated net (UTN), against field-derived Anopheles gambiae sensu lato mosquitoes from Côte d’Ivoire exhibiting a 1500-fold increase in pyrethroid resistance relative to a standard susceptible strain. The study revealed that the standard ITN induced negligible instantaneous mortality against the resistant mosquitoes, whereas the resistance-breaking net caused high mortality and a reduction in blood-feeding. However, both ITNs still impacted long-term survival relative to the UTN. The impact on longevity depended on feeding status, with blood-fed mosquitoes living longer than unfed mosquitoes following ITN exposure. Exposure to both ITNs also reduced the blood-feeding success, the time spent on the net and blood-feeding duration, relative to the untreated net. Although a standard ITN did not have as substantial instantaneous impact as the resistance-breaking net, it still had significant impacts on traits important for transmission. These results highlight the benefit of improved bioefficacy assays that allow for realistic exposure and consider sub- or pre-lethal effects to help assess the functional significance of insecticide resistance.

Mathematical models of vector-borne infections, including malaria, often assume age-independent mortality rates of vectors, despite evidence that many insects senesce. In this study we present survival data on insecticide-resistant Anopheles gambiae s.l . from experiments in Côte d’Ivoire. We fit a constant mortality function and two age-dependent functions (logistic and Gompertz) to the data from mosquitoes exposed (treated) and not exposed (control) to insecticide-treated nets (ITNs), to establish biologically realistic survival functions. This enables us to explore the effects of insecticide exposure on mosquito mortality rates, and the extent to which insecticide resistance might impact the effectiveness of ITNs. We investigate this by calculating the expected number of infectious bites a mosquito will take in its lifetime, and by extension the vectorial capacity. Our results show that the predicted vectorial capacity is substantially lower in mosquitoes exposed to ITNs, despite the mosquitoes in the experiment being highly insecticide-resistant. The more realistic age-dependent functions provide a better fit to the experimental data compared to a constant mortality function and, hence, influence the predicted impact of ITNs on malaria transmission potential. In models with age-independent mortality, there is a great reduction for the vectorial capacity under exposure compared to no exposure. However, the two age-dependent functions predicted an even larger reduction due to exposure, highlighting the impact of incorporating age in the mortality rates. These results further show that multiple exposures to ITNs had a considerable effect on the vectorial capacity. Overall, the study highlights the importance of including age dependency in mathematical models of vector-borne disease transmission and in fully understanding the impact of interventions.