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Dabire, R. K.

Publications and source records attributed to Dabire, R. K..

At least 19 recordsLinked to original sources

Evidence of fitness costs associated with Ace-1R-mediated resistance to pirimiphos-methyl in Anopheles gambiae sensu lato following the withdrawal of indoor residual spraying in Burkina Faso

IntroductionChanges in vector control strategies alter the selection pressures exerted on natural populations of Anopheles gambiae s.l. and may influence the dynamics of insecticide resistance mechanisms. However, the consequences of discontinuing indoor residual spraying (IRS) campaigns on the evolution of Ace-1-mediated resistance remain poorly documented under natural conditions. This study aimed to assess the spatiotemporal evolution of resistance to pirimiphos-methyl following the cessation of IRS and to investigate evidence consistent with the existence of a biological cost associated with Ace-1-mediated resistance. MethodsNatural populations of An. gambiae s.l. were collected between 2017 and 2023 in three districts in Burkina Faso that had undergone IRS campaigns (Kampti, Solenzo, and Kongoussi). Susceptibility tests with pirimiphos-methyl (0.25%) were conducted out following WHO protocols, and a subsample of exposed mosquitoes was genotyped to detect the Ace-1 G119S mutation. Spatiotemporal trends in mortality, allele frequencies and genotypes were analyzed according to the pre-IRS, IRS, and post-IRS periods. The association between the Ace-1 genotype and survival following exposure to pirimiphos-methyl was assessed using logistic regression, while the concordance between phenotypic and molecular indicators of resistance was examined using Spearmans correlation. ResultsThe susceptibility of An. gambiae s.l. populations to pirimiphos-methyl was gradually restored after the discontinuation of IRS at all sites. At the same time, the frequencies of the Ace-1 119S resistance allele declined sharply, particularly in Kampti and Solenzo, while they remained low in Kongoussi throughout the study period. Mosquitoes carrying resistant genotypes had a significantly higher probability of survival after exposure to pirimiphos-methyl than susceptible homozygotes, with resistant homozygotes (RR) exhibiting the greatest survival advantage (OR = 27.62; 95% CI: 6.91-110.45; p < 0.001). A significant negative correlation was observed between the frequency of the Ace-1 119S allele and phenotypic mortality ({rho} = -0.48; p = 0.033), indicating a concordance between the two indicators of resistance. The progressive decline in allele frequencies, the decreasing prevalence of resistant genotypes, and the concomitant restoration of susceptibility are field observations consistent with the existence of biological costs associated with Ace-1-mediated resistance. ConclusionThis study provides field evidence consistent with the existence of biological costs associated with Ace-1-mediated resistance in natural populations of An. gambiae s.l. These results underscore the value of an adaptive resistance management strategy based on alternating selection pressures and could guide future vector control strategies, particularly if indoor residual spraying campaigns or other interventions relying on organophosphates were reintroduced.

zoology↗

Multi-site phenotypic characterisation of Kisumu colonies for comparison of insecticide susceptibility between testing centres

Testing of insecticides and insecticide-based vector control tools relies on the use of bioassays whereby insects are exposed and mortality, or another relevant entomological endpoint, is measured. To be able to compare results between products and across time and space standard laboratory strains are used. Insecticide-susceptible strains are often used as comparators in studies involving insecticide-resistant populations. Kisumu is a long-established, widely-used insecticide-susceptible strain of Anopheles gambiae. In this study, 16 facilities across different countries exposed their Kisumu colonies aged 3-5 days to four insecticides (permethrin, alpha-cypermethrin, DDT and pirimiphos-methyl) at a range of concentrations in WHO tube assays to assess susceptibility. Insecticide-treated filter papers were made at the Liverpool School of Tropical Medicine and sent to testing centres, along with a standard protocol and testing conditions requirements, to standardise testing as much as possible. A first observation was that DDT results were affected by the use of Risella oil, the WHO-recommended carrier oil but immiscible in acetone, leading to uneven coating of papers and increased variability in bioassay results (40x variance between colonies). Bioassay data generated by the testing facilities suggest a wide range of susceptibility to different insecticides between colonies of Kisumu: LC50 values between colonies differed, though not significantly, by up to 4x for permethrin, 6x for pirimiphos-methyl, and 15x for alpha-cypermethrin. Some colonies are classified as insecticide resistant based on the WHO definition of <98% mortality on exposure to a discriminating concentration. The assumption that Kisumu is a standard susceptible strain, consistent between facilities is challenged, which has implications when comparing results between studies. We propose genotypic analysis of the colonies to identify signs of resistance markers indicative of contamination from resistant strains or wild mosquitoes, and generation of guidance to support the maintenance and monitoring of susceptible mosquito strains.

zoology↗

Anopheles mosquitoes exposed to long-acting antimalarials via drug-spiked bloodmeal absorb drug but do not suffer fitness costs

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

microbiology↗

Effect of pharmacokinetically-relevant ivermectin concentrations on survivorship and fecundity of Anopheles coluzzii and Aedes aegypti in Burkina Faso: a laboratory experimental study

BackgroundThe control of vector-borne diseases is increasingly challenged by widespread insecticide resistance. Therefore, innovative vector control strategies with alternative modes of action are urgently needed. Ivermectin (IVM), an endectocide, has demonstrated toxicity to mosquito species such as Anopheles and Aedes when they feed on treated humans or livestock. In this study, we conducted a laboratory experiment to assess the effect of IVM, at concentrations equivalent to human plasma levels following mass drug administration (MDA), on the survival and fecundity of Anopheles coluzzii and Aedes aegypti in Burkina Faso. MethodsTwo laboratory experiments were conducted using 3-5-day old wild-derived female An. coluzzii and Aedes aegypti. Each experiment included four replicates per IVM concentration and was performed on separate dates. Mosquitoes were fed via membrane feeding on rabbit blood treated with five concentrations of IVM (C=112 ng/ml, C2=29 ng/ml, C3=15 ng/ml, C4=6.5 ng/ml, C5=2.5ng/ml), corresponding to the mean human plasma levels at 2, 4, 7, 14, and 28 days post-MDA with IVM at a dose of 300 g/kg. A negative control (C6=0.0 ng/ml) was also included. Mosquito mortalities were recorded daily for 7 days. Fecundity was measured by counting both laid eggs and developed eggs (via ovary dissection). ResultsIVM significantly reduced the survival of An. coluzzii compared to the control group (p<0.001), with the risk of death increasing from 4.2-fold at the lowest concentration (2.5 ng/ml) to 64.2-fold at the highest (112 ng/ml). In contrast, IVM had no significant effect on Aedes aegypti (p>0.05). Additionally, in An. coluzzii, IVM significantly reduced both egg laying and egg development (p<0.0001 and p<0.001, respectively), whereas no significant impact on fecundity was observed in Ae. aegypti (all p>0.80). ConclusionIvermectin concentrations typically achieved in human plasma during mass drug administration campaigns were sufficient to significantly reduce both survival and fecundity of wild type An. coluzzii, but had no measurable effect on recently colonized Ae. aegypti. These findings highlight the species-specific efficacy of ivermectin and support its potential role in integrated vector control strategies targeting malaria vectors in Africa.

zoology↗

Pixel intensity of wing photos used to predict age of Anopheles gambiae caught during the RIMDAMAL II clinical trial

Mosquito age-grading is important for evaluating mosquito control efforts and estimating pathogen transmission risk. We previously developed a simple, low-cost, and high-throughput method to age-grade mosquitoes by computing the pixel intensity (PI) of wing photos, which reflects wing scale loss over time. Here the technique was refined and used to understand wild Anopheles gambiae population structures from the RIMDAMAL II clinical trial. Wing photos from lab-reared An. gambiae had narrower PI ranges compared to wild An. gambiae s.l., but the PI distributions reflected wild population structures where most have lower PI values and very few high PI values. A model was then fitted to samples from lab mosquitoes of known ages and used to interpolate unknown ages from the wild populations (median age of 4.96 [0.8-14.93] days old). Analyses from the RIMDAMAL II trial indicate that while ivermectin mass drug administrations in the intervention arm may have modestly influenced PI and predicted age relative to controls, distributions of new dual-chemistry bed nets in both arms were associated with a strong effect on PI and predicted age structure. These data suggest this method can be used to rapidly age-grade wild mosquito populations and infer the efficacy of vector control interventions.

microbiology↗

Pfs230 Domain 12 is a potent malaria transmission-blocking vaccine candidate

Malaria transmission-blocking vaccines (TBV) target sexual stage parasites that are transmitted to mosquitoes and critical for spread of the pathogen. The clinically most advanced TBV candidate contains part of the Pro-domain (Pro) and Domain 1 (D1) of Plasmodium falciparum surface protein Pfs230. Subunit vaccines that contain other domains of Pfs230 have so far failed to induce functional antibodies. Here, we produced eight single domain fragments of Pfs230 in Drosophila melanogaster S2 cells and assessed their immunogenicity in mouse immunizations. In addition to D1-specific antibodies, antibodies raised against Domain 12 (D12) showed strong recognition of Pfs230 on the surface of female parasites. Importantly, D12-specific antibodies showed strong functional transmission-reducing activity in membrane feeding assays with cultured parasites, an activity that was complement-dependent. Murine D12-specific antibodies further reduced mosquito transmission of parasites acquired from naturally infected parasite carriers. The D12 antigen was recognized by sera from an all-age cohort of individuals who had been naturally exposed to Plasmodium falciparum with antibody levels increasing with age. In conclusion, we identified Pfs230D12 as a promising new TBV candidate. Impact statementPfs230 Domain 12 induces antibodies in mice that strongly reduce transmission of lab-cultured and naturally circulating malaria parasites to mosquitoes.

immunology↗

Near-infrared spectroscopy discriminates mass-reared sterile and wild tsetse flies

In the frame of the Pan African Tsetse and Trypanosomosis Eradication Campaign, an integrated pest management approach has been adopted to manage tsetse fly populations using a sterile insect technique (SIT).. Monitoring the efficacy of the SIT programs requires the discrimination between wild and sterile males collected in monitoring traps. The discrimination between sterile and wild males relies mainly on marking of sterile males with a fluorescent dye powder (before the releases) and their identification using a fluorescence camera and /or a fluorescence microscope. However, the accuracy of this method remains limited with defective marking and wild flies contaminated with a few dye particles in the monitoring traps. The molecular techniques developed to discriminate doubtful flies are costly for endemic countries. Here, we investigate the ability of a new generation monitoring tool, the near-infrared spectroscopy (NIRS) to discriminate between lab-reared Glossina palpalis gambiensis and their counterparts in the field. NIRS technique discriminates wild flies males with 86% accuracy to Glossina palpalis gambiensis males reared in an insectarium. Interestingly, the prediction accuracy between wild and laboratory-reared flies improved to 88% when the Glossina lab colony flies were irradiated. In light of these results, NIRS can discriminate tsetse flies even when identification with the UV camera is doubtful. However, more investigations integrating some natural variables are required before the validation of the technical as a complementary method for potential future tsetse eradication programs.

evolutionary biology↗

Spatial and temporal characteristics of laboratory-induced Anopheles coluzzii swarms: shape, structure and flight kinematics

Anopheles mosquitoes mate at sunset in aerial swarms. The development of mating-based methods for effective malaria vector control requires a good knowledge of the flight behaviour of Anopheles species in mating swarms. However, the process of how swarms are formed and maintained remains poorly understood. Here, we characterized the three-dimensional spatial and temporal flight kinematics of Anopheles coluzzii males swarming above a ground marker. We observed that the location, shape and volume of swarms were highly stereotypic, consistent over the swarming duration, regardless of the number of individuals in the swarm. The swarm had an elliptical cone shape, and we observed a differential spatial distribution of flight kinematics parameters within the swarm volume. Among these parameters, only swarm density varied with swarm size. Using a sensory system-informed model, we show that swarm location and shape can accurately be modelled based on visual perception of the marker. To control swarm height, swarming individuals maintain an optical angle of the marker ranging from 24{degrees} to 55{degrees}. Limiting the viewing angle deviation to 4.5% of the maximum value results in the observed elliptical cone swarm shape. We discuss the implications of these finding in mating success, speciation and for vector control.

animal behavior and cognition↗

A metagenomics-based survey of the virus diversity in mosquito vectors allows the first detection of Sindbis virus in Burkina Faso

Mosquito-borne viruses represent a threat to human health worldwide. This taxonomically-diverse group includes numerous viruses that recurrently spread into new regions. Thus, periodic surveillance of the arbovirus diversity in a given region can help optimizing the diagnosis of arboviral infections. Nevertheless, such screenings are rarely carried out, especially in low-income countries. Consequently, case investigation is often limited to a fraction of the arbovirus diversity. This situation probably results in undiagnosed cases. Here, we have explored the diversity of mosquito-borne viruses in two regions of Burkina Faso. To this end, we have screened mosquitoes collected along three years in six urban and rural areas using untargeted metagenomics. The analysis focused on two mosquito species, Aedes aegypti and Culex quinquefasciatus, considered among the main vectors of arboviruses worldwide. The screening detected Sindbis virus (SINV, Togaviridae) for the first time in Burkina Faso. This zoonotic arbovirus has spread from Africa into Europe. SINV causes periodic outbreaks in Europe but its distribution and epidemiology in Africa remains largely unstudied. SINV was detected in one of the six areas of the study, and at a single year. Detection was validated with isolation in cell culture. SINV was only detected in Cx. quinquefasciatus, thus extending the list of potential vectors of SINV in nature. SINV infection rate in mosquitoes was similar to those observed in European regions that experience SINV outbreaks. A phylogenetic analysis placed the nearly-full genome within a cluster of Central African strains of lineage I. This cluster is supposedly at the origin of the SINV strains introduced into Europe. Thus, West Africa should also be considered as a potential source of the European SINV strains. Our results call for studies on the prevalence of SINV infections in the region to estimate disease burden and the interest of SINV diagnostic in case investigation. Author summaryMosquito-borne viruses are responsible for millions of cases worldwide every year. Moreover, they have repeatedly shown an ability to spread over large distances. Thus, periodic surveys of the arbovirus diversity in a given region can help to define the diagnostic tests to use during case investigation. However, comprehensive surveys are rarely carried out, especially in low-income countries. Here, the arbovirus diversity was assessed in two main mosquito vectors in Burkina Faso using untargeted metagenomics. This screening identified Sindbis virus (SINV), a zoonotic arbovirus, for the first time in Burkina Faso. Moreover, SINV was found in nature for the first time in Culex quinquefasciatus, a main mosquito vector of several pathogens and with a cosmopolitan distribution. SINV leads to periodic outbreaks mainly in Europe. Despite a likely African origin, its distribution and epidemiology in Africa remains largely unstudied. The SINV sequence from Burkina Faso felt within the cluster of Central African strains thought to be at the origin of the European SINV strains. Thus, our results indicate that West Africa should be considered as another potential source of the SINV introductions in Europe. Further studies are required to characterize SINV epidemiology in Burkina Faso and the West African region.

microbiology↗

Impact of blood meals taken on ivermectin-treated livestock on survival and fecundity of the malaria vector Anopheles coluzzii under laboratory conditions

Treatment of livestock with endectocides such as ivermectin is viewed as a complementary vector control approach to address residual transmission of malaria. However, efficacy of this treatment may vary between animal species. Hence, our purpose was to investigate the effects of ivermectin treatments of common livestock species on life history traits of the opportunistic malaria vector Anopheles coluzzii. Sheep, goats and pigs were treated using injectable veterinary ivermectin formulation at the species-specific doses (recommended dose for all species and high dose in pig). Mosquito batches were exposed to treated and control (not injected) animals at different days after treatment. Daily mosquito mortality was recorded and fecundity assessed through the count of gravid females and the number of eggs they developed. The recommended dose of ivermectin induced a significant decrease in mosquito survival for up to 7 days after injection (DAI), with a decrease of 89.7%, 66.7%, and 48.4% in treated pigs, goats and sheep, respectively, compared to control animals. In treated pigs, the triple therapeutic dose decreased mosquito survival of 68.97% relatively to controls up to 14 DAI. The average number in gravid females Anopheles that survived after feeding on treated animals were reduced when blood-meals were taken on sheep (2.57% and 42.03% at 2 and 7 DAI), or on goats (decrease of the 28.28% and 73.64% respectively at 2 and 7 DAI). This study shows that ivermectin treatments to animals negatively impacts An. coluzzii life history traits and could reduce vector densities in areas where livestock live near humans. However, due to short-term efficacy of single dose treatments, repeated treatments and potentially increased dosages would be required to span the transmission season. The use of long-acting ivermectin formulations is discussed as a mean for extending efficacy while remaining cost effective.

systems biology↗

The paradox of plant preference: the malaria vectors Anopheles gambiae and Anopheles coluzzii select suboptimal food sources for their survival and reproduction

Anopheles gambiae s.l. mosquitoes, the primary malaria vectors in sub-Saharan Africa, exhibit selectivity among plant species as potential food sources. However, it remains unclear if their preference aligns with optimal nutrient intake and survival. Following an extensive screening of the effects of 31 plant species on An. coluzzii in Burkina Faso, we selected three species for their contrasting effects on mosquito survival, namely Ixora coccinea, Caesalpinia pulcherrima and Combretum indicum. We assessed the sugar content of these plants and their impact on mosquito fructose-positivity, survival, and insemination rate, using Anopheles coluzzii and Anopheles gambiae, and with glucose 5% and water as controls. Plants displayed varying sugar content and differentially affected the survival, sugar intake and insemination rate of mosquitoes. All three plants were more attractive to mosquitoes than controls, with An. gambiae being more responsive than An. coluzzii. Notably, C. indicum was the most attractive but had the lowest sugar content and offered the lowest survival, insemination rate, and fructose positivity. Our findings unveil a performance-preference mismatch in An. coluzzii and An. gambiae regarding plant food sources. Several possible reasons for this negative correlation between performance and preference are discussed.

ecology↗

Insecticide resistance and biting behaviour of malaria vectors in rural West-Africa : a data mining study to adress their fine-scale spatiotemporal heterogeneity, drivers, and predictability

AO_SCPLOWBSTRACTC_SCPLOWInsecticide resistance and behavioural adaptation of malaria mosquitoes affect the efficacy of long-lasting insecticide nets - currently the main tool for malaria vector control. To develop and deploy complementary, efficient and cost-effective control interventions, a good understanding of the drivers of these physiological and behavioural traits is needed. In this data-mining exercise, we modelled a set of indicators of physiological resistance to insecticide (prevalence of three target-site mutations) and behavioural resistance phenotypes (early- and late-biting, exophagy) of anopheles mosquitoes in two rural areas of West-Africa, located in Burkina Faso and Cote dIvoire. To this aim, we used mosquito field collections along with heterogeneous, multi-source and multi-scale environmental data. The objectives were i) to assess the small-scale spatial and temporal heterogeneity of physiological resistance to insecticide and behavioural resistance phenotypes, ii) to better understand their drivers, and iii) to assess their spatio-temporal predictability, at scales that are consistent with operational action. The explanatory variables covered a wide range of potential environmental determinants of vector resistance to insecticide or behavioural resistance phenotypes : vector control, human availability and nocturnal behaviour, macro and micro-climatic conditions, landscape, etc. The resulting models revealed many statistically significant associations, although their predictive powers were overall weak. We interpreted and discussed these associations in light of several topics of interest, such as : respective contribution of public health and agriculture in the selection of physiological resistances, biological costs associated with physiological resistances, biological mechanisms underlying biting behaviour, and impact of micro-climatic conditions on the time or place of biting. To our knowledge, our work is the first modeling insecticide resistance and feeding behaviour of malaria vectors at such fine spatial scale with such a large dataset of both mosquito and environmental data.

ecology↗

Assessment of Culicidae collection methods for xenomonitoring lymphatic filariasis in malaria co-infection context in Burkina Faso

BackgroundEntomological surveillance of lymphatic filariasis (LF) and malaria infections play an important role in the decision-making of national programs, to control or eliminate these both diseases. In order to corroborate infections in the human population, sampling large numbers of mosquitoes is necessary. To overcome this challenge, this study was design to assess the efficiency of four mosquito collection methods for monitoring LF and malaria infections in mosquito population. Methodology/Principle FindingsMosquito collections were performed between August and September 2018 in four villages (Koulpissy, Seiga, and Peribgan, Saptan), distributed in East and South-West health regions of Burkina Faso. Different collection methods were used: Human Landing Catches (HLC) executed indoor and outdoor, Window Exit-Trap, Double Net Trap (DNT) and Pyrethrum Spray Catches (PSC). Molecular analyses were performed to identify Anopheles gambiae s.l. sibling species and to detect Wuchereria bancrofti and Plasmodium falciparum infection in mosquitoes. A total of 3,322 mosquitoes were collected among this, Anopheles gambiaes.l. was the vector caught in largest proportion (63.82%). An. gambiae s.l. sibling species molecular characterization showed that Anopheles gambiae was the dominant specie in all health regions. The Human Landing Catches (indoor and outdoor) collected the highest proportion of mosquitoes (between 61.5%and 82.79%). For sampling vectors infected to W. bancrofti and P. falciparum, PSC, HLC and Window Exit-Trap were been find as the most effective collection methods. Conclusions/SignificanceThis study revealed that HLC indoor and outdoor remained the most effective collection methods. Likewise, the results showed the probability to use Window Exit-Trap and PSC collection methods to sample Anopheles infected and can be useful for xenomonitoring for both LF and malaria. Author summaryIn Burkina Faso the monitoring and evaluation scheme to assess the impact of LF and malaria interventions is only focusing on parasitological tests. While nowadays, the most simple and direct measure of vector borne diseases is xenomonitoring. Thus, in order to confirm both diseases infection rate in the human population, sampling large numbers of mosquitoes is necessary. This study was undertaken in this context to assess the efficiency of four mosquito collection methods for xenomonitoring LF and malaria. Mosquito collections were performed between August and September 2018 in four villages, distributed in East and South-West health regions of Burkina Faso. Human Landing Catches (HLC), Window Exit-Trap, Double Net Trap (DNT) and Pyrethrum Spray Catches (PSC) were evaluated. The results showed that HLC remained the most effective collection method by collecting the highest number of Anopheles (2,388; 71.88% of total). Across the study, mosquito infection rate for Wuchereria bancrofti and Plasmodium falciparum were 0.004 and 0.13 respectively. To collect vectors infected it was found that Window Exit-Trap and PSC were efficiencies. In conclusion, HLC has shown to be appropriate for collect large number of mosquitoes. Likewise, Window Exit-Trap and PSC can be useful for xenomonitoring for both LF and malaria.

pathology↗

A six-months, long acting, one-shot injectable formulation of Ivermectin as a complementary malaria vector control tool to target zoophagic Anopheles : laboratory and model-based proofs of concept.

ContextIn the current context of residual plasmodium transmission where zoophagic proclivities of Anopheles intervene, we propose to treat peridomestic animals using the endectocide Ivermectin as a complementary approach to bednets. As Ivermectin remanence with classic veterinary compounds is insufficient to induce a significant decrease in vectors populations, we developed a long-lasting injectable formulation of ivermectin from the BEPO(R) technology designed to release insecticidal concentrations of the molecule for 6 months. The work reported here is a proof of concept that using this new technology could help decrease field Anopheles populations. MethodsEight calves were injected with Ivermectin therapeutic doses of 1.2 mg/kg body weight using 2 long lasting formulations (A and B). Efficacy of the product at killing wild derived An. coluzzii has been evaluated by direct-skin feeding assays from 1 to 210 days after injection (DAI). Efficacy on survival was estimated with Cox proportional hazards mixed models and Kaplan meier estimates. To predict efficacy in field-based scenarii, we used a transmission model fed with an entomological model considering different levels for the Anopheles zoophagic preference, calves vs humans ratios, and bed net use variables. ResultsThe release at mosquitocidal plasmatic concentrations of Ivermectin during 6 months is confirmed for both formulations (Hazard ratios > 1 for both formulations against their vehicle for 210 days). The Ivermectin concentration allowing to kill 90% of the mosquitoes before the extrinsic incubation period of the parasite is achieved (10 days) are 11 and 9 ng/ml for formulations A and B if the blood meal is taken before the infectious one, and 15 and 13 ng/ml if it was taken after. Modeling showed that Ivermectin treatment of calves using BEPO(R) technology would reduce infectious vector populations, from at least 35% for most anthropophagic Anopheles in villages where cattle to human ratio is the lowest, to more than 75% if vectors were zoophagic and calves numbers superior to humans. ConclusionOur study gives the proof of concept that a long-lasting formulation of Ivermectin administered to calves could help decrease field malaria vectors populations, which may, ultimately, have an impact at the epidemiological level.

pharmacology and toxicology↗

Lack of robust evidence for a Wolbachia infection in Anopheles gambiae from Burkina Faso

The endosymbiont Wolbachia can have major effects on the reproductive fitness, and vectorial capacity of host insects and may provide new avenues to control mosquito borne pathogens. Anopheles gambiae s.l is the major vector of malaria in Africa but the use of Wolbachia in this species has been limited by challenges in establishing stable transinfected lines and uncertainty around native infections. High frequencies of infection of Wolbachia have been previously reported in An. gambiae collected from the Valle du Kou region of Burkina Faso in 2011 and 2014. Here we re-evaluated the occurrence of Wolbachia in natural samples, collected from Valle du Kou over a 12-year time span, and in addition, expanded sampling to other sites in Burkina Faso. Our results showed that, in contrast to earlier reports, Wolbachia is present at an extremely low prevalence in natural population of An. gambiae. From 5,341 samples analysed only 29 were positive for Wolbachia by nested PCR representing 0.54% of prevalence. No positive samples were found with regular PCR. Phylogenetic analysis of 16S rRNA gene amplicons clustered across supergroup B, with some having similarity to sequences previously found in Anopheles from Burkina Faso. However, we cannot discount the possibility that the amplicon positive samples we detected were due to environmental contamination or were false positives. Regardless, the lack of a prominent native infection in An. gambiae s.l. is encouraging for applications utilising Wolbachia traninsfected mosquitoes for malaria control.

ecology↗

Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors

Anopheles coluzzii females, important malaria vectors in Africa, mate only once in their lifetime. Mating occurs in aerial swarms with a high male-to-female ratio, where the traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence mating success in natural mating swarms in Burkina Faso. As insecticides are widely used in this area for malaria control, we also determined whether CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than unmated controls, suggesting CHCs could be a determinant of mating success. Additionally, mated males have higher insecticide resistance under pyrethroid challenge, and we show a link between resistance intensity and CHC abundance. Taken together, our results reveal overlapping roles played by CHCs in mate choice and insecticide resistance, and point to sexual selection for insecticide resistance traits that limit the efficacy of our best malaria control tools.

ecology↗

Data-driven and interpretable machine-learning modeling to explore the fine-scale environmental determinants of malaria vectors biting rates in rural Burkina Faso

BackgroundImproving the knowledge and understanding of the environmental determinants of malaria vectors abundances at fine spatiotemporal scales is essential to design locally tailored vector control intervention. This work aimed at exploring the environmental tenets of human-biting activity in the main malaria vectors (Anopheles gambiae s.s., Anopheles coluzzii and Anopheles funestus) in the health district of Diebougou, rural Burkina Faso. MethodsAnopheles human-biting activity was monitored in 27 villages during 15 months (in 2017-2018), and environmental variables (meteorological and landscape) were extracted from high resolution satellite imagery. A two-step data-driven modeling study was then carried-out. Correlation coefficients between the biting rates of each vector species and the environmental variables taken at various temporal lags and spatial distances from the biting events were first calculated. Then, multivariate machine-learning models were generated and interpreted to i) pinpoint primary and secondary environmental drivers of variation in the biting rates of each species and ii) identify complex associations between the environmental conditions and the biting rates. ResultsMeteorological and landscape variables were often significantly correlated with the vectors biting rates. Many nonlinear associations and thresholds were unveiled by the multivariate models, both for meteorological and landscape variables. From these results, several aspects of the bio-ecology of the main malaria vectors were precised or hypothesized for the Diebougou area, including breeding sites typologies, development and survival rates in relation to weather, flight ranges from breeding sites, dispersal related to landscape openness. ConclusionsUsing high resolution data in an interpretable machine-learning modeling framework proved to be an efficient way to enhance the knowledge of the complex links between the environment and the malaria vectors at a local scale. More broadly, the emerging field of interpretable machine-learning has significant potential to help improving our understanding of the complex processes leading to malaria transmission.

ecology↗

Antimalarials in mosquitoes overcome Anopheles and Plasmodium resistance to malaria control strategies

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these issues an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions. Significance StatementEffective control of malaria is hampered by resistance to vector-targeted insecticides and parasite-targeted drugs. This situation is exacerbated by a critical lack of chemical diversity in both interventions and, as such, new interventions are badly needed. Recent laboratory studies have shown that an alternative approach based on treating Anopheles mosquitoes directly with antimalarial compounds can render the vector incapable of transmitting the Plasmodium parasites that cause malaria. While promising, showing that mosquito-targeted antimalarials remain effective against wild parasites and mosquitoes, including drug- and insecticide-resistant populations, respectively, is crucial to the future viability of this approach. In this study, carried out in the US and Burkina Faso, we show that antimalarial exposure is highly effective, even against extremely resistant mosquitoes, and can block transmission of drug-resistant parasites. By combining lab, and field-based studies in this way we have demonstrated that this novel approach can be effective in areas where conventional control measures are no longer as effective.

microbiology↗