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Biology subjects

Ranson, H.

Publications and source records attributed to Ranson, H..

At least 19 recordsLinked to original sources

Assessing the additional effects of piperonyl butoxide (PBO) exposure on Anopheles mosquitoes

Insecticide treated nets (ITNs) remain one the frontline tool in malaria control in Africa. The synergist piperonyl butoxide (PBO) has been incorporated into ITNs to combat pyrethroid resistance and these pyrethroid-PBO ITNs are now in widespread use across Africa. PBO is known to inhibit the degradation of pyrethroids and other insecticide classes, but little is known about other biological or behavioural effects of PBO exposure. This work assessed the impact of PBO on Anopheles gambiae s.l. male longevity as well as female host-seeking and blood feeding behaviours using laboratory assays. PBO had an immediate impact on blood feeding of female An. gambiae s.l. whereas the effect was not observed 24h post-exposure. Kaplan-Meier survival curves showed a significant difference in mosquito longevity post-exposure to PBO with male mosquitoes living nearly three times as long if exposed to control papers compared to PBO. In olfactometer assays, after exposure to control papers, control mosquitoes were significantly more attracted to host-odours, however, this attraction preference was reversed following PBO exposure. This study shows that in experimental assays, PBO has other effects on mosquito physiology and this is likely to contribute to the impact of pyrethroid - PBO ITNs in vector control programmes.

ecology↗

Widely circulating pyrethroid resistance mechanisms reduce the efficacy of transfluthrin and pose a risk for mosquito-borne disease control with spatial emanators

Spatial emanators (SE) are a promising complement to existing tools for preventing mosquito transmitted diseases. In 2025, the WHO updated the WHO Guidelines for Malaria to include a conditional recommendation for the indoor use of prequalified SE products in malaria control. Both prequalified, and many other SE products contain the volatile pyrethroid transfluthrin, which shares the same target site as other (contact/solid phase) pyrethroids. Therefore, an assessment of cross resistance is critical to predict effectiveness against mosquitoes with existing pyrethroid resistance. Our results show that resistance to solid phase pyrethroids is correlated with resistance to transfluthrin in Anopheles and Aedes species. Moreover, commonly-selected resistance mechanisms including target site mutations and over-expression of P450 detoxification enzymes can confer resistance to transfluthrin. Furthermore, we show that resistant mosquitoes are less impacted by transfluthrin in terms of flight activation (irritancy) and reduced blood feeding inhibition, with the response correlating with resistance strength. Transfluthrin did not elicit an electroantennography response in Anopheles gambiae and surgically ablating mosquitoes antennae did not result in differences in flight activation upon transfluthrin exposure, suggesting the antennae are not required for transfluthrin to elicit behavioral responses. These results provide new insight regarding the mode of action of transfluthrin and the risk of resistance reducing transfluthrins efficacy in vector control interventions.

pharmacology and toxicology↗

The metabolic resistance blueprint: Genomic dissection of DDT resistance in historical kdr-free East African Anopheles gambiae

Insecticide resistance in Anopheles gambiae poses a significant threat to malaria control and eradication efforts across sub-Saharan Africa. While target-site resistance mechanisms are well-characterised, the evolutionary origins of metabolic resistance remain poorly understood. We employed bulk segregant analysis (BSA) using unique historical genetic crosses established in the late 1990s between a DDT-resistant ZAN/U strain (Originally from Zanzibar) and a susceptible strain to map the genomic architecture of early metabolic resistance. Critically, the ZAN/U strain exhibited DDT resistance without kdr mutations, providing an ideal genetic background for isolating glutathione S-transferase epsilon (GSTe)-mediated resistance mechanisms that evolved during the DDT control program era. BSA analysis revealed a major quantitative trait locus on chromosome 3R spanning the GSTe gene cluster (GSTe1-8). BSA identified 20 significant amino acid substitutions distributed across all eight GSTe genes, in addition to variations in the promoter region of GSTe2 and GSTe3, which were previously determined to be overexpressed in the ZAN/U strain. East African field-collected samples from the MalariaGEN Ag1000G project confirmed that many of these mutations are under long-term selection pressure in natural populations. This work provides a characterisation of the GSTe clusters role in establishing the metabolic resistance foundation that continues to compromise vector control efforts today. Additionally, BSA analysis was performed on progeny from crosses established in early 2000s between a permethrin-resistant RSP-ST strain originating from Western Kenya and a susceptible strain, identifying expected target-site resistance at the vgsc locus.

genomics↗

Multi-omics analysis identifies loci associated with pyrethroid resistance across sister species in the Anopheles gambiae species complex

The Anopheles gambiae species complex includes An. gambiae, An. coluzzii, and An. arabiensis, three of the four major malaria vector species across Africa. Insecticide-based vector control remains the most critical tool in the fight against malaria, with a heavy reliance on pyrethroid insecticides. However, widespread pyrethroid resistance jeopardises the effectiveness of these methods. Currently, the number of diagnostic markers available to track pyrethroid resistance in endemic settings is limited, focusing mainly on changes at the insecticide target site. Genetic analysis of seven insecticide-resistant populations from West Africa, a region with intense insecticide resistance, reveals shared loci associated with pyrethroid resistance among the sister species of the An. gambiae complex including kdr, GSTE1-8 and the CYP6P region. Notably, a mutation in the voltage-gated sodium channel, I1527T, previously identified in An. coluzzii and An. gambiae, was detected in wild-caught An. arabiensis from Burkina Faso. Additionally, a mutation, L207I, in GSTE7 common to An. coluzzii and An. arabiensis, significantly increases survivorship to deltamethrin. With the additional integration of RNAseq and data from the Anopheles gambiae 1000 genomes project, we were able to identify putative eQTLs associated with the expression of major insecticide resistance-related transcripts, such as CYP6P3, CYP9K1 and CYP6AA1. This study reveals several potential diagnostic markers of resistance that can be implemented in endemic settings and identifies putative introgression between An. arabiensis and An. coluzzii in Burkina Faso.

genetics↗

Do epidemiologically impactful vector control interventions disrupt mosquito population structure?

Large epidemiological impacts resulting from disease vector control interventions are typically associated with significant disruption of vector populations. While vector density is a frequently measured response, impacts on demography and connectivity are suspected but rarely quantified. We analysed low-coverage whole-genome sequence data of 893 Anopheles gambiae mosquitoes collected between 2014-2015 during a cluster-randomized control trial (cRCT) in Burkina Faso to compare a pyrethroid-only net (ITN) with a pyrethroid-pyriproxyfen (ITN-PPF) net. Despite reductions of clinical malaria by 12%, and vector density by 22% in the ITN-PPF arm, we found no significant changes in An. gambiae population genetic structure or diversity. We found remarkably low population differentiation, and a lack of discernible clustering by treatment, time, or space. Nucleotide diversity and inbreeding coefficient remained stable between treatments, and genome-wide scans showed no putative signatures of selection between trial arms. These results show that ITN-PPF did not alter An. gambiae genetic structure, possibly due to large, vagile populations in West Africa. More widely, this is first evidence that epidemiologically meaningful reductions in vector density may not impact genetic diversity or connectivity, and challenges what constitutes adequate vector control in large populations.

ecology↗

Modelling the effects of adult emergence on the surveillance and age distribution of medically important mosquitoes

Entomological 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 natural 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 estimates affected by short-term and seasonal fluctuations in mosquito emergence.

ecology↗

Machine Learning Reveals Immediate Disruption in Mosquito Flight when exposed to Olyset Nets

Insecticide-treated nets (ITNs) remain a critical intervention in controlling malaria transmission, yet the behavioural adaptations of mosquitoes in response to these interventions are not fully understood. This study examined the flight behaviour of insecticide-resistant (IR) and insecticide-susceptible (IS) Anopheles gambiae strains around an Olyset net (OL), a permethrin-impregnated ITN, versus an untreated net (UT). Using machine learning (ML) models, we classified mosquito flight trajectories with high accuracy (0.838) and ROC AUC (0.925). Contrary to assumptions that behavioural changes at OL would intensify over time, our findings show an immediate onset of convoluted, erratic flight paths for both IR and IS mosquitoes around the treated net. SHAP analysis identified three key predictive features of OL exposure: frequency of zero-crossings in flight angle change, first quartile of flight angle change, and zero-crossings in horizontal velocity. These suggest disruptive flight patterns, indicating insecticidal irritancy. While IS mosquitoes displayed rapid, disordered trajectories and mostly died within 30 minutes, IR mosquitoes persisted throughout the 2-hour experiments but exhibited similarly disturbed behaviour, suggesting resistance does not fully mitigate disruption. Our findings challenge literature suggesting permethrins repellency in solution form, instead supporting an irritant or contactdriven effect when incorporated into net fibres. This study highlights the value of ML-based trajectory analysis for understanding mosquito behaviour, refining ITN configurations and evaluating novel active ingredients aimed at disrupting mosquito flight behaviour. Future work should extend these methods to other ITNs to further illuminate the complex interplay between mosquito behaviour and insecticidal intervention.

animal behavior and cognition↗

Discrimination of inherent characteristics of susceptible and resistant strains of Anopheles gambiae by explainable Artificial Intelligence Analysis of Flight Trajectories

Understanding mosquito behaviours is vital for development of insecticide-treated bednets (ITNs), which have been successfully deployed in sub-Saharan Africa to reduce disease transmission, particularly malaria. However, rising insecticide resistance (IR) among mosquito populations, owing to genetic and behavioural changes, poses a significant challenge. We present a machine learning pipeline that successfully distinguishes between IR and insecticide-susceptible (IS) mosquito behaviours by analysing trajectory data. Data driven methods are introduced to accommodate common tracking system shortcomings that occur due to mosquito positions being occluded by the bednet or other objects. Trajectories, obtained from room-scale tracking of two IR and two IS strains around a human-baited, untreated bednet, were analysed using features such as velocity, acceleration, and geometric descriptors. Using these features, an XGBoost model achieved a balanced accuracy of 0.743 and a ROC AUC of 0.813 in classifying IR from IS mosquitoes. SHAP analysis helped decipher that IR mosquitoes tend to fly slower with more directed flight paths and lower variability than IS--traits that are likely a fitness advantage by enhancing their ability to respond more quickly to bloodmeal cues. This approach provides valuable insights based on flight behaviour that can reveal the action of interventions and insecticides on mosquito physiology.

animal behavior and cognition↗

ABCH2 transporter in the first line of defense protects malaria vectors from pyrethroids

Contact insecticides are primarily used for the control of Anopheles malaria vectors. These chemicals penetrate mosquito legs and other appendages, the first barrier to reaching their neuronal targets. An ATP-Binding Cassette transporter from the H family (ABCH2) is highly expressed in Anopheles coluzzii legs, and further induced upon insecticide exposure. RNAi-mediated silencing of the ABCH2 caused a significant increase in deltamethrin mortality compared to control mosquitoes, coincident with a corresponding increase in 14C-deltamethrin penetration. RT-qPCR analysis and immunolocalization revealed that ABCH2 is mainly localized in the legs and head appendages, and more specifically, the apical part of appendage epidermis, underneath the cuticle. To unravel the molecular mechanism underlying the role of ABCH2 in modulating pyrethroid toxicity, two hypotheses were investigated: An indirect role, based on the orthology with other insect ABCH transporters involved with lipid transport and deposition of CHC lipids in Anopheles legs which may increase cuticle thickness, slowing down the penetration rate of deltamethrin; or the direct pumping of deltamethrin out of the organism. Evaluation of the leg cuticular hydrocarbon (CHC) content showed that this was not affected by ABCH2 silencing, indicating this transporter in is not associated with the transport of leg CHCs. Homology-based modeling suggested that the ABCH2 half-transporter adopts a physiological homodimeric state, in line with its ability to hydrolyze ATP in vitro when expressed on its own in insect cells. Docking analysis revealed a deltamethrin pocket on the homodimeric transporter. Furthermore, deltamethrin-induced ATP hydrolysis in ABCH2-expressing cell membranes, further supports that deltamethrin is indeed a ABCH2 substrate. Overall, our findings pinpoint ABCH2 as a key regulator of deltamethrin toxicity.

evolutionary biology↗

Behaviour of pyrethroid-resistant Anopheles gambiae at the interface of two dual active-ingredient bed nets, assessed by room-scale infrared video tracking

BackgroundThe success of Insecticide Treated Bednets (ITNs) for malaria vector control in Africa relies on the behaviour of the major malaria vectors, Anopheles species. Research into mosquito behavioural traits influencing the performance of ITNs has focused largely on time or location of biting. Here we investigated less tractable behaviours including timings of net contact, willingness to refeed and longevity post exposure to two next-generation nets, PermaNet(R) 3.0 (P3) and Interceptor(R) G2 (IG2) in comparison with a standard pyrethroid only net (Olyset (OL)) and an untreated net. MethodsSusceptible and resistant Anopheles gambiae mosquitoes were exposed to the nets with a human volunteer host in a room scale assay. Mosquito movements were tracked for two hours using an infrared video system, collecting flight trajectory, spatial position and net contact data. Post-assay, mosquitoes were monitored for a range of sublethal insecticide effects. ResultsOL, P3 and IG2 all killed over 90% of susceptible mosquitoes 24 hours after exposure, but this effect was not seen with resistant mosquitoes where mortality ranged from 16% to 72%. Total mosquito activity was higher around untreated nets than ITNs. There was no difference in total activity, the number, or duration, of net contact, between any mosquito strain, with similar behaviours recorded in susceptible and resistant strains at all ITNs. Net contact was focussed predominantly on the roof for all bednets. We observed a steep decay in activity for both susceptible strains when P3 and OL were present and with IG2 for one of the two susceptible strains. All treated nets reduced the willingness of resistant strains to re-feed when offered blood one-hour post-exposure, with a more pronounced effect seen with P3 and OL than IG2. ConclusionResults indicate that the effects of ITNs on mosquito behaviour are consistent, with no major differences in responses between strains of different pyrethroid susceptibility.

animal behavior and cognition↗

Rapid identification of mosquito species, sex and age by mass spectrometric analysis

BackgroundA rapid, accurate method to identify and to age grade mosquito populations would be a major advance in predicting the risk of pathogen transmission and evaluating the public health impact of vector control interventions. Whilst other chemometric methods show promise, current approaches rely on challenging morphological techniques or simple binary classifications that cannot identify the subset of the population old enough to be infectious. In this study, the ability of Rapid Evaporative Ionisation Mass Spectrometry (REIMS) to identify the species, sex and age of mosquitoes reared in the laboratory and derived from the wild was investigated. ResultsThe accuracy of REIMS in identifying morphologically identical species of the Anopheles gambiae complex exceeded 97 % using principal component/linear discriminant analysis (PC-LDA) and 84 % based on random forest analysis. Age separation into 3 different age categories (1 d, 5-6 d, 14-15 d.) was achieved with 99 % (PC-LDA) and 94 % (random forest) accuracy, after including three species and storing samples at room temperature for up to 11 days. When tested on wild mosquitoes from the UK, REIMS data could determine the species and age of the specimens with accuracies of 91 and 90 % respectively. ConclusionsThe accuracy of REIMS to resolve the species and age of Anopheles mosquitoes is comparable to that achieved by chemometric approaches. The processing time and ease of use represent significant advantages over current, dissection-based methods. Importantly the accuracy was maintained when using wild mosquitoes reared under differing environmental conditions, and when mosquitoes were stored frozen or desiccated. This high throughput approach thus has potential to conduct rapid, real- time monitoring of vector populations, providing entomological evidence of the impact of alternative interventions.

ecology↗

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↗

Integration of whole genome sequencing and transcriptomics reveals a complex picture of insecticide resistance in the major malaria vector Anopheles coluzzii

Insecticide resistance is a major threat to gains in malaria control, which have been stalling and potentially reversing since 2015. Studies into the causal mechanisms of insecticide resistance are painting an increasingly complicated picture, underlining the need to design and implement targeted studies on this phenotype. In this study, we compare three populations of the major malaria vector An. coluzzii: a susceptible and two resistant colonies with the same genetic background. The original colonised resistant population rapidly lost resistance over a 6-month period, a subset of this population was reselected with pyrethroids a third population of this colony that did not lose resistance was also available. The original resistant, susceptible and re-selected colonies were subject to RNAseq and whole genome sequencing, which identified a number of changes across the transcriptome and genome linked with resistance. Firstly, an increase in the expression of genes within the oxidative phosphorylation pathway were seen in both resistant populations compared to the susceptible control; this translated phenotypically through an increased respiratory rate, indicating that elevated metabolism is linked directly with resistance. Genome sequencing highlighted several blocks clearly associated with resistance, including the 2Rb inversion. Finally, changes in the microbiome profile were seen, indicating that the microbial composition may play a role in the resistance phenotype. Taken together, this study reveals a highly complicated phenotype in which multiple transcriptomic, genomic and microbiome changes combine to result in insecticide resistance.

genomics↗

CRISPR/Cas9 modified An. gambiae carrying kdr mutation L1014F functionally validate its contribution in insecticide resistance and interaction with metabolic enzymes.

Insecticide resistance in Anopheles mosquitoes is a major obstacle in maintaining the momentum in reducing the malaria burden; mitigating strategies require improved understanding of the underlying mechanisms. Mutations in the target site of insecticides (the voltage gated sodium channel for the most widely used pyrethroid class) and over-expression of detoxification enzymes are commonly reported, but their relative contribution to phenotypic resistance remain poorly understood. Here we present a genome editing pipeline to introduce single nucleotide polymorphisms in An. gambiae which we have used to study the effect of the classical kdr mutation L1014F (L995F based on An. gambiae numbering), one of the most widely distributed resistance alleles. Introduction of 1014F in an otherwise fully susceptible genetic background increased levels of resistance to all tested pyrethroids and DDT ranging from 9.9-fold for permethrin to >24-fold for DDT. The introduction of the 1014F allele was sufficient to reduce mortality of mosquitoes after exposure to deltamethrin treated bednets, even as the only resistance mechanism present. When 1014F was combined with over-expression of glutathione transferase Gste2, resistance to permethrin increased further demonstrating the critical combined effect between target site resistance and detoxification enzymes in vivo. We also show that mosquitoes carrying the 1014F allele in homozygosity showed fitness disadvantages including increased mortality at the larval stage and a reduction in fecundity and adult longevity, which can have consequences for the strength of selection that will apply to this allele in the field. Author SummaryEscalation of pyrethroid resistance in Anopheles mosquitoes threatens to reduce the effectiveness of our most important tools in malaria control. Studying the mechanisms underlying insecticide resistance is critical to design mitigation strategies. Here, using genome modified mosquitoes, we functionally characterize the most prevalent mutation in resistant mosquitoes, showing that it confers substantial levels of resistance to all tested pyrethroids and undermines the performance of pyrethroid-treated nets. Furthermore, we show that combining this mutation with elevated levels of a detoxification enzyme further increases resistance. The pipeline we have developed provides a robust approach to quantifying the contribution of different combinations of resistance mechanisms to the overall phenotype, providing the missing link between resistance monitoring and predictions of resistance impact.

genetics↗

Sub-lethal pyrethroid exposure and ageing lead to pronounced changes in gene expression in insecticide resistance Anopheles coluzzii.

BackgroundMalaria control is heavily reliant on the use of insecticides that target and kill the adult female Anopheline vector. The intensive use of insecticides of the pyrethroid class has led to widespread resistance in mosquito populations. The intensity of pyrethroid resistance in some settings in Africa means mosquitoes can contact bednets treated with this insecticide class multiple times with minimal mortality effects. However, the sublethal exposure may affect other traits controlling the vectorial capacity or fitness of the mosquito. ResultsHere we show that sublethal exposure of a highly resistant Anopheles coluzzii population originally from Burkina Faso to the pyrethroid deltamethrin results in large and sustained changes to transcript expression. We identify five clear patterns in the data showing changes to transcripts relating to: DNA repair, respiration, translation, ion transport and oxioreductase processes. Further, we highlight differential regulation of transcripts from detoxification families previously linked with insecticide resistance, in addition to clear down-regulation of the oxidative phosphorylation pathway both indicative of changes in metabolism post-exposure. Finally, we show that both ageing and diel cycle have major effects on known insecticide resistance related transcripts. ConclusionSub-lethal pyrethroid exposure, ageing and the diel cycle results in large-scale changes in the transcriptome of the major malaria vector Anopheles coluzzii. Our data strongly supports further phenotypic studies on how transcriptional changes such as reduced expression of the oxidative phosphorylation pathway or pyrethroid induced changes to redox state might impact key mosquito traits, such as vectorial capacity and life history traits.

genomics↗

A population genomic unveiling of a new cryptic mosquito taxon within the malaria-transmitting Anopheles gambiae complex

The Anopheles gambiae complex consists of multiple morphologically indistinguishable mosquito species including the most important vectors of the malaria parasite Plasmodium falciparum in sub-Saharan Africa. Several lineages have only recently been described as distinct, including the cryptic taxon GOUNDRY in central Burkina Faso. The ecological, immunological, and reproductive differences among these taxa will critically impact population responses to disease control strategies and environmental changes. Here we examine whole-genome sequencing data from a longitudinal study of putative A. coluzzii in western Burkina Faso. Surprisingly, many samples are genetically divergent from A. coluzzii and all other Anopheles species and represent a new taxon, here designated Anopheles TENGRELA (AT). Population genetic analysis suggests that GOUNDRY sensu stricto represents an admixed population descended from both A. coluzzii and AT. AT harbors low nucleotide diversity except for the 2La inversion polymorphism which is maintained by overdominance. It shows numerous fixed differences with A. coluzzii concentrated in several regions reflecting selective sweeps, but the two taxa are identical at standard diagnostic loci used for taxon identification and thus AT may often go unnoticed. We present an amplicon-based genotyping assay for identifying AT which could be usefully applied to numerous existing samples. Misidentified cryptic taxa could seriously confound ongoing studies of Anopheles ecology and evolution in western Africa, including phenotypic and genotypic surveys of insecticide resistance. Reproductive barriers between cryptic species may also complicate novel vector control efforts, for example gene drives, and hinder predictions about evolutionary dynamics of Anopheles and Plasmodium.

evolutionary biology↗

Cuticular hydrocarbon biosynthesis in malaria vectors: insights from the adult oenocyte transcriptome

The surface of insects is coated in cuticular hydrocarbons (CHCs); variations in the composition of this layer affect a range of traits including adaptation to arid environments and defence against pathogens and toxins. In the African malaria vector, Anopheles gambiae quantitative and qualitative variance in CHC composition have been associated with speciation, ecological habitat and insecticide resistance. Understanding how these modifications arise will inform us of how mosquitoes are responding to climate change and vector control interventions. CHCs are synthesised in sub-epidermal cells called oenocytes that are very difficult to isolate from surrounding tissue. Here we utilise a transgenic line with fluorescent oenocytes to purify these cells for the first time. Comparative transcriptomics revealed the enrichment of biological processes related to long chain fatty acyl-CoA biosynthesis and elongation of mono-, poly-unsaturated and saturated fatty acids and enabled us to delineate, and partially validate, the hydrocarbon biosynthetic pathway in An gambiae.

physiology↗

Steroid hormone agonists reduce female fitness in insecticide-resistant Anopheles populations

Insecticide based vector control tools such as insecticide treated bednets and indoor residual spraying represent the cornerstones of malaria control programs. Resistance to chemistries used in these programs is now widespread and represents a significant threat to the gains seen in reducing malaria-related morbidity and mortality. Recently, disruption of the 20-hydroxyecdysone steroid hormone pathway was shown to reduce Plasmodium development time and significantly reduce both longevity and egg production in a laboratory susceptible Anopheles gambiae population. Here, we demonstrate that disruption of this pathway by application of methoxyfenozide (MET) to insecticide resistant An. coluzzii, An. gambiae sl and An. funestus populations significantly reduces egg production in both topical and tarsal application. Moreover, MET reduces adult longevity when applied topically, and tarsally after blood feeding. As the cytochrome p450s elevated in pyrethroid resistant Anopheles only bind MET very weakly, this compound is unlikely to be subject to cross-resistance in a field-based setting. Manipulation of this hormonal signalling pathway therefore represents a potential complementary approach to current malaria control strategies, particularly in areas where high levels of insecticide resistance are compromising existing tools.

pharmacology and toxicology↗