Search bioRxiv⌕ Search

Biology subjects

Corbel, V.

Publications and source records attributed to Corbel, V..

8 recordsLinked to original sources

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↗

Multi-centre laboratory study to determine discriminating concentrations for broflanilide and isocycloseram resistance monitoring in mosquitoes

1In 2024-2025 a multi-centre study involving seven international laboratories was conducted with the support of the World Health Organization (WHO). The aim of the study was to establish and validate discriminating concentrations (DCs) in WHO bottle bioassays for monitoring susceptibility to broflanilide and isocycloseram in Anopheles gambiae s.s., An. funestus, An. stephensi and Aedes aegypti. The following values are recommended for adoption as DCs for broflanilide: 10 {micro}g/bottle for An. gambiae and Ae. aegypti, 15 {micro}g/bottle for An. funestus, and 25 {micro}g/bottle for An. stephensi. The recommended DCs for isocycloseram are 15 {micro}g/bottle for Ae. aegypti, 30 {micro}g/bottle for An. gambiae, 50 {micro}g/bottle for An. stephensi, and 60 {micro}g/bottle for An. funestus. Based on the experiences of conducting this study, which represents the application of a generic protocol for establishing discriminating concentrations produced by the WHO, technical recommendations are made on the generation and analysis of DC data for insecticides in future.

zoology↗

Wolbachia introgression in Rio de Janeiro remains at sub-optimal levels 30 months after its crash: challenges in the sustainability of wMel interventions for dengue control

The deployment of the Wolbachia wMel strain is currently underway in multiple dengue-endemic municipalities across Brazil. The efficacy of this strategy in Rio de Janeiro remains uncertain, primarily due to the difficulty in sustaining high wMel prevalence in regions previously subjected to large-scale releases. A key contributing factor was the routine rotation of insecticides within the framework of Integrated Vector Management (IVM), which led to the use of the larvicide Spinosad for Aedes control in urban areas. This compound was associated with a precipitous decline in Aedes aegypti mosquitoes, regardless the wMel infection status. While wMel-uninfected population recovered within weeks, wMel-infected population remained at low levels likely due to the fitness costs imposed by wMel on egg viability. To assess the long-term persistence of wMel following this demographic collapse, we conducted mosquito sampling across 12 neighborhoods in Rio de Janeiro, 30 months after mosquito populations crashed. Our findings reveal that wMel introgression remains suboptimal, with a mean frequency of 9.87% across the sampled areas. Only two neighborhoods exhibited wMel frequencies exceeding 15%, likely reflecting ongoing localized releases. The reduced prevalence underscores the challenges of achieving self-sustaining wMel establishment in complex urban environments and highlight critical considerations for the implementation of Wolbachia-based dengue control programs in endemic regions. SponsorshipThis study was supported by grants from the CNPq - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (312282/2022-2, 307209/2023-7) and by FAPERJ - Fundacao Carlos Chagas Filho de Amparo a Pesquisa no Estado do Rio de Janeiro (E-26/211.159/2019, E-26/204.108/2024, E26/2001.844/2017, E-26/210.335/2022, E-26/210.537/2024).

ecology↗

Cytochrome P450 inhibition impedes pyrethroid effects on insects through Nav channel regulation

Insecticides used in various formulations are inevitable in agricultural pest control and prevention of vector-borne diseases. Piperonyl butoxide (PBO) is a synergist widely used to enhance the effectiveness of insecticides, notably pyrethroids, by inhibiting the detoxifying cytochrome P450 enzymes, thus reducing the capacity of insects to metabolize and resist insecticides. Recent studies, however, reveal an unexpectedly weak restoration of pyrethroid efficacy by PBO, but the underlying mechanism is unknown. Here, we demonstrate that the PBO-induced inhibition of cytochrome P450 impedes the effect of deltamethrin by mainly affecting its interaction with the inactivated state of voltage-gated sodium channels (Nav). We describe a new octopamine-dependent regulatory mechanism involving Gs, PKA, DARPP-32, and PP1-2A, which affect the cytochrome P450 conformation, thus limiting the effect of PBO and modulating the Nav gating. As a result, deltamethrin cannot reach its final binding site in the fenestration to exert its full effect. We confirmed in vivo that under chemical stressor, the level of octopamine is elevated, which decreases the deltamethrin efficacy. Our findings reveal a novel adaptation mechanism that increases insect survival by reducing insecticide efficacy, thus emphasizing the necessity of developing more effective formulations and technologies for pest and vector control.

pharmacology and toxicology↗

MALDI-TOF MS profiling and its contribution to mosquito-borne diseases: a systematic review

Mosquito-borne diseases are responsible for hundreds of thousands of deaths per year. The identification and control of the vectors that transmit pathogens to humans are crucial for disease prevention and management. Currently, morphological and molecular approaches are the standard methods used for vector identification, however, they present several limitations. In the last decade, matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) profiling emerged as an innovative technology in Biological Sciences and is now considered as a relevant tool for the identification of pathogens and arthropods. Beyond species identification, this tool can be relevant for the determination of different life traits of arthropod vectors. The purpose of the present systematic review was to highlight the contribution of MALDI-TOF MS to the surveillance and control of mosquito-borne diseases. Published articles from January 2003 to September 2023 were retrieved, considering different aspects of mosquito life traits which could be determinant in the transmission of diseases and vector management. The screening of scientific literature resulted in the selection of 54 published articles that assessed MALDI-TOF MS profiling to study various biological factors such species identification, life expectancy, gender, trophic preferences, microbiota and insecticide resistance. Although a large majority of the selected articles focused on species identification, the present review shows that MALDI-TOF MS profiling is promising for identifying various mosquito life traits with rapidity, high throughput capacity, reliability and low cost. The strength and weakness of this proteomic tool for vector control and surveillance are discussed.

ecology↗

Potential of MALDI-TOF MS biotyping to detect deltamethrin resistance in the dengue vector Aedes aegypti.

Insecticide resistance in mosquitoes is spreading worldwide and represents a growing threat to vector control. Insecticide resistance is caused by different mechanisms including higher metabolic detoxication, target-site modification, reduced penetration and behavioral changes that are not easily detectable with simple diagnostic methods. Indeed, most molecular resistance diagnostic tools are costly and labor intensive and then difficult to use for routine monitoring of insecticide resistance. The present study aims to determine whether mosquito susceptibility status against the pyrethroid insecticides (mostly used for mosquito control) could be established by the protein signatures of legs and/or thoraxes submitted to MALDI-TOF Mass Spectrometry (MS). The quality of MS spectra for both body parts was controlled to avoid any bias due to unconformity protein profiling. The comparison of MS profiles from three inbreeds Ae. aegypti lines from French Guiana (IRF, IR03, IR13), with distinct deltamethrin resistance genotype / phenotype and the susceptible reference laboratory line BORA (French Polynesia), showed different protein signatures. On both body parts, the analysis of whole protein profiles revealed a singularity of BORA line compared to the three inbreeding lines from French Guiana origin, suggesting that the first criteria of differentiation is the geographical origin and/or the breeding history rather than the insecticide susceptibility profile. However, a deeper analysis of the protein profiles allowed to identify 10 and 11 discriminating peaks from leg and thorax spectra, respectively. Among them, a specific peak around 4870 Da was detected in legs and thoraxes of pyrethroid resistant lines compared to the susceptible counterparts hence suggesting that MS profiling may be promising to rapidly distinguish resistant and susceptible phenotypes. Further work is needed to confirm the nature of this peak as a deltamethrin resistant marker and to validate the routine use of MS profiling to track insecticide resistance in Ae. aegypti field populations. Author SummaryThe monitoring of mosquito insecticide resistance in local populations is essential to guide the choice of the vector control strategy. Current methods for resistance monitoring rely on biological, biochemical and molecular assays that all have their weakness. To circumvent these limitations, alternative methods have to be explored. In previous studies, MALDI-TOF MS profiling have proved it performance to classify mosquitoes at the species and sub-species levels. The present work aim was to assess whether MALDI-TOF MS profiling strategy could be useful for determination of mosquito susceptibility to the most used pyrethroid insecticide. In this way, four mosquito lines with distinct deltamethrin resistance genotype / phenotype were submitted to MS analysis. The accurate comparison of MS spectra showed different peak intensities between mosquitoes exhibiting different insecticide resistance profiles. Among discriminant peaks, one may be promising to detect insecticide-resistance mechanisms in public health mosquitoes. A better characterization of mosquito life traits will help countries to implement timely and locally adapted vector control interventions.

bioengineering↗

A ticket to ride: genetic structure and kdr mutations in Aedes aegypti populations along a road crossing the Amazon Rainforest in Amapa State, Brazil

Insecticide resistance in Aedes aegypti is a major threat to the control of this mosquito species that transmits viruses that cause diseases like dengue, Zika, and chikungunya. One type of resistance is caused by alterations in the Nav gene, known as kdr mutations. In Brazil, different kdr haplotypes are present in Ae. aegypti and they may impede vector control operations based on pyrethroids. Although natural populations tend to accumulate genetic differences among isolated localities, this mosquito can actively and passively disperse, hitchhiked with human transportation. In this study, we investigated the genetic structure and kdr dispersion in Ae. aegypti populations in six localities of the Amapa State, Brazil located along a north-south transect of the Amazonian Forest. Genetic structure was assessed using 12 microsatellite loci in a fragment analysis sequencing procedure, and qPCR methods were used to detect the presence and frequency of three well known kdr mutations (V410L, V1016I and F1534C). We found a high prevalence of kdr alleles in all localities, indicating that kdr is spreading in the Amapa State. The microsatellite analyses suggested a certain level of differentiation among the mosquito populations, dividing them into two well-defined clusters, as evidenced by Bayesian and DAPC analyses. The population from Oiapoque (located in the north along the border with French Guiana) had the highest kdr frequencies and the highest genetic differentiation compared to the other localities. Our findings suggest that there is genetic structure among Ae. aegypti from the Amapa State, but with some level of passive gene flow between population clusters. The study highlights the importance of continued surveillance of Ae. aegypti populations to monitor the spread of insecticide resistance and inform on vector control strategies. Author summaryAmapa, a State in northern Brazil, is crucial as a gateway for diseases due to its border with French Guiana. One notable example was chikungunya, transmitted by the Aedes aegypti mosquito, also responsible for dengue, Zika, and yellow fever viruses. Chemical insecticides have been the primary means of control, however, resistance to these compounds is spreading among Ae. aegypti populations, compromising their effectiveness. Mutations known as "kdr" contribute to resistance to pyrethroid insecticides. Our study focused on these mutations and genetic differentiation in Ae. aegypti populations from six cities along the road nestled amidst the Amazonian Forest, linking the capital, Macapa, to Oiapoque on the Brazil-French Guiana border. The results revealed high frequencies of kdr mutations in all populations, indicating probable resistance to pyrethroids. Genetic analysis showed two distinct groups among the mosquitoes, with evidence of mosquito flow, particularly between Macapa and Oiapoque, facilitated by human transportation. Monitoring insecticide resistance and mosquito migration is essential for effective vector control strategies. Understanding these factors enables us to combat mosquito-borne diseases and safeguard public health.

evolutionary biology↗

Herd protection against Plasmodium falciparum infections conferred by mass antimalarial drug administrations and the implications for malaria elimination

IntroductionAll nations of the Greater Mekong Subregion have committed to elimination of malaria by the year 2030. Elimination efforts rely on increasing access to diagnosis and treatment. However, asymptomatic infections pose a major challenge for these efforts. One approach towards eliminating asymptomatic reservoirs is targeted mass antimalarial drug administration (MDA). Here we present a fine scale spatiotemporal analysis of malaria incidence and prevalence in villages undergoing MDA.\n\nMethodsFour villages along the Myanmar-Thailand border were selected for a MDA pilot study based on clinical records and prevalence surveys. Passive detection of clinical episodes was facilitated through community based malaria clinics in each village. All villagers were screened using venous blood and ultra-sensitive qPCR (uPCR) for detection of parasites at baseline and every subsequent 3 months until month 18 (M18). A final screening was done at M24. MDAs were conducted on M0, M1 and M2 in two villages and on M9, M10, M11 in the remaining two villages. Which villages received early or deferred MDA was decided using restricted randomization. MDA participation, clinical episodes and uPCR detected infections were mapped to participant houses. Scan statistics were used to test for clusters of malaria episodes, malaria infections and non-adherence to MDA. Mixed effects regressions were used to test for risk factors for clinical episodes after MDA.\n\nResultsNeighborhood level MDA adherence was a major predictor for clinical episodes of malaria post-MDA, suggesting a strong herd effect. Each village had a cluster of P. falciparum infections at M0. After M0, there were no clusters of uPCR detectable P. falciparum infections. Clinical episodes of P. falciparum occurred in one village only which had a cluster of non-adherence to MDA and a high mosquito vector human biting rate. Individuals with subclinical P.falciparum infections were more likely to have subsequent clinical episodes than individuals who had no subclinical infections. Individuals who lived in a house with someone who had a clinical episode were more likely to also have a clinical episode subsequently than individuals residing in a house free of P.falciparum infections.\n\nConclusionTo our knowledge this is the first study to show a herd effect from MDA for malaria. These data and results have significance for spatial targeting of interventions for malaria elimination. Clusters of non-adherence to MDA participation can lead to failed elimination if they occur among individuals with asymptomatic infections and given sufficient mosquito vector exposure. Community participation, which can be facilitated through community engagement, is key to MDA success.

epidemiology↗