Antoine Mignotte

Background: Resistance of the arbovirus vector Aedes albopictus to pyrethroid insecticides is an emerging threat to vector control programs in Europe. Three knock-down resistance (’ Kdr ’) mutations affecting the voltage-gated sodium channels targeted by pyrethroids are known to confer resistance: V1016G, I1532T and F1534C . As these Kdr mutations are actively circulating in Europe, their monitoring is crucial for resistance surveillance programs. However, current Kdr genotyping methods are labor-intensive and costly, limiting their applicability for large-scale high-throughput surveillance. Methodology: Novel digital droplet PCR (ddPCR) TaqMan assays were developed, allowing the quantification of these Kdr mutations from pooled mosquito samples from field populations. The specificity of these assays was validated by using mosquitoes of known genotypes together with synthetic DNA constructs carrying haplotype combinations previously unseen in the field. The assays’ accuracy was assessed by comparing Kdr frequencies measured from pooled mosquitoes to those derived from individual genotypes. These assays were then used in a pilot surveillance study in mainland France, integrating deltamethrin bioassays, pooled Kdr mutation tracking and vector control interventions data. Findings: The developed ddPCR assays demonstrated high accuracy and specificity, with matching Kdr mutation frequencies between pooled samples and individual genotyping. The pilot surveillance study confirmed the low prevalence of Kdr V1016G and I1532T mutations in most French populations, though some populations exhibited a moderate decrease in susceptibility to deltamethrin. Deltamethrin spraying intensity was weakly correlated with Kdr I1532T mutation frequency while no correlation was observed with deltamethrin susceptibility, suggesting that insecticide selective pressure from curative vector control activities is at most a minor driver of resistance. Conclusion: These novel ddPCR assays provide a simple, cost-effective and high-throughput method for quantifying the frequency of Kdr mutations in Ae. albopictus populations. Their implementation in routine country-wide surveillance programs will enhance the detection of emerging resistance, and inform vector control strategies, preventing arboviral disease transmission. Author summary: Aedes albopictus , the Asian tiger mosquito, is an emerging global threat due to its ability to transmit the dengue, chikungunya and Zika viruses among others. Recurrent use of insecticides to prevent infections selects resistant mosquitoes. Kdr (knock-down resistance) mutations confer resistance to pyrethroid insecticides, like deltamethrin. In order to track the arrival of these mutations in a population, individual PCR tests are routinely used, which is very inefficient and costly. The digital droplet PCR tests presented in this study can instead be performed on pools of mosquitoes from the field, greatly increasing the output while reducing the costs. This makes them ideal for use in the surveillance of these mutations in field populations. We first confirmed that the tests are as efficient in pools as they are on single mosquitoes, then we applied these tests in a pilot study on French field mosquitoes to demonstrate their applicability for use in surveillance. Finally, we explored the link between deltamethrin sprayings, bioassay mortality and Kdr mutations frequency, which is non-existent. This means the current management of mosquito populations via insecticide use is sensible. We believe these tests have a place in streamlining the future surveillance programs of these mutations in the field.

In 2025, mainland France experienced an unprecedented chikungunya outbreak in Europe, likely associated with suitable climatic conditions and established presence of Aedes albopictus , the primary European vector of chikungunya virus (CHIKV). During the early phase of the outbreak (May-July 2025), when only limited case data were available, public health decision-making required rapid situational assessment under substantial uncertainty. Here, we apply a state-of-art, climate-sensitive eco-epidemiological modelling framework to infer transmission dynamics in real-time and to characterise early progression of outbreaks across affected locations in France. The framework is designed to infer transmission relevant information from early epidemic data, including relative outbreak risk across locations, potential timing of the initial amplification phase of transmission, and likely size of outbreaks in the absence of public-health control interventions. The analysis indicates that early epidemic data can be used to identify locations likely to experience substantial transmission episodes and to refining estimates of the timing of key transition phases of transmission, including the initial amplification phase of transmission approximately 2–3-months ahead of peak transmission. Predicted outbreak potential varied considerably across locations, reflecting differences in local climatic conditions and population density incorporated within the modelling framework. This framework supports real-time situational awareness and can be employed to improve the response and targeting of public health interventions during the emerging phase of outbreaks. Furthermore, insights into location-specific differences in predicted outbreak size and response priorities are particularly useful for understanding the localised transmission risk and informing targeted interventions.

Depuis 2006, des épizooties importantes de fièvre catarrhale ovine et de virus (FCO) de Schmallenberg (SB) sont observées dans la région ouest paléarctique, ces deux virus étant transmis par des moucherons hématophages autochtones du genre Culicoides (Diptera : Ceratopogonidae). Ces virus affectent les bovins, les ovins, les caprins et les ruminants sauvages. La dispersion des Culicoides correspond à ce que les écologues appellent dispersion stratifiée ou « stratified dispersal ». Elle résulte de la combinaison de dispersion active de proche en proche, sur de courtes distances, et de sauts sur de longues distances via le vent de manière passive ou semi-passive, permettant des sauts de dispersion de plusieurs centaines de kilomètres. Culicoides obsoletus est une espèce vectrice importante pour les virus de la FCO et de SB et abondante en région paléarctique. Si la dispersion des Culicoides par le vent au-dessus des masses d’eaux est bien établie, il est aussi important d’évaluer la dispersion au-dessus des terres et de déterminer l'influence des facteurs biotiques et abiotiques influant sur celle-ci.L'objectif de ce travail de thèse est de déterminer, par l'observation des patrons de distribution des fréquences alléliques, comment la dispersion a pu façonner l'arrangement spatial de la diversité génétique et comment elle est influencée par les paysages et par les caractéristiques des habitats qui peuvent favoriser ou limiter les mouvements des Culicoides. Pour cela, deux plans d’échantillonnage ont été utilisés : un échantillonnage populationnel à l’échelle de l’Europe (de la Scandinavie aux îles Canaries, à la Turquie), et un échantillonnage individuel à l’échelle française. L’utilisation complémentaire de marqueurs mitochondriaux et nucléaires à ces différentes échelles spatiales nous ont permis (i) de clarifier la distribution et de réviser le schéma taxonomique du Complexe Obsoletus/Scoticus, (ii) de mettre en évidence des flux de gènes importants permettant d'homogénéiser la structure génétique des populations à l'échelle d'un pays et d’un continent, (iii) de quantifier l’impact d’un large éventail de facteurs environnementaux et météorologiques sur la dispersion des Culicoides et de mettre en évidence l’importance de la densité d’hôtes, (iv) et de proposer un scénario présentant l’histoire évolutive récente des populations européennes de C. obsoletus. L’hypothèse retenue est une recolonisation post-glaciaire récente depuis le refuge glaciaire des Balkans et un refuge plus au nord-est. Ces populations auraient recolonisé ensemble l’ouest de l’Europe, engendrant une admixture des populations.Nos résultats démontrent une capacité de dispersion de C. obsoletus à l'intérieur des terres très importante, qui doit être prise en compte pour les travaux à venir sur la compétence des vecteurs et la modélisation épidémiologique de la transmission des virus transmis.

The spread of the highly invasive mosquito, Aedes albopictus , across Europe, combined with climate change and human travel and trade, has led to new epidemic threats from mosquito-borne viruses, most significantly dengue and chikungunya, which are increasing in frequency and magnitude. In 2025, mainland France has seen a record number of autochthonous cases and outbreaks of chikungunya, spread across multiple locations, primarily introduced by travellers from the French Overseas Territory of La Réunion which is experiencing severe chikungunya outbreaks. Here, we describe one of the largest French outbreaks and subsequent control measures in the city of Bergerac, Dordogne, which resulted in 102 cases as of 5 ^th November 2025. Using a state-of-the-art mathematical model, we accurately predict the course of the outbreak, suggesting that the initial control measures in the first four weeks after the discovery of the outbreak, limited in their intervention radius, had little effect on reducing the number of cases, given the high incidence and the wide geographic extent of viral circulation. However, subsequent more widespread and intense control efforts, combined with likely increased public awareness, substantially reduced case numbers. These findings underscore the need to tailor control measures to intensity and scale of viral circulation combined with effective preventive and proactive arbovirus surveillance. We conclude that adulticides combined with public awareness campaigns can be effective for public health protection and are an important part of mitigating against the risk of Aedes -borne arboviruses and the ongoing outbreaks in mainland France.

The presence and the activity of Aedes albopictus are a growing concern for nuisance and public health in Europe. Vector control operators, public health officers, and communities look for weather-based decision support systems to inform mosquito management policies. Despite an increasing number of entomological and modelling studies, our incomplete understanding of mosquito population response to weather drivers in natural conditions restricts the development of sound vector management policies. Here, we aim to clarify the role of weather conditions on Ae. albopictus presence and abundance in four sites in southwestern France. We rely on ovitrap longitudinal records collected on a 1-2 weeks basis and weather time series over 2023 and 2024 to model oviposition activity. Our analysis combines a mechanistic model from literature and a new machine learning model fitted on cross-correlated lagged weather predictors. Both models satisfactorily reproduce the observed oviposition dynamics, correctly predicting the onset and the end of the activity – periods that existing models have often inadequately captured. Temperature plays a major role in triggering the presence of Ae. albopictus , explaining the interannual variation of oviposition in all sites, especially in spring and autumn. In fact, warm springs and autumns extend the periods in which Ae. albopictus life-history traits (fertility, development, survival) approach their thermal optima. In summer, a more prominent role of rain and humidity emerges among secondary drivers of oviposition intensity. This work contributes to the development of operational weather-driven forecasting tools for Ae. albopictus activity to support vector control operations in different biogeographical contexts.

Mainland France is experiencing an unprecedented number of autochthonous cases of chikungunya in multiple locations, primarily in southern France, likely linked to the recent outbreak in La Réunion and associated travel. Given the region’s suitable climate and the widespread and abundant presence of Aedes albopictus , the primary European mosquito vector of chikungunya, further cases are anticipated in the coming months. Here, we apply a state-of-the-art, climate-sensitive eco-epidemiological model to forecast chikungunya transmission dynamics at affected outbreak locations. With a 2–3-month lead time in predictions of peak transmission, the model identifies foci most likely to experience severe outbreaks (e.g., Salon-de-Provence, Bernis, Castries) this year and helps to inform prioritisation and public health impact.

The risk of mosquito-borne diseases transmission is moving fast toward temperate climates with the colonization and proliferation of the Asian tiger mosquito vector Aedes albopictus and the rapid and mass transport of passengers returning from tropical regions where the viruses are endemic. The prevention of major Aedes -borne viruses heavily relies on the use of insecticides for vector control, mainly pyrethroids In Europe. High-throughput molecular assays can provide a cost-effective surrogate to phenotypic insecticide resistance assays when mutations have been previously linked to a resistance phenotype. Here, we screened for the spatial distribution of kdr mutations at a large scale using a two-step approach based on multiplexed amplicon sequencing and an unprecedented collection of field-derived mosquitoes in South of France. We identified the presence of the V1016G allele in 14 sites. The V1016G allele was predominantly found in South-East France close to the Italian border with two additional isolated sites close to Bordeaux and Marmande. All mosquitoes were heterozygous for this mutation and should not be phenotypically resistant to pyrethroid insecticide. Four other mutations were identified in our targeted genomic sequence: I1532T, M1006L, M1586L, M995L. Sequencing a section of maternally inherited mitochondrial genome confirmed that the spread of Ae. albopictus in France originated from founders with haplogroup A1. These findings contribute to the broader understanding of resistance dynamics in Europe and can inform targeted approaches to mitigate the impact of resistance on vector control.