The mosquito-borne disease, Yellow fever (YF), has been largely controlled via mass delivery of an effective vaccine and mosquito control interventions. However, there are warning signs that YF is re-emerging in both Sub-Saharan Africa and South America. Imported from Africa in slave ships, YF was responsible for devastating outbreaks in the Caribbean. In Martinique, the last YF outbreak was reported in 1908 and the mosquito Aedes aegypti was incriminated as the main vector. We evaluated the vector competence of fifteen Ae. aegypti populations for five YFV genotypes (Bolivia, Ghana, Nigeria, Sudan, and Uganda). Here we show that mosquito populations from the Caribbean and the Americas were able to transmit the five YFV genotypes, with YFV strains for Uganda and Bolivia having higher transmission success. We also observed that Ae. aegypti populations from Martinique were more susceptible to YFV infection than other populations from neighboring Caribbean islands, as well as North and South America. Our vector competence data suggest that the threat of re-emergence of YF in Martinique and the subsequent spread to Caribbean nations and beyond is plausible.

Abstract Mosquito-borne diseases are spreading globally due to the expansion of the geographic range of competent mosquito vector species and increased human movement, especially infected travelers from endemic to non-endemic regions. Yellow fever (YF) has been largely controlled via mass delivery of an effective vaccine and mosquito control interventions. However, there are warning signs that YF is re-emerging in both Sub-Saharan Africa and South America. Imported from Africa to the Americas in slave ships, YF was responsible for devastating urban outbreaks for several centuries. In the Caribbean, the last YF outbreak was reported in 1908 in Martinique. The mosquito Aedes aegypti is the main vector for urban transmission in YF-endemic regions. However, it is unclear if all Ae. aegypti populations can effectively vector yellow fever virus (YFV), as there is growing evidence that intrinsic virus and mosquito host factors can significantly influence arbovirus transmission. We evaluated the vector competence of fifteen Ae. aegypti populations (nine from Martinique, two from Haiti, one from Guadeloupe, one from Cuba, one from Florida (USA), and one from Colombia) for five YFV genotypes (Bolivia, Ghana, Nigeria, Sudan, and Uganda) at 14 and 21 days post-infectious feeding. Mosquito populations from the Caribbean and the Americas were able to transmit the five YFV genotypes, in some cases achieving viral loads in mosquito saliva of up to several thousands of infectious virus particles, with YFV strains for Uganda and Bolivia having higher transmission success. We also observed that Ae. aegypti populations from Martinique were more susceptible to YFV infection than other populations from neighboring Caribbean islands, as well as North and South America. Our vector competence data suggest that the threat of re-emergence of YF in Martinique and the subsequent spread to Caribbean nations and beyond is plausible.

First identified in 1947, Zika virus took roughly 70 years to cause a pandemic unusually associated with virus-induced brain damage in newborns. Zika virus is transmitted by mosquitoes, mainly Aedes aegypti , and secondarily, Aedes albopictus , both colonizing a large strip encompassing tropical and temperate regions. As part of the international project ZIKAlliance initiated in 2016, 50 mosquito populations from six species collected in 12 countries were experimentally infected with different Zika viruses. Here, we show that Ae. aegypti is mainly responsible for Zika virus transmission having the highest susceptibility to viral infections. Other species play a secondary role in transmission while Culex mosquitoes are largely non-susceptible. Zika strain is expected to significantly modulate transmission efficiency with African strains being more likely to cause an outbreak. As the distribution of Ae. aegypti will doubtless expand with climate change and without new marketed vaccines, all the ingredients are in place to relive a new pandemic of Zika.

Since its emergence in Yap Island in 2007, Zika virus (ZIKV) has affected all continents except Europe. Despite the hundreds of cases imported to European countries from ZIKV-infested regions, no local cases have been reported in localities where the ZIKV-competent mosquito Aedes albopictus is well established. Here we analysed the vector competence of European Aedes (aegypti and albopictus) mosquitoes to different genotypes of ZIKV. We demonstrate that Ae. albopictus from France was less susceptible to the Asian ZIKV than to the African ZIKV. Critically we show that effective crossing of anatomical barriers (midgut and salivary glands) after an infectious blood meal depends on a viral load threshold to trigger: (i) viral dissemination from the midgut to infect mosquito internal organs and (ii) viral transmission from the saliva to infect a vertebrate host. A viral load in body ≥4800 viral copies triggered dissemination and ≥12,000 viral copies set out transmission. Only 27.3% and 18.2% of Ae. albopictus Montpellier mosquitoes meet respectively these two criteria. Collectively, these compelling results stress the poor ability of Ae. albopictus to sustain a local transmission of ZIKV in Europe and provide a promising tool to evaluate the risk of ZIKV transmission in future outbreaks.

Understanding the spatio-temporal dynamics of endemic infections is of critical importance for a deeper understanding of pathogen transmission, and for the design of more efficient public health strategies. However, very few studies in this domain have focused on emerging infections, generating a gap of knowledge that hampers epidemiological response planning. Here, we analyze the case of a Chikungunya outbreak that occurred in Martinique in 2014. Using time series estimates from a network of sentinel practitioners covering the entire island, we first analyze the spatio-temporal dynamics and show that the largest city has served as the epicenter of this epidemic. We further show that the epidemic spread from there through two different propagation waves moving northwards and southwards, probably by individuals moving along the road network. We then develop a mathematical model to explore the drivers of the temporal dynamics of this mosquito-borne virus. Finally, we show that human behavior, inferred by a textual analysis of messages published on the social network Twitter, is required to explain the epidemiological dynamics over time. Overall, our results suggest that human behavior has been a key component of the outbreak propagation, and we argue that such results can lead to more efficient public health strategies specifically targeting the propagation process.

As part of a collaborative research project aimed at designing new chemicals active on mosquito larvae, we sought accessible raw materials and an efficient synthesis method for preparing large amounts of active substances. For this we selected retinoic acid, which has functionality close to that of juvenile hormones. From this molecule we developed ester and trifluoromethyl ketone synthesis that was fast and led to good yields.

Dengue and chikungunya viruses are transmitted by Aedes mosquitoes. In Martinique, an island of the French West Indies, Aedes aegypti is the suspected vector of both arboviruses; there is no Aedes albopictus on the island. During the concomitant outbreak of 2013 - 2015, the authors collected wild A. aegypti populations, and for the first time, detected dengue and chikungunya viruses in field-collected females. This paper demonstrates the mosquito's role in transmission of both dengue and chikungunya on the island, and also highlights a tool that public health authorities can use for preventing outbreaks.

Nonlinear quantitative structure–activity relationship (QSAR) models were derived for predicting the adulticidal activity of piperidines against mosquitoes. Thirty-three chemicals with their 24-hour LD50 values, obtained under the same experimental conditions on Aedes aegypti females, were used. Energy optimization allowed us to consider two conformational series of structures that were described by means of CODESSA descriptors. Only those encoding physicochemical information were considered. The 1-octanol/water partition coefficient (log P) of the molecules was also computed from the AUTOLOGP™ software. Each series was subject to modeling from a three-layer perceptron (TLP). The models were derived from training sets including 70% of the molecules, which were randomly selected. The remaining molecules were used as external test sets. Only 3/2/1 TLP models were considered. A consensus model was computed with an interesting configuration coming from each series. The selected hybrid TLP model showed correlation coefficients of 0.93 and 0.97 on 298the training set and external test set, respectively. From the simulation results, various molecules were identified and searched for their availability in existing free databases. A list of molecules of potential interest was elaborated that will be further refined in order to find new molecules having a synergistic activity with pyrethroids, especially deltamethrin.

Most arthropod-borne viruses (arboviruses), perpetuated by alternation between a vertebrate host and an insect vector, are likely to emerge through minor genetic changes enabling the virus to adapt to new hosts. In the past decade, chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged on La Réunion Island following the selection of a unique substitution in the CHIKV E1 envelope glycoprotein (E1-A226V) of an East-Central-South African (ECSA) genotype conferring a higher transmission rate by the mosquito Aedes albopictus. Assumed to have occurred independently on at least four separate occasions, this evolutionary convergence was suspected to be responsible for CHIKV worldwide expansion. However, assumptions on CHIKV emergence were mainly based on viral genetic changes and the role of the mosquito population quasispecies remained unexplored. Here we show that the nature of the vector population is pivotal in selecting the epidemic CHIKV. We demonstrate using microsatellites mosquito genotyping that Ae. albopictus populations are genetically differentiated, contributing to explain their differential ability to select the E1-226V mutation. Aedes albopictus, newly introduced in Congo coinciding with the first CHIKV outbreak, was not able to select the substitution E1-A226V nor to preferentially transmit a CHIKV clone harboring the E1-226V as did Ae. albopictus from La Réunion.

BACKGROUND:Since the major outbreak in 2007 in the Yap Island, Zika virus (ZIKV) causing dengue-like syndromes has affected multiple islands of the South Pacific region. In May 2015, the virus was detected in Brazil and then spread through South and Central America. In December 2015, ZIKV was detected in French Guiana and Martinique. The aim of the study was to evaluate the vector competence of the mosquito spp. Aedes aegypti and Aedes albopictus from the Caribbean (Martinique, Guadeloupe), North America (southern United States), South America (Brazil, French Guiana) for the currently circulating Asian genotype of ZIKV isolated from a patient in April 2014 in New Caledonia.METHODOLOGY/PRINCIPAL FINDINGS:Mosquitoes were orally exposed to an Asian genotype of ZIKV (NC-2014-5132). Upon exposure, engorged mosquitoes were maintained at 28° ± 1 °C, a 16h:8h light:dark cycle and 80% humidity. 25-30 mosquitoes were processed at 4, 7 and 14 days post-infection (dpi). Mosquito bodies (thorax and abdomen), heads and saliva were analyzed to measure infection, dissemination and transmission, respectively. High infection but lower disseminated infection and transmission rates were observed for both Ae. aegypti and Ae. albopictus. Ae. aegypti populations from Guadeloupe and French Guiana exhibited a higher dissemination of ZIKV than the other Ae. aegypti populations examined. Transmission of ZIKV was observed in both mosquito species at 14 dpi but at a low level.CONCLUSIONS/SIGNIFICANCE:This study suggests that although susceptible to infection, Ae. aegypti and Ae. albopictus were unexpectedly low competent vectors for ZIKV. This may suggest that other factors such as the large naïve population for ZIKV and the high densities of human-biting mosquitoes contribute to the rapid spread of ZIKV during the current outbreak.

Understanding the spatio-temporal dynamics of endemic infections is of critical importance for a deeper understanding of pathogen transmission, and for the design of more efficient public health strategies. However, very few studies in this domain have focused on emerging infections, generating a gap of knowledge that hampers epidemiological response planning. Here, we analyze the case of a Chikungunya outbreak that occurred in Martinique in 2014. Using time series estimates from a network of sentinel practitioners covering the entire island, we first analyze the spatio-temporal dynamics and show that the largest city has served as the epicenter of this epidemic. We further show that the epidemic spread from there through two different propagation waves moving northwards and southwards, probably by individuals moving along the road network. We then develop a mathematical model to explore the drivers of the temporal dynamics of this mosquito-borne virus. Finally, we show that human behavior, inferred by a textual analysis of messages published on the social network Twitter, is required to explain the epidemiological dynamics over time. Overall, our results suggest that human behavior has been a key component of the outbreak propagation, and we argue that such results can lead to more efficient public health strategies specifically targeting the propagation process.

Cet article presente les premiers resultats issus d’un programme de recherche associant chercheurs et operateurs de lutte anti-vectorielle. La mise en œuvre d’un protocole interdisciplinaire permet l’analyse des interactions entre facteurs socio-ecologiques concourant a l’exposition des populations urbaines et periurbaines a Aedes aegypti et Aedes albopictus. Une comparaison est effectuee entre les Antilles francaises et le littoral mediterraneen francais. L’analyse revele que des processus communs se degagent par-dela les specificites territoriales des sites etudies : la presence d’eau, la structure des jardins, les representations du risque vectoriel et l’experience de la maladie par les habitants. Dans les Antilles, la presence de gites larvaires est en outre favorisee par un deficit d’equipements urbains. Deux categories de gites larvaires sont identifiees : les gites comportementaux et les gites structuraux. Les premiers sont lies aux comportements des habitants et les seconds a la conception initiale du bâti et du jardin. Cette recherche conforte la necessite de davantage integrer la prevention de la formation de gites larvaires des la conception du bâti et l’elargit a la conception du jardin, formulant des preconisations en ce sens.

Background Chikungunya virus (CHIKV), mainly transmitted in urban areas by the mosquitoes Aedes aegypti and Aedes albopictus, constitutes a major public health problem. In late 2013, CHIKV emerged on Saint-Martin Island in the Caribbean and spread throughout the region reaching more than 40 countries. Thus far, Ae. aegypti mosquitoes have been implicated as the sole vector in the outbreaks, leading to the hypothesis that CHIKV spread could be limited only to regions where this mosquito species is dominant. Methodology/Principal Findings We determined the ability of local populations of Ae. aegypti and Ae. albopictus from the Americas and Europe to transmit the CHIKV strain of the Asian genotype isolated from Saint-Martin Island (CHIKV_SM) during the recent epidemic, and an East-Central-South African (ECSA) genotype CHIKV strain isolated from La Réunion Island (CHIKV_LR) as a well-characterized control virus. We also evaluated the effect of temperature on transmission of CHIKV_SM by European Ae. albopictus. We found that (i) Aedes aegypti from Saint-Martin Island transmit CHIKV_SM and CHIKV_LR with similar efficiency, (ii) Ae. aegypti from the Americas display similar transmission efficiency for CHIKV_SM, (iii) American and European populations of the alternative vector species Ae. albopictus were as competent as Ae. aegypti populations with respect to transmission of CHIKV_SM and (iv) exposure of European Ae. albopictus to low temperatures (20°C) significantly reduced the transmission potential for CHIKV_SM. Conclusions/Significance CHIKV strains belonging to the ECSA genotype could also have initiated local transmission in the new world. Additionally, the ongoing CHIKV outbreak in the Americas could potentially spread throughout Ae. aegypti- and Ae. albopictus-infested regions of the Americas with possible imported cases of CHIKV to Ae. albopictus-infested regions in Europe. Colder temperatures may decrease the local transmission of CHIKV_SM by European Ae. albopictus, potentially explaining the lack of autochthonous transmission of CHIKV_SM in Europe despite the hundreds of imported CHIKV cases returning from the Caribbean.

Controlling dengue virus transmission mainly involves integrated vector management. Risk maps at appropriate scales can provide valuable information for assessing entomological risk levels. Here, results from a spatio-temporal model of dwellings potentially harboring Aedes aegypti larvae from 2009 to 2011 in Tartane (Martinique, French Antilles) using high spatial resolution remote-sensing environmental data and field entomological and meteorological information are presented. This tele-epidemiology methodology allows monitoring the dynamics of diseases closely related to weather/climate and environment variability. A Geoeye-1 image was processed to extract landscape elements that could surrogate societal or biological information related to the life cycle of Aedes vectors. These elements were subsequently included into statistical models with random effect. Various environmental and meteorological conditions have indeed been identified as risk/protective factors for the presence of Aedes aegypti immature stages in dwellings at a given date. These conditions were used to produce dynamic high spatio-temporal resolution maps from the presence of most containers harboring larvae. The produced risk maps are examples of modeled entomological maps at the housing level with daily temporal resolution. This finding is an important contribution to the development of targeted operational control systems for dengue and other vector-borne diseases, such as chikungunya, which is also present in Martinique.

Human arboviral diseases have emerged or re-emerged in numerous countries worldwide due to a number of factors including the lack of progress in vaccine development, lack of drugs, insecticide resistance in mosquitoes, climate changes, societal behaviours, and economical constraints. Thus, Aedes aegypti is the main vector of the yellow fever and dengue fever flaviviruses and is also responsible for several recent outbreaks of the chikungunya alphavirus. As for the other mosquito species, the A. aegypti control relies heavily on the use of insecticides. However, because of increasing resistance to the different families of insecticides, reduction of Aedes populations is becoming increasingly difficult. Despite the unquestionable utility of insecticides in fighting mosquito populations, there are very few new insecticides developed and commercialized for vector control. This is because the high cost of the discovery of an insecticide is not counterbalanced by the 'low profitability' of the vector control market. Fortunately, the use of quantitative structure-activity relationship (QSAR) modelling allows the reduction of time and cost in the discovery of new chemical structures potentially active against mosquitoes. In this context, the goal of the present study was to review all the existing QSAR models on A. aegypti. The homology and pharmacophore models were also reviewed. Specific attention was paid to show the variety of targets investigated in Aedes in relation to the physiology and ecology of the mosquito as well as the diversity of the chemical structures which have been proposed, encompassing man-made and natural substances.

Gene duplications have long been advocated to contribute to the evolution of new functions. The role of selection in their early spread is more controversial. Unless duplications are favored for a direct benefit of increased expression, they are likely detrimental. In this article, we investigated the case of duplications favored because they combine already functionally divergent alleles. Their gene-dosage/fitness relations are poorly known because selection may operate on both overall expression and duplicates relative dosage. Using the well-documented case of Culex pipiens resistance to insecticides, we compared strains with various ace-1 allele combinations, including two duplicated alleles carrying both susceptible and resistant copies. The overall protein activity was nearly additive, but, surprisingly, fitness correlated better with the relative proportion of susceptible and resistant copies rather than any absolute measure of activity. Gene dosage is thus crucial, duplications stabilizing a "heterozygote" phenotype. It corroborates the view that these were favored because they fix a permanent heterosis, thereby solving the irreducible trade-off between resistance and synaptic transmission. Moreover, we showed that the contrasted successes of the two duplicated alleles in natural populations depend on genetic changes unrelated to ace-1, confirming the probable implication of recessive sublethal mutations linked to structural rearrangements in some duplications.

The SIRIS multicriteria analysis was applied to 129 insecticides to identify those which could be potentially used as larvicides and/or adulticides in vector control against mosquitoes. Their selection was made without a priori restrictions, even on the basis of criteria of toxicity or regulatory interdictions. The unique condition was that they had to be already marketed. Each insecticide was described by six toxicity/ecotoxicity criteria and five exposure/environmental fate criteria identified as important by a panel of experts with complementary skills. A scenario for the larvicides and another one for the aldulticides were considered. The toxicity/ecotoxicity criteria were ranked differently in the two scenarios while the same hierarchy was used in both scenarios for the exposure/environmental fate criteria. In addition, only 114 substances were considered for the adulticide scenario because some insecticides can only be used as larvicides on mosquitoes. Each insecticide being characterized by two SIRIS scores, one score value per hierarchy, a map was designed for each scenario. The substances located in the left bottom part of each map are the most interesting because they present low SIRIS score values on both the Toxicity/Ecotoxicity and Exposure/ Environmental fate scales. Their interest as potential candidates in vector control was discussed. Nevertheless, the need to complete this multicriteria identification by a full risk assessment study is a necessary condition before their use.

Effective vector control is currently challenged worldwide by the evolution of resistance to all classes of chemical insecticides in mosquitoes. In Martinique, populations of the dengue vector Aedes aegypti have been intensively treated with temephos and deltamethrin insecticides over the last fifty years, resulting in heterogeneous levels of resistance across the island. Resistance spreading depends on standing genetic variation, selection intensity and gene flow among populations. To determine gene flow intensity, we first investigated neutral patterns of genetic variability in sixteen populations representative of the many environments found in Martinique and experiencing various levels of insecticide pressure, using 6 microsatellites. Allelic richness was lower in populations resistant to deltamethrin, and consanguinity was higher in populations resistant to temephos, consistent with a negative effect of insecticide pressure on neutral genetic diversity. The global genetic differentiation was low, suggesting high gene flow among populations, but significant structure was found, with a pattern of isolation-by-distance at the global scale. Then, we investigated adaptive patterns of divergence in six out of the 16 populations using 319 single nucleotide polymorphisms (SNPs). Five SNP outliers displaying levels of genetic differentiation out of neutral expectations were detected, including the kdr-V1016I mutation in the voltage-gated sodium channel gene. Association tests revealed a total of seven SNPs associated with deltamethrin resistance. Six other SNPs were associated with temephos resistance, including two non-synonymous substitutions in an alkaline phosphatase and in a sulfotransferase respectively. Altogether, both neutral and adaptive patterns of genetic variation in mosquito populations appear to be largely driven by insecticide pressure in Martinique.