Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.

BackgroundThe landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control.Methodology and principal findingsThis Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors.Conclusions and significanceAlthough IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp.

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BackgroundThe capacity of Aedes mosquitoes to resist chemical insecticides threatens the control of major arbovirus diseases worldwide. Until alternative control tools are widely deployed, monitoring insecticide resistance levels and identifying resistance mechanisms in field mosquito populations is crucial for implementing appropriate management strategies. Metabolic resistance to pyrethroids is common in Aedes aegypti but the monitoring of the dynamics of resistant alleles is impeded by the lack of robust genomic markers.Methodology/Principal findingsIn an attempt to identify the genomic bases of metabolic resistance to deltamethrin, multiple resistant and susceptible populations originating from various continents were compared using both RNA-seq and a targeted DNA-seq approach focused on the upstream regions of detoxification genes. Multiple detoxification enzymes were over transcribed in resistant populations, frequently associated with an increase in their gene copy number. Targeted sequencing identified potential promoter variations associated with their over transcription. Non-synonymous variations affecting detoxification enzymes were also identified in resistant populations.Conclusion /SignificanceThis study not only confirmed the role of gene copy number variations as a frequent cause of the over expression of detoxification enzymes associated with insecticide resistance in Aedes aegypti but also identified novel genomic resistance markers potentially associated with their cis-regulation and modifications of their protein structure conformation. As for gene transcription data, polymorphism patterns were frequently conserved within regions but differed among continents confirming the selection of different resistance factors worldwide. Overall, this study paves the way of the identification of a comprehensive set of genomic markers for monitoring the spatio-temporal dynamics of the variety of insecticide resistance mechanisms in Aedes aegypti.

A previously described modular high-throughput screening system was used to characterize the spatial repellent, contact irritant, and toxicant chemical actions of 14 compounds historically used or under investigation for vector control. The response of F1-F4 Aedes aegypti (Thailand strain) to various concentrations of 4 organochlorines (chlordane, DDT, dieldrin, methoxychlor); 4 pyrethroids (alphacypermethrin, cypermethrin, deltamethrin, permethrin); 3 organophosphates (chlorpyrophos methyl, fenitrothion, malathion); 2 carbamates (bendiocarb, propoxur); and 1 pyrazole (chlorfenapyr) were evaluated. Results show chemicals exert different combinations of contact irritant, spatial repellent, and toxic actions. This is true even within the same chemical class. These actions can be ordered for each chemical based on the testing dose at which the specific response is elicited. Data also indicate that behavioral responses to spatial repellent and contact irritant actions are separate (or independent) from the toxic action of a compound. Results from pyrethroid and DDT assays also show chemicals can induce behavior-modifying actions, such as contact irritancy and spatial repellency, which will reduce man-vector contact, despite evidence of insecticide resistance within the test population. These findings support previous laboratory and field studies showing man-vector contact and disease transmission are routinely interrupted by spatial repellent and contact irritant actions of common public health insecticides. Studies similar to that presented here can be used as baseline evidence for expected vector responses and support best approaches for more detailed behavioral research.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) that recently caused outbreaks in the Americas. Over the past 60 years, this virus has been observed circulating among African, Asian, and Pacific Island populations, but little attention has been paid by the scientific community until the discovery that large-scale urban ZIKV outbreaks were associated with neurological complications such as microcephaly and several other neurological malformations in fetuses and newborns. This paper is a systematic review intended to list all mosquito species studied for ZIKV infection or for their vector competence. We discuss whether studies on ZIKV vectors have brought enough evidence to formally exclude other mosquitoes than Aedes species (and particularly Aedes aegypti) to be ZIKV vectors. From 1952 to August 15, 2017, ZIKV has been studied in 53 mosquito species, including 6 Anopheles, 26 Aedes, 11 Culex, 2 Lutzia, 3 Coquillettidia, 2 Mansonia, 2 Eretmapodites, and 1 Uranotaenia. Among those, ZIKV was isolated from 16 different Aedes species. The only species other than Aedes genus for which ZIKV was isolated were Anopheles coustani, Anopheles gambiae, Culex perfuscus, and Mansonia uniformis. Vector competence assays were performed on 22 different mosquito species, including 13 Aedes, 7 Culex, and 2 Anopheles species with, as a result, the discovery that A. aegypti and Aedes albopictus were competent for ZIKV, as well as some other Aedes species, and that there was a controversy surrounding Culex quinquefasciatus competence. Although Culex, Anopheles, and most of Aedes species were generally observed to be refractory to ZIKV infection, other potential vectors transmitting ZIKV should be explored.

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.