Immunomodulation in dengue: towards deciphering dengue severity markers.

BACKGROUND: Dengue is a vector-borne debilitating disease that is manifested as mild dengue fever, dengue with warning signs, and severe dengue. Dengue infection provokes a collective immune response; in particular, the innate immune response plays a key role in primary infection and adaptive immunity during secondary infection. In this review, we comprehensively walk through the various markers of immune response against dengue pathogenesis and outcome. MAIN BODY: Innate immune response against dengue involves a collective response through the expression of proinflammatory cytokines, such as tumor necrosis factors (TNFs), interferons (IFNs), and interleukins (ILs), in addition to anti-inflammatory cytokines and toll-like receptors (TLRs) in modulating viral pathogenesis. Monocytes, dendritic cells (DCs), and mast cells are the primary innate immune cells initially infected by DENV. Such immune cells modulate the expression of various markers, which can influence disease severity by aiding virus entry and proinflammatory responses. Adaptive immune response is mainly aided by B and T lymphocytes, which stimulate the formation of germinal centers for plasmablast development and antibody production. Such antibodies are serotype-dependent and can aid in virus entry during secondary infection, mediated through a different serotype, such as in antibody-dependent enhancement (ADE), leading to DENV severity. The entire immunological repertoire is exhibited differently depending on the immune status of the individual. SHORT CONCLUSION: Dengue fever through severe dengue proceeds along with the modulated expression of several immune markers. In particular, TLR2, TNF-α, IFN-I, IL-6, IL-8, IL-17 and IL-10, in addition to intermediate monocytes (CD14+CD16+) and Th17 (CD4+IL-17+) cells are highly expressed during severe dengue. Such markers could assist greatly in severity assessment, prompt diagnosis, and treatment.

Assessing dengue risk globally using non-Markovian models.

Dengue is a vector-borne disease transmitted by Aedes mosquitoes. The worldwide spread of these mosquitoes and the increasing disease burden have emphasized the need for a spatio-temporal risk map capable of assessing dengue outbreak conditions and quantifying the outbreak risk. Given that the life cycle of Aedes mosquitoes is strongly influenced by habitat temperature, numerous studies have utilized temperature-dependent development rates of these mosquitoes to construct virus transmission and outbreak risk models. In this study, we contribute to existing research by developing a mechanistic model for the mosquito life cycle that accurately captures its non-Markovian nature. Beginning with integral equations to track the mosquito population across different life cycle stages, we demonstrate how to derive the corresponding differential equations using phase-type distributions. This approach can be further applied to similar non-Markovian processes that are currently described with less accurate Markovian models. By fitting the model to data on human dengue cases, we estimate several model parameters, allowing the development of a global spatiotemporal dengue risk map. This risk model employs temperature and precipitation data to assess the environmental suitability for dengue outbreaks in a given area.

The microbiota's role in flavivirus control: Rosenbergiella_YN46.

The transmission of flaviviruses, such as dengue virus (DENV) and Zika virus (ZIKV), poses a significant threat to global public health. Zhang et al. recently showed that Rosenbergiella sp. YN46 (Rosenbergiella_YN46), a bacterium from the mosquito gut, inhibits flavivirus transmission and thus offers a potential biocontrol strategy with broad public health implications.

Impact of the exposure of sublethal dose of mosquito coil on the development of insecticide resistance in Aedes aegypti (L.) (Diptera: Culicidae).

Mosquito coil is commonly used in many African households for protection against mosquito bites. The coil usually has semi-volatile pyrethroids as an active ingredient, which usually diffuse across open space, and the cloud either kills mosquitoes that are exposed, or mosquitoes can be exposed to sublethal doses of the insecticides. This study was conducted to assess the impact of sublethal doses of mosquito coil on the development of insecticide resistance in Aedes aegypti, a major vector for dengue fever and several other arboviral diseases. A laboratory colony of Ae. aegypti was exposed to sublethal doses of a meperfluthrin-based mosquito coil in a Peet-Grady chamber once per generation for 16 generations. The susceptibility of the exposed colony to a diagnostic dose of the mosquito coil as well as to three other insecticides was determined. Three different kdr mutations and five enzyme activities were evaluated in both the exposed and control colonies. After 16 generations of sublethal exposure to mosquito coils, the full diagnostic dose of the coil caused 68% mortality to the exposed colony compared to 100% mortality in the control colony. Mortality caused by deltamethrin (0.05%) was also significantly lower in the exposed colony. The frequency of 1016I kdr mutation as well as MFO and alpha esterase activities were higher in the exposed colony compared to the control colony. This study provides evidence of the development of pyrethroid resistance in an Ae. aegypti population due to sublethal exposure to mosquito coil for 16 generations. Given the large-scale use of mosquito coils in many African households, its role as a pyrethroid resistance selection source should be taken into consideration when designing resistance management strategies.

Neofunctionalization driven by positive selection led to the retention of the loqs2 gene encoding an Aedes specific dsRNA binding protein.

BACKGROUND: Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects. RESULTS: Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference. CONCLUSIONS: Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors.

Geographic expansion of the introduced Aedes albopictus and other native Aedes species in the Democratic Republic of the Congo.

BACKGROUND: Aedes albopictus has been reported in several Central African countries, including the Democratic Republic of the Congo (DRC). The establishment of this mosquito species poses a serious threat as a vector of various infectious diseases. Although Ae. albopictus has been reported in the western region of the DRC, information about its distribution is still scarce in the country. The aim of this study was to investigate the current nationwide distribution of the invasive Ae. albopictus, as well as other native Aedes mosquitoes, in the DRC and to identify suitable areas for its future expansion. METHODS: Two entomological surveys were conducted in 2017-2019 and 2022. Based on the occurrence sites of Ae. albopictus, important environmental variables were identified. Then, geographical areas suitable for Ae. albopictus establishment were determined using the maximum entropy model. The distribution and abundance of Ae. albopictus were also compared with those of the major native Aedes species. RESULTS: Aedes albopictus was found in the western, northern, central, and eastern regions of the DRC, but it was not found in the southeastern region. The maximum entropy model predicted that most parts of the DRC are suitable for the establishment of this mosquito. The unsuitable areas encompassed the eastern highlands, known for their low temperatures, and the southeastern highlands, which experience both low temperatures and a long dry season. The native Aedes species found were Aedes aegypti, Aedes simpsoni, Aedes africanus, and Aedes vittatus. Aedes albopictus dominated in the western and northern regions, while Ae. aegypti was more prevalent in other regions. CONCLUSIONS: Aedes albopictus has been well established in the western and northern regions of the DRC. This mosquito is expanding its distribution while replacing the native Aedes species. Most of the country is suitable for the establishment of this mosquito species, except the highlands of the eastern and the southeastern regions.

Development of microsatellite markers for the invasive mosquito Aedes koreicus.

BACKGROUND: Aedes koreicus is a mosquito species native to East Asia which has recently invaded several countries in Europe. In Italy, this mosquito was first detected in the North-East in 2011 and is now widely distributed in the entire northern part of the country. The development of specific genetic markers, such as microsatellites, is necessary to uncover the dispersal routes of this mosquito from its native areas and, eventually, to plan future control interventions. METHODS: Available raw sequences of genomic DNA of Ae. koreicus were screened in silico using BLASTn to identify possible microsatellite-containing sequences. Specific primer pairs were then designed, and their efficiency was determined through polymerase chain reaction (PCR) on 32 individuals of Ae. koreicus collected in Italy. PCR conditions were optimised in three multiplex reactions. Genotyping of individual mosquitoes was performed on both single and multiplex PCR reactions. Finally, analysis of intra-population variation was performed to assess the level of polymorphism of the markers. RESULTS: Mosquito genotyping provided consistent results in both single and multiplex reactions. Out of the 31 microsatellite markers identified in the Ae. koreicus genome raw sequences, 11 were polymorphic in the examined mosquito samples. CONCLUSIONS: The results show that the 11 microsatellite markers developed here hold potential for investigating the genetic structure of Ae. koreicus populations. These markers could thus represent a novel and useful tool to infer the routes of invasion of this mosquito species into Europe and other non-native areas.

Genomic signatures of local adaptation in recent invasive Aedes aegypti populations in California.

BACKGROUND: Rapid adaptation to new environments can facilitate species invasions and range expansions. Understanding the mechanisms of adaptation used by invasive disease vectors in new regions has key implications for mitigating the prevalence and spread of vector-borne disease, although they remain relatively unexplored. RESULTS: Here, we integrate whole-genome sequencing data from 96 Aedes aegypti mosquitoes collected from various sites in southern and central California with 25 annual topo-climate variables to investigate genome-wide signals of local adaptation among populations. Patterns of population structure, as inferred using principal components and admixture analysis, were consistent with three genetic clusters. Using various landscape genomics approaches, which all remove the confounding effects of shared ancestry on correlations between genetic and environmental variation, we identified 112 genes showing strong signals of local environmental adaptation associated with one or more topo-climate factors. Some of them have known effects in climate adaptation, such as heat-shock proteins, which shows selective sweep and recent positive selection acting on these genomic regions. CONCLUSIONS: Our results provide a genome wide perspective on the distribution of adaptive loci and lay the foundation for future work to understand how environmental adaptation in Ae. aegypti impacts the arboviral disease landscape and how such adaptation could help or hinder efforts at population control.

What Are the Functional Roles of Piwi Proteins and piRNAs in Insects?

Research on Piwi proteins and piRNAs in insects has focused on three experimental models: oogenesis and spermatogenesis in Drosophila melanogaster, the antiviral response in Aedes mosquitoes and the molecular analysis of primary and secondary piRNA biogenesis in Bombyx mori-derived BmN4 cells. Significant unique and complementary information has been acquired and has led to a greater appreciation of the complexity of piRNA biogenesis and Piwi protein function. Studies performed in other insect species are emerging and promise to add to the current state of the art on the roles of piRNAs and Piwi proteins. Although the primary role of the piRNA pathway is genome defense against transposons, particularly in the germline, recent findings also indicate an expansion of its functions. In this review, an extensive overview is presented of the knowledge of the piRNA pathway that so far has accumulated in insects. Following a presentation of the three major models, data from other insects were also discussed. Finally, the mechanisms for the expansion of the function of the piRNA pathway from transposon control to gene regulation were considered.

Aedes mosquitoes in the emerging threat of urban yellow fever transmission.

This last decade has seen a resurgence of yellow fever (YF) in historical endemic regions and repeated attempts of YF introduction in YF-free countries such as the Asia-Pacific region and the Caribbean. Infected travellers are the main entry routes in these regions where competent mosquito vectors proliferate in appropriate environmental conditions. With the discovery of the 17D vaccine, it was thought that YF would be eradicated. Unfortunately, it was not the case and, contrary to dengue, chikungunya and Zika, factors that cotribute to YF transmission remain under investigation. Today, all the signals are red and it is very likely that YF will be the next pandemic in the YF-free regions where millions of people are immunologically naïve. Unlike COVID-19, YF is associated with a high case-fatality rate and a high number of deaths are expected. This review gives an overview of global YF situation, including the non-endemic Asia-Pacific region and the Caribbean where Aedes aegypti is abundantly distributed, and also proposes different hypotheses on why YF outbreaks have not yet occurred despite high records of travellers importing YF into these regions and what role Aedes mosquitoes play in the emergence of urban YF.

Interplay between autophagy and Sindbis virus in cells derived from key arbovirus vectors, Aedes albopictus and Aedes aegypti mosquitoes.

Aedes albopictus and Aedes aegypti are two species of Aedes mosquitoes which transmit multiple arboviruses causing serious diseases in human. Intriguingly, infection of arbovirus in both Aedes mosquitoes does not cause dramatic pathology, indicating that both mosquitoes have evolved mechanisms to tolerate persistent infection and restrict viral replication to nonpathogenic levels. Therefore, understanding how these mosquitoes interact with viruses would help to find targets for controlling the related mosquito-borne diseases. Autophagy is a conserved cellular recycling process functioning in maintenance of cellular homeostasis and recirculation of cytoplasmic materials under stressful conditions. Autophagy also acts as a cellular defense mechanism against viral infection. It is known that autophagy plays important roles in the replication of several Aedes mosquito-borne viruses in mammalian systems. However, little information is available regarding the role of autophagy in replication of those viruses in their primary vector, Aedes mosquitoes. This study found that interaction between autophagy and replication of Sindbis virus (SINV) occurred in Aedes albopictus C6/36 cells and Ae. aegypti Aag2 cells. Moreover, it discovered that the patterns of interaction between autophagy and SINV replication are different in C6/36 cells and Aag2 cells. It was shown that replication of SINV induced complete autophagy in C6/36 cells but suppressed autophagy in Aag2 cells. Moreover, induction of autophagy by rapamycin treatment restricted SINV replication in C6/36 cells but promoted SINV replication in Aag2 cells. Consistent with this, suppression of autophagy by down regulation of Atg8 promoted SINV replication in C6/36 cells but restricted SINV replication in Aag2 cells. It was also found that, in both C6/36 and Aag2 cells, interaction between autophagy and SINV replication occurred after viral entry and prior to viral assembly. Collectively, this work demonstrated that SINV replication manipulated autophagy in Aedes mosquito cells and provided strong evidence of the role autophagy played in viral replication in Aedes mosquitoes. The findings have laid a foundation to elucidate the correlation between autophagy and arbovirus replication in Aedes mosquitoes and could help to understand the difference in viral transmission capacity of the two Aedes mosquitoes, Ae. albopictus and Ae. aegypti.

Dengue fever and dengue virus in the People's Republic of China.

Infection with dengue virus (DENV) leads to symptoms variable from dengue fever to severe dengue, which has posed a huge socioeconomic and disease burden to the world population, particularly in tropical and subtropical regions. To date, four serotypes of DENV (DENV-1 to DENV-4) have been identified to sustain the transmission cycle in humans. In the past decades, dengue incidences have become more frequent, and four serotypes and various genotypes have been identified in PR China. Several large-scale dengue outbreaks and frequent local endemics occurred in the southern and coastal provinces, and the imported dengue cases accounted primarily for the initiation of the epidemics. No antiviral drug exists for dengue, and no vaccine has been approved to use in PR China, however strategies including public awareness, national reporting system of infectious diseases and public health emergencies, vector mosquito control, personal protection, and improved environmental sanitation have greatly reduced dengue prevalence. Some new technologies in vector mosquito control are emerging and being applied for dengue control. China's territory spans tropical, subtropical, and temperate climates, hence understanding the dengue status in China will be of beneficial for the global prevention and control of dengue. Here, we review the dengue status in PR China for the past decades and the strategies emerging for dengue control.

Genetic diversity of Dengue virus serotypes circulating among Aedes mosquitoes in selected regions of northeastern Nigeria.

The flaviviruses are mosquito borne pathogens that continue to pose a considerable public health risk to animals and humans. The members of this group includes, Dengue virus (DENV), Yellow fever virus (YVF), Japanese encephalitis virus (JEV), West Nile virus (WEV) and Zika virus (ZKV). The DENV mosquito vector is endemic to tropical and subtropical climates, placing ∼40% of the world's population at direct risk of dengue infection. Currently, in Nigeria the status of DENV serotypes circulating among mosquito vectors is unknown. Our study was designed to identify and characterize the DENV serotypes circulating in Aedes mosquito populations collected in selected sites in Nigeria. The mosquitoes were collected and identified morphologically to species level using colored identification keys of Rueda. Generally, each species identified was tested in pools of 20 individuals of each Aedes species. RT-PCR and semi nested PCR were used to detect DENV serotypes in mosquitoes and characterized using Sanger sequencing methods. The results showed that DENV serotypes were detected in 58.54% (24/41) of the pools of Aedes mosquitoes from Mubi, Numan and Yola screened. All DENV1-4 serotypes were detected in Ae. aegypti. While DENV 1, 2 and 4 were detected in Ae. albopictus. And only DENV 2 was detected in Ae. galloisi with DENV4 serotype being reported for the first time in Nigeria. DENV2 (37.8%) was the most detected serotypes, while double and triple co-infections of serotypes were detected in 24.4% of the pools. Phylogenetic analysis revealed a strong evolutionary relatedness of DENV serotypes in our study with that of South and Southeast Asia, North America, and other African countries. This is the first reports on the natural DENV serotypes co-infection among Aedes species pools in Nigeria, which can create possible interaction with other flaviviruses causing animal and human diseases. In addition, our study postulates the possible linkage between DENV serotypes infection and human febrile flu-like disease burden being experienced by host communities in northeastern Nigeria.

The role of heterogenous environmental conditions in shaping the spatiotemporal distribution of competing Aedes mosquitoes in Panama: implications for the landscape of arboviral disease transmission.

Monitoring the invasion process of the Asian tiger mosquito Aedes albopictus and its interaction with the contender Aedes aegypti, is critical to prevent and control the arthropod-borne viruses (i.e., Arboviruses) they transmit to humans. Generally, the superior ecological competitor Ae. albopictus displaces Ae. aegypti from most geographic areas, with the combining factors of biology and environment influencing the competitive outcome. Nonetheless, detailed studies asserting displacement come largely from sub-tropical areas, with relatively less effort being made in tropical environments, including no comprehensive research about Aedes biological interactions in Mesoamerica. Here, we examine contemporary and historical mosquito surveillance data to assess the role of shifting abiotic conditions in shaping the spatiotemporal distribution of competing Aedes species in the Republic of Panama. In accordance with prior studies, we show that Ae. albopictus has displaced Ae. aegypti under suboptimal wet tropical climate conditions and more vegetated environments within the southwestern Azuero Peninsula. Conversely, in the eastern Azuero Peninsula, Ae. aegypti persists with Ae. albopictus under optimal niche conditions in a dry and more seasonal tropical climate. While species displacement was stable over the course of two years, the presence of both species generally appears to fluctuate in tandem in areas of coexistence. Aedes albopictus was always more frequently found and abundant regardless of location and climatic season. The heterogenous environmental conditions of Panama shape the competitive outcome and micro-geographic distribution of Aedes mosquitoes, with potential consequences for the transmission dynamics of urban and sylvatic zoonotic diseases. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s10530-021-02482-y).

Risk factors for occurrence and abundance of Aedes aegypti and Aedes bromeliae at hotel compounds in Zanzibar.

BACKGROUND: A field survey was performed to investigate local environmental factors promoting occurrence and abundance of Aedes aegypti and Ae. bromeliae mosquitoes at hotel compounds in the south-east coastal region of Zanzibar Island. METHODS: The potential risk factors were determined using generalized linear mixed models. Aedes (Stegomyia) spp. indices such as container index (CI) and pupae per container (PPC) index were also estimated. RESULTS: Aedes aegypti and Ae. bromeliae were the most abundant vector species, accounting for 70.8% of all Aedes mosquitoes collected. The highest CI was observed for plastic containers irrespective of the season, whereas the highest PPC was observed for coconut shells and aluminium containers in the rainy and dry seasons, respectively. The risk of Aedes mosquito occurrence and abundance were significantly associated with presence of plastic containers, coconut shells, used tyres and steel containers. These were discarded in shaded places, in the open and gardens, or found in plant nurseries. CONCLUSION: This study shows that Aedes species of global health significance occur at hotel compounds on this part of Zanzibar Island. The occurrence and abundance are sustained by the presence of abundant and poorly managed solid wastes and containers used for gardening tasks. This highlights an urgent need for the adoption of area-wide environmentally sustainable Aedes mosquito management interventions that also integrate solid waste management and ornamental plant production practices for reducing the risk of arboviral disease epidemics.

Blood Meals With Active and Heat-Inactivated Serum Modifies the Gene Expression and Microbiome of Aedes albopictus.

The Asian "tiger mosquito" Aedes albopictus is currently the most widely distributed disease-transmitting mosquito in the world. Its geographical expansion has also allowed the expansion of multiple arboviruses like dengue, Zika, and chikungunya, to higher latitudes. Due to the enormous risk to global public health caused by mosquitoes species vectors of human disease, and the challenges in slowing their expansion, it is necessary to develop new and environmentally friendly vector control strategies. Among these, host-associated microbiome-based strategies have emerged as promising options. In this study, we performed an RNA-seq analysis on dissected abdomens of Ae. albopictus females from Manhattan, KS, United States fed with sugar and human blood containing either normal or heat-inactivated serum, to evaluate the effect of heat inactivation on gene expression, the bacteriome transcripts and the RNA virome of this mosquito species. Our results showed at least 600 genes with modified expression profile when mosquitoes were fed with normal vs. heat-inactivated-containing blood. These genes were mainly involved in immunity, oxidative stress, lipid metabolism, and oogenesis. Also, we observed bacteriome changes with an increase in transcripts of Actinobacteria, Rhodospirillaceae, and Anaplasmataceae at 6 h post-feeding. We also found that feeding with normal blood seems to particularly influence Wolbachia metabolism, demonstrated by a significant increase in transcripts of this bacteria in mosquitoes fed with blood containing normal serum. However, no differences were observed in the virome core of this mosquito population. These results suggest that heat and further inactivation of complement proteins in human serum may have profound effect on mosquito and microbiome metabolism, which could influence interpretation of the pathogen-host interaction findings when using this type of reagents specially when measuring the effect of Wolbachia in vector competence.

Zika Virus Potential Vectors among Aedes Mosquitoes from Hokkaido, Northern Japan: Implications for Potential Emergence of Zika Disease.

The Zika virus (ZIKV) is a rapidly expanding mosquito-borne virus that causes febrile illness in humans. Aedes aegypti and Ae. albopictus are the primary ZIKV vectors; however, the potential vector competence of other Aedes mosquitoes distributed in northern Japan (Palearctic ecozone) are not yet known. In this study, the susceptibility to Zika virus infection of three Aedes mosquitoes distributed in the main city of the northern Japan and their capacities as vectors for ZIKV were evaluated. Field-collected mosquitoes were fed ad libitum an infectious blood meal containing the ZIKV PRVABC59. The Zika virus was detected in the abdomen of Ae. galloisi and Ae. japonicus at 2-10 days post infection (PI), and from the thorax and head of Ae. galloisi at 10 days PI, resulting in 17.6% and 5.9% infection rates, respectively. The Zika virus was not detected from Ae. punctor at any time. Some northern Japanese Aedes could be suspected as vectors of ZIKV but the risk may be low when compared with major ZIKV vectors.

Dengue fever and insecticide resistance in Aedes mosquitoes in Southeast Asia: a review.

Dengue fever is the most important mosquito-borne viral disease in Southeast Asia. Insecticides remain the most effective vector control approach for Aedes mosquitoes. Four main classes of insecticides are widely used for mosquito control: organochlorines, organophosphates, pyrethroids and carbamates. Here, we review the distribution of dengue fever from 2000 to 2020 and its associated mortality in Southeast Asian countries, and we gather evidence on the trend of insecticide resistance and its distribution in these countries since 2000, summarising the mechanisms involved. The prevalence of resistance to these insecticides is increasing in Southeast Asia, and the mechanisms of resistance are reported to be associated with target site mutations, metabolic detoxification, reduced penetration of insecticides via the mosquito cuticle and behavioural changes of mosquitoes. Continuous monitoring of the status of resistance and searching for alternative control measures will be critical for minimising any unpredicted outbreaks and improving public health. This review also provides improved insights into the specific use of insecticides for effective control of mosquitoes in these dengue endemic countries.

The genomic signal of local environmental adaptation in Aedes aegypti mosquitoes.

Local adaptation is important when predicting arthropod-borne disease risk because of its impacts on vector population fitness and persistence. However, the extent that vector populations are adapted to the environment generally remains unknown. Despite low population structure and high gene flow in Aedes aegypti mosquitoes across Panama, excepting the province of Bocas del Toro, we identified 128 candidate SNPs, clustered within 17 genes, which show a strong genomic signal of local environmental adaptation. This putatively adaptive variation occurred across fine geographical scales with the composition and frequency of candidate adaptive loci differing between populations in wet tropical environments along the Caribbean coast and dry tropical conditions typical of the Pacific coast. Temperature and vegetation were important predictors of adaptive genomic variation in Ae. aegypti with several potential areas of local adaptation identified. Our study lays the foundations of future work to understand whether environmental adaptation in Ae. aegypti impacts the arboviral disease landscape and whether this could either aid or hinder efforts of population control.