Vector competence of Aedes aegypti from Havana,Cuba, for dengue virus type 1, chikungunya,and Zika viruses

BackgroundLike many countries from the Americas, Cuba is threatened by Aedes aegypti-associated arboviruses such as dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses. Curiously, when CHIKV was actively circulating in the region in 2013–2014, no autochthonous transmission of this virus was detected in Havana, Cuba, despite the importation of chikungunya cases into this city. To investigate if the transmission ability of local mosquito populations could explain this epidemiological scenario, we evaluated for the first time the vector competence of two Ae. aegypti populations (Pasteur and Párraga) collected from Havana for dengue virus type 1 (DENV-1), CHIKV, and ZIKV.Methodology/Principal findingsMosquito populations were fed separately using blood containing ZIKV, DENV-1, or CHIKV. Infection, dissemination, and transmission rates, were estimated at 3 (exclusively for CHIKV), 7, and 14 days post exposure (dpe) for each Ae. aegypti population-virus combination. Both mosquito populations were susceptible to DENV-1 and ZIKV, with viral infection and dissemination rates ranging from 24–97% and 6–67% respectively. In addition, CHIKV disseminated in both populations and was subsequently transmitted. Transmission rates were low (<30%) regardless of the mosquito population/virus combination and no ZIKV was detected in saliva of females from the Pasteur population at any dpe.Conclusions/SignificanceOur study demonstrated the ability of Ae. aegypti from Cuba to transmit DENV, ZIKV, and CHIKV. These results, along with the widespread distribution and high abundance of this species in the urban settings throughout the island, highlight the importance of Ae. aegypti control and arbovirus surveillance to prevent future outbreaks.     

Diagnostic performance of anti-Zika virus IgM,IgAM and IgG ELISAs during co-circulation of Zika,dengue, and chikungunya viruses in Brazil and Venezuela

BackgroundSerological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela.Methodology/Principal findingsAcute (day of illness 1–5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%.Conclusions/SignificanceOur findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.     

Working with Zika and Usutu Viruses In Vitro

Usutu (USUV) and Zika (ZIKV) viruses are emerging arboviruses of significant medical and veterinary importance. These viruses have not been studied as well as other medically important arboviruses such as West Nile (WNV), dengue (DENV), or chikungunya (CHIKV) viruses. As such, information regarding the behavior of ZIKV and USUV viruses in the laboratory is dated. Usutu virus re-emerged in Austria in 2001 and has since spread throughout the European and Asian continents causing significant mortality among birds. Zika virus has recently appeared in the Western Hemisphere and has exhibited high rates of birth defects and sexual transmission. Information about the characteristics of USUV and ZIKV viruses are needed to better understand the transmission, dispersal, and adaptation of these viruses in new environments. Since their initial characterization in the middle of last century, technologies and reagents have been developed that could enhance our abilities to study these pathogens. Currently, standard laboratory methods for these viruses are limited to 2–3 cell lines and many assays take several days to generate meaningful data. The goal of this study was to characterize these viruses in cells from multiple diverse species. Cell lines from 17 species were permissive to both ZIKV and USUV. These viruses were able to replicate to significant titers in most of the cell lines tested. Moreover, cytopathic effects were observed in 8 of the cell lines tested. These data indicate that a variety of cell lines can be used to study ZIKV and USUV infection and may provide an updated foundation for the study of host-pathogen interactions, model development, and the development of therapeutics.     

Impact of the introduction of chikungunya and zika viruses on the incidence of dengue in endemic zones of Mexico

BackgroundWith the arrival of chikungunya (CHIKV) and zika (ZIKV) viruses in Mexico, there was a decrease in diagnosed dengue virus (DENV) cases. During the first years of cocirculation (2015–2017), the algorithms established by epidemiological surveillance systems and the installed capacity limited us to one diagnostic test per sample, so there was an underestimation of cases until September 2017, when a multiplex algorithm was implemented. Therefore, the objective of this study was determine the impact of the introduction of CHIKV and ZIKV on the incidence of diagnosed DENV in endemic areas of Mexico, when performing the rediagnosis, using the multiplex algorithm, in samples from the first three years of co-circulation of these arboviruses.Methodology and principal findingsFor this, 1038 samples received by the Central Laboratory of Epidemiology between 2015 and 2017 were selected for this work. Viruses were identified by multiplex RT-qPCR, and the χ² test was used to compare categorical variables. With the new multiplex algorithm, we identified 2.4 times the rate of arbovirosis as originally reported, evidencing an underestimation of the incidence of the three viruses. Even so, significantly less dengue was observed than in previous years. The high incidence rates of chikungunya and Zika coincided with periods of dengue decline. The endemic channel showed that the cases caused by DENV rose again after the circulation of CHIKV and ZIKV decreased. In addition, 23 cases of coinfection were identified, with combinations between all viruses.Conclusions and significanceThe results obtained in this study show for the first time the real impact on the detected incidence of dengue after the introduction of CHIKV and ZIKV in Mexico, the degree of underestimation of these arboviruses in the country, as well as the co-infections between these viruses, whose importance clinical and epidemiological are still unknown.     

Development of a Specific CHIKV-E2 Monoclonal Antibody for Chikungunya Diagnosis

Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes. There have been many outbreaks of CHIKV infection worldwide, and the virus poses ongoing risks to global health. To prevent and control CHIKV infection, it is important to improve the current CHIKV diagnostic approaches to allow for the detection of low CHIKV concentrations and to correctly distinguish CHIKV infections from those due to other mosquito-transmitted viruses, including dengue virus(DENV), Japanese encephalitis virus(JEV), and Zika virus(ZIKV). Here, we produced monoclonal antibodies(mAbs) against the CHIKV envelope 2 protein(CHIKV-E2) and compared their sensitivity and specificity with commercially available m Abs using enzyme-linked immunosorbent assays(ELISA). Two anti-CHIKV-E2 mAbs, 19-1 and 21-1, showed higher binding affinities to CHIKV-E2 protein than the commercial mAbs did. In particular, the 19-1 m Ab had the strongest binding affinity to inactivated CHIKV. Moreover, the 19-1 mAb had very little cross-reactivity with other mosquito-borne viruses, such as ZIKV, JEV, and DENV. These results suggest that the newly produced anti-CHIKV-E2 mAb, 19-1, could be used for CHIKV diagnostic approaches.     

Zika Virus,a New Threat for Europe?

BackgroundSince its emergence in 2007 in Micronesia and Polynesia, the arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported. Together with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted by Aedes mosquitoes. Any countries where these mosquitoes are present could be potential sites for future ZIKV outbreak. We assessed the vector competence of European Aedes mosquitoes (Aedes aegypti and Aedes albopictus) for the currently circulating Asian genotype of ZIKV.Conclusions/SignificanceIn combination with the restricted distribution of European Ae. albopictus, our results on vector competence corroborate the low risk for ZIKV to expand into most parts of Europe with the possible exception of the warmest regions bordering the Mediterranean coastline.     

Risk factors for infection with chikungunya and Zika viruses in southern Puerto Rico: A community-based cross-sectional seroprevalence survey

Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika virus (ZIKV) outbreak in 2016. Communities Organized for the Prevention of Arboviruses (COPA) is a cohort study in southern Puerto Rico, initiated in 2018 to measure arboviral disease risk and provide a platform to evaluate interventions. To identify risk factors for infection, we assessed prevalence of previous CHIKV infection and recent ZIKV and DENV infection in a cross-sectional study among COPA participants. Participants aged 1–50 years (y) were recruited from randomly selected households in study clusters. Each participant completed an interview and provided a blood specimen, which was tested by anti-CHIKV IgG ELISA assay and anti-ZIKV and anti-DENV IgM MAC-ELISA assays. We assessed individual, household, and community factors associated with a positive result for CHIKV or ZIKV after adjusting for confounders. During 2018–2019, 4,090 participants were enrolled; 61% were female and median age was 28y (interquartile range [IQR]: 16–41). Among 4,035 participants tested for CHIKV, 1,268 (31.4%) had evidence of previous infection. CHIKV infection prevalence was lower among children 1–10 years old compared to people 11 and older (adjusted odds ratio [aOR] 2.30; 95% CI 1.71–3.08). Lower CHIKV infection prevalence was associated with home screens (aOR 0.51; 95% CI 0.42–0.61) and air conditioning (aOR 0.64; 95% CI 0.54–0.77). CHIKV infection prevalence also varied by study cluster of residence and insurance type. Few participants (16; 0.4%) had evidence of recent DENV infection by IgM. Among 4,035 participants tested for ZIKV, 651 (16%) had evidence of recent infection. Infection prevalence increased with older age, from 7% among 1–10y olds up to 19% among 41–50y olds (aOR 3.23; 95% CI 2.16–4.84). Males had an increased risk of Zika infection prevalence compared with females (aOR 1.31; 95% CI 1.09–1.57). ZIKV infection prevalence also decreased with the presence of home screens (aOR 0.66; 95% CI 0.54–0.82) and air conditioning (aOR 0.69; 95% CI 0.57–0.84). Similar infection patterns were observed for recent ZIKV infection prevalence and previous CHIKV infection prevalence by age, and the presence of screens and air conditioners in the home decreased infection risk from both viruses by as much as 50%.     

Aedes (Stegomyia) albopictus (Skuse): A Potential Vector of Zika Virus in Singapore

Background

Zika virus (ZIKV) is a little known arbovirus until it caused a major outbreak in the Pacific Island of Yap in 2007. Although the virus has a wide geographic distribution, most of the known vectors are sylvatic Aedes mosquitoes from Africa where the virus was first isolated. Presently, Ae. aegypti is the only known vector to transmit the virus outside the African continent, though Ae. albopictus has long been a suspected vector. Currently, Ae. albopictus has been shown capable of transmitting more than 20 arboviruses and its notoriety as an important vector came to light during the recent chikungunya pandemic. The vulnerability of Singapore to emerging infectious arboviruses has stimulated our interest to determine the competence of local Ae. albopictus to transmit ZIKV.

Methodology/Principal Findings

To determine the competence of Ae. albopictus to ZIKV, we orally infected local mosquito strains to a Ugandan strain virus. Fully engorged mosquitoes were maintained in an environmental chamber set at 29°C and 80–85%RH. Twelve mosquitoes were then sampled daily from day one to seven and on day 10 and 14 post infection (pi). Zika virus titre in the midgut and salivary glands of each mosquito were determined using tissue culture infectious dose₅₀ assay, while transmissibility of the virus was determined by detecting viral antigen in the mosquito saliva by qRT-PCR. High dissemination and transmission rate of ZIKV were observed. By day 7-pi, all mosquitoes have disseminated infection and 73% of these mosquitoes have ZIKV in their saliva. By day 10-pi, all mosquitoes were potentially infectious.

Conclusions/Significance

The study highlighted the potential of Ae. albopictus to transmit ZIKV and the possibility that the virus could be established locally. Nonetheless, the threat of ZIKV can be mitigated by existing dengue and chikungunya control program being implemented in Singapore.     

Dengue,Zika, and Chikungunya viral circulation and hospitalization rates in Brazil from 2014 to 2019: An ecological study

BackgroundIn addition to their direct pathogenic effects, arthropod-borne (arboviruses) have been hypothesized to indirectly contribute to hospitalizations and death through decompensation of pre-existing comorbidities. Using nationwide data routinely collected from 1 January 2014 to 31 December 2019 in Brazil, we investigated whether local increases in arbovirus notifications were associated with excess hospitalization.MethodsWe estimated the relative risks for the association between municipality- and state-level increases in arboviral case notifications and age-standardized hospitalization rates (i.e., classified as direct or indirect based on ICD-10 codes) using Bayesian multilevel models with random effects accounting for temporal and geographic correlations. For municipality-level analyses, we excluded municipalities with <200 notifications of a given arbovirus and further adjusted the models for the local Gini Index, Human Development Index, and Family Healthcare Strategy (Estratégia de Saúde da Família) coverage. Models for dengue, Zika, and chikungunya were performed separately.ResultsFrom 2014 to 2019, Brazil registered 7,566,330 confirmed dengue cases, 159,029 confirmed ZIKV cases, and 433,887 confirmed CHIKV cases. Dengue notifications have an endemic and seasonal pattern, with cases present in 5334 of the 5570 (95.8%) Brazilian municipalities and most (69.5%) registered between February and May. Chikungunya notifications followed a similar seasonal pattern to DENV but with a smaller incidence and were restricted to 4390 (78.8%) municipalities. ZIKV was only notified in 2581 (46.3%) municipalities. Increases in dengue and chikungunya notifications were associated with small increases in age-standardized arbovirus-related hospitalizations, but no consistent association was found with all-cause or other specific indirect causes of hospitalization. Zika was associated to increases in hospitalizations by neurological diseases.ConclusionsAlthough we found no clear association between increased incidence of the three arboviruses and excess risks of all-cause or indirect hospitalizations at the municipality- and state-levels, follow-up investigations at the individual-level are warranted to define any potential role of acute arbovirus infection in exacerbating risks of hospitalization from underlying conditions.     

A comparison of mosquito densities,weather and infection rates of Aedes aegypti during the first epidemics of Chikungunya (2014) and Zika (2016) in areas with and without vector control in Puerto Rico

In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively. Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in August 2016. The emergence of these mosquito‐transmitted arboviruses in the context of a lack of human population immunity allowed observations of whether the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities and weather. Mosquito density was monitored weekly in four communities using sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide data to be compared with the findings of a previous study carried out during the 2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti using mass AGO trapping (three traps per house in most houses) were compared with those in two nearby communities without vector control. Mosquito pools were collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without vector control, mosquito densities and rates of ZIKV detection in 2016 were significantly higher, similarly to those observed for CHIKV in 2014. The density of Ae. aegypti in treated sites was less than two females/trap/week, which is similar to the putative adult female threshold for CHIKV transmission. No significant differences in mosquito density or infection rates with ZIKV and CHIKV at the same sites between years were observed. Although 2016 was significantly wetter, mosquito densities were similar.     

The Aedes aegypti siRNA pathway mediates broad-spectrum defense against human pathogenic viruses and modulates antibacterial and antifungal defenses

The mosquito’s innate immune system defends against a variety of pathogens, and the conserved siRNA pathway plays a central role in the control of viral infections. Here, we show that transgenic overexpression of Dicer2 (Dcr2) or R2d2 resulted in an accumulation of 21-nucleotide viral sequences that was accompanied by a significant suppression of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) replication, thus indicating the broad-spectrum antiviral response mediated by the siRNA pathway that can be applied for the development of novel arbovirus control strategies. Interestingly, overexpression of Dcr2 or R2d2 regulated the mRNA abundance of a variety of antimicrobial immune genes, pointing to additional functions of DCR2 and R2D2 as well as cross-talk between the siRNA pathway and other immune pathways. Accordingly, transgenic overexpression of Dcr2 or R2d2 resulted in a lesser proliferation of the midgut microbiota and increased resistance to bacterial and fungal infections.

This study shows that transgenic overexpression of siRNA pathway factors in mosquitoes mediates a broad-spectrum antiviral action against human pathogenic viruses such as dengue, Zika and Chikungunya virus, with implications for novel arbovirus control strategies; the siRNA pathway also regulates antimicrobial immune responses against bacterial and fungal infections.     

The worldwide seroprevalence of DENV,CHIKV and ZIKV infection: A systematic review and meta-analysis

BackgroundAs the three major arthropod-borne viruses, dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) are posing a growing threat to global public health and socioeconomic development. Our study aimed to systematically review the global seroprevalences of these arboviruses from existing publications.MethodsArticles published between Jan 01, 2000 and Dec 31, 2019 in the databases of Embase, Pubmed and Web of Science were searched and collected. Countries or areas with known local presence of Aedes vector mosquitoes were included. Random effects model was utilized to estimate the pooled seroprevalences and the proportion of inapparent infection.ResultsOut of 1375, a total of 133 articles involving 176,001 subjects were included for our analysis. The pooled seroprevalences of DENV, CHIKV and ZIKV were 38%, 25% and 18%, respectively; and their corresponding proportions of inapparent infections were 80%, 40% and 50%. The South-East Asia Region had the highest seroprevalences of DENV and CHIKV, while the Region of the Americas had the highest seroprevalence of ZIKV. The seroprevalences of DENV and CHIKV were similar when comparing developed and developing countries, urban and rural areas, or among different populations. In addition, we observed a decreased global seroprevalences in the new decade (2010–2019) comparing to the decade before (2000–2009) for CHIKV. For ZIKV, the positive rates tested with the nucleic acid detection method were lower than those tested with the antibody detection method. Lastly, numerous cases of dual seropositivity for CHIKV and DENV were reported.ConclusionsOur results revealed a varied prevalence of arbovirus infections in different geographical regions and countries, and the inapparent infection accounted an unneglected portion of infections that requires more attention. This study will shed lights on our understanding of the true burden of arbovirus infections and promote appropriate vaccination in the future.     

Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases

Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson’s χ² and student’s t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson’s χ² and Fisher’s exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28–16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever—aOR: 0.56 [0.40–0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71–0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which can be used to triage patients for appropriate care in the clinical setting.     

Co-infection of Dengue,Zika and Chikungunya in a group of pregnant women from Tuxtla Gutiérrez,Chiapas: Preliminary data. 2019

IntroductionDengue, Zika and Chikungunya are RNA Arboviruses present in some areas of Mexico, mainly in the endemic state of Chiapas that is characterized by presence of the vector that transmit them and an ecology that favors high transmission. According to the national epidemiological surveillance system, Dengue has intensified since 2018 and outbreaks continue in various states while for Zika and Chikungunya a decrease in cases has been reported in recent years. The main objective of this study was to determine the incidence of Dengue, Zika and Chikungunya infections during pregnancy in the state of Chiapas.Principal findingsThe presence of previous and current infections and coinfections diagnosed by molecular (RT-PCR) and immunological (ELISA for IgG determination) techniques indicates a wide circulation of viruses in asymptomatic people, specifically in pregnant women showing that silent infections in dry season contributes to the preservation of viruses.ConclusionsFrom 136 studied samples, 27.7% tested positive for DENV, 8% for ZIKV and 24.1% for CHIKV by RTPCR and the values of IgG in sera show that 83.9% were positive for IgG antibodies against DENV, 65% against ZIKV and 59.1% against CHIKV. Results demonstrated presence of ZIKV and CHIKV, not detected by the epidemiological surveillance system, so the importance of establishing proactive epidemiological systems more strict, especially because these infections in pregnant women can cause severe health problems for newborn children.     

Protective Effects of Caffeine on Chikungunya and Zika Virus Infections: An in Vitro and in Silico Study

Infection by viruses Chikungunya (CHIKV) and Zika (ZIKV) continue to be serious problems in tropical and subtropical areas of the world. Here, we evaluated the antiviral and virucidal activity of caffeine against CHIKV and ZIKV in Vero, A549, and Huh-7 cell lines. Results showed that caffeine displays antiviral properties against both viruses. By pre-and post-infection treatment, caffeine significantly inhibited CHIKV and ZIKV replication in a dose-dependent manner. Furthermore, caffeine showed a virucidal effect against ZIKV. Molecular docking suggests the possible binding of caffeine with envelope protein and RNA-dependent RNA polymerase of CHIKV and ZIKV. This is the first study that showed an antiviral effect of caffeine against CHIKV and ZIKV. Although further studies are needed to better understand the mechanism of caffeine-mediated repression of viral replication, caffeine appears to be a promising compound that could be used for in vivo studies, perhaps in synergy with other compounds present in daily beverages.     

Modeling intra-mosquito dynamics of Zika virus and its dose-dependence confirms the low epidemic potential of Aedes albopictus

Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus’ vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.     

Coupled small molecules target RNA interference and JAK/STAT signaling to reduce Zika virus infection in Aedes aegypti

The recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is the best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. Previous work has evaluated the effect of insulin signaling on antiviral JAK/STAT and RNAi in vector mosquitoes. Specifically, insulin-fed mosquitoes resulted in reduced virus replication in an RNAi-independent, ERK-mediated JAK/STAT-dependent mechanism. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both RNAi and JAK/STAT antiviral pathways. ZIKV-infected Aedes aegypti were fed blood containing demethylasterriquinone B1 (DMAQ-B1), a potent insulin mimetic, in combination with AKT inhibitor VIII. Activation of this coordinated response additively reduced ZIKV levels in Aedes aegypti. This effect included a quantitatively greater reduction in salivary gland ZIKV levels up to 11 d post-bloodmeal ingestion, relative to single pathway activation. Together, our study indicates the potential for field delivery of these small molecules to substantially reduce virus transmission from mosquito to human. As infections like Zika virus are becoming more burdensome and prevalent, understanding how to control this family of viruses in the insect vector is an important issue in public health.     

Characterization of Lethal Zika Virus Infection in AG129 Mice

BackgroundMosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage.Conclusions/SignificanceFoot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing.     

Climatic and socio-economic factors supporting the co-circulation of dengue,Zika and chikungunya in three different ecosystems in Colombia

Dengue, Zika and chikungunya are diseases of global health significance caused by arboviruses and transmitted by the mosquito Aedes aegypti, which is of worldwide circulation. The arrival of the Zika and chikungunya viruses to South America increased the complexity of transmission and morbidity caused by these viruses co-circulating in the same vector mosquito species. Here we present an integrated analysis of the reported arbovirus cases between 2007 and 2017 and local climate and socio-economic profiles of three distinct Colombian municipalities (Bello, Cúcuta and Moniquirá). These locations were confirmed as three different ecosystems given their contrasted geographic, climatic and socio-economic profiles. Correlational analyses were conducted with both generalised linear models and generalised additive models for the geographical data. Average temperature, minimum temperature and wind speed were strongly correlated with disease incidence. The transmission of Zika during the 2016 epidemic appeared to decrease circulation of dengue in Cúcuta, an area of sustained high incidence of dengue. Socio-economic factors such as barriers to health and childhood services, inadequate sanitation and poor water supply suggested an unfavourable impact on the transmission of dengue, Zika and chikungunya in all three ecosystems. Socio-demographic influencers were also discussed including the influx of people to Cúcuta, fleeing political and economic instability from neighbouring Venezuela. Aedes aegypti is expanding its range and increasing the global threat of these diseases. It is therefore vital that we learn from the epidemiology of these arboviruses and translate it into an actionable local knowledge base. This is even more acute given the recent historical high of dengue cases in the Americas in 2019, preceding the COVID-19 pandemic, which is itself hampering mosquito control efforts.