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1.
Nat Commun ; 12(1): 1671, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33723237

RESUMEN

Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.


Asunto(s)
Infecciones por Flavivirus/epidemiología , Infecciones por Flavivirus/transmisión , Animales , Culicidae , Dengue/transmisión , Virus del Dengue , Brotes de Enfermedades , Epidemias , Fiji/epidemiología , Flavivirus , Humanos , Mosquitos Vectores/virología , Estaciones del Año , Virus Zika , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión
2.
Nat Commun ; 12(1): 1810, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33753725

RESUMEN

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens.


Asunto(s)
Algoritmos , Virus del Dengue/genética , Dengue/transmisión , Modelos Teóricos , Adulto , Aedes/virología , Animales , Niño , Dengue/epidemiología , Dengue/virología , Virus del Dengue/clasificación , Virus del Dengue/fisiología , Genoma Viral/genética , Interacciones Huésped-Patógeno , Humanos , Mosquitos Vectores/virología , Filogenia , Filogeografía/métodos , Filogeografía/estadística & datos numéricos , Dinámica Poblacional , Tailandia/epidemiología
3.
PLoS Negl Trop Dis ; 15(3): e0009259, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33705409

RESUMEN

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.


Asunto(s)
Fiebre Chikungunya/epidemiología , Dengue/epidemiología , Infección por el Virus Zika/epidemiología , Aedes/fisiología , Aedes/virología , Animales , Fiebre Chikungunya/economía , Fiebre Chikungunya/virología , Virus Chikungunya/fisiología , Clima , Colombia/epidemiología , Dengue/economía , Dengue/virología , Virus del Dengue/fisiología , Ecosistema , Humanos , Mosquitos Vectores/fisiología , Mosquitos Vectores/virología , América del Sur , Temperatura , Virus Zika/fisiología , Infección por el Virus Zika/economía , Infección por el Virus Zika/virología
4.
Mem Inst Oswaldo Cruz ; 115: e200313, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33533870

RESUMEN

BACKGROUND: Aedes aegypti is the sole vector of urban arboviruses in French Guiana. Overtime, the species has been responsible for the transmission of viruses during yellow fever, dengue, chikungunya and Zika outbreaks. Decades of vector control have produced resistant populations to deltamethrin, the sole molecule available to control adult mosquitoes in this French Territory. OBJECTIVES: Our surveillance aimed to provide public health authorities with data on insecticide resistance in Ae. aegypti populations and other species of interest in French Guiana. Monitoring resistance to the insecticide used for vector control and to other molecule is a key component to develop an insecticide resistance management plan. METHODS: In 2009, we started to monitor resistance phenotypes to deltamethrin and target-site mechanisms in Ae. aegypti populations across the territory using the WHO impregnated paper test and allelic discrimination assay. FINDINGS: Eight years surveillance revealed well-installed resistance and the dramatic increase of alleles on the sodium voltage-gated gene, known to confer resistance to pyrethroids (PY). In addition, we observed that populations were resistant to malathion (organophosphorous, OP) and alpha-cypermethrin (PY). Some resistance was also detected to molecules from the carbamate family. Finally, those populations somehow recovered susceptibility against fenitrothion (OP). In addition, other species distributed in urban areas revealed to be also resistant to pyrethroids. CONCLUSION: The resistance level can jeopardize the efficiency of chemical adult control in absence of other alternatives and conducts to strongly rely on larval control measures to reduce mosquito burden. Vector control strategies need to evolve to maintain or regain efficacy during epidemics.


Asunto(s)
Aedes/efectos de los fármacos , Insectos Vectores/genética , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Mosquitos Vectores/efectos de los fármacos , Piretrinas/farmacología , Aedes/genética , Aedes/virología , Animales , Guyana Francesa , Insectos Vectores/efectos de los fármacos , Control de Mosquitos/métodos , Mosquitos Vectores/virología , Análisis Espacio-Temporal
5.
Parasit Vectors ; 14(1): 22, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407778

RESUMEN

BACKGROUND: Due to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities. METHODS: The Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO). RESULTS: A total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days). CONCLUSIONS: To control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community.


Asunto(s)
Dengue/prevención & control , Dengue/transmisión , Infecciones Asintomáticas/epidemiología , China/epidemiología , Control de Enfermedades Transmisibles , Industria de la Construcción , Dengue/epidemiología , Dengue/virología , Virus del Dengue/fisiología , Brotes de Enfermedades/prevención & control , Susceptibilidad a Enfermedades/epidemiología , Susceptibilidad a Enfermedades/virología , Humanos , Incidencia , Modelos Teóricos , Control de Mosquitos , Mosquitos Vectores/crecimiento & desarrollo , Mosquitos Vectores/virología , Características de la Residencia , Lugar de Trabajo
6.
Parasit Vectors ; 14(1): 76, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482887

RESUMEN

BACKGROUND: On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence of Culex pipiens and Aedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour of Ae. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus. METHODS: For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test, Ae. albopictus females were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence. RESULTS: Culex pipiens and Ae. albopictus were found not be competent vectors for SARS-CoV-2, and Ae. albopictus was unable to mechanically transmit the virus. CONCLUSIONS: This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and that Ae. albopictus is unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding.


Asunto(s)
Aedes/virología , Culex/virología , Mosquitos Vectores/virología , /fisiología , Animales , Sangre/virología , Europa (Continente) , Femenino , ARN Viral/análisis , ARN Viral/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Ovinos/sangre
7.
Nat Commun ; 12(1): 151, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33420058

RESUMEN

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.


Asunto(s)
Fiebre Chikungunya/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Dengue/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Enfermedades Endémicas/estadística & datos numéricos , Infección por el Virus Zika/epidemiología , Adolescente , Aedes/virología , Animales , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/transmisión , Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/virología , Dengue/prevención & control , Dengue/transmisión , Dengue/virología , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades/prevención & control , República Dominicana/epidemiología , Enfermedades Endémicas/prevención & control , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Control de Mosquitos , Mosquitos Vectores/virología , Análisis Espacio-Temporal , Adulto Joven , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología
8.
Viruses ; 13(1)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466915

RESUMEN

Mosquito-borne arthropod-borne viruses (arboviruses) such as the dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) are important human pathogens that are responsible for significant global morbidity and mortality. The recent emergence and re-emergence of mosquito-borne viral diseases (MBVDs) highlight the urgent need for safe and effective vaccines, therapeutics, and vector-control approaches to prevent MBVD outbreaks. In nature, arboviruses circulate between vertebrate hosts and arthropod vectors; therefore, disrupting the virus lifecycle in mosquitoes is a major approach for combating MBVDs. Several strategies were proposed to render mosquitoes that are refractory to arboviral infection, for example, those involving the generation of genetically modified mosquitoes or infection with the symbiotic bacterium Wolbachia. Due to the recent development of high-throughput screening methods, an increasing number of drugs with inhibitory effects on mosquito-borne arboviruses in mammalian cells were identified. These antivirals are useful resources that can impede the circulation of arboviruses between arthropods and humans by either rendering viruses more vulnerable in humans or suppressing viral infection by reducing the expression of host factors in mosquitoes. In this review, we summarize recent advances in small-molecule antiarboviral drugs in mammalian and mosquito cells, and discuss how to use these antivirals to block the transmission of MBVDs.


Asunto(s)
Aedes/virología , Antivirales/farmacología , Infecciones por Arbovirus/transmisión , Infecciones por Arbovirus/virología , Arbovirus/efectos de los fármacos , Mosquitos Vectores/virología , Aedes/efectos de los fármacos , Animales , Antivirales/química , Antivirales/uso terapéutico , Infecciones por Arbovirus/tratamiento farmacológico , Arbovirus/clasificación , Células Cultivadas , Descubrimiento de Drogas/métodos , Evaluación Preclínica de Medicamentos , Humanos , Control de Mosquitos/métodos , Enfermedades Transmitidas por Vectores/tratamiento farmacológico , Enfermedades Transmitidas por Vectores/transmisión , Enfermedades Transmitidas por Vectores/virología , Replicación Viral/efectos de los fármacos
9.
PLoS Pathog ; 16(12): e1009068, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33382858

RESUMEN

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.


Asunto(s)
Mosquitos Vectores/metabolismo , Mosquitos Vectores/virología , Infección por el Virus Zika/transmisión , Aedes/metabolismo , Aedes/virología , Animales , Brotes de Enfermedades , Vectores de Enfermedades , Epidemias , Humanos , Modelos Teóricos , Saliva/virología , Carga Viral , Viremia/transmisión , Virus Zika/patogenicidad , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/virología
10.
Viruses ; 12(12)2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33327649

RESUMEN

A crucial, but unresolved question concerning mosquito-borne virus transmission is how these viruses can remain endemic in regions where the transmission is halted for long periods of time, due to mosquito inactivity in, e.g., winter. In northern Europe, Sindbis virus (SINV) (genus alphavirus, Togaviridae) is transmitted among birds by Culex mosquitoes during the summer, with occasional symptomatic infections occurring in humans. In winter 2018-19, we sampled hibernating Culex spp females in a SINV endemic region in Sweden and assessed them individually for SINV infection status, blood-feeding status, and species. The results showed that 35 out of the 767 collected mosquitoes were infected by SINV, i.e., an infection rate of 4.6%. The vast majority of the collected mosquitoes had not previously blood-fed (98.4%) and were of the species Cx. pipiens (99.5%). This is the first study of SINV overwintering, and it concludes that SINV can be commonly found in the hibernating Cx. pipiens population in an endemic region in Sweden, and that these mosquitoes become infected through other means besides blood-feeding. Further studies on mosquito ecology and viral interactions are needed to elucidate the mechanisms of the persistence of these viruses over winter.


Asunto(s)
Infecciones por Alphavirus/epidemiología , Infecciones por Alphavirus/virología , Culex/virología , Mosquitos Vectores/virología , Virus Sindbis/fisiología , Infecciones por Alphavirus/transmisión , Animales , Vigilancia en Salud Pública , ARN Viral , Estaciones del Año , Suecia/epidemiología
11.
Viruses ; 12(12)2020 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339099

RESUMEN

RNA of Kyzylagach virus (KYZV), a Sindbis-like mosquito-borne alphavirus from Western equine encephalitis virus complex, was detected in four pools (out of 221 pools examined), encompassing 10,784 female Culex modestus mosquitoes collected at a fishpond in south Moravia, Czech Republic, with a minimum infection rate of 0.04%. This alphavirus was never detected in Central Europe before.


Asunto(s)
Infecciones por Alphavirus/transmisión , Infecciones por Alphavirus/virología , Culicidae/virología , Mosquitos Vectores/virología , Virus Sindbis , Animales , Europa (Continente)/epidemiología , Femenino
12.
Viruses ; 12(12)2020 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339336

RESUMEN

Using molecular techniques and bioinformatics tools, we studied the vector-host interactions and the molecular epidemiology of West Nile virus (WNV) in western Iran. Mosquitoes were collected during 2017 and 2018. DNA typing assays were used to study vector-host interactions. Mosquitoes were screened by RT-PCR for the genomes of five virus families. WNV-positive samples were fully sequenced and evolutionary tree and molecular architecture were constructed by Geneious software and SWISS-MODEL workspace, respectively. A total of 5028 mosquito specimens were collected and identified. The most prevalent species was Culex (Cx.) pipiens complex (57.3%). Analysis of the blood-feeding preferences of blood-fed mosquitoes revealed six mammalian and one bird species as hosts. One mosquito pool containing non-blood-fed Cx. theileri and one blood-fed Culex pipiens pipiens (Cpp.) biotype pipiens were positive for WNV. A phylogram indicated that the obtained WNV sequences belonged to lineage 2, subclade 2 g. Several amino acid substitutions suspected as virulence markers were observed in the Iranian WNV strains. The three-dimensional structural homology model of the E-protein identified hot spot domains known to facilitate virus invasion and neurotropism. The recent detection of WNV lineage 2 in mosquitoes from several regions of Iran in consecutive years suggests that the virus is established in the country.


Asunto(s)
Vectores de Enfermedades , Interacciones Huésped-Patógeno , Fiebre del Nilo Occidental/transmisión , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental/fisiología , Secuencia de Aminoácidos , Animales , Evolución Molecular , Genoma Viral , Genómica/métodos , Geografía Médica , Humanos , Irán/epidemiología , Mosquitos Vectores/virología , Filogenia , Dinámica Poblacional , Prevalencia , Conformación Proteica , Proteínas Estructurales Virales/química , Proteínas Estructurales Virales/metabolismo , Virulencia , Factores de Virulencia , Secuenciación Completa del Genoma
13.
Viruses ; 13(1)2020 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-33375455

RESUMEN

The emergence of arthropod-borne viruses (arboviruses) as linked to land-use changes, especially the growing agricultural intensification and expansion efforts in rural parts of Africa, is of growing health concern. This places an additional burden on health systems as drugs, vaccines, and effective vector-control measures against arboviruses and their vectors remain lacking. An integrated One Health approach holds potential in the control and prevention of arboviruses. Land-use changes favour invasion by invasive alien plants (IAPs) and investigating their impact on mosquito populations may offer a new dimension to our understanding of arbovirus emergence. Of prime importance to understand is how IAPs influence mosquito life-history traits and how this may affect transmission of arboviruses to mammalian hosts, questions that we are exploring in this review. Potential effects of IAPs may be significant, including supporting the proliferation of immature and adult stages of mosquito vectors, providing additional nutrition and suitable microhabitats, and a possible interaction between ingested secondary plant metabolites and arboviruses. We conclude that aspects of vector biology are differentially affected by individual IAPs and that while some plants may have the potential to indirectly increase the risk of transmission of certain arboviruses by their direct interaction with the vectors, the reverse holds for other IAPs. In addition, we highlight priority research areas to improve our understanding of the potential health impacts of IAPs.


Asunto(s)
Infecciones por Arbovirus/epidemiología , Infecciones por Arbovirus/transmisión , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/transmisión , Culicidae/virología , Especies Introducidas , Mosquitos Vectores/virología , Plantas , Animales , Infecciones por Arbovirus/virología , Enfermedades Transmisibles Emergentes/virología , Ecosistema , Humanos
14.
PLoS Negl Trop Dis ; 14(12): e0008971, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33338046

RESUMEN

Aedes aegypti is a vector of dengue, chikungunya, and Zika viruses. Current vector control strategies such as community engagement, source reduction, and insecticides have not been sufficient to prevent viral outbreaks. Thus, interest in novel strategies involving genetic engineering is growing. Female mosquitoes rely on flight to mate with males and obtain a bloodmeal from a host. We hypothesized that knockout of genes specifically expressed in female mosquitoes associated with the indirect flight muscles would result in a flightless female mosquito. Using CRISPR-Cas9 we generated loss-of-function mutations in several genes hypothesized to control flight in mosquitoes, including actin (AeAct-4) and myosin (myo-fem) genes expressed specifically in the female flight muscle. Genetic knockout of these genes resulted in 100% flightless females, with homozygous males able to fly, mate, and produce offspring, albeit at a reduced rate when compared to wild type males. Interestingly, we found that while AeAct-4 was haplosufficient, with most heterozygous individuals capable of flight, this was not the case for myo-fem, where about half of individuals carrying only one intact copy could not fly. These findings lay the groundwork for developing novel mechanisms of controlling Ae. aegypti populations, and our results suggest that this mechanism could be applicable to other vector species of mosquito.


Asunto(s)
Aedes/genética , Sistemas CRISPR-Cas , Insecticidas/farmacología , Control de Mosquitos , Mosquitos Vectores/genética , Infección por el Virus Zika/prevención & control , Virus Zika/fisiología , Aedes/fisiología , Aedes/virología , Animales , Femenino , Vuelo Animal , Técnicas de Inactivación de Genes , Humanos , Masculino , Mosquitos Vectores/fisiología , Mosquitos Vectores/virología , Fenotipo , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología
15.
PLoS Negl Trop Dis ; 14(12): e0008867, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33382725

RESUMEN

BACKGROUND: Aedes aegypti mosquito-borne viruses including Zika (ZIKV), dengue (DENV), yellow fever (YFV), and chikungunya (CHIKV) have emerged and re-emerged globally, resulting in an elevated burden of human disease. Aedes aegypti is found worldwide in tropical, sub-tropical, and temperate areas. The characterization of mosquito blood meals is essential to understand the transmission dynamics of mosquito-vectored pathogens. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report Ae. aegypti and Culex quinquefasciatus host feeding patterns and arbovirus transmission in Northern Mexico using a metabarcoding-like approach with next-generation deep sequencing technology. A total of 145 Ae. aegypti yielded a blood meal analysis result with 107 (73.8%) for a single vertebrate species and 38 (26.2%) for two or more. Among the single host blood meals for Ae. aegypti, 28.0% were from humans, 54.2% from dogs, 16.8% from cats, and 1.0% from tortoises. Among those with more than one species present, 65.9% were from humans and dogs. For Cx. quinquefasciatus, 388 individuals yielded information with 326 (84%) being from a single host and 63 (16.2%) being from two or more hosts. Of the single species blood meals, 77.9% were from dogs, 6.1% from chickens, 3.1% from house sparrows, 2.4% from humans, while the remaining 10.5% derived from other 12 host species. Among those which had fed on more than one species, 11% were from dogs and humans, and 89% of other host species combinations. Forage ratio analysis revealed dog as the most over-utilized host by Ae. aegypti (= 4.3) and Cx. quinquefasciatus (= 5.6) and the human blood index at 39% and 4%, respectively. A total of 2,941 host-seeking female Ae. aegypti and 3,536 Cx. quinquefasciatus mosquitoes were collected in the surveyed area. Of these, 118 Ae. aegypti pools and 37 Cx. quinquefasciatus pools were screened for seven arboviruses (ZIKV, DENV 1-4, CHIKV, and West Nile virus (WNV)) using qRT-PCR and none were positive (point prevalence = 0%). The 95%-exact upper limit confidence interval was 0.07% and 0.17% for Ae. aegypti and Cx. quinquefasciatus, respectively. CONCLUSIONS/SIGNIFICANCE: The low human blood feeding rate in Ae. aegypti, high rate of feeding on mammals by Cx. quinquefasciatus, and the potential risk to transmission dynamics of arboviruses in highly urbanized areas of Northern Mexico is discussed.


Asunto(s)
Aedes/virología , Infecciones por Arbovirus/veterinaria , Arbovirus/fisiología , Culex/virología , Vertebrados/virología , Animales , Infecciones por Arbovirus/sangre , Infecciones por Arbovirus/transmisión , Código de Barras del ADN Taxonómico , Conducta Alimentaria , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno , Modelos Biológicos , Mosquitos Vectores/virología , Especificidad de la Especie , Vertebrados/sangre
16.
PLoS Pathog ; 16(12): e1009134, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33351855

RESUMEN

Mosquitoes are responsible for the transmission of many clinically important arboviruses that cause significant levels of annual mortality and socioeconomic health burden worldwide. Deciphering the mechanisms by which mosquitoes modulate arbovirus infection is crucial to understand how viral-host interactions promote vector transmission and human disease. SUMOylation is a post-translational modification that leads to the covalent attachment of the Small Ubiquitin-like MOdifier (SUMO) protein to host factors, which in turn can modulate their stability, interaction networks, sub-cellular localisation, and biochemical function. While the SUMOylation pathway is known to play a key role in the regulation of host immune defences to virus infection in humans, the importance of this pathway during arbovirus infection in mosquito vectors, such as Aedes aegypti (Ae. aegypti), remains unknown. Here we characterise the sequence, structure, biochemical properties, and tissue-specific expression profiles of component proteins of the Ae. aegypti SUMOylation pathway. We demonstrate significant biochemical differences between Ae. aegypti and Homo sapiens SUMOylation pathways and identify cell-type specific patterns of SUMO expression in Ae. aegypti tissues known to support arbovirus replication. Importantly, depletion of core SUMOylation effector proteins (SUMO, Ubc9 and PIAS) in Ae. aegypti cells led to enhanced levels of arbovirus replication from three different families; Zika (Flaviviridae), Semliki Forest (Togaviridae), and Bunyamwera (Bunyaviridae) viruses. Our findings identify an important role for mosquito SUMOylation in the cellular restriction of arboviruses that may directly influence vector competence and transmission of clinically important arboviruses.


Asunto(s)
Aedes/virología , Arbovirus/fisiología , Interacciones Huésped-Patógeno/fisiología , Mosquitos Vectores/virología , Replicación Viral/fisiología , Animales , Infecciones por Arbovirus/transmisión , Humanos , Sumoilación
17.
PLoS Negl Trop Dis ; 14(12): e0008986, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33370301

RESUMEN

Japanese encephalitis virus (JEV) is maintained in an enzootic cycle between swine, water birds, and mosquitoes. JEV has circulated indigenously in Asia, with Culex tritaeniorhynchus as the primary vector. In some areas where the primary vector is scarce or absent, sporadic cases of Japanese encephalitis have been reported, with Aedes japonicus japonicus presumed to have the potential as a secondary vector. As one of the world's most invasive culicid species, Ae. j. japonicus carries a considerable health risk for spreading diseases to wider areas, including Europe and North America. Thus, evaluation of its competency as a JEV vector, particularly in a native population, will be essential in preventing potential disease spread. In this study, the two mosquito species' vector competence in transmitting three JEV genotypes (I, III, and V) was assessed, with Cx. tritaeniorhynchus serving as a point of reference. The mosquitoes were virus-fed and the infection rate (IR), dissemination rate (DR), and transmission rate (TR) evaluated individually by either RT-qPCR or focus forming assay. Results showed striking differences between the two species, with IR of 95% (261/274) and 9% (16/177) in Cx. tritaeniorhynchus and Ae. j. japonicus, respectively. Both mosquitoes were susceptible to all three JEV genotypes with significant differences in IR and mean viral titer. Results confirm the primary vector's competence, but the fact that JEV was able to establish in Ae. j. japonicus is of public health significance, and with 2%-16% transmission rate it has the potential to successfully transmit JEV to the next host. This may explain the human cases and infrequent detection in primary vector-free areas. Importantly, Ae. j. japonicus could be a relevant vector spreading the disease into new areas, indicating the need for security measures in areas where the mosquito is distributed or where it may be introduced.


Asunto(s)
Aedes/virología , Culex/virología , Virus de la Encefalitis Japonesa (Especie)/crecimiento & desarrollo , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Encefalitis Japonesa/transmisión , Mosquitos Vectores/virología , Animales , Asia/epidemiología , Línea Celular , Chlorocebus aethiops , Virus de la Encefalitis Japonesa (Especie)/genética , Encefalitis Japonesa/epidemiología , Genotipo , Humanos , Células Vero , Proteínas del Envoltorio Viral/genética
18.
PLoS One ; 15(10): e0227239, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33064724

RESUMEN

Species of the genus Flavivirus are widespread in Brazil and are a major public health concern. The country's largest city, São Paulo, is in a highly urbanized area with a few forest fragments which are commonly used for recreation. These can be considered to present a potential risk of flavivirus transmission to humans as they are home simultaneously to vertebrate hosts and mosquitoes that are potential flavivirus vectors. The aim of this study was to conduct flavivirus surveillance in field-collected mosquitoes in the Capivari-Monos Environmental Protection Area (EPA) and identify the flavivirus species by sequence analysis in flavivirus IFA-positive pools. Monthly mosquito collections were carried out from March 2016 to April 2017 with CO2-baited CDC light traps. Specimens were identified morphologically and grouped in pools of up to 10 individuals according to their taxonomic category. A total of 260 pools of non-engorged females were inoculated into C6/36 cell culture, and the cell suspensions were analyzed by indirect immunofluorescence assay (IFA) after the incubation period. IFA-positive pools were tested by qRT-PCR with genus-specific primers targeting the flavivirus NS5 gene to confirm IFA-positive results and sequenced to identify the species. Anopheles cruzii (19.5%) and Wyeomyia confusa (15.3%) were the most frequent vector species collected. IFA was positive for flaviviruses in 2.3% (6/260) of the sample pools. This was confirmed by qRT-PCR in five pools (83.3%). All five flavivirus-positive pools were successfully sequenced and the species identified. DENV serotype 2 (DENV-2) was detected in Culex spp. and Culex vaxus pools, while ZIKV was identified in An. cruzii, Limatus durhamii and Wy. confusa pools. To the best of our knowledge, detection of flavivirus species of medical importance has never previously been reported in these species of wild-caught mosquitoes. The finding of DENV-2 and ZIKV circulating in wild mosquitoes suggests the existence of an enzootic cycle in the area. In-depth studies of DENV-2 and ZIKV, including investigation of mosquito infection, vector competence and infection in sylvatic hosts, are needed to shed light on the transmission dynamics of these important viruses and the potential risk of future outbreaks of DENV-2 and ZIKV infections in the region.


Asunto(s)
Virus del Dengue/aislamiento & purificación , Mosquitos Vectores/virología , Proteínas no Estructurales Virales/genética , Virus Zika/aislamiento & purificación , Animales , Anopheles/virología , Brasil/epidemiología , Culex/virología , Virus del Dengue/genética , Femenino , Vigilancia de la Población , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vida Silvestre , Virus Zika/genética
19.
PLoS Negl Trop Dis ; 14(9): e0008614, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32956355

RESUMEN

The emergence of mosquito-transmitted viruses poses a global threat to human health. Combining mechanistic epidemiological models based on temperature-trait relationships with climatological data is a powerful technique for environmental risk assessment. However, a limitation of this approach is that the local microclimates experienced by mosquitoes can differ substantially from macroclimate measurements, particularly in heterogeneous urban environments. To address this scaling mismatch, we modeled spatial variation in microclimate temperatures and the thermal potential for dengue transmission by Aedes albopictus across an urban-to-rural gradient in Athens-Clarke County GA. Microclimate data were collected across gradients of tree cover and impervious surface cover. We developed statistical models to predict daily minimum and maximum microclimate temperatures using coarse-resolution gridded macroclimate data (4000 m) and high-resolution land cover data (30 m). The resulting high-resolution microclimate maps were integrated with temperature-dependent mosquito abundance and vectorial capacity models to generate monthly predictions for the summer and early fall of 2018. The highest vectorial capacities were predicted for patches of trees in urban areas with high cover of impervious surfaces. Vectorial capacity was most sensitive to tree cover during the summer and became more sensitive to impervious surfaces in the early fall. Predictions from the same models using temperature data from a local meteorological station consistently over-predicted vectorial capacity compared to the microclimate-based estimates. This work demonstrates that it is feasible to model variation in mosquito microenvironments across an urban-to-rural gradient using satellite Earth observations. Epidemiological models applied to the microclimate maps revealed localized patterns of temperature suitability for disease transmission that would not be detectable using macroclimate data. Incorporating microclimate data into disease transmission models has the potential to yield more spatially precise and ecologically interpretable metrics of mosquito-borne disease transmission risk in urban landscapes.


Asunto(s)
Aedes/virología , Dengue/epidemiología , Dengue/transmisión , Mosquitos Vectores/virología , Animales , Arbovirus/patogenicidad , Virus del Dengue/patogenicidad , Ecosistema , Georgia/epidemiología , Humanos , Microclima , Modelos Biológicos , Árboles
20.
PLoS Negl Trop Dis ; 14(9): e0008531, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32911504

RESUMEN

Pathogens may manipulate their human and mosquito hosts to enhance disease transmission. Dengue, caused by four viral serotypes, is the fastest-growing transmissible disease globally resulting in 50-100 million infections annually. Transmission of the disease relies on the interaction between humans and the vector Aedes aegypti and is largely dependent on the odor-mediated host seeking of female mosquitoes. In this study, we use activity monitors to demonstrate that dengue virus-1 affects the locomotion and odor-mediated behavior of Ae. aegypti, reflecting the progression of infection within the mosquito. Mosquitoes 4-6 days post-infection increase locomotion, but do not alter their odor-driven host-seeking response. In contrast, females 14-16 days post-infection are less active, yet more sensitive to human odors as assessed by behavioral and electrophysiological assays. Such an increase in physiological and behavioral sensitivity is reflected by the antennal-specific increase in abundance of neural signaling transcripts in 14 days post-infection females, as determined by transcriptome analysis. This suggests that the sensitivity of the mosquito peripheral olfactory system is altered by the dengue virus by enhancing the overall neural responsiveness of the antenna, rather than the selective regulation of chemosensory-related genes. Our study reveals that dengue virus-1 enhances vector-related behaviors in the early stages post-infection that aid in avoiding predation and increasing spatial exploration. On the other hand, at the later stages of infection, the virus enhances the host-seeking capacity of the vector, thereby increasing the risk of virus transmission. A potential mechanism is discussed.


Asunto(s)
Aedes/virología , Dengue , Conducta de Búsqueda de Hospedador , Aedes/genética , Aedes/metabolismo , Aedes/fisiología , Animales , Antenas de Artrópodos/fisiología , Conducta Animal , Virus del Dengue/fisiología , Femenino , Perfilación de la Expresión Génica , Humanos , Locomoción , Mosquitos Vectores/fisiología , Mosquitos Vectores/virología
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