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1.
PLoS Negl Trop Dis ; 13(10): e0007783, 2019 Oct 07.
Article in English | MEDLINE | ID: mdl-31589616

ABSTRACT

The case-fatality rate of yellow fever virus (YFV) is one of the highest among arthropod-borne viruses (arboviruses). Although historically, the Asia-Pacific region has remained free of YFV, the risk of introduction has never been higher due to the increasing influx of people from endemic regions and the recent outbreaks in Africa and South America. Singapore is a global hub for trade and tourism and therefore at high risk for YFV introduction. Effective control of the main domestic mosquito vector Aedes aegypti in Singapore has failed to prevent re-emergence of dengue, chikungunya and Zika viruses in the last two decades, raising suspicions that peridomestic mosquito species untargeted by domestic vector control measures may contribute to arbovirus transmission. Here, we provide empirical evidence that the peridomestic mosquito Aedes malayensis found in Singapore can transmit YFV. Our laboratory mosquito colony recently derived from wild Ae. malayensis in Singapore was experimentally competent for YFV to a similar level as Ae. aegypti controls. In addition, we captured Ae. malayensis females in one human-baited trap during three days of collection, providing preliminary evidence that host-vector contact may occur in field conditions. Finally, we detected Ae. malayensis eggs in traps deployed in high-rise building areas of Singapore. We conclude that Ae. malayensis is a competent vector of YFV and re-emphasize that vector control methods should be extended to target peridomestic vector species.

2.
PLoS Comput Biol ; 15(9): e1007355, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31545790

ABSTRACT

Yellow fever is a vector-borne disease endemic in tropical regions of Africa, where 90% of the global burden occurs, and Latin America. It is notoriously under-reported with uncertainty arising from a complex transmission cycle including a sylvatic reservoir and non-specific symptom set. Resulting estimates of burden, particularly in Africa, are highly uncertain. We examine two established models of yellow fever transmission within a Bayesian model averaging framework in order to assess the relative evidence for each model's assumptions and to highlight possible data gaps. Our models assume contrasting scenarios of the yellow fever transmission cycle in Africa. The first takes the force of infection in each province to be static across the observation period; this is synonymous with a constant infection pressure from the sylvatic reservoir. The second model assumes the majority of transmission results from the urban cycle; in this case, the force of infection is dynamic and defined through a fixed value of R0 in each province. Both models are coupled to a generalised linear model of yellow fever occurrence which uses environmental covariates to allow us to estimate transmission intensity in areas where data is sparse. We compare these contrasting descriptions of transmission through a Bayesian framework and trans-dimensional Markov chain Monte Carlo sampling in order to assess each model's evidence given the range of uncertainty in parameter values. The resulting estimates allow us to produce Bayesian model averaged predictions of yellow fever burden across the African endemic region. We find strong support for the static force of infection model which suggests a higher proportion of yellow fever transmission occurs as a result of infection from an external source such as the sylvatic reservoir. However, the model comparison highlights key data gaps in serological surveys across the African endemic region. As such, conclusions concerning the most prevalent transmission routes for yellow fever will be limited by the sparsity of data which is particularly evident in the areas with highest predicted transmission intensity. Our model and estimation approach provides a robust framework for model comparison and predicting yellow fever burden in Africa. However, key data gaps increase uncertainty surrounding estimates of model parameters and evidence. As more mathematical models are developed to address new research questions, it is increasingly important to compare them with established modelling approaches to highlight uncertainty in structures and data.

4.
Mem Inst Oswaldo Cruz ; 114: e190076, 2019.
Article in English | MEDLINE | ID: mdl-31038550

ABSTRACT

BACKGROUND: In Brazil, the Yellow Fever virus (YFV) is endemic in the Amazon, from where it eventually expands into epidemic waves. Coastal south-eastern (SE) Brazil, which has been a YFV-free region for eight decades, has reported a severe sylvatic outbreak since 2016. The virus spread from the north toward the south of the Rio de Janeiro (RJ) state, causing 307 human cases with 105 deaths during the 2016-2017 and 2017-2018 transmission seasons. It is unclear, however, whether the YFV would persist in the coastal Atlantic Forest of RJ during subsequent transmission seasons. OBJECTIVES: To conduct a real-time surveillance and assess the potential persistence of YFV in the coastal Atlantic Forest of RJ during the 2018-2019 transmission season. METHODS: We combined epizootic surveillance with fast diagnostic and molecular, phylogenetic, and evolutionary analyses. FINDINGS: Using this integrative strategy, we detected the first evidence of YFV re-emergence in the third transmission season (2018-2019) in a dying howler monkey from the central region of the RJ state. The YFV detected in 2019 has the molecular signature associated with the current SE YFV outbreak and exhibited a close phylogenetic relationship with the YFV lineage that circulated in the same Atlantic Forest fragment during the past seasons. This lineage circulated along the coastal side of the Serra do Mar mountain chain, and its evolution seems to be mainly driven by genetic drift. The potential bridge vector Aedes albopictus was found probing on the recently dead howler monkey in the forest edge, very close to urban areas. MAIN CONCLUSIONS: Collectively, our data revealed that YFV transmission persisted at the same Atlantic Forest area for at least three consecutive transmission seasons without the need of new introductions. Our real-time surveillance strategy permitted health authorities to take preventive actions within 48 h after the detection of the sick non-human primate. The local virus persistence and the proximity of the epizootic forest to urban areas reinforces the concern with regards to the risk of re-urbanisation and seasonal re-emergence of YFV, stressing the need for continuous effective surveillance and high vaccination coverage in the SE region, particularly in RJ, an important tourist location.


Subject(s)
Aedes/virology , Yellow Fever/epidemiology , Yellow Fever/virology , Yellow fever virus/genetics , Alouatta , Animals , Brazil/epidemiology , Disease Outbreaks , Humans , Phylogeography , Seasons , Urban Population , Yellow Fever/transmission
5.
Article in Spanish | PAHO-IRIS | ID: phr-50939

ABSTRACT

[RESUMEN]. El aumento en la incidencia y distribución geográfica de las arbovirosis constituye uno de los principales problemas de salud pública en la Región de las Américas. La incidencia del dengue ha experimentado una tendencia creciente en los últimos decenios en la Región, donde se ha pasado de una endemicidad baja a hiperendemicidad. También, la incidencia de la fiebre amarilla se ha intensificado en este período, y ha pasado de una actividad restringida a zonas selváticas a presentar brotes urbanos. El chikunguña comenzó a propagarse de forma pandémica en el 2005 a un ritmo sin precedentes y llegó al continente americano en el 2013. Al año siguiente, la infección por el virus del Zika irrumpió también en la Región con un brote explosivo acompañado de gravísimas anomalías congénitas y trastornos neurológicos, hasta convertirse en una de las mayores crisis de salud en los últimos años. La inadecuada vigilancia de las arbovirosis en la Región y la carencia de pruebas serológicas para diferenciar entre los distintos virus plantean retos considerables. Sigue habiendo pocas evidencias científicas en respaldo de las intervenciones de control de vectores. El manejo clínico sigue siendo la piedra angular del control de estas enfermedades. En la actualidad, solo están autorizadas en la Región de las Américas las vacunas contra la fiebre amarilla y contra el dengue, si bien hay varias vacunas experimentales en fase de investigación en ensayos clínicos. El Grupo Mundial de Expertos en Arbovirus ofrece en este artículo un panorama de los progresos, los retos y las recomendaciones sobre prevención y control de las arbovirosis en los países de la Región de las Américas.


[ABSTRACT]. The increasing geographical spread and disease incidence of arboviral infections are among the greatest public health concerns in the Americas. The region has observed an increasing trend in dengue incidence in the last decades, evolving from low to hyperendemicity. Yellow fever incidence has also intensified in this period, expanding from sylvatic-restricted activity to urban outbreaks. Chikungunya started spreading pandemically in 2005 at an unprecedented pace, reaching the Americas in 2013. The following year, Zika also emerged in the region with an explosive outbreak, carrying devastating congenital abnormalities and neurologic disorders and becoming one of the greatest global health crises in years. The inadequate arbovirus surveillance in the region and the lack of serologic tests to differentiate among viruses poses substantial challenges. The evidence for vector control interventions remains weak. Clinical management remains the mainstay of arboviral disease control. Currently, only yellow fever and dengue vaccines are licensed in the Americas, with several candidate vaccines in clinical trials. The Global Arbovirus Group of Experts provides in this article an overview of progress, challenges, and recommendations on arboviral prevention and control for countries of the Americas.


Subject(s)
Arbovirus Infections , Aedes , Dengue , Yellow Fever , Chikungunya virus , Zika Virus , Communicable Diseases , Americas , Arbovirus Infections , Yellow Fever , Chikungunya virus , Zika Virus , Communicable Diseases
6.
Insect Biochem Mol Biol ; 111: 103169, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31103782

ABSTRACT

The yellow fever mosquito, Aedes aegypti, serves as the primary vector for epidemic transmission of yellow fever, dengue, Zika (ZIKV), and chikungunya viruses to humans. Control of Ae. aegypti is currently limited to insecticide applications and larval habitat management; however, to combat growing challenges with insecticide resistance, novel genetic approaches for vector population reduction or transmission interruption are being aggressively pursued. The objectives of this study were to assess the ability of the Ae. aegypti antiviral exogenous-small interfering RNA (exo-siRNA) response to inhibit ZIKV infection and transmission, and to identify the optimal RNA interference (RNAi) target region in the ZIKV genome. We accomplished these objectives by in vitro transcription of five long double-stranded RNAs (dsRNAs) from the genome region spanning the NS2B-NS3-NS4A genes, which were the most highly conserved among ZIKV RNA sequences representing both East and West African and Asian-American clades, and evaluation of the ability of these dsRNAs to trigger an effective antiviral exo-siRNA response after intrathoracic injection into Ae. aegypti. In a pilot study, five ZIKV dsRNAs were tested by intrathoracic inoculation of 250 ng dsRNA into groups of approximately 5-day-old mosquitoes. Three days post-inoculation, mosquitoes were provided an infectious blood-meal containing ZIKV strain PRVABC59 (Puerto Rico), MR766 (Uganda), or 41525 (Senegal). On days 7 and 14 post-infection individual whole mosquito bodies were assessed for ZIKV infectious titer by plaque assays. Based on the results of this initial assessment, three dsRNAs were selected for further evaluation of viral loads of matched body and saliva expectorants using a standardized infectious dose of 1 × 107 PFU/mL of each ZIKV strain. Fourteen days post-exposure to ZIKV, paired saliva and carcass samples were harvested from individual mosquitoes and assessed for ZIKV RNA load by qRT-PCR. Injection of each of the three dsRNAs resulted in significant inhibition of replication of all three strains of ZIKV in mosquito bodies and saliva. This study lays critical groundwork for pursuing ZIKV transmission-blocking strategies that exploit the Ae. aegypti exo-siRNA response for arbovirus suppression in natural populations.

7.
Nat Ecol Evol ; 3(4): 561-569, 2019 04.
Article in English | MEDLINE | ID: mdl-30886369

ABSTRACT

Zika virus (ZIKV), discovered in the Zika Forest of Uganda in 1947, is a mosquito-borne flavivirus related to yellow fever, dengue and West Nile viruses. From its discovery until 2007, only sporadic ZIKV cases were reported, with mild clinical manifestations in patients. Therefore, little attention was given to this virus before epidemics in the South Pacific and the Americas that began in 2013. Despite a growing number of ZIKV studies in the past three years, many aspects of the virus remain poorly characterized, particularly the spectrum of species involved in its transmission cycles. Here, we review the mosquito and vertebrate host species potentially involved in ZIKV vector-borne transmission worldwide. We also provide an evidence-supported analysis regarding the possibility of ZIKV spillback from an urban cycle to a zoonotic cycle outside Africa, and we review hypotheses regarding recent emergence and evolution of ZIKV. Finally, we identify critical remaining gaps in the current knowledge of ZIKV vector-borne transmission.


Subject(s)
Mosquito Vectors/physiology , Zika Virus Infection/transmission , Zika Virus/physiology , Animals , Culicidae , Evolution, Molecular , Humans
8.
Viruses ; 11(2)2019 02 12.
Article in English | MEDLINE | ID: mdl-30759739

ABSTRACT

Mosquito-borne diseases constitute a large portion of infectious diseases, causing more than 700,000 deaths annually. Mosquito-transmitted viruses, such as yellow fever, dengue, West Nile, chikungunya, and Zika viruses, have re-emerged recently and remain a public health threat worldwide. Global climate change, rapid urbanization, burgeoning international travel, expansion of mosquito populations, vector competence, and host and viral genetics may all together contribute to the re-emergence of arboviruses. In this brief review, we summarize the host and viral genetic determinants that may enhance infectivity in the host, viral fitness in mosquitoes and viral transmission by mosquitoes.


Subject(s)
Arbovirus Infections/transmission , Arboviruses/genetics , Evolution, Molecular , Host Microbial Interactions/genetics , Mosquito Vectors/virology , Animals , Chikungunya Fever/transmission , Communicable Diseases, Emerging/virology , Dengue/transmission , Genetic Fitness , Humans , Mice , Public Health , Yellow Fever/transmission
9.
Acta Trop ; 192: 129-137, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30763563

ABSTRACT

The yellow fever mosquito, Aedes aegypti, has facilitated the re-emergence of dengue virus (DENV) and emergence of chikungunya virus (CHIKV) and Zika virus (ZIKV) in the Americas and the Caribbean. The recent transmission of these arboviruses in the continental United States has been limited, to date, to South Florida and South Texas despite Ae. aegypti occurring over a much larger geographical region within the country. The main goal of our study was to provide the first long term longitudinal study of Ae. aegypti and enhance the knowledge about the indoor and outdoor relative abundance of Ae. aegypti as a proxy for mosquito-human contact in South Texas, a region of the United States that is at high risk for mosquito-borne virus transmission. Here, the relative abundance of indoors and outdoors mosquitoes of households in eight different communities was described. Surveillance was done weekly from September 2016 to April 2018 using the CDC Autocidal Gravid Ovitraps in low- and middle-income communities. A total of 69 houses were included in this survey among which 36 were in the low-income communities (n = 11 for Donna, n = 15 for Progresso, n = 5 for Mesquite, n = 5 for Chapa) and 33 in middle-income communities (n = 9 for La Feria, n = 8 for Weslaco, n = 11 for McAllen, and n = 5 for Rio Rico). Overall, Ae. aegypti was the dominant species (59.2% of collections, n = 7255) followed by Culex spp. mosquitoes (27.3% of collections, n = 3350). Furthermore, we demonstrated for Ae. aegypti that 1) outdoor relative abundance was higher compared to indoor relative abundance, 2) low-income communities were associated with an increase in mosquito relative abundance indoors when compared to middle-income communities, 3) no difference was observed in the number of mosquitoes collected outdoors between low-income and middle-income communities, and 4) warmer months were positively correlated with outdoor relative abundance whereas no seasonality was observed in the relative abundance of mosquitoes indoors. Additionally, Ae. aegypti mosquitoes collected in South Texas were tested using a specific ZIKV/CHIKV multiplex real-time PCR assay, however, none of the mosquitoes tested positive. Our data highlights the occurrence of mosquitoes indoors in the continental United States and that adults are collected nearly every week of the calendar year. These mosquito data, obtained concurrently with local ZIKV transmission of 10 locally acquired cases in nearby communities, represent a baseline for future studies in the Lower Rio Grande Valley (LRGV) including vector control interventions relying on the oviposition behavior to reduce mosquito populations and pathogen transmission.


Subject(s)
Aedes/virology , Chikungunya Fever/transmission , Culex/virology , Dengue/transmission , Mosquito Vectors/virology , Yellow Fever/transmission , Zika Virus Infection/transmission , Animals , Chikungunya Fever/virology , Chikungunya virus/isolation & purification , Dengue/virology , Dengue Virus/isolation & purification , Family Characteristics , Female , Humans , Longitudinal Studies , Texas , United States , Yellow Fever/virology , Zika Virus/isolation & purification
10.
FP Essent ; 476: 11-17, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30615405

ABSTRACT

Due to rapid globalization and ease of travel, mosquito-borne viral infections are now a concern for family physicians throughout the United States. Zika virus infection is one such concern. It is spread via mosquito bites or by sexual contact with an infected individual. Most patients are asymptomatic, and when symptoms occur, they are mild and nonspecific. The main concern is the potential of the infection to cause fetal anomalies. Dengue is another mosquito-borne viral infection. Symptoms of initial infection are mild, and may include arthralgias. Subsequent infection with a different serotype can cause life-threatening hemorrhagic fever or shock. Chikungunya virus infection is widespread in the Americas and symptoms are similar to those of dengue. However, it can cause a postviral chronic inflammatory rheumatism in up to half of patients. Yellow fever occurs mostly in sub-Saharan Africa and can cause hepatic failure. Encephalitis viruses, most commonly West Nile in the United States and others such as Japanese encephalitis virus, can cause neuroinvasive disease, most often in older adults. Vaccines are available for yellow fever and Japanese encephalitis viruses but the keys to prevention are insect avoidance, mosquito eradication, and use of mosquito repellants.


Subject(s)
Culicidae , Dengue , Yellow Fever , Zika Virus Infection , Animals , Dengue/diagnosis , Dengue/therapy , Dengue/transmission , Humans , United States , Yellow Fever/diagnosis , Yellow Fever/therapy , Yellow Fever/transmission , Zika Virus Infection/diagnosis , Zika Virus Infection/therapy , Zika Virus Infection/transmission
11.
Parasitol Res ; 118(3): 733-742, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30671730

ABSTRACT

Aedes aegypti and Ae. albopictus are key vectors in the spread of arboviruses such as dengue, chikungunya, yellow fever, and Zika. Triatoma rubrofasciata is an "assassin bug" whose populations and association with humans have dramatically increased and may represent a serious health concern. Control of insect vectors is a logical course of action to prevent the spread of these insect-borne infections. This work presents the leaf essential oil composition, mosquito larvicidal activities, and insect-repellent activity of Severinia monophylla. The essential oil of S. monophylla from Vietnam was obtained by hydrodistillation and analyzed by gas chromatography and mass spectrometry. The major components were sabinene, ß-caryophyllene, bicyclogermacrene, germacrene D, (E)-nerolidol, globulol, and linalool. The leaf essential oil showed remarkable larvicidal activity against Ae. aegypti with LC50 (48 h) of 7.1 µg/mL and Ae. albopictus with LC50 (48 h) of 36 µg/mL. The essential oil also showed repellent activity on T. rubrofasciata at a concentration of 0.5%.


Subject(s)
Aedes/drug effects , Dengue/prevention & control , Insect Repellents/pharmacology , Insecticides/pharmacology , Oils, Volatile/pharmacology , Rutaceae/chemistry , Triatoma/drug effects , Aedes/parasitology , Animals , Dengue/transmission , Gas Chromatography-Mass Spectrometry , Humans , Insect Repellents/chemistry , Insecticides/chemistry , Mass Spectrometry , Mosquito Control , Mosquito Vectors/drug effects , Mosquito Vectors/parasitology , Oils, Volatile/chemistry , Plant Leaves/chemistry , Plant Oils/chemistry , Plant Oils/pharmacology , Terpenes/chemistry , Terpenes/pharmacology , Vietnam
12.
Am J Public Health ; 109(3): 387-392, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30676796

ABSTRACT

The increasing geographical spread and disease incidence of arboviral infections are among the greatest public health concerns in the Americas. The region has observed an increasing trend in dengue incidence in the last decades, evolving from low to hyperendemicity. Yellow fever incidence has also intensified in this period, expanding from sylvatic-restricted activity to urban outbreaks. Chikungunya started spreading pandemically in 2005 at an unprecedented pace, reaching the Americas in 2013. The following year, Zika also emerged in the region with an explosive outbreak, carrying devastating congenital abnormalities and neurologic disorders and becoming one of the greatest global health crises in years. The inadequate arbovirus surveillance in the region and the lack of serologic tests to differentiate among viruses poses substantial challenges. The evidence for vector control interventions remains weak. Clinical management remains the mainstay of arboviral disease control. Currently, only yellow fever and dengue vaccines are licensed in the Americas, with several candidate vaccines in clinical trials. The Global Arbovirus Group of Experts provides in this article an overview of progress, challenges, and recommendations on arboviral prevention and control for countries of the Americas.

14.
PLoS Negl Trop Dis ; 13(1): e0006822, 2019 01.
Article in English | MEDLINE | ID: mdl-30605475

ABSTRACT

BACKGROUND: Mosquito-borne viruses-such as Zika, chikungunya, dengue fever, and yellow fever, among others-are of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses. METHODS AND FINDINGS: This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact. CONCLUSIONS: As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission.


Subject(s)
Aedes/drug effects , Aedes/virology , Arbovirus Infections/prevention & control , Biological Control Agents/pharmacology , Insecticide Resistance/physiology , Insecticides/pharmacology , Mosquito Control/methods , Animals , Arbovirus Infections/transmission , Arboviruses/classification , Arboviruses/isolation & purification , Mosquito Vectors/drug effects , Mosquito Vectors/virology
15.
Mem. Inst. Oswaldo Cruz ; 114: e190076, 2019. tab, graf
Article in English | LILACS | ID: biblio-1002689

ABSTRACT

BACKGROUND In Brazil, the Yellow Fever virus (YFV) is endemic in the Amazon, from where it eventually expands into epidemic waves. Coastal south-eastern (SE) Brazil, which has been a YFV-free region for eight decades, has reported a severe sylvatic outbreak since 2016. The virus spread from the north toward the south of the Rio de Janeiro (RJ) state, causing 307 human cases with 105 deaths during the 2016-2017 and 2017-2018 transmission seasons. It is unclear, however, whether the YFV would persist in the coastal Atlantic Forest of RJ during subsequent transmission seasons. OBJECTIVES To conduct a real-time surveillance and assess the potential persistence of YFV in the coastal Atlantic Forest of RJ during the 2018-2019 transmission season. METHODS We combined epizootic surveillance with fast diagnostic and molecular, phylogenetic, and evolutionary analyses. FINDINGS Using this integrative strategy, we detected the first evidence of YFV re-emergence in the third transmission season (2018-2019) in a dying howler monkey from the central region of the RJ state. The YFV detected in 2019 has the molecular signature associated with the current SE YFV outbreak and exhibited a close phylogenetic relationship with the YFV lineage that circulated in the same Atlantic Forest fragment during the past seasons. This lineage circulated along the coastal side of the Serra do Mar mountain chain, and its evolution seems to be mainly driven by genetic drift. The potential bridge vector Aedes albopictus was found probing on the recently dead howler monkey in the forest edge, very close to urban areas. MAIN CONCLUSIONS Collectively, our data revealed that YFV transmission persisted at the same Atlantic Forest area for at least three consecutive transmission seasons without the need of new introductions. Our real-time surveillance strategy permitted health authorities to take preventive actions within 48 h after the detection of the sick non-human primate. The local virus persistence and the proximity of the epizootic forest to urban areas reinforces the concern with regards to the risk of re-urbanisation and seasonal re-emergence of YFV, stressing the need for continuous effective surveillance and high vaccination coverage in the SE region, particularly in RJ, an important tourist location.


Subject(s)
Yellow Fever/therapy , Amino Acid Transport Systems , Mosquito Vectors/pathogenicity , Alouatta , Phylogeography
17.
Parasit Vectors ; 11(Suppl 2): 655, 2018 Dec 24.
Article in English | MEDLINE | ID: mdl-30583735

ABSTRACT

BACKGROUND: Aedes aegypti is an important mosquito vector that transmits arboviruses that cause devastating diseases including Zika, dengue fever, yellow fever and chikungunya. Improved understanding of gene regulation in the early development of Ae. aegypti will facilitate genetic studies and help the development of novel control strategies of this important disease vector. RESULTS: In this study, we demonstrated through transgenic assays that the promoter of an endogenous early zygotic gene KLC2 could drive gene expression in the syncytial blastoderm and early cellular blastoderm, which is a stage that the developing germline and the rest of embryo are accessible to genetic manipulation. An unexpected expression of the reporter gene in transgenic male testes was also observed. Further analysis confirmed the expression of the endogenous KLC2 in the testes, which was not detected in the previous RNA sequencing data. CONCLUSIONS: Our finding provided a new promoter element that can be used in future genetic studies and applications in Ae. aegypti. Moreover, our transgenic reporter assays showed that cautions are needed when interpreting RNA sequencing data as transient or tissue-specific transcription may go undetected by RNAseq.


Subject(s)
Aedes/genetics , Arbovirus Infections/prevention & control , Insect Proteins/genetics , Mosquito Vectors/genetics , Promoter Regions, Genetic/genetics , Aedes/embryology , Aedes/virology , Animals , Animals, Genetically Modified , Arbovirus Infections/transmission , Arboviruses/physiology , Female , Gene Dosage , Gene Drive Technology , Gene Expression Regulation , Genes, Reporter , Humans , Male , Mosquito Vectors/embryology , Mosquito Vectors/virology , Sequence Analysis, RNA
18.
Parasit Vectors ; 11(Suppl 2): 645, 2018 Dec 24.
Article in English | MEDLINE | ID: mdl-30583736

ABSTRACT

Vector control programs based on population reduction by matings with mass-released sterile insects require the release of only male mosquitoes, as the release of females, even if sterile, would increase the number of biting and potentially disease-transmitting individuals. While small-scale releases demonstrated the applicability of sterile males releases to control the yellow fever mosquito Aedes aegypti, large-scale programs for mosquitoes are currently prevented by the lack of efficient sexing systems in any of the vector species.Different approaches of sexing are pursued, including classical genetic and mechanical methods of sex separation. Another strategy is the development of transgenic sexing systems. Such systems already exist in other insect pests. Genome modification tools could be used to apply similar strategies to mosquitoes. Three major tools to modify mosquito genomes are currently used: transposable elements, site-specific recombination systems, and genome editing via TALEN or CRISPR/Cas. All three can serve the purpose of developing sexing systems and vector control strains in mosquitoes in two ways: first, via their use in basic research. A better understanding of mosquito biology, including the sex-determining pathways and the involved genes can greatly facilitate the development of sexing strains. Moreover, basic research can help to identify other regulatory elements and genes potentially useful for the construction of transgenic sexing systems. Second, these genome modification tools can be used to apply the gained knowledge to build and test mosquito sexing strains for vector control.


Subject(s)
Aedes/genetics , Mosquito Control/methods , Mosquito Vectors/genetics , Yellow Fever/prevention & control , Aedes/physiology , Animals , Animals, Genetically Modified , DNA Transposable Elements/genetics , Female , Gene Editing , Humans , Infertility, Male , Male , Mosquito Vectors/physiology , Mutagenesis, Site-Directed , Yellow Fever/transmission
19.
PLoS Negl Trop Dis ; 12(10): e0006886, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30356234

ABSTRACT

Arthropod-borne flaviviruses such as yellow fever (YFV), Zika and dengue viruses continue to cause significant human disease globally. These viruses are transmitted by mosquitoes when a female imbibes an infected blood-meal from a viremic vertebrate host and expectorates the virus into a subsequent host. Bamaga virus (BgV) is a flavivirus recently discovered in Culex sitiens subgroup mosquitoes collected from Cape York Peninsula, Australia. This virus phylogenetically clusters with the YFV group, but is potentially restricted in most vertebrates. However, high levels of replication in an opossum cell line (OK) indicate a potential association with marsupials. To ascertain whether BgV could be horizontally transmitted by mosquitoes, the vector competence of two members of the Cx. sitiens subgroup, Cx. annulirostris and Cx. sitiens, for BgV was investigated. Eleven to thirteen days after imbibing an infectious blood-meal, infection rates were 11.3% and 18.8% for Cx. annulirostris and Cx. sitiens, respectively. Cx. annulirostris transmitted the virus at low levels (5.6% had BgV-positive saliva overall); Cx. sitiens did not transmit the virus. When mosquitoes were injected intrathoracially with BgV, the infection and transmission rates were 100% and 82%, respectively, for both species. These results provided evidence for the first time that BgV can be transmitted horizontally by Cx. annulirostris, the primary vector of pathogenic zoonotic flaviviruses in Australia. We also assessed whether BgV could interfere with replication in vitro, and infection and transmission in vivo of super-infecting pathogenic Culex-associated flaviviruses. BgV significantly reduced growth of Murray Valley encephalitis and West Nile (WNV) viruses in vitro. While prior infection with BgV by injection did not inhibit WNV super-infection of Cx. annulirostris, significantly fewer BgV-infected mosquitoes could transmit WNV than mock-injected mosquitoes. Overall, these data contribute to our understanding of flavivirus ecology, modes of transmission by Australian mosquitoes and mechanisms for super-infection interference.

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