Engineered #resistance to #Zika virus in transgenic #Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs

Anna Buchman, Stephanie Gamez, Ming Li, Igor Antoshechkin, Hsing-Han Li, Hsin-Wei Wang, Chun-Hong Chen, Melissa J. Klein, Jean-Bernard Duchemin, Prasad N. Paradkar, and Omar S. Akbari

PNAS published ahead of print February 5, 2019 / DOI: https://doi.org/10.1073/pnas.1810771116

Edited by Alexander S. Raikhel, University of California, Riverside, CA, and approved December 31, 2018 (received for review June 22, 2018)

 

Significance

Here, we describe the generation of Aedes aegypti mosquitoes that are engineered to be resistant to Zika virus (ZIKV) transmission. Our results demonstrate that engineered mosquitoes express a polycistronic cluster of synthetic small RNAs designed to target the ZIKV genome. As a result, homozygous mosquitoes were refractory to ZIKV infection, and therefore could not transmit the virus. Additionally, mosquitoes heterozygous for the transgene showed significantly lower levels of viral infection, dissemination, and transmission compared with wild-type mosquitoes; importantly, these levels were low enough to make such mosquitoes unlikely to transmit ZIKV to a susceptible host. Finally, we discuss how such an engineering approach can be used to combat the major health burden of ZIKV, and potentially other arboviruses, in the future.

 

Abstract

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.

ZIKA – resistance – Aedes aegypti – mosquito

Keywords: Zika Virus; Mosquitoes; Aedes aegypti; Genetics.

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#Arbovirus #coinfection and co-transmission: A neglected #publichealth concern? (PLoS Biol., abstract)

[Source: PLoS Biology, full page: (LINK). Abstract, edited.]

OPEN ACCESS / UNSOLVED MYSTERY

Arbovirus coinfection and co-transmission: A neglected public health concern?

Chantal B. F. Vogels , Claudia Rückert , Sean M. Cavany , T. Alex Perkins, Gregory D. Ebel, Nathan D. Grubaugh

Published: January 22, 2019 / DOI: https://doi.org/10.1371/journal.pbio.3000130 / This is an uncorrected proof.

 

Abstract

Epidemiological synergy between outbreaks of viruses transmitted by Aedes aegypti mosquitoes, such as chikungunya, dengue, and Zika viruses, has resulted in coinfection of humans with multiple viruses. Despite the potential impact on public health, we know only little about the occurrence and consequences of such coinfections. Here, we review the impact of coinfection on clinical disease in humans, discuss the possibility for co-transmission from mosquito to human, and describe a role for modeling transmission dynamics at various levels of co-transmission. Solving the mystery of virus coinfections will reveal whether they should be viewed as a serious concern for public health.

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Citation: Vogels CBF, Rückert C, Cavany SM, Perkins TA, Ebel GD, Grubaugh ND (2019) Arbovirus coinfection and co-transmission: A neglected public health concern? PLoS Biol 17(1): e3000130. https://doi.org/10.1371/journal.pbio.3000130

Published: January 22, 2019

Copyright: © 2019 Vogels et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: CBFV is supported by NWO Rubicon 019.181EN.004, CR and GDE are supported by NIH NIAID AI067380, SMC and TAP are supported by NIH NIAID 1P01AI098670, and TAP is supported by DARPA D16AP00114. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: CHIKV, chikungunya virus; DENV, dengue virus; NS1, nonstructural protein 1; STAT1, signal transducer and activator of transcription 1; STAT2, signal transducer and activator of transcription 2; XRN1, 5′-3′ exoribonuclease 1; ZIKV, Zika virus

Keywords: Arbovirus; Zika Virus; Chikungunya fever; Mosquitoes; Aedes aegypti.

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#Mapping the #global potential #distributions of two #arboviral vectors #Aedes aegypti and Ae. albopictus under changing #climate (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Mapping the global potential distributions of two arboviral vectors Aedes aegypti and Ae. albopictus under changing climate

Mahmoud Kamal , Mohamed A. Kenawy, Magda Hassan Rady, Amany Soliman Khaled, Abdallah M. Samy

Published: December 31, 2018 / DOI: https://doi.org/10.1371/journal.pone.0210122

 

Abstract

Background

Aedes aegypti and Ae. albopictus are the primary vectors that transmit several arboviral diseases, including dengue, chikungunya, and Zika. The world is presently experiencing a series of outbreaks of these diseases, so, we still require to better understand the current distributions and possible future shifts of their vectors for successful surveillance and control programs. Few studies assessed the influences of climate change on the spatial distributional patterns and abundance of these important vectors, particularly using the most recent climatic scenarios. Here, we updated the current potential distributions of both vectors and assessed their distributional changes under future climate conditions.

Methods

We used ecological niche modeling approach to estimate the potential distributions of Ae. aegypti and Ae. albopictus under present-day and future climate conditions. This approach fits ecological niche model from occurrence records of each species and environmental variables. For each species, future projections were based on climatic data from 9 general circulation models (GCMs) for each representative concentration pathway (RCP) in each time period, with a total of 72 combinations in four RCPs in 2050 and 2070. All ENMs were tested using the partial receiver operating characteristic (pROC) and a set of 2,048 and 2,003 additional independent records for Ae. aegypti and Ae. albopictus, respectively. Finally, we used background similarity test to assess the similarity between the ENMs of Ae. aegypti and Ae. albopictus.

Results

The predicted potential distribution of Ae. aegypti and Ae. albopictus coincided with the current and historical known distributions of both species. Aedes aegypti showed a markedly broader distributional potential across tropical and subtropical regions than Ae. albopictus. Interestingly, Ae. albopictus was markedly broader in distributional potential across temperate Europe and the United States. All ecological niche models (ENMs) were statistically robust (P < 0.001). ENMs successfully anticipated 98% (1,999/2,048) and 99% (1,985/2,003) of additional independent records for both Ae. aegypti and Ae. albopictus, respectively (P < 0.001). ENMs based on future conditions showed similarity between the overall distributional patterns of future-day and present-day conditions; however, there was a northern range expansion in the continental USA to include parts of Southern Canada in case of Ae. albopictus in both 2050 and 2070. Future models also anticipated further expansion of Ae. albopictus to the East to include most of Europe in both time periods. Aedes aegypti was anticipated to expand to the South in East Australia in 2050 and 2070. The predictions showed differences in distributional potential of both species between diverse RCPs in 2050 and 2070. Finally, the background similarity test comparing the ENMs of Ae. aegypti and Ae. albopictus was unable to reject the null hypothesis of niche similarity between both species (P > 0.05).

Conclusion

These updated maps provided details to better guide surveillance and control programs of Ae. aegypti and Ae. albopictus. They have also significant public health importance as a baseline for predicting the emergence of arboviral diseases transmitted by both vectors in new areas across the world.

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Citation: Kamal M, Kenawy MA, Rady MH, Khaled AS, Samy AM (2018) Mapping the global potential distributions of two arboviral vectors Aedes aegypti and Ae. albopictusunder changing climate. PLoS ONE 13(12): e0210122. https://doi.org/10.1371/journal.pone.0210122

Editor: Nagila Francinete Costa Secundino, Instituto de Pesquisas de Rene Rachou, BRAZIL

Received: September 21, 2018; Accepted: December 17, 2018; Published: December 31, 2018

Copyright: © 2018 Kamal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files. GeoTIFF dataset for different general circulation models are openly available via Figshare repository, https://figshare.com/s/6b18c6ce273a3ecaaddc.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Arbovirus; Mosquitoes; Worldwide; Clima change; Aedes aegypti; Aedes albopictus.

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#Genetic variability of the #Aedes aegypti (Diptera: Culicidae) #mosquito in #ElSalvador, #vector of #dengue, yellow fever, #chikungunya and #Zika (Parasit Vector., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Parasit Vectors. 2018 Dec 14;11(1):637. doi: 10.1186/s13071-018-3226-5.

Genetic variability of the Aedes aegypti (Diptera: Culicidae) mosquito in El Salvador, vector of dengue, yellow fever, chikungunya and Zika.

Joyce AL1, Torres MM2, Torres R3, Moreno M2.

Author information: 1 Public Health, University of California, 5200 North Lake Road, Merced, CA, 95343, USA. ajoyce2@ucmerced.edu. 2 Departmento de Biología, Universidad de El Salvador, Final de Av. Mártires y Héroes del 30 Julio, San Salvador, El Salvador. 3 Public Health, University of California, 5200 North Lake Road, Merced, CA, 95343, USA.

 

Abstract

BACKGROUND:

Aedes aegypti is associated with dengue, yellow fever, chikungunya and Zika viruses. This vector is widespread in tropical and subtropical areas, and can also occur in temperate areas at higher latitudes. The geographical distribution of Ae. aegypti continues to spread due to human activities. This is the first study to examine the population genetic structure of this insect in El Salvador, Central America.

METHODS:

Aedes aegypti larvae were collected from six geographical regions of El Salvador: Sonsonate, San Salvador, Chalatenango, Usulután, San Miguel and Morazán. Larvae were raised into adults, identified and preserved. Two molecular markers, amplified fragment length polymorphism (AFLP) genotyping and mitochondrial DNA (mtDNA) cytochrome c oxidase subunit 1 (cox1) sequencing, were used to investigate population genetic structure.

RESULTS:

Structure analysis found two genetically distinct populations; one occurs predominantly in the north and west, and a mix of two populations occurs in the southeast of the country. Genetic distances ranged from 0.028 (2.8%) to 0.091 (9%), and an AMOVA analysis found 11% variation between populations. Mitochondrial DNA cox1 sequences produced a haplotype network which consisted of 3 haplogroups and 10 haplotypes. Haplogroup 1 had low haplotype and nucleotide diversity and was found in all six regions. Haplogroups 2 and 3 had higher haplotype and nucleotide diversity, and were less abundant; haplogroup 3 was found in only 3 of the six regions studied. Bottleneck tests were significant, suggesting that populations had undergone a recent bottleneck. A maximum likelihood tree, which combined samples from this study with available sequences in GenBank, suggested that two genetically divergent lineages had been introduced.

CONCLUSIONS:

Relatively high genetic diversity was found in Ae. aegypti in El Salvador. The mtDNA sequences clustered into two lineages, as found in previous studies. Samples in El Salvador may be introduced from regions in North and South America where past eradication was not complete. Future study of genotypes in surrounding countries would provide a more complete picture of the movement and potential source of introductions of this vector. The distribution of the lineages and haplogroups may further our understanding of the epidemiology of Ae. aegypti associated vector borne diseases.

KEYWORDS: AFLPs; Aedes aegypti; Barcode; Central America; Chikungunya; Dengue; Eradication; Haplotype; Mitochondrial DNA cox1; Yellow fever; Zika

PMID: 30547835 PMCID: PMC6295114 DOI: 10.1186/s13071-018-3226-5 [Indexed for MEDLINE]  Free PMC Article

Keywords: Mosquitoes; Aedes aegypti; Arbovirus; El Salvador.

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#Construction sites in #Miami-Dade County, #Florida are highly favorable #environments for vector #mosquitoes (PLoS One, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

PLoS One. 2018 Dec 20;13(12):e0209625. doi: 10.1371/journal.pone.0209625. eCollection 2018.

Construction sites in Miami-Dade County, Florida are highly favorable environments for vector mosquitoes.

Wilke ABB1, Vasquez C2, Petrie W2, Caban-Martinez AJ1, Beier JC1.

Author information: 1 Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, United States of America. 2 Miami-Dade County Mosquito Control Division, Miami, FL, United States of America.

 

Abstract

Urbanization is increasing globally, and construction sites are an integral part of the urbanization process. It is unknown to what extent construction sites create favorable breeding conditions for mosquitoes. The main objectives of the present study were to identify what species of mosquitoes are present at construction sites and the respective physical features associated with their production. Eleven construction sites were cross-sectionally surveyed for the presence of mosquitoes in Miami-Dade County, Florida including in areas previously affected by the Zika virus outbreak in 2016. A total of 3.351 mosquitoes were collected; 2.680 adults and 671 immatures. Aedes aegypti and Culex quinquefasciatus comprised 95% of all collected mosquitoes and were the only species found in their immature forms breeding inside construction sites. Results for the Shannon and Simpson indices, considering both immature and adult specimens, yielded the highest values for Cx. quinquefasciatus and Ae. aegypti. The individual rarefaction curves indicated that sampling sufficiency was highly asymptotic for Cx. quinquefasciatus and Ae. aegypti, and the plots of cumulative species abundance (ln S), Shannon index (H) and log evenness (ln E) (SHE) revealed the lack of heterogeneity of species composition, diversity and evenness for the mosquitoes found breeding in construction sites. The most productive construction site breeding features were elevator shafts, Jersey plastic barriers, flooded floors and stair shafts. The findings of this study indicate that vector mosquitoes breed in high numbers at construction sites and display reduced biodiversity comprising almost exclusively Ae. aegypti and Cx. quinquefasciatus. Such findings suggest that early phase construction sites have suitable conditions for the proliferation of vector mosquitoes. More studies are needed to identify modifiable worker- and organizational-level factors to improve mosquito control practices and guide future mosquito control strategies in urban environments.

PMID: 30571764 DOI: 10.1371/journal.pone.0209625

Keywords: Mosquitoes; Aedes spp.; Culex spp.; Aedes aegypti; Culex quinquefasciatus; USA; Florida.

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#Sequential #Infection of #Aedes aegypti #Mosquitoes with #Chikungunya Virus and #Zika Virus Enhances Early Zika Virus Transmission (Insects, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Insects. 2018 Dec 1;9(4). pii: E177. doi: 10.3390/insects9040177.

Sequential Infection of Aedes aegypti Mosquitoes with Chikungunya Virus and Zika Virus Enhances Early Zika Virus Transmission.

Magalhaes T1, Robison A2, Young MC3, Black WC 4th4, Foy BD5, Ebel GD6, Rückert C7.

Author information: 1 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Tereza.Magalhaes@colostate.edu. 2 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. lexir5394@gmail.com. 3 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. emceeyoung@gmail.com. 4 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. William.Black@colostate.edu. 5 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Brian.Foy@colostate.edu. 6 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Gregory.Ebel@colostate.edu. 7 Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Claudia.Rueckert@Colostate.edu.

 

Abstract

In urban settings, chikungunya, Zika, and dengue viruses are transmitted by Aedes aegypti mosquitoes. Since these viruses co-circulate in several regions, coinfection in humans and vectors may occur, and human coinfections have been frequently reported. Yet, little is known about the molecular aspects of virus interactions within hosts and how they contribute to arbovirus transmission dynamics. We have previously shown that Aedes aegypti exposed to chikungunya and Zika viruses in the same blood meal can become coinfected and transmit both viruses simultaneously. However, mosquitoes may also become coinfected by multiple, sequential feeds on single infected hosts. Therefore, we tested whether sequential infection with chikungunya and Zika viruses impacts mosquito vector competence. We exposed Ae. aegypti mosquitoes first to one virus and 7 days later to the other virus and compared infection, dissemination, and transmission rates between sequentially and single infected groups. We found that coinfection rates were high after sequential exposure and that mosquitoes were able to co-transmit both viruses. Surprisingly, chikungunya virus coinfection enhanced Zika virus transmission 7 days after the second blood meal. Our data demonstrate heterologous arbovirus synergism within mosquitoes, by unknown mechanisms, leading to enhancement of transmission under certain conditions.

KEYWORDS: Zika; arboviruses; chikungunya; coinfection; mosquitoes; sequential infection

PMID: 30513725 DOI: 10.3390/insects9040177

Keywords: Arbovirus; Chikungunya fever; Zika Virus; Dengue fever; Mosquitoes; Aedes spp.; Aedes aegypti.

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Conserved motifs in the hypervariable domain of #chikungunya virus nsP3 required for #transmission by #Aedes aegypti #mosquitoes (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Conserved motifs in the hypervariable domain of chikungunya virus nsP3 required for transmission by Aedes aegypti mosquitoes

Giel P. Göertz, Marit Lingemann, Corinne Geertsema, Marleen H. C. Abma-Henkens, Chantal B. F. Vogels, Constantianus J. M. Koenraadt, Monique M. van Oers, Gorben P. Pijlman

Published: November 9, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006958 / This is an uncorrected proof.

 

Abstract

Background

Chikungunya virus (CHIKV) is a re-emerging arthropod-borne (arbo)virus that causes chikungunya fever in humans and is predominantly transmitted by Aedes aegypti mosquitoes. The CHIKV replication machinery consists of four non-structural proteins (nsP1-4) that additionally require the presence of a number of host proteins for replication of the viral RNA. NsP3 is essential for CHIKV replication and has a conserved macro, central and C-terminal hypervariable domain (HVD). The HVD is intrinsically disordered and interacts with various host proteins via conserved short peptide motifs: A proline-rich (P-rich) motif that has affinity for SH3-domain containing proteins and duplicate FGDF motifs with affinity for G3BP and its mosquito homologue Rasputin. The importance of these motifs for infection of mammalian cells has previously been implicated. However, their role during CHIKV infection of mosquito cells and transmission by mosquitoes remains unclear.

Methodology / Principal findings

Here, we show that in-frame deletion of the P-rich motif is lethal for CHIKV replication in both mosquito and mammalian cells. However, while mutagenesis of the P-rich motif negatively affects replication both in mammalian and mosquito cells, it did not compromise the infection and transmission of CHIKV by Ae. aegypti mosquitoes. Mutagenesis of both FGDF motifs together completely inactivated CHIKV replication in both mammalian and mosquito cells. Importantly, mutation of a single FGDF motif attenuated CHIKV replication in mammalian cells, while replication in mosquito cells was similar to wild type. Surprisingly, CHIKV mutants containing only a single FGDF motif were efficiently transmitted by Ae. aegypti.

Conclusions / Significance

The P-rich motif in CHIKV nsP3 is dispensable for transmission by mosquitoes. A single FGDF motif is sufficient for infection and dissemination in mosquitoes, but duplicate FGDF motifs are required for the efficient infection from the mosquito saliva to a vertebrate host. These results contribute to understanding the dynamics of the alphavirus transmission cycle and may help the development of arboviral intervention strategies.

 

Author summary

Chikungunya virus (CHIKV) is a re-emerging arthropod-borne virus that is transmitted predominantly by Aedes aegypti mosquitoes. In 2016 alone CHIKV caused over 100.000 infections in South-America, exemplifying the impact of CHIKV disease. Previous research has suggested that the CHIKV non-structural protein 3 (nsP3) may determine the infection of mosquitoes. NsP3 is known to interact with several host proteins through a conserved proline (P)-rich and duplicate FGDF motifs that are present in its C-terminal domain. Here we investigated the importance of these conserved motifs for the infection and replication of CHIKV in both Aedes mosquito cells and mammalian cells. Furthermore, we assessed the role of these motifs for the transmission by Ae. aegypti mosquitoes via infectious bloodmeal experiments. We show that mutation of the P-rich motif negatively affects the replication of CHIKV in both mammalian and mosquito cells. In contrast, mutating the P-rich motif did not affect the transmission by Ae. aegypti. Mutation of both FGDF motifs together completely inactivated CHIKV in mammalian and mosquito cells, while mutation of a single FGDF motif negatively affected replication only in mammalian cells. Importantly, CHIKV containing only a single FGDF motif was still efficiently transmitted by Ae. aegypti mosquitoes. These results contribute to understanding the key interactions between alphaviruses and their mosquito vector.

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Citation: Göertz GP, Lingemann M, Geertsema C, Abma-Henkens MHC, Vogels CBF, Koenraadt CJM, et al. (2018) Conserved motifs in the hypervariable domain of chikungunya virus nsP3 required for transmission by Aedes aegypti mosquitoes. PLoS Negl Trop Dis 12(11): e0006958. https://doi.org/10.1371/journal.pntd.0006958

Editor: Lyric C. Bartholomay, University of Wisconsin Madison, UNITED STATES

Received: August 3, 2018; Accepted: October 29, 2018; Published: November 9, 2018

Copyright: © 2018 Göertz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: The authors received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Chikungunya Fever; Mosquitoes; Aedes aegypti.

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