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      Acceptability of Aedes aegypti blood feeding on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru

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          Abstract

          As part of a study to investigate drivers of dengue virus (DENV) transmission dynamics, this qualitative study explored whether DENV-infected residents of Iquitos, Peru, considered it acceptable (1) to participate in direct mosquito feeding experiments (lab-reared Aedes aegypti mosquitoes fed directly on human volunteers) and (2) to provide blood meals indirectly ( Ae. aegypti fed on blood drawn from participants by venipuncture). Twelve focus group discussions (FGDs; 94 participants: 82 females and 12 males) were conducted in January 2014 to explore six themes: (1) concerns and preferences regarding direct mosquito feeds and blood draws, (2) comprehension of and misconceptions about study procedures, (3) motivating factors for participation, (4) acceptability of children’s participation, (5) willingness to provide multiple samples over several days, and (6) preference for direct feedings in homes versus the study laboratory. Results of FGDs, including one with 5 of 53 past direct mosquito feed participants, indicated that mosquito feeding procedures are acceptable to Iquitos residents when they are provided with information and a few key messages are properly reinforced. FGD participants’ concerns focused primarily on safety issues rather than discomfort associated with mosquito bites. A video explaining the study dramatically increased comprehension of the study procedures. The majority of participants expressed a preference for mosquito feeding over venipuncture. Adults supported child participation if the children themselves assented. For most participants, home feedings were preferred over those in a laboratory. A major impetus for participation was the idea that results would contribute to an improved understanding of DENV transmission in Iquitos. Findings from our study will support future large-scale studies that employ direct mosquito feeding, a low-risk, non-invasive procedure that is experimentally superior to artificial mosquito feeding methods.

          Author summary

          Approximately half of the world’s population is at risk of contracting dengue virus (DENV). Ethical and logistical concerns with feeding lab-raised mosquitoes directly on naturally infected human subjects, and the lack of a relevant animal model for DENV experimental infection, are important obstacles to better understanding DENV transmission from humans to mosquitoes. Results from artificial infectious blood meals can bias estimates of mosquito infection and transmission rates. Based on 12 focus group discussions, we determined that the practice of feeding uninfected lab-raised mosquitoes on naturally infected human subjects is highly acceptable to people living in Iquitos, Peru, especially after common concerns are addressed. The majority of participants were willing to have mosquitoes feed on them directly and to give venous blood samples to feed to mosquitoes indirectly. Most participants stated a preference for direct feeding. This formative research, including recognition of and addressing common misconceptions, will help guide future development of protocols using biologically relevant direct mosquito feeding methods.

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          House-to-house human movement drives dengue virus transmission.

          Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti, local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vector-borne pathogens, especially the importance of human movement, will lead to improvements in disease prevention.
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            Epidemic arboviral diseases: priorities for research and public health.

            For decades, arboviral diseases were considered to be only minor contributors to global mortality and disability. As a result, low priority was given to arbovirus research investment and related public health infrastructure. The past five decades, however, have seen an unprecedented emergence of epidemic arboviral diseases (notably dengue, chikungunya, yellow fever, and Zika virus disease) resulting from the triad of the modern world: urbanisation, globalisation, and international mobility. The public health emergency of Zika virus, and the threat of global spread of yellow fever, combined with the resurgence of dengue and chikungunya, constitute a wake-up call for governments, academia, funders, and WHO to strengthen programmes and enhance research in aedes-transmitted diseases. The common features of these diseases should stimulate similar research themes for diagnostics, vaccines, biological targets and immune responses, environmental determinants, and vector control measures. Combining interventions known to be effective against multiple arboviral diseases will offer the most cost-effective and sustainable strategy for disease reduction. New global alliances are needed to enable the combination of efforts and resources for more effective and timely solutions.
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              Asymptomatic humans transmit dengue virus to mosquitoes.

              Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantly more to virus transmission to mosquitoes than previously recognized.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Writing – original draft
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                11 February 2019
                February 2019
                : 13
                : 2
                : e0007090
                Affiliations
                [1 ] Department of Entomology and Nematology, University of California, Davis, Davis, California, United States of America
                [2 ] Virology and Emerging Infections Department, U.S. Naval Medical Research Unit No. 6, Washington DC, Lima and Iquitos, Peru
                [3 ] Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
                [4 ] Insect-Virus Interactions Group, Department of Genomes and Genetics, Institut Pasteur, Paris, France
                [5 ] Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Paris, France
                [6 ] Global Community Health and Behavioral Sciences, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America
                International Centre for Genetic Engineering and Biotechnology, INDIA
                Author notes

                NO authors have competing interests.

                [¤]

                Current address: Department of Pathology, Microbiology, and Immunology (PMI), School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America

                Author information
                http://orcid.org/0000-0001-6224-5984
                Article
                PNTD-D-18-01184
                10.1371/journal.pntd.0007090
                6386403
                30742621
                1259830d-0b33-4b0d-83f6-2884c7c962e3

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 3 August 2018
                : 18 December 2018
                Page count
                Figures: 1, Tables: 3, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R03AI107446
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R01AI069341
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: P01AI098670
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100005326, Yale University;
                Award ID: Parker Huang Undergraduate Travel Fellowship
                Award Recipient :
                We would also like to thank the Parker Huang Undergraduate Travel Fellowship from Yale University for funding JS while working on this project. This research was funded by a grants from the U.S. National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIH/NIAID): principally award number R03AI107446-01 (to A.C.M and L.L.), secondarily, R01 AI069341 and P01 AI098670 (to T.W.S). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Infectious Diseases
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                2019-02-22
                All relevant data are within the manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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