Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti

Neil M. Ferguson, Duong Thi Hue Kien, Hannah Clapham, Ricardo Aguas, Vu Tuan Trung, Tran Nguyen Bich Chau, Jean Popovici, Peter A. Ryan, Scott L. O'Neill, Elizabeth A. McGraw, Vo Thi Long, Le Thi Dui, Hoa L. Nguyen, Nguyen Vinh Van Chau, Bridget Wills, Cameron P. Simmons

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75%. Our results suggest that establishment of wMelPop-infected A. aegypti at a high frequency in a dengue-endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel-infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.

Original languageEnglish (US)
Article number279ra37
JournalScience Translational Medicine
Volume7
Issue number279
DOIs
StatePublished - Mar 18 2015

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Wolbachia
Dengue Virus
Aedes
Virus Diseases
Culicidae
Dengue
Viruses
Abdomen
Basic Reproduction Number
Infection
Saliva
Mental Competency
Theoretical Models
Public Health
Bacteria

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Ferguson, N. M., Kien, D. T. H., Clapham, H., Aguas, R., Trung, V. T., Chau, T. N. B., ... Simmons, C. P. (2015). Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti. Science Translational Medicine, 7(279), [279ra37]. https://doi.org/10.1126/scitranslmed.3010370
Ferguson, Neil M. ; Kien, Duong Thi Hue ; Clapham, Hannah ; Aguas, Ricardo ; Trung, Vu Tuan ; Chau, Tran Nguyen Bich ; Popovici, Jean ; Ryan, Peter A. ; O'Neill, Scott L. ; McGraw, Elizabeth A. ; Long, Vo Thi ; Dui, Le Thi ; Nguyen, Hoa L. ; Van Chau, Nguyen Vinh ; Wills, Bridget ; Simmons, Cameron P. / Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti. In: Science Translational Medicine. 2015 ; Vol. 7, No. 279.
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abstract = "Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75{\%}. Our results suggest that establishment of wMelPop-infected A. aegypti at a high frequency in a dengue-endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel-infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.",
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Ferguson, NM, Kien, DTH, Clapham, H, Aguas, R, Trung, VT, Chau, TNB, Popovici, J, Ryan, PA, O'Neill, SL, McGraw, EA, Long, VT, Dui, LT, Nguyen, HL, Van Chau, NV, Wills, B & Simmons, CP 2015, 'Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti', Science Translational Medicine, vol. 7, no. 279, 279ra37. https://doi.org/10.1126/scitranslmed.3010370

Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti. / Ferguson, Neil M.; Kien, Duong Thi Hue; Clapham, Hannah; Aguas, Ricardo; Trung, Vu Tuan; Chau, Tran Nguyen Bich; Popovici, Jean; Ryan, Peter A.; O'Neill, Scott L.; McGraw, Elizabeth A.; Long, Vo Thi; Dui, Le Thi; Nguyen, Hoa L.; Van Chau, Nguyen Vinh; Wills, Bridget; Simmons, Cameron P.

In: Science Translational Medicine, Vol. 7, No. 279, 279ra37, 18.03.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti

AU - Ferguson, Neil M.

AU - Kien, Duong Thi Hue

AU - Clapham, Hannah

AU - Aguas, Ricardo

AU - Trung, Vu Tuan

AU - Chau, Tran Nguyen Bich

AU - Popovici, Jean

AU - Ryan, Peter A.

AU - O'Neill, Scott L.

AU - McGraw, Elizabeth A.

AU - Long, Vo Thi

AU - Dui, Le Thi

AU - Nguyen, Hoa L.

AU - Van Chau, Nguyen Vinh

AU - Wills, Bridget

AU - Simmons, Cameron P.

PY - 2015/3/18

Y1 - 2015/3/18

N2 - Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75%. Our results suggest that establishment of wMelPop-infected A. aegypti at a high frequency in a dengue-endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel-infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.

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