title: Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti.
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.
authors: Medical Research Council Centre for Outbreak Analysis and Modelling, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK. neil.ferguson@imperial.ac.uk.
authors: Neil M
authors: NM
authors: Ferguson
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Duong Thi Hue
authors: DT
authors: Kien
authors: Medical Research Council Centre for Outbreak Analysis and Modelling, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors: Hannah
authors: H
authors: Clapham
authors: Medical Research Council Centre for Outbreak Analysis and Modelling, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors: Ricardo
authors: R
authors: Aguas
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Vu Tuan
authors: VT
authors: Trung
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Tran Nguyen Bich
authors: TN
authors: Chau
authors: School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors: Jean
authors: J
authors: Popovici
authors: School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors: Peter A
authors: PA
authors: Ryan
authors: School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors: Scott L
authors: SL
authors: O'Neill
authors: School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors: Elizabeth A
authors: EA
authors: McGraw
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Vo Thi
authors: VT
authors: Long
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Le Thi
authors: le T
authors: Dui
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Hoa L
authors: HL
authors: Nguyen
authors: Hospital for Tropical Diseases, 190 Ben Hám Tú, District 5, Ho Chi Minh City 748010, Vietnam.
authors: Nguyen Van Vinh
authors: NV
authors: Chau
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX1 7FZ, UK.
authors: Bridget
authors: B
authors: Wills
authors: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, 764 Võ Vǎn Kiêt, District 5, Ho Chi Minh City 748010, Vietnam. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX1 7FZ, UK. Department of Microbiology and Immunology and Nossal Institute of Global Health, University of Melbourne, Carlton, Victoria 3010, Australia.
authors: Cameron P
authors: CP
authors: Simmons
mesh_terms: D000293:Adolescent; D000328:Adult; D000330:Aedes / Q000382:microbiology* / Q000821:virology*; D000818:Animals; D003715:Dengue / Q000382:microbiology* / Q000635:transmission / Q000821:virology*; D003716:Dengue Virus / Q000502:physiology*; D004199:Disease Vectors; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D011446:Prospective Studies; D012463:Saliva / Q000382:microbiology / Q000821:virology; D020577:Wolbachia / Q000502:physiology*; D055815:Young Adult