Mechanical transmission of dengue virus by Aedes aegypti may influence disease transmission dynamics during outbreaks

Hsing-Han Li; Matthew P Su; Shih-Cheng Wu; Hsiao-Hui Tsou; Meng-Chun Chang; Yu-Chieh Cheng; Kuen-Nan Tsai; Hsin-Wei Wang; Guan-Hua Chen; Cheng-Kang Tang; Pei-Jung Chung; Wan-Ting Tsai; Li-Rung Huang; Yueh Andrew Yueh; Hsin-Wei Chen; Chao-Ying Pan; Omar S Akbari; Hsiao-Han Chang; Guann-Yi Yu; John M Marshall; Chun-Hong Chen

doi:10.1016/j.ebiom.2023.104723

Mechanical transmission of dengue virus by Aedes aegypti may influence disease transmission dynamics during outbreaks

EBioMedicine. 2023 Aug:94:104723. doi: 10.1016/j.ebiom.2023.104723. Epub 2023 Jul 22.

Authors

Hsing-Han Li¹, Matthew P Su², Shih-Cheng Wu³, Hsiao-Hui Tsou⁴, Meng-Chun Chang⁵, Yu-Chieh Cheng⁶, Kuen-Nan Tsai⁷, Hsin-Wei Wang⁸, Guan-Hua Chen⁹, Cheng-Kang Tang¹⁰, Pei-Jung Chung¹¹, Wan-Ting Tsai¹¹, Li-Rung Huang⁷, Yueh Andrew Yueh¹², Hsin-Wei Chen¹¹, Chao-Ying Pan¹³, Omar S Akbari¹⁴, Hsiao-Han Chang⁵, Guann-Yi Yu¹¹, John M Marshall¹⁵, Chun-Hong Chen¹⁶

Affiliations

¹ National Mosquito-Borne Disease Control Research Center, NHRI, Miaoli, 350401, Taiwan; National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan; Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, 92093, USA.
² Graduate School of Science, Nagoya University, Nagoya, 464-8602, Japan; Institute for Advanced Research, Nagoya University, Nagoya, 464-8601, Japan.
³ National Mosquito-Borne Disease Control Research Center, NHRI, Miaoli, 350401, Taiwan; National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 10048, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, 10021, Taiwan.
⁴ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, 350401, Taiwan; Graduate Institute of Biostatistics, College of Public Health, China Medical University, Taichung, 40402, Taiwan.
⁵ Department of Life Science & Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
⁶ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, 350401, Taiwan.
⁷ Institute of Molecular and Genomic Medicine, NHRI, Miaoli, 350401, Taiwan.
⁸ National Mosquito-Borne Disease Control Research Center, NHRI, Miaoli, 350401, Taiwan; National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan.
⁹ National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan.
¹⁰ National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan; Program of Plant Protection and Health, Academy of Circular Economy, National Chung Hsing University, Taichung, 402202, Taiwan.
¹¹ National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan.
¹² Institute of Biotechnology and Pharmaceutical Research, NHRI, Miaoli, 350401, Taiwan.
¹³ Department of Health, Kaohsiung City Government, Kaohsiung, 800852, Taiwan.
¹⁴ Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA, 92093, USA.
¹⁵ Divisions of Biostatistics and Epidemiology, School of Public Health, University of California, Berkeley, CA, 94720, USA.
¹⁶ National Mosquito-Borne Disease Control Research Center, NHRI, Miaoli, 350401, Taiwan; National Institute of Infectious Diseases and Vaccinology, NHRI, Miaoli, 350401, Taiwan. Electronic address: chunhong@gmail.com.

Abstract

Background: Dengue virus outbreaks are increasing in number and severity worldwide. Viral transmission is assumed to require a minimum time period of viral replication within the mosquito midgut. It is unknown if alternative transmission periods not requiring replication are possible.

Methods: We used a mouse model of dengue virus transmission to investigate the potential of mechanical transmission of dengue virus. We investigated minimal viral titres necessary for development of symptoms in bitten mice and used resulting parameters to inform a new model of dengue virus transmission within a susceptible population.

Findings: Naïve mice bitten by mosquitoes immediately after they took partial blood meals from dengue infected mice showed symptoms of dengue virus, followed by mortality. Incorporation of mechanical transmission into mathematical models of dengue virus transmission suggest that this supplemental transmission route could result in larger outbreaks which peak sooner.

Interpretation: The potential of dengue transmission routes independent of midgut viral replication has implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes.

Funding: This study was funded by grants from the National Health Research Institutes, Taiwan (04D2-MMMOST02), the Human Frontier Science Program (RGP0033/2021), the National Institutes of Health (1R01AI143698-01A1, R01AI151004 and DP2AI152071) and the Ministry of Science and Technology, Taiwan (MOST104-2321-B-400-016).

Keywords: Aedes aegypti mosquito; Animal models of dengue virus; Dengue transmission; Mathematical modelling of disease outbreak.

MeSH terms

Aedes*
Animals
Dengue Virus*
Dengue* / epidemiology
Disease Outbreaks
Humans
Mice
Mosquito Vectors

Abstract

MeSH terms

Grants and funding