Within-host viral dynamics of dengue serotype 1 infection.
Dengue, the most common mosquito-borne viral infection of humans, is endemic across much of the world, including much of tropical Asia and is increasing in its geographical range. Here, we present a mathematical model of dengue virus dynamics within infected individuals, detailing the interaction between virus and a simple immune response. We fit this model to measurements of plasma viral titre from cases of primary and secondary DENV 1 infection in Vietnam. We show that variation in model parameters governing the immune response is sufficient to create the observed variation in virus dynamics between individuals. Estimating model parameter values, we find parameter differences between primary and secondary cases consistent with the theory of antibody-dependent enhancement (namely enhanced rates of viral entry to target cells in secondary cases). Finally, we use our model to examine the potential impact of an antiviral drug on the within-host dynamics of dengue. We conclude that the impact of antiviral therapy on virus dynamics is likely to be limited if therapy is only started at the onset of symptoms, owing to the typically late stage of viral pathogenesis reached by the time symptoms are manifested and thus treatment is started.
Department for Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College, London W2 1PG, UK hannah.clapham08@imperial.ac.uk.
Hannah E
HE
Clapham
Institut Pasteur de Bangui, Bangui, Central African Republic.
Vianney
V
Tricou
Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam.
Nguyen
N
Van Vinh Chau
Oxford University Clinical Research Unit, University of Oxford, District 5, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX1 2JD, UK Nossal Institute for Global Health, University of Melbourne, Melbourne, Victoria 3010, Australia.
Cameron P
CP
Simmons
Department for Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, Imperial College, London W2 1PG, UK.
Neil M
NM
Ferguson
D000330:Aedes; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D003141:Communicable Diseases; D003715:Dengue / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008962:Models, Theoretical; D065288:Serogroup; D019562:Viral Load
D000998:Antiviral Agents
dengue; virus dynamics; within-host modelling