부산대학교 도서관

Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7–16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies. Author summary: In this study, we examined the potential for people with mild illness to transmit dengue virus to mosquitoes. Although people with mild dengue illness can be infectious, they often are undetected by surveillance systems and research teams. Variation in infectiousness over the course of a person's infection is a largely unexplored but potentially important component of dengue epidemiology. In an effort to better understand the factors that underlie this variation, we blood fed laboratory-reared, uninfected mosquitoes directly on mildly ill people naturally infected with dengue virus in Iquitos, Peru. Detection of virus in mosquito saliva after feeding on an infected person was considered positive for mosquito transmission. As has been reported previously, transmission to mosquitoes was positively associated with the amount of virus in a person's blood and the number of days after the mosquito fed on an infected person. Unlike results from previous studies, which reported peak transmission during the first day of a person's illness, we found that for mildly ill people infectiousness to mosquitoes peaked on the second day of illness. Because people with mild illness are thought to contribute more to dengue virus transmission than more severely ill people, subtle differences in the dynamics of their infectiousness to mosquitoes could be epidemiologically significant. [ABSTRACT FROM AUTHOR]