Direct mosquito feedings on dengue-2 virus-infected people reveal dynamics of human infectiousness.
Direct mosquito feedings on dengue-2 virus-infected people reveal dynamics of human infectiousness.
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DOI：
10.1371/journal.pntd.0011593
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发表时间：
2023-09
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
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登革病毒（DENV）从人到蚊子的传播是一个记录不多，但关键组成部分的DENV流行病学。病毒血症的程度是DENV在人与蚊子之间成功传播的主要决定因素。然而，具有相同水平病毒血症的人，其对蚊子的感染性可能因其他因素而异，这些因素仍有待阐明。在这里，我们报告了在秘鲁伊基托斯市进行的一项基于实地的研究，在那里我们对自然感染DENV的人进行了直接的蚊子喂养，这些人经历了轻微的疾病。我们还招募了在研究期间在伊基托斯引入ZIKV后自然感染ZIKV的人。在54名参与直接喂食蚊子的研究参与者中，43人感染了DENV-2，2人感染了DENV-3，9人感染了ZIKV。我们的分析排除了在入组时可检测到病毒血症但在蚊子喂养时无法检测到的参与者，所有DENV-3和ZIKV感染的参与者都是这种情况。我们分析了在涉及27名感染DENV-2的参与者的50次喂食事件期间，基于血餐后7-16天蚊子唾液中感染性病毒的存在，向前传播的概率。传播概率呈正相关的病毒血症水平和持续时间的外来孵化的蚊子。此外，传播概率以非单调的方式受到患病日期的影响;即，传播概率增加，直到症状发作后2天，此后下降。我们的结论是，在症状发作后的前两天内具有相似病毒血症水平的轻度登革病毒感染者在其疾病的第二天对蚊子的感染性最强。量化人内和人与人之间在DENV传播方面的差异对于更好地了解人类传染性的生物决定因素，参数化流行病学模型以及改善疾病监测和预防策略至关重要。在这项研究中，我们检查了患有轻症的人将登革热病毒传播给蚊子的可能性。尽管患有轻度登革热的人可能具有传染性，但监测系统和研究团队往往无法发现他们。在一个人的感染过程中，感染性的变化在很大程度上是未知的，但可能是登革热流行病学的重要组成部分。为了更好地了解这种变异的基础因素，我们在秘鲁的伊基托斯将实验室饲养的未感染的蚊子直接喂给自然感染登革热病毒的轻度患者。在蚊子吸食受感染者后的唾液中检测到病毒被认为是蚊子传播的阳性。正如以前所报告的那样，传播给蚊子与人血液中的病毒量和蚊子在感染者身上进食后的天数呈正相关。与以前的研究结果不同，这些研究报告了一个人患病第一天的传播高峰，我们发现，对于轻度疾病的人来说，蚊子的传染性在患病的第二天达到峰值。由于人们认为，病情较轻的人比病情较重的人更容易传播登革热病毒，因此他们对蚊子的感染力动态的细微差异可能在流行病学上具有重要意义。
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. 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 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.
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