From alternative hosts to alternative interventions: identifying drivers of epidemic dynamics for Japanese encephalitis virus in Bangladesh

一些由蚊子传播的病原体会在人类之间传播，比如登革热。然而，有许多蚊子传播的病毒在其他动物之间传播，人类因此被意外感染。这些病毒很难控制；人类接种疫苗无法消除它们。此外，由于它们通常可以感染不止一个物种，它们可以在一系列环境中出现。这种类型的一种样本病毒是日本脑炎病毒(JEV)，它是亚洲病毒性脑炎的最常见原因。这种疾病通常与稻田和养猪场有关。稻田为媒介蚊子幼虫提供了合适的栖息地，而猪很容易将病毒传播给媒介。尽管如此，近年来亚洲城市周边地区也报告了乙脑疾病，在孟加拉国，这种疾病发生在猪密度较低的地区。此外，这里的牛密度很高。乙脑在孟加拉国是如何发生的尚不清楚；乙脑病毒的媒介偏爱牛，但牛不能传播病毒。我将阐述替代宿主物种对乙脑病毒在孟加拉国流行负有责任的假设。在孟加拉国北部，家养的鸭子、鸡和鸽子经常被饲养在稻米种植区的家庭中。实验表明，家禽可以将病毒传播给蚊子，但尚不清楚它们是否在自然界中促成了传播，哪些鸟类物种对传播最重要，以及涉及哪些媒介物种。我将首先确定允许乙脑病毒在高密度牛的情况下传播的条件。为了做到这一点，我将开发传动的机械模型。我将使用这些模型来测试，与家禽和牛均匀分布在村庄的情况相比，家禽聚集在一个村庄的几个家庭中，是放大还是稀释传播。在不能传播病毒的宿主密度很高的情况下，可以传播病毒的宿主的聚集可能对继续传播至关重要。估计每个宿主物种上的血粉比例特别重要，因为它影响从宿主到蚊子以及蚊子到宿主的传播率。使用鸟饵诱捕器，我将量化潜在媒介物种相对于鸭子、鸡和鸽子的相对偏好。聚焦于对潜在媒介最具吸引力的鸟类物种，然后我将确定家庭寄主群落的组成和密度如何影响鸟类的血粉比例。在用从现场收集的数据更新模型后，我将使模型与牛JEV免疫状态和感染JEV的蚊子比例的估计相匹配。使用拟合的模型，我将通过将每只鸟从系统中移除并量化对模拟疫情的影响来确定每只鸟的相对作用。我还将测试模型预测乙脑病毒传播相对高风险和低风险地区的能力，并使用高风险和低风险村庄的牛免疫状态数据验证这些预测。最后，我将使用经过验证的模型来评估各种控制方法，包括侧重于减少病媒与最重要宿主之间的接触的潜在生态干预措施。了解传播是如何维持的，对于确定潜在的控制策略和更好地确定能够支持乙脑病毒传播的环境是重要的。孟加拉国目前没有人类疫苗接种方案，尽管在引入疫苗之前，该疾病的发生与其他国家类似。将人类疫苗接种目标对准高风险地区的能力可能会使控制在财务和后勤上更加可行。此外，从长远来看，考虑其他干预措施可能更可持续，并在与人类疫苗一起使用时有效地减少人类乙脑。

Some mosquito-borne pathogens that cause disease in humans, like dengue, are transmitted between humans. However, there are many mosquito-borne viruses that are transmitted between other animals, for which humans are infected incidentally. These viruses are difficult to control; human vaccination cannot eliminate them. In addition, because they can usually infect more than one species, they can be present across a range of settings. One exemplar virus of this type is Japanese encephalitis virus (JEV), which is the most common cause of viral encephalitis in Asia. The disease is usually associated with rice fields and pig farming. Rice fields contain suitable habitat for larvae of vector mosquitoes and pigs can easily transmit virus to vectors. Despite this, JE disease has been reported from peri-urban areas of Asia in recent years and, in Bangladesh, the disease occurs in regions with low density of pigs. Here, also, there is a high density of cattle. How JE occurs in Bangladesh is unknown; cattle are preferred by vectors of JEV, but they cannot transmit the virus. I will address the hypothesis that alternative host species are responsible for epidemics of JEV in Bangladesh. In northern Bangladesh domestic ducks, chickens and pigeons are regularly kept together in households in rice-growing areas. Experiments have shown that poultry can transmit virus to mosquitoes, but it is not known whether they contribute to transmission in nature, which bird species is most important to transmission and which vector species are involved. I will first establish the conditions which would permit JEV transmission in the presence of a high density of cattle. To do this, I will develop mechanistic models of transmission. I will use the models to test whether aggregation of poultry in a few households of a village either amplifies or dilutes transmission, compared with the scenario where poultry are evenly spread across a village with cattle. Aggregation of hosts that can transmit virus may be essential for onward transmission in cases where there is high density of hosts that cannot transmit the virus.The proportion of blood meals on each host species is particularly important to estimate because it influences the rate of transmission from hosts to mosquitoes as well as mosquitoes to hosts. Using bird-baited traps I will quantify the relative preference of potential vector species to ducks, chickens, and pigeons. Focusing on the bird species most commonly attractive to potential vectors I will then determine how household host community composition and density influences the proportion of blood meals on birds. After updating models with data collected from the field, I will fit models to estimates of cattle JEV immune status and proportion of mosquitoes infected with JEV. Using fitted models, I will determine the relative role of each bird by removing them from the system and quantifying the effects on simulated outbreaks. I will also test the ability of models to predict relatively high and low risk areas of JEV transmission and validate these predictions using cattle immune status data from high and low risk villages. Lastly, I will use validated models to assess various control approaches, including potential ecological interventions that focus on reducing contact between vectors and the most important hosts.An understanding of how transmission is maintained is important to inform potential control strategies and to better determine the environments that can support JEV transmission. There is currently no human vaccination programme in Bangladesh, despite the occurrence of the disease being similar to other countries before introduction of vaccine. The ability to target human vaccination to high-risk areas may make control more financially and logistically feasible. In addition, consideration of other interventions may be more sustainable in the long-term and be effective at reducing human JE when used with human vaccination.