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

一些引起人类疾病的蚊媒病原体，如登革热，是在人与人之间传播的。然而，有许多蚊子传播的病毒在其他动物之间传播，人类偶然感染。这些病毒很难控制；人类接种疫苗不能消除它们。此外，由于它们通常可以感染不止一个物种，因此它们可以出现在一系列环境中。这种类型的一个典型病毒是日本脑炎病毒（JEV），它是亚洲病毒性脑炎的最常见病因。这种疾病通常与稻田和养猪业有关。稻田是病媒蚊子幼虫的适宜栖息地，而猪容易将病毒传播给病媒。尽管如此，近年来在亚洲城市周边地区报告了乙脑疾病，在孟加拉国，该病发生在猪密度低的地区。这里的牛密度也很高。乙脑如何在孟加拉国发生尚不清楚；牛是乙脑病毒载体的首选，但它们不能传播病毒。我将讨论替代宿主物种导致孟加拉国乙脑病毒流行的假设。在孟加拉国北部的水稻种植区，家鸭、鸡和鸽子经常被养在一起。实验表明，家禽可以将病毒传播给蚊子，但是尚不清楚它们是否有助于自然界的传播，哪些鸟类对传播最重要，以及哪些媒介物种参与其中。我将首先确定在牛密度较高的情况下允许乙脑病毒传播的条件。为了做到这一点，我将开发传播的机械模型。我将使用这些模型来测试家禽聚集在一个村庄的几个家庭中，与家禽均匀分布在一个有牛的村庄的情况相比，是放大还是稀释了传播。在不能传播病毒的高密度宿主的情况下，能够传播病毒的宿主的聚集可能对进一步传播至关重要。估计每个宿主物种的血食比例特别重要，因为它影响宿主对蚊子以及蚊子对宿主的传播速度。使用鸟饵陷阱，我将量化潜在病媒物种对鸭、鸡和鸽子的相对偏好。我将重点关注对潜在病媒最具吸引力的鸟类，然后确定家庭宿主群落组成和密度如何影响鸟类血食的比例。在用实地收集的数据更新模型后，我将把模型拟合到牛乙脑病毒免疫状况和感染乙脑病毒的蚊子比例的估计中。使用拟合模型，我将通过将每只鸟从系统中移除并量化它们对模拟爆发的影响来确定它们的相对作用。我还将测试模型预测乙脑病毒传播相对高风险区和低风险区的能力，并使用来自高风险区和低风险区的牛免疫状况数据验证这些预测。最后，我将使用经过验证的模型来评估各种控制方法，包括潜在的生态干预措施，重点是减少媒介与最重要宿主之间的接触。了解传播是如何维持的，对于告知潜在的控制策略和更好地确定可能支持乙脑病毒传播的环境非常重要。尽管在引入疫苗之前，该病的发病率与其他国家相似，但孟加拉国目前没有人接种疫苗规划。针对高危地区的人接种疫苗的能力可能使控制在财政和后勤上更加可行。此外，考虑其他干预措施在长期内可能更具可持续性，并且在与人类疫苗接种一起使用时可有效减少人类乙脑。

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.