Model-guided assessment of rotavirus vaccine impact in developing countries

 描述(申请人提供)：轮状病毒是导致儿童严重腹泻的主要原因，也是发展中国家发病率和死亡率的主要来源。在发达国家，接种疫苗已被证明是控制轮状病毒相关性胃肠炎负担的一种安全有效的手段，但后勤限制和对疫苗在发展中国家效力降低的担忧阻碍了它们的更广泛采用。需要更好的证据来支持在发展中国家接种疫苗的预期影响，以克服引入疫苗的障碍。我们试图利用统计和数学建模相结合的方法解决这些关切，以便更好地了解影响发展中国家轮状病毒疫苗接种的直接和间接影响的因素。 首先，我们将重新分析在墨西哥和印度进行的关键出生队列研究的数据，以探索这样一个假设：与墨西哥相比，印度轮状病毒传播率更高，感染时年龄更小，这可能有助于解释这些环境中对自然感染的保护差异。其次，我们将使用数学模型来研究轮状病毒在孟加拉国、马拉维和加纳传播动态的重要驱动因素。我们将使用这些模型来预测轮状病毒疫苗接种在这些环境中的影响 接种疫苗的直接和间接影响。最后，我们将通过与在马拉维布兰太尔和加纳阿克拉和纳夫隆戈正在进行的疫苗接种影响研究中收集的数据进行比较，来验证和完善模型预测。这些项目将提高我们对轮状病毒潜在传播动态如何影响发展中国家疫苗接种的预期直接和间接影响的理解，并将提供一个有效的平台，将建模分析扩展到其他国家，为轮状病毒疫苗的引入提供循证支持。

 DESCRIPTION (provided by applicant): Rotavirus is the leading cause of severe diarrhea in children, and a major source of morbidity and mortality in developing countries. Vaccination has proven to be a safe and effective means of controlling the burden of rotavirus-associated gastroenteritis in developed countries, but logistical constraints and concerns over the reduced efficacy of the vaccines in developing country settings have hindered their wider adoption. Better evidence is needed to support the expected impact of vaccination in developing countries to overcome the barriers to vaccine introduction. We seek to address these concerns using a combination of statistical and mathematical modeling to gain a better understanding of the factors affecting the direct and indirect effects of rotavirus vaccination in developing countries. First, we will reanalyze data from pivotal birth cohort studies conducted in Mexico and India to explore the hypothesis that higher rates of rotavirus transmission and the younger age at infection in India compared to Mexico may help to explain the differences in protection from natural infection in these settings. Second, we will use mathematical models to examine the important drivers of rotavirus transmission dynamics in Bangladesh, Malawi, and Ghana. We will use the models to predict the impact of rotavirus vaccination in these settings accounting for both the direct and indirect effects of vaccination. Finally, we will validate and refine model predictions by comparing to data collected as part of ongoing studies of the impact of vaccination in Blantyre, Malawi and Accra and Navrongo, Ghana. These projects will improve our understanding of how the underlying transmission dynamics of rotavirus affect the expected direct and indirect effects of vaccination in developing countries, and will provide a validated platform for extending the modeling analyses to other countries to provide evidence-based support for rotavirus vaccine introduction.