Modeling the impact and cost-effectiveness of next-generation rotavirus vaccine strategies in low- and middle-income countries

项目摘要/摘要 尽管轮状病毒活疫苗被引入全球90多个国家，但轮状病毒仍然 是儿童严重腹泻的主要原因，也是低收入和低收入人群发病率和死亡率的主要来源 中等收入国家(LMIC)。轮状病毒疫苗接种已经有效地控制了 轮状病毒相关性胃肠炎(RVGE)在高收入国家，但 由于仍不完全清楚的多种原因，目前口服轮状病毒活疫苗在LMICs中的比例较低。新的 可能需要疫苗和方法来克服对当前活的口腔轮状病毒免疫反应差的问题。 LMIC中的疫苗。下一代轮状病毒疫苗，包括新生儿和非肠道亚单位疫苗， 目前正在开发中，并在我们位于马拉维和加纳的现场进行临床试验。模特是 需要将这些试验的结果外推到人口水平。我们将使用数学模型来 预测不同轮状病毒疫苗接种策略的潜在影响，包括直接和 接种疫苗的间接影响。然后，我们将进行经济评估，以确定最具成本效益的 减轻轮状病毒引起的腹泻负担的方法。我们将首先关注马拉维和加纳， 在那里，我们以前开发了模型，并拥有良好的疫苗接种前和接种后监测数据。我们 然后将扩展我们的方法，以预测所有LMIC的疫苗影响和成本效益。我们的分析 将有助于更好地定义疫苗反应、免疫持续时间和下一代疫苗的价格 轮状病毒疫苗可能具有成本效益，并将提供一个经过验证的平台，供决策者使用 LMIC可以用来权衡本国不同轮状病毒疫苗接种策略的成本和收益。

PROJECT SUMMARY/ABSTRACT Despite the introduction of live oral rotavirus vaccines into more than 90 countries worldwide, rotavirus remains a leading cause of severe diarrhea in children and a major source of morbidity and mortality in low- and middle-income countries (LMICs). Rotavirus vaccination has been effective at controlling the burden of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but the response, efficacy, and impact of current live oral rotavirus vaccines is lower in LMICs for multiple reasons that are still not fully understood. New vaccines and approaches may be needed to overcome the poor immune response to current live oral rotavirus vaccines in LMICs. Next-generation rotavirus vaccines, including neonatal and parenteral subunit vaccines, are currently in development and undergoing clinical trials at our field sites in Malawi and Ghana. Models are needed to extrapolate the results of these trials to the population level. We will use mathematical models to predict the potential impact of different rotavirus vaccination strategies, accounting for both the direct and indirect effects of vaccination. We will then conduct economic evaluations to determine the most cost-effective approach to reducing the burden of diarrhea due to rotavirus. We will begin by focusing on Malawi and Ghana, where we have previously developed models and have good pre- and post-vaccination surveillance data. We will then extend our approach to predict vaccine impact and cost-effectiveness across all LMICs. Our analyses will help to better define the vaccine response, duration of immunity, and price at which next-generation rotavirus vaccines are likely to be cost-effective, and will provide a validated platform that decision-makers in LMICs can use to weigh the costs and benefits of different rotavirus vaccination strategies in their country.