Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT 06520-8034, USA.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre 3, Malawi.
Sci Transl Med. 2019 Aug 14;11(505). doi: 10.1126/scitranslmed.aav6419.
Rotavirus vaccination has substantially reduced the incidence of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but vaccine impact and estimated effectiveness are lower in low-income countries for reasons that are poorly understood. We used mathematical modeling to quantify rotavirus vaccine impact and investigate reduced vaccine effectiveness, particularly during the second year of life, in Malawi, where vaccination was introduced in October 2012 with doses at 6 and 10 weeks. We fitted models to 12 years of prevaccination data and validated the models against postvaccination data to evaluate the magnitude and duration of vaccine protection. The observed rollout of vaccination in Malawi was predicted to lead to a 26 to 77% decrease in the overall incidence of moderate-to-severe RVGE in 2016, depending on assumptions about waning of vaccine-induced immunity and heterogeneity in vaccine response. Vaccine effectiveness estimates were predicted to be higher among 4- to 11-month-olds than 12- to 23-month-olds, even when vaccine-induced immunity did not wane, due to differences in the rate at which vaccinated and unvaccinated individuals acquire immunity from natural infection. We found that vaccine effectiveness during the first and second years of life could potentially be improved by increasing the proportion of infants who respond to vaccination or by lowering the rotavirus transmission rate. An additional dose of rotavirus vaccine at 9 months of age was predicted to lead to higher estimated vaccine effectiveness but to only modest (5 to 16%) reductions in RVGE incidence over the first 3 years after introduction, regardless of assumptions about waning of vaccine-induced immunity.
轮状病毒疫苗接种大大降低了高收入国家轮状病毒相关胃肠炎(RVGE)的发病率,但由于原因尚不清楚,低收入国家的疫苗效果和估计效果较低。我们使用数学模型来量化轮状病毒疫苗的影响,并研究了马拉维的疫苗效力降低,该国于 2012 年 10 月开始接种疫苗,6 周和 10 周时接种疫苗。我们对 12 年的疫苗接种前数据进行了模型拟合,并根据疫苗接种后数据对模型进行了验证,以评估疫苗保护的强度和持续时间。观察到的马拉维疫苗接种的推出预计将导致 2016 年中度至重度 RVGE 的总发病率降低 26%至 77%,具体取决于疫苗诱导免疫衰减和疫苗反应异质性的假设。即使疫苗诱导的免疫没有减弱,由于接种疫苗和未接种疫苗个体从自然感染中获得免疫力的速度不同,4 至 11 个月大的婴儿的疫苗效力估计值也高于 12 至 23 个月大的婴儿。我们发现,通过增加对疫苗有反应的婴儿比例或降低轮状病毒传播率,有可能提高疫苗在生命的第一年和第二年的效力。在 9 个月大时接种额外的轮状病毒疫苗预计会导致更高的疫苗效力估计值,但无论疫苗诱导免疫衰减的假设如何,在引入后的头 3 年中,仅能适度降低(5%至 16%)RVGE 的发病率。