Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America.
PLoS Comput Biol. 2019 Jul 26;15(7):e1007014. doi: 10.1371/journal.pcbi.1007014. eCollection 2019 Jul.
Cohort studies, randomized trials, and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis (RVGE) in low- and middle-income countries. While susceptibility of children to rotavirus is known to vary within and between settings, implications for estimation of immune protection are not well understood. We sought to re-estimate naturally-acquired protection against rotavirus infection and RVGE, and to understand how differences in susceptibility among children impacted estimates. We re-analyzed data from studies conducted in Mexico City, Mexico and Vellore, India. Cumulatively, 573 rotavirus-unvaccinated children experienced 1418 rotavirus infections and 371 episodes of RVGE over 17,636 child-months. We developed a model that characterized susceptibility to rotavirus infection and RVGE among children, accounting for aspects of the natural history of rotavirus and differences in transmission rates between settings. We tested whether model-generated susceptibility measurements were associated with demographic and anthropometric factors, and with the severity of RVGE symptoms. We identified greater variation in susceptibility to rotavirus infection and RVGE in Vellore than in Mexico City. In both cohorts, susceptibility to rotavirus infection and RVGE were associated with male sex, lower birth weight, lower maternal education, and having fewer siblings; within Vellore, susceptibility was also associated with lower socioeconomic status. Children who were more susceptible to rotavirus also experienced higher rates of rotavirus-negative diarrhea, and higher risk of moderate-to-severe symptoms when experiencing RVGE. Simulations suggested that discrepant estimates of naturally-acquired immunity against RVGE can be attributed, in part, to between-setting differences in susceptibility of children, but result primarily from the interaction of transmission rates with age-dependent risk for infections to cause RVGE. We found that more children in Vellore than in Mexico City belong to a high-risk group for rotavirus infection and RVGE, and demonstrate that unmeasured individual- and age-dependent susceptibility may influence estimates of naturally-acquired immune protection against RVGE.
队列研究、随机试验和上市后研究报告称，在中低收入国家，轮状病毒胃肠炎（RVGE）的自然和疫苗衍生保护作用降低。虽然已知儿童对轮状病毒的易感性在不同环境中存在差异，但对免疫保护作用的影响尚不清楚。我们试图重新估计自然获得的轮状病毒感染和 RVGE 保护作用，并了解儿童易感性的差异如何影响估计值。我们重新分析了在墨西哥城和印度维洛尔进行的研究数据。在 17636 个儿童月中，共有 573 名未接种轮状病毒疫苗的儿童经历了 1418 次轮状病毒感染和 371 次 RVGE 发作。我们开发了一种模型，该模型描述了儿童对轮状病毒感染和 RVGE 的易感性，考虑了轮状病毒自然史和不同环境中传播率的差异。我们测试了模型生成的易感性测量值是否与人口统计学和人体测量学因素以及 RVGE 症状的严重程度相关。我们发现，与墨西哥城相比，维洛尔的轮状病毒感染和 RVGE 的易感性差异更大。在两个队列中，轮状病毒感染和 RVGE 的易感性与男性、出生体重较低、母亲教育程度较低以及兄弟姐妹较少有关；在维洛尔，易感性还与社会经济地位较低有关。对轮状病毒更易感的儿童也经历了更高的轮状病毒阴性腹泻率，并且在经历 RVGE 时发生中度至重度症状的风险更高。模拟表明，RVGE 自然获得性免疫的差异估计部分归因于儿童在不同环境中的易感性差异，但主要归因于传播率与年龄相关的感染导致 RVGE 的风险之间的相互作用。我们发现，与墨西哥城相比，维洛尔有更多的儿童属于轮状病毒感染和 RVGE 的高风险群体，并证明未测量的个体和年龄相关的易感性可能会影响对 RVGE 的自然获得性免疫保护的估计。
