From the Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.
Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA.
Epidemiology. 2022 Sep 1;33(5):660-668. doi: 10.1097/EDE.0000000000001501. Epub 2022 May 18.
Estimates of rotavirus vaccine effectiveness (VE) in the United States appear higher in years with more rotavirus activity. We hypothesized rotavirus VE is constant over time but appears to vary as a function of temporal variation in local rotavirus cases and/or misclassified diagnoses.
We analyzed 6 years of data from eight US surveillance sites on 8- to 59-month olds with acute gastroenteritis symptoms. Children's stool samples were tested via enzyme immunoassay (EIA); rotavirus-positive results were confirmed with molecular testing at the US Centers for Disease Control and Prevention. We defined rotavirus gastroenteritis cases by either positive on-site EIA results alone or positive EIA with Centers for Disease Control and Prevention confirmation. For each case definition, we estimated VE against any rotavirus gastroenteritis, moderate-to-severe disease, and hospitalization using two mixed-effect regression models: the first including year plus a year-vaccination interaction, and the second including the annual percent of rotavirus-positive tests plus a percent positive-vaccination interaction. We used multiple overimputation to bias-adjust for misclassification of cases defined by positive EIA alone.
Estimates of annual rotavirus VE against all outcomes fluctuated temporally, particularly when we defined cases by on-site EIA alone and used a year-vaccination interaction. Use of confirmatory testing to define cases reduced, but did not eliminate, fluctuations. Temporal fluctuations in VE estimates further attenuated when we used a percent positive-vaccination interaction. Fluctuations persisted until bias-adjustment for diagnostic misclassification.
Both controlling for time-varying rotavirus activity and bias-adjusting for diagnostic misclassification are critical for estimating the most valid annual rotavirus VE.
在美国，轮状病毒疫苗有效性 (VE) 的估计值在轮状病毒活动较多的年份似乎更高。我们假设轮状病毒 VE 是随时间而保持不变的，但似乎会随着当地轮状病毒病例的时间变化和/或诊断错误而发生变化。
我们分析了美国 8 个监测点的 6 年数据，这些监测点针对 8 至 59 个月大的急性胃肠炎症状儿童。通过酶联免疫吸附试验 (EIA) 检测儿童的粪便样本；美国疾病控制与预防中心通过分子检测确认轮状病毒阳性结果。我们通过 EIA 现场检测结果阳性或 EIA 现场检测结果阳性且美国疾病控制与预防中心确认阳性这两种方式定义轮状病毒胃肠炎病例。对于每种病例定义，我们使用两种混合效应回归模型来估计针对任何轮状病毒胃肠炎、中重度疾病和住院的 VE：第一个模型包括年份和年份-疫苗接种相互作用，第二个模型包括每年的轮状病毒阳性检测百分比和阳性疫苗接种百分比相互作用。我们使用多次过拟合来偏置调整仅通过 EIA 阳性定义病例的错误分类。
针对所有结果的年度轮状病毒 VE 估计值随时间波动，尤其是当我们仅通过 EIA 现场检测结果阳性且使用年份-疫苗接种相互作用来定义病例时。使用确认检测来定义病例减少了，但并没有消除波动。当我们使用阳性疫苗接种百分比相互作用时，VE 估计值的时间波动进一步减弱。当我们偏置调整诊断错误分类时，波动持续存在。
控制时间变化的轮状病毒活动和偏置调整诊断错误分类对于估计最有效的年度轮状病毒 VE 都非常重要。
