Morris Sinead E, Nguyen Huong Q, Grijalva Carlos G, Hanson Kayla E, Zhu Yuwei, Biddle Jessica E, Meece Jennifer K, Halasa Natasha B, Chappell James D, Mellis Alexandra M, Reed Carrie, Biggerstaff Matthew, Belongia Edward A, Talbot H Keipp, Rolfes Melissa A
Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
Goldbelt Professional Services, Chesapeake, VA 23320, USA.
PNAS Nexus. 2024 Aug 21;3(9):pgae338. doi: 10.1093/pnasnexus/pgae338. eCollection 2024 Sep.
Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.
隔离有症状的感染者可减少流感传播。然而，无症状情况下的病毒 shedding 不受此类措施影响。确定有效的流感隔离策略需要了解个体病毒 shedding 与症状表现之间的相互作用。2017 年至 2020 年，我们开展了一项病例确诊的家庭传播研究，对鼻拭子进行流感实时 RT-qPCR 检测，并在入组后最多 7 天（索引发病后≤14 天）进行每日症状日记报告。我们假定实时 RT-qPCR 循环阈值（Ct）值是定量病毒 shedding 的指标，并使用症状日记创建一个追踪流感样疾病（ILI）症状（发热、咳嗽或喉咙痛）的评分。我们拟合了按年龄和疫苗接种状况分层的现象学非线性混合效应模型，并估计了影响隔离效果的两个量：症状出现前的 shedding 和隔离结束后可能发生的 shedding。我们考虑了不同的隔离终点（包括发热消退后 24 小时或症状出现后 5 天）以及关于 Ct shedding 轨迹传染性的假设。在 116 名进行纵向分析且检测结果≥2 次呈阳性的家庭接触者中，105 名（91%）出现了≥1 种 ILI 症状。平均而言，与其他年龄组相比，5 岁以下儿童的 shedding 峰值更高、shedding 持续时间更长且 ILI 症状评分更高。大多数个体（63/105）在症状出现前 shed 的病毒量不到其总 shed 病毒量的 10%，隔离后的 shedding 在个体、隔离终点和传染性假设之间差异很大。我们的结果可为减少感染流感的有症状个体传播的策略提供参考。
