Chan Louis Yat Hin, Morris Sinead E, Stockwell Melissa S, Bowman Natalie M, Asturias Edwin, Rao Suchitra, Lutrick Karen, Ellingson Katherine D, Nguyen Huong Q, Maldonado Yvonne, McLaren Son H, Sano Ellen, Biddle Jessica E, Smith-Jeffcoat Sarah E, Biggerstaff Matthew, Rolfes Melissa A, Talbot H Keipp, Grijalva Carlos G, Borchering Rebecca K, Mellis Alexandra M
Centers for Disease Control and Prevention, USA.
Centers for Disease Control and Prevention, USA; Goldbelt Professional Services, USA.
Epidemics. 2025 Mar;50:100815. doi: 10.1016/j.epidem.2025.100815. Epub 2025 Jan 18.
The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially since the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days, completing daily symptom diaries and collecting nasal swabs, which were then tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission occurring before symptomatic onset, the infectious period, and the latent period. We estimated a mean intrinsic generation time of 3.2 (95 % credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95 % CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variations in the incubation period. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts.
代时代表了原发性和继发性病例感染之间的间隔时间，对于理解和预测季节性流感的传播动态至关重要，包括实时有效繁殖数（Rt）。然而，目前缺乏对季节性流感的全面代时估计，特别是自2009年流感大流行以来。我们利用美国一项在2021/2022和2022/2023两个流感季节进行的7个地点的病例确诊家庭研究数据，对代时进行了估计。在家庭中首例发病后的7天内，招募了200多名流感检测呈阳性的个体及其家庭接触者。所有参与者均前瞻性随访10天，完成每日症状日记并采集鼻拭子，然后通过逆转录聚合酶链反应（RT-PCR）检测流感。我们通过修改先前发表的贝叶斯数据增强方法来分析这些数据，该方法推算病例的感染时间，以获得内在（假设无易感人群耗竭）和实际（家庭内观察到的）代时。我们通过改变潜伏期来评估代时估计的稳健性，并生成了症状出现前传播比例、传染期和潜伏期的估计值。我们估计平均内在代时为3.2天（95%可信区间，CrI：2.9 - 3.6），家庭实际代时为2.8天（95% CrI：2.7 - 3.0）。代时对潜伏期变化的敏感性有限。症状出现前传播比例、传染期和潜伏期的估计值对潜伏期变化敏感。我们的研究有助于不断完善流感代时的估计。我们从新冠疫情后的近期数据得出的估计值与大流行前的先前估计值一致，并将纳入实时Rt估计工作中。
