BACKGROUND Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies. METHODS AND FINDINGS We leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p ≤ 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden. CONCLUSIONS We have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children.

中文翻译：

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低收入和中等收入国家学龄前儿童呼吸道合胞病毒负担的年龄特征：半参数元回归方法。

背景呼吸道合胞病毒（RSV）感染是全世界5岁以下儿童死亡的主要原因之一。许多即将推出的针对 RSV 的预防性干预措施的一个显着挑战是它们的保护持续时间较短，这使得年龄特征成为预防策略设计的关键关注点。方法和结果 我们利用收集到的病例、住院和死亡的 RSV 数据进行系统评价，并结合灵活的广义加性混合模型 (GAMM) 来描述 RSV 发病率、住院率和医院病死率的年龄负担。 hCFR）。由于 GAMM 的灵活性，我们估计了感染的峰值、中位数和平均发病率，以便为有关预防性干预措施的理想“保护窗口”的讨论提供信息。在二次分析中，我们重新估计了所有低收入和中等收入国家的 RSV 负担。社区发病高峰年龄为4.8个月，感染平均年龄和中位年龄分别为18.9个月和14.7个月。使用基于医院的研究的发病率来估计年龄概况，得出的年龄概况稍年轻，其中感染的高峰年龄为 2.6 个月，感染的平均年龄和中位年龄分别为 15.8 个月和 11.6 个月。更严重的后果，例如住院和院内死亡，年龄较小。6 个月以下儿童占 5 岁以下人口的 10%，但承担了 20% 至 29% 的病例、28% 至 39% 的住院治疗以及 38% 至 50% 的死亡。我们估计，低收入、中低收入和中高收入国家平均每年有 28.23 至 3134 万例 RSV 病例、2.95 至 335 万人住院治疗、16,835 至 19,909 例院内死亡。此外，我们估计社区死亡人数为 17,254 至 23,875 人，总计死亡人数为 34,114 至 46,485 人。在全球范围内，有证据表明，基于社区的发病率可能因世界银行收入组别而异，但基于医院的发病率、住院概率或院内死亡概率则没有差异（p ≤ 0.01、p = 1、p = 0.86、0.63 ， 分别）。我们的研究受到限制，主要是由于数据稀疏，特别是对于低收入国家（LIC）。某些人群缺乏信息使得检测收入群体之间的异质性变得困难，并且获得护理的机会的差异可能会影响报告的负担。结论 我们已经展示了一种以统计原则方式综合 RSV 结果信息的方法，并且我们估计 RSV 负担的年龄特征取决于发病率信息是在医院还是在社区收集。我们的结果表明，理想的预防策略可能需要多种产品来避免学龄前儿童的风险。