BACKGROUND Precision public health is a novel set of methods to target disease prevention and mitigation interventions to high-risk subpopulations. We applied a precision public health strategy to syndromic surveillance for severe acute respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with genomic sequencing to detect and characterize viral respiratory pathogens with epidemic potential. METHODS Using a national surveillance network we identified patients with unexplained, influenza-negative SARI from 2010 to 2015. Spatiotemporal analyses were performed retrospectively to identify clusters of unexplained SARI. Within clusters, respiratory viruses were detected and characterized in naso- and oropharyngeal swab samples using a novel oligonucleotide probe capture (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional epidemiologic strategies further characterized transmission dynamics of identified pathogens. RESULTS Among 2901 unexplained SARI cases, 9 clusters were detected, accounting for 301 (10.4%) cases. Clusters were more likely to occur in urban areas and during biannual rainy seasons. Within detected clusters, we identified an unrecognized outbreak of measles-associated SARI; sequence analysis implicated cocirculation of endemic genotype B3 and genotype D4 likely imported from England. We also detected a likely nosocomial SARI cluster associated with a novel picobirnavirus most closely related to swine and dromedary viruses. CONCLUSIONS Using a precision approach to public health surveillance, we detected and characterized the genomics of vaccine-preventable and zoonotic respiratory viruses associated with clusters of severe respiratory infections in Uganda. Future studies are needed to assess the feasibility, scalability, and impact of applying similar approaches during real-time public health surveillance in low-income settings.

中文翻译：

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病毒性呼吸道病原体的精确监测：用于乌干达严重急性呼吸道感染检测和基因组表征的病毒组捕获测序。

背景精准公共卫生是一套针对高危人群进行疾病预防和缓解干预的新方法。我们将时空分析与基因组测序相结合，将精确的公共卫生策略应用于乌干达严重急性呼吸道感染 (SARI) 的综合征监测，以检测和表征具有流行潜力的病毒性呼吸道病原体。方法使用国家监测网络，我们确定了 2010 年至 2015 年患有不明原因流感阴性 SARI 的患者。进行时空分析以识别不明原因的 SARI 集群。在集群内，使用新型寡核苷酸探针捕获 (VirCapSeq-VERT) 和高通量测序平台在鼻和口咽拭子样本中检测和表征呼吸道病毒。与传统流行病学策略的联系进一步表征了已识别病原体的传播动态。结果 2901例不明原因SARI病例中，共发现9个集群，占301例（10.4%）。集群更有可能发生在城市地区和一年两次的雨季。在检测到的集群中，我们发现了一个未被识别的麻疹相关 SARI 暴发；序列分析表明地方性基因型 B3 和基因型 D4 可能从英国进口的共同循环。我们还检测到一个可能的院内 SARI 集群，它与一种与猪和单峰骆驼病毒最密切相关的新型 picobirna 病毒相关。结论 使用精确的方法进行公共卫生监测，我们检测并表征了与乌干达严重呼吸道感染群相关的疫苗可预防和人畜共患呼吸道病毒的基因组学。未来的研究需要评估在低收入环境中实时公共卫生监测期间应用类似方法的可行性、可扩展性和影响。