Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

西部马脑炎病毒 (WEEV) 是一种蚊媒病毒，于 2023 年 12 月在阿根廷和乌拉圭重新出现，引发大规模疫情。我们利用流行病学、昆虫​​学和基因组分析对此次疫情进行了调查，重点关注巴西南里奥格兰德州阿根廷和乌拉圭边境附近的 WEEV 循环。 2023 年 11 月至 2024 年 4 月，阿根廷和乌拉圭爆发疫情，造成 217 例人感染病例，其中 12 例死亡，以及 2,548 例马病例。我们根据实验室和临床流行病学标准确定病例。我们对 3 起致命的马病例进行了描述，这些病例是由通过近乎完整的编码序列分析确定的新型 WEEV 谱系引起的，我们将其命名为谱系 C。我们的研究结果强调了持续监测和马疫苗接种对于控制南美洲未来 WEEV 爆发的重要性。