Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.我们探讨了当前正在发生的巴西黄热病（yellow fever, YF）暴发中病毒意外快速传播这一谜题所涉及的复杂生态社会因素；此次暴发自1942年以来，首次让巴西这个此前无本土城市黄热病例的国家面临该疾病再城市化的风险。事实上，病毒快速向东南部与南部地区空间扩散，目前正于巴西主要大都市（圣保罗与里约热内卢）近郊区域附近的大西洋森林破碎化栖息地中循环传播，这一情况导致黄热病病例数呈指数级增长。在不到18个月的时间内，累计记录到1833例确诊病例与578例死亡病例，其中99.9%的病例报告来自东南部地区。该国境内出现了大规模的非人灵长类（non-human primates, NHPs）动物流行病：仅在2017/2018年度监测期内，就有732起经实验室确认的黄热病毒（yellow fever virus, YFV）感染事件。此外，我们还对比了本次暴发与既往大型流行事件的异同点，探讨了多个用以解释近期黄热病毒丛林循环中动物流行病浪潮意外加速的假说，同时分析了人类、非人灵长类以及蚊媒的移动性对病毒传播的作用。我们得出结论：能够解释此次快速传播的最可行假说，与人类行为及生态环境变化相关——后者显著提升了蚊媒与非人灵长类的种群密度，并增加了它们与人类的接触概率。我们强调，必须紧急采取恰当措施应对此次暴发：例如将黄热病疫苗接种覆盖范围扩大至全体巴西民众，并针对栖息于指定保护区与动物园内的非人灵长类研发新型免疫接种策略。最后，我们强调亟需提升应对工作的质量，以防止未来暴发疫情以及该疾病在巴西与其他南美国家发生灾难性的城市化扩散。持续监测黄热病毒（YFV）易感易感性与脆弱性状况、有效控制城市传播媒介埃及伊蚊（Aedes aegypti）、大幅提升黄热疫苗生产能力，并投入研发以降低疫苗不良反应，均为当前最高优先级任务。