人类狂犬病暴露前和暴露后的预防措施–最新动态

作者：Bernadette Abela-Ridder ，Kaushi Kanakege

此文为在泰国曼谷召开的国际狂犬病专家会议上的发言摘要。

此次会议由国际生物标准化联盟（IABS)和泰国国立疫苗研究所（NVI）共同组织。会议于2019年9月25日至26日召开，会议的主题是：在亚太地区消除狂犬病——从理论到实践。

本文作者Bernadette Abela-Ridder博士是WHO被忽视的热带病管理署被忽视的人畜共患病团队的领导人之一，分工专门负责全球的狂犬病控制工作，Kaushi Kanakege是WHO实习生。

狂犬病是一种被忽视的人畜共患病，估计每年造成59,000人死亡，主要影响非洲和亚洲的发展中国家或地区。 狂犬病造成的死亡可通过对高风险人群或符合WHO II和III类暴露水平的人群进行及时且充分的暴露前预防（PrEP）和暴露后预防（PEP）来避免。

尽管以前WHO推荐的狂犬病疫苗接种方案仍然可以接受，但WHO还是建议采用更新的、较短的疫苗接种方案，以减少PEP和PrEP所需的成本、疫苗数量和门诊次数。 有证据表明，无论是用于PEP还是用于PrEP，现代肌肉内（IM）接种所用的狂犬病疫苗（> 2.5IU / IM剂量）在以皮内（ID）接种的方式施用时的效果与以IM接种的方式施用相当。 这种具有成本效益的多位点ID疫苗接种适用于狂犬病高负担的国家。

狂犬病疫苗和狂犬病免疫球蛋白（RIG）被认为可安全用于孕妇/哺乳期妇女和免疫功能低下的个体。 所有暴露均应立即用肥皂、清洁剂和大量水彻底冲洗伤口。 如果只能获得有限数量的RIG，则应优先分配高风险和III类暴露的患者。 RIG终生仅应使用一次，最好在PEP开始时且在接种首针狂犬病疫苗后不超过7天内使用。

当计算出的RIG剂量太大而无法全部渗入伤口部位时，WHO不再建议将剩余的RIG以IM方式注射到远离伤口的部位。PrEP仅应考虑使用于狂犬病高风险人群（例如给狗接种疫苗者、蝙蝠处理者和流行地区的其他动物卫生工作者）。

现在推荐给所有年龄段的人的PrEP时间表是（a）在第0天和第7天进行2位点ID接种，或（b）在第0天和第7天进行1位点IM接种（PrEP的上述两种方案都是总共进行2次接种）。

给所有年龄段的从未接种过疫苗的人的PEP时间表是（a）第0、3和7天的2位点ID接种，或（b）第0、3、7天的1位点IM，然后在上述两种方案中，都是在第14-28天进行最后一次接种（PEP的上述两种方案都是总共进行4次接种）。

这些新的时间表被认为具有减少时间、成本，改善依从性以及减少患者数量的优点。 WHO与合作伙伴一起，投资于未来的狂犬病预防研究，使用国际标准化的问卷调查和监测来提高成本效益、计划可行性以及患者和临床医生的可接受度。

附录：

Bernadette Abela-Ridder 在泰国曼谷召开的国际狂犬病专家会议上的上述发言摘要的英文原文：

Pre- and post-exposure prophylaxis in humans – an update

Bernadette Abela-Ridder, Kaushi Kanakege (WHO Intern)

        Rabies is a neglected zoonotic disease responsible for an estimated 59,000 human deaths annually, affecting mainly the developing economies in Africa and Asia. Deaths due to rabies are preventable through timely and adequate pre (PrEP) and post-exposure prophylaxis (PEP) to people at high risk or comply under WHO category II and III exposures. While previously WHO-recommended rabies vaccine schedules remain acceptable, WHO also recommends newer, shorter vaccine regimens that reduce costs, quantity of vaccine, and number of clinic visits required for both PEP and PrEP. Evidence shows that intradermal (ID) administration of modern intramuscular (IM) rabies vaccines (>2.5IU/IM dose), for either PEP or PrEP, is comparable to IM administration. This cost-effective multi-site ID vaccination is suited for high burden countries. Rabies vaccines and Rabies immunoglobulin (RIG) are considered safe to use in pregnant/lactating women and immunocompromised individuals. Vigorous wound washing with soap, detergent and copious amounts of water should be performed immediately for all exposures. If a limited amount of RIG is available, its allocation should be prioritised for patients with high risk and category III exposures. RIG should be administered only once, preferably at initiation of PEP and not more than 7 days following the first rabies vaccine dose. When the calculated RIG dose is too large to infiltrate around the wound site, WHO no longer recommends IM injecting the remainder at a site distant from the wound. PrEP should only be considered for persons at high risk of rabies exposure such as dog vaccinators, bat handlers and other animal health workers in endemic areas. The PrEP schedules that are now recommended for people in all age groups are (a) 2-site ID on days 0 and 7, or (b) 1-site IM on days 0 and 7. The PEP schedules for immunologically naïve individuals for all age groups include (a) 2-site ID on days 0, 3 and 7 or (b) 1-site IM on days 0, 3, 7 and a final dose between days 14-28. These schedules are considered to have advantages of reducing time, cost, improving adherence/compliance, as well as reducing the volume of patients. Along with partners, WHO is invested in future research on rabies prevention using internationally standardized questionnaires and surveillance to improve cost-effectiveness, programmatic feasibility and acceptability to patients and clinicians.