Paris-Saclay Institute of Neuroscience (UMR9197) CNRS - Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Thai Red Cross Society Emerging Infectious Disease Health Science Centre and World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Curr Opin Infect Dis. 2018 Feb;31(1):93-101. doi: 10.1097/QCO.0000000000000420.
Despite great progress in decoding disease mechanisms, rabies remains one of the leading causes of human death worldwide. Towards the elimination of human rabies deaths by 2030, feasible and affordable post (PEP) and pre-exposure prophylaxis (PrEP) must be available with expansion to rural areas in rabies endemic countries. Vaccination and population control of dogs, principal reservoirs and transmitters, must be done in concert.
Advances in the understanding of rabies neuropathogenesis and pathophysiology are reviewed, including recent experimental findings on host- and virus-specific mechanisms mediating neuronal survival and explaining clinical differences in furious and paralytic rabies. The forthcoming World Health Organization guide on rabies based on pathogenesis and immunization mechanisms data with support by clinical evidence provide new accelerated 1 week intradermal PrEP and PEP schedules. Rabies immunoglobulin injected into the wound only is endorsed at amounts not exceeding the dose interfering with active immunization. Potential therapeutics as designed in accord with rabies neuro-pathophysiology are plausible.
Clinical practice and rabies awareness can be leveraged by transboundary collaboration among different areas. Advancement in prophylaxis and perspectives on animal control offer a new path to conquer rabies by 2030.
尽管在破译疾病机制方面取得了重大进展，但狂犬病仍是全球导致人类死亡的主要原因之一。为了在 2030 年消除人类狂犬病死亡病例，必须在狂犬病流行国家的农村地区提供可行和负担得起的接触后（PEP）和接触前预防（PrEP）。必须协调开展犬（主要的储存宿主和传播媒介）的免疫接种和种群控制。
本文回顾了对狂犬病神经发病机制和病理生理学的理解进展，包括关于宿主和病毒特异性机制的最新实验发现，这些机制介导神经元存活，并解释了狂躁型和麻痹型狂犬病的临床差异。即将发布的世界卫生组织狂犬病指南基于发病机制和免疫机制数据，并得到临床证据的支持，提供了新的加速一周皮内 PrEP 和 PEP 方案。仅在伤口处注射狂犬病免疫球蛋白的剂量不得超过干扰主动免疫的剂量，这一建议得到了认可。根据狂犬病的神经病理生理学设计的潜在治疗方法是合理的。
通过不同领域的跨境合作，可以利用狂犬病的临床实践和认识来推动进展。预防措施的进步和对动物控制的看法为 2030 年消灭狂犬病提供了新途径。
