4.7 Article

A One Medicine Mission for an Effective Rabies Therapy

期刊

FRONTIERS IN VETERINARY SCIENCE
卷 9, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fvets.2022.867382

关键词

rabies; treatment; pathogenesis; prognosis; canine; neurodegeneration; immunotherapy; blood-brain barrier

资金

  1. Wellcome Foundation

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Despite the long history of rabies, little progress has been made in finding a treatment for this disease. The prognosis for patients remains bleak. The high cost, required clinical expertise, and uncertain outcomes make it difficult for physicians in rabies endemic areas to provide aggressive critical care. Additionally, the sporadic occurrence of cases hampers systematic clinical research. This perspective suggests using a One Medicine approach to accelerate the development of an effective therapy for rabies by treating naturally infected dogs and studying their response to treatment.
Despite the disease's long history, little progress has been made toward a treatment for rabies. The prognosis for patient recovery remains dire. For any prospect of survival, patients require aggressive critical care, which physicians in rabies endemic areas may be reluctant or unable to provide given the cost, clinical expertise required, and uncertain outcome. Systematic clinical research into combination therapies is further hampered by sporadic occurrence of cases. In this Perspective, we examine the case for a One Medicine approach to accelerate development of an effective therapy for rabies through the veterinary care and investigational treatment of naturally infected dogs in appropriate circumstances. We review the pathogenesis of rabies virus in humans and dogs, including recent advances in our understanding of the molecular basis for the severe neurological dysfunction. We propose that four categories of disease process need to be managed in patients: viral propagation, neuronal degeneration, inflammation and systemic compromise. Compassionate critical care and investigational treatment of naturally infected dogs receiving supportive therapy that mimics the human clinical scenario could increase opportunities to study combination therapies that address these processes, and to identify biomarkers for prognosis and therapeutic response. We discuss the safety and ethics of this approach, and introduce the Canine Rabies Treatment Initiative, a non-profit organization with the mission to apply a One Medicine approach to the investigation of diagnostic, prognostic, and therapeutic options for rabies in naturally infected dogs, to accelerate transformation of rabies into a treatable disease for all patients.

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