4.5 Article

Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus

Journal

VACCINE
Volume 37, Issue 33, Pages 4736-4742

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2018.05.065

Keywords

Rabies; Therapy; Combination treatment; Blood-brain barrier

Funding

  1. EU FP7 project ASKLEPIOS [602825]
  2. Niedersachsen Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony

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Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-alpha. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups. (C) 2018 The Authors. Published by Elsevier Ltd.

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