Are We Getting Closer to the Treatment of Rabies?

Rodney E Willoughby Jr

Disclosures

Future Virology. 2009;4(6):563-570. 

In This Article

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Improvements in human survival have better delineated the immune and metabolic responses to rabies. (For the latest survival curve, see [102].) We identified adverse immunological effects of ribavirin and new complications associated with the immune response, such as cardiac atrioventricular block and cerebral edema. We can differentiate the kinetics of the immune response to rabies viruses of dog and bat origin [WILLOUGHBY R, UNPUBLISHED DATA].

There is progressive lactic acidosis (up to 5–6 mM) in CSFs of patients who do not survive rabies, while a recent survivor and another near-survivor did not develop acidosis.[19] CBF, as measured by TCD, near-infrared or nuclear spectroscopy, did not explain these trends. CSF lactic acidosis was also reported by Warrell during early attempts at intensive care of rabies patients.[40] Given that we have clearly established a disorder of BH4 metabolism (and downstream neurotransmission) in human rabies, it is reasonable to posit a more upstream metabolic disorder as well. In collaboration with C Slupsky at the University of California at Davis, CA, USA, we are examining the metabolomics of human CSF during rabies by nuclear magnetic resonance. The progressive lactic acidosis was confirmed, and markedly elevated levels of QA at very early times in symptomatic rabies were also identified.[19] QA is excitotoxic to the brain, acting on NMDA glutamate receptors.[41] Serendipitously, ketamine, the original rabies antiviral/anesthetic used in the improvised protocol, is a potent inhibitor of QA-mediated neuronal toxicity.[41] Other metabolic consequences of rabies virus infection in humans and other animals should become clearer as metabolomic analyses accrue.

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