Emerging treatments
Milwaukee protocol
This is a detailed protocol for the treatment of symptomatic rabies.[48] The intent is to avoid fatal dysautonomia through deep, nonbarbiturate sedation pending immune clearance. Active drugs, including ketamine and nimodipine for prophylaxis against generalized basal artery spasm, are theoretically neuroprotective. Prerequisites for using this protocol include good logistics and access to a rabies reference laboratory and rehabilitation facilities.[49][50] The protocol requires further evaluation to establish its efficacy, as data relate to a limited number of cases. Occasional survivors were reported.
Monoclonal antibodies
The World Health Organization (WHO) is undertaking a project to develop a cocktail of unique combinations of monoclonal antibodies capable of neutralizing a diverse range of rabies isolates. Products such as CL184, RMAb, Rabimabs, and SYN023 are undergoing clinical trials.[51]SII RMAb has been shown to be safe and noninferior to human rabies immune globulin for postexposure prophylaxis.[52]
Antivirals
Favipiravir has shown efficacy against rabies virus in vitro and in vivo. One study found that early administration reduced the morbidity and mortality associated with rabies virus infection in mice.[53] Ribavirin has also shown in vitro activity against rabies virus but has not been effective in animal studies.[47][54]
PIKA® vaccine
The PIKA® rabies vaccine contains a novel adjuvant, a synthetic analog of double-strand RNA and a refined form of polyinosinic-polycytidylic acid stabilized with kanamycin and calcium, as well as the inactivated and purified rabies virus. It acts as an agonist at toll-like receptor-3 (TLR-3) and is capable of inducing nonspecific immunity. A phase II, randomized study in healthy adults found that an accelerated regimen using the PIKA® vaccine was well tolerated and demonstrated noninferior immunogenicity compared to the classic vaccine regimen using Rabipur®.[55] Phase 3 trials are due to commence in some countries in 2023. The PIKA® vaccine was granted orphan drug designation by the Food and Drug Administration in 2016.
Use of this content is subject to our disclaimer