The doctors who treated the first known patient to survive rabies without prior vaccination have published their aggressive and previously untested treatment protocol, but they caution that it requires further study.
“Clearly, our experience with this patient requires replication in other patients and proof-of-concept experiments in animal models,” said Rodney E. Willoughby Jr., M.D., of the Medical College of Wisconsin, Milwaukee, and his colleagues.
The 15-year-old patient developed confirmed clinical rabies 1 month after being bitten on the left index finger by a bat. She was treated with a strategy that involved induction of therapeutic coma, and antiexcitatory and antiviral drug therapy under supportive intensive care. The concept was to protect the brain from injury while allowing the launch of a natural immune response against the virus (N. Engl. J. Med. 2005;352:2508–14).
The patient was treated with ketamine, midazolam, ribavirin, and amantadine. Doses were adjusted as needed due to responses and probable drug-related toxicities, which included hemolysis, pancreatitis, acidosis, and hepatotoxicity. She did not receive rabies vaccine or rabies immunoglobulin because she demonstrated immune response and because of concern regarding harm from a potentiated immune response.
On the 8th day, a lumbar puncture indicated an increased level of rabies antibody, and sedation was tapered. On hospital day 31, the patient was determined to be cleared of transmissible rabies and was removed from isolation. She was discharged to home on hospital day 76.
At a follow-up visit 131 days after her initial hospitalization, the patient was progressing, and had returned to school part time. She continues to experience dysarthrotic speech, buccolingual choreoathetosis with generalized choreoathetosis and intermittent dystonia and ballismus, which affect her gait and fine-motor skills.
Prior to this case, five cases of survival following rabies had been well documented, but all received occupationally related preexposure rabies vaccination or postexposure prophylaxis; this is the first known patient to survive with only naturally acquired immunity. It should be noted that the patient was young and athletic, and may have received a limited quantity of inoculum, the investigators stressed, adding that since the bat was not recovered, it is unclear if the patient's survival was due to an “unusual, more temperate or attenuated variant of the virus, or a rare host polymorphism.”
“Therapy may have been more effective than in past cases because of the inferred limited exposure to rabies virus, early recognition of the disease, and aggressive management,” the investigators said, noting that the survival of this patient does not change the fact that rabies has the highest case fatality ratio of any infectious disease.