The following is from a fax from Dr. Rupprecht of the Centers For Disease Control in Atlanta. Pathogenesis of Bat Rabies Virus Variants in Domestic Ferrets M. Niezgoda D.J. Briggs J.S. Shaddock C.E. Rupprecht Centers for Disease Control & Prevention, Viral and Zoonosis Branch, Atlanta, GA Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA. Kansas State University, College of Veterinary Medicine, Manhattan, KS. The domestic ferret is increasing in popularity as a pet in the United States, raising critical questions for public health officials responsible for the management of ferret bites to human beings, in regards to the potential risk for rabies. Although the first licensed rabies vaccine was approved for use in domestic ferrets in 1990, healthy vaccinated ferrets that bite human beings may, based on review of the case report, be routinely euthanatized and examined for rabies, rather than be held and observed. Current recommendations result largely from the lack of information on ferret response to rabies virus infection. Neither clinical signs nor a determination of virus secretion in salvia prior to clinical signs are well documented. As a continuation of studies investigating the pathogenesis of rabies in domestic ferrets, preliminary studies investigated ferret response using virus variants associated with North American bats. Ferrets received virus by intermuscular inoculation and were held for a minimum observation period of 120 days. Ferrets were observed daily, and weekly samples included swabs of the oral cavity, body weights, rectal temperatures, and blood for serology. Twelve ferrets received a virus variant associated with the big brown bat (Epiesicus fucus) at concentrations that ranged from 104.1 to 103.4 MICLD50. Nine of 12 ferret were euthanatized with severe clinical signs of rabies. Mean incubation period was 20 days (range 16 to 22 d). Mean morbidity period was 3 to 4 days (range 2 to 6 d). Additionally, 12 ferrets received a rabies virus variant associated with the Brazilian free tailed bat (Tadarida brasiliensis) at concentrations that ranged from 104.7 to 103.7 MICLD5O. Ten of 12 ferrets were euthanized with severe clinical signs. Mean incubation period was 23 days (range 10 to 44 d). Mean morbidity period was 2 to 3 days (range 1 to 3 d). Common clinical signs of rabies included ataxia, paresis, paraparesis, and paralysis. Ferrets receiving the big, brown rabies virus variant had additional signs of lethargy, fever, and cachexia. One ferret from this group was aggressive. Ferrets receiving the Brazilian free tailed bat rabies virus variant had additional signs of vocalization and the majority of rabid ferrets had aggressive behavior. To date, nearly half of the ferrets receiving the big brown bat rabies virus variant had detectable rabies virus neutralizing antibodies at the time of euthanasia, and one survivor seroconverted, whereas, no ferret from the group given the Brazilian free tailed bat rabies virus variant was seropositive at euthanasia, and similarly 1 survivor seroconverted, In ferrets receiving the big brown bat rabies virus variant, rabies virus was isolated from the salivary glands of 2 of 9 ferrets euthanatized with severe clinical signs and one of these shed virus in their saliva (concomitant with clinical signs), whereas, virus was isolated from the salivary gland of only 1 ferret given the Brazilian free tailed bat rabies virus variant and no rabies virus was detected in saliva. To adequately ensure the publics health, continuing studies must be completed before any changes in ferret rabies control recommendations can be considered. [Posted in FML issue 2102]