Rabies-update on a global disease.

Rabies, a fatal viral zoonosis, persists in both developed and developing countries worldwide in spite of successful preventive public health measures and postexposure therapies. Considering the years of life lost, rabies ranks seventh among all infectious diseases in the world. Public health campaigns, emphasizing rabies immunization of pets and development of effective preand postexposure immunization regimens, have reduced acquired human rabiesrelated fatalities in the U.S. to less than 3 per year. These few cases almost always involve a bat variant of the rabies virus causing fatal encephalitis. Etiology. The RNA, neurotropic virus causing rabies has a bullet-shaped nucleocapsid surrounded by a lipoprotein envelope. The unique genetic patterns in the nucleocapsid and glycoprotein components of rabies virus isolates provide an opportunity through molecular techniques to identify reservoir hosts (eg, bat, dog, fox, raccoon, skunk) providing useful epidemiological data. Epidemiology. Each year, an estimated 55,000 people die of rabies in Africa and Asia where infection is endemic in dogs. In contrast, only 19 indigenously acquired rabies-related human fatalities were reported in the U.S. from 2000 to 2006, 17 of which were associated with rabies virus variants maintained by bats. Mass immunization of pet dogs and cats at an estimated annual cost of 300 million dollars in great part accounts for the low incidence of human rabies in the U.S. Wildlife, primarily raccoons, skunks, bats and foxes, accounted for more than 92% of all animal rabies cases reported to the CDC in 2005. Oral rabies vaccine projects are being evaluated to control rabies in wildlife in Texas, Florida, Alabama and Ohio with over 4.1 million baits distributed in July of 2006. Transmission. Transmission requires introduction of rabies virus from saliva or infected neural tissue into bite wounds or open cuts in skin or mucous membranes. Minor, possibly unrecognized bites from bats (contributing to inaccurate recall), appear to have played a role in recent human fatalities in the U.S. Human to human transmission of rabies has been described in 8 patients receiving corneal transplants and, recently, 4 U.S. patients receiving organ transplants (lung, liver, and kidney) from one donor, raising new questions about tissue tropism and rabies screening of organ and tissue donors. Clinical Signs. The incubation period ranges from 2 weeks to 6 years, averaging 2 to 3 months, depending upon inoculum and proximity to the brain. Viral replication at dorsal root ganglion causes the first clinical sign of neuropathic pain near the inoculation site. The virus migrates to the central nervous system at 15–100 mm per day and then outward within peripheral nerves infecting adjacent organs such as salivary glands with viral shedding in saliva. Two clinical presentations, furious form (anterior horn cell dysfunction) and paralytic form (peripheral nerve dysfunction), lead to death within 5 days without intensive care. Diagnosis. Diagnosis based on clinical signs of phobic spasms (hydroor aerophobia), paralytic or Guillaine–Barrelike syndrome, or excitation is difficult and unreliable especially considering that typical or nonclassic rabies is being increasingly recognized. Magnetic resonance imaging, specifically hypersignal T2 images in brainstem, hippocampus, hypothalamus, deep subcortical and cortical white and gray matter, respectively, as well as gadolinium enhancement contribute to a rabies diagnosis. Antigen detection using fluorescent antibody test in skin biopsies taken from From the Department of Comparative Medicine, University of Rochester, Rochester, NY. Copyright © 2007 by Lippincott Williams & Wilkins ISSN: 0891-3668/07/2604-0351 DOI: 10.1097/01.inf.0000258776.47697.97 CONTENTS Rabies Update Autoinflammatory Syndromes