Definition of Rabies
Rabies: A potentially fatal viral infection that attacks the central nervous system.
The rabies virus is carried primarily by wild animals, especially bats and raccoons. It finds its way to humans by direct contact with infected wild animals or by contact with domestic animals that have contracted the virus. Most cases of rabies
can be traced to animal bites, but cases have been
documented where the virus was inhaled in bat caves,
contracted in lab accidents, or received from transplanted
donor tissue.
The symptoms of rabies include fever, myalgia (aching muscles), and
headache, which can progress to inflammation of the
brain, confusion, seizures, paralysis, coma, and death.
There is no cure for rabies once it has settled in the
brain, so immediate emergency care for any suspicious
animal contact is a must. Rabies immunoglobulin (RIG)
shots, antibiotics, and rabies vaccine may be used
immediately after contact.
To prevent rabies, vaccinate all pets against the virus, and avoid contact with wild or unknown animals. A human rabies vaccine is available, but immunization with it is recommended only for people in high-risk occupations (game wardens, zookeepers, animal control officers, etc.).
Patterns of occurrence: The patterns of rabies have changed dramatically over the past 100 years. Before 1960 the majority of known animal cases of rabies in the US were in domestic animals. Now the principal hosts are wild carnivores and bats. The numbers of human deaths due to rabies in the US have declined from more than 100 annually at the turn of the 20th century to 1 or 2 per year in the 1990's. Contemporary prophylaxis has proven nearly 100% successful. In the US, human deaths from rabies are due to failure to seek medical assistance, usually because the individual was unaware of their exposure to rabies.
Public health costs: Even as the toll in disease has declined, the public health costs of rabies detection, prevention, and control have steadily risen, exceeding $300 million annually in the US. These costs include the vaccination of companion animals, animal control programs, maintenance of rabies laboratories, and medical costs, such as those incurred for rabies postexposure prophylaxis (PEP).
Cost of a course of postexposure prophylaxis (PEP): A course of rabies immune globulin and five doses of vaccine given over a 4-week period typically exceeds $1,000. The public health cost to save one human life from rabies ranges from approximately $10,000 to $100 million, depending on the nature of the exposure and the probability of rabies in a given region.
The genome of rabies: The rabies virus has an RNA genome of approximately 12 kb that consists of a leader (LDR) of 50 nucleotides, followed by N, P, M, G, and L genes that encode 5 proteins designated as N, P, M, G, and L. A viral polymerasease transcribes the negative strand of RNA into leader RNA and five capped and polyadenylated mRNAs, which are translated into proteins. Translation, which involves the synthesis of the N, P, M, G and L proteins, occurs on free ribosomes in the cytoplasm. Although G protein synthesis is initiated on free ribosomes, completion of synthesis and glycosylation (processing of the glycoprotein), occurs in the endoplasmic reticulum (ER) and golgi apparatus. The leader RNA and N protein ratio regulate the switch from transcription to replication, and synthesis of a full-length positive strand RNA. During replication, transcription is "non-stop"; the polymerase (L-P) has a single entry site on the 3' end of the genome, and proceeds to the 5' end of the genome ignoring all stop codons. This full-length positive strand acts as a template for the synthesis of a full-length negative strand.
The molecular biology of rabies: During the assembly process, the N-P-L complex encapsulates the negative genomic RNA strand to form the RNP core, and the M protein forms a capsule, or matrix, around the RNP. The RNP-M complex migrates to an area of the plasma membrane containing glycoprotein inserts, and the M-protein initiates coiling. The M-RNP complex binds with the glycoprotein, and the completed virus buds from the plasma membrane. Within the central nervous system (CNS), there is preferential viral budding from plasma membranes. Conversely, virus in the salivary glands buds primarily from the cell membrane into the acinar lumen. Specific viral budding into the salivary milieu, coupled with virus-induced behavioral changes, maximizes the chance of viral perpetuation through the directed bite and infection of a new host.
Last Editorial Review: 3/31/2002
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