Rhabdoviruses

Rhabdoviridae Rhabdos (greek)rod Pathogens of mammals, birds, fish, plants

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Rhabdoviridae Vesiculovirus (VSV) Lyssavirus (rabies & rabies-like V) Plant rhabdovirus group Ungrouped rhabdoviruses

Rabies virus Unique features of Rhabdoviruses Bullet-shaped Enveloped Negative, single-stranded RNA Prototype for (-) RNA viruses Replication in the cytoplasm

Rabies virus/Disease Mechanisms Rabies is usually transmitted in saliva and is acquired from the bite of a rabid animal Virus is not very cytolytic and seems to remain cell-associated Virus replicates in the muscle at the site of the bite with minimal or no symptoms The length of the incubation phase is determined by the infectious dose and the proximity of the infection site to the CNS and brain

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Rabies virus/Disease Mechanisms After weeks to months, the virus infects the peripheral nerves and travels up the CNS to the brain (prodrome phase) Infection of the brain causes classic symptoms, coma, and death (neurologic phase) During the neurologic phase, the virus spread to the glands, skin, and other body parts, including the salivary glands, from where it is transmitted

Rabies virus/Disease Mechanisms Antibody response at the late stages Antibody can block the progression of the virus The long incubation period allows active immunization as a postexposure treatment

Rabies virus/Epidemiology Disease/Viral factors  Virus induced aggressive behavior in animlas promotes virus spread  Disease has long asymptomatic period

Rabies virus/Epidemiology Transmission  Zoonosis Reservoir: wild animals Vector: wild animals and unvaccinated dogs and cats Source of virus:  Major: saliva in bite of a rabid animal  Minor: aerosols in bat caves containing rabid bats

Rabies virus/Epidemiology At risk:  Veterinarians and animal handlers  Person bitten by a rabid animal  Inhabitants of countries with no pet vaccination program

Rabies virus/Epidemiology Geography/Season  Worldwide  Except in some island nations  No seasonal incidence

Rabies virus/Epidemiology Modes of control  Vaccination For pets For at-risk personnel “Vaccination program have been implemented to control rabies in forest mammals”

Rabies virus/Laboratory diagnosis Occurence of neurologic symptoms in a person who has been bitten by an animal... too late... Laboratory tests are usually performed to confirm the diagnosis and to determine whether a suspected individual or animal is rabid post mortem

Rabies virus/Laboratory diagnosis Ag detection (IF) Isolation Serologic In: CNS or Skin Negri bodies: intracytoplasmic inclusions consisting of aggregates of viral nucleocapsids in affected neurons.

Rabies virus/Treatment & Prophylaxis Clinical rabies is almost always fatal unless treated Only hope:  Post exposure prophylaxis  For anyone exposed by bite or by contamination of an open wound or mucous membrane to the saliva or brain tissue of an animal suspected to be infected with the virus

Rabies virus/Treatment & Prophylaxis First protective measure  Local treatment Washing(soap and water) Rabies antiserum Then  Vaccination  Ig - human rabies immunoglobulin (HRIG) or equine antirabies serum ( EAS)

Rabies virus/Treatment & Prophylaxis Vaccine  Cell culture vaccine  HDCV On, days

Treatment Clinical rabies is almost always fatal unless treated. Once the symptoms have appeared, little other than supportive care can be given. Postexposure prophylaxis is the only hope for preventing overt clinical illness in the affected person. Although human cases of rabies are rare, approximately 20,000 people receive rabies prophylaxis each year in the United States alone. Prophylaxis should be initiated for anyone exposed by bite or by contamination of an open wound or mucous membrane to the saliva or brain tissue of an animal suspected to be infected with the virus, unless the animal is tested and shown not to be rabid.

Prophylaxis The first protective measure is local treatment of the wound. The wound should be washed immediately with soap and water or another substance that inactivates the virus. The World Health Organization Expert Committee on Rabies also recommends the instillation of antirabies serum around the wound. Subsequently, immunization with vaccine in combination with administration of one dose of human rabies immunoglobulin (HRIG) or equine antirabies serum is recommended. Passive immunization with HRIG provides antibody until the patient produces antibody in response to the vaccine. A series of five vaccinations is then administered over the course of a month. The slow course of rabies disease allows active immunity to be generated in time to afford protection.

The rabies vaccine is a killed-virus vaccine prepared through the chemical inactivation of rabies infected-tissue culture human diploid cells (HDCV) or fetal rhesus lung cells. These vaccines cause fewer negative reactions than the older vaccines (Semple and Fermi), which were prepared in the brains of adult or suckling animals. The HDCV is administered intramuscularly on the day of exposure and then on days 3, 7, 14, and 28 or intradermally with a lower dose of vaccine to multiple sites on days 0, 3, 7, 28, and 90. There is one case of successful cessation of disease progression by postexposure ribavirin treatment.

Preexposure vaccination should be performed on animal workers, laboratory workers who handle potentially infected tissue, and people traveling to areas where rabies is endemic. HDCV administered intramuscularly or intradermally in three doses is recommended and provides 2 years of protection.

Ultimately the prevention of human rabies hinges on the effective control of rabies in domestic and wild animals. Its control in domestic animals depends on the removal of stray and unwanted animals and the vaccination of all dogs and cats. A variety of attenuated oral vaccines have also been used successfully to immunize foxes. A live recombinant vaccinia virus vaccine expressing the rabies virus G protein is in use in the United States. This vaccine, which is injected into bait and parachuted into the forest, successfully immunizes raccoons, foxes, and other animals. Accidental injection of a woman with this vaccinia-rabies hybrid vaccine resulted in immunization against both smallpox and rabies viruses (see references).

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