Dania JaradatTiffany Chang

Family: Rhabdoviridae Enveloped (-) ssRNA virus Rod or “bullet” shaped Approximately 70x180 nm Coiled nucleocapsid into cylindrical structure RNA genome codes for N, P, M, G, L Replication occurs in the cytoplasm inside

Negri Bodies

Genus: Lyssavirus

What is rabies virus? An acute, central nervous system

infection characterized by CNS irritation, paralysis, and death

Found worldwide, except for Antarctica due to isolation

How is it transmitted? Animal bite – saliva of infected

animals▪ Dogs, bats, coyotes, foxes, raccoons,

skunks, etc.

Two forms: Furious rabies (encephalitic)

Replication in the hippocampus, amygdala, anterior thalamic nuclei, and limbic cortex

Headaches, high fever, irritability, restlessness and anxiety, muscle pain, excessive salivation and vomiting

Dumb rabies (paralytic) Replication in the neocortex Depression, isolation, paralysis

Five general stages: (1) incubation period (2) prodrome (3) acute neurologic

period (4) coma (5) death (or rarely,

recovery)

http://www.ncbi.nlm.nih.gov/books/NBK8618/

Fever Headache Fatigue Loss of appetite Nausea/ vomiting Sore throat Nonproductive cough Irritability Malaise Pain/ paresthesia (abnormal burning sensation)

Anxiety Irritability Confusion Hallucination Hydrophobia Aerophobia Hyperactivity Seizures Focal and generalized convulsions Paralysis Hyperventilation Hypersalivation

An 11-year-old boy was brought to a hospital in California after falling; his bruises were treated and he was released. The following day he refused to drink water with his medicine, and he became more anxious. That night he began to act up and hallucinate. He also was salivating and had difficulty breathing. Two days later, he had a fever of 40.8°C (105.4ºF) and experienced two episodes of cardiac arrest. Although rabies was suspected, no remarkable data were obtained from a computed tomographic image of the brain or cerebrospinal fluid analysis. A skin biopsy from the nape of the neck was negative for viral antigen on day 3 but was positive for rabies on day 7. The patient’s condition continued to deteriorate, and he died 11 days later. When the parents were questioned, it was learned that 6 months earlier, the boy had been bitten on the finger by a dog while on a trip to India.

An 11-year-old boy was brought to a hospital in California after falling; his bruises were treated and he was released. The following day he refused to drink water with his medicine, and he became more anxious. That night he began to act up and hallucinate. He also was salivating and had difficulty breathing. Two days later, he had a fever of 40.8°C (105.4ºF) and experienced two episodes of cardiac arrest. Although rabies was suspected, no remarkable data were obtained from a computed tomographic image of the brain or cerebrospinal fluid analysis. A skin biopsy from the nape of the neck was negative for viral antigen on day 3 but was positive for rabies on day 7. The patient’s condition continued to deteriorate, and he died 11 days later. When the parents were questioned, it was learned that 6 months earlier, the boy had been bitten on the finger by a dog while on a trip to India.

An 11-year-old boy was brought to a hospital in California after falling; his bruises were treated and he was released. The following day he refused to drink water with his medicine, and he became more anxious. That night he began to act up and hallucinate. He also was salivating and had difficulty breathing. Two days later, he had a fever of 40.8°C (105.4ºF) and experienced two episodes of cardiac arrest. Although rabies was suspected, no remarkable data were obtained from a computed tomographic image of the brain or cerebrospinal fluid analysis. A skin biopsy from the nape of the neck was negative for viral antigen on day 3 but was positive for rabies on day 7. The patient’s condition continued to deteriorate, and he died 11 days later. When the parents were questioned, it was learned that 6 months earlier, the boy had been bitten on the finger by a dog while on a trip to India.

Inoculation of virus at site of wound Replication occurs in

muscle tissue near the bite

Entry into sensory nerve endings of PNS

Advances to CNS, reaching dorsal root ganglia and spinal cord Causes trademark

encephalitis

Spreads to salivary glands and other organs

Most commonly, lasts 3-8 weeks But, can be as short as few days or long as >2 years

Depends on several factors Site of bite wound Proximity to CNS Severity of bite Type of virus Quantity of virus Age of patient Immune status of host

The long duration of the incubation period is what makes post-exposure rabies treatment effective

Post-exposure prophylaxis Local treatment of the wound▪ Flushing and washing for a minimum of 15 minutes with soap, water,

detergent, or iodine

Administration of Human Rabies Immunoglobulin (HRIG), if indicated▪ Only given once on first day of PEP regimen (designated day 0)▪ Dosage given calculated based on subject’s weight (20 IU/Kg body

weight)▪ Infiltrated around the wound or intramuscularly at a different site from

vaccine▪ Should not be given if previously vaccinated

Course of potent and effective rabies vaccine (human diploid cell, purified chick embryo cell, or rabies vaccine adsorbed) ▪ 1 mL doses given intramuscularly in the deltoid area (adults) or in the

thigh region: days 0, 3, 7, 14 ▪ An additional 5th dose is administered on day 28 to immunosuppressed

patients▪ If previously vaccinated, 2 doses given on: days 0, 3

http://www.who.int/mediacentre/factsheets/fs099/en/index.html

Question the parents about patient’s history Presence of any flu-like symptoms? (prodromal

period) Animal – wild or domesticated, location?

Once symptoms appear, very rare survival rate▪ Usually caused by death from respiratory failure within

7 days of the symptoms▪ If untreated, can lead to coma

Direct fluorescent antibody test (dFA) Confirm the presence or absence of rabies

antigen in tissue or saliva

Tests are performed on samples of: Saliva Serum Spinal fluid Hair follicles Skin biopsy

Amplification of sample by virus isolation and reverse transcriptase polymerase chain reaction (RT-PCR) Can confirm dFA results and detect rabies virus in

saliva and skin biopsy samples

Rabies differs from other neurological viruses because it has: a complete different strategy for

virus pathogenesis and spread▪ Rabies is spread by animal bites,

thus behavioral changes (i.e. excitability, irritability, etc.) induced by the virus are important for spread

▪ High replication of rabies in salivary glands of rabid host makes the infected animal a walking “time bomb”

100% mortality rate (if not treated)

Many common viruses that cause encephalitis have low neuroinvasiveness, but high neurovirulence Neuroinvasive: can enter the CNS after infection of a

peripheral site Neurovirulent: can cause disease of the nervous tissue

Rabies has both high neuroinvasiveness and high neurovirulence Neuronal spread is the definitive characteristic of

pathogenesis

Examples of neurological viral diseases Mumps virus ▪ High neuroinvasiveness, low neurovirulence▪ Enters the CNS, but has mild symptoms

Herpes simplex virus▪ Low neuroinvasiveness, high neurovirulence▪ Enters the PNS (rarely CNS)

http://www.ncbi.nlm.nih.gov/books/NBK8618/ http://pathmicro.med.sc.edu/virol/rabies.htm http://www.cdc.gov/rabies/index.html http://www.who.int/mediacentre/factsheets/fs099/en/index.html