CNS Infections- Rabies Virus Flashcards
Rabies Dx is an acute, fulminant, fatal, _________ due to infection of brain and spinal column. This virus can infect nearly all mammals and is transmitted between them by ________ and is fatal to virtually all humans and nearly all mammals. Human survivors are very rare.
focal encephalitis and myelitis
infected secretions, usually saliva
Rabies description
- a neurotrophic virus
- Rhabdoviridae group, a Lyssavirus
- a (-) ssRNA, bullet–shaped virus (enveloped with helical symmetry)
- Single serotype (one major surface antigen)
- Each virus possess many copies of a single glycoprotein peplomer which is specific for the brain, alter one amino acid in the glycoprotein results in an attenuated strain
Virus replicates in the cytoplasm, forming _________ consisting of viral nucleoprotein
(Negri bodies)
eosinophilic cytoplasmic inclusions
Transmitted by
Animal bites or scratches, contact with animal saliva or excretions
- Inhalation of aerosols, e.g., bat droppings
- Transplants (Corneal, others) is rare
Control of human rabies is contingent on control of __________
dog and cat rabies
Worldwide, infected dogs are the most important source of infection for humans
most common source of rabies today in US
Bats
Pathogenesis: Virus is injected/passes through the epidermis (at the bite or lick site) and initially replicates in __________. When the virus titer is high enough, it enters the ________ at unmyelinated sensory terminals and neuromuscular junctions where it is ___________
the adjacent striated skeletal muscle
peripheral nervous system (PNS)
sequestered from the immune system
Pathogenesis: Virus travels slowly (mm per day) by retrograde axoplasmic flow (like polio and herpes viruses) up the nerves to the _____________________. The slow axoplasmic flow accounts, in part, for the long incubation period for person with a bite which occurred at a site far from the brain/CNS.
CNS where it disseminates via transynaptic spread first to the spinal chord and then rapidly to the brain.
Pathogenesis: The virus predominates in the _______, but localizes in the _________, and also infects neurons in almost all brain areas.
Virus then travels back down the autonomic nerves to the _________ (6 locations)
Gray matter
limbic region (focal symptoms)
salivary glands, cornea, lungs, adrenal medulla,
kidneys, bite site
The patient is considered to be potentially infectious during the period from ____ before onset of symptoms (when humans can begin to shed rabies virus in saliva and tears) until his/her death.
2 weeks
The moment the virus enters sensory terminals & neuromuscular junctions, the pt. _________, because the virus is sequestered from ________. Explains importance of post-exposure prophylaxis - it can prevent an infected person from developing rabies!
will eventually die
rabies-specific Ab (and the immune system)
The virus can spread throughout the body, but is never isolated from _________.
the blood
Prodrome is nonspecific flu-like illness lasting 2→4 d and includes:
fever, headache, malaise, nausea and vomiting, loss of appetite/anorexia, anxiety, pain, itching, paresthesias at bite site, if one exists
Describe disease
- usually 5 → 6 days and is always fatal.
- Highly variable presentation: One person may present with paralytic symptoms, another may present with all stages from prodrome to paralytic, while another may lack one or more stages.
Paralytic/Dumb rabies form S/S:
- Less common manifestation (20%)
- S/S are indistinguishable from viral encephalitis
- Patient manifests with paralysis starting at extremities and then spreads to the trunk.
- Paralysis leads to hypoventilation (inhibition of the pharyngeal and respiratory center of brain causes respiratory paralysis), hypotension (cardiac failure), eventually coma and death
Neurological phase/Excitation-Furious form:
- More common manifestation (80%)
- Increased sensory sensitivity to external stimuli (light/photophobia; sound/phonophobia)
-Encephalitic symptoms - CNS dysfunction:
hyperactivity, loss of natural timidity, aggressive sexual behavior (focal signs), agitation, anxiety, insomnia, confusion, delirium, hydrophobia and foaming at the mouth arise from excruciatingly painful, laryngeal spasms which occur when the patent tries to swallow so that excessive salivation is really failure to swallow their own saliva
-Signs and symptoms → coma → death
CSF shows
protein and glucose levels as per viral infection and mononuclear pleocytosis
Can show there are intracytoplasmic viral inclusions via direct fluorescent antibody (DFA) testing using:
- corneal impression smears
- skin biopsy from nape of neck
- brain biopsy - the definitive test
A negative DFA test on animal brain specimen means virus is not in saliva, thus no post-exposure prophylaxis is needed.
Isolation of virus via _________ is very sensitive and required by law in some states…
Isolation of virus via mouse inoculation is very sensitive and required by law in some states in cases of human exposure to a potentially rabid animal.
Cerebral inoculation of mice with brain tissue from sacrificed, captured animal should result in encephalitis and death of mouse in 3→10d
Can test for _______ to prove rabies is present
**Negri bodies – Rabies virus inclusion bodies
Treatment and Prophylaxis
Treatment: None – so called Milwaukee Protocol is not reproducible
Pre-exposure management and prophylaxis: Prevention is mainstay of controlling human rabies
For people at risk, CDC says pre-exposure prophylaxis by vaccination should occur for:
- veterinarians.
2. spelunkers.
3. laboratory workers.
4. animal handlers.
Vaccination/Pre-exposure prophylaxis protocol is
3 doses IM in deltoid muscle in adult or anterolateral zone of thigh in children
Post-exposure protocol for someone who received pre-expsoure prophylaxis is
3 doses IM in deltoid muscle in adult or anterolateral zone of thigh in children.
People provided pre-exposure vaccination, who were bitten by a rapid dog and then failed to receive appropriate post-exposure prophylaxis ______
died
Vaccination is NEVER done as a ________
gluteal injection → neuropathy, lower antirabies antibody titers, true for both Pre- and Post-exposure vaccination!!!!
Post-exposure management: It is efficacious (it works), if done _________
properly, in time!! “But treatment is an urgency, NOT an emergency”
Knowledge of the animals in which rabies is endemic and the geographic distribution/range and where the reserves are is imperative when considering initiation of prophylaxis in a case of human exposure.
Immediate and through __________ is of primary importance
cleansing of the wound(s) with soap and water
_______ must be done unless patient is protected by appropriate immunization
Tetanus prophylaxis
Vaccination + antirabies serum. Must do both unless pre-exposure prophylaxis is done Describe:
- Human antirabies immune globulin (HRIG)
- 2 forms: HyperRab & Imogam
- from hyperimmunized human donors
* *Given at the same time as the vaccine but at a different site:** Half of the dose IM in gluteal region, Half of the dose should be injected in and around the wound site. - Human diploid cell strain rabies vaccine (HDCV)
-2 forms used in US: HDCV and purified chick embryo cell vaccine (PCECV, RabAvert)
-Both are killed vaccines (by chemical treatment)
Administer vaccine: IM in deltoid muscle in adult, anterolateral zone of thigh in young children, on 5 days: 0, 3, 7, 14, 28→30
(7 shots)
Observe biting animal for ___________
10 d for symptoms, rabid animals (dogs) die in 4→5d
