a Virology 12 Zoonoses and Prions

- spread from animals to humans (dead end host, we are not reservoirs)
- more than 50% of the viruses known to infect man are zoonotic
- spread by vertebrates by biting, contaminated excreta
- also spread by invertebrates, like mosquitoes, ticks, sandflies

- most established for years in small, isolated animal populations
-Viral changes
a) reassortment (influenza), recombination (WEE virus), point mutation (chicken influenza)
b) travel (smallpox, syphilis, dengue), or behavioor(STDs)
c) Vector changes: mosquitoes change range (yellow fever), birds migrate (West Nile virus)
d) Environment changes: irrigation (Rift Valley Fever), agriculture (Argentine HF), natural climate changes(hantaan virus)

virus enters the body(via injection) and replicates locally -> transient viremia
-> infection of RES -> secondary viremia
-> prodromal symptoms of fever, chills, headache, muscle ache, malaise
-> after incubation period (2-14 days), other organs can infect -> more serious disease may occur

1) Inapparent infection is most common
2) Fever, chills, headache, back pain, muscle and joint pain, with or without a rash appearing on the third or fourth day
3) if rash, slow convalescence (1o dengue fever, Colorado tick fever)
3a)possibly hemorrhagic fever w/ blotches and orifice bleeding
-may die from hypotensive shock (Dengue hemorrhagic fever/ Dengue shock syndrome, Ebola virus)
-kidney targeted in hemorrhagic fever with renal syndrome
-liver targeted in yellow fever
3b)symptoms of (2)(w/o rash) followed by acute respiratory syndrome w/ edema (SARS and Hanta pulmonary syndrome)
3c)head-ache, fever, chills, malaise -> encephalitis (EEE, WEE West Nile, SLE)

- difficult initially
- easier as specific organs are targeted.
- take a complete history
- travel, pets, hobbies or jobs that might expose the Pt to animals or insects
- Serology, PCR

- Vectors are rodents (Lassa fever, Hantavirus with renal syndrome, Argentine HF, Bolivian HF) - Arthropods (Yellow fever, dengue, Rift Valley fever) - Ebola and Marburg viruses have unknown vectors - Human to human spread in Ebola, Marburg and Lassa fevers

- supportive – restore physiology and nutrition - Ribavirin for arenaviruses (Lassa fever, Argentine and Bolivian HF) and bunyaviruses (hemorrhagic fever with renal syndrome) - Vaccines available for yellow fever and Rift Valley fever - Dengue vaccine most needed and most problematic – must get all 4 strains or it will increase your likelihood

- Sin Nombre (Hantaan virus) gets mice in Americas w/ no apparent ill effects - shed in urine and stool, transmitted to humans via aerosol - SARS coronavirus from palm civet cats (probably) - both spread via human to human

- Rodent control, exposure control - No drugs

- EEE, WEE, SLE, West Nile - Mosquito vectors, so usually seasonal - we are dead end host - Migratory birds play an important role

- Rodent control, exposure control - Supportive care - immune serum might help - no drugs or vaccine

- saliva of infected animal - multiplies in striated muscle and CT (days -> months) - reaches nerve endings _> passively spread in axoplasm to spinal ganglia and replicates -> faster pace to the spinal cord -> brain -> salivary glands via efferent nerves

- 2-8 wk incubation depending on amt of inoculum, virulence, proximity to neural tissue (head and neck wounds the worst) - 2-4 day prodromal period - 1st fever, headache, malaise, sensations at the wound site - then increased irritability, anxiety, depression, sensitivity to sound and light - difficulty swallowing - generalized encephalitis develops and is always fatal

- in resource-poor nations, mainly from domesticated animals (dogs) - in developed countries from wild animals (vaccination) - 74% in US from bats - rapidly increasing epidemic in SE US in raccoons and foxes

- definitive diagnosis from post-mortem examination of the animal - neck biopsy can be used in symptomatic humans - darkly-staining viral nucleocapsids (Negri bodies) in cytoplasm of CNS cells

- vaccination of domestic animals - wound site immediately cleaned to and injected w/ human rabies hyperimmune globulin to neutralize slow growing virus - attempt to develop active immunity in the exposed person with a vaccine

- transmitted by inoculation or ingestion of diseased nervous tissue - incubation can last decades - death is usually months after symptoms appear - loss of motor control, dementia, wasting, with progressive loss of brain function -> death - large vacuoles in the cortex and cerebellum

- prion disease - small, proteinaceous infectious particle that resists inactivation by procedures that modify nucleic acid - the altered protein (PrPsc) forces normal proteins (PrPc) in alpha helices into abnormal or beta sheets -> fibrils and amyloid plaque - very hard to inactivate (remember the brains in lab)

- rapidly fatal, presenile dementia of old people - memory loss w/ confusion, vertigo, blurred vision -> dementia and motor Dysfunction - usually acquired sporadically, but some genetic from amyloid precursor protein mutation - can be transmitted by surgical instruments, transplanted dura and corenea - no immune response, no treatment , and no recovery or remission

- scrapie is a naturally occurring spongiform encephalopathy of sheep - developed from feeding cattle scrapie-infected sheep by-products - Mad Cow Disease - may have adapted to be more stable in humans

- like CJD, but ataxia and memory loss more common - younger age group (16-45 years), mainly in UK - methionine homozygosity at position 129 of the prion protein predisposes to CJD, kuru, and vCJD - possibly from exposure to BSE - similar glycosylation patterns, abundant, distinct amyloid plaques in both, and mice inoculated w/ either show similar disease