2. When it disseminates to the CNS, it can cause meningoencephalitis, h/a, lethargy, altered mental status. This is more common among those immunocompromised.
How do you treat Cryptococcus species?
Start with Amphotericin B + Flucytosine;
Fluconazole for suppression of cryptococcosis.
How do you prevent C. neoformans?
Immunocompromised people should avoid areas of high bird droppings and birds in general.
What is the life-cycle of Cryptococcus species?
Asexual: the budding basidiospore form.
Sexual: only seen in the lab; conjugation.
What is the organism that causes tape worm in humans after ingesting infected pork?
Describe the lifecycle of T.solium
The tapeworm has 2 stages:
1. Sexual reproduction in the definitive host (humans)
2. Asexual reproduction in the intermediate host (swine + humans)
What is the transmission path of T.solium?
1. Pigs/cattle ingest the eggs + proglottids from the environment.
2. Eggs hatch and penetrate the animals' intestines and makes it way to organs, such as muscles, brain, and eyes. The oncospheres develop into cysticerci here.
3. Humans consume infected undercooked meat and the cysticerci uses its scolex to attach to the intestines to develop into adult tape worm. Additionally, may travel lymphohematogenously to other organs.
4. Egg production and proglottid segments released via human feces and ultimately to the environment again.
What is the pathology of T.solium?
The proglottids rupture within the host intestine, causing the larvae to migrate to tissue and causing cysticercosis.
What are the clinical manifestations of T.solium?
GI issues: abdominal pain, loss of appetite, weight loss.
Cysticercosis: happens via autoinfection; cyst formation in the brain, eyes, and muscles. Neuorocysticercosis symptoms include headaches, dementia, dizziness, and seizures. It is the most common cause of acquired epilepsy in the developing world.
How do you treat T.solium?
How do you treat cysticercosis?
1. Antiparasitic: Praziquantel
2. #1 + corticosteroid --dying cysticerci may cause inflammatory response.
How do you diagnose T.solium?
How do you diagnose cysticercosis?
1. The proglottids are visible in a stool sample.
2. CT/MRI, biopsy or immunoblot.
How do you prevent T.solium?
COOK YOUR PORK CORRECTLY.
When would anti-parasitic drug be ineffective for T.solium?
When the cysts are already dead (calcified) within the body.
What organism causes toxoplasmosis?
T. gondii, an obligate intracellular parasite (sporozoan).
What are the definitive and intermediate hosts for T. gondii?
Definitive host: domesticated cats; sexual reproduction occurs in this host.
Intermediate host: humans and other warm-blooded mammals; asexual reproduction occurs in these host.
How is T. gondii transmitted?
1. Handling cat feces in the litter box.
2. Environment/gardening near cat feces.
3. Bigger animals eating infected cats.
4. Vertical transmission from mom to baby
5. Blood transfusions (rare).
What are the 3 stages of how T. gondii can exist?
1. Trophozoite: rapidly dividing and invasive. The tachyzoites look crescent shaped.
2. Bradyzoite: slow dividing; resides in tissue cyst within body to evade immune response.
3. Sporozoite: protected from environment by residing in the oocyte.
What is the pathology of T.gondii?
Ingested sporozoite --> intestinal cells --> GI proteases release free parasites --> mature tachyzoites that multiplies a lot --> continues multiplying in tissue cyst (bradyzoite) to avoid immune system --> ruptures when cell dies --> can invade monocytes --> dissemination.
What are the clinical presentation of T. gondii?
-Mostly asymptomatic and very common.
-Self-limiting mono-like disease, fever, and lymphadenopathy.
-For immunocompromised, highly lethal.
-Congenital: stillbirth, abortion, neonatal disease that can present later in life.
How do you diagnose T. gondii?
1. Detection of specific T.gondii IgG, IgM, IgA
2. PCR amniotic fluid
3. See the parasite on a tissue section stain
4. CT: for lesions in AIDS patients--encephalitis.
How to you treat T. gondii?
Anti-parasitic drugs, however these are only supportive since the tissue cysts are resistant.
How do you prevent T. gondii?
Hand washing after handling litter box, gardening outside, etc.
Why do we not have an immune response to prions?
Prions are neither virus nor bacteria. It is an infectious protein that is very resistant to being killed.
What types of diseases can be caused by prions? (animals + humans)
Scrapies: goats and sheep
CJD, vCJD, kuru, FFI, GSS: humans
What is the pathology for prions?
There is a post-translational change in the cellular protein PrPc --> PrPsc that causes it to change its shape from alpha helices to beta sheets. This allows the prion to spread and vacuolization of neurons to occur --> neuronal death.
How do you diagnose for prions?
1. CSF analysis
2. Western blot for PrPsc
4. protein assay
What is the treatment for prion diseases?
There is no treatment.
How do you prevent prion diseases?
1. Ban animal products in feed.
2. Sterilize hospital equipment (latrogenic CJD)
How does one acquire vCJD?
By eating infected cow meat
How does one acquire kuru?
By ingesting infected human tissue
What is the most common way to get CJD?
1. sporadic via somatic mutation (most common)
2. Latrogenic --via bad grafts, dirty electrodes
How do you get FFI?
It's genetics, and you die from insomnia and dementia.
Describe the morphology of HIV
Has core viral enzymes:
RT - reverse transcriptase
PR - protease
IN - integrin
Why would you get a negative Ab test early during HIV infection?
There is a lag time where viremia>Ab but the person is still infectious.
What are the 2 types of HIV, and which is more common?
HIV-1: more common; has many subtypes including M,N,O,P.
HIV-2: less common, primarily found in W. Africa. Harder to detect but not as aggressive.
How does the term quasispecies apply to HIV?
Within the same host, HIV can evolve due to:
1. high mutation rate during replication
2. Template switching due to being diploid
3. high replication rate
= new variants formed within the host.
What are some clinical manifestations of HIV?
Neurologically: cognitive and behavioral symptoms such as--decline in memory, concentration, weakness and tremors. Depression and dementia.
HIV mechanism of pathology
Kills CD4+ T-cells, making the body susceptible to opportunistic infections
How do you diagnose HIV?
1. immunoassay for IgM initially
3. Western blotting
How do you treat HIV?
ART/HAART--because HIV mutates so fast, you want to inhibit as many targets as you can; such as the core viral proteins + adhesion
How do you prevent HIV?
Less risky behavior
Don't share needles
What is the organism that causes syphilis?
T. pallidum, a spirochete that is very infectious and has low antigenicity (doesn't really trigger immune response)
What are the stages of syphilis, and the clinical presentations involved?
Primary: lesion that heals
Secondary: rash that heals; systemic infection with variable lesion manifestations. Latency some time around here
Tertiary: focal lesions with that can cause neurosyphilis and damages to the parenchyma of the brain and spinal cord
How is syphilis transmitted?
1. sexual contact with infectious lesions
2. vertical transmission
3. blood product transfusion
How do you diagnose syphilis?
-Don't culture it, it's too slow
-Analysis of CSF --especially if the eye or brain is involved or it's in the tertiary stage, or patient is HIV+.
How do you treat syphilis?
It is sensitive to PCN--which is also why you don't see many tertiary cases in the U.S
How do you prevent syphilis?
Don't come into contact with the lesions
What is the morphology of rhabdovirus (rabies)
-Brings its own RNA-dep-RNA-pol
How is rabies usually transmitted?
Contact with infected nervous tissue
What is the pathology of rabies?
Rabies virus replicates at the site of inoculation - muscle/CT --> enters peripheral nerves --> CNS --> ENCEPHALITIS --> peripheral nerves --> disseminates.
What are the clinical presentation of rabies?
Initially: fever, headache, weakness, discomfort
Later on: insomnia, agitation, hydrophobia, hypersalivation --> death in a few days.
How do you diagnose rabies?
1. Presence of negri bodies/cytoplasmic inclusion
3. CSF for antibodies
4. Skin biopsy at site of bite
How do you treat rabies?
If rabies is suspected, give post-exposure anti-rabies vaccine.
How do you prevent rabies?
Pre-exposure anti-rabies vaccine for spelunkers and vets.
What disease must you have had in order to get SSPE? (subacute sclerosing panencephalitis)
Measles --usually wild-type and not from vaccine
When does SSPE usually appear?
7-10 years after initial measles infections
What are the stages of SSPE?
Stage 1: Treatable at this stage; impaired memory, abnormal behavior, myoclonic spasms and jerks.
Stage 2: Increased intensity of spasms and mental deterioration
Stage 3: Decline in body function, blindness, mute, comatose.
What is the pathophysiology of SSPE?
It is a degenerative CNS disease characterized: 1. Change in personality --> convulsions --> dementia --> death.
2. Diffuse encephalitis with sclerosing inflammation of gray and white matter.
3. Presence of viral nucleocapsid in the cytoplasm of neurons and glial cells. No envelope = no immune response
How do you treat SSPE?
Antivirals: Ribavirin + interferon
What causes PML and what does it affect?
(Progressive multifocal leukoencephalopathy)
JC virus; Demyelinates the white matter
What is the pathophysiology of PML?
Inhalation of virus causes infection in the tonsils --> travels to the kidneys and bone marrow where it remains latent --> reactivation --> neuroinvasion by crossing blood-brain barrier via B-cells --> infects oligodendroglia.
Who is susceptible to PML?
Describe aseptic meningitis?
1. Usually associated with virus, but is not always caused by a virus.
2. Presence of mononuclear pleocytosis
What are some causes of viral meningitis?
What are some causes of viral encephalitis?
What are positive Kernig's and Brudzinski tests indicative of?
1. All herpesvirus establish latency.
2. Circularizes its genome
3. Resides in the sensory neuron where immune response is lacking.
4. Silences all lytic gene expression, expresses only LAT (latency assoc. transcript) to suppress viral replication
5. Blocks apoptosis
6. Reactivation occurs upon immune stress.
Compare reservoir v. vector
Reservoir: the source of infection; infects the vector.
Vector: what transports/transmits the agent.
Yellow Fever Virus (Flavivirus) Clinical signs
Most are asymptomatic or have mild systemic symptoms. 15% progress to severe symptoms including: hemorrhagic fever, jaundice, bleeding, shock, and multiple organ failure.
Yellow Fever Virus Pathogenesis
Vector = mosquito --> replicates in lymph nodes and infects dendritic cells --> liver --> degradation of cells (presence of necrotic mass) --> release of cytokines.
Yellow Fever Virus
Clinical diagnosis--location is tropical and subtropical S. America + Africa.
Blood culture (1-4 wks)
Yellow Fever Virus Treatment and prevention
No treatment, just relief of symptoms.
There is a vaccine.
Dengue Fever (Flavivirus) Clinical signs
Mild fever --> high fever, severe headache, pain behind eyes, muscle and joint pains.
Febrile illness is the most common--fever, chills, headaches, pain behind eyes.
2 stages of fever: 2nd stage is high fever + increased symptoms.
Vector: wood tick
Hosts: squirrels, chipmunks, rabbits, deers
Bite at site --> lymph --> blood --> CNS
Blood work: virus can live in blood for 6 months
No specific treatment, but remove the tick if still attached.
Don't go hiking or camping in the Rocky Mtns.
It is seasonal and occurs mostly during the summer.
Avoid tick-infected areas
Wear proper attire if you must hike.
California Encephalitis Virus Group (CEV) Bunyavirus (Midwest, SE states) Clinical symptoms
Children: fever, drowsiness, lack of mental alertness + orientation. Encephalitis, seizure in 50% of children affected.
Adults: asymptomatic, mild fever.
Vector: mosquito A. triseriatus
Reservoir: chipmunks, squirrels, rabbits
Spreads the same way all the other viruses spread.
Same prevention as other mosquito viruses
St. Louis Encephalitis Virus (SLEV) East + Central US (Flavivirus) Clinical symptoms
Most are asymptomatic or have headache and fever.
Severe encephalitis can occur
Reservoir: wild birds
Dead-end host: humans
Same way other virus infections occur
Mosquito prevention stuff
WEST (west of MS) + EAST (Atlantic + gulf) equine encephalitis virus (EEEV, WEEV) Togavirus Clinical symptoms
Ranges from flu-like to encephalitis, coma and death
Reservoir: small birds
Dead-end host: humans and horses
Spreads the same way other viruses spread
Blood test/ CSF analysis
Treat the symptoms
Mosquito related prevention--EEEV has a higher mortality + morbidity than WEEV.
What is the pathology for arboviruses?
bite --> replication at site --> viremia --> spreads via blood and lymph to other organs depending on tropism --> immune response --> inflammation + necrosis
How do you treat most arboviruses?
Treat the symptoms only
How do you prevent arboviruses?
Eliminate or control the vector
Wear protective clothing
HSV-1: mostly children, fever, headache, mouth sores and lesions, lymphadenopathy.
HSV-2: genital sores
It is ubiquitous and host-adapted. Transmitted via close contact and inoculation into susceptible mucosal surfaces.
Cell culture to observe for cytopathic effect (Cowdry cells)
PCR the CSF to diagnose encephalitis and meningitis.
Anti-viral: acyclovir/foscarnet to inhibit viral DNA polymerase. IV version to treat HSV encephalitis and neonatal diseases. This only decreases duration but doesn't cure or stop the virus shedding. Has no effect on latent infection.
Don't touch the lesions
What should you know about non-polio enterovirus?
1. Infects GI tract, prefers low pH
2. Transmission via fecal-oral route, blister, childbirth, and indirect transmission.
3. Resistant to most disinfectant, but sensitive to formaldehyde and bleach4. No vaccine and specific treatment
5. Hand-washing is the best prevention
6. Disease manifestation: due to virus-induced cell lysis.