Saviola: Fungal, Parasitic Infections of the CNS, TORCH and Prions Flashcards
What are fungi? What is the difference between yeast and mold?
fungi are eukaryotic and rarely are pathogenic to humans. they normally live in water, soil or decaying vegetation
yeasts are unicellular and reproduce from budding. they have a slower growth rate than bacteria.
molds are multicellular structures with hyphae. these tend to exist in the environment while yeasts exist in human tissues at body temperatures.
What is coccidioides meningitis and how is it diagnosed?
Caused by Coccidioides immitis, a saprophytic soil fungus (has dimorphic physiology), which when inhaled may cause serious disease in man. Can be brought up in soil from earthquakes
most infections are subclinical
when clinical, causes Valley Fever and is usually a pneumonia
it can cause chronic meningitis.
diagnosed by history, positive skin test, serum antibody to C. immitis, positive culture from an extraneural site and exclusion of other etiologies for chronic meningitis
What causes cryptococcosis?
Cryptococcus neoformans, a usually saphrophytic fungus related to rusts and smuts of plants. It looks like a yeast expresses a polysaccharide capsule during human infection that inhibits phagocytosis
What are some characteristics of Cryptococcus neoformans?
*it is NOT dimorphic.
Encapsulated yeast
opportunistic
Acquired especially through inhalation of avian droppings, especially from pigeons. May survive up to two years in dust
inhaled particles are engulfed by pulmonary macrophages
lungs–> hilar lymph nodes –> blood–> anywhere
capsule=antiphagocytic
can cause meningitis and encephalitis (in HIV pts) –> compresses surrounding structures
diagnose:
- by exclusion
- see in CSF culture,
- budding, encapsulated yeast in india ink prep of CSF
- cryptococcal polysaccharide Ag in serum and CSF by latex agglutination
- increase pressure and WBCs in CSF tests
fatal if untreated.
sequelae: optic atrophy, deafness, ataxia, personality change
What are the modes of entry of parasitic infections?
- ingestion
- direct penetration by arthropod bite
- transplacental penetration
- organism directed penetration
What is primary amoebic meningoencephalitis (PAM)? What causes it? Who is affected? Pathogensis? Symptoms?
- Caused by a protozoan, Naegleria fowleri, an amoeboflagellate found in fresh water, especially stagnant water
- affects healthy young people acquired by swimming
- pathogenesis: enters nares–> nasal mucosa covering cribiform plate–> CNS and multiplies–> damage to meninges, olfactory bulbs and extents into the brain
- causes: acute inflammatory response in meninges, PMN in large numbers, elevated protein, low–> normal glucose in the CSF
*boil water before using a netipot
What is African Trypanosomiasis?
- Caused by protozoans, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, motile hemoflagglates
- causes african sleeping sickness
- Vector- tsetse fly
- pathogensis: symptomatic infection at first then to brain –> meningoencephalitis with perivascular infiltration (esp of mononuclear cells)
- Symptoms: HA, apathy, coma, fatal w/o treatment
- dx: recovery of organism
How can cysticerocosis spread?
only from coming into contact with the eggs from a person who is infected with Taenia solum (tapeworm)
you canNOT get the infection from eating undercooked pork
How does cysticerocosis develop? what is the common symptoms?
fecal-oral transmission. Eggs develops, the larva penetrates the gut wall and can go almost anywhere in the body and develop into cysticerci, especially in muscle.
Most common clinical problem is neurocysticercosis, with cysticerci found within the cerebrum, in the subarachnoid space, or in the ventricles. Also in eyes
Much more dangerous than Taeniasis (tapeworms)
What are the TORCH pathogens? How are these infections normally spread and what are their symptoms?
Toxoplasmosis, Other, Rubella, Cytomegalovirus, Herpesvirus
- group of infections that babies might get from their mothers in utero, natally, or postnatally
- Usually from a primary infections in mom
- Infants symptomatic at birth, may have microcephaly, hydrocephaly, cerebral calcification, blindness, chorioretinitis, hearing loss, liver problems, jaundice, and skin manifestations.
- Infants asymptomatic at birth may go on to develop blindness, epilepsy, psychomotor or learning disabilities months or years later.
What is toxoplasmosis? How is toxoplasmosis spread?
- Caused by Toxoplasma gondii, obligate intracellular protozoan
- life cycle that involves cats and carnivores as definitive hosts and other animals like cattle, pigs and chickens as intermediate hosts.
- acquired form eating undercooked meat and exposure to cat feces
- previously infected mothers do not pass a reinfection on to the fetus due to immunity
What does the “O” in TORCH include?
HIV, HBV, HCV, Treponema pallidum, Parvovirus B19, Enteroviruses, VZV
What are some symptoms of congenital syphilis?
In utero infections can lead to serious fetal disease
- Most infected infants are born without clinical evidence of the disease, but rhinitis then develops and is followed by a widespread desquamating maculopapular rash (sloughs off).
- Late bony destruction and cardiovascular syphilis are common in untreated infants who survive the initial course of disease.
What virus causes Erythema infectiosum? How is it transmitted? What symptoms can occur in the fetus of an infected pregnant woman?
- Human parvovirus B-19
- Mildly contagious, spread by droplet infection or blood transfusion. Most common in children, but also occurs in adults.
- In primary infection in pregnant women, the virus may cross the placenta. The fetus may develop necrosis of heptocytes, hemolysis, anemia, cardiac failure and ultimately hydrops fetalis, and death of the fetus may occur. Only 5% of women who are infected during pregnancy have a serious outcome to the fetus.
When is a varicella-zoster infection more likely to affect the fetus of a pregnant woman? What are the symptoms associated?
- Primary varicella infection in the first 20 weeks of gestation –> RARE to see effects
- abnormalities: low birth weight, hypoplasia of an extremity, cicatricial skin scarring, localized muscular atrophy, encephalitis, cortical atrophy, chorioretinitis, and microcephaly.
When can rubella be a major health problem?
When pregnant women get a primary infection. The virus can spread to the fetus at any time in gestation
What virus is associated with cytomegalovirus (CMV) congenital disease? When is this likely to cause fetal problems?
herpesvirus
Mother with primary CMV infection may pass this to the fetus. Reactivated CMV infection in the mother is less likely to lead to fetal problems.
When do infants normally get HSV-2?
When passing through the genital area at birth
worse when the mother is having a primary infection
What causes prion diseases?
- PRION= Proteinaceous infectious particles
- a variation in the conformation of a normal cellular protein found in the central nervous system. The disease is caused by the aberrant conformation of the persons own protein but it can start from the introduction of a foreign homolog with an aberrant conformation from humans or other animals.
-can be a genetic mutation or sporadic
What are prions resistant to? Sensitive to?
Prions are resistant to UV, ionizing radiation, formaldehyde and other agents that damage DNA as well as proteases.
They are sensitive to protein denaturing agents, phenol, urea, guanidine HCL, NaOH.
What is the disease process of Prions? What can cause the initial molecular switch?
- protease resistant prion protein causes molecular switch of cellular protein PrPc to the prion conformation.
- Altered protein cannot be degraded by cellular proteases and accumulates in cytoplasm and extracellular areas of cells in the brain.
- Could be caused by a mutation in the gene encoding the PrP protein, by a random event, or by ingesting PrPsc protein from another source (Kuru, Mad Cow)
What prions cause disease in humans?
- Kuru= from cannibalism
- Gerstmann-Straussler Scheinker Syndrome (GSS)
- Creutzfeldt-Jakob Disease (CJD)-especially found in jewish Libyans. It may be sporadic, passed accidentally via human tissue transplantation, or hereditary.
- Fatal Familial Insomnia (FFI)- severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Insomnia and ultimately death.
- Variant CJD (vCJD)- most likely dervied from Bovine Spongiform Encephalopathy (animal disease).
What are some characteristics of CJD?
- Mean age of onset 63 yrs.
- The genetic form arises from mutation in PRP.
- There has been transmission in Japan by grafts of dura mater during neurosurgery
- CJD can also arise spontaneously
What prions cause disease in animals?
- Scrapie- in sheep . causes progressive and fatal neuropathy
- Bovine spongiform encephalopathy (BSE)- progressive neurological disorder in cattle resulting in tremors staggering and ultimately death
- Chronic wasting disease (CWD)- in deer and elk resulting in weight loss, and neurologic symptoms culminating in death
What are some characteristics of bovine spongiform encephalopathy? Symptoms? Pathology?
Mad Cow disease:
-BSE now associated with human disease- variant CJD (vCJD). It is epidemiologically related to eating British beef.
-results in distinctive amyloid plaques (spontaneous CJD has only 5-10% amyloid plaque incidence), has prolonged illness, psychiatric symptoms and prominent ataxia.
-symptoms: Prodromal- vague symptoms, Dementia becomes rapidly progressive, blindness, myoatrophy, and ataxia.
Late, patient mute and demented and jerking disappears quite often. Over 80% die within 12 months of symptoms.
pathology:
CSF normal, no inflammation
Cerebral atrophy, neuronal loss, vacuoles in neurons contain proteinaceous granules.
Fibrils resembling amyloid consisting of PrP are found in infected cells
What is the association between genotype and vCJD disease?
All those diagnosed with vCJD are homozygous for Methionine at position 129 of the PRP gene (your cellular prion protein).
In the population the incidence is Met/Val 50%, Met/Met 40% and Val/Val 10%.
What must be used to disinfect instruments used on a person with CJD or vCJD?
1N NaOH 1 hr, 134 C autoclave
Or 2N NaOH (if it cannot be autoclaved).
