Neuroparasitology Flashcards by Emily Prazak

Why are parasites special in terms of infectious disease?

they are eukaryotes that have life cycle stages that influence what sorts of symptoms they cause when.

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What parasite causes african sleeping sickness?

trypanosoma brucei

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What are the two subspecies of trypanosoma brucei and how are they different?

trypanosoma brucei gambiense - from west africa - less severe, longer lasting

trypanosoma brucei rhodesiense - from east africa - more acute illness

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How is trypanosoma brucei spread?

transmission by tsetse fly

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Is trypanosoma brucie always intracellualr or extracellular?

always extracellular

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How does trypanosoma brucei reproduce?

binary fission

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Describe the symptoms of the first stage of african sleeping sickness.

possible chancre at bite site, fever, headache, swollen lymph nodes, muscle and joint ahces, possibly rashes or itchiness

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What happens in the 2nd stage of african sleeping sickness?

CNS involvement and neurological symptoms

especially somnolence, but also altered gait, tremors, cranial neuropathies, urinary incontinence, personality changes, abnormal GCS

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What are the different time scales for gambiense and rhodesiense?

gambiense - CNS involvedment after 1-2 years, death in 3

rhodesiense: CNS involvement after a few weeks death in a few months

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How do you diagnose trypanosomiasis?

you look for the organism in the blood for 1st stage and look for it in the CSF for second stage - remember it’s an extracellular organism

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Why is trypanomiasis brucei gambiense so tricky for the immune system?

as they replicate, some alter their surface proteins to evade the immune system such that they come in “waves” of parasitemia

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Why does trypanosome affect the neurological system at all?

it’s life cycle depends on the rodents getting eaten by cats, so it makes the rodents not run away from the smell of cats

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How do the trypanosome reach the CNS?

they gain access thorugh the blood-CSF barrier, not the BBB

(so via the choroid plexus, trigeminal and dorsal root ganglia, and circum-ventricular organs)

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What are the neurological symptoms ultimatley stem from?

factors delivered by the trypanosomes
immune response ot host in the CNS
further compromise of BBB

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At latest stages of the disease, you can get demyelination likely because of what?

auto-immune response against epitopes that are shared between the host and trypanosomes

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How does Pentamidine work? Early or late stage trypanosomiasis?

it binds DNA minor grooves and forms tight complexes

early stages before CNS involvement (doesn’t cross BBB)

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How does pentamidine get its specificity?

it’s selectively taken up by the trypanosome by protein transporters only present in tyrpanosomes

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Is Suramin used for early or late stage trypanosomiasis? More or less toxic than pentamidine?

early - before CNS involvement (doesn’t cross BBB)

mechanism unknown

MORE toxic - N/V, shock, LOC, peripheral neuropathy, photophobia, urticaria, pruritis, nephrotoxicity

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WHat are the two nitroaromatics used for treating trypanoplasmosis?

nifurtimox

benznidazole

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What is the mechanism of action for nifurtimox and Benznidazole?

induces oxidative stress due to inhibition by NADPH-dependent dehydrogenases with subsequent impairment of the mitochondrai membrane potential

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What is the ONLY option for trypanosomiasis that has progressed to CNS involvement for T. Brucei rhodesiense?

Melarsoprol

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How does Melarsoprol have to be administered?

it’s liposoluble, so it can cross the BBB, but insoluble in water

thie means you have to give it IV, dissolved in propylene glycol

this is really painful

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What are the significant toxicities of melarsoprol?

fever, HTN, vomiting, albuminaria, and ENCEPHALOPATHY

5-10% hav encephalopathy and half of those people will die form it

What is the stage 2 treatment for trypanomomiasis?

eflornithine

it can cross the BBB, but it’s trypanostatic

How do you have to give eflornithine

14 day IV infusion (becuase is has poor absorption and rapid excretion in urine)

What is the mechanism for eflornithine?

it inhibits ornithine decarboxylase it turns over rapidly in human cells, but not in trypanosomes, so you get specfcity

What combination treatment is the best option for late stage african trypanosomiasis gabiense?

eflornithine + nifurtimox

What disease is caused by the trypanosoma cruzi parasite? WHere is it endemic?

Chagas' disease latin america and mexico

How is trypanosoma cruzi transmitted?

kidding bug (reduviid insect)

Describe the two stages of Chagas' Disease.

1. acute stage: symptoms very mild or asymptomatic 20-40% of people progress to chronic disease 2. chronic disease: **myocarditic,** megaesophagus, megacolon

How is Leishmania transmitted?

by the sand fly

What type of host cell is needed for Leishmania's life cycle?

it requires uptake by a phagocytic cell - macrophages

What are the three forms of leishmaniasis?

cutaneous (skin ulcerations) visceral (splenomegaly) mucocutaneous (this is the bad one)

What is the first line treatment for leishmaniasis?

the organic antimonials sodium stibogluconate meglumine antimoniate

What is the mechanism of action for the organic antimonials?

it interferes with glycolysis and fatty acid beta-oxidation in leishmania

What two drugs can be used if the leishmaniasis is resistant to antimonial treatment?

liposomal amphotericin B (only for visceral) miltefosine (mechanism unknown)

Why is eflornithine best used in combination with another trypanocidal drug in stage 2 HAT?

eflornithin is trpanostatic rather than trypanocidal

For toxoplasma gondii, what are the two life cycle stages that are transmissible to humans?

oocysts tissue cysts

What percentage of the US population is infectedw ith tooplasma?

25%

How is toxoplasma gondii acquired?

consuming the cysts: tissue cysts in uncooked meat oocysts on unwashed produce occysts form cat feces

Although most toxoplasmosis infections are asymptomatic, what populations are vulnerable to serious disease?

immunocompromised individuals fetuses - remember this is a TORCH organism

Where in the body does toxoplasma have tropism?

it's neurotropic with intracellular encystment in host muscle and brain cells this is because the life cycle requries the rates to be eaten by cats and this makes it so that the rats don;t run away from cat odor

What neurotransmitter is likely altered in toxoplasma infection?

dopamine - probably increase in neural dopamine synthesis and release

Describe toxoplasmosis in an immunocompromised patient.

1. initial infection is most severe 2. non-growing toxoplasma in muscle cysts can be "reactivated" and resume growth symptoms include fver, confusion, headach,e seizures, nausea, and poor cordination

WHat is the ultimate cause of the neurological symptoms in toxoplasmosis

cerebral abscesses often in the basal ganglia, so tremore, chorea and hemiballism is common

Besides intracranial toxoplasmosis, what is a common way it can present?

ocular toxoplasmosis - can be reactivated infeciton or congenital you get toxoplasmic chorioretinitis - inflammation of the uveal tract causing redness, pain, photophobia, decrease in visual acuity

What will you see in an ocular toxoplasmosis eye?

"headlight in the fog" lesion with surrounding healed chorioretinal scars

What is the affect of toxoplasmosis on neonates?

- often causes miscarriages - especially earlier on - abnormal head size - often seem normal at birth, but within first few months develop vision loss, mental disability and seizures

Who receives treatment for tosoplasmosis?

most people don't get treatment people who do: pregnant women, newborns, those wiht ocular toxoplasmosis and immunocompromised

What are some meds you can use for toxoplasmosis and what are they typically used for?

they're mostly antimalarial combos: atovaquone sulfdiazine pyrimethamine

What experimental drug can be used for treatment of toxoplasmosis in pregnant women?

spiramycin - it's a macrolide that blocks ribosome function and congregates int he placental, but doesn't cross over the barrier to affect the fetus great for treating ine arly infection

What is the carnivorous amoeba that can enter the CNS after swimming in warm infected lakes?

naegleria fowleri

How does naegleria penetrate the CNS?

It goes into the nose and enters the nasal olfactory epithelium, then travels thorugh the olfacotry nerves to the olfacotry bulb. then enters circulation to the meninges

Describe the presentation of primary amebic meningoencephalitis?

symptoms begin about 5 days post-infeciton initial symptoms include headche, nausea, fever, and vomiting later symptoms include stiff neck, confusion, lack of attention, loss of balance, seizures, hallucinations rapid disease progression with death usually within about 5 days

What are the diganostic hints pointing to primary amebci meningoencephalitis?

june, july or august unusually hot and dry weather southern US freshwater nasal saline rinsing

What is the new experimental treatment for amebic meningoencephalitis?

miltefosine