Neuroparasitology Flashcards
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.
What parasite causes african sleeping sickness?
trypanosoma brucei
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
How is trypanosoma brucei spread?
transmission by tsetse fly
Is trypanosoma brucie always intracellualr or extracellular?
always extracellular
How does trypanosoma brucei reproduce?
binary fission
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
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
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
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
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
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
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)
What are the neurological symptoms ultimatley stem from?
- factors delivered by the trypanosomes
- immune response ot host in the CNS
- further compromise of BBB
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
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)
How does pentamidine get its specificity?
it’s selectively taken up by the trypanosome by protein transporters only present in tyrpanosomes
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
WHat are the two nitroaromatics used for treating trypanoplasmosis?
nifurtimox
benznidazole
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
What is the ONLY option for trypanosomiasis that has progressed to CNS involvement for T. Brucei rhodesiense?
Melarsoprol
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
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.
- acute stage: symptoms very mild or asymptomatic
20-40% of people progress to chronic disease
- 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.
- initial infection is most severe
- 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
