Neuro-Parasitology - Zimmer Flashcards
What are the two subspecies of trypanosoma brucei?
What disease do they cause?
Where in Africa are they found?
Trypanosoma brucei gambiense
- West Africa
- Less severe, longer lasting African Sleeping Sickness (Trypanosomiasis)
Trypanosoma brucei rhodesiense
- East Africa
- More acute African Sleeping sickness
What is the timeline like in the subtypes of African Trypanosomiais?
First stage: Fever, headache, swollen lymph nodes, muscle/joint aches, rash
Second Stage: CNS, neuro symptoms
Gambiense: CNS involvement after 1-2 years, death after 3 if untreated
Rhodiense: CNS involvement after a few weeks, death in a few months without treatment
What is one big way that T.b. Gamiense can evade host defenses?
Using a VSG (variable surface glycoprotein) switch.
The type that made the switch can then proliferate before the host gathers forces again
What are some of the neuro symptoms seen in the neurological stage of Tryptanosomiasis?
Somnolence - extreme sleepiness at random times Altered gait Tremors Personality changes Urinary incontinence
How do parasite gain access to the brain?
Through the blood-CSF barrier (sneaky devils…)
aka : choroid plexus, dorsal root ganglia, circumventricular organs. etc.
What is suramin used for?
Does it cross BBB?
Mechanism?
Toxicity?
Used for 1st stage trypanosomiasis
Does NOT penetrate BBB
Mechanism = Unknown, give by IV
Very toxic: Nausea, peripheral neuropathy, photophobia, urticaria, pruritis, nephrotoxicity
What is Pentamidine used for?
Does it cross BBB?
Mechanism?
Toxicity?
Used for 1st stage trypanosomiasis
Does NOT penetrate BBB, intramuscular injection
Mechanism - DNA minor groove binder
Toxicity: Hypotension, tachycardia, vomiting, hypoglycemia
What are the nitroaromatics? What are they used for?
Does it cross BBB?
Mechanism?
Toxicity?
Nitroaromatics: Nifurtimox & Benznidazole
Do not cross BBB
Nifurtimox induces oxidative stress due to inhibition by NAD(P)H-dependent dehydrogenases
Benznidalole = similar mechanism
Toxicity: Side effects common; nausea, vomiting, myalgia, weakness, peripheral neuropathy
What is Melarsoprol used for?
Does it cross BBB?
Mechanism?
Toxicity?
Only option for T.b.rhodiense that has progressed to involve CNS
-CAN cross BBB
-Adminstration by IV and is painful
-Mechanism : Unknown
-Toxicity: Encephalopathy, Fever, Hypertension, Vomiting, Albuminuria, very painful!
5-10% taking Melarsoprol suffer reactive encephalopathy, and half of those will die from it.
- High rate of failure
What is Eflornithine used for?
What is it’s mechanism?
Toxicity?
Able to cross BBB in order to treat stage 2 Trypanosomiasis Gambiense
Toxicity: Fever, headache, hypertension, rash, peripheral neuropathy, tremor, GI
Why must you take Eflornithine for a long time to clear the infection?
What is its mechanism?
Why is the toxicity less in this drug?
It is trypanostatic rather than trypanocidal
Mechanism inhibits ornithine decarboxylase (ODC)
Enzyme turns over faster in human cells than in trypanosomes, so it hurts us less! Nice!
You are working at a school in East Africa and your good friend has taken ill in the last few weeks. Recently he has been showing signs of tremor, cognitive difficulties, and is falling asleep in front of his class…
What is the ONLY drug that can help him now?
Melarsoprol
Only option for trypanosomiasis that has progressed to CNS involvement for subspecies T. brucei rhodesiense
So what is the best treatment option for late stage T.b. Gambiense?
Eflornitine & Nifurtimox Drug combo!
Eflornithine takes care of tryps in CNS, nifurtimox + eflornithine takes care of those in bloodstream
What parasite causes Chaga’s disease?
Trypanosoma Cruzi
Transmitted by reduviid insect “kissing bug”
Endemic in Mexico and latin america
MAJOR problems caused by Chaga’s disease?
Myocarditis, megaesophagus, megacolon
