Krafts, Regal- Malaria Module Flashcards
Which plasmodia species have:
low parasite burden
mild anemia
relapses because of hypnozoite forms
Plasmodium vivax, P. Ovale, P. malariae
ONLY Vivax and Ovale have hypnozoites
What are plasmodia species has: high parasite burden severe anemia cerebral and multi-organ sxs high fatality rate
Plasmodium falciparum
Which plasmodia species are the most common?
P. vivax
P. falciparum
Which plasmodia species is the most deadly?
P. falciparum
Which plasmodia species causes relapses?
P. vivax
P. ovale
Describe the life-cycle of plasmodia…
Mosquito injects sporozite into human skin. The sporozites travel to and infect hepatic cells. There they proliferate and become schizonts. Eventually the cell ruptures releasing merozoites. The merozoites then enter the blood and infect RBCs.
In RBCs most organisms take a ring form. Then become trophozoites, then shizonts, then the cell ruptures and the merozoites are released.
Some continue to re-infect you and turn into male and female forms.
Sexual reproduction happens IN the mosquito.
What are the names of the different parasite forms in the hepatic, erythrocytic, and mosquito stages?
Mosquito: Sporozoite
Hepatic cells: sporozomite, schizonts, merozoites
Erythrocytic: Merozoites, trophozoites, schizonts, merozoites, gametocyte
Which species form hypnozoites, and why is this important?
Plasmodium vivax, P. ovale are more likely to cause relapses because of the hypnozoite forms that have a laten phase in liver cells
What is the mechanism that makes plasmodium falciparum a more dangerous species?
They can infect red cells at ANY age
Causes red cell pathology: (rosettes)
Stimulates high production of cytokines
What is meant by “red cell pathology”?
abnormal binding to the endothelium (knobs!)–> blood flow is impeded–> cerebral ischemia (main cause of death in children)
How do the bugs produce cytokines and what cytokines do they produce?
TNF, INF-y, IL-1
Suppress red cell production, cause fever, tissue damage and red cell binding to the epithelium
What are the typical sxs of malaria?
Incubation 1-2 weeks
Flu- like illness
Paroxysms-fever/chills, sweating, myalgia
Which species characterize quotidian, tertian, and quartan fevers?
Quotidian (daily) – P. falciparum
Tertian (every 48 hours) – P. vivax or ovale
Quartan (every 72 hours) – P. malariae
What is the gold standard test for diagnosis of malaria?
Identification of plasmodia in red cells on regularly-stained blood smear
- clinical sxs plus appropriate hx (travel, contact w/ infected blood)
What species does this gametocyte belong to?
gametocyte stage in Plasmodium falciparum
What species does this gametocyte belong to?
p. Vivax
What drugs are most commonly used as suppressive prophylaxis?
Chloroquine
OR atovaquone/proguanil
CRA: Atovaquone/proguanil, OR Doxycycline or Mefloquine
What drugs are used to tx acute attack from malariae and ovale?
Chloroquine
What is used to tx acute attacks from chloro-resistant p. falciparum?
Quinine + doxy
OR
Atovaqunoe/proguanil or artemether/lumefantrine or mefloquine
What is used to tx acute attacks from resistant p. vivax?
Quinine + doxy
OR
Mefloquine
What is used to tx severe disease?
Quindine + doxy
OR
Artesunate
What is the “radical cure”/ prevention of relapse?
Primaquine
What is the basis for selectivity of Cholorquine?
Parasitized RBC concentrates chloro at least 25 fold more than unparasitized RBC–> chloro accum in acid ph of food vacoule.
What is the mechanism of chloroquine?
Normally, parasites take your HB and make FPIX (toxic) and detoxify it to hemozin.
Chloroquine converts FPIX to CQ-FPIX, maintaining the toxicity and sequestering heme as hemozoin.
What are the adverse effects of chloroquine for both prophylaxis and acute attacks?
Low dose prophylaxis- none
Acute attack dose: Vision problems (large doses for prolonged periods can cause eye damage/blindness)
What are the characteristics of Quinine and Quinidine?
More toxic than chloroquine but resistance hasn’t developed
Used for chloro resis p. falciparum
Same mechanism of chloroquine
What are the adverse effects of Quinine and Quinidine?
Acute attack doses–> Cinchonism
tinnitus, blurred vision, N, HA, decreased hearing, balance issues
What else is Quinidine used for?
Anti-arrhythmic drug that blocks Na and K currents (used to maintain sinus rhythm in pts w/ atrial flutter)
IV for severe malaria
What are the adverse effects of quinidine?
Cardiac problems
What is the mech of Mefloquine?
Same as chloro
What are the SE of Mefloquine?
N adn V, dizziness, visual/auditory disturbances
Disorientation/hallucinations and depression
Mefloquine is only indicated for the tx of one type of plasmodia. Why?
P. Falciparum
Because of hte possibility of neuropsychiatric rxns
What is the MOA of Atovaquone-Proguanil?
Atovaquone- depolarizes parasitic mitochondria and inhibits their ETC
Proguanil- metabolite of proguanil inhibits DHFR and is selective for the plasmodial enzyme. It ENHANCES the toxicity of atovaquone, reduces the frequency of resistance to atovaquone.
Concentrated in RBCs so not active against vivax or ovale
What are the problems with atovaquone-proguanil?
slow unset
unclear effectiveness against exo-erythrocytic forms
expensive and needs to be taken daily
Gi disturbances
What are the two ways to take artemisinins?
Artemisinin + mefloquine
Artemether + lumefantrine
DON’T USE ALONE
What is the MOA of artemisinins?
Heme iron in the malarial pigment acts on the drug to produce free radicals that damage parasite proteins.
Inhibits Ca ion ATPase in P. falciparum.
What is a pro and con of artemisinins?
+ rapid and potent agnst MDR orgs
- should use alone to avoid selection of resistant orgs
What is primaquine?
The RADICAL CURE
It eliminates hepatic forms of vivax and ovale
MOA is unknown
What are the SE of Primaquine?
HEMOLYTIC ANEMIA in ppl w/ G6PD def.
GI distress, nausea, HA, pruritis, leukopenia
