Krafts, Regal- Malaria Module

Question 1

Which plasmodia species have:
low parasite burden
mild anemia
relapses because of hypnozoite forms

Answer 1

Plasmodium vivax, P. Ovale, P. malariae

ONLY Vivax and Ovale have hypnozoites

Question 2

What are plasmodia species has:
high parasite burden
severe anemia
cerebral and multi-organ sxs
high fatality rate

Answer 2

Plasmodium falciparum

Question 3

Which plasmodia species are the most common?

Answer 3

P. vivax

P. falciparum

Question 4

Which plasmodia species is the most deadly?

Answer 4

P. falciparum

Question 5

Which plasmodia species causes relapses?

Answer 5

P. vivax

P. ovale

Question 6

Describe the life-cycle of plasmodia…

Answer 6

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.

Question 7

What are the names of the different parasite forms in the hepatic, erythrocytic, and mosquito stages?

Answer 7

Mosquito: Sporozoite

Hepatic cells: sporozomite, schizonts, merozoites

Erythrocytic: Merozoites, trophozoites, schizonts, merozoites, gametocyte

Question 8

Which species form hypnozoites, and why is this important?

Answer 8

Plasmodium vivax, P. ovale are more likely to cause relapses because of the hypnozoite forms that have a laten phase in liver cells

Question 9

What is the mechanism that makes plasmodium falciparum a more dangerous species?

Answer 9

They can infect red cells at ANY age
Causes red cell pathology: (rosettes)
Stimulates high production of cytokines

Question 10

What is meant by “red cell pathology”?

Answer 10

abnormal binding to the endothelium (knobs!)–> blood flow is impeded–> cerebral ischemia (main cause of death in children)

Question 11

How do the bugs produce cytokines and what cytokines do they produce?

Answer 11

TNF, INF-y, IL-1

Suppress red cell production, cause fever, tissue damage and red cell binding to the epithelium

Question 12

What are the typical sxs of malaria?

Answer 12

Incubation 1-2 weeks
Flu- like illness
Paroxysms-fever/chills, sweating, myalgia

Question 13

Which species characterize quotidian, tertian, and quartan fevers?

Answer 13

Quotidian (daily) – P. falciparum
Tertian (every 48 hours) – P. vivax or ovale
Quartan (every 72 hours) – P. malariae

Question 14

What is the gold standard test for diagnosis of malaria?

Answer 14

Identification of plasmodia in red cells on regularly-stained blood smear

• clinical sxs plus appropriate hx (travel, contact w/ infected blood)

Question 15

What species does this gametocyte belong to?

Answer 15

gametocyte stage in Plasmodium falciparum

Question 16

What species does this gametocyte belong to?

Answer 16

p. Vivax

Question 17

What drugs are most commonly used as suppressive prophylaxis?

Answer 17

Chloroquine

OR atovaquone/proguanil

CRA: Atovaquone/proguanil, OR Doxycycline or Mefloquine

Question 18

What drugs are used to tx acute attack from malariae and ovale?

Answer 18

Chloroquine

Question 19

What is used to tx acute attacks from chloro-resistant p. falciparum?

Answer 19

Quinine + doxy

OR

Atovaqunoe/proguanil or artemether/lumefantrine or mefloquine

Question 20

What is used to tx acute attacks from resistant p. vivax?

Answer 20

Quinine + doxy

OR

Mefloquine

Question 21

What is used to tx severe disease?

Answer 21

Quindine + doxy

OR

Artesunate

Question 22

What is the “radical cure”/ prevention of relapse?

Answer 22

Primaquine

Question 23

What is the basis for selectivity of Cholorquine?

Answer 23

Parasitized RBC concentrates chloro at least 25 fold more than unparasitized RBC–> chloro accum in acid ph of food vacoule.

Question 24

What is the mechanism of chloroquine?

Answer 24

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.

Question 25

What are the adverse effects of chloroquine for both prophylaxis and acute attacks?

Answer 25

Low dose prophylaxis- none ``` Acute attack dose: Vision problems (large doses for prolonged periods can cause eye damage/blindness) ```

Question 26

What are the characteristics of Quinine and Quinidine?

Answer 26

More toxic than chloroquine but resistance hasn't developed Used for chloro resis p. falciparum Same mechanism of chloroquine

Question 27

What are the adverse effects of Quinine and Quinidine?

Answer 27

Acute attack doses--> Cinchonism tinnitus, blurred vision, N, HA, decreased hearing, balance issues

Question 28

What else is Quinidine used for?

Answer 28

Anti-arrhythmic drug that blocks Na and K currents (used to maintain sinus rhythm in pts w/ atrial flutter) IV for severe malaria

Question 29

What are the adverse effects of quinidine?

Answer 29

Cardiac problems

Question 30

What is the mech of Mefloquine?

Answer 30

Same as chloro

Question 31

What are the SE of Mefloquine?

Answer 31

N adn V, dizziness, visual/auditory disturbances | Disorientation/hallucinations and depression

Question 32

Mefloquine is only indicated for the tx of one type of plasmodia. Why?

Answer 32

P. Falciparum Because of hte possibility of neuropsychiatric rxns

Question 33

What is the MOA of Atovaquone-Proguanil?

Answer 33

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

Question 34

What are the problems with atovaquone-proguanil?

Answer 34

slow unset unclear effectiveness against exo-erythrocytic forms expensive and needs to be taken daily Gi disturbances

Question 35

What are the two ways to take artemisinins?

Answer 35

Artemisinin + mefloquine Artemether + lumefantrine DON'T USE ALONE

Question 36

What is the MOA of artemisinins?

Answer 36

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.

Question 37

What is a pro and con of artemisinins?

Answer 37

+ rapid and potent agnst MDR orgs - should use alone to avoid selection of resistant orgs

Question 38

What is primaquine?

Answer 38

The RADICAL CURE It eliminates hepatic forms of vivax and ovale MOA is unknown

Question 39

What are the SE of Primaquine?

Answer 39

HEMOLYTIC ANEMIA in ppl w/ G6PD def. GI distress, nausea, HA, pruritis, leukopenia