Malaria Module -Krafts/Regal

Question 1

How was the organism discovered?

Answer 1

Infected RBC containing parasite forms hemozoin that is pigmented. Laveran found pigment

Question 2

What transmits malaria?

Answer 2

Anopheles mosquito

Question 3

Organism that causes malaria?

Answer 3

Plasmodium (Protazoa)

–it is a parasite in the blood

Question 4

Plasmodium vivax, P. ovale, P. malariae

Answer 4

low parasite burden
mild anemia
relapses (in P. vivax and P. ovale)

Question 5

Plasmodium falciparum

Answer 5

• infects any stage of RBC
• high parasite burden
• severe anemia
• cerebral and multi-organ symptoms
• high fatality rate

Question 6

Most common?
Most deadly?
Relapses?

Answer 6

Most common = P. vivax, P. falciparum

Most deadly = P. falciparum

Relapses = P. vivax and P. ovale

Question 7

Infection cycle?

Answer 7

1. Sporozoite gets into hepatic cell
2. Replication of little baby particles in cell == hepatic schizonts
3. Get released and are called Merozoites that infect RBC
4. Ring form in RBC becomes trophozoite
5. Trophozoite –> schizont —->Merozoites get released from RBC —>become gametes that will infect another mosquito

Question 8

Characteristics of P. falciparum life cycle?

Answer 8

Lots of rings in torphozoite stage

Crescent or sickle shaped gametocytes!

Question 9

Characteristics of P. malariae life cycle?

Answer 9

“rosette” arrangement of merozoites

Question 10

Characteristics of P. ovale and P. vivax life cycle?

Answer 10

enlarged red cells

Schuffner’s dots in trophozoites

Question 11

Why is P. faciparum so much worse?

Answer 11

1. Able to infect RBC at ANY age.
2. Causes RBC pathology:
   
   • “rosettes” -cells clump around infected cell
   • abnormal binding to endothelium - has “knobs” to help bind
   • blood flow impeded
3. Stimulates high production of cytokines: causes fever, tissue damage

Question 12

Main cause of death in children with P. falciparum?

Answer 12

Cerebral ischemia

Question 13

Clinical symptoms:

Answer 13

1. Enlarged spleen: fibrosis, grayish color
   
   • Where infected RBCs are getting destroyed
2. Liver enlarged and pigmented
3. Brain vessels get plugged

Question 14

Incubation?
Prodrome?
Symptoms?

Answer 14

Incubation: 1-2 weeks

Prodrome: flu-like illness

Paroxysms (episodic): fever/chills, sweating, myalgia

Question 15

Paroxysms of:

P.falciparum:
P. vivax or ovale:
P. malariae:

Answer 15

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

Question 16

Host resistances to malaria:

Inherieted and immune mediated

Answer 16

Inherited: hemoglobinopathies, thalassemias, G6PD def, RBC antigens

Partial immune mediated: develops over time, reduces severity,

**P. falciparum uses antigenic variation to get around this (PfEMP proteins that stick out change)

Question 17

Diagnosis:

Answer 17

Gold standard: blood smear (regular and thick)

Rapid immunochromatographic tests if no one is trained to do/read blood smears.

Clinical symptoms

Question 18

Considerations in tx:

Answer 18

What area is visited? Resistance? previous use of antimalarials?

Probability of persistent hepatic forms?

Clinical status of disease–Severe?

Question 19

Radical cure?

Answer 19

For hepatic forms: P. vivax and P. ovale that can cause relapse.

Primaquine

Question 20

Primaquine

Answer 20

• Radical cure
• MOA-unknown (maybe generates reactive O2 species?)

gets rid of hyponozoite forms dormant in liver

Unexpected effects: GI distress, nausea, headache, pruritis, leukopenia

**Hemolytic anemin in G6PD def pts

Question 21

1st and 2nd choices for prophylaxis

Answer 21

1. Chloroquine

2. Atoqaquone/proguanil

Question 22

1st and 2nd prophylaxis drugs if chloroquine resistant area?

Answer 22

1. Atovaquone/proguanil

2. Doxycycline or Mefloquine

Question 23

Chloroquine selectivity

Answer 23

Parasitized RBC concentrates the drug at least 25 fold more than unparasitized RBC

-drug accumulated in acid pH of the food vacuole

Question 24

Chloroquine MOA:

Answer 24

Malaria digests host Hbg –> FPIX (toxic)
Malaria enzyme heme polymerase crystalizes it to Hemozoin (non toxic)

Chloroquine keeps it in toxic form (CQ-FPIX)

Question 25

Chloroquine adverse effects at acute attack doses?

Answer 25

dizziness, headache, itching, vomiting, skin rashes. difficulty in visual accommodation Large doses for prolonged periods = severe EYE DAMAGE and even BLINDNESS

Question 26

Quinine and Quinidine

Answer 26

- More toxic than chloro but no resistance to it | - MOA probs the same

Question 27

Cinchonism = Adverse effects of quinine

Answer 27

- Tinnitus, blurred vision, nausea - headache, decreased hearing acuity - permanent damage to vision, balance, and hearing can result

Question 28

Quinidine: MOA: AE:

Answer 28

Blocks Na and K currents -give IV for severe malaria AE: cardiac problems

Question 29

Mefloquine | This drug is as serious as Mifflin party in Madison!

Answer 29

MOA: same as chloroquine AE: same as chloroquine -only used for tx and prevent of chloroquine resistant P.falciparum ****possible neuropsychiatric reaction (hallucinations, depression, disorientation)

Question 30

Atovaquone: MOA

Answer 30

Given with Proguanil Depolarizes parasitic mitochondria and inhibits their electron transport -->selective for parasites :)

Question 31

Proguanil MOA

Answer 31

Given with Atovaquone to enhance the MT toxicity and reduce resistance to Ato inhibits DHFR Selective for plasmodial enzyme :) concentrated in erythrocytes

Question 32

Atovaquone-Proguanil

Answer 32

Slow onset GI disturbances :(

Question 33

Artemisinins Combos

Answer 33

Artensunate + mefloquine Artemether + lumefantrine

Question 34

Artemisinins | MOA

Answer 34

* *Produces free radicals that damage parasite proteins - inhibit a calcium ion ATPase in P.falciparum RAPID and potent against MDR organisms DO NOT USE ALONE --we don't want to select resistant organisms dude.

Question 35

Lumefantrine Give with what else?

Answer 35

give with Artemether Rapid initial reduction in parasite biomass :)

Question 36

I'm going to a place with Chloroquine resistant P. falciparum. What should I do, Doc?

Answer 36

1. Quinine + doxycycline | 2. Attovaquone/proguanil or Artemether/lumefantrine or Mefloquine

Question 37

Similarities between Chloroquine, Mefloquine, Quinine, and Quinidine?

Answer 37

Vision problems as A.E.'s | All probably have similar mechanism to Chloroquine (block FPIX--->hemozoin)

Question 38

What drug might give me pysch problems? Maybe don't prescribe this to people with depression...

Answer 38

Mefloquine Serious as Mifflin

Question 39

What gives me GI problems?

Answer 39

Atovaquone/Proguanil

Question 40

Doxycycline

Answer 40

Inhibits Protein synthesis