Malaria Module -Krafts/Regal Flashcards
How was the organism discovered?
Infected RBC containing parasite forms hemozoin that is pigmented. Laveran found pigment
What transmits malaria?
Anopheles mosquito
Organism that causes malaria?
Plasmodium (Protazoa)
–it is a parasite in the blood
Plasmodium vivax, P. ovale, P. malariae
low parasite burden
mild anemia
relapses (in P. vivax and P. ovale)
Plasmodium falciparum
- infects any stage of RBC
- high parasite burden
- severe anemia
- cerebral and multi-organ symptoms
- high fatality rate
Most common?
Most deadly?
Relapses?
Most common = P. vivax, P. falciparum
Most deadly = P. falciparum
Relapses = P. vivax and P. ovale
Infection cycle?
- Sporozoite gets into hepatic cell
- Replication of little baby particles in cell == hepatic schizonts
- Get released and are called Merozoites that infect RBC
- Ring form in RBC becomes trophozoite
- Trophozoite –> schizont —->Merozoites get released from RBC —>become gametes that will infect another mosquito
Characteristics of P. falciparum life cycle?
Lots of rings in torphozoite stage
Crescent or sickle shaped gametocytes!
Characteristics of P. malariae life cycle?
“rosette” arrangement of merozoites
Characteristics of P. ovale and P. vivax life cycle?
enlarged red cells
Schuffner’s dots in trophozoites
Why is P. faciparum so much worse?
- Able to infect RBC at ANY age.
- Causes RBC pathology:
- “rosettes” -cells clump around infected cell
- abnormal binding to endothelium - has “knobs” to help bind
- blood flow impeded
- Stimulates high production of cytokines: causes fever, tissue damage
Main cause of death in children with P. falciparum?
Cerebral ischemia
Clinical symptoms:
- Enlarged spleen: fibrosis, grayish color
- Where infected RBCs are getting destroyed
- Liver enlarged and pigmented
- Brain vessels get plugged
Incubation?
Prodrome?
Symptoms?
Incubation: 1-2 weeks
Prodrome: flu-like illness
Paroxysms (episodic): fever/chills, sweating, myalgia
Paroxysms of:
P.falciparum:
P. vivax or ovale:
P. malariae:
P.falciparum: Quotidian (daily)
P. vivax or ovale: Tertian (every 48 hrs)
P. malariae: Quartan (every 72 hrs)
Host resistances to malaria:
Inherieted and immune mediated
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)
Diagnosis:
Gold standard: blood smear (regular and thick)
Rapid immunochromatographic tests if no one is trained to do/read blood smears.
Clinical symptoms
Considerations in tx:
What area is visited? Resistance? previous use of antimalarials?
Probability of persistent hepatic forms?
Clinical status of disease–Severe?
Radical cure?
For hepatic forms: P. vivax and P. ovale that can cause relapse.
Primaquine
Primaquine
- 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
1st and 2nd choices for prophylaxis
- Chloroquine
2. Atoqaquone/proguanil
1st and 2nd prophylaxis drugs if chloroquine resistant area?
- Atovaquone/proguanil
2. Doxycycline or Mefloquine
Chloroquine selectivity
Parasitized RBC concentrates the drug at least 25 fold more than unparasitized RBC
-drug accumulated in acid pH of the food vacuole
Chloroquine MOA:
Malaria digests host Hbg –> FPIX (toxic)
Malaria enzyme heme polymerase crystalizes it to Hemozoin (non toxic)
Chloroquine keeps it in toxic form (CQ-FPIX)
Chloroquine adverse effects at acute attack doses?
dizziness, headache, itching, vomiting, skin rashes. difficulty in visual accommodation
Large doses for prolonged periods = severe EYE DAMAGE and even BLINDNESS
Quinine and Quinidine
- More toxic than chloro but no resistance to it
- MOA probs the same
Cinchonism = Adverse effects of quinine
- Tinnitus, blurred vision, nausea
- headache, decreased hearing acuity
- permanent damage to vision, balance, and hearing can result
Quinidine:
MOA:
AE:
Blocks Na and K currents
-give IV for severe malaria
AE: cardiac problems
Mefloquine
This drug is as serious as Mifflin party in Madison!
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)
Atovaquone: MOA
Given with Proguanil
Depolarizes parasitic mitochondria and inhibits their electron transport –>selective for parasites :)
Proguanil MOA
Given with Atovaquone to enhance the MT toxicity and reduce resistance to Ato
inhibits DHFR
Selective for plasmodial enzyme :)
concentrated in erythrocytes
Atovaquone-Proguanil
Slow onset
GI disturbances :(
Artemisinins Combos
Artensunate + mefloquine
Artemether + lumefantrine
Artemisinins
MOA
- *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.
Lumefantrine
Give with what else?
give with Artemether
Rapid initial reduction in parasite biomass :)
I’m going to a place with Chloroquine resistant P. falciparum. What should I do, Doc?
- Quinine + doxycycline
2. Attovaquone/proguanil or Artemether/lumefantrine or Mefloquine
Similarities between Chloroquine, Mefloquine, Quinine, and Quinidine?
Vision problems as A.E.’s
All probably have similar mechanism to Chloroquine (block FPIX—>hemozoin)
What drug might give me pysch problems?
Maybe don’t prescribe this to people with depression…
Mefloquine
Serious as Mifflin
What gives me GI problems?
Atovaquone/Proguanil
Doxycycline
Inhibits Protein synthesis
