Malaria Module - Krafts/Regal Flashcards
Where is malaria most prevalent?
Africa, Asia, Latin America
(90% of deaths occur in sub-Saharan Africa)
How many cases of malaria occur in the USA each year?
1500
(mostly from blood transfusions, few from mosquito bites)
How many people total die from malaria each year?
655,000 die each year
(one child dies from malaria each minute in Africa)
What organism is a vector for malaria?
- Anopheles mosquito (not native to U.S.) carries Plasmodia (only female bites humans)
- Culex = what we have in the U.S. (harmless)
What is the causative agent of malaria?
-
Plasmodium
- protozoan parasite
- infectious in the blood!
What are the different species of Plasmodium?
Remember:
- most common = P. vivax, P. falciparum
- most deadly = P. falciparum
- relapses = P. vivax and P. ovale
What species of Plasmodium has a low parasite burden, “rosette” arrangement of merozoites, and causes mild anemia?
P. malariae
What species of Plasmodium has a low parasite burden, results in enlarged red cells/Schuffner’s dots, has potential for relapse, and causes mild anemia?
P. vivax and P. ovale
What species of Plasmodium has a high parasite burden, causes severe anemia, may lead to cerebral and multi-organ sx, and has a high fatality rate?
P. falciparum
What is the life cycle of Plasmodium falciparum?
- sporozoite (infected stage) → goes to liver (min-hr) first
- becomes schizont (divided into little babies) →
- busts open liver cell→
- releases merozoites into blood → infect RBCs
- In RBC: ring form → trophozoite → schizont → releases merozoites
What are the morphologic features of P. falciparum?
- can have lots of ring forms within a single cell
- gametocytes are crescent/banana-shaped
How does P. falciparum affect RBCs and blood flow?
- Able to infect red cells of any age
- Blood flow is impeded
- Forms “Rosettes” – RBC clump together around infected cell → can block blood flow in small vessels and brain
- Abnormal binding to vascular endothelium (knobs on RBC membrane) → impedes blood flow
- important in brain and in children
What is the main cause of death in children with malaria?
cerebral ischemia
P. falciparum stimulates high production of what cytokines? What is the result?
- TNF
- INF-Υ
- IL-1
***Suppresses RBC production, cause fever, tissue damage, and RBC binding to endothelium
What is the incubation period for malaria?
1-2 weeks
What is the malaria prodrome?
flu-like illness
What happens in a patient with infected with malaria?
- Spleen becomes enlarged
- Parasites in red cells
- Super-active macrophages
- If chronic: fibrosis, grayish color
- Liver becomes enlarged and pigmented
- Brain vessels get plugged
- red cell rosettes
- hypoxia around vessels
- eventually, ischemia
- Heart, lungs may also be involved
What are the episodic Paroxysms of malaria infections?
- fever/chills, sweating, myalgia
- depends on species
- *Quotidian (daily) = P. falciparum
- Tertian (every 48 hrs) = P. vivax or ovale
- Quartan (every 72 hrs) = P. malariae
What are the two types of host resistance to malaria?
-
Inherited RBC alterations: hemoglobinopathies (sickle cell), thalassemias, G6PD deficiency
- RBC antigens (ABO, Duffy) – blood type affects binding (O is least adhesive)
- Doesn’t necessarily prevent infection, but you just won’t get as sick (RBC die off sooner)
-
Partial immune-mediated resistance: develops over time in patients in endemic areas
- Reduces severity of disease (kids have it worse due to development of immune system)
- P. falciparum uses antigenic variation – changes antigen just when you get used to it (PfEMP proteins that stick out of RBC, every generation 2% make new PfEMPs)
How do you diagnose malaria?
- Clinical sx + appropriate hx (travel, contact with infected blood)
- Gold standard: identification of plasmodia in red cells on regularly-stained blood smear (tons of ring forms)
- Rapid immunochromatographic tests sometimes used (quicker but less sensitive/specific) – can use in the field
What is the best treatment plan for malaria?
- Don’t get bit – netting & insect repellents; avoid mosquito areas & exposure during periods of high insect activity
- Plan B:
- Take advantage of drugs used for prophylaxis – if you are planning a trip to a malaria area, take prophylactic drugs
- Treat active malaria with the appropriate drug, depending on resistance, etc.
- Use the ‘radical cure’ if indicated
What are important considerations to make when treating malaria?
- Which area is visited? Resistance or not?
- Places will be listed as chlorquine resistant or not (P. falciparum and P. vivax)
- Previous use of antimalarials?
- Severity of DZ?
- dictates how aggressive the therapy will be (P. falciparum)
- possibility of relapse (P. vivax and P. ovale)
- What is the probability of persistent hepatic forms of the organism?
- Clinical status of the disease? Uncomplicated disease?
- Severity of the DZ and necessity to achieve therapeutic levels quickly
- Most deaths from severe malaria occur within the first 24-48 hrs
- Severity of the DZ and necessity to achieve therapeutic levels quickly
What is the “radical cure” for malaria?
only drug to act in exoerythrocytic stage
What are the two types of Plasmodium infection result in latent forms in the liver? Tx?
P. vivax and P. ovale
Primaquine: eradicates hypnozoite forms dormant in liver
How should you treat someone going into an area with malaria?
- suppressive prophylaxis
- lower doses, fewer side effects
- If going to chloroquine-resistant area DON’T treat with chloroquine (DUH) BUT chloroquine is first line in all other areas
What is the basis for selection of Chloroquine?
- Selective accumulation by the parasite in erythrocytes
- parasitized RBC concentrates Chloroquine at least 25xmore than unparasitized RBC
- Chloroquine accumulates in the acid pH of the food vacuole
What is the MOA for Chloroquine?
- interferes with heme handling, disrupts sequestration of heme as hemozoin
- Parasite digests host Hb within the acidic food vacuole of plasmodia → results in production of large amounts of ferriprotoporphyrin IX (FPIX) inside the food vacuole
- FPIX is toxic to the parasite so the parasite uses heme polymerase to convert it to hemozoin
- Chloroquine binds to FPIX and prevents its conversion to hemozoin
- Either free FPIX or chloroquine bound to FPIX is toxic to the plasmodium
- Parasite digests host Hb within the acidic food vacuole of plasmodia → results in production of large amounts of ferriprotoporphyrin IX (FPIX) inside the food vacuole
What are the adverse side effects of Chloroquine?
- Low dose suppressive therapy used in prophylaxis – no significant toxicity
- Acute attack doses = dizziness, headache, itching, vomiting, skin rashes, difficulty in visual accommodation
- Large doses for prolonged periods can cause severe eye damage and even blindness
- Less toxicity than quinine and quinidine
When should you use Quinine to treat malaria?
- used in chloroquine resistant P. falciparum
- more toxic than chloroquine but resistance has not readily developed
What is the MOA of Quinine?
Unknown
(probably the same as chloroquine)
What are the adverse side effects of Quinine?
- acute attack doses
- cinchonism – tinnitus, blurred vision, nausea, HA, decreased hearing acuity
- Permanent damage to vision, balance and hearing can result
When should you use Quinidine to treat malaria?
IV for severe malaria
What is the MOA of Quinidine?
- anti-arrhythmic drug that blocks Na+ and K+ currents
- used to maintain sinus rhythm for atrial flutter/a fib & to prevent recurrence of ventricular tachycardia
What are the adverse side effects of Quinidine?
cardiac problems – patients need cardiac monitoring
When is Mefloquine indicated?
- Only for the treatment and prevention of Chloroquine resistant P. falciparum
What is the MOA of Mefloquine?
Unknown
(probably acts like chloroquine)
What are the adverse side effects of Mefloquine?
- sometimes nausea, vomiting, dizziness, visual or auditory disturbances
- may cause disorientation, hallucinations and depression
- due to possibility of neuropsychiatric rxns, chloroquine is preferred if resistance is not a problem
