Malaria

Question 1

Malaria life cycle

Answer 1

• Due to plasmodium sp
• 2 phases: asexual (in humans-intermediate host) and sexual (in female anopheles mosquito- definitive host)
• Overview: mosquito salivary gland-> blood-> liver (replication)-> RBCs (replication)-> mosquito
• Human (asexual, schizogeny) phase broken up to exoerythrocytic (liver) and erythrocytic (RBC)

Question 2

Exoerythrocytic

Answer 2

• Sporozoites enter blood and infect hepatocytes
• After replication (days-months), merozoites are released from hepatocytes
• Some malaria (only P vivax or P ovale) remains in hepatocyte, must be treated w/ primaquine to destroy and prevent relapse

Question 3

Erythrocytic

Answer 3

• Merozoites (released from liver) infect RBCs and develop into trophozoites inside cell
• They will either mature into a schizont (which bursts to release many merozoites which then infect more RBCs), or mature into a gametocyte and be picked up by a mosquito

Question 4

Alteration of host cells

Answer 4

• Shape and deformability of RBC
• Protrusion and knobs
• Expression of new surface molecules
• Autoagglutination
• Adherence to normal RBCs and endothelial cells

Question 5

Sexual phase

Answer 5

• In the female anopheles mosquito
• Female picks up gametocytes of both sexes
• The two gametocytes in the mosquito meet in the gut and sexually reproduce into ookinete, which invades gut epithelial cell
• Ookinete matures into Oocyst, which moves to mosquito salivary gland
• Oocyst ruptures and releases sporozoites, which are ready to infect a new human upon mosquito bite

Question 6

Symptoms of malaria

Answer 6

• Non-specific: headache, fatigue, abdominal pain, myalgia, arthralgia, fever, chills, anorexia, nausea
• Classical paroxysmal fevers (intermittent, appear and disappear quickly): due to all organisms in RBCs lysing the cells at the same time every 48 hrs (not always regular)
• Lab findings: anemia, normal WBC, thrombocytopenia, elevated ACR protein, elevated bili and hepatic nzs

Question 7

Pathogenesis of malaria

Answer 7

• RBC lysis, destruction by spleen, erythropoiesis suppression all lead to anemia
• Release of TNFa and IL1 by macrophages in response to glycosyl phosphatidylinositol, leading to fever, hypoglycemia, microvascular obstruction, and hypoxia

Question 8

Resistance to malaria

Answer 8

• People who have abnormal RBCs or Hb sometimes have a selective advantage against malaria
• These include: SCD, thalassemia, G6PD deficiency, distribution of various RBC surface molecules (glycophorin, duffy Ag)
• These phenotypes are seen in higher prevalence in the malaria belt

Question 9

Types of Plasmodium sp

Answer 9

• Plasmodium falciparum
• plasmodium vivax/ovale (these two are very similar)
• plasmodium malariae
• plasmodium knowleski
• Most important are the falciparum, vivax, and ovale
• Stable transmission: high rate of exposure (>10 inoculation/yr)
• Unstable transmission: rate of inoculation fluctuates over seasons and years (slows acquisition of immunity)

Question 10

Plasmodium vivax/ovale

Answer 10

• Both found world wide, but ovale more in sub-saharan Africa and P vivax in other areas
• Rarely cause serious illness, resistance to drugs uncommon
• Likelihood of recurrence even if patient receives cholorquine (due to hypnozoites remaining dormant in hepatocytes)
• Frequency of paroxysms: tertian

Question 11

Dx of malaria

Answer 11

• Light microscopy of blood smears (thick and thin)
• Thick smears tell you if the patient has malaria (look for ring-form and mature trophozoites, schizonts, gametocytes)
• Thin smears tell you what kind of malaria it is
• Can also do fluorescent microscopy, rapid diagnostic test (RDT, but these are vulnerable to high temp and humidity as they require fresh Abs on test strips)

Question 12

Plasmodium falciparum

Answer 12

• Infects erythrocytes of all ages, leads to high parasite burden
• Able to sequester in the deep venous microvasculature, avoiding destruction by spleen
• Binds to endothelium w/ P falciparum erythrocyte membrane protein1 (PfEMP1)
• Found all over the world (worst type)
• Complications: cerebral malaria, severe anemia, respiratory failure, renal failure, hypoglycemia
• Causes acute distress then resolves, no recurrence w/out reinfection
• Drug resistance major problem
• Frequency of paroxysm: quartan

Question 13

Cell interactions in P falciparum malaria

Answer 13

-Opsonization and phagocytosis of infected RBCs
-Soluble Ag-immune complexes lead to anemia, vasculitis, nephritis, splenomegaly
Immune cell responses: CD8, CD4, plasma/B cells (IgG, IgM)
-There is both innate (lack of adhesion receptor) and acquired (due to past exposure, Ab to PfEMP1) immunity to plasmodium, but acquired must be maintained by repeated exposure or it will be lost

Question 14

Lab blood work findings

Answer 14

• Anemia
• Normal WBC
• Thrombocytopenia
• Elevated acute phase proteins
• Elevated bili, liver nzs

Question 15

Severe malaria

Answer 15

• Only caused by P falciparum
• Impaired consciousness, coma, seizures
• Due to cerebral malaria (lack of circulation in brain due to adherence of RBCs), hyperparasitemia

Question 16

Dx and Rx

Answer 16

• In high transmission areas, confirmatory Dx is not required to begin Rx
• Rx for plasmodium except falciparum: chloroquine for 3 days, plus primaquine for 14 days (for vivax/ovale, to kill dormant organisms in liver)
• Primaquine is contraindicated in G6PD patients
• For all Rx: make sure it is not counterfeit

Question 17

Rx for falciparum

Answer 17

• Due to drug resistance, and the fact that it can bind endothelial cells, falciparum requires special Rx
• Requires mixed Rx of Artemisinin-based plus lumefantrine Rx for 3 days, with daily blood draws during those 3 days to check for level of parasite
• Can also use atovoquone-proguanil (malarone)

Question 18

Prevention and prophylaxis

Answer 18

• Prevention: mosquito nets, vaccine development

- Prophylaxis: mefloquine (can cause tremors, psychosis, depression, bad dreams), atovoquone-proguanil (malarone)