Malaria Prophylaxis and Chemotherapy

Study Notes

Travelers visiting countries with common malaria are strongly encouraged to undergo chemoprophylaxis using five drugs: chloroquine, malarone, mefloquine, doxycycline, and primaquine.
These drugs are used depending on the type of malaria and the area of travel.

Chloroquine is the oldest antimalarial drug and is commonly used but also misused, leading to high rates of resistance in most countries affected by malaria.
It is still an effective drug but its use is restricted to areas without resistance.
Chloroquine is a highly effective blood schizonticide, but it has no effect against other forms of malaria, such as liver stage parasites.
The mechanism of action involves inhibiting the metabolism of heme groups, which are toxic to malarial parasites.
Resistance to chloroquine is common among strains of P.falciparum and is increasing for P.vivax.

Mutations in the PfCRT (P.falciparum chloroquine resistance transporter) are the primary mediators of resistance.
Chloroquine resistance can be reversed by certain agents, including verapamil, desipramine, and chlorpheniramine.

Chloroquine is rapidly absorbed after oral administration, reaching Tmax in about 3 hours.
It is rapidly distributed to tissues, including crossing the blood-brain barrier and placenta.
It concentrates heavily in the spleen, kidneys, lungs, and leukocytes.
It is excreted into the urine and has an early half-life of 3-5 days and an elimination half-life of 1-2 months.
It exhibits a very long terminal elimination half-life.

Chloroquine is the drug of choice in areas without parasitic resistance and for uncomplicated non-falciparum and sensitive falciparum malaria.
It is a wide-spectrum drug for parasites but clinical resistance is very high.
It does not eliminate hypnozoites of P.vivax and ovale, so primaquine must be added to completely eradicate these hypnozoites.
Chloroquine is safe to use in pregnancy.