Selection of Antimalarial Drugs

SELECTION OF DRUGS

The particular agent employed in the treatment of acute malarial infections will depend on the severity of the in-fection, the strain of the infecting organism, and the de-gree to which the organism is drug resistant. In addition, chemoprophylaxis is considered a valid indication for the use of antimalarial drugs when individuals are traveling in areas where malaria is endemic. The following para-graphs may provide useful guidelines in the therapeutic management and prevention of malarial infections.

Prophylactic Measures for Use in Endemic Areas

Chloroquine may be the drug of choice, but only in areas where chloroquine-sensitive P. falciparum organisms are present. Chloroquine prophylaxis is no longer effective for travel to many regions. Daily atovaquone–proguanil appears to be the first choice for chemoprophylaxis for travel to areas of chloroquine resistance. Prophylactic drugs, such as chloroquine or mefloquine, should be started 2 to 4 weeks prior to travel and continued for 6 to 8 weeks after leaving the endemic areas. The atovaquone–proguanil combination is the exception in that it is started 1 to 2 days prior to departure and is con-tinued 1 week after return.

Treatment of an Acute Uncomplicated Attack

Chloroquine phosphate, administered orally, is again the drug of choice unless one suspects the presence of a chloroquine-resistant organism. Oral mefloquine orMalarone is indicated for uncomplicated infections re-sistant to chloroquine. For severe infections, parenteral administration of quinidine is indicated with hourly monitoring of serum glucose levels.

Mechanism of Chloroquine Resistance

A particular protein (P₁₇₀ glycoprotein) has been identi-fied in the resistant parasite that appears to function as a drug-transporting pump mechanism to rid the cell of drug. This resistance mechanism is similar to the mul-tidrug resistance system in cancer. Thus, when drug en-ters the organism, it is rapidly removed before it can ex-ert its toxicity. Drug therapy directed at inhibiting this pump mechanism may be able to reverse this resistance. This is a potentially important new approach to the chemotherapy of malaria.

Treatment of Chloroquine-Resistant P. Falciparum Infection

In areas where chloroquine-resistant P. falciparum is common, a combination of a rapidly acting blood schi-zonticide and pyrimethamine–sulfadoxine may be the treatment of choice. An acute attack of malaria caused

by chloroquine-resistant P. falciparum complicated by renal failure or cerebral manifestations may be termi-nated with parenteral quinidine gluconate alone or with oral pyrimethamine and sulfadiazine. Oral mefloquine has been used in place of chloroquine in uncomplicated infections with chloroquine-resistant organisms, but se-rious CNS side effects (e.g., flashbacks) are frequently seen with its use. Consequently, the atovaquone– proguanil combination is now considered as effective as and better tolerated than mefloquine.

Mixed Infections

Every patient with malaria should be examined for si-multaneous infection with more than one species of Plasmodium. Infections with both P. falciparum and P. vivax are among the most commonly encountered mixed infections. In patients with falciparum malaria, attacks of P. vivax malaria may later develop; it is im-portant not to misinterpret this delayed P. vivax form as a relapse of P. falciparum infection. If a mixed infection is identified, a combination of 4-aminoquinoline and primaquine should be administered, since the pri-maquine helps to eliminate any persisting tissue forms of P. vivax.