Antimalarial chemotherapy

The first priority in treating all cases of malaria is starting an appropriate antimalarial drug. In cases of severe falciparum malaria the choices are limited ( Wit® 19.9.6).

Parenteral quinine is the current gold standard and should be used in all cases except where there is a high chance of quinine resistance. Significant quinine resistance is currently limited to a very restricted geographical area (see below). Parenteral quinine is not available in the United States, and quinidine should be substituted. Quinidine is a more active antimalarial drug but has a four times greater effect on the heart. Both quinine and quinidine are proarrhythmogenic drugs and should never be given as bolus injections. Quinidine should be administered with ECG monitoring; if the QT interval is prolonged by more than 25 per cent the infusion must be stopped. Both quinine and quinidine can cause hypoglycemia.

Quinine doses are started with a loading dose in severe cases of malaria. The two most commonly used regimens are as follows:

1. 20 mg/kg quinine dihydrochloride salt over 4 h in 5 per cent glucose or 0.9 per cent sodium chloride;

2. 7 mg/kg quinine dihydrochloride salt infused over 30 min, followed by 10 mg/kg over 4 h.

A maintenance dose of 10 mg/kg every 8 to 12 h should follow. This should be given by infusion over 4 h. Cinchonism (ringing in the ears, deafness, and vertigo) is not an indication to stop therapy. The therapeutic range for quinine has not been defined, but plasma concentrations between 5 and 10 mg/l (15 to 30 pmol/l) are safe and effective. Trough quinine levels should be checked after the third parenteral dose where available.

The quinidine loading dose is 10 mg/kg infused over 1 h, followed by 1.2 mg/kg/h (0.02 mg/kg/min). The therapeutic range has not been determined, but plasma concentrations of 5 to 8 mg/l are considered effective and are usually safe. If plasma concentration monitoring is not available, reduction of the quinidine dose by a third should be considered on day 3 of treatment.

Once the patient has begun to respond to treatment he or she can be converted to oral therapy if tolerated. Quinine or quinidine should be continued until asexual parasites are eliminated from the peripheral blood. A second-line drug such as sulfadoxine-pyrimethamine (Fansidar) once, or doxycycline for 7 days, should then be administered to eliminate any residual parasites.

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