Medication Summary
The 4 major drug classes currently used to treat malaria include quinoline-related compounds, antifolates, artemisinin derivatives, and antimicrobials. No single drug that can eradicate all forms of the parasite's life cycle has been discovered or manufactured yet. Therefore, 1 or more classes of drugs often are given at the same time to combat malarial infection synergistically. Treatment regimens are dependent on the geographic location of infection, the likely Plasmodium species, and the severity of disease presentation.
Beware of counterfeit antimalarial drugs being taken by patients that may have been purchased overseas or via the Internet. They may not contain any active ingredients at all and may contain dangerous materials.
Antipyretics, such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), are indicated to reduce the level of discomfort caused by the infection and to reduce fever. NSAIDs should be used with caution if bleeding disorder or hemolysis is suspected.
Antimalarials can cause significant prolongation of the QT interval, which can be associated with an increased risk of potentially lethal ventricular dysrhythmias. Patients receiving these drugs should be assessed for QT prolongation at baseline and carefully monitored if this is present. Patients with normal QT intervals on electrocardiogram (ECG) may not be at a significantly increased risk for drug-induced dysrhythmia, but caution is advised, particularly if the patient is taking multiple drug regimens or if he or she is on other drugs affecting the QT interval.
Methemoglobinemia is a complication that may be associated with high-dose regimens of quinine or the derivatives chloroquine and primaquine.[31] A patient presenting with cyanosis and a normal PaO2 on room air should be suspected of having methemoglobinemia.
Antimalarials
Class Summary
These agents inhibit growth by concentrating within acid vesicles of the parasite, increasing the internal pH of the organism. They also inhibit hemoglobin utilization and parasite metabolism.
Chloroquine phosphate (Aralen)
Chloroquine phosphate is effective against P vivax, P ovale, P malariae, and drug-sensitive P falciparum. It can be used for prophylaxis or treatment. This is the prophylactic drug of choice for sensitive malaria.
Quinine (Qualaquin)
Quinine is used for malaria treatment only; it has no role in prophylaxis. It is used with a second agent in drug-resistant P falciparum. For drug-resistant parasites, the second agent is doxycycline, tetracycline, pyrimethamine sulfadoxine, or clindamycin.
Quinidine gluconate
Quinidine gluconate is indicated for severe or complicated malaria and is used in conjunction with doxycycline, tetracycline, or clindamycin. Quinidine gluconate can be administered IV and is the only parenterally available quinine derivative in the United States.
Doxycycline (Vibramycin, Adoxa, Doryx)
Doxycycline is used for malaria prophylaxis or treatment. When it is administered for treatment of P falciparum malaria, this drug must be used as part of combination therapy (eg, typically with quinine or quinidine).
Tetracycline
Tetracycline may specifically impair the progeny of apicoplast genes, resulting in their abnormal cell division. Loss of apicoplast function in progeny of treated parasites leads to slow, but potent, antimalarial effect.
Clindamycin (Cleocin HCl, Cleocin Phosphate)
Clindamycin is part of combination therapy for drug-resistant malaria (eg, typically with quinine or quinidine). It is a good second agent in pregnant patients.
Mefloquine
Mefloquine acts as a blood schizonticide. It may act by raising intravesicular pH within the parasite's acid vesicles. Mefloquine is structurally similar to quinine. It is used for the prophylaxis or treatment of drug-resistant malaria.
Atovaquone and proguanil (Malarone)
Atovaquone may inhibit metabolic enzymes, which in turn inhibits the growth of microorganisms.
Used for pediatric patients, this combination should be administered for uncomplicated P falciparum; can also be used in combination with chloroquine.
This agent is approved in the United States for the prophylaxis and treatment of mild chloroquine-resistant malaria. It may be a good prophylactic option for patients who are visiting areas with chloroquine-resistant malaria and who cannot tolerate mefloquine. Each tab combines 250 mg of atovaquone and 100 mg of proguanil hydrochloride. The dosage for children is based on body weight; in children 40 kg (88 lb) or less, a lower-dose pediatric tablet (62.5 mg of atovaquone and 25 mg of proguanil hydrochloride) is available.
Primaquine
Primaquine is not used to treat the erythrocytic stage of malaria. Administer the drug for the hypnozoite stage of P vivax and P ovale to prevent relapse.
Artemether and lumefantrine (Coartem)
This drug combination is indicated for the treatment of acute, uncomplicated P falciparum malaria. It contains a fixed ratio of 20 mg artemether and 120 mg lumefantrine (1:6 parts). Both components inhibit nucleic acid and protein synthesis. Artemether is rapidly metabolized into the active metabolite dihydroartemisinin (DHA), producing an endoperoxide moiety. Lumefantrine may form a complex with hemin, which inhibits the formation of beta hematin.
Artesunate
Artesunate, a form of artemisinin that can be used intravenously, is available from the CDC. It is not licensed for use in the United States but is available as part of an investigational new drug protocol.
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| Findings | P falciparum | P vivax | P ovale | P malariae |
| Only early forms present in peripheral blood | Yes | No | No | No |
| Multiply-infected RBCs | Often | Occasionally | Rare | Rare |
| Age of infected RBCs | RBCs of all ages | Young RBCs | Young RBCs | Old RBCs |
| Schüffner dots | No | Yes | Yes | No |
| Other features | Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms. | Late trophozoites develop pleomorphic cytoplasm. | Infected RBCs become oval, with tufted edges. | Bandlike trophozoites are distinctive. |
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