Severe malaria: Oral regimens

IV: intravenous; ACT: artemisinin combination therapy; CDC: United States Centers for Disease Control and Prevention; WHO: World Health Organization.

* If an antimalarial is taken for chemoprophylaxis, a different drug should be used for treatment.

¶ In general, the course of ACT is administered for three days.

Δ Take after a full meal or with whole milk. If the patient vomits within 30 minutes of taking a dose, then they should repeat the dose. Ideally, the first 2 doses should be taken 8 hours apart. Late recrudescence rates of approximately 5% have been reported in nonimmune males, treated with 6 doses of artermether-lumefrantrine^[3]; in such cases, close follow-up is warranted and, if retreatment is needed, an alternative regimen should be used.

◊ Artemether-lumefantrine (Coartem 20 mg + 120 mg) is the only ACT available in the United States. Other combination strengths listed in the table are available in other areas.

§ Artemether-lumefantrine can be used in second and third trimesters of pregnancy and, if no other options available, in first trimester as well. Not for infants <5 kg or women breastfeeding infants <5 kg.

¥ Artesunate + amodiaquine is associated with severe neutropenia, particularly in patients coinfected with HIV and especially in those on zidovudine and/or trimethoprim-sulfamethoxazole (cotrimoxazole). Avoid concomitant use in patients taking zidovudine, efavirenz, and cotrimoxazole unless this is the only ACT promptly available.

‡ Piperaquine prolongs the QT interval by approximately the same amount as chloroquine but by less than quinine. Dihydroartemisinin-piperaquine should not be used in patients with congenital QT prolongation or who are on medications that prolong the QT interval. Dihydroartemisinin-piperaquine may be taken with food but should not be taken with a high-fat meal. The dosing for children weighing <25 kg is in alignment with the WHO; it exceeds manufacturer dosing, which has been associated with insufficient piperaquine serum concentrations and increased treatment failures in younger children.

† Regimens containing mefloquine should be avoided in patients who presented with altered consciousness, since there is an increased incidence of neuropsychiatric toxic effects associated with mefloquine in the setting of cerebral malaria. In addition, treatment with mefloquine is not recommended in persons who have acquired infections from Southeast Asia due to drug resistance. Mefloquine hydrochloride (55 mg) is equivalent to mefloquine base (50 mg); mefloquine hydrochloride (220 mg) is equivalent to mefloquine base (200 mg).

** The alternative regimens summarized in the table are for completion of treatment for severe malaria acquired in areas where ACTs are not available.

¶¶ Doxycycline is preferred over other tetracyclines because it does not accumulate in renal failure and has a longer half-life. Tetracycline may be used as an alternative (adult dosing 250 mg orally 4 times daily for 7 days; pediatric dosing 6.25 mg/kg orally every 6 hours for 7 days). Tetracycline antibiotics may cause permanent tooth discoloration for children <8 years if used repeatedly. However, doxycycline binds less readily to calcium than other tetracyclines and may be used for ≤21 days in children of all ages.^[1] Clindamycin is preferred over tetracyclines in pregnancy.

ΔΔ For infections acquired in Southeast Asia, oral treatment consists of quinine (7 days) plus doxycycline or clindamycin (7 days). For infections acquired outside Southeast Asia, oral treatment consists of quinine (3 days) plus doxycycline, tetracycline, or clindamycin (7 days).

◊◊ Pediatric dosing may be difficult due to unavailability of noncapsule forms of quinine in the United States.

§§ Mefloquine is associated with adverse psychiatric and neurologic events and should be used only if the preceding agents are not available. Treatment with mefloquine is not recommended in individuals who have acquired infections from Southeast Asia due to drug resistance. The dosing regimen for mefloquine above is in alignment with the WHO^[4], which differs from the CDC approach; the WHO approach is associated with greater bioavailability and is better tolerated^[5].