Practical info Adjustment of parenteral dosing in renal failure of hepatic dysfunction The dosage of artemisinin derivatives does not have to be adjusted for patients with vital organ dysfunction. However, quinine accumulates in severe vital organ dysfunction. If a patient with severe malaria has persisting acute kidney injury or there is no clinical improvement by 48 h, the dose of quinine should be reduced by one third, to 10 mg salt/kg bw every 12 h. Dosage adjustments are not necessary if patients are receiving either haemodialysis or haemofiltration. Follow-on treatment The current recommendation of experts is to give parenteral antimalarial drugs for the treatment of severe malaria for a minimum of 24 h ounce started (irrespective of the patient’s ability to tolerate oral medication earlier) or until the patient can tolerate oral medication, before giving the oral follow-up treatment. After initial parenteral treatment, once the patient can tolerate oral therapy, it is essential to continue and complete treatment with an effective oral antimalarial drug by giving a full course of effective ACT (artesunate + amodiaquine, artemether + lumefantrine or dihydroartemisinin + piperaquine). If the patient presented initially with impaired consciousness, ACTs containing mefloquine should be avoided because of an increased incidence of neuropsychiatric complications. When an ACT is not available, artesunate + clindamycin, artesunate + doxycycline, quinine + clindamycin or quinine + doxycycline can be used for follow-on treatment. Doxycycline is preferred to other tetracyclines because it can be given once daily and does not accumulate in cases of renal failure, but it should not be given to children < 8 years or pregnant women. As treatment with doxycycline is begun only when the patient has recovered sufficiently, the 7-day doxycycline course finishes after the artesunate, artemether or quinine course. When available, clindamycin may be substituted in children and pregnant women. Continuing supportive care Patients with severe malaria require intensive nursing care, preferably in an intensive care unit where possible. Clinical observations should be made as frequently as possible and should include monitoring of vital signs, coma score and urine output. Blood glucose should be monitored every 4 h, if possible, particularly in unconscious patients.

Other considerations The guideline development group could find no plausible explanation for the finding of increased mortality among older children and adults in Asia who received rectal artesunate, which may be due to chance. Further trials would provide clarification but are unlikely to be done. The group was therefore unable to recommend its use in older children and adults. In the absence of direct evaluations of parenteral antimalarial drugs for pre- referral treatment, the guideline development group considered the known benefits of artesunate in hospitalized patients and downgraded the quality of evidence for pre-referral situations. When intramuscular injections can be given, the group recommends intramuscular artesunate in preference to rectal artesunate. Remarks This recommendation applies to all people with suspected severe malaria, including infants, lactating women and pregnant women in all trimesters. Where intramuscular artesunate is not available, use rectal artesunate (in children < 6 years), intramuscular artemether or intramuscular quinine.