Uncomplicated falciparum malaria

All children suspected or diagnosed with P falciparum malaria should be admitted to hospital for at least 24 hours, because of the possibility of rapid progression in severity of malaria and also potential poor tolerance of oral therapies.

Children with uncomplicated malaria, low parasitaemia (<2%) and no vomiting may be treated with oral antimalarials. Oral quinine, atovaquone-proguanil (Malarone, GlaxoSmithKline) and co-artem (Riamet, Novartis) can all be used for the treatment of uncomplicated malaria in children (table 2). The combination of oral quinine with a single dose of sulphadoxine-pyrimethamine (Fansidar, Roche) remains highly effective in the UK, with very low relapse rates in children.12 If Fansidar is contraindicated (eg, in children with glucose-6-phosphate dehydrogenase (G6PD) deficiency) or is not available, alternatives include clindamycin or doxycycline (for children >12 years age). In contrast to the views of some authors,15 the Health Protection Agency Advisory Committee on Malaria Prevention in UK travellers recommended that oral quinine be used in the treatment of uncomplicated falciparum malaria in the UK since it is usually well tolerated by children.12 16 Alternative oral antimalarial combinations, such as arthemeter-lumefantrine (Riamet) and atovaquone-proguanil (Malarone), are available but there is limited experience in their use in non-endemic paediatric setting. Mefloquine is also effective but is not recommended in the UK because of its side effects and high rate of non-completion of treatment courses. Halofantrine has also been used in some countries to treat acute, uncomplicated malaria but is associated with potentially fatal cardiac arrhythmias, particularly in individuals receiving drugs that may prolong the QT interval.

Severe malaria

The main presentations of severe malaria in children are cerebral malaria, severe anaemia and respiratory distress/acidosis. Features of cerebral malaria include depressed conscious level, seizures altered respiration and posturing (decorticate or decerebrate). Hypoglycaemia, metabolic acidosis, circulatory shock and electrolyte disturbance may also be present. Prostration (the inability to sit or stand) may also be an indicator of severe disease in children.16

Supportive care

Guidelines for the management of severe or complicated imported childhood malaria in the UK have been proposed recently.15 This involves emergency assessment and provision of supportive care as advocated by the Advanced Paediatric Life Support guidelines, including respiratory and cardiovascular support. Children with features of severe or complicated malaria should be managed in a paediatric intensive care unit or high dependency unit together with support/advice from a paediatric infectious diseases/tropical medicine specialist who has experience in managing malaria. Initial assessment will include a blood gas, blood culture, lactate, clotting profile, as well as urine dipstick and culture on admission. Children with respiratory distress should have a chest x-ray. Febrile patients with impaired consciousness or repeated seizures should have a lumbar puncture to exclude meningitis once their condition is stable. Aggressive management is recommended for those with depressed conscious level, active seizure activity, irregular breathing, hypoxia, shock, dehydration, hypoglycaemia, metabolic acidosis and hyperkalaemia. Children with anaemia associated with severe malaria may require blood transfusion, although the haemoglobin level at which transfusion should be given remains uncertain. A Cochrane review found that routine transfusion did not reduce mortality, but caused more adverse events17 Exchange transfusion has been advocated for hyperparasitaemia >20% (or >10% in the presence of severe symptoms) in adult intensive care settings despite little evidence to indicate improved outcome.18 Concurrent bacterial infections (meningitis or septicaemia) are rare in children with imported malaria, even in severe cases, but most clinicians would advocate empiric broad-spectrum antibiotics, such as a third-generation cephalosporin, with collection of appropriate cultures before commencing antibiotics. Platelet transfusions for thrombocytopenia, even at platelet levels <20×109/l, are generally not recommended because thrombocytopenia is not associated with bleeding problems in children. Serious complications such as renal or liver impairment or raised intracranial pressure may warrant early transfer to an intensive care unit for careful assessment, close monitoring and specialist management.

Antimalarial therapy

Parenteral quinine is the recommended antimalarial therapy for patients with severe falciparum malaria or non-severe malaria who are unable to tolerate oral medication. Current UK guidelines recommend a loading dose of 20 mg/kg quinine dihydrochloride in 5% dextrose or dextrose saline as a slow infusion over 4 hours, followed by 10 mg/kg (maximum 600 mg) every 8 hours for first 48 hours or until the patient can swallow.16 The frequency of dosing should subsequently be reduced to 12 hourly if intravenous quinine continues for more than 48 hours. Close monitoring is required for hypoglycaemia, hypoxia and seizures. Intravenous treatment should be changed to oral medication once the patient's condition improves and parasite levels fall.

Artemisinin derivatives (mainly artesunate and artemether) are a potential alternative to quinine for the treatment of severe malaria. This class of drugs has the advantage of a more rapid reduction of parasite burden. Treatment with intravenous artesunate has been shown to significantly reduce the risk of death and reduce parasite clearance time in adults with severe malaria compared with quinine.19 However, two systematic reviews have shown no difference in mortality between artemisin derivatives and quinine in children with severe malaria and cerebral malaria.20 21

Non-falciparum malaria

Antimalarial therapy should target both the asexual erythrocytic forms that cause symptoms and, for P ovale and P vivax infections, ensuring eradication of liver hypnozoites to prevent relapse. Chloroquine (initial dose 10 mg/kg/base (max 600 mg) then 5 mg/kg base (max 300 mg) 6–8 hours later and on days 2 and 3) remains the treatment of choice for eliminating the erythrocytic forms of non-falciparum malaria (table 3). Chloroquine is highly effective against all strains of P malariae and P ovale and is effective in most cases of P vivax malaria. Chloroquine resistance leading to poor clinical outcomes has been recognised in vivax malaria, although this is uncommon and may occur in regions of Papua New Guinea and Indonesia.22 In cases of treatment failure (persistent symptoms and/or parasitaemia) or mixed infection with P falciparum, any of the antimalarial combinations recommended for treating P falciparum malaria would be effective in treating the erythrocytic forms of non-falciparum malaria.

Blood schizonticides, such as chloroquine, do not eliminate liver hypnozoite forms seen in P ovale and P vivax and may cause relapse in up to 25% of cases treated with chloroquine alone.23 Therefore children screened negative for G6PD deficiency should also be treated with primaquine. In P ovale malaria, a single daily dose of 0.25 mg/kg (maximum dose 15 mg) should be given for 14 days. For P vivax malaria, however, because of increasing resistance to primaquine, particularly in South East Asia where most UK cases are acquired, a higher single daily dose of 0.5 mg/kg (maximum dose 30 mg) for 14 days is recommended.24

Expert opinion should be sought when treating children with G6PD deficiency. In children with mild deficiency, primaquine 0.5–0.75 mg/kg (max 30 mg) as a single weekly dose for 8 weeks may be well tolerated. In those with severe deficiency or severe primaquine adverse effects, it may be prudent to withhold primaquine but treat any relapse promptly.16