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UK treatment of malaria
  1. Delane Shingadia,
  2. Shamez Ladhani
  1. Health Protection Agency, London
  1. Correspondence to Dr Delane Shingadia, Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK; shingd{at}


Imported malaria has become an increasingly significant cause of mortality and morbidity in children travelling to areas of the world endemic for malaria. Malaria is one of the commonest imported tropical diseases in the UK, with children accounting for 15–20% of all cases. Over 80% of all cases of malaria are due to Plasmodium falciparum infection, which can cause severe or life-threatening multi-organ disease in children. The clinical features of malaria in children are often non-specific, resulting in missed or delayed diagnosis. Children are more likely than adults to deteriorate rapidly and to develop severe malaria, particularly cerebral malaria. Malaria should be suspected in all children with a history of travel to a malaria-endemic country who present with fever. Diagnosis is usually made with repeated thick and thin blood films. Delays in diagnosis are associated with an increased risk of developing severe malaria and death. Appropriate antimalarial therapy and supportive care should be instituted as soon as possible, particularly in children with severe malaria. Advice should be sought from an appropriate specialist.

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Malaria is a vector-borne infection caused by protozoan parasites of the genus Plasmodium. Five species that infect humans are usually transmitted by anopheline mosquitoes (P falciparum, P vivax, P ovale, P malariae and P knowlesi). P falciparum causes the most severe disease and is responsible for most of the long-term complications, whereas P vivax, P ovale and P malariae usually cause milder disease and are not fatal except in individuals with underlying comorbidities. P knowlesi usually causes malaria in primates and only infects humans opportunistically, but recent studies have suggested that P knowlesi may contribute to a significant proportion of malaria cases in parts of South East Asia. where such infections may be misdiagnosed as P malariae.1 Unlike P malariae, however, P knowlesi has a higher rate of replication (every 24 hours), resulting high level of parasitaemia, and may be associated with severe infection and death.2 Chronically infected humans are the major reservoir of malaria. Both P vivax and P malariae can remain dormant in the liver (so-called hypnozoite form) and emerge months to years after initial infection. Malaria may rarely be transmitted by blood transfusion or needlestick injury from infected donors. Airport malaria has also been described near international airports, presumably following a bite from an infected mosquito that has survived a long-distance air flight from an endemic country.3

Malaria is one of the most common infectious diseases globally and a major cause of morbidity and mortality. In 2008, there were an estimated 243 million malaria cases worldwide and almost one million deaths, mostly in the African region and in children.4 In Europe, the UK has one of the highest burdens of imported malaria with cases peaking in 1995 at 2500 cases followed by a gradual fall to 1370 cases in 2008.5 Children account for 15–20% of all cases and the estimated burden of imported malaria in the UK is 2.8/100 000 children, with P falciparum accounting for over 80% of childhood cases.6 7 Over 90% of all imported malaria cases in the UK occurred among black African children, who acquired their infection in Africa while visiting friends and relatives (so-called VFR).8 VFRs have been identified as a specific group of travellers who are less likely to seek pre-travel advice or take antimalarial prophylaxis and have different risk factors from conventional travellers.9 They are also more likely to be exposed to infection because they travel to rural areas for longer periods.9 VFRs are also more likely to delay seeking medical help when they return to their country of residence, often because of cultural and language barriers.10

Clinical presentation

The symptoms of malaria are varied and often mimic other common childhood illnesses. Malaria should be considered in any child presenting with fever who has travelled to an area where malaria is endemic. Nausea and vomiting are also common clinical presentations. Compared with adults, children are less likely to complain of chills, arthralgia/myalgia or headache but are more likely to have hepatomegaly, splenomegaly and jaundice.11

Severe malaria occurs almost exclusively with P falciparum infections. In the UK, 5–15% of children with imported malaria present with features of severe malaria as defined by the World Health Organization (table 1).12 In imported cases, severe malaria is associated with young age (<5 years), delayed diagnosis and non-immunity to malaria. Children with severe malaria may also develop focal neurological signs, decerebrate or decorticate posturing, spontaneous bleeding, disseminated intravascular coagulation, hypotension, cardiovascular shock, pulmonary oedema, haemoglobinuria, acute renal failure and multi-organ failure. Concurrent bacterial septicaemia is rare (<5%) but should be considered in children presenting with severe malaria.

Table 1

Severe or complicated malaria


Diagnosis of malaria is usually made by microscopic examination of thick and thin blood films, which should be requested in any febrile child who has travelled to a malaria-endemic area in the preceding 12 months, irrespective of any chemoprophylaxis taken. If there is clinical suspicion of malaria but initial blood films are negative (may occur in up to 7% of cases), repeat films should be examined after 12–24 hours and again after a further 24 hours. Thick blood smears are more sensitive in detecting malaria parasites because the blood is more concentrated, allowing for a greater volume of blood to be examined. Thin blood smears are used for identifying the Plasmodium species as well as parasite count, usually reported as percentage of red blood cells parasitised. Rapid diagnostic tests (RDT), based on detection of parasite antigens in blood, are being increasingly used to diagnose malaria. Although slightly less sensitive than good quality blood films, they are easier for the non-expert to use to detect falciparum infections. RDTs are not as specific and sensitive for detection of non-falciparum infections.13 Thrombocytopenia is highly suggestive of malaria in non-immune children, both in falciparum and non-falciparum malaria, and should be a prompt to repeat blood films where the initial blood films are negative.14


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.

Table 2

Treatment of falciparum malaria

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.

Table 3

Treatment 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



  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.