Severe Malaria

Severe malaria is falciparum parasitaemia with one or more features of vital organ dysfunction or high risk of death. It is a medical emergency, and delays of hours increase mortality.

• Criteria: impaired consciousness (Glasgow Coma Scale under 11, Blantyre under 3), prostration, multiple convulsions (over 2 in 24 hours), respiratory distress or acidotic breathing, shock (systolic pressure under 80 mmHg adults, under 50 mmHg children), pulmonary oedema, abnormal bleeding, jaundice (bilirubin over 50 micromol/L) with other organ dysfunction, severe anaemia (haemoglobin under 5 g/dL children, under 7 g/dL adults), hypoglycaemia (under 2.2 mmol/L), acidosis (bicarbonate under 15 mmol/L, lactate over 5 mmol/L), renal impairment (creatinine over 265 micromol/L), hyperparasitaemia (over 10 percent).
• Risk groups: children under 5 years, pregnant women, non immune travellers, HIV, asplenia.

Altered consciousness, convulsions, deep acidotic breathing, severe pallor, jaundice, oliguria, dark urine, shock, hypoglycaemia, bleeding.

• Examination: fever (may be absent), hepatosplenomegaly, retinal whitening or haemorrhages in cerebral malaria, abnormal posturing.
• Differential diagnosis: bacterial meningitis, sepsis, severe dengue, typhoid, encephalitis, hepatitis, leptospirosis, diabetic ketoacidosis, poisoning, severe pneumonia, heat stroke, febrile seizures.
• Complications: neurological sequelae, acute kidney injury, acute respiratory distress syndrome, secondary bacterial sepsis, lactic acidosis, post artesunate delayed haemolysis, death.

Malaria diagnosis plus assessment of organ function.

• Rapid test and blood film with parasite density (repeat every 12 hours until negative); plasmodium PCR if needed.
• Glucose (immediately and every 4 hours), haemoglobin, full blood count, urea, creatinine, electrolytes, bicarbonate, lactate, liver function, blood gas, coagulation, blood group and crossmatch, blood culture, urine output; HIV test.
• Lumbar puncture when meningitis cannot be excluded; chest radiograph if respiratory distress.

Give IV artesunate immediately and correct life threatening problems.

• Supportive: high dependency or intensive care, left lateral position, airway protection, oxygen to saturation of 94 percent or more, strict fluid balance, nurse head up 30 degrees if consciousness is impaired, catheterise, avoid steroids and mannitol.
• Pharmacological: artesunate 2.4 mg/kg IV (children under 20 kg 3 mg/kg) at 0, 12 and 24 hours, then once daily; the IM route at 2.4 mg/kg if IV access fails. When able to swallow after at least 24 hours (3 doses), complete with a full course of artemether lumefantrine or dihydroartemisinin piperaquine at the doses for uncomplicated malaria. If artesunate is unavailable: artemether 3.2 mg/kg IM on day 1 then 1.6 mg/kg daily; or quinine dihydrochloride 20 mg/kg loading dose in 5 percent dextrose over 4 hours (omit if quinine received in the last 24 hours) then 10 mg/kg every 8 hours over 4 hours, switching to oral artemisinin combination when possible. Hypoglycaemia: 10 percent dextrose 5 mL/kg in children (50 percent dextrose 50 mL in adults), then infusion of 10 percent dextrose. Seizures: diazepam 0.2 to 0.3 mg/kg IV or rectal (adults 10 mg IV), repeat once; if continuing, phenobarbital 15 mg/kg IV or phenytoin 15 to 20 mg/kg IV over 30 minutes. Severe anaemia: transfuse packed cells 10 mL/kg (whole blood 20 mL/kg) over 3 to 4 hours when haemoglobin is under 5 g/dL, or under 7 g/dL with respiratory distress. Shock or sepsis: ceftriaxone 2 g IV daily (children 80 mg/kg/day) after blood cultures; crystalloid 10 to 20 mL/kg bolus for shock with reassessment, avoiding overload. Antipyretic: paracetamol 15 mg/kg every 6 hours.
• Procedures: renal replacement therapy for refractory acute kidney injury or acidosis; mechanical ventilation for respiratory failure or coma; exchange transfusion is not recommended.
• Special groups: pregnancy, IV artesunate in all trimesters, monitor glucose closely for hypoglycaemia and fetal wellbeing; children, glucose and fluid boluses carefully (avoid bolus in non shocked children); HIV, give artesunate at the usual doses and review antiretroviral interactions; sickle cell disease, transfusion thresholds.
• Red flags: coma, repeated seizures, respiratory distress, shock, hypoglycaemia, rising creatinine, lactate over 5 mmol/L, bleeding, parasitaemia not falling at 24 hours.
• Follow-up: parasite count every 12 hours until negative; haemoglobin weekly for 4 weeks after artesunate (delayed haemolysis); neurological and hearing follow-up in children.