Blackwater Fever

Blackwater fever is massive intravascular haemolysis in falciparum malaria, producing haemoglobinuria (dark brown or black urine), jaundice and acute kidney injury. It is associated with repeated infections, inadequate prophylaxis or treatment, quinine exposure, G6PD deficiency and post artesunate delayed haemolysis.

• More frequent in non immune adults and travellers; also seen in children in endemic areas.
• Immune mediated destruction of parasitised and unparasitised red cells is central.

Sudden fever, rigors, loin pain, vomiting, jaundice, pallor, dark red or black urine, oliguria or anuria, splenomegaly.

• Rapid fall in haemoglobin, tachycardia, hypotension in severe cases.
• Differential diagnosis: severe malaria with intravascular haemolysis, G6PD haemolytic crisis, drug induced haemolysis (primaquine, dapsone, nitrofurantoin), leptospirosis, haemolytic uraemic syndrome, rhabdomyolysis, transfusion reaction, paroxysmal nocturnal haemoglobinuria, sepsis, snake envenomation.
• Complications: acute kidney injury, severe anaemia, hyperkalaemia, pulmonary oedema, shock, disseminated intravascular coagulation, death.

Haemoglobinuria with positive malaria test and haemolysis.

• Malaria film (often scanty parasites) or rapid test; haemoglobin, reticulocytes, bilirubin (indirect), LDH, haptoglobin (low), direct antiglobulin test, urinalysis (blood positive without red cells), creatinine, urea, potassium, bicarbonate, lactate.
• G6PD quantitative test after recovery; blood film for fragments and Heinz bodies; blood group and crossmatch.
• Exclude other causes of dark urine.

Treat malaria with an artemisinin, stop quinine if implicated, maintain urine output and transfuse as required.

• Supportive: admit to intensive or high dependency care, catheterise and measure hourly urine output, maintain euvolaemia with isotonic fluids, avoid nephrotoxins and quinine, monitor potassium, bicarbonate and haemoglobin 4 hourly, oxygen.
• Pharmacological: artesunate 2.4 mg/kg IV (children under 20 kg 3 mg/kg) at 0, 12 and 24 hours then daily, followed by a full oral artemisinin combination when able. Fluid resuscitation with 0.9 percent sodium chloride or Ringer lactate 10 to 20 mL/kg bolus if hypovolaemic then 1 to 2 mL/kg/h maintenance targeting urine output over 1 mL/kg/h. If oliguric after volume repletion: furosemide 1 to 2 mg/kg IV (adults 40 to 80 mg); sodium bicarbonate 8.4 percent 50 mL IV for severe acidosis; hyperkalaemia: calcium gluconate 10 percent 10 mL IV over 5 minutes, insulin 10 units with 50 mL of 50 percent dextrose IV, salbutamol 10 to 20 mg nebulised. Packed red cells 10 mL/kg for haemoglobin under 5 g/dL or symptoms; ceftriaxone 2 g IV daily if sepsis suspected.
• Procedures: haemodialysis or peritoneal dialysis for refractory hyperkalaemia, acidosis, fluid overload, uraemia; mechanical ventilation as required.
• Special groups: G6PD deficiency, avoid primaquine, dapsone, nitrofurantoin, sulfonamides in high doses, methylene blue and rasburicase; pregnancy, artesunate in all trimesters; children, careful fluids; previous blackwater fever, avoid quinine.
• Red flags: anuria, rising creatinine or potassium over 6.5 mmol/L, haemoglobin falling under 5 g/dL, respiratory distress, shock, persistent parasitaemia.
• Follow-up: haemoglobin, creatinine and electrolytes daily until stable; weekly haemoglobin for 4 weeks after artesunate; test G6PD after recovery; give chemoprevention advice.