An otherwise healthy 30-year-old man had been ill for 2 days when he presented with a temperature of 39°C and reported passing dark urine (his case was noted in Bhatt et al., East African Medical Journal 1994;71:755-7). He reported taking no medication before coming to the hospital. Laboratory evaluation on admission was notable for a hemoglobin level of 7.6 g per deciliter, a serum urea nitrogen level of 4.8 mmol per liter (0.13 mg per deciliter), and a creatinine level of 89 µmol per liter (1.0 mg per deciliter). The total bilirubin level was 15 µmol per liter (0.88 mg per deciliter), and the conjugated bilirubin level 1 µmol per liter (0.06 mg per deciliter). A urinary dipstick test was positive for blood but microscopical examination showed no red blood cells (the dipstick test used could not differentiate red blood cells from hemoglobin). The blood smear showed 5% parasitemia of red blood cells with Plasmodium falciparum. Progressive clearance of his urine is shown, from dark brown on admission (T0, or zero hour) to yellow 42 hours after admission (T42). His condition improved on treatment with quinine, initially administered intravenously and then orally for a total of 7 days. He stayed in the hospital for 48 hours. The qualitative glucose-6-phosphate dehydrogenase (G6PD) level 28 days later was very low. Black-water fever is most often associated with the use of antimalarial medication, especially quinine, but in this patient, dark urine developed before quinine therapy, making this diagnosis less likely. As many Africans are heterozygotes for G6PD deficiency, which is thought to provide protection against malaria, this may be the cause of his hemolysis.
Martin Tombe, M.D.
Mpilo Central Hospital
NEJM Volume 358:1837 April 24, 2008 Number 17