Blackwater fever: the rise and fall of an exotic disease

After several descriptions by Hippocrates and a single possible medieval description by Gilles de Corbeil, a severe febrile illness accompanied by the passage of dark urine burst upon the medical scene in West Africa in 1819, described by an English surgeon named Tidlie. Most of his patients died within a few days. Further reports appeared from tropical regions until the turn of the century, J. Farrell Easmon having given the condition the name blackwater fever in 1884. Controversy raged about its relationship to malaria, as well as over its treatment with cinchona bark and quinine. Evidence evolved that it was a complication of falciparum malaria in which hemoglobinuria causing acute renal failure resulted from massive quinine-induced lysis of red blood cells. People with red cell abnormalities such as glucose-6-phosphate dehydrogenase deficiency proved particularly prone to developing it. Its incidence fell as more mildly acting antimalarial drugs replaced quinine. Several enigmatic issues bedeviled understanding of it, but a careful analysis of its historical development has enabled resolution of each of these.