The Multifactorial Epidemiology of Blackwater Fever

Abstract

Blackwater fever is a massive hemolytic event usually occurring in the context of repeated falciparum malaria infections and intermittent quinine use. Its etiology is poorly understood, and it is rarely seen today. Historical epidemiological observations from the 20th century demonstrated variable patterns in prisoners in Andaman Islands, refugees in Macedonia, canal workers in Panama, expatriates in Rhodesia, and Second World War soldiers. Rates of blackwater fever per 1,000 malaria cases varied over two orders of magnitude. Islands, such as the Andaman Islands and New Guinea, had lower blackwater fever rates than continental areas. During the Second World War, blackwater fever rates in British soldiers in West Africa and Australian soldiers in New Guinea differed by a factor of 40 despite similar treatment regimens and falciparum malaria transmission risks. Blackwater fever is a complex interaction between host erythrocyte, falciparum malaria, and antimalarial drugs which remains poorly understood.

A Report of Four Cases of Blackwater Fever after Quinine Treatment at Zinder National Hospital, Niger Republic

“…Also, certain viral and bacterial diseases have been linked to the occurrence of BWF [9, 10]. Its pathophysiology thus remains unclear [1, 9, 10]. In the present study, we report on four blackwater fever cases in adults treated with quinine for severe malaria.…”

“…BWF is found in areas where malaria is endemic [1, 11]. Several authors have reported on its recrudescence, especially in Africa [9, 12].…”

“…BWF pathophysiology is complex and not yet well known, but according to some authors, the disease is secondary to double red blood cell sensitivity to antimalarial drugs and Plasmodium falciparum , causing acute hemolysis [1, 2]. Intravascular hemolysis occurs after taking the offending drug [4].…”

“…Blackwater fever (BWF) is an acute intravascular hemolysis that results from antimalarial drug use [1–3]. It clinically manifests as hemolytic anaemia, hemoglobinuria, acute renal failure, and hypovolemia [3].…”

“…Glucose-6-phosphate dehydrogenase deficiency (G6PD) also is frequently associated with this syndrome; however, its role is not clearly demonstrated [1, 6]. More recently, cases have been reported in patients taking artemisinin for malaria treatment [1, 7, 8]. Also, certain viral and bacterial diseases have been linked to the occurrence of BWF [9, 10].…”