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[Blackwater fever].

DEFINITION: Blackwater fever is a clinical entity characterized by acute intravascular hemolysis classically occuring after the re-introduction of quinine in long-term residents in Plasmodium falciparum endemic areas and repeatedly using the product. CLINICAL PROFILE: The symptomatology appears brutally with emission of porto-colored urine, icterus, pallor, nausea, fever and acute renal failure. The hemolytic-like anemia is immediately severe. Parasitemia is mild or absent. The mechanism of renal failure is tubular necrosis. QUININE AND SIMILAR MOLECULES: Well known at the start of the 20th century, blackwater fever has become exceptional since 1950, when quinine was replaced by chloroquine. The disease reappeared in 1990, following the re-utilization of quinine because of resistance to chloroquine. Thereafter, several cases have been described with halofantrine and mefloquine, two new molecules similar to quinine (amino-alcohol family). The physiopathogenesis of the disease is not well known, however it would appear that the concomitance of a double sensitivization of the red blood cells to the P. falciparum red blood cells and to the amino-alcohols is necessary to provoke the hemolysis. EVOLUTION: The severity of the clinical picture often requires initial management in intensive care unit. Nowadays, however, prognosis is good and the disease usually regresses without after effects.

Adolescent↗

BLACKWATER fever.

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Blackwater Fever↗

Blackwater fever treated with artemether.

Blackwater fever is a rare manifestation of falciparum malaria characterized by sudden intravascular hemolysis followed by fever and hemoglobinuria. We present a case of blackwater fever, having occurred after administration of quinine, which was treated successfully with artemether.

Adult↗

[Blackwater fever in adults with sickle cell anemia. Two fatal cases].

Blackwater fever is characterized by severe intravascular hemolysis with renal failure caused by recurrent use of quinine for prophylaxis. Once described in European patients, sporadic cases have been reported more and more often in autochthonous Africans and Asians. Newer antimalarials including aminoalchohol mefloquine, and halofantrine have also been implicated in Blackwater fever. In this report we describe two cases of blackwater fever involving patients with sickle cell anemia (HbSS). Symptoms including fever, acute hemolytic anemia, emesis, back pain, and hemoglobinuria were characteristic of blackwater fever. Both patients died. Although the underlying mechanism of blackwater fever remains unclear, a likely explanation is an immunoallergic reaction to quinine. Association with glucose-6-phosphate dehydrogenase deficiency has often been reported. Our cases suggest that blackwater fever may also be correlated with hemoglobinopathy such as HbSS.

Adolescent↗

Blackwater fever in children, Burundi.

Blackwater fever is characterized by acute intravascular hemolysis with hemoglobinuria in patients with Plasmodium falciparum malaria. Its pathogenesis and management are still debated. Nine cases of this syndrome occurred in 2003 at Kiremba Hospital in Burundi in children receiving multiple quinine treatments.

Adolescent↗

Blackwater fever at the Kenyatta National Hospital in Kenya: a case report.

Blackwater fever was an important cause of morbidity and mortality in the beginning of this century particularly in West and Central Africa. There has been a marked reduction in the incidence of blackwater fever since 1950 and only sporadic cases occur nowadays. At the Kenyatta National Hospital, three cases of blackwater fever have been seen in the past four years whereas not a single case had been reported between 1975 and 1988. Two of the patients fit into the classical description of blackwater fever and one was possibly due to drug induced haemolysis in a G6PD deficiency patient.

Adult↗

[Methemalbuminnemia after massive hemolysis during blackwater fever].

We report a case of blackwater fever with brown plasma due to the presence of methemalbumin. The discovery of plasma with this color is a rare event at the laboratory. This compound appears during intravascular hemolysis or hemorrhagic pancreatitis when the ability of haptoglobin and hemopexin to bind free hemoglobin has been exceeded. In these cases some of heme is oxidized to hematin and taken up by serum albumin to form an albumin-hematin complex called methemalbumin. The major clinical problem is to evoke the diagnosis of methemalbuminemia and not confuse with methemoglobinemia. In our case, methemalbumin was detected and quantified using a scanning spectrophotometer. Its diagnostic and clinicals consequences are discussed.

Anemia, Hemolytic↗

[A mild blackwater fever].

We report a highly probable case of moderately severe blackwater fever. A French woman, living in Guinea Bissau, was used to taking self-medication halofantrine for malaria. On this occasion, she felt unusual chills and pyrexia after a non documented bout of malaria, followed by nausea, then jaundice with dark-red urines despite another treatment with halofantrine. A sepsis was eliminated by two negatives thick peripheral blood drop examinations. Hemolysis was noted with 8.1 g/dl of hemoglobin, Coombs positive, and LDH at 1,452 IU/l, associated to renal failure with 34 ml per minute of clearance. The outcome was favourable with rehydration. Blackwater fever has been described with the three aminoalcohols, but mainly in severe presentations. Clinicians are not familiar with this disease, even though it has major therapeutic implications: quinine, halofantrine, and mefloquine become strictly contra-indicated. Moderate forms may be unknown, and this observation should be taken into account to prevent mistreatment in future patients.

Acute Kidney Injury↗

[Blackwater fever during antimalarial treatment in Abidjan (West Africa): report of 41 cases].

Intravascular haemolysis, particularly blackwater fever is a rare but severe clinical syndrome, occurring after ingestion of antimalarials. A resurgence of this affection which occurred frequently during the colonization has lately been noticed. We have conducted a prospective study in order to identify the main antimalarials which are responsible for this syndrome. We reported 41 cases from 1996 to 2000, among which 80% of blackwater fever cases were associated with quinine ingestion or similar structural molecules. Their causal role is well established. For the other molecules it is difficult to underscore their role. The mortality rate is around 18%. The morbidity is high because 90% of patients have suffered from renal failure. Among them, 47% required dialysis. We are facing a public health issue thus a rational use of antimalarials is necessary.

Adolescent↗

[Blackwater fever: a case report].

The first case of blackwater fever was reported in Cuban medical literature. It is an uncommon complication of paludism due to Plasmodium falciparum, characterized by fever, hemoglobinuria, and kidney failure, with dramatic development and high mortality. The patient came from the People's Republic of Angola, where he stayed 7 years, with history of various episodes of malaria. He was admitted with fever, icterus and thick film test positive for P. falciparum. Treatment with quinine was started, but dark red urine and an increase of icterus were observed 12 hours later. Treatment with quinine was suspended. Red blood cells and platelets were transfused and hemodialysis and plasmapheresis were performed. The patient was discharged 2 weeks later asymptomatic and with negative thick film test. The pathogeny of this disease was discussed, specially kidney failure, making emphasis on the importance of the symptomatic and maintenance treatment in the patient's evolution.

Blackwater Fever↗

Epidemiological and clinical aspects of blackwater fever among African children suffering frequent malaria attacks.

Blackwater fever (BWF), one of the commonest causes of death of Europeans living in Africa at the beginning of the twentieth century, but rarely diagnosed since the 1950s, is related to Plasmodium falciparum malaria but there is considerable debate and controversy about its aetiology. From 1990 to 2000, the whole population of Dielmo, a village in Senegal, was involved in a prospective study of malaria. Three cases of BWF occurred in 3 children aged 4, 7 and 10 years, belonging to a subgroup of children who suffered malaria attacks every 4 to 6 weeks over many years, who had received repeated quinine treatment. The spread of chloroquine resistance, by increasing the use of more toxic alternative drugs, may expose endemic populations to a high incidence of severe side effects of antimalarials.

Antimalarials↗

Recurrence of blackwater fever: triggering of relapses by different antimalarials.

Five cases of blackwater fever (BWF) are described, all of whom had a history of recent quinine therapy. In two cases a second haemolytic crisis was induced by halofantrine, in one case also a third. Increasing frequency of this syndrome with its dramatic clinical presentation is to be expected as imported P. falciparum infection, parasite resistance to chloroquine and the use of quinine and other related antimalarials become more frequent.

Adult↗

Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review.

Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically exposed to Plasmodium falciparum and irregularly taking quinine. BWF virtually disappeared after 1950, when chloroquine superseded quinine. We report 21 cases of BWF seen in France from 1990 through 1999 in European expatriates who lived in sub-Saharan Africa. All patients had macroscopic hemoglobinuria, jaundice, and anemia. Acute renal failure occurred in 15 patients (71%), 7 of whom required dialysis. The presumed triggers of BWF were halofantrine (38%), quinine (24%), mefloquine (24%), and halofantrine or quinine (14%). Glucose-6-phosphate dehydrogenase (G6PD) activity was normal in the 14 patients who underwent this test. Low-level P. falciparum parasitemia was found in 8 patients. All 21 patients survived. Our data and 13 cases reported in the literature suggest a resurgence of classic BWF among Europeans living in Africa and a need to discuss attendant therapeutic implications.

Adolescent↗