A case of blackwater fever with persistent Plasmodium falciparum parasitaemia detected by PCR after artemether-lumefantrine treatment.

BACKGROUND: Blackwater fever is a complication of malaria infection consisting of a syndrome of febrile intra-vascular haemolysis with severe anaemia and intermittent passage of dark-red to black colour urine. Despite numerous reports and studies of this condition, its pathogenesis remains incompletely understood. CASE PRESENTATION: This report describes a case of classic blackwater fever in a returning traveller, without prior history of malaria infection nor usage of anti-malarial prophylaxis, treated with two courses of oral artemether-lumefantrine combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum parasitaemia was detected by PCR for 18 days after initiation of treatment. CONCLUSION: To the authors' knowledge this is the first reported occurrence of a case of blackwater fever associated with prolonged submicroscopic parasitaemia. This unusual case challenges the current knowledge of the pathogenesis of this condition and opens questions that may have important diagnostic and treatment implications.

High Frequency of Blackwater Fever Among Children Presenting to Hospital With Severe Febrile Illnesses in Eastern Uganda.

BACKGROUND: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). METHODS: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. RESULTS: Of 3170 trial participants, 394 (12.4%) had BWF. The majority (318 [81.0%]) presented in eastern Uganda and were the subjects of further analysis. BWF cases typically presented with both clinical jaundice (254/318 [80%]) and severe anemia (hemoglobin level <5 g/dL) (238/310 [77%]). Plasmodium falciparum parasitemia was less frequent than in non-BWF controls, but a higher proportion were positive for P. falciparum histidine rich protein 2 (192/246 [78.0%]) vs 811/1154 [70.3%]; P = .014), suggesting recent antimalarial treatment. Overall, 282 of 318 (88.7%) received transfusions, with 94 of 282 (33.3%) and 9 of 282 (3.4%) receiving 2 or 3 transfusions, respectively. By day 28, 39 of 318 (12.3%) BWF cases and 154 of 1554 (9.9%) non-BWF controls had died (P = .21), and 7 of 255 (3.0%) vs 13/1212 (1%), respectively, had severe anemia (P = .036). We found no association with G6PD deficiency. The prevalence of both the sickle cell trait (10/218 [4.6%]) and homozygous α+thalassemia (8/216 [3.7%]) were significantly lower among cases than among population controls (334/2123 [15.7%] and 141/2114 [6.6%], respectively), providing further support for the role of malaria. CONCLUSIONS: We report the emergence of BWF in eastern Uganda, a condition that, according to local investigators, was rare until the last 7 years. We speculate that this might relate to the introduction of artemisinin-based combination therapies. Further studies investigating this possibility are urgently required.

Severe malaria in children: A descriptive report from Kinshasa, the Democratic Republic of Congo.

The decline of susceptibility of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine resulted in the change of drug policy. This policy has probably changed the facies of the severe form of malaria. A prospective study was conducted in Kinshasa, the Democratic Republic of Congo. Data on children aged ≤13 years, diagnosed with severe malaria were analyzed. In total, 378 children were included with an overall median age of 8 years (age range: 1-13 years). Dark urine was seen in 25.1% of cases. Metabolic acidosis (85.2%), hypoglycemia (62.2%) and hemoglobin ≤5 g/dl (39.1%) were the common laboratories features. Severe malaria anemia, cerebral malaria and Blackwater fever (BWF) were found in 39.1, 30.1 and 25.4%, respectively. Mortality rate was 4%. BWF emerges as a frequent form of severe malaria in our midst. Availing artemisin-based combination treatments in the health care system is a priority to reduce the incidence of BWF in our environment.

Polymorphisms in the K13-propeller gene in artemisinin-susceptible Plasmodium falciparum parasites from Bougoula-Hameau and Bandiagara, Mali.

Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.

Black water fever associated with acute renal failure among Congolese children in Kinshasa.

Acute renal failure (ARF) is reported in some severe forms of malaria such as black water fever (BWF). It is associated with a high mortality rate and can be managed effectively with adequate renal replacement. A prospective survey of children with dark urine after a malarial infection with Plasmodium falciparum was coupled with a chart review study of patients managed in the past 11 years in the Pediatrics' Kinshasa University Hospital. Eighty-nine cases of ARF were identified, but data from only 63 patients were available, of whom 44 (69.8%) had severe malaria (39 with BWF and 5 with cerebral malaria). The mean age of the patients was 8.2±1.73 years. Of the 39 cases of BWF, an association with quinine ingestion was observed in 32 children (82%). Urea and creatinine levels were elevated in all cases (135.4±88.2 and 3.83±2.81 mg/dL, respectively). Oligo-anuria was observed in 44.4%, severe metabolic acidosis (bicarbonate<15 mEq/L) in 61.5% and hyponatremia (<130 mEq/L) in 33.3%. Peritoneal dialysis was required in 36 patients, including 20 with BWF. The remaining patients were managed with conservative treatment. Twenty-eight children (44.4%), including 20 on dialysis, fully recovered and 14 died (22.2%), including eight cases of BWF. Our study suggests that ARF is commonly associated with BWF in Congolese children. Elevated urea and creatinine and severe metabolic acidosis were observed more often than other clinical/metabolic disturbances. Severe renal impairment remains a significant complication with a high mortality rate in low-resource settings.

Blackwater fever like in murine malaria.

Blackwater fever (BWF) is the term used to designate the occurrence of hemoglobin pigments in the urine of patients infected with malaria parasites. BWF is more often associated with Plasmodium falciparum infection in man. The pathogenesis of BWF has not been explained satisfactorily. In the present study, the clinical and pathological observations made upon CD1 mice infected with Plasmodium yoelii yoelii lethal strain with clinical signs of hemoglobinuria and acute renal failure were evaluated. From the 40 P. yoelii yoelii-infected mice, 14 presented hemoglobinuria. In the observations, it was emphasized that hemoglobinuria occurred in the animals 1-2 days before they die. At 6 days post-infection, infected hemoglobinuric mice (HM) exhibited clinical signs such as dark red urine, apnea, and evident oliguria and hematuria; urine microscopical examination showed very few red blood cells. The entire non hemoglobinuric infected mice had a high parasitemia preceding the time of death, while the HM parasitemia was just detectable. In HM, marked hepatosplenomegaly, anemia, and renal and hepatic dysfunction were observed with the blood chemistry analysis at 6 days post-infection. Severe renal lesions were demonstrated in histopathological and scanning electron microscopy samples. Occlusion and necrosis of convoluted tubules were the main lesions found. The conditions required for the experimental production of hemoglobinuria in CD1 mouse infected by P. yoelii yoelii is still unknown. The clinical picture of a BWF, like in our rodents, was produced exclusively by the interaction between the parasite and its host. Results showed that hemoglobinuria in CD1 mice infected with P. yoelii yoelii and BWF in man infected with P. falciparum are similar in their pathogenesis.

[Blackwater fever in children during cerebral malaria: 3 case reports in Bamako]. / La fièvre bilieuse hémoglobinurique chez l'enfant: à propos de 3 observations à Bamako.

BACKGROUND: Blackwater fever is a rare but serious form of malaria in children. Diagnosis relies on clinical symptoms and on the color of the urines. OBJECTIVES: To describe blackwater fever in children, a disease whose prevalence seems to be increasing. METHOD: We report 3 cases of blackwater fever observed in our institution. RESULTS: In 2 cases, acute renal insufficiency with oligoanuria was observed. In all the 3 cases, treatment with quinine was stopped and replaced by injectable artemether. Evolution was dependent on renal function, and included in 1 patient neurological sequels consisting in aphasia. CONCLUSION: Blackwater fever is a severe affection whose diagnosis should be evoked using the color of urine. Evolution is usually favorable in the pediatric population, when adequate care can be provided.

[Clinical study on 24 cases of eclampsia with cerebral malaria].

OBJECTIVE: To explore the clinical characteristics of eclampsia with cerebral malaria. METHODS: A retrospective analysis was done in 24 in-patient cases of eclampsia with cerebral malaria in Mnazimmoja Hospital of Zanzibar from Jul. 1995-Oct. 1998. All had varying degrees of coma, high fever and convulsion with anemia and splenomeguly. In all cases, malarial parasitein in blood smear was positive and underwent anti-malaria treatment, anti-eclamptic convulsion treatment and complex treatment for the prevention of complications, so that 20 of them could terminate pregnancy rapidly. RESULTS: 17 patients were conscious 2-3 days after complex treatment. Their vital signs were gradually stable and pregnancy termination was smooth. 7 patients died, 4 of them due to complicated with blackwater fever and renal failure, one with cardiopneumatic failure, postpartum hemorrhage and puerperal infection respectively. The number of fetal deaths, stillbirth and live births was 8, 7 and 9 respectively. CONCLUSION: Eclampsia with cerebral malaria is an acute and dangerous obstetrical disease. Complex therapy, we think, should be given mainly to the patients. Termination of pregnancy is the key to effective cure of the disease.