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Clinical Microbiology and Infection :... Jan 2024Blackwater fever (BWF) is a severe syndrome occurring in patients with malaria upon antimalarial treatment, characterized by massive intravascular haemolysis and... (Review)
Review
BACKGROUND
Blackwater fever (BWF) is a severe syndrome occurring in patients with malaria upon antimalarial treatment, characterized by massive intravascular haemolysis and haemoglobinuria. BWF is a neglected condition and management recommendations are unavailable.
OBJECTIVES
We performed a scoping review to appraise available data on clinical picture, treatment and physiopathology of BWF, which could guide rationally its clinical management.
METHODS
MEDLINE, EMBASE, LILACS, Web of Science, and Scopus databases, and the reference list of relevant publications, were searched. Papers reporting original data on BWF cases or investigating the physiopathology of BWF were eligible. Data regarding case characteristics, trigger event, clinical management and outcome were extracted. For papers investigating the physiopathology of BWF, study design and principal findings were extracted. No quality assessment was performed. Data are presented as numbers and percentages, and summary of findings, grouped by paper focus (clinical description or physiopathology).
RESULTS
101 papers were included. The majority of BWF cases were observed in autochthonous children (75.7%) and adults (15.3%), in contrast with historical perception that BWF patients were typically expatriates. Clinical management was described for 794 cases; corticosteroids were used in 23. Outcome was reported for 535 patients, with 18.1% mortality. The trigger was reported for 552 (47.5%) cases; in 70.4% identified as quinine. However, two RCT comparing artesunate and quinine for falciparum malaria treatment did not find significant difference in BWF occurrence after their administration. Two case-control studies did not find significant difference in G6PDH deficiency between malaria patients with and without BWF.
CONCLUSIONS
The physiopathology and optimal treatment of BWF remain similarly unknown as they were over a century ago. Empirical supporting treatment approach seems reasonable, while change of antimalarial drug and use of corticosteroids remain object of debate.
Topics: Child; Adult; Humans; Blackwater Fever; Quinine; Malaria, Falciparum; Antimalarials; Malaria; Adrenal Cortex Hormones
PubMed: 37739261
DOI: 10.1016/j.cmi.2023.09.009 -
BMC Medicine Jul 2022Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and... (Observational Study)
Observational Study
BACKGROUND
Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood.
METHODS
A prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host markers of immune and endothelial activation were quantified on admission plasma samples. The relationships between BWF and AKI and clinical and biologic factors were evaluated using multivariable regression.
RESULTS
We evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7 years (standard deviation 1.06), 55.7% male). At enrollment, 8.2% of children had a history of BWF, 49.5% had AKI, and 11.1% had severe AKI. A history of BWF was independently associated with 2.18-fold increased odds of AKI (95% CI 1.15 to 4.16). When examining host response, severe AKI was associated with increased immune and endothelial activation (increased CHI3L1, sTNFR1, sTREM-1, IL-8, Angpt-2, sFlt-1) while BWF was predominantly associated with endothelial activation (increased Angpt-2 and sFlt-1, decreased Angpt-1). The presence of severe AKI, not BWF, was associated with increased risk of in-hospital death (RR, 2.17 95% CI 1.01 to 4.64) adjusting for age, sex, and disease severity.
CONCLUSIONS
BWF is associated with severe AKI in children hospitalized with a severe febrile illness. Increased awareness of AKI in the setting of BWF, and improved access to AKI diagnostics, is needed to reduce disease progression and in-hospital mortality in this high-risk group of children through early implementation of kidney-protective measures.
Topics: Acute Kidney Injury; Biomarkers; Blackwater Fever; Child; Female; Hospital Mortality; Humans; Infant; Male; Prognosis; Prospective Studies
PubMed: 35773743
DOI: 10.1186/s12916-022-02410-4 -
The American Journal of Tropical... Aug 2016Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century.... (Review)
Review
Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds.
Topics: Africa; Antimalarials; Asia; Australia; Blackwater Fever; Chemoprevention; Cinchona; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Malaria, Falciparum; Plasmodium falciparum; Quinine
PubMed: 27185766
DOI: 10.4269/ajtmh.16-0138 -
Cureus May 2022Despite advances in treatment and prevention, malaria still carries significant morbidity and mortality. Cases of malaria in the United States are rare and cases of...
Despite advances in treatment and prevention, malaria still carries significant morbidity and mortality. Cases of malaria in the United States are rare and cases of severe malaria, mostly attributable to , are even more uncommon. With the coronavirus disease 2019 (COVID-19) pandemic, there have been distractions in evaluation and diagnosis leading to a rise in cases and deaths. We present a case of autoimmune dysregulation and blackwater fever secondary to severe malaria, requiring multiple courses of antimalarial therapy. Careful travel history and prompt recognition and treatment facilitates improved patient survival and recovery.
PubMed: 35774704
DOI: 10.7759/cureus.25458 -
The American Journal of Tropical... Dec 2017Blackwater fever is a massive hemolytic event usually occurring in the context of repeated falciparum malaria infections and intermittent quinine use. Its etiology is...
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.
Topics: Africa, Western; Antimalarials; Blackwater Fever; Europe; Host-Parasite Interactions; Humans; Malaria, Falciparum; New Guinea; Panama; Quinine
PubMed: 29016337
DOI: 10.4269/ajtmh.17-0533 -
BMJ Open Jul 2022Blackwater fever (BWF), a complication of malaria, has in the past been considered as a rare complication of malaria in children living in high transmission settings....
INTRODUCTION
Blackwater fever (BWF), a complication of malaria, has in the past been considered as a rare complication of malaria in children living in high transmission settings. More recently, however, a growing number of paediatric clusters of BWF cases have been reported predominantly in sub-Saharan Africa (SSA). The aim of this study is to map evidence on BWF among children in SSA from 1 January 1960 to 31 December 2021.
METHODS AND ANALYSIS
This review will be guided by Arksey and O' Malley's methodological framework for scoping reviews with methodological refinements by Levac and will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews' guidelines. Five electronic databases (MEDLINE via PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO) will be systematically searched using predefined keywords. In addition, reference lists of included articles will be searched. Our multidisciplinary team has formulated search strategies and two reviewers will independently complete study eligibility screening, final selection and data extraction. A third reviewer will adjudicate the final decision on disputed articles. Bibliographic data and abstract content will be collected and analysed using a data-charting tool developed iteratively by the research team.
ETHICS AND DISSEMINATION
This scoping review being a secondary analysis does not require ethics approval. We anticipate results of this review will broaden understanding of paediatric BWF in SSA and identify its research gaps in SSA. We will be disseminating results through journals and conferences targeting primary care providers.
Topics: Africa South of the Sahara; Blackwater Fever; Child; Humans; Mass Screening; Systematic Reviews as Topic
PubMed: 35793920
DOI: 10.1136/bmjopen-2021-059875 -
The American Journal of Tropical... Apr 2023The U.S. Civil War (1861-1865) pre-dated modern understanding of malaria. Yet, malarial diseases (remittent fever, intermittent fever, typho-malarial fever) were...
The U.S. Civil War (1861-1865) pre-dated modern understanding of malaria. Yet, malarial diseases (remittent fever, intermittent fever, typho-malarial fever) were frequently reported as causes of morbidity and mortality in soldiers. Modern readers find Civil War-era descriptions of malaria contradictory or paradoxical. For example, although the concept of race-specific immunity to tropical diseases was widely accepted, malaria mortality rates were reportedly more than three times higher among Black than White Union soldiers (16/1,000/year versus 5/1,000/year). Also, malaria rates were reportedly lower among prisoners of war at the infamous Andersonville, GA, prison camp than among Confederate soldiers in the same area. Literally tons of quinine were given prophylactically to Union soldiers deployed in the southern United States, but blackwater fever was not reported by medical officers. All three paradoxes have reasonable modern explanations that give credence to the astute clinical observations of our scientific predecessors during the U.S. Civil War.
Topics: Humans; United States; Malaria; Quinine; Military Personnel; Morbidity; Prisoners
PubMed: 36878215
DOI: 10.4269/ajtmh.22-0672 -
Malaria Journal Jan 2020Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often...
BACKGROUND
Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association between MBL2 gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children.
METHODS
This is a case-control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping.
RESULTS
A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87-829) and p = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, with p = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06-0.78)) with p = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF.
CONCLUSION
This pilot study is a preliminary research on MBL2 gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.
Topics: Adolescent; Alleles; Blackwater Fever; Case-Control Studies; Child; Child, Preschool; Cohort Studies; DNA; Democratic Republic of the Congo; Female; Gene Frequency; Genotyping Techniques; Haplotypes; Hemoglobinuria; Humans; Logistic Models; Male; Mannose-Binding Lectin; Polymorphism, Genetic
PubMed: 31941497
DOI: 10.1186/s12936-020-3100-8 -
IJID Regions Jun 2022Blackwater fever (BWF) is one of the severe forms of malaria manifested by hemoglobinuria that causes dark-colored urine, fever, anemia, jaundice and acute kidney...
Successful Oral Antimalarial Therapy in A 14-Year-Old Child with Blackwater Fever: A Case in a Rural Area of Asmat Regency of Papua, Indonesia: Successful Oral Antimalarial in Blackwater Fever.
BACKGROUND
Blackwater fever (BWF) is one of the severe forms of malaria manifested by hemoglobinuria that causes dark-colored urine, fever, anemia, jaundice and acute kidney injury. BWF is most commonly associated with infection and its treatment. Parenteral antimalarial therapy is recommended as the treatment of choice for BWF. Here we present the first case of successful oral antimalarial therapy in BWF to the best of our knowledge.
CASE PRESENTATION
A 14-year-old boy was hospitalized with BWF as the primary diagnosis based on the presence of fever, jaundice and "coca-cola"-colored urine, along with laboratory results which showed infection, anemia, and impaired kidney function. Uncomplicated malaria manifestations had been appearing for seven days before admission, but the syndrome of BWF developed several hours following the first dose of dihydroartemisinin-piperaquine (DHP). Treatment with a 3-day course of DHP was continued because parenteral antimalarials were unavailable at that time. Remarkable improvements were seen following the second and third doses of DHP along with adequate supportive medical care.
CONCLUSION
The unavailability of parenteral antimalarials makes oral antimalarials a possible alternative treatment for BWF. In addition, close monitoring and supportive medical care are critical in the treatment of BWF.
PubMed: 35755479
DOI: 10.1016/j.ijregi.2022.03.021 -
Cureus Dec 2021We present the case of imported malaria in pregnancy to the United Kingdom (UK) from Nigeria, where a 28-year-old primigravida presented to our maternity assessment unit...
We present the case of imported malaria in pregnancy to the United Kingdom (UK) from Nigeria, where a 28-year-old primigravida presented to our maternity assessment unit (MAU) with complaints of pyrexia, rigors and passing dark coloured urine. She gave a travel history of recent migration from Nigeria 10 days before presenting to our emergency department. She initially became unwell five days after her arrival with general malaise and myalgia. On day six, she developed lower abdominal pain and observed that her urine was dark in colour. This prompted her to contact her general practitioner (GP). Treatment for a urinary tract infection was initiated by the GP after a phone consultation in keeping with COVID-19 contingency guidance, and the patient was prescribed antibiotics for three days. She presented to the emergency department two days after completing the course of antibiotics where she complained of worsening pelvic pain, reduced foetal movements and passing black urine. She was treated as suspected COVID-19 and red flag sepsis. Obstetric review led to investigation and diagnosis of severe malaria in pregnancy, which was accompanied by blackwater fever (BWF). The patient recovered after three doses of artesunate. An ultrasound scan of the foetus revealed a congenital cardiac anomaly, which had not been detected in an earlier scan. There was no evidence of congenital malaria in the neonate after delivery. There are several novel aspects in this case as maternal mortality in severe can be significantly high. Those who survive the disease in pregnancy are also known to develop several complications such as intrauterine death and preterm labour. There was also the component of blackwater fever, which is a rare event associated with severe malaria, and it also has a mortality rate. Significant in her medical history was a diagnosis of the sickle cell trait, and we postulate that this feature gave an added protection from the complications of severe malaria in pregnancy as well as blackwater fever.
PubMed: 34900503
DOI: 10.7759/cureus.20170