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Plants (Basel, Switzerland) Jan 2024DC is an indigenous medicinal plant belonging to the genus of the Fabaceae family. It is used to treat stomach problems, headaches, mouth ulcers, malaria, blackwater...
DC is an indigenous medicinal plant belonging to the genus of the Fabaceae family. It is used to treat stomach problems, headaches, mouth ulcers, malaria, blackwater fever, gonorrhea, ringworm, diarrhea, heavy menstruation, and breast milk stimulation. Column chromatography of the stem bark extracts resulted in the isolation of eight compounds, which included friedelan-3-one (), 3α-hydroxyfriedel-2-one (), 3-hydroxyfriedel-3-en-2-one (), lup-20(29)-en-3-ol (), Stigmasta-5-22-dien-3-ol (), 4--methylangolensis (), (3)-3-acetoxyolean-12-en-28-oic acid (), and tetradecyl (E)-ferulate (). The structures were established based on NMR, IR, and MS spectroscopic analyses. Triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-cancerous mammary epithelial cell lines (MCF-12A) were used to test the compounds' cytotoxicity. Overall, the compounds showed either no toxicity or very low toxicity to all three cell lines tested, except for the moderate toxicity displayed by lupeol () towards the non-cancerous MCF-12A cells, with an IC value of 36.60 μM. Compound (3)-3-acetoxyolean-12-en-28-oic acid () was more toxic towards hormone-responsive (MCF-7) breast cancer cells than either triple-negative breast cancer (HCC70) or non-cancerous breast epithelial (MCF-12A) cells (IC values of 83.06 vs. 146.80 and 143.00 μM, respectively).
PubMed: 38276759
DOI: 10.3390/plants13020301 -
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 -
BMJ Open Jul 2023Acute kidney injury (AKI) has in the past been considered a rare complication of malaria in children living in high-transmission settings. More recently, however, a...
PARIST study protocol: a phase I/II randomised, controlled clinical trial to assess the feasibility, safety and effectiveness of paracetamol in resolving acute kidney injury in children with severe malaria.
BACKGROUND
Acute kidney injury (AKI) has in the past been considered a rare complication of malaria in children living in high-transmission settings. More recently, however, a growing number of paediatric case series of AKI in severe malaria studies in African children have been published (Artesunate vs Quinine in the Treatment of Severe Malaria in African children and Fluids Expansion as Supportive Therapy trials). The Paracetamol for Acute Renal Injury in Severe Malaria Trial (PARIST) therefore, aims to assess feasibility, safety and determine the effective dose of paracetamol, which attenuates nephrotoxicity of haemoproteins, red-cell free haemoglobin and myoglobin in children with haemoglobinuric severe malaria.
METHODS
PARIST is a phase I/II unblinded randomised controlled trial of 40 children aged >6 months and <12 years admitted with confirmed haemoglobinuric severe malaria (blackwater fever), a positive blood smear for malaria and either serum creatinine (Cr) increase by ≥0.3 mg/dL within 48 hours or to ≥1.5 times baseline and elevated blood urea nitrogen (BUN) >20 mg/dL. Children will be randomly allocated on a 1:1 basis to paracetamol intervention dose arm (20 mg/kg orally 6-hourly for 48 hours) or to a control arm to receive standard of care for temperature control (ie, tepid sponging for 30 min if fever persists give rescue treatment). Primary outcome is renal recovery at 48 hours as indicated by stoppage of progression and decrease of Cr level below baseline, BUN (<20 mg/dL). Data analysis will be on the intention-to-treat principle and a per-protocol basis.Results from this phase I/II clinical trial will provide preliminary effectiveness data of this highly potential treatment for AKI in paediatric malaria (in particular for haemoglobinuric severe malaria) for a larger phase III trial.
ETHICS AND DISSEMINATION
Ethical and regulatory approvals have been granted by the Mbale Hospital Institutional Ethics Review Committee (MRRH-REC OUT 002/2019), Uganda National Council of Science and Technology (UNCST-HS965ES) and the National drug Authority (NDA-CTC 0166/2021). We will be disseminating results through journals, conferences and policy briefs to policy makers and primary care providers.
TRIAL REGISTRATION NUMBER
ISRCTN84974248.
Topics: Humans; Child; Acetaminophen; Feasibility Studies; Uganda; Malaria; Malaria, Falciparum; Acute Kidney Injury; Treatment Outcome; Randomized Controlled Trials as Topic; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic
PubMed: 37524553
DOI: 10.1136/bmjopen-2022-068260 -
Malaria Journal Jun 2023In sub-Saharan Africa (SSA), malaria remains a public health problem despite recent reports of declining incidence. Severe malaria is a multiorgan disease with...
BACKGROUND
In sub-Saharan Africa (SSA), malaria remains a public health problem despite recent reports of declining incidence. Severe malaria is a multiorgan disease with wide-ranging clinical spectra and outcomes that have been reported to vary by age, geographical location, transmission intensity over time. There are reports of recent malaria epidemics or resurgences, but few data, if any, focus on the clinical spectrum of severe malaria during epidemics. This describes the clinical spectrum and outcomes of childhood severe malaria during the disease epidemic in Eastern Uganda.
METHODS
This prospective cohort study from October 1, 2021, to September 7, 2022, was nested within the 'Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda' (TMA2016SF-1514-MEPIE Study) at Mbale Regional Referral Hospital, Uganda. Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical WHO criteria for surveillance of severe malaria were enrolled on the study. Follow-up was performed until day 28. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, malaria RDT (SD BIOLINE Malaria Ag P.f/Pan, Ref. 05FK60-40-1) and blood slide, lactate, glucose, blood gases and electrolytes. In addition, urinalysis using dipsticks (Multistix 10 SG, SIEMENS, Ref.2300) at the bedside was done. Data were analysed using STATA V15.0. The study had prior ethical approval.
RESULTS
A total of 300 participants were recruited. The median age was 4.6 years, mean of 57.2 months and IQR of 44.5 months. Many children, 164/300 (54.7%) were under 5 years, and 171/300 (57.0%) were males. The common clinical features were prostration 236/300 (78.7%), jaundice in 205/300 (68.3%), severe malarial anaemia in 158/300 (52.7%), black water fever 158/300 (52.7%) and multiple convulsions 51/300 (17.0%), impaired consciousness 50/300(16.0%), acidosis 41/300(13.7%), respiratory distress 26/300(6.7%) and coma in 18/300(6.0%). Prolonged hospitalization was found in 56/251 (22.3%) and was associated with acidosis, P = 0.041. The overall mortality was 19/300 (6.3%). Day 28 follow-up was achieved in 247/300 (82.3%).
CONCLUSION
During the malaria epidemic in Eastern Uganda, severe malaria affected much older children and the spectrum had more of prostration, jaundice severe malarial anaemia, black water fever and multiple convulsions with less of earlier reported respiratory distress and cerebral malaria.
Topics: Child; Male; Humans; Infant; Adolescent; Child, Preschool; Female; Prospective Studies; Blackwater Fever; Uganda; Malaria, Cerebral; Anemia; Lactic Acid; Epidemics; Seizures; Jaundice; Respiratory Distress Syndrome
PubMed: 37259110
DOI: 10.1186/s12936-023-04586-3 -
Case Reports in Infectious Diseases 2023Blackwater fever (BWF) is a severe clinical syndrome occurring as a complication of malarial infection characterized by intravascular hemolysis, hemoglobinuria, and...
BACKGROUND
Blackwater fever (BWF) is a severe clinical syndrome occurring as a complication of malarial infection characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure in people exposed to and, to some extent, in people who were exposed to medications like quinine and mefloquine. The exact pathogenesis of classic BWF remains unclear. The mechanism leading to damage to the red blood cells (RBCs) can be immunologic nonimmunologic, leading to massive intravascular hemolysis. . We present a case of classic blackwater fever in a 24-year-old otherwise previously healthy male without any history of antimalarial prophylaxis use, returning from recent travel to Sierra Leone. He was detected to have malaria in the peripheral smear test. He was treated with artemether/lumefantrine combination therapy. Unfortunately, his presentation was complicated by renal failure and was managed with plasmapheresis and renal replacement therapy.
CONCLUSION
Malaria continues to be a parasitic disease that can have devastating effects and continues to be a challenge globally. Although cases of malaria in the United States are rare and cases of severe malaria, mainly attributed to , are even more uncommon. Care should be taken to retain a high level of suspicion to consider the diagnosis, especially in returning travelers from endemic areas.
PubMed: 37179741
DOI: 10.1155/2023/5796881 -
Emerging Infectious Diseases Apr 2023Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not...
Causes of blackwater fever, a complication of malaria treatment, are not completely clear, and immune mechanisms might be involved. Clinical management is not standardized. We describe an episode of blackwater fever in a nonimmune 12-year-old girl in Italy who was treated with steroids, resulting in a rapid clinical resolution.
Topics: Female; Humans; Child; Blackwater Fever; Antimalarials; Malaria; Italy; Steroids; Malaria, Falciparum
PubMed: 36958024
DOI: 10.3201/eid2904.221267 -
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 -
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 -
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 -
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