Physiopathology and clinical management of blackwater fever: a scoping 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 man-agement 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 ex-patriates. 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. Paola Rodari, Clin Microbiol Infect 2024;30:59 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).