Effect of corticosteroids on haemoglobinuria resolution among children with blackwater fever at Soroti regional referral hospital, Uganda: a retrospective cohort study

(2025) 24:366 Odiit et al. Malaria Journal https://doi.org/10.1186/s12936-025-05623-z Malaria Journal Open Access RESEARCH Effect of corticosteroids on haemoglobinuria resolution among children with blackwater fever at Soroti regional referral hospital, Uganda: a retrospective cohort study Amos Odiit1,2, Patrick Lubogo3, Moses Ochora1,2, Isaac Ebiju4 and Ronald Opito5*    Abstract Background Corticosteroids are sometimes used in clinical practice in the treatment of blackwater fever (BWF), a complication of severe malaria, despite limited evidence of benefit. This study aimed to compare the time to haemoglobinuria resolution between children with BWF who received corticosteroids and those who did not, and determine if corticosteroid use significantly influences this outcome. Methods This was a retrospective cohort study carried out at Soroti Regional Referral Hospital in Soroti, Uganda, among children diagnosed with blackwater fever (BWF), between 1st January 2023 to 31st December 2024. Participants included in the study were 889. Time to haemoglobinuria resolution was determined using the Kaplan–Meier survival function and compared using log rank test. Predictors of time to haemoglobinuria resolution were determined using an extended cox proportional hazard model, with results expressed as adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results The median time to haemoglobinuria resolution was 3 days in both the corticosteroid and non-corticosteroid groups. Corticosteroid use was not significantly associated with time to haemoglobinuria resolution (aHR: 0.90; 95% CI 0.75–1.07, p = 0.239). The predictors of time to haemoglobinuria resolution were: antibiotic use (aHR: 0.68; 95% CI 0.58–0.81, p < 0.001), blood transfusion (specifically for those who received transfusions twice [aHR: 0.78; 95% CI 0.62–0.97, p = 0.024], three times [aHR: 0.59; 95% CI 0.40–0.88, p = 0.010], and four times [aHR: 0.36; 95% CI 0.24–0.53, p < 0.001]), presence of jaundice (aHR: 1.49; 95% CI 1.14–1.94, p = 0.003), and administration of normal saline (aHR: 0.57, 95% CI 0.45–0.74, p < 0.001). Conclusion Corticosteroid use did not accelerate haemoglobinuria resolution in children with blackwater fever, supporting current WHO guidance against their use. These findings suggest limited benefit of corticosteroids in BWF management. *Correspondence: Ronald Opito Full list of author information is available at the end of the article © The Author(s) 2025. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. Odiit et al. Malaria Journal (2025) 24:366 Background Blackwater fever (BWF) is a severe complication of Plasmodium falciparum malaria characterized by massive intravascular haemolysis leading to haemoglobinuria (typically seen as intermittent tea-coloured urine), anaemia, and potentially acute kidney injury. It primarily affects children and non-immune individuals in malariaendemic regions [1–3]. The prevalence of BWF was reported to be 12.4% in a multicentre trial conducted in East Africa [4]. In eastern Uganda, the prevalence rates were higher, with 14.5% reported among sick children at Mbale Regional Referral Hospital and 21.8% at Soroti Regional Referral Hospital (SRRH) [4]. BWF is associated with adverse outcomes such as death and frequent admissions as observed in Uganda where up to 46% of children who had BWF and severe anaemia were readmitted atleast once during a 6 month follow up period [5]. It is documented to cause substantial morbidity among children in sub-Saharan Africa SSA [6, 7]. A scoping review involving 100 studies reported 18.1% mortality from BWF, highlighting its clinical severity and public health importance [8]. Effective management of BWF involves prompt initiation of antimalarial therapy, typically with intravenous artesunate followed by a full course of oral artemisininbased combination therapy (ACT), alongside supportive care to mitigate the effects of intravascular haemolysis [9–11]. Intravenous fluids are administered to maintain renal perfusion and prevent or manage acute kidney injury, while folic acid supplementation supports erythropoiesis during recovery. Blood transfusion is often necessary to correct severe anaemia and stabilize haemodynamics [9, 11]. Corticosteroids have been empirically used as adjunctive therapy for haemoglobinuria associated with BWF, based on the hypothesis that their anti-inflammatory effects might mitigate immune-mediated haemolysis and reduce renal inflammation [1, 12]. However, their use remains controversial. Although some clinicians continue to administer corticosteroids in clinical practice, current evidence supporting their effectiveness is limited, and the World Health Organization (WHO) does not recommend their use in the management of BWF, neither is it recommended by the Uganda clinical guidelines [9, 11]. Despite this, corticosteroids are still used in routine practice at SRRH and other hospitals in Uganda, reflecting ongoing uncertainty among clinicians. To date, no systematic study has evaluated whether corticosteroids influence recovery in children with BWF, particularly with respect to haemoglobinuria resolution, a key clinical marker of improvement. Addressing this gap is especially important in eastern Uganda, where BWF prevalence and associated morbidity remain high. This study, therefore, Page 2 of 9 aimed to compare the time to haemoglobinuria resolution between children with BWF who received corticosteroids and those who did not. By addressing this gap, the study seeks to generate evidence that can inform clinical decision-making, rationalize the use (or non-use) of corticosteroids, and potentially guide updates to treatment protocols in malaria-endemic, resource-limited settings. Methods Study design and setting This retrospective cohort study was conducted at Soroti Regional Referral Hospital (SRRH) in Soroti District, approximately 294 kms northeast of Kampala, Uganda’s capital city. SRRH is one of the country’s 13 regional referral (...truncated)