The resurgence of blackwater fever among children in sub-Saharan Africa: a scoping review

Abstract

Blackwater fever (BWF), a life-threatening complication of Plasmodium falciparum malaria, has re-emerged as a significant health concern among children in sub-Saharan Africa (SSA). Characterized by acute intravascular hemolysis, hemoglobinuria, and severe anemia, necessitating urgent medical intervention. Despite its clinical severity, data on its burden, risk factors, and management remain fragmented. Therefore, this scoping review aimed to systematically map the existing literature on BWF in SSA, focusing on its epidemiology, clinical presentation, risk factors, management strategies, and outcomes among children in SSA. Following the Arksey and O’Malley framework, enhanced by Levac et al., and reported according to PRISMA-ScR, we conducted a scoping review registered on the Open Science Framework. We searched six databases and grey literature from inception to December 2024. Eligibility was guided by a PCC framework focused on children aged 0 to 18 years with blackwater fever in sub-Saharan Africa. Two reviewers independently screened all records using predefined inclusion and exclusion criteria. Data were extracted and synthesized narratively, with findings categorized thematically by epidemiology, clinical features, risk factors, management, and outcomes. BWF was geographical clustered in East and Central Africa, particularly Uganda (53.8%) and the DRC (26.9%). Prevalence ranged from 4.4% to 52.7%, with higher incidence during rainy seasons. MBL2 AA polymorphisms, elevated IgG1, and prior quinine treatment showed strong associations with blackwater fever, while the role of glucose-6-phosphate dehydrogenase deficiency (G6PDd) varied across studies. Clinical hallmarks were dark urine (100% of cases), jaundice (22.7–100%), and severe anemia (23.7–77%), corresponding to the classic ‘hemolytic triad’ of hemoglobinuria, jaundice, and profound anemia seen in BWF. Acute kidney injury (AKI) (16.2–90.6% of cases) and recurrent episodes (50–68% readmission rates) exacerbated morbidity. These wide ranges reflect differences in study design, case definitions, and the concentration of severe cases at tertiary hospitals where most included studies were conducted. Diagnosis relied on clinical criteria, with limited laboratory confirmation, while management emphasized artemisinin-based therapies and supportive care. Delays in blood transfusions and renal replacement therapy contributed to poor outcomes. Evidence from recent cohorts suggests an apparent resurgence and increasing recognition of childhood BWF in high-transmission regions of SSA. Persistent gaps in diagnostic capacity, timely access to transfusion and renal support, and consistent use of artemisinin-based therapy highlight the need for harmonized diagnostic criteria, improved surveillance, and expanded supportive care. Not applicable.