Refining organ dysfunction assessment in severe malaria: implications of the SOFA-2 paradigm for malaria-endemic settings

Abstract The recently published Sequential Organ Failure Assessment (SOFA)-2 score represents the first major revision of organ dysfunction assessment in adult critical care in nearly three decades. Developed and validated using more than three million intensive care unit (ICU) encounters across diverse healthcare systems, SOFA-2 modernises the conceptual and operational framework of organ dysfunction evaluation while preserving the simplicity and bedside applicability that contributed to the widespread adoption of the original SOFA score. Severe Plasmodium falciparum malaria shares several pathophysiological and clinical features with sepsis, including dysregulated host response, endothelial activation, microvascular dysfunction, tissue hypoxia and multi-organ dysfunction. Nevertheless, organ dysfunction assessment in severe malaria remains largely dependent on World Health Organization (WHO) severity criteria rather than integrated ICU-oriented severity models. The emergence of SOFA-2 creates an opportunity to revisit the interface between malaria and sepsis within critical care medicine. Several WHO severe malaria criteria align closely with SOFA-2 domains, particularly neurological, cardiovascular, respiratory, renal and hepatic dysfunction. However, malaria-specific biological characteristics may influence the interpretation of some SOFA-2 components, especially thrombocytopenia and neurological dysfunction. Existing African ICU data suggest that severity of organ dysfunction measured by SOFA is strongly associated with mortality in severe malaria. Context-specific adaptations and validation studies are therefore required to determine whether SOFA-2 could improve prognostic discrimination, triage standardisation and research harmonisation in malaria-endemic regions. The integration of malaria into organ dysfunction paradigms may also strengthen the conceptual convergence between severe malaria and sepsis.