Whose sepsis? Tropical infections and the limits of contemporary sepsis evidence

Dear Editor, Sepsis is among the leading causes of death worldwide. Before the COVID-19 pandemic, the Global Burden of Disease Study estimated 48.9 million incident cases and 11.0 million sepsis-related deaths in 2017, almost one in five deaths globally.1 Over recent decades, randomized controlled trials have substantially refined the management of sepsis and critical illness. Lung-protective ventilation, safer haemodynamic strategies, appropriate vasopressor use, and evidence-based supportive care now underpin contemporary practice and represent some of the most important achievements of modern critical care. Yet a paradox persists. The greatest burden of sepsis falls on sub-Saharan Africa, South and Southeast Asia, and Oceania,1 precisely the regions where dengue, malaria, leptospirosis, scrub typhus, melioidosis, and other tropical infections drive a substantial share of severe illness and critical-care admission. Despite this, the representation of these infections in landmark sepsis and acute respiratory distress syndrome trials is difficult to determine. Causative pathogens are frequently absent, grouped into broad microbiological categories, or not reported separately, making it unclear whether individual tropical infections were excluded, underrepresented, or simply not identifiable (Table S1). The practical consequence is the same. Clinicians must extrapolate evidence largely generated in sepsis populations dominated by pneumonia, intra-abdominal infection, urinary infection, and healthcare-associated infection to pathogen-defined syndromes with potentially different pathophysiology.