Sepsis, endemic and emerging infectious diseases: converging concepts and clinical implications

Studies on the global burden of sepsis confirm its major mortality, morbidity, and societal impact, with 85% of cases and deaths occurring in low-income and middle-income countries. Importantly, these analyses have blurred the boundaries between sepsis, defined as a dysregulated host response to infection causing life-threatening organ dysfunction, and endemic and emerging infectious diseases, such as malaria, leptospirosis, tuberculosis, and gastroenteric illnesses, which often follow clinical trajectories distinct from those of so-called standard sepsis. Framing these disease-specific deaths within the broader context of sepsis highlights the unacceptably high mortality from preventable and treatable endemic infectious diseases in resource-limited settings. However, important differences remain. Sepsis management focuses on early diagnosis, timely intervention, organ support, and, increasingly, patient stratification and precision-targeted therapies. In contrast, endemic and emerging infectious diseases often involve lengthy and complex courses before hospital admission and require disease-specific diagnostic and therapeutic approaches. In this Personal View, we discuss how this conceptual overlap affects estimates of disease burden, interpretation of pathophysiological mechanisms, therapeutic decision making, and the development of precision medicine strategies. We propose applying disease-specific stratification to endemic and emerging infectious diseases to distinguish milder cases from life-threatening forms associated with organ dysfunction (sepsis from an endemic and emerging infectious disease [SEEID]). Early recognition and diagnosis of SEEIDs are essential, and expert disease-specific guidance is urgently needed, particularly given the scarcity of randomised clinical trials evaluating treatment strategies for these conditions.