Umaporn Limothai, Nattachai Srisawat, David A. Haake
Leptospirosis is a globally prevalent zoonotic infection causing more than one million cases and nearly 60,000 deaths annually yet is often diagnosed late after organ dysfunction and other complications have arisen. Delayed diagnosis leads to late initiation of antibiotics and other therapeutic interventions, at which point complications such as renal failure, jaundice, or pulmonary hemorrhage are more common and therapy is less effective. This review highlights the critical importance of early recognition and intervention, emphasizing the therapeutic window during the leptospiremic phase when antibiotics are most effective. We examine the limitations of current clinical and laboratory diagnostic methods, the evolving role of molecular and biomarker-based platforms, and the potential of integrated scoring systems for frontline triage. Evidence supporting early antibiotic therapy, supportive care strategies, and severity prediction tools is summarized. We propose a paradigm shift toward field-adaptable, point-of-care diagnostics and integrated care pathways to ensure earlier treatment, improved outcomes, and reduced global disease burden.