State-of-the-Art Review: Chagas Disease—an Enduring Challenge

Chagas disease remains the most significant neglected tropical disease in the Western Hemisphere, with Trypanosoma cruzi infection presenting unique challenges for healthcare systems. This zoonotic disease persists through a complex interplay of socioeconomic disparities, cultural practices, and historical inequities that disproportionately affect impoverished rural communities throughout Latin America and underrepresented populations in the Global North. In this review, we describe the most relevant aspects of the pathogenesis of Chagas disease and examine critical aspects of patient care, including identification of high-risk populations for targeted screening and analysis of current barriers to diagnosis and treatment implementation. Our comprehensive assessment covers the spectrum of clinical presentations based on transmission pathways and individual host factors, alongside current approaches to disease staging, diagnostic methodology, and therapeutic interventions for both acute infection and chronic complications. Furthermore, we provide key and practical evidence-based care concepts for the immunosuppressed patient with T. cruzi infection, an increasingly important patient subset that highlights evolving treatment paradigms in specialized populations.