Paracoccidioidomycosis in the 21st century: Challenges and milestones

Background: Paracoccidioidomycosis (PCM) is a neglected tropical fungal disease endemic to Latin America that predominantly affects rural and socioeconomically vulnerable communities. Despite significant morbidity, mortality, and substantial public health implications, PCM remains frequently underdiagnosed and underreported, mainly due to inadequate disease awareness and insufficient surveillance systems. This narrative review highlights recent milestones in the etiology, ecology, epidemiology, clinical manifestations, diagnosis, treatment, antifungal drugs, host–pathogen interactions, genetics, omics approaches, sequelae, and social aspects of PCM. Additionally, it identifies ongoing challenges and critical knowledge gaps for future research. Methods: A systematic retrieval of articles published between 2001 and 2025 was conducted from PubMed and the Virtual Health Library (BVS), using descriptors (“Paracoccidioidomycosis” OR “Paracoccidioides”). Duplicate records were removed through the Rayyan QCRI, and two reviewers independently evaluated the articles according to predefined thematic areas. Findings: Recent advancements have enhanced our understanding of PCM epidemiology, driven by ecological shifts and socioeconomic transformations that alter disease distribution and clinical presentation. Although substantial progress has been made in identifying and characterizing the causative agent, Paracoccidioides spp., challenges persist in the diagnostic process owing to limited laboratory methodologies and the absence of standardized tests. Current therapeutic options face limitations such as prolonged treatment durations, frequent drug interactions, and complicating disease management. Moreover, PCM significantly affects patients’ quality of life through persistent physical sequelae, psychological impacts, and socioeconomic consequences, including stigmatization and reduced work capacity. Conclusion: Addressing these multifaceted challenges requires integrated approaches that combine improved surveillance, enhanced diagnostic tools, novel therapeutic strategies, and targeted social support programs. Sustained collaborative research and international cooperation are essential to fill existing knowledge gaps and achieve better health outcomes for affected populations.