New clinical and genomic insights into paracoccidioidomycosis in Paraguay: A neglected endemic area.

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp., predominantly affecting individuals in Latin America. While extensive epidemiological and molecular studies have been conducted in Brazil, Colombia, and Venezuela, where PCM is a recognized public health concern, Paraguay remains largely overlooked. The scarcity of epidemiological and molecular data hinders accurate disease surveillance, early diagnosis, and effective treatment strategies. This study provides the first comprehensive epidemiological and molecular characterization of PCM in Paraguay. We report the patient demographics, clinical presentations of PCM patients, and estimates of genetic diversity among isolates. A retrospective analysis of 66 confirmed PCM cases from the Mycology Section at the Center for Dermatological Specialties in San Lorenzo (2014-2024) was conducted. Diagnoses were confirmed through direct microscopy or fungal culture, and clinical isolates were genotyped using whole-genome sequencing. Findings indicate that PCM is more common among male patients, as 69% were agricultural workers representing high occupational risk. The chronic form was the most prevalent, commonly affecting the lungs and mucosa in males 40-60 years of age. Less frequent manifestations included the kidneys, central nervous system, gastrointestinal tract, and adrenal glands. Most PCM cases were treated with itraconazole; severe cases received amphotericin B. Molecular analysis demonstrated that Paraguayan isolates belong to both S1b and S1a clades; however, they are distinct from Argentina and Mato Grosso do Sul, Brazil. These findings highlight the complexity of P. brasiliensis population structure in South America, emphasizing the need for enhanced diagnostic and treatment strategies in endemic regions.