Fig 1.
Geographical distribution and endemicity levels of paracoccidioidomycosis (PCM) in the Americas.
Areas are categorized as no or sporadic cases (white), low endemicity (light green/teal), and medium/high endemicity (blue). The classification was based on expert consensus (modified Delphi process) conducted during the International Conference on Paracoccidioidomycosis (PCM XXI, Campo Grande, Brazil, 2024), integrating published data and local expert knowledge. This map was created using ArcGIS software by Esri. ArcGIS and Arc-Map are the intellectual property of Esri and are used herein under license. Copyright Esri. All rights reserved. For more information about Esri software, please visit www.esri.com. Basemap: GADM layers (https://gadm.org/download_country.html) under CC BY 4.0 license.
Fig 2.
Paracoccidioides–host interaction.
(A) Host responses related to the immune system activation and inflammatory response. Note that the immune system direct activation of the defense barriers, innate, and adaptative responses are influenced by the nutritional status, since malnutrition negatively impacts the immune system effectiveness. The immunological response can also change during antifungal treatment, when the specific T-cell response tends to recover, followed by persistent low-grade inflammation. Considering the inflammatory response, it can be impacted by the genetic background, specifically by single-nucleotide polymorphisms (SNPs) (IL-10, CTLA4, DC-SIGN, VDR, NLRP1) and innate immune errors, IIE (STAT4, CD40L, IL-12Rbeta1, CARD9). (B) Mechanisms of fungal adaptation and pathogenesis, pointing out extracellular vesicles, biofilms, metabolic adaptation, and other virulence factors. Biofilms have been detected in pulmonary epithelial cells and keratinocytes; they protect the fungi against the immune attack and antifungal drugs. Besides, microbial associations with Candida albicans, Mycobacterium tuberculosis, and Klebsiella pneumoniae negatively impact disease severity and treatment. Virulence factors include Hsp90, proteases, elastase, formamidase, adhesins gp43 and enolase, anti-oxidant superoxide dismutase, and cell wall alpha-1,3-glucan; many are moonlight proteins. The figure was created by us using Adobe Illustrator. All icons included in the figure, except for the Paracoccidioides spp. illustration (created by the authors), were obtained from The Noun Project (https://thenounproject.com/), under the Creative Commons Attribution 3.0 (CC BY 3.0) license.
Table 1.
Overview of the main limitations of diagnostic tools for PCM.
Fig 3.
Comparative overview of the main diagnostic tools for paracoccidioidomycosis (PCM), detailing their sensitivity and laboratory difficulty.
Each diagnostic method is presented with its typically required biological material(s). The performance sensitivity is visually rated via color-coded horizontal bars (green: >85%; orange: 60%–84%; red: <59%), and the laboratory difficulty is similarly displayed (green: easy; orange: moderate; red: hard). The figure was created by us using Adobe Illustrator/), under the Creative Commons Attribution 3.0 (CC BY 3.0) license.