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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. 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. 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. 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.

About the Authors: Joshua Griffiths Affiliation: The University of Manchester, Manchester, United Kingdom Arnaldo Lopes Colombo Affiliation: Division of Infectious Diseases, Universidade Federal de São Paulo, São Paulo, Brazil David W. Denning * E-mail: ddenning@manchester.ac.uk, ddenning@GAFFI.org Affiliations The University of Manchester, Manchester, United Kingdom, National Aspergillosis Centre, Wythenshawe Hospital, Manchester Academic Health Science Centre, Manchester, United Kingdom, Global Action Fund for Fungal Infections, Geneva, Switzerland ORCID logo http://orcid.org/0000-0001-5626-2251 Introduction The World Health Organization’s (WHO) neglected tropical disease (NTD) portfolio is a diverse group of diseases with profound impacts on affected populations. Public health impact and association with poverty Previous reviews of the epidemiology of PCM have attempted to estimate the incidence of the disease using case series [5,10]. Additionally, patients usually present with pulmonary lesions (a feature of the chronic form, which otherwise is almost the exclusive form affecting those over 30 years old) as well as generalised lymphadenopathy, splenomegaly, bone lesions, and skin lesions as a result of haematogenous dissemination (a feature of the acute/subacute form of the disease, which tends to affect children) [26]. First WHO report on neglected tropical diseases.

Paracoccidioides species have always been surrounded by taxonomic uncertainties. The continuing nomenclatoral muddle was caused in part by the failure of Adolfo Lutz and Jorge Lôbo to name the etiologic agents of human paracoccidioidomycosis and Jorge Lôbo’s diseases, respectively. Early in their history, it was postulated that the cultivable species causing systemic infections belonged in the genus Paracoccidioides , whereas the uncultivable species, causing skin disease, were not part of the genus. The taxonomy of these pathogens was further complicated when a similar skin disease with numerous yeast-like cells in infected dolphins was also reported. Due to its phenotypic similarities with that described by Jorge Lôbo in human and its uncultivable nature, it was assumed that the disease in dolphins was caused by the same fungus. Recent molecular and population genetic analysis, however, found the DNA extracted from the uncultivable yeast-like cells affecting dolphins shared common phylogenetic traits with cultivable Paracoccidioides species. The study revealed that the uncultivable pathogens comprised 2 different Paracoccidioides species, now known as P . ceti and P . loboi , correspondingly. To validate P . loboi binomial, a comprehensive historical critical review of Jorge Lôbo etiology was performed. This review showed the proposed binomial P . loboi was previously used, and, thus, a replacement name is introduced, Paracoccidioides lobogeorgii nom. nov. In addition, in this review, several cultivable human Paracoccidioides species are validated, and the generic type species, P . brasiliensis , is neotypified as the original material could not be traced.

Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.

Jorge Lobo's disease (JLD), caused by Paracoccidioides lobogeorgii, primarily affects inhabitants of the Amazon Forest. We report a 9-year-old boy in Brazil who had JLD diagnosed after a tick bite. The rarity of pediatric cases likely reflects surveillance gaps. Increased clinical awareness is crucial for early JLD detection and intervention, especially in endemic regions.

Acquired by inhalation of the thermal dimorphic fungi spp. conidia, paracoccidioidomycosis ranges from symptomatic to severe and potentially fatal disseminated disease. The main focus of this review is to highlight clinical aspects of paracoccidioidomycosis and, its pathogens diversity ecology and particularities. In addition, we present strategies for therapy, including DNA vaccines and nanostructured drugs. Molecular and morphological data supported the split of the genus into two species, and . An acute form of the disease affects approximately 5% of cases and involves the phagocytic mononuclear system, resulting in progressive lymphadenopathy. The chronic form affects adult men and frequently involves lungs, skin and mucous membranes, lymph nodes, and adrenal glands. The clinical manifestations depend on the ability of the host to control the fungal multiplication and dissemination. The long survival time of the fungus in the host tissues allows it to evade immune responses; therefore, successful treatment often requires long-time therapy. The consensus for treatment must consider the severity of the disease and includes sulfone derivatives, amphotericin B and azoles. Novel strategies for therapy, based on DNA vaccines and nanostructured drugs are also presented and discussed in this review.

Paracoccidioidomycosis (PCM) defines a broad spectrum of human and animal diseases caused by Paracoccidioides species (Onygenales). In the twenty-first century, Paracoccidioides advanced from a monotypic taxon to a genus that harbors seven species, including P. brasiliensis sensu stricto, P. americana , P. restrepiensis , P. venezuelensis , P. lutzii, P. loboi, and P. cetii . Classic PCM, acquired upon inhalation of propagules from P. brasiliensis sensu stricto, P. americana , P. restrepiensis , P. venezuelensis, and P. lutzii , affects the human lungs and may progress to systemic granulomatous disease with tegumentary and visceral involvement. On the other hand, PCM loboi and PCM ceti caused by the unculturable P. loboi and P. cetii are subcutaneous mycoses, typically observed as keloid lesions in humans and dolphins. Such heterogeneity highlights the importance of recognizing species boundaries in Paracoccidioides to gain insights into the ecology, evolution, clinical features, and mitigation strategies to tackle the advance of PCM.

Background. Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV. Methods. The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed. Results. Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2–331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events. Conclusions. ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents. Clinical Trials Registration. NCT00634049.

Genotyping of the genus Paracoccidioides showed its diversity and geographical distribution. Four species constituting the Paracoccidioides brasiliensis complex and Paracoccidioides lutzii are etiological agents of paracoccidioidomycosis (PCM). However, there are no studies comparing the clinical and epidemiological aspects between PCM caused by the P. brasiliensis complex and by P. lutzii. Demographic and clinical data from 81 patients with PCM-confirmed by mycological and/or histopathological examination-from Mato Grosso do Sul state (Brazil) were studied. All patients underwent serology by immunodiffusion with antigens obtained from the P. brasiliensis complex (ExoPb and gp43) and Cell Free Antigens obtained from P.lutzii (CFAPl).The cases were classified regarding their serological profile into three groups: G1: PCM patients seropositive to ExoPb and/or gp43 and seronegative to CFAPl (n = 51), assumed to have PCM caused by P. brasiliensis complex; G2: PCM patients seronegative to gp43 and seropositive to CFAPl (n = 16), with PCM caused by P. lutzii; and G3: PCM patients seropositive to ExoPb or gp43 and seropositive to CFAPl (n = 14), with undetermined serological profile, was excluded from the analyses. The Fisher's exact test or the Mann-Whitney U test, and cluster analysis according to Ward's method and Euclidean distance were used to analyze the results. Patients with serological profile suggestive of P. lutzii lived predominantly in municipalities in the Central and Southern regions of the state, while those with serological profile indicative of the P. brasiliensis complex were distributed throughout the state. No differences were found between the two groups regarding gender, age, schooling, rural work, clinical form, severity, organs involved, intensity of pulmonary involvement, degree of anemia, erythrocyte sedimentation rate values, and therapeutic response. PCM patients with serological profile suggestive of P. lutzii and PCM patients with serological profile indicative of P. brasiliensis complex showed the same clinical and radiological presentations.

Endemic mycoses such as histoplasmosis, coccidioidomycosis, blastomycosis, paracoccidioidomycosis, and talaromycosis are well-known causes of focal and systemic disease within specific geographic areas of known endemicity. However, over the past few decades, there have been increasingly frequent reports of infections due to endemic fungi in areas previously thought to be “non-endemic.” There are numerous potential reasons for this shift such as increased use of immune suppressive medications, improved diagnostic tests, increased disease recognition, and global factors such as migration, increased travel, and climate change. Regardless of the causes, it has become evident that our previous understanding of endemic regions for these fungal diseases needs to evolve. The epidemiology of the newly described Emergomyces is incomplete; our understanding of it continues to evolve. This review will focus on the evidence underlying the established areas of endemicity for these mycoses as well as new data and reports from medical literature that support the re-thinking these geographic boundaries. Updating the endemic fungi maps would inform clinical practice and global surveillance of these diseases.