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Abstract Introduction/Objective Developed in 1946 by J. F. A. McManus, the Periodic Acid Schiff (PAS) stain is among the most frequently used stains in histopathology as a cost-effective ancillary study for the detection of fungal organisms. Despite its wide use in dermatopathology, little research exists comparing PAS to its commonly used counterpart, Gomori methenamine silver (GMS), or to hematoxylin and eosin (H&E) alone. The variation in PAS staining between different fungi causing skin infections has been poorly studied. Methods/Case Report Eighteen cases of fungal skin infections from 1995-2023 were reviewed by a resident pathologist and attending medical mycologist. All eighteen cases possessed H&E, GMS, and PAS stains (staining preservation was confirmed). These cases were selected to represent the following categories of fungal skin infections: 1) superficial or cutaneous; 2) subcutaneous; and 3) systemic (including opportunistic mycoses and endemic dimorphic fungi). The following criteria were used to grade each specimen: ability of PAS to stain the organism’s cell wall; the demonstration of fungal morphology by PAS; and the ease of differentiating PAS-stained organisms from background compared to H&E alone. Results (if a Case Study enter NA) PAS allowed for ready visualization of fungal morphology for all organisms except for Histoplasma spp. and Blastomyces spp. in which organisms tended to blend in with background staining particularly in inflamed tissues. Both fungi were visualized better by GMS. The muriform bodies of chromoblastomycosis, while staining well with PAS, were easy to miss due to their tiny size. Conclusion Compared to H&E alone, PAS allowed for detection of organisms at a lower magnification (40X) for fungal infections except for those in chromoblastomycosis, histoplasmosis, and blastomycosis. PAS is a useful, cost- effective ancillary study for the detection of fungal organisms in dermatopathology; however, care must be taken when there is clinical suspicion for certain fungal organisms that are less well-visualized by PAS.

Fungi often infect mammalian hosts via the respiratory route, but traumatic transcutaneous implantation is also an important source of infections. Environmental exposure to spores of pathogenic fungi can result in subclinical and unrecognised syndromes, allergic manifestations, and even overt disease. After traumatic cutaneous inoculation, several fungi can cause neglected mycoses such as sporotrichosis, chromoblastomycosis, mycetoma, entomophthoramycosis, and lacaziosis. Most of these diseases have a subacute to chronic course and they can become recalcitrant to therapy and lead to physical disabilities, including inability to work, physical deformities, and amputations. For many years, paracoccidioidomycosis was considered the most prevalent endemic systemic mycosis in the Americas, but this situation might be changing with recognition of the worldwide presence of Histoplasma capsulatum. Both paracoccidioidomycosis and histoplasmosis can mimic several infectious and non-infectious medical conditions and lead to death if not recognised early and treated. Cutaneous implantation and systemic mycoses are neglected diseases that affect millions of individuals worldwide, especially in low-income countries where their management is suboptimum because challenges in diagnosis and therapeutic options are substantial issues.

The second World Neglected Tropical Diseases (NTDs) Day was celebrated on 30 January 2021. To mark the occasion, the World Health Organization (WHO) launched its roadmap for NTDs for the period 2021 to 2030, which is aimed at increasing prevention and control of these too-long neglected diseases. Described here is a global overview on past achievements, current challenges, and future prospects for the WHO NTDs roadmap 2021–2030.

Chromoblastomycosis (CBM), represents one of the primary implantation mycoses caused by melanized fungi widely found in nature. It is characterized as a Neglected Tropical Disease (NTD) and mainly affects populations living in poverty with significant morbidity, including stigma and discrimination. In order to estimate the global burden of CBM, we retrospectively reviewed the published literature from 1914 to 2020. Over the 106-year period, a total of 7,740 patients with CBM were identified on all continents except Antarctica. Most of the cases were reported from South America (2,619 cases), followed by Africa (1,875 cases), Central America and Mexico (1,628 cases), Asia (1,390 cases), Oceania (168 cases), Europe (35 cases), and USA and Canada (25 cases). We described 4,022 (81.7%) male and 896 (18.3%) female patients, with the median age of 52.5 years. The average time between the onset of the first lesion and CBM diagnosis was 9.2 years (range between 1 month to 50 years). The main sites involved were the lower limbs (56.7%), followed by the upper limbs (19.9%), head and neck (2.9%), and trunk (2.4%). Itching and pain were reported by 21.5% and 11%, respectively. Malignant transformation was described in 22 cases. A total of 3,817 fungal isolates were cultured, being 3,089 (80.9%) Fonsecaea spp., 552 (14.5%) Cladophialophora spp., and 56 Phialophora spp. (1.5%). This review represents our current knowledge on the burden of CBM world-wide. The global incidence remains unclear and local epidemiological studies are required to improve these data, especially in Africa, Asia, and Latin America. The recognition of CBM as NTD emphasizes the need for public health efforts to promote support for all local governments interested in developing specific policies and actions for preventing, diagnosing and assisting patients.

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021–2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy.

Neglected Tropical Diseases (NTDs) affect more than one billion people globally. A Public Library of Science (PLOS) journal dedicated to NTDs lists almost forty NTDs, while the WHO prioritises twenty NTDs. A person can be affected by more than one disease at the same time from a range of infectious and non-infectious agents. Many of these diseases are preventable, and could be eliminated with various public health, health promotion and medical interventions. This scoping review aims to determine the extent of the body of literature on NTD interventions and health promotion activities, and to provide an overview of their focus while providing recommendations for best practice going forward. This scoping review includes both the identification of relevant articles through the snowball method and an electronic database using key search terms. A two-phased screening process was used to assess the relevance of studies identified in the search-an initial screening review followed by data characterization using the Critical Appraisal Skills Program (CASP). Studies were eligible for inclusion if they broadly described the characteristics, methods, and approaches of (1) NTD interventions and/or (2) community health promotion. 90 articles met the CASP criteria partially or fully and then underwent a qualitative synthesis to be included in the review. 75 articles specifically focus on NTD interventions and approaches to their control, treatment, and elimination, while 15 focus specifically on health promotion and provide a grounding in health promotion theories and perspectives. 29 of the articles provided a global perspective to control, treatment, or elimination of NTDs through policy briefs or literature reviews. 19 of the articles focused on providing strategies for NTDs more generally while 12 addressed multiple NTDs or their interaction with other infectious diseases. Of the 20 NTDs categorized by the WHO and the expanded NTD list identified by PLOS NTDs, several NTDs did not appear in the database search on NTD interventions and health promotion, including yaws, fascioliasis, and chromoblastomycosis. Based on the literature we have identified the four core components of best practices including programmatic interventions, multi sectoral and multi-level interventions, adopting a social and ecological model and clearly defining 'community.' NTD interventions tend to centre on mass drug administration (MDA), particularly because NTDs were branded as such based on their being amenable to MDA. However, there remains a need for intervention approaches that also include multiple strategies that inform a larger multi-disease and multi-sectoral programme. Many NTD strategies include a focus on WASH and should also incorporate the social and ecological determinants of NTDs, suggesting a preventative and systems approach to health, not just a treatment-based approach. Developing strong communities and incorporating social rehabilitation at the sublocation level (e.g. hospital) could benefit several NTDs and infectious diseases through a multi-disease, multi-sectoral, and multi-lateral approach. Finally, it is important the 'community' is clearly defined in each intervention, and that community members are included in intervention activities and viewed as assets to interventions.

A 41-year-old farmer presented with a 20-year history of slowly growing lesions on the right leg. Cultures grew Fonsecaea pedrosoi , and a diagnosis of chromoblastomycosis was made.

IntroductionMacrophage NLRP3 activation is crucial for antifungal immunity, yet its role in chromoblastomycosis—a chronic subcutaneous mycosis typically caused by Fonsecaea pedrosoi —remains unclear. Unlike prior self-resolving models using conidia and hyphae, clinical disease features muriform cells, a parasitic form resistant to macrophages and linked to chronicity. Notably, chitin, a weak NLRP3 agonist, accumulates on the surface of muriform cells. This study investigates whether chitin accumulation modulates NLRP3 activation and promotes fungal persistence.MethodsHuman chromoblastomycosis lesions were analyzed by IHC (MPO, CD86, NLRP3) and RT-PCR for cytokine transcripts. WT and NLRP3–/– mice were footpad-inoculated with F. pedrosoi muriform cells for in vivo assessment. Flow cytometric bead array quantified IL-1β, IL-6, IL-10, TNF-α, and IL-17A in footpad homogenates, and the same panel (excluding IL-17A) in stimulated BMDM supernatants. NLRP3 pathway activation in BMDMs was confirmed by western blotting and immunofluorescence.ResultsIn human lesions, marked MPO+ neutrophil recruitment encapsulated muriform cells, yet multinucleated giant cells sequestered some fungal elements from neutrophils. Despite robust NLRP3 expression and elevated IL-1β, IL-6, TNF-α, and IL-10 versus normal skin (all p < 0.01), muriform cells persisted in tissue. In WT mice, lesions transitioned from purulent (day 7) to granulomatous (day 90), concurrent with declining IL-1β, IL-17A, IL-6, and TNF-α. MPO+ neutrophils abundantly surrounded muriform cells at day 7; at day 90, F4/80+ macrophages enveloped most fungi without elimination, forming multinucleated giant cells—recapitulating human pathology. In NLRP3–/– mice, IL-1β and IL-17A were produced in an NLRP3-independent manner and showed no decline over time. Muriform cells progressively budded and transitioned to hyphae both inside and outside giant cells; MPO+ neutrophils preferentially localized to hyphal areas, while macrophages remained around muriform cells, suggesting compartmentalized inflammation. In vitro , chitinase-treated muriform cells induced higher NLRP3-dependent IL-1β, IL-6, TNF-α, and IL-10 in WT BMDMs versus intact cells (all p < 0.01). Mechanistically, chitin accumulation partially suppressed NF-κB phosphorylation, reducing NLRP3 expression, caspase-1 cleavage, and ASC speck formation.ConclusionNLRP3 mediates host defense against muriform cells yet fails to resolve chronic infection. Chitin accumulation on muriform cells attenuates NLRP3 activation, thereby promoting chromoblastomycosis chronicity.

Fungal infections commonly present with myriad symptoms that mimic other clinical entities, notable amongst which is tuberculosis. Besides histoplasmosis and chronic pulmonary aspergillosis, which can mimic TB, this review has identified several other fungal infections which also do. A total of 80 individual cases misdiagnosed as TB are highlighted: aspergillosis (n = 18, 22.5%), histoplasmosis (n = 16, 20%), blastomycosis (n = 14, 17.5%), cryptococcosis (n = 11, 13.8%), talaromycosis (n = 7, 8.8%), coccidioidomycosis (n = 5, 6.3%), mucormycosis (n = 4, 5%), sporotrichosis (n = 3, 3.8%), phaeohyphomycosis (n = 1, 1.3%) and chromoblastomycosis (n = 1, 1.3%). Case series from India and Pakistan reported over 100 cases of chronic and allergic bronchopulmonary aspergillosis had received anti-TB therapy before the correct diagnosis was made. Forty-five cases (56.3%) had favorable outcomes, and 25 (33.8%) died, outcome was unclear in the remainder. Seventeen (21.3%) cases were infected with human immunodeficiency virus (HIV). Diagnostic modalities were histopathology (n = 46, 57.5%), culture (n = 42, 52.5%), serology (n = 18, 22.5%), cytology (n = 2, 2.5%), gene sequencing (n = 5, 6.3%) and microscopy (n = 10, 12.5%) including Gram stain, India ink preparation, bone marrow smear and KOH mount. We conclude that the above fungal infections should always be considered or ruled out whenever a patient presents with symptoms suggestive of tuberculosis which is unconfirmed thereby reducing prolonged hospital stay and mortalities associated with a delayed or incorrect diagnosis of fungal infections.