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CMAJ : Canadian Medical Association... Apr 2024
Topics: Humans; Tinea Capitis; Male; Alopecia; Child; Antifungal Agents
PubMed: 38649169
DOI: 10.1503/cmaj.231613 -
Microbiology Spectrum Jun 2024Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against sp., both and in a murine model of...
UNLABELLED
Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against sp., both and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by . In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis.
IMPORTANCE
This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.
Topics: Cats; Animals; Itraconazole; Sporotrichosis; Antifungal Agents; Cat Diseases; Sporothrix; Drug Therapy, Combination; Hydrazones; Female; Male; Microbial Sensitivity Tests; Biofilms; Treatment Outcome
PubMed: 38647345
DOI: 10.1128/spectrum.03967-23 -
Mycopathologia Apr 2024The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small...
The cutaneous fungal infections in male genitalia are relatively rare, and often present with various atypical clinical symptoms. It was mainly reported in a small number of case reports, while data with large number of patients were rarely reported. In this study, we reported 79 male patients with cutaneous fungal infections on scrotum or penis. The fungal infections were confirmed by microscopic examination directly and fungus culture. Clinical characteristics and predisposing factors were also collected. Of these 79 patients, 72 has lesions on scrotum, 5 on penis and 2 on both scrotum and penis. Trichophyton (T.) rubrum is the most common pathogen, found in 50 (67.6%) patients, which presented diverse clinical manifestation such as majorly erythematous, dry diffused scaly lesions without a clear border, slightly powdery and scutular scalings. Candida (C.) albicans is the secondly common pathogen, found in 21 (28.4%) patients, which also presented diverse lesions such as erythematous with dry whitish scaly lesions and erythematous erosion. The predisposing factors mainly included concomitant fungal infections on sites other than genitalia, especially inguinal region (tinea cruris), application of corticosteroid and high moisture. In conclusion, cutaneous fungal infections in male genitalia could be caused by different fungi, showed atypical or mild clinical appearances in most cases and might be a fungus reservoir, emphasizing the necessity to timely perform the fungi examinations and corresponding therapy.
Topics: Humans; Male; Dermatomycoses; Skin; Trichophyton; Microscopy; Scrotum
PubMed: 38627263
DOI: 10.1007/s11046-024-00839-0 -
Clinical Medicine & Research Mar 2024To determine if host genetics may be a risk factor for severe blastomycosis. A cohort of patients who had contracted blastomycosis underwent targeted SNP (single...
To determine if host genetics may be a risk factor for severe blastomycosis. A cohort of patients who had contracted blastomycosis underwent targeted SNP (single nucleotide polymorphism) genotyping. The genetics of these patients were compared to a set of age and gender-matched controls and between patients with severe versus mild to moderate blastomycosis. The Marshfield Clinic Health System in central and northern Wisconsin Patients with a diagnosis of blastomycosis prior to 2017 were contacted for enrollment in this study. A phone hotline was also set up to allow interested participants from outside the Marshfield Clinic Health System to request enrollment. SNP frequency was assessed for significant differences between the patient cohort and controls and between patients with severe versus mild to moderate blastomycosis. We also tested the effect of species identified in clinical isolates on disease symptoms and severity. No significant differences were found in SNP frequency between cases and controls or between those with severe or mild to moderate blastomycosis. We did detect significant differences in symptom frequency and disease severity by species. Our study did not identify any genetic risk factors for blastomycosis. Instead, the species of causing the infection had a significant effect on disease severity.
Topics: Humans; Blastomycosis; Blastomyces; Genotype; Ambulatory Care Facilities; Hotlines
PubMed: 38609141
DOI: 10.3121/cmr.2024.1880 -
Communications Biology Apr 2024Infectious diseases are influenced by interactions between host and pathogen, and the number of infected hosts is rarely homogenous across the landscape. Areas with...
Infectious diseases are influenced by interactions between host and pathogen, and the number of infected hosts is rarely homogenous across the landscape. Areas with elevated pathogen prevalence can maintain a high force of infection and may indicate areas with disease impacts on host populations. However, isolating the ecological processes that result in increases in infection prevalence and intensity remains a challenge. Here we elucidate the contribution of pathogen clade and host species in disease hotspots caused by Ophidiomyces ophidiicola, the pathogen responsible for snake fungal disease, in 21 species of snakes infected with multiple pathogen strains across 10 countries in Europe. We found isolated areas of disease hotspots in a landscape where infections were otherwise low. O. ophidiicola clade had important effects on transmission, and areas with multiple pathogen clades had higher host infection prevalence. Snake species further influenced infection, with most positive detections coming from species within the Natrix genus. Our results suggest that both host and pathogen identity are essential components contributing to increased pathogen prevalence.
Topics: Animals; Dermatomycoses; Disease Hotspot; Snakes; Europe; Prevalence
PubMed: 38600171
DOI: 10.1038/s42003-024-06092-x -
Revista Do Instituto de Medicina... 2024Sporotrichosis is a neglected mycosis that affects human and animal hosts, including domestic cats. In Brazil, its most frequently diagnosed etiological agent is...
Sporotrichosis is a neglected mycosis that affects human and animal hosts, including domestic cats. In Brazil, its most frequently diagnosed etiological agent is Sporothrix brasiliensis. Zoonotic transmission of S. brasiliensis occurs via direct contact between an infected cat and a susceptible human host. Notification of confirmed cases of feline sporotrichosis is not mandatory in Brazil. The metropolitan area of Goiania city can be considered a silent area for the occurrence of feline sporotrichosis. In this context, voluntary reporting of feline sporotrichosis cases is recommended for all healthcare professionals. This study aimed to report the first occurrence of S. brasiliensis in a cat from the metropolitan area of Goiania city. Cytopathology, mycology, thermal dimorphism and calmodulin gene amplification tests were performed. The mycological and molecular biological diagnoses corresponded to S. brasiliensis. The etiological agent of zoonotic sporotrichosis was detected in the metropolitan area of Goiania city, and therefore there is a risk of the emergence of new cases of cats infected with S. brasiliensis and the occurrence of zoonotic transmission of this fungus.
Topics: Animals; Cats; Humans; Sporotrichosis; Brazil; Sporothrix; Health Personnel; Cat Diseases
PubMed: 38597519
DOI: 10.1590/S1678-9946202466019 -
PLoS Neglected Tropical Diseases Apr 2024Madurella mycetomatis is the main cause of mycetoma, a chronic granulomatous infection for which currently no adequate therapy is available. To improve therapy, more...
Madurella mycetomatis is the main cause of mycetoma, a chronic granulomatous infection for which currently no adequate therapy is available. To improve therapy, more knowledge on a molecular level is required to understand how M. mycetomatis is able to cause this disease. However, the genetic toolbox for M. mycetomatis is limited. To date, no method is available to genetically modify M. mycetomatis. In this paper, a protoplast-mediated transformation protocol was successfully developed for this fungal species, using hygromycin as a selection marker. Furthermore, using this method, a cytoplasmic-GFP-expressing M. mycetomatis strain was created. The reported methodology will be invaluable to explore the pathogenicity of M. mycetomatis and to develop reporter strains which can be useful in drug discovery as well as in genetic studies.
Topics: Hygromycin B; Madurella; Protoplasts; Transformation, Genetic; Drug Resistance, Fungal; Mycetoma; Cinnamates
PubMed: 38578808
DOI: 10.1371/journal.pntd.0012092 -
Journal of Clinical Immunology Apr 2024The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is...
INTRODUCTION
The signal transducer and activator of transcription (STAT1) gain-of-function (GOF) syndrome accounts for most cases of chronic mucocutaneous candidiasis but is characterized by a broader clinical phenotype that may include bacterial, viral, or invasive fungal infections, autoimmunity, autoinflammatory manifestations, vascular complications, or malignancies. The severity of lymphopenia may vary and influence the infectious morbidity.
METHODS
In our cohort of seven STAT1-GOF patients, we investigated the mechanisms that may determine T lymphopenia, we characterized the interferon gene signature (IGS) and analyzed the effect of ruxolitinib in reverting the immune dysregulation.
RESULTS
STAT1-GOF patients exhibited increased T lymphocyte apoptosis that was significantly augmented in both resting conditions and following stimulation with mitogens and IFNα, as evaluated by flow cytometry by Annexin V/ Propidium iodide assay. The JAK inhibitor ruxolitinib significantly reduced the IFNα-induced hyperphosphorylation of STAT1 and reverted the stimulation-induced T-cell apoptosis, in vitro. In two adult STAT1-GOF patients, the JAKinib treatment ameliorated chronic mucocutaneous candidiasis and lymphopenia. Most STAT1-GOF patients, particularly those who had autoimmunity, presented increased IGS that significantly decreased in the two patients during ruxolitinib treatment.
CONCLUSION
In STAT1-GOF patients, T lymphocyte apoptosis is increased, and T lymphopenia may determine higher risk of severe infections. The JAKinib target therapy should be evaluated to treat severe chronic candidiasis and lymphopenia, and to downregulate the IFNs in patients with autoinflammatory or autoimmune manifestations.
Topics: Adult; Humans; Gain of Function Mutation; Janus Kinase Inhibitors; Candidiasis, Chronic Mucocutaneous; Interferons; Lymphopenia; STAT1 Transcription Factor; Thrombocytopenia; Nitriles; Pyrazoles; Pyrimidines
PubMed: 38578354
DOI: 10.1007/s10875-024-01684-y -
European Review For Medical and... Mar 2024A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections....
OBJECTIVE
A large number of patients applying to the dermatology clinics are affected by fungal diseases, and a significant portion of which are superficial fungal infections. Dermatophyte infections are a notable public health concern and frequently encountered in clinical practice. Dermatophytosis not only compromises the quality of life but also predisposes individuals to various comorbidities due to its role as a gateway for secondary bacterial agents. This study aims to determine the species distribution of dermatophytes prevalent and assess their susceptibility to antifungal drugs.
PATIENTS AND METHODS
Skin, nail, and hair samples were obtained from patients with a clinical diagnosis of dermatophytosis. Samples were all cultured to isolate and identify the species. In vitro liquid microdilution tests were conducted to assess the susceptibility of the isolated strains against terbinafine, fluconazole, griseofulvin, and butenafine.
RESULTS
A total of 353 samples were obtained from the hair, skin, and nail lesions of 326 patients. Dermatophyte was isolated in 71 of the samples (20.1%). The cultured dermatophyte subtypes included Trichophyton rubrum (13.8% in 49 samples), Microsporum audouini (5.7% in 20 samples), and Trichophyton mentagrophytes (0.6% in 2 samples). Antifungal susceptibility testing revealed that terbinafine was the most effective antifungal drug against all dermatophyte species, while fluconazole exhibited the highest resistance.
CONCLUSIONS
The most common dermatophytosis agent in our region is T. rubrum. The least antifungal resistance was found against terbinafine. Conducting antifungal susceptibility tests is crucial for selecting effective treatment regimens and early detection of resistance development.
Topics: Humans; Antifungal Agents; Arthrodermataceae; Terbinafine; Fluconazole; Turkey; Black Sea; Quality of Life; Trichophyton; Microbial Sensitivity Tests; Tinea
PubMed: 38567576
DOI: 10.26355/eurrev_202403_35717 -
PloS One 2024Guinea pigs are popular as domestic pets but there is limited information on the health of the wider pet population. This study aimed to report demography, commonly...
INTRODUCTION
Guinea pigs are popular as domestic pets but there is limited information on the health of the wider pet population. This study aimed to report demography, commonly diagnosed disorders and mortality of guinea pigs under UK primary veterinary care.
METHODS
Diagnosis and mortality information on guinea pigs was extracted from anonymised UK primary-care clinical records in VetCompass.
RESULTS
From 51,622 guinea pigs under primary veterinary care during 2019, a specific breed was not recorded in 50,098 (97.05%). Of guinea pigs with information recorded, 23,206 (47.33%) were female and 25,828 (52.67%) were male. There were 1,020 (2.08%) neutered and 48,014 (97.92%) entire. Median adult bodyweight overall was 1.05kg (interquartile range [IQR] 0.90-1.19, range 0.40-2.66). From a random sample of 3,785/51,622 (7.33%) guinea pigs, the most prevalent disorders were overgrown nail(s) (n = 1,005, 26.55%, 95% confidence interval [CI] 25.15-27.99), dermatophytosis (228, 6.02%, 95% CI 5.29-6.83) and corneal ulceration (189, 4.99%, 95% CI 4.32-5.74). Among the 30 most common disorders, females showed predisposition for 3 disorders and males showed predisposition for 5 disorders. The disorder with the youngest age of affected animals was dermatophytosis (1.11 years) while weight loss had the oldest age of affected animals (4.64 years). From 757 recorded deaths, the median age at death overall was 4.03 years (IQR 2.56-5.44, range 0.17-10.00). Among deaths with a recorded cause, the most common causes of death were anorexia (n = 82, 13.87%, 95% CI 11.19-16.93), collapsed (58, 9.81%, 95% CI 7.54-12.50) and peri-anaesthetic death (20, 3.38%, 95% CI 2.08-5.18).
CONCLUSIONS
These results can assist veterinarians and owners by providing demographic, disorder and mortality benchmarks that support improved clinical care and welfare outcomes in guinea pigs. Many common disorders in guinea pigs were husbandry related.
Topics: Animals; Male; Guinea Pigs; Female; Records; Demography; Tinea; United Kingdom
PubMed: 38536813
DOI: 10.1371/journal.pone.0299464