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Background: The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD., Materials and Methods: Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests., Results: A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94)., Conclusion: Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3-87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene-deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis., (© 2020 Wiley-VCH GmbH.)

Background: Malassezia pachydermatis is a rare cause of systemic infection in infants., Methods: A total of 4 cases of M. pachydermatis fungemia that occurred in our neonatal intensive care unit over a 21-month period were reviewed, as well as 27 cases reported in the literature since 1988., Results: The patients were preterm with multiple complications and had birth weights ranging from 490 to 810 g and gestational age between 23 and 26 weeks. All patients had received prophylactic fluconazole, broad-spectrum antibiotics and parenteral lipid supplements before fungemia onset, which occurred between the age of 7 and 28 days. Symptoms were nonspecific and thrombocytopenia was the primary laboratory finding. All patients received intravenous antifungal treatment and recovered from their infection. The 27 cases from review of the literature also indicated that the infected infants were extremely low birth weight (77.8%), with multiple underlying diseases (94.7%), receiving lipid-supplementation (100%) from a central vascular catheter. Most infants received antifungal treatment (73.1%) and catheter removal (73.1%) as the management., Conclusions: M. pachydermatis is a pathogenic agent that causes late onset sepsis in critically ill low birth weight infants with generally good outcomes. Targeted antifungal treatment as well as catheter removal appear to be key factors for infection management.

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17  cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4 + CD161 + IL23R + ) and Treg (CD4 + CD25 + FoxP3 + ) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4 + T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Importance: Terbinafine hydrochloride and griseofulvin are effective oral treatments for dermatophyte infections but have been associated with hepatic and hematologic abnormalities. The prevalence of alanine aminotransferase elevations, aspartate aminotransferase elevations, anemia, lymphopenia, and neutropenia among adults and children taking terbinafine and griseofulvin is unclear., Objective: To measure the rate of laboratory test result abnormalities in healthy adults and children taking terbinafine or griseofulvin for dermatophyte infections., Design, Setting, and Participants: This retrospective study assessed adults and children taking terbinafine or griseofulvin for dermatophyte infections from January 1, 2006, to December 31, 2016. Data were collected from one Midwest health care system. Exclusion criteria were preceding diagnosis of hepatic or hematologic condition and preceding or concurrent use of oral ketoconazole, amphotericin, or itraconazole., Main Outcomes and Measures: The rates of elevated alanine aminotransferase measurements, elevated aspartate aminotransferase measurements, anemia, lymphopenia, and neutropenia in adults and children taking terbinafine, griseofulvin microsize, or griseofulvin ultramicrosize were calculated. Secondary measures included rates of baseline abnormalities, frequency of laboratory test results that required additional testing or discontinued use of medication, and laboratory test result monitoring practices., Results: This study included laboratory data from 4985 patients (mean [SD] age, 42.8 [20.3] years; 2288 [45.9%] female) receiving 4309 courses of terbinafine, 634 courses of griseofulvin microsize, and 159 courses of griseofulvin ultramicrosize. We identified a low rate of laboratory test result abnormalities in patients taking terbinafine or griseofulvin. When laboratory test result abnormalities occurred, most were low grade (212 [93.4%] grade 1) and did not require subsequent laboratory test result evaluation or discontinued use of medication (15 051 [99.9%]). Elevations in alanine aminotransferase measurements were detected infrequently and were comparable to baseline detection rates (61 [3.5%] vs 95 [3.6%] for terbinafine, 2 [2.1%] vs 3 [3.7%] for griseofulvin microsize, and 0 vs 2 [5.0%] for griseofulvin ultramicrosize). Rates of elevated aspartate aminotransferase measurements, anemia, lymphopenia, and neutropenia were also infrequent and comparable to baseline rates., Conclusions and Relevance: In this study. the rates of alanine aminotransferase elevations, aspartate aminotransferase elevations, anemia, lymphopenia, and neutropenia in adults and children taking terbinafine or griseofulvin were low and equivalent to the baseline rates of abnormalities in this population. Routine interval laboratory test result monitoring appears to be unnecessary in adults and children without underlying hepatic or hematologic conditions taking terbinafine or griseofulvin for dermatophyte infections. Abandoning frequent laboratory monitoring can decrease unnecessary health care spending, decrease patient psychological angst associated with blood draws, and allow for expanded use of these effective oral medications.

Purpose: The aim of this study was to develop and evaluate the diagnostic potential of indirect enzyme-linked immunosorbent assay (I-ELISA) for the rapid and precise diagnosis of Microsporum canis infection in humans., Basic Procedures: The present study reports the production, partial purification and SDS-PAGE analysis of M. canis mycelial antigens and production of specific polyclonal antibodies. It also reports the development and optimization of indirect ELISA and evaluation of its potential for the diagnosis of M. canis infection in humans., Main Findings: An I-ELISA showed the sensitivity of 94.55% and specificity of 93.33%. Positive and negative predictive values were 96.30% and 90.32% respectively. Receiver operating characteristic (ROC) curve analysis of the data showed higher diagnostic accuracy. The area under the curve (AUC) was 0.925. A significant correlation coefficient of 0.8771 (P<0.0001) was obtained between I-ELISA and fungal culture method., Principal Conclusions: In conclusion, the present study clearly shows the detection of specific antibodies by indirect ELISA using M. canis antigens. The assay is sensitive, specific and easy to perform, could enable rapid and more convenient diagnosis of dermatophytosis in humans., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Mucormycosis is a relatively rare fungal infection seen in immunocompromised patients. Very few cases of invasive cutaneous mucormycosis occurring in neonates have been reported in literature. It is an aggressive disease with a mortality rate of around 64% in neonates, so a high index of suspicion is essential for rapid diagnosis and definitive treatment with broad-spectrum antifungals such as Amphotericin B. We present a case of a premature infant born at 25 weeks of gestation who developed vesicobullous lesions all over the body on day 5 of life. Biopsy from the vesicles confirmed the presence of angioinvasive fungal hyphae of mucormycosis which were highlighted on Periodic acid-Schiff and Grocott stain., Competing Interests: There are no conflicts of interest

Non-Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non-Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non-Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin-resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains., (© 2016 Blackwell Verlag GmbH.)

OBJECTIVE To determine the pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. ANIMALS 123 bats from a P destructans-infected hibernation site in Virginia. PROCEDURES 3 bats were euthanized and necropsied to confirm the presence of P destructans within the population. The remaining 120 bats were systematically assigned to 6 groups (20 bats/group). Bats in each of 3 groups received 6, 20, or 60 mg of terbinafine/kg, SC, once daily for 10 days. Bats in another group received 200 mg of terbinafine/kg, SC, once daily for 5 days. Bats in 1 group received the terbinafine vehicle solution (0.1 mL/kg, SC, once daily for 10 days). Bats in the remaining group did not receive any treatment. Following the treatment period (days 1 through 10), bats were housed in a hibernation chamber and monitored daily until euthanasia on day 42, 75, or 109. Tissue specimens were collected from all bats as soon as possible after death or euthanasia to determine terbinafine concentration. Within each group and tissue type, terbinafine concentration data were pooled, and pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS Adverse neurologic effects and a high mortality rate before day 10 were observed in bats that received the highest terbinafine dose (200 mg/kg) but not those that received lower doses. Presumed therapeutic terbinafine concentrations (≥ 2 μg/g) were maintained in skin and wing for at least 30 and 6 days in bats that received the 60 and 20 mg/kg doses, respectively, but were not achieved in most bats that received the 6 mg/kg dose. Tissue terminal half-life ranged from 14 to 22 days. Terbinafine concentration in hair was positively correlated with that in skin and wing. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated terbinafine doses > 6 but < 200 mg/kg should be further evaluated for the treatment of P destructans-infected bats. Collection of serial hair specimens may represent a noninvasive method for monitoring terbinafine concentration in treated bats.

The mechanisms involved in the establishment of the specific immune response against dermatophytes remain unknown. Polymorphonuclear neutrophils (PMNs) are recruited early during the infection process and participate in the elimination of dermatophytes. They could therefore be involved in the induction of the immune response during dermatophytoses by producing specific cytokines. The aim of this work was to assess the in vitro cytokine production by feline PMNs exposed to living arthroconidia from the dermatophyte species Microsporum canis or stimulated with either a secreted or a structural component of M. canis, the latter consisting of heat-killed arthroconidia. The levels of specific cytokines produced by PMNs were determined by capture ELISA and/or quantitative RT-PCR. Results showed that PMNs secrete TNFα, IL-1β and IL-8 following exposure to M. canis living arthroconidia and stimulation with both a secreted component and heat-killed arthroconidia. The level of IL-8 mRNA was also increased in PMNs stimulated with M. canis living arthroconidia. In conclusion, infective M. canis arthroconidia induce the production of pro-inflammatory cytokines by feline PMNs that can be activated either by secreted or structural fungal components. Our results suggest that these granulocytes are involved in the initiation of the immune response against M. canis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Systemic and focal infections caused by microorganisms have been known to induce or exacerbate psoriasis. Although the role of yeast species of the genus Malassezia in the pathogenesis of psoriasis is not fully understood, it is thought that these lipophilic yeasts may represent a triggering factor in the exacerbation of psoriatic lesions., Objectives: This study investigated the effects of Malassezia yeasts on serum Th1 and Th2 cytokines in patients with guttate psoriasis (GP) in order to define their role in the pathogenesis of psoriasis., Methods: Fifty patients with GP and 29 clinically healthy individuals were included in the study. All samples consisted of scales and scrapings taken from the scalps, trunks, and upper limbs of both psoriasis patients and healthy subjects. Psoriasis patients and healthy subjects were grouped according to their positivity or negativity for Malassezia yeasts as ascertained by direct microscopy and/or culture. An enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of Th1 and Th2 cytokines in these groups., Results: No significant differences in positivity for Malassezia yeasts were found between psoriatic skin and healthy skin in samples taken from different body sites. Serum interleukin-13 (IL-13) levels were significantly lower in the psoriasis group compared with the control group (P = 0.04). Levels of other cytokines did not differ significantly between the psoriasis and control groups. Mean levels of Th2 cytokines (IL-4, IL-10, IL-13), but not of Th1 cytokines (IL-2 and IFN-γ), were significantly lower in psoriasis patients positive for Malassezia yeasts compared with those negative for Malassezia yeasts and control subjects (P = 0.04, P < 0.001 and P = 0.01, respectively)., Conclusions: The isolation of Malassezia yeasts from GP lesions does not necessarily mean that these species are pathogenic, but their downregulating effects on anti-inflammatory Th2 cytokines may contribute to the occurrence of GP., (© 2012 The International Society of Dermatology.)

The disease chytridiomycosis is responsible for declines and extirpations of amphibians worldwide. Chytridiomycosis is caused by a fungal pathogen (Batrachochytrium dendrobatidis) that infects amphibian skin. Although we have a basic understanding of the pathophysiology from laboratory experiments, many mechanistic details remain unresolved and it is unknown if disease development is similar in wild amphibian populations. To gain a better understanding of chytridiomycosis pathophysiology in wild amphibian populations, we collected blood biochemistry measurements during an outbreak in mountain yellow-legged frogs (Rana muscosa) in the Sierra Nevada Mountains of California. We found that pathogen load is associated with disruptions in fluid and electrolyte balance, yet is not associated with fluctuations acid-base balance. These findings enhance our knowledge of the pathophysiology of this disease and indicate that disease development is consistent across multiple species and in both laboratory and natural conditions. We recommend integrating an understanding of chytridiomycosis pathophysiology with mitigation practices to improve amphibian conservation.

Cutaneous infection by histoplasmosis in Cuban HIV patients was researched. In a case series study, all HIV patients admitted to "Pedro Kouri" Institute from January 1st, 1992 to June 30th, 2003, who had been diagnosed with cutaneous histoplasmosis, were included. Of 44 patients with histoplasmosis, 52% (23 cases) developed the progressive disseminated form of histoplasmosis, which behaved as a subacute weakening disease. Young adults represented 56.5% and 82.6% were males mainly Caucasian (91.3%). Most of cases came from the Western provinces. Histoplasmosis was a marker disease in 39.1% of cases. CD4+ T-lymphocyte counting under 200 cell/mm3 was present in 78.9% of patients. Histoplasmosis seems to behave as an important marker disease for AIDs in seropositive patients. Serology was not the diagnosing method of choice for this cutaneous disease in AIDS patients.

The purpose of this study was to determine the zinc levels in calves with trichophytosis and to research the importance of zinc for fungi. The sera of 20 calves with trichophytosis and 10 healthy calves were used in this study. Zinc levels of the sera were measured by the atomic absorption spectrophotometer method. Serum zinc levels of diseased and healthy animals were found to be 42.0+/-16.6 microg/dL and 75.8+/-5.9 microg/dL, respectively. Serum zinc levels of diseased calves were lower than healthy ones and this difference were found to be important statistically (p<0.001), whereas there is no statistical difference on the levels of lymphocyte, monocyte, granulocyte, erythrocyte, hemoglobin, hematocrit, and mean corpuscular volume between groups. These parameters were not influenced by low zinc levels.

Background: The opportunistic yeast Malassezia is considered to be one of the factors that can contribute to atopic eczema (AE). Elevated serum IgE levels, T-cell proliferation and positive skin prick test (SPT) and atopy patch test (APT) reactions to Malassezia are found among AE patients., Methods: Sera from 127 AE patients, 14 patients with seborrheic dermatitis (SD) and 33 healthy controls were investigated for IgE and IgG4 to M. sympodialis extract and four recombinant Malassezia allergens; rMala s 1, rMala s 5, rMala s 6, and rMala s 9. In addition, IgG to the recombinant allergens was analyzed. The IgG and IgG4 levels were compared to IgE levels and in vivo reactions (SPT and APT) to Malassezia., Results: AE patients with serum IgE levels >0.35 kU/l to M. sympodialis extract had significantly higher IgG4 levels to M. sympodialis extract than AE patients without detectable serum IgE to M. sympodialis extract, SD patients and healthy controls. Among the AE patients with and without detectable serum IgE to M. sympodialis extract, respectively, there were no differences in IgG4 levels between patients with positive or negative in vivo reactions to M. sympodialis extract. IgG4 to the rMala s allergens was almost exclusively found among patients with IgE to the same allergen. Within the four tested rMala s allergens, most IgG4 reactions were found to rMala s 6, an allergen with homology to cyclophilin., Conclusions: Elevated serum IgG4 to M. sympodialis extract accompanies elevated serum IgE to the extract. This is further confirmed by the association between IgG/IgG4 and IgE to recombinant Malassezia allergens.

Few studies are available about the participation of the immune response in the control or the development of Jorge Lobo's disease. Thus, the objective of the present study was to quantify macrophage and lymphocyte cytokines in the supernatant of cell cultures and in blood serum from patients with this disease. The study was conducted on 15 patients with the mycosis and on 15 healthy adult individuals (control group). Blood samples were collected in order to obtain serum and mononuclear cells. Monocytes were cultured for 24 h in the presence or absence of LPS and L. loboi, and lymphocytes were cultured for 48 h in the presence or absence of PHA and L. loboi. Cytokines IL-1beta, TNF-alpha and IL-6 were quantified by ELISA in the supernatants of monocyte cultures and in serum. Cytokines IL-2, IFN-gamma, IL-4 and IL-10 were quantified by FLISA in the supernatants of lymphocyte cultures and in serum. The quantification of the cytokines in the culture supernatant revealed a greater IL-4 and IL-6 production and lower IL-2 levels in patients compared to control. The production of IL-1beta, TNF-alpha, IL-10 and INF-gamma was similar in patients and controls. The mononuclear cells from patients with the non-localized form of the disease produced higher INF-gamma levels than those of patients with the localized form. The results suggest that patients with Jorge Lobo's disease show altered cytokine profiles represented by a predominance of the Th2 profile. However, further studies are needed to assess the participation of cytokines in the cell-fungus interaction in situ.

A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality.

Studies on host-parasite interaction in Jorge Lobo's disease are scarce, with no report in the literature on the phagocytosis of Lacazia loboi by phagocytic mononuclear cells. Thus, the objective of the present study was to assess the phagocytic activity of blood monocytes in the presence of L. loboi in patients with the disease and in healthy subjects (controls) over 3 and 24 hours of incubation. Statistical analyses of the results showed no significant difference in percent phagocytosis of the fungus between patient and control monocytes. With respect to incubation time, however, there was a significant difference, in that percent phagocytosis was higher at 3 hours than at 24 hours (p <0.01). These results suggest that monocytes from patients with the mycosis are able to phagocyte the fungus, as also observed in control individuals.

In order to better understand the host-fungus relationship in Microsporum canis dermatophytosis and to identify major fungal antigens, the immune response to a crude exoantigen preparation and to a purified recombinant keratinolytic metalloprotease (r-MEP3) was evaluated in guinea pigs experimentally infected with M. canis. Humoral and cellular immune responses were assessed from day 0 to day 57 post-infection (PI), the former by enzyme-linked immunosorbent assay (ELISA) and the latter via a lymphocyte proliferation assay. Infected guinea pigs developed humoral and cellular responses to both M. canis exoantigen and r-MEP3, while no specific immune response to these antigens was observed in control animals. This is the first report on the development of both humoral and cell-mediated immune responses to a purified keratinase in M. canis dermatophytosis.

An in-house prepared M. furfur antigen was used to carry out a seroprevalence study in an urban population in Malaysia by indirect immunofluorescence assay. Of the 800 serum samples from all ages screened, 738 samples were positive for M. furfur specific IgG, giving an overall seropositive rate of 92.3%. There was no significant difference in the seropositive rates among the different gender group and races. However, there was a statistical significant difference in the seropositive rate among different age groups with a lower rate (73%) for the age group 5 years old and below, which increased rapidly to 99% for the 16 to 20 years old age group but declined slightly for the oldest age group. The degree of seropositivity, which semi-quantitatively reflect the anti-M. furfur specific IgG titre, did not show any significant difference among the gender and racial groups. On the other hand, there was a significant difference in the degree of seropositivity among the various age groups, with the 16 to 20 years old age group having the highest antibody titre and the extreme of age groups having the lower antibody titre.

Objective: To investigate the potential cell-mediated immune response of atopic dogs to the yeast Malassezia pachydermatis and to correlate it with the type-1 hypersensitivity (humoral) response of the same population of dogs., Animals: 16 clinically normal dogs, 15 atopic dogs with Malassezia dermatitis, 5 atopic dogs with Malassezia otitis, and 7 atopic control (ie, without Malassezia dermatitis or otitis) dogs., Procedure: A crude extract of M pachydermatis was extracted for use as an intradermal allergy testing reagent and for stimulation of isolated peripheral blood mononuclear cells in vitro. Flow cytometry was also used to assess cell surface antigenic determinants (CD3, CD4, CD8, CD14, CD21, CD45RA, surface immunoglobulin) on peripheral blood mononuclear cells., Results: Atopic dogs with cytologic evidence of Malassezia dermatitis had an increased lymphocyte blastogenic response to crude M pachydermatis extract, compared with clinically normal dogs and dogs with Malassezia otitis. Atopic control dogs did not differ significantly in their responses from atopic dogs with Malassezia dermatitis or otitis. A significant correlation was not found between the lymphocyte blastogenic response and the type-1 hypersensitivity response to M pachydermatis within any of the groups., Conclusions and Clinical Relevance: Cell-mediated and humoral reactivities to M pachydermatis contribute to the pathogenesis of atopic dermatitis in dogs but are not directly correlated. Modification of the dysregulated immune response toward M pachydermatis may assist in the reduction of pathologic changes associated with an atopic dermatitis phenotype in dogs.

Griseofulvin is a metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fongistatic, the exact mechanism in witch it inhibits the growth of dermatophytes is doubtful. Several ways are invoked: inhibition of fungal cell mitosis and nuclear acid synthesis, probable interference with the function of microtubules. Griseofulvin is poorly absorbed from the gastrointestinal tract. Absorption is enhanced by administration with fatty meal. Peak plasma occurs four hours after oral administration. Griseofulvin is detected in the outer layer of the stratum corneum soon after it is ingested, it is diffused from the extracellular fluid and sweat. There is no information regarding the mechanism by witch the drug is delivered to nails and hair. Deposition in the newly formed cells could be the major factor. Griseofulvin has also anti-inflammatory properties and some direct vasodilatory effects when it is used in high doses. It is metabolised by the liver microsomial enzyme system and excreted in the urine. The half-life is 9 to 21 hours. Griseofulvine has been used in the therapy of dermatophyte onychomycosis, treatment periods from 6 to 18 months were necessary with disappointing results and numerous relapses. Newer oral antifungal agents are now preferred especially in toenail infections. For many authors griseofulvin is still the treatment of choice of tinea capitis. Doses are 15-20 mg/kg/d for 6 to 8 weeks in children with the microsized form. Clinical response rates have been reported between 80 and 90 p. 100 in controlled studies. Griseofulvin is well-tolerated particulary in children. More frequent side effects are minor: headaches, gastrointestinal reactions and cutaneous eruptions. The major drug interactions has been noted with phenobarbital, anticoagulants and oral contraceptives.

Human T helper (Th) cells (Th1- or Th2-oriented memory T cells as well as Th1- or Th2-polarized naive T cells) were infected in vitro with an R5-tropic HIV-1 strain (BaL) and assessed for their profile of cytokine production, CCR5 receptor expression, and HIV-1 p24 antigen (p24 Ag) production. Higher p24 Ag production was found in CCR5-negative Th2-like memory T cells than in CCR5-positive Th1-like memory T cells. By contrast, p24 Ag production was higher in Th1-polarized activated naive T cells in the first 4 days after infection. However, p24 Ag production in Th1-polarized T cells became comparable or even lower than the production in Th2-polarized populations later in infection or when the cells were infected with HIV-1BaL after secondary stimulation. The higher levels of p24 Ag production by Th1-polarized naive T cells soon after infection reflected a higher virus entry, as assessed by the single round infection assay using the HIV-chloramphenicol acetyl transferase (HIV-CAT) R5-tropic virus that contains the envelope protein of HIV-1 YU2 strain. The limitation of viral spread in the Th1-polarized populations, despite the initial higher level of T-cell entry of R5-tropic strains, was due to the ability of Th1 cells to produce greater amounts of beta-chemokines than Th2 cells. In fact, an inverse correlation was observed between Th1-polarized naive T cells and Th1-like memory-activated T cells in regards to p24 Ag production and the release of the following CCR5-binding chemokines: regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Moreover, infection with the HIV-1BaL strain of Th1-polarized T cells in the presence of a mixture of anti-RANTES, anti-MIP-1alpha, and anti-MIP-1beta neutralizing antibodies resulted in a significant increase of HIV-1 expression. These findings suggest that Th1-type responses may favor CD4(+) T-cell infection by R5-tropic HIV-1 strains, but HIV-1 spread in Th1 cells is limited by their ability to produce CCR5-binding chemokines. (Blood. 2000;95:1167-1174)

Objective: To determine whether there are haematological, serum biochemical and serological differences between platypuses (Ornithorhynchus anatinus) with and without granulomatous dermatitis due to Mucor amphibiorum infection. An additional objective was to establish reference haematological and serum biochemical ranges for the species in Tasmania., Design: A clinicopathological and serological study., Animals: A total of 37 free-living adult platypuses captured from streams and dams in Northern Tasmania were used in the clinicopathological study. Twenty-seven were clinically normal and 10 had mycotic granulomatous dermatitis. A total of 22 platypuses (20 adult and 2 juvenile) were used for the serosurvey. Eighteen were captured from streams in Northern Tasmania, and four were submitted for necropsy., Results: Platypuses with mycotic ulcerative dermatitis had significantly smaller packed red cell volumes, haemoglobin concentrations, lymphocyte counts, serum cholesterol and calcium concentrations, and higher serum globulin and potassium concentrations than clinically normal animals. The lymphopenia and hyperkalaemia were thought to be clinically significant. Numbers of Trypanosoma binneyi in blood smears were similar between the two groups. Diseased platypuses had higher concentrations of serum antibody against Mucor amphibiorum as determined by ELISA compared to clinically normal platypuses., Conclusion: Platypuses affected by mycotic granulomatous dermatitis showed haematological and serum biochemical changes when compared to clinically normal animals from the same Tasmanian sites. A serological survey may be a useful method for detecting the prevalence of exposure to Mucor amphibiorum and humoral immunity in platypus populations both in Tasmania and the mainland of Australia.

Background: Two new systemic antifungal agents, terbinafine and itraconazole, have expanded the choices for treatment of onychomycosis. The pharmacokinetic and pharmacologic properties provide the basis of their activity and are related to their efficacy and safety in dermatophyte infections., Objective: We describe the pharmacodynamics, pharmacokinetics, and pharmacology of terbinafine and itraconazole and the features that form a framework for comparing their efficacy. PHARMACODYNAMICS: Both terbinafine and itraconazole ultimately block ergosterol synthesis; terbinafine disrupts fungal cell wall synthesis earlier (squalene to squalene epoxide) than does itraconazole (lanosterol to ergosterol). In vitro, terbinafine exposure results in a toxic accumulation of squalene and decreased production of ergosterol. Minimal inhibitory concentrations (MICs) of terbinafine for dermatophytes are essentially equal to minimal fungicidal concentrations (MFCs). However, the MFCs of itraconazole are much higher than the MICs. PHARMACOLOGIC PROFILE: Both itraconazole and terbinafine penetrate keratinizing tissue; levels reached in nail plate exceed those in plasma. Therapeutic levels of the itraconazole persist in nails for up to 6 months after discontinuation of 3 months of therapy (200 mg/day) and during various pulsed cycles. After discontinuation of 1 month of therapy, terbinafine persists at therapeutic levels in the nail. Itraconazole has an affinity for mammalian cytochrome P-450 enzymes as well as for fungal P-450-dependent enzyme, and thus has the potential for clinically important interactions (e.g., astemizole, terfenadine, rifampin, oral contraceptives, H2 receptor antagonists, warfarin, cyclosporine). Terbinafine is not metabolized through this system and has little potential for drug-drug interactions., Conclusion: The low MFCs exhibited by terbinafine for dermatophytes may be important in its clinical efficacy and low relapse rates. The safety profile of terbinafine directly reflects its mechanism of action.

Some measures of systemic host defences, i.e. white cell counts, lymphocyte subsets, delayed-type hypersensitivity and polymorphonuclear leucocyte functions, were evaluated in 42 patients suffering from cutaneous superficial mycoses and in 35 healthy volunteers. Patients were divided according to the extent of their lesions into two groups: group A (30 patients) with skin involvement > or = 30% and group B (12 patients) with skin involvement < or = 1%. No significant abnormalities in systemic defence mechanisms were observed in group B patients, whereas multiple alterations of polymorphonuclear phagocyte activities, i.e. chemotaxis, phagocytosis, mitogen-induced superoxide anion production, were observed in patients with extensive lesions. The values of these phagocytic functions remained significantly reduced (P < 0.01) in these patients after recovery and during a 6-month follow-up period.

Microsporum canis infection was induced in five of six adult cats by the application of mycelium to shaved and mildly abraided skin. The clinical course of the disease was monitored over 16 weeks by physical examination and Wood's lamp illumination. The incubation period (time from inoculation to first appearance of infected hairs) varied between 8 and 13 days and was followed by a progressive phase of slow peripheral expansion of lesions accompanied by scaling, alopecia and skin thickening that lasted for approximately 2 weeks. In four of the five cats the lesions then remained stable for between 1 and 6 weeks before regression occurred, with clinical resolution evident in these cats by 11-14 weeks post-infection. In one cat disease was more prolonged, with regression only beginning at the end of the study, and this cat also developed a satellite lesion. Immunological responses during infection were monitored every 2 weeks and consisted of ELISA to measure serum M. canis-specific IgG, IgM and IgA antibody concentrations, M. canis antigen-specific lymphocyte proliferation assay, and mitogen-induced (ConA) lymphocyte proliferation assay. In all three immunoglobulin classes evaluated, a significant (P < or = 0.020) rise in antibody concentration was seen in response to infection, and occurred earliest with the IgM class (2 weeks post-infection). Overall, a heterogeneous antibody response was found, and changes in antibody concentration showed no clear temporal relationship to recovery from disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary coccidioidomycosis is frequently accompanied by eosinophilia in the range of 5%-10% of the peripheral white blood cell count. Dissemination of Coccidioides immitis to organs such as skin, bone, joints, and CNS usually is associated with risk factors such as sex (male), race (non-Caucasian), pregnancy, and immunosuppression. We report a case of coccidioidomycosis in an otherwise healthy African-American man with 72% eosinophilia who had dissemination to the skin, and we review cases in the literature of disseminated disease associated with eosinophilia. Marked eosinophilia may be an important early clue that dissemination of coccidioidomycosis has occurred.

A Curvularia species was isolated from a chronic ulcer on the lower limb of a 21-year-old man. The histopathological findings supported the mycological diagnosis. An enzyme-linked immunosorbent assay (ELISA) was performed using a crude soluble fungal antigen. The patient's serum contained significantly more antibodies than 10 sera from control subjects (P < 0.05, t-test).

Peripheral blood lymphocytes isolated from cattery cats which were culture positive for Microsporum canis, or from cats which had recovered from M. canis infection, showed a significantly greater mean in vitro blastogenic response to M. canis antigen than lymphocytes from uninfected cats. Mean lymphocyte reactivity to concanavalin A was higher in cats which had recovered from infection than in either culture positive or uninfected cats, whereas reactivity to phytohemagglutinin was highest in the culture positive group. Antibody (both IgG and IgM) against dermatophyte glycoprotein antigen was detectable in the plasma of all cats, but was present in significantly higher titres in the culture positive group. Our results demonstrate that M. canis infected cats mount strong humoral and cellular immune responses to the organism; these responses can be detected by use of anti-dermatophyte antibody quantitation and lymphocyte blastogenesis assays, as has been reported previously for dermatophytosis in other species. Asymptomatic, culture positive cats were found in only three of seven catteries and were genetically related, raising the possibility of genetic predisposition to persisting asymptomatic infection.

A total of 102 patients were examined, 32 of these with true eczema, 38 with exudative mycosis of the soles, and 32 with eczema etiologically related to a fungal infection. Analysis of the immune and biochemical reactions in the examinees has shown a marked reduction of adenyl nucleotides in the leukocytic suspension and neutrophils of patients with a mycotic infection as against those with true eczema. The lowest creatine phosphate levels were detected in the leukocytic suspension and neutrophils of the patients suffering from eczema etiologically related to mycosis and exudative mycosis of the soles. These results give grounds to search for effective corrective therapy.

Sporothrix cyanescens has been recovered from blood and a finger lesion at several medical centers in the United States. The morphology and physiology of these and three additional isolates were studied. S. cyanescens was distinguished from S. schenckii and S. fungorum by white to lavender colonial pigmentation and from S. schenckii also by the formation of secondary conidia. All isolates of S. cyanescens grew well at 37 degrees C, were cycloheximide susceptible, strongly urease positive, and benomyl resistant, failed to hydrolyze starch, and were inhibited by sodium chloride in vitro at a concentration of greater than or equal to 12%. Study of S. cyanescens in a murine model by using intravenous inoculation failed to demonstrate an invasive pathogenic potential. The validity of the transfer of S. cyanescens to the new genus Cerinosterus Moore is discussed.

Changed glycogen levels in the neutrophils and monocytes is a pathogenetic component contributing to the development of mycoses of the soles and a characteristic feature of nonspecific immune reactivity. The neutrophilic phagocytic activity is depressed in such patients, and the monocytes are functionally inert. Furazolidonum, potassium orotate, and riboflavin are effective stimulants of the cell-mediated defense in such patients.

The factor present in normal human serum which inhibits growth of dematophytic fungi is characterized and identified. Serum inhibitory factor (SIF) is nondialyzable, heat stable at 56 degrees C. for 4 hours, and fungistatic. SIF was found to be an inhibitor of the dermatophyte genera Trichophyton, Microsporium, and Epidermophyton as well as the dimorphic yeast Candida albicans. SIF activity directly correlated with a serum's unbound iron-binding capacity (UIBC) in that lower UIBC'S were less inhibitory. Addition of iron to serum neutralized the inhibitory activity and this neutrilization was shown to be specific for iron since zinc, magnesium, managnese, and copper failed to alter serum inhibitory activity. Furthermore, addition of purified iron-free transferrin to a neutralized serum restored the SIF activity in parallel with the UIBC. Removal of transferrin from serum by affinity chromatography was confirmed by polyacrylamide gel electrophoresis and iron-binding assays. Transferrin-free serum produced by this procedure was shown to lack inhibitory activity. These data indicate that SIF is unsaturated transferrin and strongly suggests that it inhibits dermatophytes by binding iron which many organisms need for growth.

In the present study we intended to obtain information on the evolution of near-peak blood levels during long-term treatment. 56 patients with an indication for systemic treatment of nail or skin mycoses obtained a daily dose of 200 mg ketoconazole. They were periodically checked for blood level of ketoconazole, clinical and mycological status and enzyme values. The average blood level was 2.8 +/- 1.3 micrograms/ml plasma. The blood level was not influenced by the length of the treatment. A correlation between blood level and weight or sex was not observed, whereas a significant negative correlation occurred between blood level and age (age group 15-30 years: 3.9 +/- 1.3 micrograms/ml; 46-60 years: 2.4 +/- 0.9 micrograms/ml).

A 61-year-old male with leukemia manifested multiple cutaneous nodules on his whole body surface, subcutaneous nodules on his arms and a tongue tumor. Septate hyphae were observed microscopically in scrapings from the surfaces of the cutaneous lesions. Fusarium solani and F. anthophilum were isolated from scrapings from the several skin lesions. Histological examination revealed the presence of numerous septate hyphae in the lumina of vessels in the dermis. The fungal elements in the cutaneous tissues were suggested to be Fusarium by an immunoperoxidase method using a genus-specific anti-Fusarium antibody. Although no evidence of fungal infection was found in other organs by clinical examinations, F. solani and/or F. anthophilum were considered to have undergone hematogenous dissemination, because of the presence of thrombi containing abundant fungal elements in the skin lesion. The present case is a case of disseminated cutaneous Fusarium infection, in which fungal elements in skin tissue sections were immunohistochemically regarded as Fusarium, though fungus cultures from biopsied specimens were negative.