Fungal Skin Disease Classification Using the Convolutional Neural Network.

Skin is the outer cover of our body, which protects vital organs from harm. This important body part is often affected by a series of infections caused by fungus, bacteria, viruses, allergies, and dust. Millions of people suffer from skin diseases. It is one of the common causes of infection in sub-Saharan Africa. Skin disease can also be the cause of stigma and discrimination. Early and accurate diagnosis of skin disease can be vital for effective treatment. Laser and photonics-based technologies are used for the diagnosis of skin disease. These technologies are expensive and not affordable, especially for resource-limited countries like Ethiopia. Hence, image-based methods can be effective in reducing cost and time. There are previous studies on image-based diagnosis for skin disease. However, there are few scientific studies on tinea pedis and tinea corporis. In this study, the convolution neural network (CNN) has been used to classify fungal skin disease. The classification was carried out on the four most common fungal skin diseases: tinea pedis, tinea capitis, tinea corporis, and tinea unguium. The dataset consisted of a total of 407 fungal skin lesions collected from Dr. Gerbi Medium Clinic, Jimma, Ethiopia. Normalization of image size, conversion of RGB to grayscale, and balancing the intensity of the image have been carried out. Images were normalized to three sizes: 120 × 120, 150 × 150, and 224 × 224. Then, augmentation was applied. The developed model classified the four common fungal skin diseases with 93.3% accuracy. Comparisons were made with similar CNN architectures: MobileNetV2 and ResNet 50, and the proposed model was superior to both. This study may be an important addition to the very limited work on the detection of fungal skin disease. It can be used to build an automated image-based screening system for dermatology at an initial stage.

Children onychomycosis, a neglected dermatophytosis: A retrospective study of epidemiology and treatment.

BACKGROUND: Onychomycosis was an ignored disease in children, and the prevalence was still unknown worldwide. OBJECTIVES: This study was conducted to investigate the prevalence and treatment regimens of onychomycosis in children younger than 18 years old. METHODS: We systemically reviewed all publications by searching the key terms to reveal the onychomycosis in children from 1990 to 2022. RESULTS: A total of 44 articles including 2,382 children with onychomycosis were enrolled in this study. The male to female ratio was 1.29:1. The youngest child was 35 days old and the average age was 9.8 years old. The duration of disease usually ranged from 7 days to 4 years. Onychomycosis in children was more prevalent in toenails compared to fingernails (77.6% vs. 18.4%), and 4% patients had both. A total of 527 children (22.12%) had concomitant tinea pedis infection, and in 267 patients (11.21%), their family members had onychomycosis or tinea pedis. The most common clinical type of onychomycosis was DLSO (67.74%) and the predominant isolates were T. rubrum (66.13%), followed by C. albicans (9.08%) and T. mentagrophytes complex (5.34%). There were 419 children (74.03%) receiving systematic treatment only, 74 patients (13.07%) receiving topical treatment only, and 73 patients (12.90%) receiving both systematic and topical treatment. Twelve patients (2.12%) had mild drug-related side effects. During the follow-up, 71.25% children were cured, 17.50% symptoms improved and 4.17% failed. CONCLUSIONS: Onychomycosis was underestimated in children and the diagnosis of onychomycosis should be properly considered in children with nail disorders. For mild patients, topical treatment can be a good choice, and oral antifungal drugs could be added to severe individuals under monitoring.

Age changes of foot microbiome estimated by microscopy method.

Despite of great number of investigations in the area of tinea pedis, question is opened: to what extent dermatophyte fungi are spread among modern population and does their occurrence interrelated with host age? Investigated group included 99 volunteers from 14 to 73 years old. Skin scales were collected from heel area of foot, and signs of heel skin trouble were expressed in points. In contrast to usual laboratory microscope magnification x900 we worked at x1750, what allowed to estimate not only fungal, but bacterial forms too. Average abundances of microbial morphotypes were expressed in points. Heel skin trouble increased in the process of aging (Pirsons` coefficient r=0.954). Bacilli occurred in all persons independently from age, but their abundance increased with aging (0.821). On the contrary cocci were more common and abundant in young person`s feet (-0.620). Occurrence of dermatophytes increased with age (0.891), at that relatively high values took place in young persons (10.5% with mycelium and 73.7% with spores) and in group without any heel skin trouble symptoms (7.7% and 76.9%), what allow to refer these fungi to normal habitats of foot skin.

First Isolation of Neoscytalidium dimidiatum from Human Dermatomycosis in Japan.

Neoscytalidium dimidiatum is a common fungus that causes non-dermatophyte dermatomycosis in tropical regions, but there have been no reports of infection with N. dimidiatum in Japan. Here, we report the first isolation of N. dimidiatum from human dermatomycosis in Japan. A 62-year-old healthy Japanese male had been treated with oral terbinafine for tinea pedis diagnosed from a microscopic examination in 2003 with a lesion that was intractable. In 2020, re-identification by sequencing the internal transcribed spacer regions and the D1/D2 domain of the large-subunit (LSU) ribosomal RNA gene revealed that the pathogen was N. dimidiatum. Antifungal susceptibility tests showed that the minimum inhibitory concentration of the drug luliconazole (LLCZ) against the pathogen was 0.00049 µg/mL. The patient's lesions were cured by topical LLCZ. The clinical course and drug susceptibility suggest that LLCZ is a suitable first-line drug for treatment.

DNA chip-based diagnosis of onychomycosis and tinea pedis.

BACKGROUND AND OBJECTIVES: Onychomycosis (OM) and tinea pedis (TP) are common fungal infections. Currently, diagnosis is based on direct microscopy and culture that have a low to moderate sensitivity and/or require up to 3-4 weeks until results are obtained. PCR techniques have emerged for the diagnosis of fungal infections, but little is known about their sensitivity and specificity in diagnosing. Here, we compared the diagnostic value of a DNA-chip technology, that detects 56 fungal pathogens, in a single-center prospective diagnostic study with microscopy and culture in suspected OM/TP. PATIENTS AND METHODS: Microscopy, culture and DNA microarray assays were performed on scraping material from patients with suspected OM (n = 67) or TP (n = 73). To test whether swabs can be used as an alternative for scraping, PCR yields were compared in a further 13 patients with OM and 11 patients with TP. RESULTS: DNA microarrays had the highest sensitivity. Combination of DNA-chip technology with microscopy further increased the sensitivity, and results from this combined laboratory diagnosis can be obtained within 24 hours. Comparison of sampling techniques (scraping, dry or wet swab) for DNA-chip assays showed similar results in suspected OM or TP. CONCLUSIONS: DNA-chip technology shows high sensitivity for OM and TP diagnosis, especially when combined with microscopy.

FT-IR investigation of Terbinafine interaction with stratum corneum constituents.

Terbinafine (Tbf) is a well-established anti-fungal agent used for management of a variety of dermal conditions including ringworm and athlete's foot. Both the biochemical mechanism of Tbf fungicidal action (based on squalene epoxidase inhibition) and the target region for Tbf in vivo (the stratum corneum (SC)) are well determined. However, the biochemical and pharmacokinetic approaches used to evaluate Tbf biochemistry provide no biophysical information about molecular level physical changes in the SC upon Tbf binding. Such information is necessary for improved drug and formulation design. IR spectroscopic methods were used to evaluate the effects of Tbf on keratin structure in environments commonly used in pharmaceutics to mimic those in vivo. The Amide I and II spectral regions (1500-1700 cm-1) provided an effective means to monitor keratin secondary structure changes, while a Tbf spectral feature near 775 cm-1 provides a measure of relative Tbf levels in skin. Interaction of Tbf with the SC induced substantial ß-sheet formation in the keratin, an effect which was partially reversed both by ethanol washing and by exposure to high relative humidity. The irreversibility suggests the presence of a Tbf reservoir (consistent with kinetic studies), permitting the drug to be released in a controlled manner into the surrounding tissue.

Use of MALDI-TOF MS for fungal species distribution of interdigital intertrigo in seafarers, Dakar, Senegal.

To determine fungal species distribution of interdigital intertrigo among seafarers in Dakar, Senegal, a cross-sectional study was carried out from May to August 2017 among seafarers clinically diagnosed with interdigital intertrigo. A questionnaire was filled to each patient before sampling the affected folds and transporting to Aristide Le Dantec University Hospital where mycological analyses were realized. Species identification by MALDI-TOF MS was performed in Marseille, France. In total, 169 men (21-66 years) were included. Few of them (3%) had a high level of education and the duration of the mycosis exceed 10 years for 88% of patients. Direct microscopic examination (ME) was positive in 34.3%. Among samples with positive ME, 58.6% had positive culture. An overall incidence of 30.2% was found. Patients with confirmed cases aged between 28 and 66 years. Among them, those between 36-50 years were predominant (52.9%). Those with a high level of education were less representative (2%). For 52.1% of patients, the duration of the mycosis was superior to 10 years. Furthermore, 57% of cases were significantly associated with other types of tinea pedis and/or onychomycosis (P=0.03). Culture was positive in 23.7% isolating 43 strains successfully identified at the species level by MALDI-TOF MS for 31 isolates: 20 Candida and 11 dermatophytes. The rest was identified only at the genus level belonged to Fusarium. In definitive, MALDI-TOF MS could be a useful tool for routine and fast identification of dermatophytes, yeasts and NDFF in clinical mycology laboratories.

Comparison of in vitro antifungal activity of novel triazoles with available antifungal agents against dermatophyte species caused tinea pedis.

OBJECTIVE: Dermatophytes are a group of keratinophilic fungi that invade and infect the keratinized tissues and cause dermatophytosis. We investigated effectiveness of novel triazole (luliconazole and lanaconazole) in comparison with available antifungal agents against dermatophyte species isolated from patients with tinea pedis. MATERIAL AND METHODS: A total of 60 dermatophytes species were isolated from the patients with tinea pedis. Identification of species was done by DNA sequencing of the ITS1-5.8S rDNA-ITS2 rDNA region. In vitro antifungal susceptibility testing with luliconazole and lanaconazole and available antifungal agent was done in accordance with the Clinical and Laboratory Standards Institute, M38-A2 document. RESULTS: In all investigated isolates, luliconazole had the lowest minimum inhibitory concentration (MIC) (MIC range=0.0005-0.004µg/mL), while fluconazole (MIC range=0.4-64µg/mL) had the highest MICs. Geometric mean MIC was the lowest for luliconazole (0.0008µg/mL), followed by lanoconazole (0.003µg/mL), terbinafine (0.019µg/mL), itraconazole (0.085 µg/mL), ketoconazole (0.089µg/mL), econazole (0.097µg/mL), griseofulvin (0.351 µg/mL), voriconazole (0.583µg/mL) and fluconazole (11.58µg/mL). CONCLUSION: The novel triazoles showed potent activity against dermatophytes and promising candidates for the treatment of tinea pedis caused by Trichophyton and Epidermophyton species. However, further studies are warranted to determine the clinical implications of these investigations.

Molecular identification of isolates of the Trichophyton mentagrophytes complex.

Background: The Trichophyton mentagrophytes complex is the second most common causal agent of dermatophytosis. It comprises five species-T. mentagrophytes, T. interdigitale, T. erinacei, T quinckeanum, and T. benhamie, as well as nine different genotypes of T. mentagrophytes / T. interdigitale-which are morphologically similar; however, their susceptibility to antifungal agents may differ. For targeted therapy and better prognosis, it is important to identify these species at a molecular level. However, since many hospitals lack molecular methods, the actual aetiology of dermatophytosis caused by this complex remains unknown. Objective: To characterize 55 anthropophilic isolates of the T. mentagrophytes complex recovered from a dermatological centre in Yucatán, Mexico. Material and methods: Fifty-five isolates of the T. mentagrophytes complex were obtained from patients with tinea capitis, tinea pedis, tinea corporis, tinea barbae, and tinea unguium. They were characterized by their colonial and microscopic morphology on Sabouraud dextrose agar (SDA) and through the sequencing of a fragment from the region ITS1-5.8S-ITS2. Results: All colonies grown on SDA were white. Forty-six isolates formed colonies with a powdery texture, while nine isolates formed colonies with a velvety texture. The micromorphological features were typical of the T. mentagrophytes complex. The molecular analysis revealed that 55 isolates were microorganisms that belonged to the T. mentagrophytes complex, that 46 formed powdery colonies representing T. mentagrophytes, and that the other nine isolates that formed velvety colonies represented T. interdigitale. The latter nine isolates were obtained from patients with tinea pedis, tinea corporis, and tinea unguium. Conclusions: The colony morphology on SDA led to the identification of 46 isolates as T. mentagrophytes and nine isolates as T. interdigitale. At a molecular level, the species identified by their morphology were identified only as T. mentagrophytes complex.

Viability of pathogenic dermatophytes during a 4-week treatment with 1% topical luliconazole for tinea pedis.

The viability of pathogenic fungi in the scale was investigated during topical administration of 1% luliconazole (LLCZ). Thirteen tinea pedis patients found to be positive on KOH examination were assessed by mycological examinations and quantitative real-time polymerase chain reaction (PCR) targeted internal transcribed spacer (ITS) in ribosomal RNA gene at the initial visit and after 2 and 4 weeks of treatment. Assays showed that the average copy number of ITS DNA had significantly decreased to 22.9% at 2 weeks and 4.8% at 4 weeks compared with the initial visit. LLCZ topical treatment could defeat almost pathogenic dermatophytes in the scales within 4 weeks.

A Case of Tinea Pedis in a Child Caused by Trichophyton interdigitale with Two Different Colony Phenotypes on Primary Culture.

An otherwise healthy 3-year-old girl presented with a several-month history of scaly lesions on her palms and soles. The lesions on the palms and right sole had been successfully treated with a steroid for pompholyx by a nearby dermatology clinic, but the lesion on the left sole persisted and spread to the back of the foot. On the initial visit, the patient exhibited an itchy and scaly erythematous left foot lesion. Direct microscopic examination of the scales revealed a considerable amount of fungal elements. A diagnosis of tinea pedis was made, and antifungal treatment with a neticonazole ointment was initiated. Complete cure was achieved after 4 weeks of treatment. The primary mycological cultures from the scales simultaneously revealed two types of colonies: a white powdery flat colony and a white downy elevated colony with a reddish-yellow bottom. Although the powdery colony was identified as Trichophyton mentagrophytes complex on slide culture, the downy colonies could not be identified based on cultural and morphological characteristics. The nucleotide sequences of the internal transcribed spacer region from both colonies showed an exact match, which eventually led to their identification as Trichophyton interdigitale. Further genotyping at three points in the non-transcribed spacer region in both colonies also showed the same NTS type of D2II. It is very rare for two morphologically different colonies to be isolated from the primary culture under the same conditions in tinea cases. Genetic tests are of extreme value to identify the strain in such cases.

2016 Epidemiological Survey of Dermatomycoses in Japan.

We report here the results of the 2016 epidemiological survey of dermatomycosis in Japan. In total, 6,776 cases were analyzed as follows: dermatophytosis, 5,772 cases (85.2%); candidiasis, 757 cases (11.2%); Malassezia infection, 235 cases (3.5%); and other fungal infections, 11 cases (0.2%). In dermatophytosis, tinea pedis was the most frequent (3,314 cases: male, 1,705; female, 1,609), followed by tinea unguium (1,634 cases: male, 766; female, 868), tinea corporis (423 cases: male, 241; female, 182); tinea cruris (316 cases: male, 242; female, 74); tinea manuum (58 cases: male, 29; female, 29); tinea capitus, Celsus' kerion (26 cases: male, 19; female, 7); and tinea barbae (1 case: male, 1). The most frequent pathogen was Trichophyton rubrum. In candidiasis, candidal intertrigo was the most frequent (181 cases: male, 98; female, 83), followed by oral candidiasis (165 cases: male, 84; female, 81), genital candidiasis (119 cases: male, 45; female, 74), diaper candidiasis (113 cases: male, 49; female, 64), erosio interdigitalis (63 cases: male, 13; female, 50), onychomycosis (41 cases: male, 17; female, 24), onychia et paronychia (28 cases: male, 2; female, 26), and angular cheilitis (23 cases: male, 6; female, 17). Although the number of cases varied depending on the role of each cooperating medical institution in the area and on population composition, no significant differences in the frequencies of clinical types were observed.

Terbinafine-resistant strain of Trichophyton interdigitale strain isolated from a tinea pedis patient.

Trichophyton interdigitale is an anthropophilic species that is frequently isolated from tinea unguium and tinea pedis throughout the world. In the present study, antifungal susceptibility testing was performed on T. interdigitale isolates from Japanese patients (isolated in 2017-2018; 24 strains) to assess itraconazole (ITZ) and terbinafine (TRF) susceptibility of these strains. E-test determinations revealed that the mean ITZ minimum inhibitory concentration (MIC) of the 24 strains was 0.023 mg/L (range, 0.064-1). Clinical Laboratory Standards Institute M38-A2 determinations revealed that the mean TRF MIC of 23 of the 24 strains was less than 0.03125 mg/L. Among these strains, one (NUBS18016) had a TRF MIC of 2 mg/L, confirming its resistance to TRF. The predicted amino acid sequences of the squalene epoxidase (SQLE) gene from the TRF-resistant strain (NUBS18016) was 100% identical to the SQLE gene sequence of the reference strain T. interdigitale, indicating that no gene mutations were present in NUBS18016. Therefore, the TRF-resistance mechanism of our TRF-resistant strain NUBS18016 has not been defined. Dermatologists should be cautious about the prevalence of foot dermatophytosis due to antifungal drug-resistant strains.

Nitric Oxide-Releasing Macromolecule Exhibits Broad-Spectrum Antifungal Activity and Utility as a Topical Treatment for Superficial Fungal Infections.

Cutaneous and superficial fungal infections affecting the skin, nails, and hair of humans are caused primarily by dermatophytes of the genera Trichophyton and Epidermophyton or by yeasts of the genera Candida and Malassezia. Onychomycosis is a common fungal infection of the nail that frequently coexists with tinea pedis, the most prevalent mycotic skin infection. Efficacy rates for current topical onychomycosis therapies are hampered by low drug penetration across the nail plate, which is theoretically obviated with nitric oxide (NO)-based topical therapies. The Nitricil technology platform is comprised of polysiloxane-based macromolecules that stably release therapeutic levels of NO. In the reported studies, NVN1000, the lead candidate of the platform, was assessed for its spectrum of in vitro activity against a broad range of filamentous fungi and yeast species commonly associated with cutaneous fungal infections. Time-kill assays demonstrated that NVN1000 exhibited fungicidal activity as early as 4 h. Additionally, the penetration of several unique NVN1000 NO-releasing drug product formulations (gel, cream, and lacquer) was evaluated following a single topical application in an in vitro infected human nail assay, with all formulations showing similar inhibition of fungal growth. Repeated topical application in this model demonstrated that a lower-strength dose of NO could achieve the same efficacy as a higher-strength dose after 7 days. Together, these in vitro results demonstrate that NO-releasing treatments rapidly penetrate the nail plate and eradicate the fungal infection, representing promising novel topical therapies for the treatment of onychomycosis and other cutaneous fungal infections.

Tinea pedis acquired in mosques?

We present four cases of interdigital tinea pedis in Italian tourists which was probably acquired in Turkish mosques and holy Muslim places. In all patients mycological examinations were positive for Trichophyton rubrum. All patients were successfully treated with bifonazole cream (one application/day for three weeks). It is advisable for tourists to wear socks when visiting mosques and holy Muslim places.

Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor.

PURPOSE: The lack of novel antifungal drugs and the increasing incidence and severity of fungal infections are major concerns worldwide. Herein, we tested the activity of the Blad-containing oligomer (BCO), a new antifungal molecule already in use for agriculture, on Malassezia spp. and dermatophytes, the causal agents of human tinea versicolor and tinea pedis. Given the lack of a standard method for Malassezia susceptibility testing and the plethora of published methods, we also developed an improved method for this genus. METHODOLOGY: The efficacy of BCO was assessed in vitro and compared to that of the drugs currently utilized in the treatment of tinea versicolor (fluconazole and itraconazole) and tinea pedis (itraconazole and terbinafine). For dermatophytes, the standard microdilution broth-based method was used, with small adjustments, and several broth formulations and inocula sizes were tested to develop an improved susceptibility method for Malassezia spp. RESULTS: We successfully developed a microdilution broth-based method with considerable advantages over other available methods, and used it for all in vitro susceptibility tests of Malassezia spp. isolates. We report that, on a molar basis, BCO was more effective than fluconazole or itraconazole on most strains of Malassezia spp. isolated from clinical samples (n=29). By contrast, BCO was less effective than itraconazole or terbinafine on the common dermatophytes Trichophyton rubrum and Trichophyton interdigitale. CONCLUSION: These data place BCO as a promising drug for the treatment of Malassezia-associated skin diseases. Further in vivo studies are now required to ascertain its applicability in the clinical setting.

In vitro biofilms and antifungal susceptibility of dermatophyte and non-dermatophyte moulds involved in foot mycosis.

Tinea pedis and onychomycosis are among the commonest fungal diseases in the world. Dermatophytes and, less frequently, non-dermatophyte moulds are aetiological agents of foot mycosis and are capable of forming biofilms. Fungal biofilm has demonstrated increasing drug resistance. This work aims to evaluate, in vitro, the ability to form biofilm and the susceptibility to antifungal drugs of sessile dermatophytes and non-dermatophyte moulds involved in foot mycosis. Thirty-six dermatophytes and non-dermatophyte moulds isolated from Tunisian patients with foot mycoses, and identified with MALDI-TOF have been tested. MICs of fluconazole, econazole, itraconazole, terbinafine and griseofulvin were carried out using CLSI broth microdilution method. The ability to form biofilm and antifungal activities of drugs against fungal biofilm formation has been quantified by Crystal Violet and Safranin Red staining. Biomass quantification revealed that all species studied were able to form biofilms in vitro after 72 hours. Fluconazole, econazole, itraconazole and terbinafine inhibited fungal growth with MIC values ranging from 0.031 to >64 µg mL-1 . The best antifungal activity has been obtained with terbinafine against Fusarium solani. Econazole showed the highest activity against fungal biofilm formation. These findings can help clinicians to develop the appropriate therapy of foot mycosis.

The survey of tinea capitis and scalp dermatophyte carriage in nursing home residents.

Tinea capitis is a contagious dermatophyte infection of scalp and associated hairs. On the other hand, asymptomatic carriage is a status of positive dermatophyte scalp culture, but without signs or symptoms of tinea capitis, and no evidence of hair shaft invasion confirmed by direct microscopy. Tinea capitis and asymptomatic carriage mostly occur in children, but adult females are becoming another population in recent decades. In this study, we focused on the prevalence and related fungi of tinea capitis and asymptomatic carriage in elderly by the shampoo brush method, as well as the source of transmission, in 10 nursing home residents. Two hundred and thirteen residents were screened, and 186 isolates were identified, of which only three were dermatophytes (1.4%). The scalp dermatophyte isolates were identified as Trichophyton rubrum by morphological characters and sequences comparisons in all three cases. After revisiting, these cases were proved to be asymptomatic carriers by negative microscopic and culture examination; however, two cases were found to have concurrent tinea pedis and onychomycosis, which were identified as T. rubrum and Trichophyton interdigitale. The source of the T. rubrum scalp carriage may come from tinea elsewhere on the body of the same subject or from other people in the same institute. Finding and treating the source of carriage, as well as treating scalp carriage patients according to the colony counts, may help prevent disease spreading.