Publications by authors named "Pietro Nenoff"

86 Publications

The unprecedented epidemic-like scenario of dermatophytosis in India: III. Antifungal resistance and treatment options.

Indian J Dermatol Venereol Leprol 2021 [SEASON];87(4):468-482

Department of Dermatology, Bhojani Clinic, Mumbai, Maharashtra, India.

One of the canonical features of the current outbreak of dermatophytosis in India is its unresponsiveness to treatment in majority of cases. Though there appears to be discordance between in vivo and in vitro resistance, demonstration of in vitro resistance of dermatophytes to antifungals by antifungal susceptibility testing is essential as it may help in appropriate management. The practical problem in the interpretation of antifungal susceptibility testing is the absence of clinical breakpoints and epidemiologic cutoff values. In their absence, evaluation of the upper limit of a minimal inhibitory concentration of wild type isolates may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility. In the current scenario, most of the cases are unresponsive to standard dosages and duration of treatment recommended until now. This has resulted in many ex-cathedra modalities of treatment that are being pursued without any evidence. There is an urgent need to carry out methodical research to develop an evidence base to formulate a rational management approach in the current scenario.
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http://dx.doi.org/10.25259/IJDVL_303_20DOI Listing
March 2020

Phaeohyphomycosis caused by Cladosporium cladosporioides in an immunosuppressed boy with Ewing sarcoma.

J Dtsch Dermatol Ges 2021 Jun 23. Epub 2021 Jun 23.

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Leipzig.

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http://dx.doi.org/10.1111/ddg.14503DOI Listing
June 2021

Authors' Reply.

Indian J Dermatol Venereol Leprol 2021 [SEASON];87(4):531-532

Laboratory for Medical Microbiology, Mölbis, Germany.

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http://dx.doi.org/10.25259/IJDVL_4_2020DOI Listing
July 2021

Identification of Zoophilic Dermatophytes Using MALDI-TOF Mass Spectrometry.

Front Cell Infect Microbiol 2021 28;11:631681. Epub 2021 Apr 28.

Institute of Bacteriology and Mycology, Centre of Infectious Diseases, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.

Dermatophytoses represent a major health burden in animals and man. Zoophilic dermatophytes usually show a high specificity to their original animal host but a zoonotic transmission is increasingly recorded. In humans, these infections elicit highly inflammatory skin lesions requiring prolonged therapy even in the immunocompetent patient. The correct identification of the causative agent is often crucial to initiate a targeted and effective therapy. To that end, matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents a promising tool. The objective of this study was to evaluate the reliability of species identification of zoophilic dermatophytes using MALDI-TOF MS. The investigation of isolates from veterinary clinical samples suspicious of dermatophytoses suggests a good MALDI-TOF MS based identification of the most common zoophilic dermatophyte spp. usually achieved scores only around the cutoff value for secure species identification because of a small number of reference spectra. Moreover, these results need to be interpreted with caution due to the close taxonomic relationship of dermatophytes being reflected in very similar spectra. In our study, the analysis of 50 clinical samples of hedgehogs revealed no correct identification using the provided databases, nor for zoophilic neither for geophilic causative agents. After DNA sequencing, adaptation of sample processing and an individual extension of the in-house database, acceptable identification scores were achieved ( and spp., respectively). A score-oriented distance dendrogram revealed clustering of geophilic isolates of four different species of the genus and underlined the close relationship of the important zoophilic agents and by forming a subclade within a larger cluster including different dermatophytes. Taken together, MALDI-TOF MS proofed suitable for the identification of zoophilic dermatophytes provided fresh cultures are used and the reference library was previously extended with spectra of laboratory-relevant species. Performing independent molecular methods, such as sequencing, is strongly recommended to substantiate the findings from morphologic and MALDI-TOF MS analyses, especially for uncommon causative agents.
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http://dx.doi.org/10.3389/fcimb.2021.631681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113951PMC
July 2021

Antifungal Susceptibility and Mutations in the Squalene Epoxidase Gene in Dermatophytes of the Trichophyton mentagrophytes Species Complex.

Antimicrob Agents Chemother 2021 Jul 16;65(8):e0005621. Epub 2021 Jul 16.

Department of Medical Mycology, Institute of Dermatology, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, China.

During the past decade, a prolonged and serious outbreak of dermatophytosis due to a terbinafine-resistant novel species in the Trichophyton mentagrophytesT. interdigitale complex has been ongoing in India, and it has spread to several European countries. The objective of this study was to investigate the molecular background of the squalene epoxidase () gene in order to understand the risk of emergence and spread of multiresistance in dermatophytes. Antifungal susceptibility to fluconazole, griseofulvin, itraconazole, ketoconazole, miconazole, naftifine, sertaconazole, and terbinafine was tested in 135 isolates from India, China, Australia, Germany, and The Netherlands. Based on the latest taxonomic insights, strains were identified as three species: T. mentagrophytes ( = 35), T. indotineae ( = 64, representing the Indian clone), and T. interdigitale ( = 36). High MICs of terbinafine (>16 mg/liter) were found in 34 (53%) isolates. These isolates showed an amino acid substitution in the 397th position of the gene. Elevated MICs of terbinafine (0.5 mg/liter) were noted in 2 (3%) isolates; these isolates lead to PheVal and LeuSer of the gene. The stability of the effect of the mutations was proven by serial transfer on drug-free medium. LysAsn and LeuPhe substitutions were found in susceptible T. mentagrophytes strains. The PheLeu/AlaThr double mutant showed higher MIC values for triazoles. High MICs of terbinafine are as yet limited to and are unlikely to be distributed throughout the T. mentagrophytes species complex by genetic exchange.
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http://dx.doi.org/10.1128/AAC.00056-21DOI Listing
July 2021

Kerion Celsi due to Trichophyton soudanense and Pityriasis rosea following treatment by terbinafine.

J Dtsch Dermatol Ges 2021 Jul 28;19(7):1048-1051. Epub 2021 Apr 28.

Klinik für Kinder- und Jugendmedizin, Klinikum St. Georg, Leipzig.

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http://dx.doi.org/10.1111/ddg.14413DOI Listing
July 2021

The unprecedented epidemic-like scenario of dermatophytosis in India: II. Diagnostic methods and taxonomical aspects.

Indian J Dermatol Venereol Leprol 2021 May-Jun;87(3):326-332

Department of Dermatology, Bhojani Clinic, Mumbai, Maharashtra, India.

Trichophyton (T.) mentagrophytes now accounts for an overwhelming majority of clinical cases in India, a new "Indian genotype" (T. mentagrophytes ITS genotype VIII) having been isolated from skin samples obtained from cases across a wide geographical distribution in this country. The conventional diagnostic methods, like fungal culture, are, however, inadequate for diagnosing this agent. Thus, molecular methods of diagnosis are necessary for proper characterization of the causative agent. The shift in the predominant agent of dermatophytosis from T. rubrum to T. mentagrophytes, within a relatively short span of time, is without historic parallel. The apparent ease of transmission of a zoophilic fungus among human hosts can also be explained by means of mycological phenomena, like anthropization.
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http://dx.doi.org/10.25259/IJDVL_302_20DOI Listing
March 2020

Taxonomy of the Trichophyton mentagrophytes/T. interdigitale Species Complex Harboring the Highly Virulent, Multiresistant Genotype T. indotineae.

Mycopathologia 2021 Jun 13;186(3):315-326. Epub 2021 Apr 13.

Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of Guizhou & Key Laboratory of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.

A severe outbreak of highly virulent and multi-resistant dermatophytosis by species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India. The correct identity of the etiologic agent is a much-debated issue. In order to define species limits, a taxonomic study was undertaken combining molecular, morphological, and physiological characteristics as evidence of classification. Molecular characteristics show that T. mentagrophytes s. str. and T. interdigitale s. str. can be distinguished with difficulty from each other, but are unambiguously different from the Indian genotype, T. indotineae by sequences of the HMG gene. The entities were confirmed by multilocus analysis using tanglegrams. Phenotypic characters of morphology and physiology are not diagnostic, but statistically significant differences are observed between the molecular siblings. These properties may be drivers of separate evolutionary trends. Trichophyton mentagrophytes represents the ancestral, homothallic cloud of genotypes with a probable geophilic lifestyle, while T. indotineae and T. interdigitale behave as anthropophilic, clonal offshoots. The origin of T. indotineae, which currently causes a significant public health problem, is zoonotic, and its emergence is likely due to widespread misuse of antifungals.
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http://dx.doi.org/10.1007/s11046-021-00544-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249266PMC
June 2021

[Trichophyton tonsurans-an emerging pathogen in wrestling in Germany].

Hautarzt 2021 Apr 9. Epub 2021 Apr 9.

Labor für medizinische Mikrobiologie - Partnerschaft Prof. Dr. med. Pietro Nenoff & Dr. med. Constanze Krüger, Mölbiser Hauptstr. 8, 04571, Rötha/OT Mölbis, Deutschland.

Trichophyton (T.) tonsurans is considered as the main causative agent of tinea gladiatorum (ringworm) in contact and martial arts worldwide and regularly leads to outbreaks. In the national wrestling squad in Leipzig, dermatophytoses occurred frequently and recurrently in children and adolescents for over a 2-year period. The wrestlers came to the dermatologist's office for clinical examination and sampling. Dermal scales and hair roots as well as smears were examined mycologically with fluorescence optical preparation, fungal culture, and polymerase chain reaction (PCR) for dermatophyte DNA. Sequencing of the dermatophyte rDNA served as culture confirmation test. Environmental investigations in the wrestler training center included contact cultures and smears from surfaces, in particular from the mats. T. tonsurans was culturally and/or with PCR detectable in 21 out of 25 children and adolescents plus one trainer. T. tonsurans grew in one of ten contact cultures of mats and floors in the wrestling training center, and T. interdigitale was found in another culture. Smears from the mats resulted in a culture of T. tonsurans detection twice. The PCR was positive for T. tonsurans three times. Within 14 days, T. tonsurans developed small, flat, radiating, granular and white-colored colonies with a mahogany-brown reverse side on the fungal culture media. The sequencing of the internal transcribed spacer (ITS) region of the rDNA and the translation elongation factor 1 α (TEF 1 α) gene confirmed the species T. tonsurans in all cases. T. interdigitale that was found from a mat was also identified by sequencing. Eight T. tonsurans strains were subjected to in vitro susceptibility testing to terbinafine. All isolates were sensitive to terbinafine in vitro with minimal inhibitory concentrations of ≤ 0.1 µg/ml.
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http://dx.doi.org/10.1007/s00105-021-04803-7DOI Listing
April 2021

The unprecedented epidemic-like scenario of dermatophytosis in India: I. Epidemiology, risk factors and clinical features.

Indian J Dermatol Venereol Leprol 2021 Mar-Apr;87(2):154-175

Bhojani Clinic, Mumbai, Maharashtra, India.

Dermatophytosis has attained unprecedented dimensions in recent years in India. Its clinical presentation is now multifarious, often with atypical morphology, severe forms and unusually extensive disease in all age groups. We hesitate to call it an epidemic owing to the lack of population-based prevalence surveys. In this part of the review, we discuss the epidemiology and clinical features of this contemporary problem. While the epidemiology is marked by a stark increase in the number of chronic, relapsing and recurrent cases, the clinical distribution is marked by a disproportionate rise in the number of cases with tinea corporis and cruris, cases presenting with the involvement of extensive areas, and tinea faciei.
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http://dx.doi.org/10.25259/IJDVL_301_20DOI Listing
March 2020

[Scabies-Renaissance of an ectoparasite infection : Diagnosis and therapy-How to proceed in practice].

Hautarzt 2021 Feb;72(2):125-136

Department of Dermatology and Venerology, Medical University of Graz, Auenbruggerplatz 8, 8036, Graz, Österreich.

Scabies or mange is currently a common dermatosis in Germany and other countries, and should be more important in health policy. It affects a cross-section of society, including all age groups, from infants to the aged. Locals and people with a migration background both suffer from this highly contagious ectoparasite infection with excessive, predominately nocturnal itching. Clinical diagnosis represents a challenge for the experienced dermatologist due to the variety of dermatosis to be considered in the differential diagnosis. It is still unclear whether treatment failure or the recurrences observed everywhere are due to in vitro and in vivo resistance of the pathogen agent Sarcoptes scabiei against permethrin or ivermectin. Therapeutic errors seem to play a role as often not all direct contact persons are recorded and treated with antiscabious treatment. They form the reservoir for reinfections. In the event of repeated nonresponse to topical (permethrin) and/or oral antiscabious treatment, alternative topical preparations-benzyl benzoate or crotamiton-should be used. Combination with ivermectin is mandatory.
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http://dx.doi.org/10.1007/s00105-020-04729-6DOI Listing
February 2021

Tinea capitis et barbae caused by Trichophyton tonsurans: A retrospective cohort study of an infection chain after shavings in barber shops.

Mycoses 2021 Apr 28;64(4):428-436. Epub 2020 Dec 28.

Dermatopathologie Duisburg, Prof. J. Schaller und Dr. C. Hendricks, Duisburg, Germany.

Background: Tinea capitis is a highly contagious infectious disease caused by dermatophytes. In Central Europe, it is mainly caused by zoophilic dermatophytes, as, for example Microsporum (M) canis or Trichophyton (T) mentagrophytes and increasingly by anthropophilic fungi. T tonsurans was commonly related to the Tinea gladiatorum, where transmission occurred between infected persons or via contaminated floors.

Objective: Reporting the transmission of this highly contagious dermatophyte for the first time via beard shaving and hairdressing in barber shops in Germany.

Patients And Methods: 18 young male patients developed tinea capitis and/or barbae shortly after shavings of the beard and/or hair in a barber shop. Native, cultural and molecular diagnostics as well as tissue biopsies and resistance tests were performed of skin and hair samples.

Results: In all samples, T tonsurans could be identified. The medical history and the clinical picture suggest a transmission through contaminated hairdressing tools. The patients were treated with terbinafine or itraconazole in combination with or exclusively with topical antimycotics.

Conclusion: The transmission and a resulting increase in the incidence of infections with T tonsurans may be due to shavings with direct skin contact of insufficiently disinfected hairdressing tools. This path of infection has already been observed in Africa and is now being described for the first time in Germany. Knowledge of the pathogen and its transmission ways are essential to interrupt the chain of infection.
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http://dx.doi.org/10.1111/myc.13231DOI Listing
April 2021

Spread of Terbinafine-Resistant Type VIII (India) in Germany-"The Tip of the Iceberg?"

J Fungi (Basel) 2020 Oct 5;6(4). Epub 2020 Oct 5.

Stephan Krause, Bundeswehrkrankenhaus Berlin, Klinik III Dermatologie, Scharnhorststraße 13, 10115 Berlin, Germany.

Chronic recalcitrant dermatophytoses, due to (.) Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of . Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of . Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 . isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of . . In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints ≥0.2 µg/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited PheLeu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined PheLeu and AlaThr amino acid substitutions, and one strain a single LeuPhe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight AlaThr, and in one AlaThr +, new Val Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant . Type VIII are being increasingly isolated. In Germany, transmission of . Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.
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http://dx.doi.org/10.3390/jof6040207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712673PMC
October 2020

[Report of the first case of tinea corporis bullosa by Trichophyton tonsurans].

Hautarzt 2021 Feb;72(2):153-156

Klinik für Dermatologie, SRH Zentralklinikum Suhl, Albert-Schweitzer-Str. 2, 98527, Suhl, Deutschland.

Blister formation in tinea corporis is rare. Bullous tinea is usually evoked by zoophilic dermatophytes. A 20-year-old woman presented in our out-patient department with a painful pruritic bullous skin eruption at the left forearm. Clinically, a 4 × 3 cm symmetrical plaque with sharp borders and peripheral versiculation and serous crusts was seen. Histologically there was a marked spongiotic dermatitis with fungal elements in periodic acid stain (PAS). By fungal culture, PCR and gene sequencing Trichophyton (T.) tonsurans was identified. To the best of our knowledge, this is the first published case of T. tonsurans as the causative agent of bullous tinea corporis.
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http://dx.doi.org/10.1007/s00105-020-04670-8DOI Listing
February 2021

Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance.

Mycoses 2020 Jul 29. Epub 2020 Jul 29.

Department of Dermatology, University Hospital Jena, Jena, Germany.

Background: The Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis.

Objectives: Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population.

Methods: Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay.

Results: Ala 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance.

Conclusion: The new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.
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http://dx.doi.org/10.1111/myc.13150DOI Listing
July 2020

[Occupational Trichophyton verrucosum infection in a cattle farmer].

Hautarzt 2020 Nov;71(11):899-902

Klinik für Hautkrankheiten, Universitätsklinikum Jena, Erfurter Str. 35, 07743, Jena, Deutschland.

Ringworm in cattle may cause an occupational skin disease in humans. Trichophyton verrucosum lead to a highly inflammatory fungal skin infection that is often misdiagnosed as bacterial disease and consequently mistreated with antibiotics. To establish the correct diagnosis, it is necessary to collect skin scales; in addition, a skin biopsy can be helpful. Deep dermatophyte infections by Trichophyton verrucosum can be treated effectively with oral terbinafine. In addition, it is necessary to pay careful attention to use suitable hygiene measures in the stables to protect against reinfection.
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http://dx.doi.org/10.1007/s00105-020-04655-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653785PMC
November 2020

Ciclopirox Hydroxypropyl Chitosan (HPCH) Nail Lacquer: A Review of Its Use in Onychomycosis.

Dermatol Ther (Heidelb) 2020 Oct 23;10(5):917-929. Epub 2020 Jul 23.

Dermatology-Venereology, Department of Medicine, School of Health Sciences, National and Kapodistrian University of Athens-A. Sygros Hospital, Athens, Greece.

Ciclopirox 8% hydroxypropyl chitosan (HPCH) [Marketed in different countries as the following registered (®) brands: Ciclopoli, Fulcare, Kitonail, Myconail, Niogermos, Niogermox, Onytec, Ony-Tec, Polinail, Privex, Rejuvenail] is the first topical nail lacquer developed using innovative drug formulation technology. It is indicated for the treatment of mild-to-moderate fungal infections of the nails that are caused by dermatophytes and/or other ciclopirox-sensitive fungi, without nail matrix involvement. HPCH is a patented drug formulation technology for the delivery of active principles into the nails based on a hydrosoluble semisynthetic amino-polysaccharide biopolymer derivative of chitosan. The lacquer acts as a protective barrier against microbiological attack, physical damage and/or aggressive chemicals. Results from in vitro studies suggest that the application of ciclopirox 8% HPCH nail lacquer improves drug permeation into and/or drug penetration through the nail, relative to the water-insoluble ciclopirox 8%, amorolfine 5% and efinaconazole 10% reference lacquers. In addition, in vitro and clinical studies in healthy subjects found that the concentration of ciclopirox reached in subungual fluids after application of ciclopirox 8% HPCH was sufficient for inhibiting fungal growth. In clinical studies in patients with mild-to-moderate onychomycosis, ciclopirox 8% HPCH was found to be more effective than the commercial water-insoluble ciclopirox 8% and amorolfine 5% lacquers, as indicated by higher complete cure, response and mycological cure rates at 48 weeks after treatment initiation. Ciclopirox 8% HPCH has been found to be generally well tolerated, with no treatment-related adverse events reported in patients using this nail lacquer. Thus, current evidence indicates that ciclopirox 8% HPCH represents a valuable treatment option for the treatment of patients with onychomycosis.
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http://dx.doi.org/10.1007/s13555-020-00420-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477053PMC
October 2020

Visualising virulence factors: Trichophyton benhamiaes subtilisins demonstrated in a guinea pig skin ex vivo model.

Mycoses 2020 Sep 15;63(9):970-978. Epub 2020 Jul 15.

Institute of Bacteriology and Mycology, Centre of Infectious Diseases, Faculty of Veterinary Medicine, Leipzig University, Leipzig, Germany.

Background: Dermatophytoses rank among the most frequent communicable diseases in humans, and the zoonotic transmission is increasing. The zoophilic dermatophyte Trichophyton (T.) benhamiae is nowadays one of the main causes of tinea faciei et corporis in children. However, scientific data on molecular pathomechanisms and specific virulence factors enabling this ubiquitous occurrence are scarce.

Objectives: To study tissue invasion and the expression of important virulence factors of T. benhamiae, isolates that were recovered from two groups of hosts (humans vs. guinea pigs (GP)) using an ex vivo skin model.

Methods: After confirmation of species identity by ITS sequencing, CFU suspensions of dermatophyte isolates (n = 20) were applied to the skin infection model and cultured. Employing specific immunofluorescence staining techniques, the expression of subtilisin 3 and 6 and metallocarboxypeptidase A was analysed. The general mode of invasion was explored. Results were compared with biopsies of naturally infected GP.

Results: All isolates were successfully recovered and proliferated well after application to the infection model. Progressive invasion of hyphae through all skin structures and destruction of explants were observed with early events being comparable to natural infection. An increasing expression of the examined virulence factors towards the end of culture was noticed but no difference between the two groups of isolates.

Conclusions: For the first time, important in vivo markers of dermatophytosis were visualised immunohistochemically in an ex vivo skin infection model and in skin biopsies of GP naturally infected with T. benhamiae. More research on the underlying pathomechanisms of dermatophyte infection is urgently needed.
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http://dx.doi.org/10.1111/myc.13136DOI Listing
September 2020

Nannizzia incurvata as a rare cause of favus and tinea corporis in Cambodia and Vietnam.

Indian J Dermatol Venereol Leprol 2021 [SEASON];87(4):515-521

Laboratory for Medical Microbiology, Partnership Prof. Pietro Nenoff and Dr. Constanze Krüger, Mölbis, Germany.

Nannizzia (N.) incurvata (formerly Microsporum incurvatum) represents a geophilic dermatophyte which has been previously classified as belonging to the species complex of N. gypsea (formerly Microsporum gypseum). A 42-year-old Vietnamese female from Saxony, Germany, suffered from tinea corporis of the right buttock after she returned from a 2-week-visit to her homeland Vietnam. From skin scrapings of lesions, N. incurvata grew on Sabouraud's dextrose agar. Treatment by ciclopirox olamine cream twice daily for 4 weeks was successful. A 6-year-old Cambodian boy living near river Mekong with contact history to chicken, dogs and cattle suffered from tinea faciei and capitis. Symptoms of the favus-like tinea capitis and tinea faciei were erythema and scaly patches with areas of alopecia. N. incurvata grew on Sabouraud's dextrose agar. The boy was treated with oral terbinafine 125 mg daily, topical miconazole cream and ketoconazole shampoo. The symptoms healed within 4 weeks of treatment. Cultivation of the samples revealed growth of N. incurvata. For confirmation of species identification, the isolates were subject to sequencing of ITS (internal transcribed spacer) region of the rDNA, and addition of the "translation elongation factor 1 α" (TEF 1 α) gene. Sequencing of the ITS region showed 100% accordance with the sequence of N. incurvata deposited at the NCBI database under the accession number MF415405. N. incurvata is a rare, or might be underdiagnosed geophilic dermatophyte described in Sri Lanka and Vietnam until now. This is the first isolation of N. incurvata in Cambodia, and the first description of favus in a child due to this dermatophyte.
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http://dx.doi.org/10.4103/ijdvl.IJDVL_954_18DOI Listing
January 2019

[Microsporum ferrugineum-an anthropophilic dermatophyte in Germany : Case report and review of the literature].

Hautarzt 2020 Sep;71(9):705-710

Labor für medizinische Mikrobiologie, Partnerschaft Prof. Dr. med. Pietro Nenoff & Dr. med. Constanze Krüger, Mölbiser Hauptstr. 8, 04571, Rötha OT Mölbis, Deutschland.

Three boys from the same city, treated by the same dermatologist, developed tinea capitis. Two of them, 4 and 8 years old, underwent mycological diagnostic workup. However, no pathogens familiar in this country, such as Microsporum (M.) canis or Trichophyton (T.) tonsurans, were isolated, but instead that of a dermatophyte that has not been found in Germany for decades. Both dermatophyte isolates showed white-beige-brownish colonies with a flat, radiating edge and a central, verrucous curvature. The sequencing of the internal transcribed spacer (ITS) region of the rDNA confirmed the suspicion of M. ferrugineum already expressed based on the morphological picture. The anthropophilic dermatophyte occurs in the Middle East, Asia, Eastern Europe and Africa and is considered to be the cause of tinea capitis or tinea corporis in children and adolescents. In 2016, M. ferrugineum has again been isolated in Germany, probably as a result of migration movements. The fungus is strikingly isolated to martial arts, especially wrestlers. It mainly affects children and adolescents, some with a Russian-German background. The anthropophilic dermatophyte is transmitted directly from person to person, especially in the case of tinea capitis. An indirect transmission, for example, via mats in martial arts is likely.
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http://dx.doi.org/10.1007/s00105-020-04601-7DOI Listing
September 2020

Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study.

Mycoses 2020 Jul 4;63(7):717-728. Epub 2020 May 4.

Labor für medizinische Mikrobiologie, Rötha, Germany.

Background: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario.

Objectives: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene.

Patients/methods: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE.

Results: Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole.

Conclusions: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.
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http://dx.doi.org/10.1111/myc.13091DOI Listing
July 2020

S1-Leitlinie Tinea capitis.

J Dtsch Dermatol Ges 2020 Feb;18(2):161-180

Department of Dermatology, Venerology und Allergology, Division of Evidence-based Medicine (dEBM) and Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Deutschland.

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http://dx.doi.org/10.1111/ddg.14026_gDOI Listing
February 2020

S1 guidelines: Tinea capitis.

J Dtsch Dermatol Ges 2020 02;18(2):161-179

Department of Dermatology, Venereology and Allergology, Division of Evidence-based Medicine (dEBM) and Berlin Institute of Health, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt University of Berlin, Berlin, Germany.

Tinea capitis describes a dermatophyte infection of scalp and hair that predominately occurs in children. The diagnostic workup includes microscopic examination, culture and/or molecular tests. Treatment is guided by the specific organism involved and should consist of systemic agents as well as adjuvant topical treatment. The aim of the present update of the interdisciplinary German S1 guidelines is to provide dermatologists, pediatricians and general practitioners with a decision tool for selecting and implementing appropriate diagnostic and therapeutic measures in patients with tinea capitis. The guidelines were developed based on current international guidelines, in particular the 2010 European Society for Pediatric Dermatology guidelines and the 2014 British Association of Dermatologists guidelines, as well as on a review of the literature conducted by the guideline committee. This multidisciplinary committee consists of representatives from the German Society of Dermatology (DDG), the German-Speaking Mycological Society (DMykG), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence-based Medicine (dEBM) provided methodological assistance. The guidelines were approved by the participating medical societies following a comprehensive internal and external review.
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http://dx.doi.org/10.1111/ddg.14026DOI Listing
February 2020

Modeling dermatophytosis: Guinea pig skin explants represent a highly suitable model to study Trichophyton benhamiae infections.

J Dermatol 2020 Jan 28;47(1):8-16. Epub 2019 Nov 28.

Institute of Veterinary Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.

Dermatophyte infections are a growing health concern worldwide with increasing patient numbers, especially in children. However, detailed knowledge about infection mechanisms and virulence factors are scarce. This study aimed to establish an infection model based on guinea pig skin explants mimicking the in vivo situation as closely as possible to survey the pathogenesis of dermatophytoses. A fundamental prerequisite was the detailed description of native guinea pig skin and its morphological changes during tissue culture because comprehensive data on guinea pig skin characteristics were not available. Skin explants were harvested from healthy, adult guinea pigs and transferred to cell culture inserts. One group was inoculated with defined suspensions of colony-forming units of zoonotic Trichophyton benhamiae isolates; others served as controls to assess the tissue viability during the 10-day culture. Samples were taken on days 3, 5, 7 and 10 and processed for histological and immunohistochemical analysis. Standard tissue culture conditions provoked acantholysis and regional orthokeratotic alterations. The reduced desquamation caused hyperkeratosis paralleled by hypogranulosis or regional hyperplasia. During T. benhamiae infection, keratinocyte proliferation came to a complete halt on day 5 whereas the number of terminal deoxynucleotidyl transferase dUTP nick end labeling assay-positive cells increased moderately up to day 7. Hyphae grew massively into the skin explants causing strong keratinolysis and tricholysis. By the end of the culture, complete disintegration of the basement membrane and dermal tissue was observed. A realistic and reliable skin infection model was established to study dermatophytoses in general and cutaneous T. benhamiae infections in particular.
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http://dx.doi.org/10.1111/1346-8138.15150DOI Listing
January 2020

Genes Encoding Proteolytic Enzymes Fungalysin and Subtilisin in Dermatophytes of Human and Animal Origin: A Comparative Study.

Mycopathologia 2020 Feb 2;185(1):137-144. Epub 2019 Aug 2.

Laboratory for Medical Microbiology, Mölbis, Germany.

Dermatophytes are among the most successful fungal pathogens in humans, but their virulence mechanisms have not yet been fully characterized. Dermatophytic fungi secrete proteases in vivo, which are responsible for fungal colonization and degradation of the keratinized tissue during infection. In the present study, we used PCR to investigate the presence of genes encoding fungalysins (MEP) and subtilisins (SUB) in three dermatophyte species whose incidence is increasing in Europe: the anthropophilic Trichophyton rubrum (n = 58), zoophilic Microsporum canis (n = 33), and Trichophyton benhamiae (n = 6). MEP2 and SUB4 genes were significantly correlated with T. rubrum; MEP3 and SUB1 were mostly frequently harbored by M. canis; and MEP1, 2, and 4 and SUB3-7 were most frequently harbored by T. benhamiae isolates (p < 0.05). Furthermore, MEP1-5 and SUB1-3 genes were significantly more prevalent among human clinical isolates of M. canis (n = 17) than among asymptomatic cat isolates of M. canis (n = 16; p < 0.05). Unidentified MEP and/or SUB genes in some isolates in the current study may suggest that other gene repertoires may be involved in the degradation of keratin. The presented analysis of the incidence of MEP and SUB virulence genes in three dermatophyte species of diverse origins provides an insight into the host-fungus interaction and dermatophyte pathogenesis.
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http://dx.doi.org/10.1007/s11046-019-00367-2DOI Listing
February 2020

[Extensive tinea corporis due to a terbinafine-resistant Trichophyton mentagrophytes isolate of the Indian genotype in a young infant from Bahrain in Germany].

Hautarzt 2019 Nov;70(11):888-896

Labor für Medizinische Mikrobiologie, Mölbiser Hauptstr. 8, 04571, Rötha OT Mölbis, Deutschland.

A 6 month-old-female infant from Bahrain visiting Germany with her family for a holiday was seen by us for extensive dermatophytosis of the back, buttocks, chest and groins. Topical treatment by terbinafine for over 2 months was not successful. Other family members including adults and children were treated in Bahrain with topical antifungals and oral voriconazole which was not helpful. Mycological examination performed in Germany revealed the detection of the zoophilic dermatophyte Trichophyton (T.) mentagrophytes. The newly described genotype VIII within the species T. mentagrophytes was identified by sequencing of the "internal transcribed spacer" (ITS) region of the fungal rDNA. This genotype of T. mentagrophytes is the main causative agent of the current epidemic of chronic recalcitrant dermatophytoses in India. Transmission of this Indian genotype of T. mentagrophytes to other countries due to globalization is a serious issue to be considered. Moreover, a significant percentage of these Indian T. mentagrophytes strains are resistant to terbinafine both in vitro and by the way of genetic point mutations in the squalene epoxidase (SQLE) gene. Some are also found to be partially resistant against itraconazole and voriconazole. The point mutation TTC/TTA was found by SQLE mutation analysis in this particular T. mentagrophyte isolate from Bahrain. This point mutation is closely associated with F397L amino acid substitution of the enzyme indicative of in vitro resistance of the dermatophyte against terbinafine. The girl was successfully treated by topical miconazole and later by ciclopirox olamine. This is the first report on an infection due to a terbinafine-resistant T. mentagrophytes strain of the ITS genotype VIII from India in Germany.
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http://dx.doi.org/10.1007/s00105-019-4431-7DOI Listing
November 2019

Blastomycosis-like Pyoderma.

J Dtsch Dermatol Ges 2019 May;17 Suppl 2:31-33

Klinik für Dermatologie und Phlebologie, Vivantes Klinikum im Friedrichshain, Berlin.

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http://dx.doi.org/10.1111/ddg.13788DOI Listing
May 2019

The current Indian epidemic of superficial dermatophytosis due to Trichophyton mentagrophytes-A molecular study.

Mycoses 2019 Apr 20;62(4):336-356. Epub 2019 Feb 20.

Laboratory for Medical Microbiology, Mölbis, Germany.

The disease burden of chronic-relapsing and therapy-refractory superficial dermatophytosis dramatically increased in India within the past 5-6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR-ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)-1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte-positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR-ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte-positive showing 151 (93.21%) T mentagrophytes- and 11 (6.79%) T rubrum-positive samples. In this study, we show for the first time a dramatic Indian-wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes "Indian ITS genotype" that might be disseminated Indian-wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.
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http://dx.doi.org/10.1111/myc.12878DOI Listing
April 2019
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