DOI: 10.1111/jdv.

17106 JEADV

ORIGINAL ARTICLE

Epidemiological and clinical aspects of Trichophyton

mentagrophytes/Trichophyton interdigitale infections in the
Zurich area: a retrospective study using genotyping
M. Klinger,1,2 M. Theiler,3 P.P. Bosshard1,2,*
1
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
2
Faculty of Medicine, University of Zurich, Zurich, Switzerland
3
€rich, Switzerland
Pediatric Skin Center, Dermatology Department, University Children‘s Hospital Zurich, Zu
*Correspondence: P.P. Bosshard. E-mail: philipp.bosshard@usz.ch

Abstract
Background Trichophyton mentagrophytes (formerly Arthroderma vanbreuseghemii) and its clonal offshoot Trichophy-
ton interdigitale, which are leading causes of dermatophytoses, have recently been recognized as two separate species.
Over the last 20 years, several internal transcribed spacer (ITS) genotypes of Trichophyton mentagrophytes and Tri-
chophyton interdigitale have been identified, some of which have specific characteristics and lead to typical clinical
manifestations.
Objectives The aim of this study was to determine the current epidemiology of Trichophyton mentagrophytes and Tri-
chophyton interdigitale genotypes in Switzerland, particularly in the Zurich area.
Methods Consecutive cases diagnosed by ITS sequencing between 2009 and 2019 were retrospectively analysed.
Results A total of 81 Trichophyton mentagrophytes and 81 Trichophyton interdigitale cases were investigated. T. men-
tagrophytes infections clearly differed from T. interdigitale infections by affecting younger and more frequently female
patients, targeting almost exclusively head and body rather than feet and toenails, leading to inflammatory dermatophy-
tosis and often requiring a combination of systemic and topical treatment. Seven different T. mentagrophytes genotypes
(II*, III, III*, IV, VII, VIII and XXVI) were observed, with genotype XXVI being discovered in this study. Genotype III occurred
most frequently (56% of all T. mentagrophytes cases) and affected predominantly children. Genotypes III* and VII led to
inflammatory tinea in most cases. Four strains that proved to be terbinafine resistant belonged to the ‘Indian genotype’
VIII, which mostly caused tinea glutealis and inguinalis.
Conclusion Being able to distinguish between Trichophyton mentagrophytes and Trichophyton interdigitale is of para-
mount importance as the two species cause different clinical presentations. In addition, ITS genotyping allows recogniz-
ing sources of infection and potential terbinafine resistance. The latter needs to be confirmed by resistance testing or by
sequencing part of the squalene epoxidase (SQLE) gene.
Received: 29 September 2020; Accepted: 16 December 2020

Conflicts of interest:
The authors declare no conflicts of interest.

Funding sources:
None.

Introduction classifications of dermatophytes were based on their clinical pic-

Dermatophytes are the predominant cause of superficial skin
infections in humans with up to 20–25% of the world’s popula-
tion being affected.1 They are keratinophilic fungi that generally
only infest the stratum corneum, i.e. the outer part of the epider-
mis. Since the discovery of dermatophytes as infectious patho-
gens by Sch€ onlein in 1839,2 their taxonomy and the naming
of the species have frequently changed.3–6 While former
ture or in vitro morphologies, the current taxonomy by de Hoog
et al.6 is built on a molecular multilocus phylogenetic approach;
human pathogenic dermatophytes that are anthropophilic or
zoophilic are classified into the genera Trichophyton, Microspo-
rum and Epidermophyton, while geophilic and zoophilic species
that are more distant from the human sphere are assigned
to Nannizzia, Arthroderma, Lophophyton and Paraphyton.

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1018 Klinger et al.

According to this new taxonomy, the species Trichophyton
interdigitale is regarded as a clonal offshoot of its close relative
Trichophyton mentagrophytes (formerly Arthroderma van-
breuseghemii).6 This delineation is meaningful from a clinical
point of view; T. interdigitale is exclusively anthropophilic and
mainly causes non-inflammatory tinea pedis or onychomycosis,
whereas T. mentagrophytes is predominantly of zoophilic origin
and often leads to inflammatory tinea of other variants, e.g. tinea
capitis, tinea corporis or tinea genitalis.7–10
With internal transcribed spacer (ITS) sequencing, several
genotypes have been recognized within these two species. T. in-
terdigitale currently consists of five genotypes and T. mentagro-
phytes of 21.7–10 Our present knowledge indicates that genotype
identification is reasonable from a clinical perspective; while the
T. interdigitale genotypes are very similar,8,9 some T. mentagro-
phytes genotypes distinguish themselves from others by addi-
tional features such as their way of transmission,11,12
geographical distribution,9,10 clinical appearance10–12 or resis-
tance to standard antifungals like terbinafine.13,14 T. mentagro-
phytes genotype VIII, e.g. is responsible for a current outbreak in
India, and multiple studies have detected high rates of resistance
to terbinafine for this genotype.12–14
Except for a case series on tinea genitalis,15 no data exist
regarding the incidence of T. mentagrophytes in Switzerland.
The primary aims of this study are (i) to compare demographic,
laboratory, clinical and therapeutic data of T. mentagrophytes
infections with T. interdigitale infections in the broader Zurich
area, Switzerland, and (ii) to gain insights into the current epi-
demiology of T. mentagrophytes genotypes and elucidate their
correlation with clinical presentation.
Materials and methods
Patients and clinical specimens
Trichophyton mentagrophytes and T. interdigitale cases diagnosed
between January 2009 and December 2019 at the mycology labo-
ratory of the Department of Dermatology at the University
Hospital Zurich were retrospectively analysed. Demographic
(age, gender and source of contact), laboratory (genotype and
antifungal resistance) and clinical data (illness duration, clinical

Table 1 Currently recognized Trichophyton interdigitale and Trichophyton mentagrophytes ITS genotypes, reference sequences and
corresponding isolates from this study

Current Former names32 ITS genotype Reference sequences Isolates from this study
nomenclature6 (GenBankâ Accession no.) (GenBankâ accession no.)
Trichophyton Trichophyton mentagrophytes var. interdigitale Ti-I AF506033 MT858795–MT858816
interdigitale Trichophyton interdigitale (anthropophilic strains) Ti-II AF506036 MT858817–MT858873
Ti-X MK312735 MT858875
Ti-XI MK312755
Ti-XII MF109039
Ti-XXV MT858874
Trichophyton Trichophyton mentagrophytes var. mentagrophytes Tm-II* KP132819 MT858876–MT858877
mentagrophytes Trichophyton interdigitale (zoophilic strains) Tm-III AF506034 MT858878–MT858922
Arthroderma vanbreuseghemii Tm-III* FM986758 MT858923–MT858934
Tm-IV FM986773 MT858935–MT858937
Tm-V KJ606098
Tm-VI KT285210
Tm-VII JN134101 MT858938–MT858944
Tm-VIII JN133999 MT858945–MT858955
Tm-IX MK447613
Tm-XIII MK312917
Tm-XIV MK312950
Tm-XV MK312937
Tm-XVI MK312933
Tm-XVII MK312990
Tm-XVIII MK313028
Tm-XIX MK312878
Tm-XX MK313030
Tm-XXI MK312891
Tm-XXII MK312888
Tm-XXIII MK313044
Tm-XXIV AF170453
Tm-XXVI MT858956

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Genotyping of T. mentagrophytes/interdigitale 1019

appearance and treatment) were retrieved from the laboratory
database and patient charts. Samples were obtained from
patients treated at the University Hospital Zurich, the Univer-
sity Children’s Hospital Zurich, the Triemli Hospital Zurich,
the Cantonal Hospital Frauenfeld and from private dermatolo-
gists and paediatricians. Samples consisted of nail particles, skin
scrapings, plucked hair and swabs, all obtained from the affected
areas. Only patients whose T. mentagrophytes or T. interdigitale
infection was confirmed by ITS sequencing were included in this
study. Exclusion criteria were refusals by patients to have their
data used for further research (n = 5) and missing consent of
patients treated at the University Hospital Zurich (n = 6). This
study was approved by the Ethics Committee of Zurich, Switzer-
land (BASEC-no. 2019-01947).
Culture, identification, genotype detection and
phylogenetic tree
Approximately half of each specimen was examined microscopi-
cally using a 5% SDS solution containing Congo red, and the
other half was cultured on Sabouraud dextrose agar (SDA) with
gentamicin/chloramphenicol and Mycoselâ agar containing
cycloheximide (Becton Dickinson, Allschwil, Switzerland).
Swabs were immediately inoculated on SDA by the clinician.
Cultures were incubated at 25°C for a maximum of four weeks.
Morphological examination and ITS sequencing were performed
as described previously.16 ITS sequencing was routinely per-
formed in all T. mentagrophytes/T. interdigitale strains isolated
from areas other than the feet, e.g. in cases of tinea capitis, tinea
corporis and tinea genitalis. Sequencing was additionally
performed in randomly selected cases of tinea pedis and ony-
chomycosis in order to compare two equally sized groups of T.
mentagrophytes and T. interdigitale, respectively. Identification
was carried out according to the new taxonomy of dermato-
phytes by de Hoog et al.6 and genotype assignment according to
the ITS-based classification originally proposed by Ninet et al.7
and further developed by Heidemann et al.8, Nenoff et al.9 and
Taghipour et al.10 Genotypes XXV and XXVI were added from
our own data set. Since the first genotypes were introduced
before the two species were distinguished from each other,6,7
and since in the meantime new genotypes have been found, the
numbering of the genotypes is jumbled. We propose adjusting
the ITS genotype classification to this new situation by adding a
‘Ti’ before the Roman numeral of every T. interdigitale genotype
and a ‘Tm’ for the T. mentagrophytes genotypes (Table 1). Thus,
on the genotype level, assignment to the respective species is
clearer. Our ITS sequences (GenBankâ accession no. MT858795
– MT858956) were aligned to the genotype reference sequences
(Table 1) with CLC Main Workbench.17 We set the borders of
the ITS region according to those deposited in the GenBankâ
under the accession no. KT354634.18
A maximum likelihood phylogenetic tree of all T. mentagro-
phytes and T. interdigitale ITS genotypes was constructed with
1000 Bootstrap replications and the Tamura–Nei model as a
substitution method using Mega version X.19
Detection of antifungal resistances
Resistance to terbinafine was examined by sequencing part of
the squalene epoxidase (SQLE) gene. Amplification was done

Table 2 Demographic, clinical and therapeutic data of patients with Trichophyton mentagrophytes and Trichophyton interdigitale
infections

Trichophyton Trichophyton P value

mentagrophytes (n = 81) interdigitale (n = 81)
Age, median years (IQR) 22 (8–33) 62 (48–73) <0.001
Gender, female No. (%) 51 (63) 32 (40) 0.003
Type of dermatophytosis
Tinea capitis et faciei 26 1 <0.001
Tinea corporis 41 2 <0.001
Tinea genitalis 11 0 0.002
Tinea glutealis et inguinalis 9 1 0.01
Tinea pedis 3 29 <0.001
Onychomycosis 0 51 <0.001
Multiple areas 17 7 0.01
Unknown 11 4
Inflammation, none to low/moderate to high 26/19 14/0 0.002
Number of patients, where degree of inflammation was unknown 36 67
Therapy, systemic/topical/combination of topical and systemic† 6/17/31 1/14/1 0.6/<0.001/<0.001
Number of patients, where therapy was not recorded 27 65

†Systemic antifungals were terbinafine (n = 32), itraconazole (n = 12) and fluconazole (n = 1). Topical antifungals were terbinafine cream (n = 30), clotrima-
zole cream (n = 19), ketoconazole cream (n = 5) and shampoo (n = 1), amorolfine cream (n = 5), miconazole cream (n = 2), econazole cream (n = 3), iso-
conazole cream (n = 1), amorolfine nail lacquer (n = 5) and ciclopirox nail lacquer (n = 2).

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1020 Klinger et al.

with the primers TRI SE-R3-F (primer TRI SE-R3 from Saunte
et al.20 was here used as forward primer), 50 -CTGCGTTGGA-
GAAGGGAGG-30 and TrSQLE-R1,21 50 -CTAGCTTT-
GAAGTTCGGCAAA-3 for 40 cycles with 30 s 94°C, 1 min 48°C
and 2 min 72°C. The sequences of the SQLE gene were com-
pared with a reference sequence (accession no. EZF33561) using
CLC Main Workbench.17 Antifungal susceptibility testing was
performed in vitro as previously described.22
Statistical analysis
Statistical analysis was conducted using Microsoft Excel and R
software with RStudio.23–25 Non-parametric distribution for all
numerical data (age and duration of illness) was confirmed by
quantile–quantile plots, Shapiro–Wilk and Lilliefors tests. The P
values of these data were calculated using the Wilcoxon rank-
sum test. For categorical data (gender, location and therapy) the
Pearson’s chi-squared test was used if more than 80% of the
expected frequencies in the cells of the contingency table were
greater than five. Otherwise, Fisher’s exact test was conducted. P
values of multiple comparisons (location n = 6, therapy n = 3,
comparisons of T. mentagrophytes ITS genotypes n = 7) were
adjusted by applying the Benjamini–Hochberg procedure. All
tests were two-sided with an estimated confidence interval of
95%.
Results
Between January 2009 and December 2019, a total of 1296
patients were diagnosed with T. interdigitale/T. mentagrophytes
species complex by culture and conventional identification.
ITS sequencing was performed in 162 cases identifying

Figure 1 Maximum likelihood phylogenetic tree of T. mentagrophytes and T. interdigitale genotypes based on ITS sequencing
(accession no. of the sequences are shown in Table 1). The numbers of isolates per genotype found in this study are shown in brackets.
T. tonsurans (accession no. EF043270) and T. equinum (accession no. MH858791) have been added as an outgroup. The new genotypes
Ti-XXV and Tm-XXVI are underlined in red. Only bootstrap values above 50% are shown.

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Genotyping of T. mentagrophytes/interdigitale 1021

T. mentagrophytes and T. interdigitale in 81 cases each. These
cases occurred primarily in the Zurich area (n = 104) but also in
the eastern (n = 37) and central (n = 12) parts of Switzerland
and various other regions (n = 9). Direct microscopy was per-
formed in the majority of cases (n = 140) and was positive in
67% (n = 94).
The comparison of T. mentagrophytes cases with T. interdigi-
tale cases resulted in significant differences (Table 2). Patients
with T. mentagrophytes were younger (medians of 22 vs. 62 years
of age) and more often female (63% vs. 40%) than patients with
T. interdigitale. T. mentagrophytes primarily affected areas other
than the feet and never caused onychomycosis, while T. interdig-
itale was restricted to the feet and nails except in four cases (two
cases with palmoplantar, one case with inguinal and one case
with scalp involvement). Additionally, T. mentagrophytes more
often caused inflammatory tinea and affected multiple body
sites. For T. mentagrophytes infections, combined topical and
systemic treatment was typically used, whereas T. interdigitale
infections were primarily managed topically.
Analysing the ITS sequences allowed us to assign 160/162 iso-
lates to previously published ITS genotypes with 100% sequence
identity (Table 1), while one T. interdigitale sequence (accession
no. MT858874) and one T. mentagrophytes sequence (accession
no. MT858956) were identified as two new genotypes, genotypes
Ti-XXV and Tm-XXVI, respectively. This was confirmed by phy-
logenetic analysis (Fig. 1). The isolate of genotype Ti-XXV was
retrieved from a 67-year-old female patient with tinea pedis and
tinea manuum and the isolate of genotype Tm-XXVI from a 55-
year-old male patient with tinea genitalis and tinea corporis.
Table 3 summarizes demographic, clinical and therapeutic
data of T. mentagrophytes ITS genotypes collected in this study.
The majority (56%, n = 45) of T. mentagrophytes infections in
this study were caused by genotype Tm-III. These patients were
younger than patients infected with other genotypes, had mostly
non- to low-inflammatory lesions (Fig. 2a) and were often trea-
ted topically (in contrast to other genotypes where usually a
combination of topical and systemic treatment was adminis-
tered). The actual source of infection could only be determined
in a proportion of cases. Many patients with T. mentagrophytes
genotype Tm-III infections were exposed to animals (mostly to
cats, more rarely to dogs or farm animals), but only in two cases
the mycological examination of the cat was reported positive.

Table 3 Demographic, clinical and therapeutic data of patients with Trichophyton mentagrophytes infections by ITS genotypes. P values
indicate a significant difference between a particular genotype and all the others

T. mentagrophytes genotype Tm-II* Tm-III Tm-III* Tm-IV Tm-VII Tm-VIII Tm-XXVI new
(n = 2) (n = 45) (n = 12) (n = 3) (n = 7) (n = 11) (n = 1)
Age, median years (IQR) 19 11 25 7 31 32 55
(13–24) (6–25) (9–29) (6–28) (26–42) (31–41) (N/A)
P = 0.01 P = 0.01
Gender, female no. (%) 2 (100) 32 (71) 6 (50) 2 (67) 2 (29) 7 (64) 0 (0)
Dermatophytosis
Tinea capitis et faciei 1 15 6 0 3 1 0
Tinea corporis 1 24 5 2 4 4 1
Tinea genitalis 0 1 2 0 5 2 1
Tinea glutealis et inguinalis 0 0 2 0 1 6 0
P = 0.04
Tinea pedis 0 0 1 1 0 1 0
Multiple areas 0 5 3 1 5 2 1
P = 0.04
Unknown 0 10 0 1 0 0 0
Inflammation, none to low/moderate to high 2/0 16/3 1/9 1/1 0/6 5/0 1/0
P = 0.007 P = 0.005 P = 0.008
Unknown 0 26 2 1 1 6 0
Duration of illness, median weeks (IQR) 6 (5–7) 6 (3–10) 8 (8–10) 15 (12–19) 8 (7–8) 28 (12–50) 8 (N/A)
Unknown 0 30 5 1 0 6 0
Therapy, systemic/topical/combination 0/1/1 0/15/9 2/0/7 0/0/2 3/0/4 1/1/7 0/0/1
of topical and systemic† P < 0.001‡
Unknown 0 21 3 1 0 2 0

Abbreviations: N/A, not applicable.

†Systemic antifungals were terbinafine (n = 30), itraconazole (n = 12) and fluconazole (n = 1). Topical antifungals were terbinafine cream (n = 23), clotrima-
zole cream (n = 17), ketoconazole cream (n = 4) and shampoo (n = 1), amorolfine cream (n = 5), miconazole cream (n = 2), econazole cream (n = 3) and
isoconazole cream (n = 1) were used as topical treatment.
‡Refers to topical treatment.

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1022
Figure 2 T. mentagrophytes dermatophytosis of different geno-
types: (a) type Tm-III lesion on the thigh of a 14-year-old girl; (b)
type Tm-III* Tinea capitis (Kerion celsi) of a 3-year-old boy; (c) and
(d) type Tm-VII Tinea genitalis and Tinea facialis of a 21-year-old
male patient; (e) and (f) type Tm-VIII Tinea corporis of a 32-year-
old female patient.
Infections with genotype Tm-III* led to moderately to highly
inflamed lesions (Fig. 2b). In two cases, the patient’s cat was
found to be infected by a dermatophyte as well. Two other
patients with tinea genitalis due to genotype Tm-III* infections
had reported sexual intercourse while travelling in Thailand. In
one of these cases, the partner developed tinea genitalis too.
Genotype Tm-VII also frequently led to moderately to highly
inflamed widespread lesions mostly involving the genital area
(Fig. 2c/d). Several patients experienced extensive ulcerations in
the genital area caused by this pathogen. Three of them had vis-
ited Thailand, one of whom reported having had sexual
intercourse.
We found eleven patients with a genotype Tm-VIII (the so
called ‘Indian genotype’) infections, and the first of which was
noted in the year 2014. Patients with genotype Tm-VIII were
older, the gluteal and inguinal areas were significantly more
often affected (Fig. 2e/f), and the duration of illness was highest
(28 weeks), but this was not statistically significant (P = 0.08)
possibly due to low sample size (n = 5). Three patients were of
Indian nationality, one was from Bangladesh, three were from
Europe (one of whom had travelled to Thailand) and in four
cases, the nationality is unknown.
JEADV 2021, 35, 1017–1025
Klinger et al.
We only found few Tm-II* and Tm-IV genotypes. They were
associated with tinea corporis and in case of Tm-II* also with
tinea capitis. One genotype Tm-IV infection also led to tinea
pedis by affecting the dorsum of the foot, but did not cause the
typical interdigital tinea pedis.
Terbinafine was the most commonly applied systemic and
topical antifungal in this study. Molecular testing for terbinafine
resistance was conducted for all genotype Tm-VIII strains, while
for the other strains it was done only in cases of treatment fail-
ure. Four genotype Tm-VIII isolates, the first two of which were
isolated in the year 2016, had a Phe397Leu mutation in the squa-
lene epoxidase. Antifungal susceptibility testing confirmed
terbinafine resistance for these isolates, with terbinafine
MICs ≥ 4 µg/mL. No resistances to other antifungals such as
fluconazole, itraconazole, ketoconazole or griseofulvin were
found.
Discussion
This is the largest study investigating T. mentagrophytes and T.
interdigitale infections in Switzerland and one of the largest stud-
ies investigating the two species on genotype level. Our first aim
was to compare demographic, laboratory, clinical and therapeu-
tic data of T. mentagrophytes infections with T. interdigitale
infections in the broader Zurich area, Switzerland. The new tax-
onomy of dermatophytes by de Hoog et al.6 separates Trichophy-
ton interdigitale from its close relative Trichophyton
mentagrophytes and classifies these two as separate species
because (i) even though they are closely related, T. interdigitale
isolates failed to produce fertile offspring with T. mentagrophytes
reference strains,26 and (ii) T. interdigitale and T. mentagro-
phytes infections result in two different clinical presentations.7–10
Our findings confirm that T. interdigitale infections cause non-
to low-inflammatory tinea pedis or onychomycosis, whereas T.
mentagrophytes infections affect areas other than feet and nails
and are often moderately to highly inflamed. The importance of
this distinction is further substantiated by the fact that T. inter-
digitale infections were more often solely treated by topicals,
while for T. mentagrophytes cases, predominantly a combination
of systemic and topical medications was administered. Our anal-
ysis has also shown that T. interdigitale mainly affected older and
male patients, whereas T. mentagrophytes occurred more often
in younger adults and children, with a higher prevalence of
females.
Our second aim was to elucidate the current epidemiology of
T. mentagrophytes genotypes in our area. During the last years, it
has become evident that investigating genotypes of T. mentagro-
phytes has important clinical and therapeutic consequences.
Knowing the genotype may assist the clinician in identifying the
source of infection and the likely mode of transmission, and
would also raise awareness of an increased likelihood of drug
resistance in a subset of strains. Table 4 provides an overview of
the main T. interdigitale and T. mentagrophytes genotypes and
© 2021 European Academy of Dermatology and Venereology
Genotyping of T. mentagrophytes/interdigitale 1023

Table 4 Overview of main Trichophyton interdigitale and T. mentagrophytes genotypes based on this study and the current literature.7–13,15
We propose to use ‘Ti’ and ‘Tm’ as prefix before the Roman genotype number for easier recognition of the species

Genotype† Distribution‡ Transmission Typical patient Clinical presentation Remarks

Ti-I Europe Anthropophilic Adults Tinea pedis
Tinea unguium
Ti-II Cosmopolite Anthropophilic Adults Tinea pedis
Tinea unguium
Tm-II* Cosmopolite Tinea capitis et faciei
Tm-III Europe Zoophilic, mostly by cats Children Tinea corporis Can mostly be treated with topicals
rarely by dogs or farm Tinea capitis et faciei
animals
Tm-III* Europe Zoophilic (mostly cats) and Children Tinea capitis et faciei Often inflamed lesions
sexually transmitted young adults Tinea corporis
Tinea genitalis
Tm-IV Europe Tinea corporis
Tm-V Western Asia Tinea capitis et faciei
Tinea corporis
Tm-VI Europe Tinea capitis
Tm-VII South-East Asia, Europe Anthropophilic, sexually adults Tinea genitalis Often inflamed lesions
(Germany, Switzerland, transmitted Tinea faciei
originating often from Tinea inguinalis et glutealis
Thailand)
Tm-VIII Asia (mostly India) Anthropophilic through adults Tinea glutealis et inguinalis About 30% are terbinafine resistant
close contact and lack of Tinea corporis
hygiene. Tinea pseudoimbricata
Use of combination creams§
is the major risk factor.
†Genotypes with so far >10 reported cases.
‡Geographical locations where so far >10 cases were reported.
§These creams contain corticosteroids mixed with antifungals and antibiotics.

their characteristics. Further studies will corroborate the charac-
teristics of individual genotypes. Unfortunately, at present there
are almost no data covering the American and African
continents.10
In our study, genotype Tm-III infections as well as the few
Tm-II* and Tm-IV cases occurred primarily in children, many
of whom had been exposed to animals (in two cases with proven
zoophilic origin of the infection). Cats, predominantly outdoor
hunters, have been reported by Drouot et al.27 to be the most
frequent transmitters of T. mentagrophytes infections in Switzer-
land. In addition, Heidemann et al.8 reported genotype Tm-III
as the main dermatophyte in cats. Our data support both these
findings. Genotype Tm-III*, however, seems to have two possi-
ble ways of transmission: zoophilic by cats and anthropophilic
through sexual intercourse as reported by two patients who had
been to Thailand. The transmission of genotype Tm-VII, on the
other hand, seems to be mostly due to sexual contact and
appears to occur often in Thailand.11,15,28,29 The infection fre-
quently leads to inflammatory tinea, and therefore, patients are
usually treated with oral antifungals. Phylogenetic analysis of the
elongation factor-1-a revealed that genotype Tm-III* and geno-
type Tm-VII are closely related.11 Our own findings support this
assumption since both genotypes often cause inflamed lesions
and can be sexually transmitted. Finally, the ‘Indian genotype’
Tm-VIII, which often leads to tinea corporis and tinea glutealis,
is also predominantly transmitted by humans.12 Thus, even
though according to the new species concept by de Hoog et al.
T. mentagrophytes is a zoophilic fungus,6 our data indicate that
some of its genotypes are in fact partly or predominantly anthro-
pophilic. This has important implications in terms of patient
management and counselling.
Another important fact is that 36% of genotype Tm-VIII
strains proved to be resistant to terbinafine by a point mutation
in the squalene epoxidase gene leading to the amino acid substi-
tution Phe397Leu. A similarly high percentage of terbinafine
resistance was discovered in India with 63 isolates that were later
identified as T. mentagrophytes genotype Tm-VIII.9,13 In a recent
study on the current epidemic of dermatophytosis in India,
genotype Tm-VIII was identified as the main aetiology.12
According to the authors, this outbreak of genotype Tm-VIII in
India is mainly due to the irresponsible use of combination
creams containing high-potency steroids together with antimy-
cotic and antibiotic agents. The epidemic of T. mentagrophytes
genotype Tm-VIII combined with its high resistance to terbina-
fine is especially worrisome because terbinafine is considered a
first line drug against dermatophytes.30 In terbinafine-resistant
cases, itraconazole as a systemic alternative has been recom-
mended in several studies.13,14,31

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1024
As with most research, this study has limitations. First, since
it is a retrospective analysis, the time interval between medical
consultations was not standardized and not all patients had fol-
low-ups. Second, clinical metadata were missing in several cases,
especially if patients had not been seen at the University Hospital
Zurich or were infected with T. interdigitale. In many T. interdig-
itale cases, the fungal infection was not the main reason for the
hospitalization, and therefore, clinical data concerning the der-
matophyte infection were not recorded. Third, the sample size
of this study was too small to draw a firm conclusion on geno-
types Tm-II* and Tm-IV. Fourth, incidence, prevalence and
trends over the years of T. interdigitale and T. mentagrophytes
could not be determined because ITS sequencing was not per-
formed regularly at the beginning of the observation period and
because T. mentagrophytes and T. interdigitale infections are not
notifiable in Switzerland.
In summary, this study underlines the importance of distin-
guishing between Trichophyton interdigitale and Trichophyton
mentagrophytes infections as they cause dermatophytoses that
manifest differently. Correct assignment is only possible with
ITS sequencing, which also allows precise ITS genotype identifi-
cation. This has important clinical consequences, as Trichophy-
ton mentagrophytes ITS genotypes have specific characteristics
and differ considerably from each other in terms of geographical
distribution, mode of transmission, affected patient group, type
of dermatophytosis, degree of inflammation and patient
management.
Acknowledgements
We thank Dr. Andrea Binkert, Triemli Hospital Zurich and Dr.
Stephan Nobbe, Cantonal Hospital Frauenfeld, for providing us
with clinical details of some cases. We also thank Nada Juricevic,
Barbara Fl€uckiger and Irene Fleckenstein for technical assistance.
Ethical approval
Ethical approval by the Ethics Committee of Zurich, Switzerland
(BASEC-no. 2019-01947).
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