Publications by authors named "Iman Haghani"

27 Publications

  • Page 1 of 1

Molecular Identification and Antifungal Susceptibility of Yeasts and Molds Isolated from Patients with Otomycosis.

Mycopathologia 2021 May 15;186(2):245-257. Epub 2021 Mar 15.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Fungal otitis externa, an infection of the external auditory canal caused by molds and yeasts, accounts for approximately 10-20% of ear canal infections accompanying high recurrence. The purpose of the current study was to assess the pattern of etiological agents of otomycosis and resistance profile as well as the rate of tympanic membrane perforation. A total of 1040 patients with symptoms of fungal otitis externa, in a period of two years, were investigated. The mycological tests revealed the presence of different fungi in 237 ears (22.8%). Fungal otitis was more related to filamentous fungi of the species Aspergillus flavus (54.43%), A. tubingensis (10.97%), and A. niger (8.86%), followed by yeasts, Candida orthopsilosis (7.59%), C. albicans (6.75%), and C. parapsilosis (5.06%). Tympanic membrane perforation rate was found to be 6.75% and was more common with otomycosis caused by A. flavus, A. tubingensis and C. albicans. In antifungal susceptibility tests, all tested drugs showed generally good activity against most isolates of molds and yeasts, while tolnaftate, clotrimazole, nystatin, and terbinafine had lowest effects. We found that among Aspergillus isolates, one A. niger isolate was resistant to voriconazole, and one A. flavus isolate was resistant to amphotericin B. Furthermore, among Candida species, three isolates of C. orthopsilosis showed high MIC values to fluconazole, two C. albicans isolates were considered fluconazole resistant and one isolate of C. parapsilosis was resistant to caspofungin and 3 isolates were resistant to fluconazole. Regarding the existence of the cases with perforated tympanic membrane and emerging species causing fungal otitis in the current report, the importance of the early physical examination, precise molecular identification, and the antifungal susceptibility evaluation is highlighted.
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http://dx.doi.org/10.1007/s11046-021-00537-1DOI Listing
May 2021

Regenerative effect of mesenteric fat stem cells on ccl4-induced liver cirrhosis, an experimental study.

Ann Med Surg (Lond) 2020 Dec 24;60:135-139. Epub 2020 Oct 24.

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Liver cirrhosis is a chronic disease in which normal liver tissue is replaced by fibrous tissue, leads to liver malfunction. Although transplantation is the most certain cure, stem cell therapies are shedding light on efforts to regenerate cirrhotic liver. The purpose of this study was to evaluate the regenerative potential of mesenteric fat stem cells in CCL4-induced liver cirrhosis in an animal model.

Methods: Thirty rats were treated with the mixture of CCL4 and olive oil intraperitoneally by a dose of 0.2 ml (0.1 ml CCL4 and 0.1 ml olive oil) every other day for 16 weeks till cirrhosis signs appeared. Fifteen rats were randomly selected as control group. Others treated by mesenteric fat derived mesenchymal stem cells transferred into the liver parenchyma.

Results: After 5 weeks, rats received stem cells had improved clinically by increased movements, appetite, improvement in overall behavior and decreased abdomen size. Histopathologically, liver cells showed state of regeneration and forming new colonies.

Conclusion: Liver cirrhosis was induced. The mesenchymal stem cells derived from mesenteric adipose tissue could improve hepatic status of the rats, as cirrhotic livers were regenerated back into normal appearing parenchyma. Rats' clinical behavior also reached healthy status.
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http://dx.doi.org/10.1016/j.amsu.2020.10.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593263PMC
December 2020

In vitro activities of antifungal drugs against a large collection of Trichophyton tonsurans isolated from wrestlers.

Mycoses 2020 Dec 13;63(12):1321-1330. Epub 2020 Sep 13.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Trichophyton tonsurans is the most common agent causing tinea gladiatorum in wrestlers, and limited data on susceptibility profiles of Trichophyton tonsurans are available.

Objectives: We aimed to assess the in vitro activity of the common antifungal drug against a large collection of T tonsurans.

Materials/methods: The in vitro activities to eight common antifungal drugs (sertaconazole, itraconazole, clotrimazole, fluconazole, butenafine, tolnaftate, terbinafine and griseofulvin) against 128 clinical isolates of T tonsurans strains, obtained from wrestlers with dermatophytosis, were performed according to CLSI M38-A2 broth microdilution document.

Results: The geometric mean minimum inhibitory concentration was the lowest for tolnaftate (0.022 µg/mL), followed by itraconazole (0.026 µg/mL), terbinafine (0.033 µg/mL), butenafine (0.088 µg/mL), griseofulvin (0.566 µg/mL), sertaconazole (2.875 µg/mL), clotrimazole (3.419 µg/mL) and fluconazole (12.540 µg/mL).

Conclusions: Evaluation of antifungal susceptibility of dermatophytes showed that tolnaftate and itraconazole were the most effective drugs against T tonsurans and fluconazole had the least effect.
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http://dx.doi.org/10.1111/myc.13172DOI Listing
December 2020

Echinocandin resistance in Candida parapsilosis sensu stricto: Role of alterations in CHS3, FKS1 and Rho gene expression.

J Glob Antimicrob Resist 2020 09 9;22:685-688. Epub 2020 Jul 9.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Objectives: The rate of resistance of Candida parapsilosis to echinocandins remains unexplored in Iran. The main aims of this study were to investigate the susceptibility patterns and possible mechanisms of echinocandin resistance in echinocandin-resistant clinical C. parapsilosis isolates in Iran.

Methods: A total of 105 isolates of C. parapsilosis sensu stricto underwent antifungal susceptibility testing to echinocandins by the broth microdilution reference method. Sequences of the CpERG3 and CpFKS1 genes were analysed using MEGA6 software, and alterations in CHS3, FKS1 and Rho gene expression were evaluated by quantitative reverse transcription (RT-qPCR). REST® software was used to analyse the results.

Results: The rate of echinocandin cross-resistance was 2.9% (3/105). No substitutions were detected in Fks1p except for the naturally occurring P660A amino acid substitution observed in isolates both with high and low minimum inhibitory concentrations (MICs). Moreover, the G111R amino acid substitution was not found in Erg3p. Following echinocandin exposure, expression of Rho and FKS1 genes was significantly increased in resistant isolates, whilst the CHS3 gene showed no change.

Conclusion: Alterations in the expression of some key genes may be responsible for echinocandin resistance among C. parapsilosis isolates. Understanding the mechanisms responsible for drug resistance in C. parapsilosis is not only crucial for the development of new antifungals but is also important in choosing appropriate antifungals for patient treatment at the earliest stage.
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http://dx.doi.org/10.1016/j.jgar.2020.06.025DOI Listing
September 2020

Phylogenetic Analysis of Clinically Relevant Fusarium Species in Iran.

Mycopathologia 2020 Jun 6;185(3):515-525. Epub 2020 Jun 6.

Center of Expertise in Mycology of Radboud University Medical Center, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Fungi of the genus Fusarium are well known as major plant pathogens but also cause a broad spectrum of human infections. Sixty-three clinical isolates, collected during 2014-2017, were identified using a part of the TEF1 gene as barcoding marker. Fusarium fujikuroi species complex (FFSC, n = 41, 65%) showed to be the dominant etiological agent, followed by F. solani species complex (FSSC, n = 14, 22%) and F. oxysporum species complex (FOSC, n = 7, 11%). There was one strain belonging to F. lateritium species complex (FLSC, n = 1, 1.5%). For final identification, a phylogenetic tree was constructed including the type strains of each species complex. Most cases of fusariosis were due to nail infection (n = 38, 60.3%), followed by keratitis (n = 22, 34%). Fusarium infections are difficult to be treated due to their intrinsic resistance to different azoles; however, accurate and fast identification of etiological agents may enhance management of the infection. We present the first phylogenetic study on clinical Fusarium spp. from Iran.
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http://dx.doi.org/10.1007/s11046-020-00460-xDOI Listing
June 2020

Galactomannan detection in bronchoalveolar lavage fluids: A diagnostic approach for fungus ball in patients with pulmonary tuberculosis?

Mycoses 2020 Jul 24;63(7):755-761. Epub 2020 May 24.

Invasive Fungi Research Center/Department of Medical mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Several previous studies have shown cavitary lung lesions in old pulmonary tuberculosis (PTB) increase the risk of fungus ball. Detection of galactomannan (GM) in bronchoalveolar lavage (BAL) is also proposed as a diagnostic approach for the fungus ball.

Objectives: We evaluated the diagnosis of fungus balls and GM levels in BAL samples in PTB patients.

Methods: A total of 110 PTB patients were evaluated for fungus ball during 2017-2019. The patients were evaluated for radiological, histopathological results and mycological findings of BAL including GM detection and culture. The sensitivity, specificity and positive and negative predictive value for GM test were calculated. The optimal cut-off for BAL GM testing was determined by receiver operating characteristic (ROC).

Results: Of 110 PTB patients, nine (8.18%) showed fungus ball, all with old PTB. The molecularly confirmed Aspergillus species were A. flavus, A. fumigatus and A. ochraceus. The sensitivity and specificity of BAL GM ≥ 0.5 in old PTB patients with fungus ball were 100%, 41.5%, respectively. The statistical analysis of the mean ± SEM of BAL GM levels was demonstrated a higher levels of GM in patients with fungus ball/aspergilloma compared to old PTB patients without fungus ball/aspergilloma. The optimal cut-off value for BAL GM was determined as 0.50 by ROC curve analysis.

Conclusion: According to our results, we can recommend the detection of GM in BAL samples as a diagnostic approach for fungus ball in PTB patients.
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http://dx.doi.org/10.1111/myc.13099DOI Listing
July 2020

Relationship between spirometry results and colonisation of Aspergillus species in allergic asthma.

Clin Respir J 2020 Mar 26. Epub 2020 Mar 26.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Introduction And Objectives: Exposure to fungi in patients with asthma leads to the release of various fungal antigens, which can increase the severity of asthma. Regarding this, the present study was conducted to evaluate the relationship between the colonisation of Aspergillus species and spirometry results in allergic asthma.

Materials And Methods: Two hundred sixteen patients with mild to severe asthma and 30 healthy controls were included. All participants underwent pulmonary function tests. Furthermore, sputum samples were collected from each subject. Each sputum sample was subjected to direct microscopic examination and fungal culture. All cultured Aspergillus colonies were identified at species level by molecular methods. Finally, all available data from sputum culture and spirometry test were analysed.

Results: Out of 216 sputum samples, 145 (67.1%) were positive for fungal growth. Furthermore, out of 264 grown fungal colonies, 137 (51.9%) were Aspergillus species. Among the Aspergillus isolates, A. flavus (29.2%) was the most prevalent species, followed by A. fumigatus (27.7%). The mean forced expiratory volume in one second (FEV1) in the mild, moderate and severe asthmatic patients with a positive sputum culture for fungi were obtained as 90.0 ± 11.1, 71.1 ± 15.9 and 54.9 ± 16.4, respectively. In general, Aspergillus species colonisation had no statistically significant effect on spirometry results of study patients.

Conclusion: Our results showed that there is no difference in the FEV1 and forced vital capacity between Aspergillus positive and negative patients in any asthma severity group.
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http://dx.doi.org/10.1111/crj.13192DOI Listing
March 2020

Antifungal Activity of a Novel Triazole, Efinaconazole and Nine Comparators against 354 Molecularly Identified Aspergillus Isolates.

Mycopathologia 2020 Apr 28;185(2):357-365. Epub 2020 Feb 28.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Management of superficial aspergillosis is a major challenge owing to the frequent relapses and treatment failure, which may pose a potential risk, thereby gradually developing resistant species. Therefore, necessitating the development of new antifungals with higher potency should be considered as alternative strategies for efficient management of infections. We aimed to investigate the susceptibility of Aspergillus isolates toward a novel triazole, efinaconazole, in comparison with various classes of antifungal drugs. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute M38-A2 guidelines. Efinaconazole exhibited poor activity against mutant A. fumigatus strains, A. niger sensu stricto, and A. tubingensis with GM MIC values of 3.62, 1.62, and 2 μg/ml, respectively; however, surprisingly, it efficiently inhibited the growth of A. terreus sensu stricto, followed by wild-type A. fumigatus and A. flavus with GM MIC values of 0.29, 0.42, and 0.52 μg/ml, respectively. Presumably, efinaconazole is inefficient in aspergillosis treatment due to the low susceptibility of A. niger sensu stricto, A. tubingensis, and mutant A. fumigatus; however, it may be effective in treating superficial aspergillosis caused by wild-type A. fumigatus, A. terreus sensu stricto, and A. flavus. Further studies are needed to determine how these findings may translate into in vivo efficacy.
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http://dx.doi.org/10.1007/s11046-020-00434-zDOI Listing
April 2020

Species distribution and susceptibility profiles of Candida species isolated from vulvovaginal candidiasis, emergence of C. lusitaniae.

Curr Med Mycol 2019 ;5(4):26-34

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: The aim of the current study was to investigate the epidemiology of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC), as well as the antifungal susceptibility patterns of species isolates.

Materials And Methods: A cross-sectional study was carried out on 260 women suspected of VVC from February 2017 to January 2018. In order to identify species isolated from the genital tracts, the isolates were subjected to polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using enzymes and sequencing. Moreover, antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute guidelines (M27-A3).

Results: Out of 250 subjects, 75 (28.8%) patients were affected by VVC, out of whom 15 (20%) cases had RVVC. Among the species, was the most common species (42/95; 44.21%), followed by (18/95; 18.95%), (13/95; 13.69%), (8/95; 8.42%), (6/95; 6.31%), (5/95; 5.26%), (2/95; 2.11%), and (1/95; 1.05%), respectively. Multiple species were observed in 28% (21/75) of the patients. Nystatin showed the narrowest range of minimum inhibitory concentration (MIC) (0.25-16 μg/ml) against all strains, whereas fluconazole (0.063-64 μg/ml) demonstrated the widest MIC range. In the current study, as the second most common causative agent of VVC, was susceptible to all antifungal agents. Furthermore, 61.1% of isolates were inhibited at a concentration of ≤ 2 μg/ml while 38.9% (n=7) of them exhibited fluconazole MICs above the epidemiologic cutoff values (ECV). species showed the highest overall resistance against fluconazole (61.3%), followed by itraconazole (45.2%) and caspofungin (23.7%). All of strains were resistant to itraconazole with a MIC value of ≥ 1 μg/ml; in addition, 87.5% of them were resistant to fluconazole. Moreover, 100% and 87.5% of strains were resistant to caspofungin and fluconazole, respectively.

Conclusion: As the findings revealed, the majority of VVC cases were caused by non- species which were often more resistant to antifungal agents. generally had fluconazole MICs above the ECV. Given the propensity of to develop resistance under drug pressure, antifungals should be administered with caution. The emergence of these species justify the epidemiological surveillance surveys to watch out the distribution of yeast species.
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http://dx.doi.org/10.18502/cmm.5.4.2062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034787PMC
January 2019

Molecular epidemiology of Tinea gladiatorum in contact sports in northern Iran.

Mycoses 2020 May 13;63(5):509-516. Epub 2020 Mar 13.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Tinea gladiatorum as the major health concern among combat athletes and the most common cause of a decrease in the quality of their sports activities.

Objectives: This study aimed to determine the molecular epidemiology of tinea gladiatorum in contact sports in Mazandaran Province, Northern Iran.

Materials/methods: In total, 631 suspected athletes out of 4240 ones were screened for tinea gladiatorum in this cross-sectional study from May 2018 to February 2019. The infection was confirmed by direct microscopy and culture tests. The causative agents were identified by polymerase chain reaction-restriction fragment length polymorphism method on ITS rDNA region. The indoor environmental factors were evaluated in 81 sports halls in terms of temperature (°C), humidity (%), density (m /athletes) and the number of ventilators.

Results: Tinea gladiatorum was confirmed in 6.5% (278/4240) of the athletes. Tinea corporis was the most common type of tinea (192/278; 69.0%), and 175 cases (27.7%) had more than one type of tinea. Moreover, Trichophyton tonsurans (192/203; 94.5%) was the most aetiological agent in all athletes followed by Microsporum canis (6/203; 2.9%), Trichophyton rubrum (2/203; 0.9%) and Trichophyton interdigitale (1/203; 0.4%). There was no significant association between the prevalence of tinea gladiatorum and the indoor environmental factors.

Conclusion: T. tonsurans is the most common agent of tinea gladiatorum in Northern Iran. Since no positive culture of dermatophyte was obtained from mats, it seems that skin-to-skin contact would be the most probable mode of transmission among wrestlers. Accordingly, periodical checkups should be considered by health care providers.
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http://dx.doi.org/10.1111/myc.13069DOI Listing
May 2020

High prevalence of itraconazole resistance among isolated from Iran.

Curr Med Mycol 2019 Sep;5(3):43-46

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: Candida parapsilosis isolates usually have a low minimum inhibitory concentration (MIC) against azoles. Although Candida parapsilosis isolates usually have low MICs against azoles, recent studies candida invasive infections due to azole resistant-C. parapsilosis isolates . Regarding this, the main aim of this study was to determine the susceptibility pattern of Iranian clinical against available azole antifungal drugs.

Materials And Methods: This study was conducted on 105 previously-identified isolates of For the purpose of the study, the isolates were subjected to antifungal susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and two new azole drugs, namely luliconazole (LUZU) and lanoconazole (LZN). The broth microdilution reference method adopted in this study was according to the Clinical & Laboratory Standards Institute M27-A3 and M27-S4 documents.

Results: According to the results, 89% (n=94) of isolates showed a MIC of ≥ 1 µg/ml, indicating resistance against ITZ. Multi-azole resistance was observed in 3.8% of the isolates. In addition, LUZU and LZN demonstrated the highest efficacy with the MIC values of 0.5 and 1 µg/ml, respectively.

Conclusion: The majority of the isolates showed high MIC values against ITZ. This may have been associated with the long-term ITZ prophylaxis/therapy in patients infected with candidiasis. Hence, the adoption of an appropriate antifungal agent is a crucial step for starting the treatment.
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http://dx.doi.org/10.18502/cmm.5.3.1746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910713PMC
September 2019

A multi-centered study of colonization in patients with respiratory disorders: Is there a colonization trend in the elderly?

Curr Med Mycol 2019 Sep;5(3):19-25

Department of Molecular Pathology, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Purpose: colonization plays a key role in the progression of pulmonary infection. However, there are limited data regarding the colonization of these fungi in the patients residing in different regions of Iran. Regarding this, the present study was conducted to evaluate the prevalence of colonization in non-HIV-infected patients with respiratory failure introduced by physicians using nested polymerase chain reaction (PCR).

Materials And Methods: This study was conducted on 136 samples obtained from 136 patients with respiratory disorders referring to different hospitals in the capital and north of Iran during 2013-2015. The samples were collected using bronchoalveolar lavage (BAL; n=121) and sputum induction (n=15). Nested PCR method targeting mtLSU rRNA gene was used for the detection of DNA in the specimens.

Results: The nested PCR analysis resulted in the detection of DNA in 32 (23.5%) patients. The mean age of the participants was 49.04±11.94 years (age range: 14-90 years). The results revealed no correlation between colonization and gender. The studied patients were divided into two groups of immunocompromised and immunocompetent patients. In the regard, 25.4% of the patients with detectable DNA were immunocompromised and had cancer, organ transplantation, asthma, sarcoidosis, dermatomyositis, chronic obstructive pulmonary disease, bronchiectasis, and pulmonary vasculitis. On the other hand, DNA was detected in 21.8% of the immunocompetent patients. Frequencies of DNA detection in the patients with tuberculosis, hydatid cyst, and unknown underlying diseases were obtained as 20.8%, 25%, and 22%, respectively. The prevalence of colonization varied based on age. In this regard, colonization was more prevalent in patients aged above 70 years.

Conclusion: As the findings indicated, non-HIV-infected patients, especially the elderly, had a high prevalence of colonization. Therefore, these patients are probably a potential source of infection for others. Regarding this, it is of paramount importance to adopt monitoring and prophylactic measures to reduce this infection.
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http://dx.doi.org/10.18502/cmm.5.3.1742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910707PMC
September 2019

Prevalence of specific immunoglobulin E and G against in patients with asthma.

Curr Med Mycol 2018 Dec;4(4):7-11

Invasive Fungi Research Centre, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: as a ubiquitous fungus can be found in the respiratory tract of the asthmatic and healthy people. The inhalation of spores leads to an immune response in individuals with asthma and results in the aggravation of the clinical symptoms. The present study aimed to investigate the prevalence of specific immunoglobulin E and G IgE and IgG) against in asthmatic patients.

Materials And Methods: This study was conducted on 200 consecutive patients with moderate to severe asthma referring to Masih Daneshvari hospital Tehran, Iran, from January 2016 to February 2018. Skin prick test (SPT) was performed in all subjects with allergens. Moreover, all patients underwent specific IgE testing for using Hycor method. Enzyme immune assay was applied to measure total IgE and specific IgG.

Results: According to the results, the mean age of the patients was 45.8 years (age range: 18-78 years). The mean levels of total IgE and specific IgE in asthmatic patients were obtained as 316.3 (range: 6-1300 IU/ml) and 1.5 (range: 0.1-61.3 IU/ml), respectively. Out of 200 patients, 27 (13.5%), 65 (32.5%), 22 (11.0%), and 86 (43.0%) cases had positive SPT, total IgE of > 417 IU/ml, specific IgE, and IgG, respectively. The level of these variables in patients with severe asthma were 16 (16.5%), 36 (37.1%), 15 (15.5%), and 46 (47.4%), respectively.

Conclusion: As the findings indicated, reactivity to is a remarkable phenomenon in asthmatic patients. It is also emphasised that the climatic condition may affect the positive rate of hypersensitivity to .
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http://dx.doi.org/10.18502/cmm.4.4.380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386509PMC
December 2018

Fungal epidemiology in cystic fibrosis patients with a special focus on Scedosporium species complex.

Microb Pathog 2019 Apr 8;129:168-175. Epub 2019 Feb 8.

Center of Expertise in Microbiology, Infection Biology and Antimicrobial Pharmacology, Tehran, Iran.

In this present study, for the first time, we evaluated the cystic fibrosis (CF) patients for the Scedosporium species and their antifungal susceptibility against eight antifungal agents. During one-year period, 90 Sputum samples were collected from Iranian CF patients. All samples were evaluated by direct microscopic examination, culture onto four different media including Malt extract agar, Inhibitory mold agar, Brain Heart Infusion and Scedo-Select III. The mold isolated fungi were identified by PCR-Sequencing of ITS and β-tubulin genes. In-vitro antifungal susceptibility was performed according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 guidelines. Out of 90 CF patients, 47 (52.2%) were male. The age of the patients ranged from 1 to 34 years (median of 15.84 ± 7.41 years). Overall, 3 (3.3%) cases were positive for Scedosporium spp. of which two isolates were characterized as Scedosporium boydii and one isolate as S. ellipsoideum. Among Aspergillus genus, A. flavus (29.4%) was the most prevalent species followed by A. tubingensis (24.7%), A. niger (17.0%) and A. fumigatus (14.5%). The minimum effective concentration ranges of micafungin, anidulafungin, and caspofungin were 0.008-0.031 μg/mL, 0.0625-0.25 μg/mL, and 0.0625-0.25 μg/mL, respectively. All isolates of Scedosporium species showed high minimum inhibitory concentration to the triazoles tested, except voriconazole. Our results showed that A. flavus and Scedosporium species are the most prevalent molds isolated from CF patient populations in Iran. Our findings have also showed that Scedo-Select III can be used as a reliable culture media for isolation of Scedosporium spp. in clinical samples.
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http://dx.doi.org/10.1016/j.micpath.2019.02.009DOI Listing
April 2019

Novel Point Mutations in and Genes Associated with Itraconazole and Posaconazole Resistance in Isolates.

Microb Drug Resist 2019 Jun 18;25(5):652-662. Epub 2019 Jan 18.

1 Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

is a common environmental species known to cause occupational allergic disease in grain handlers. We have recently observed azole-resistant isolates of this fungus as a cause of onychomycosis. To further characterize the cause of resistance, the genes encoding 14 α-sterol demethylase enzyme ( and ) were characterized and analyzed in 9 ITC-susceptible isolates and 6 isolates with high minimum inhibitory concentrations (MICs) of clinical (nail and sputum) and environmental strains. We found that six isolates with itraconazole MIC >16 mg/L demonstrated nonsynonymous mutations, including V51I, L378P, E483K, and E506G, and synonymous mutations, including F53F, A186A, Q276Q, and H359H. Moreover, P486S was detected in five strains with ITR MIC >16 mg/L. One mutation, F324S, was detected in an isolate with posaconazole MIC >16 mg/L. The effect of E483K and P486S mutations of CYP51A on azole resistance was further investigated using homology modeling and molecular dynamics. We found that E483K and P486S mutations were located near the ligand access channel of CYP51A that could partly lead to narrowing the entry of the ligand access channels. Therefore, we concluded that E483K and P486S mutations may potentially contribute to the limited access of inhibitors to the binding pocket and therefore confer resistance to azole agents.
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http://dx.doi.org/10.1089/mdr.2018.0300DOI Listing
June 2019

Candida auris otomycosis in Iran and review of recent literature.

Mycoses 2019 Feb;62(2):101-105

Department of Medical Mycology/Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Candida auris is a multidrug-resistant yeast emerging in immunocompromised and in otherwise healthy individuals. Due to difficulties in microbiological identification of C. auris because of the lack of available laboratory technology in developing countries, the number of patients affected is most likely underestimated. We report the first case of C. auris otitis which now adds Iran as the fifth country around the Persian Gulf, in addition to Kuwait, Oman, United Arab Emirates and Saudi Arabia. Candida auris is an unknown pathogen in routine laboratories in Iran because most Candida isolates are probably misdiagnosed. Otomycosis seems to be a different clinical presentation of C. auris mainly involving isolates from the East-Asian clade. We compared the mycological and clinical details of the Iranian patient with other cases of otitis reported since the last review of C. auris otomycosis in 2017.
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http://dx.doi.org/10.1111/myc.12886DOI Listing
February 2019

Molecular identification and antifungal susceptibility of clinical fungal isolates from onychomycosis (uncommon and emerging species).

Mycoses 2019 Feb 13;62(2):128-143. Epub 2018 Nov 13.

Department of Medical Mycology, Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Onychomycosis is a common nail problem, accounting for up to 50% of all nail diseases. The aim of the present study was to determine the species distribution based on the restriction fragment length polymorphism and susceptibility patterns of the causative agents of onychomycosis. This cross-sectional study was conducted on nail samples collected from 257 patients suspected of onychomycosis during 14 months. Fungal isolates were identified by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) with the enzymes Msp I, Mva I, Alw I and sequencing. According to the results, out of the 257 patients participating in the study, onychomycosis was diagnosed in 180 (70.03%) cases, among which 51.1% were caused by non-dermatophyte moulds (NDMs), 35% by yeast and 10.6% by dermatophytes. Numerous cryptic species recovered from onychomycosis for the first time. In the majority of cases, novel triazoles and imidazoles (ie, efinaconazole, luliconazole and lanoconazole) showed potent activity in comparison with other antifungal agents. The minimum inhibitory concentration (MIC) of luliconazole and lanoconazole ranged within 0.001 to >1 μg/mL and their geometric mean MICs were 0.0154 and 0.0309 μg/mL against all isolates, respectively. It seems that obtained data will be useful to improve the knowledge of researchers, clinicians and dermatologists about onychomycosis distribution, species diversity and adoption of appropriate treatment.
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http://dx.doi.org/10.1111/myc.12854DOI Listing
February 2019

Low Antifungal Activity of Tavaborole against Yeasts and Molds from Onychomycosis.

Antimicrob Agents Chemother 2018 12 26;62(12). Epub 2018 Nov 26.

Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

The activity of tavaborole, an FDA-approved antifungal drug, was compared to that of four antifungal agents against 170 clinical fungal isolates originating from patients with onychomycosis. Tavaborole had low activity against all isolates compared to itraconazole, terbinafine, and fluconazole, the principal choices for treatment of onychomycosis. Thus, it appears that tavaborole is not a candidate for the treatment of onychomycosis due to species, species, and dermatophytes.
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http://dx.doi.org/10.1128/AAC.01632-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256807PMC
December 2018

Identification of Mucorales in patients with proven invasive mucormycosis by polymerase chain reaction in tissue samples.

Mycoses 2018 Dec 28;61(12):909-915. Epub 2018 Aug 28.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Accurate diagnosis of mucormycosis, a life-threatening fungal infection, remains a challenge for physicians.

Objectives: To identify the causative Mucorales in fresh clinical samples and formalin-fixed paraffin-embedded (FFPE) samples of patients with proven mucormycosis by molecular method.

Patients/methods: Fresh clinical samples of patients with proven mucormycosis according to the EORTC/MSG criteria admitted between 2015 and 2017 and histopathologically proven FFPE archives collected during 2004-2007 and 2015-2017 from Mazandaran University-affiliated hospitals of northern Iran were included. Seminested PCR targeting the 18S rDNA of Mucorales and ITS region was performed, and PCR products were then sequenced.

Results: While culture was positive only in 5 of 9 (56%) of fresh specimen cases, PCR was positive in all 9 (100%) histologically proven mucormycosis. Ten of 18 (56%) FFPE samples were PCR-positive. Overall, Mucorales PCR was positive in 19 of 27 (70%) samples. Mucorales species were Rhizopus arrhizus in 16 (84%) cases, R. arrhizus/Amylomyces rouxii in 2 (10.5%) cases and Rhizopus stolonifer in one case (5.5%). Among 27 mucormycosis cases, 25 (93%) cases were rhinocerebral, and 2 (7%) cases were disseminated. Diabetes mellitus (74%) and neutropaenia (63%) were the main risk factors.

Conclusions: Seminested PCR targeting 18S rDNA region of Mucorales is useful for identification of the causative agents of mucormycosis.
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http://dx.doi.org/10.1111/myc.12837DOI Listing
December 2018

Potent Activities of Luliconazole, Lanoconazole, and Eight Comparators against Molecularly Characterized Fusarium Species.

Antimicrob Agents Chemother 2018 05 26;62(5). Epub 2018 Apr 26.

Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

A collection of clinical ( = 47) and environmental ( = 79) isolates were tested against 10 antifungal drugs, including 2 novel imidazoles. Luliconazole and lanoconazole demonstrated very low geometric mean MIC values of 0.005 and 0.013 μg/ml, respectively, compared with 0.51 μg/ml for micafungin, 0.85 μg/ml for efinaconazole, 1.12 μg/ml for natamycin, 1.18 μg/ml for anidulafungin, 1.31 μg/ml for voriconazole, 1.35 μg/ml for caspofungin, 1.9 μg/ml for amphotericin B, and 4.08 μg/ml for itraconazole. Results show that these drugs are potential candidates for (topical) treatment of skin and nail infections due to species.
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http://dx.doi.org/10.1128/AAC.00009-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923147PMC
May 2018

In vitro activity of new azoles luliconazole and lanoconazole compared with ten other antifungal drugs against clinical dermatophyte isolates.

Med Mycol 2016 Oct 26;54(7):757-63. Epub 2016 Apr 26.

Invasive Fungi Research Center (IFRC), Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

In vitro susceptibilities of 100 clinical dermatophyte isolates belonging to five species from Iran toward lanoconazole and luliconazole were compared with ten other antifungal agents including econazole, itraconazole, miconazole, fluconazole, griseofulvin, butenafine, terbinafine, caspofungin, anidulafungin and tolnaftate. MIC and MEC values were analyzed according to CLSI M38-A2 document. The isolates were previously identified to the species level using PCR-RFLP on ITS rDNA region. The range of luliconazole and lanoconazole minimum inhibitory concentrations (MICs) was 0.016-0.032 and 0.063-1 μg/ml, respectively for dermatophyte species. Luliconazole and lanoconazole revealed potent activity against all dermatophyte isolates. Anidulafungin, caspofungin, and luliconazole showed the best activity with the lowest geometric mean 0.01, 0.016, and 0.018 μg/ml, respectively, followed by tolnaftate (0.06 μg/ml), terbinafine (0.07 μg/ml), itraconazole (0.183 μg/ml), butenafine (0.188 μg/ml), econazole (0.20 μg/ml), lanoconazole (0.24 μg/ml), griseofulvin (1.28 μg/ml), miconazole (2.34 μg/ml) and fluconazole (15.34 μg/ml). The current study demonstrated luliconazole and lanoconazole displayed excellent activity against all dermatophyte isolates, although the majority of dermatophyte isolates showed low susceptibility to griseofulvin and very low to miconazole, and fluconazole.
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http://dx.doi.org/10.1093/mmy/myw016DOI Listing
October 2016

Genetic and Morphological Diversity of the Genus Penicillium From Mazandaran and Tehran Provinces, Iran.

Jundishapur J Microbiol 2016 Jan 9;9(1):e28280. Epub 2016 Jan 9.

Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran; Department of Nanobiomedicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran.

Background: The genus Penicillium contains a large number of ubiquitous environmental taxa, of which some species are clinically important. Identification of Penicillium down to the species level is currently based on polyphasic criteria, including phenotypic features and genetic markers. Biodiversity of the genus Penicillium from Mazandaran and Tehran provinces has not been described.

Objectives: The current paper focused on the environmental biodiversity of Penicillium isolates within some areas of Mazandaran and Tehran provinces, based on morphological traits and the molecular data from partial sequence of the β-tubulin (BT2) gene.

Materials And Methods: A total of 400 strains were isolated from the environment and investigated using morphological tests and sequencing of BT2, in order to characterize the spectrum of the Penicillium species.

Results: Sequence analysis of BT2 and morphological criteria of 20 strains representative of 10 species showed that Penicillium chrysogenum was the most prevalent species (n = 6), followed by P. polonicum (n = 3), P. glabrum (n = 2), P. palitans (n = 2), P. melanoconidium (n = 2), and other species, including P. expansum, P. canescense, P. griseofulvum, P. italicum, and P. raistrickii with one case each.

Conclusions: It was shown that partial β-tubulin sequence, as a reliable genetic target, supported specific morphological criteria for identification of the Penicillium species. Like other assessments throughout the world, P. chrysogenum remains the most frequent environmental Penicillium species in Mazandaran and Tehran Provinces.
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http://dx.doi.org/10.5812/jjm.28280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833887PMC
January 2016

Use of Restriction Fragment Length Polymorphism to Rapidly Identify Dermatophyte Species Related to Dermatophytosis.

Jundishapur J Microbiol 2015 Jun 30;8(6):e17296. Epub 2015 Jun 30.

Department of Medical Mycology and Parasitology, Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, IR Iran.

Background: Dermatophytes are a group of keratinophilic fungi worldwide, which can infect the skin, hair and nails of humans and animals. This genus includes several species that present different features of dermatophytosis. Although, laboratory diagnosis of dermatophytes is based on direct microscopy, biochemical tests and culture, these manners are expensive, time consuming and need skilled staff. Therefore, molecular methods like PCR-RFLP are the beneficial tools for identification, which are rapid and sensitive. Thus, dermatophyte species are able to generate characteristic band patterns on agarose gel electrophoresis using PCR-RFLP technique, which leads to successful identification at the species level within a 5-hour period.

Objectives: The purpose of this study was to study inter- and intraspecific genomic variations for identification of clinically important dermatophyte species obtained from clinical specimens in Isfahan, Iran using PCR-RFLP.

Materials And Methods: From March 2011 to August 2012, 135 clinical isolates were collected from infected patients at Isfahan, Iran. ITS1-5.8S-ITS2 region of rDNA was amplified using universal fungal primers. Subsequently, amplified products were digested by the MvaI restriction enzyme. Using discriminating band profiles on agarose gel, dermatophyte species were identified. However, DNA sequencing was used for unidentifiable strains.

Results: The specimens were obtained from skin scrapings (70.3%), nail (24.4%) and hair (5.1%) clippings. Most patients were between 21 - 30 years and the ratio of male to female was 93/42. Trichophyton interdigitale was the commonest isolate (52.5%) in our findings, followed by Epidermophyton floccosum (24.4%), T. rubrum (16.2%), Microsporum canis (2.2%), T. erinacei (1.4%), T. violaceum (1.4%), T. tonsurans (0.7%) and M. gypseum (0.7%) based on PCR-RFLP.

Conclusions: Combination of traditional methods and molecular techniques considerably improves identification of dermatophytes in the species level in clinical laboratories, which can lead to properly antifungal therapy and successful management of infections. However, restriction and specificity and sensitivity should be lowered and increased, respectively, to be useful for a wide variety of clinical applications.
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http://dx.doi.org/10.5812/jjm.8(5)2015.17296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541063PMC
June 2015

Molecular Characterization of Highly Susceptible Candida africana from Vulvovaginal Candidiasis.

Mycopathologia 2015 Dec 17;180(5-6):317-23. Epub 2015 Jul 17.

Department of Medical Mycology and Parasitology/Invasive Fungi Research Centre (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Phylogenetic studies highlight Candida africana as an atypical variant within Candida albicans species complex which is dominantly recovered from vaginal specimens. This study aimed to characterize C. africana isolates from patients with vulvovaginal candidiasis (VVC) by molecular methods and in vitro susceptibilities. One hundred and fifty-six (48.44%) Candida strains were collected from 322 patients diagnosed with VVC. Of these, 114 (73.07%) were germ tube positive and presented green color on the chromogenic medium, thus classified as C. albicans species complex. One hundred and nine (95.61%) out of 114 isolates were identified as C. albicans, while five (4.38%) isolates were identical with C. africana based on hwp1 PCR. C. africana appeared to be highly susceptible to the tested antifungals. For all strains of C. africana, fluconazole MIC was 2-log2-dilution steps less active than amphotericin B, which in turn was 2-log2-dilution steps and 3-log2-dilution steps less active than other azoles and echinocandin agents, respectively. In conclusion, among the C. albicans species complex, C. albicans predominantly and C. africana rarely occur in vaginal mucosa. Due to limited information on molecular epidemiology of this novel yeast, more studies using molecular methods are needed to elucidate the inter- and intraspecific genomic variations of C. africana isolates.
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http://dx.doi.org/10.1007/s11046-015-9924-zDOI Listing
December 2015

Endocarditis due to a co-infection of Candida albicans and Candida tropicalis in a drug abuser.

J Med Microbiol 2013 Nov 23;62(Pt 11):1763-1767. Epub 2013 Aug 23.

Department of Medical Mycology and Parasitology/Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

In recent decades the incidence of Candida endocarditis has increased dramatically. Despite the application of surgery and antifungal therapy, Candida endocarditis remains a life-threatening infection with significant morbidity and mortality. We report a 37-year-old male drug abuser presenting with high fever, chest pain, loss of appetite and cardiac failure. His echocardiography revealed mobile large tricuspid valve vegetations. Fungal endocarditis was confirmed by culturing of the resected vegetation showing mixed growth of Candida albicans and Candida tropicalis, although three consecutive blood cultures were negative for Candida species. Phenotypic identification was reconfirmed by sequencing of the internal transcribed spacer (ITS rDNA) region. The patient was initially treated with intravenous fluconazole (6 mg kg(-1) per day), followed by 2 weeks of intravenous amphotericin B deoxycholate (1 mg kg(-1) per day). Although MICs were low for both drugs, the patient's antifungal therapy combined with valve replacement failed, and he died due to respiratory failure.
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http://dx.doi.org/10.1099/jmm.0.060954-0DOI Listing
November 2013

Environmental study of azole-resistant Aspergillus fumigatus with TR34/L98H mutations in the cyp51A gene in Iran.

Mycoses 2013 Nov 14;56(6):659-63. Epub 2013 May 14.

Department of Medical Mycology and Parasitology/Invasive Fungi Research Center (IFRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Centre (MCBRC), School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Azole resistance in Aspergillus is emerging in European and Asian countries. As azoles are mainstay of therapy in the management of aspergillosis, azole resistance has serious implications in patient management. We report the emergence of resistance to triazoles in environmental Aspergillus fumigatus isolates in Iran. The TR34/L98H mutation was the only resistance mechanism. Overall 3.3% of the A. fumigatus isolates from hospital surroundings in Sari and Tehran had the same TR34/L98H STRAf genotype and were related to some resistant clinical and environmental TR34/L98H isolates from the Netherlands and India. It is emphasised that routine resistance surveillance studies focusing on environmental and clinical samples are warranted to yield the true prevalence of azole resistance in A. fumigatus in Iran.
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http://dx.doi.org/10.1111/myc.12089DOI Listing
November 2013

Comparison of diagnostic methods in the evaluation of onychomycosis.

Mycopathologia 2013 Apr 1;175(3-4):315-21. Epub 2013 Feb 1.

Department of Medical Mycology and Parasitology, Sari Medical School, Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Onychomycosis is a common nail problem, accounting for up to half of all nail diseases. Several nail disorders may mimic the onychomycosis clinically. Therefore, a sensitive, quick, and inexpensive test is essential for screening nail specimens for the administration of the proper drug. The aim of this study was to compare 4 different diagnostic methods in the evaluation of onychomycosis and to determine their sensitivity, specificity, positive predictive value, and negative predictive value. In a cross-sectional study, nail specimens were collected from 101 patients suspected to have onychomycosis during a 14-month period. The nail specimens were examined using potassium hydroxide (KOH) 20 %, KOH-treated nail clipping stained with periodic acid-Schiff (KONCPA), and calcofluor white (CFW) stain, and grew a fungal culture. The culture was chosen as the gold standard for statistical analysis using the McNemar and chi-square tests. Out of 101 patients, 100 (99 %) patients had at least 1 of the 4 diagnostic methods positive for the presence of organisms. The positive rates for the fungal culture, KOH preparation, CFW, and KONCPA were 74.2, 85.1, 91.09, and 99.01 %, respectively. The sensitivity and negative predictive value of KONCPA was 100 %. KONCPA was the most sensitive among the tests and was also superior to other methods in its negative predictive value. KONCPA was easy to perform, rapid, and gave significantly higher rates of detection of onychomycosis compared to the standard methods of KOH preparation and fungal culture. Therefore, KONCPA should be the single method of choice for the evaluation of onychomycosis.
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http://dx.doi.org/10.1007/s11046-013-9620-9DOI Listing
April 2013