Publications by authors named "Seyedmojtaba Seyedmousavi"

81 Publications

Differentiation of from Targeting the Gene.

Pathogens 2021 Oct 4;10(10). Epub 2021 Oct 4.

Clinical Center, Microbiology Service, Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, USA.

is one of the most important agents of invasive and non-invasive aspergillosis, especially in tropical and subtropical regions of the world, including Iran. is closely related to , and it is known for its economic importance in traditional fermentation industries. Reports of infection due to are scarce. Several studies reported that differentiating these two species in clinical laboratories is not possible using MALDI-TOF or by targeting fungal barcode genes, such as Internal Transcribed Spacer (ITS) and β-tubulin (). The species-level identification of causative agents and the determination of antifungal susceptibility patterns can play significant roles in the outcome of aspergillosis. Here, we aimed to investigate the discriminatory potential of PCR-sequencing versus that of the ITS, and calmodulin () genes for the differentiation of from . In a prospective study investigating the molecular epidemiology of in Iran between 2008 and 2018, out of 200 clinical isolates of , 10 isolates showed >99% similarity to both and . Overall, the ITS, β-tubulin and genes did not fulfil the criteria for differentiating these 10 isolates. However, the gene showed promising results, which warrants further studies using a larger set of isolates from more diverse epidemiological regions of the world.
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http://dx.doi.org/10.3390/pathogens10101279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541052PMC
October 2021

Genotyping and In Vitro Antifungal Susceptibility Profile of Neoscytalidium Species Isolates from Respiratory Tract.

Mycopathologia 2021 Dec 15;186(6):833-845. Epub 2021 Jul 15.

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

The fungus genus Neoscytalidium is mainly distributed in (sub) tropical regions of the world and has been essentially considered as a phytopathogen. There are however several reports of human infection caused by Neoscytalidium spp. through direct or indirect contact with contaminated plants or soil. Reliable and accurate identification to species level is critical for implementing proper therapeutic strategies. In the present study we investigated the genotypes and in vitro antifungal susceptibility patterns of Neoscytalidium species identified from respiratory tracts of patients with various underlying diseases. The identity and diversity of the isolates were done using PCR and sequencing of five different loci (the ITS region, D1/D2 domains of 28S rRNA gene, and part of the beta tubulin, elongation factor 1α and chitin synthase genes). The in-vitro antifungal susceptibility was also performed using the Clinical and Laboratory Standards Institute (CLSI) M38-Ed3-2017 guidelines. Overall, 13 isolates were identified as Neoscytalidium species (eight N. dimidiatum and five N. novaehollandiae). Two sequence types (STs) were identified by the alignment of 1846 combined base pairs among 13 clinical isolates. All isolates classified as N. dimidiatum were clustered in ST6 (61.5%) and those of N. novaehollandiae were in ST7 (38.5%). Luliconazole was the most active antifungal in vitro against species. This is the first report of N. novaehollandiae isolation from respiratory tracts samples. Further study from other regions of the world with a larger set of clinical specimens is required to provide additional insight into diversity of Neoscytalidium species.
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http://dx.doi.org/10.1007/s11046-021-00545-1DOI Listing
December 2021

Cutaneous hyalohyphomycosis due to following traumatic inoculation in an immunocompetent host.

Med Mycol Case Rep 2021 Jun 26;32:56-60. Epub 2021 Mar 26.

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

A common cause of subcutaneous mycoses in immunocompetent patients is traumatic inoculation. This is the first reported case of cutaneous infection with in a human host. A 49-year-old immunocompetent man sustained a splinter from his wooden deck, which resulted in a chronic cutaneous lesion. Originally identified as species on microscopic examination, genome sequencing of the internal transcribed spaces (ITS) region of ribosomal DNA (rDNA) identified the mold as , a common environmental fungus responsible for wood rot. The patient underwent excision and antifungal therapy with cure.
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http://dx.doi.org/10.1016/j.mmcr.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055524PMC
June 2021

Recent Advances in Genome Editing Tools in Medical Mycology Research.

J Fungi (Basel) 2021 Mar 30;7(4). Epub 2021 Mar 30.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari 481751665, Iran.

Manipulating fungal genomes is an important tool to understand the function of target genes, pathobiology of fungal infections, virulence potential, and pathogenicity of medically important fungi, and to develop novel diagnostics and therapeutic targets. Here, we provide an overview of recent advances in genetic manipulation techniques used in the field of medical mycology. Fungi use several strategies to cope with stress and adapt themselves against environmental effectors. For instance, mutations in the 14 alpha-demethylase gene may result in azole resistance in strains and shield them against fungicide's effects. Over the past few decades, several genome editing methods have been introduced for genetic manipulations in pathogenic fungi. Application of restriction enzymes to target and cut a double-stranded DNA in a pre-defined sequence was the first technique used for cloning in and . Genome editing technologies, including zinc-finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENs), have been also used to engineer a double-stranded DNA molecule. As a result, TALENs were considered more practical to identify single nucleotide polymorphisms. Recently, Class 2 type II Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology has emerged as a more useful tool for genome manipulation in fungal research.
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http://dx.doi.org/10.3390/jof7040257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067129PMC
March 2021

Antifungal Susceptibility Profiles of Olorofim (Formerly F901318) and Currently Available Systemic Antifungals against Mold and Yeast Phases of .

Antimicrob Agents Chemother 2021 05 18;65(6). Epub 2021 May 18.

Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

antifungal susceptibility profiling of 32 clinical and environmental isolates recovered from southern China was performed against olorofim and 7 other systemic antifungals, including amphotericin B, 5-flucytosine, posaconazole, voriconazole, caspofungin, and terbinafine, using CLSI methodology. In comparison, olorofim was the most active antifungal agent against both mold and yeast phases of all tested isolates, exhibiting an MIC range, MIC, and MIC of 0.0005 to 0.002 μg/ml, 0.0005 μg/ml, and 0.0005 μg/ml, respectively.
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http://dx.doi.org/10.1128/AAC.00256-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316025PMC
May 2021

Recognition of Diagnostic Gaps for Laboratory Diagnosis of Fungal Diseases: Expert Opinion from the Fungal Diagnostics Laboratories Consortium (FDLC).

J Clin Microbiol 2021 06 18;59(7):e0178420. Epub 2021 Jun 18.

Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Fungal infections are a rising threat to our immunocompromised patient population, as well as other nonimmunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing to detect and identify new, emerging or underrecognized, rare, or uncommon fungal pathogens; and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.
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http://dx.doi.org/10.1128/JCM.01784-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218742PMC
June 2021

Diagnosis of allergic bronchopulmonary aspergillosis in patients with persistent allergic asthma using three different diagnostic algorithms.

Mycoses 2021 Mar 8;64(3):272-281. Epub 2020 Dec 8.

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

Background: Allergic bronchopulmonary aspergillosis (ABPA) has been reported in various degrees among patients with persistent allergic asthma (PAA). Currently, there is no gold standard approach for diagnosis of ABPA.

Objectives: In the current study, we aimed the evaluation of three different mainly used algorithms as Rosenberg & Patterson (A), ISHAM Working Group (B) and Greenberger (C) for diagnosis of ABPA in 200 patients with underlying PAA.

Methods: All patients were evaluated using Aspergillus skin prick test (SPTAf), Aspergillus-specific IgE (sIgEAf) and IgG (sIgGAf), total IgE (tIgE), pulmonary function tests, radiological findings and peripheral blood eosinophil count. The prevalence rate of ABPA in PAA patients was estimated by three diagnostic criteria. We used Latent Class Analysis for the evaluation of different diagnostic parameters in different applied ABPA diagnostic algorithms.

Results: Aspergillus sensitisation was observed in 30 (15.0%) patients. According to algorithms A, B and C, nine (4.5%), six (3.0%) and 11 (5.5%) of patients were diagnosed with ABPA, respectively. The sensitivity and specificity of criteria B and C were (55.6% and 99.5%) and (100.0% and 98.9%) respectively. sIgEAf and sIgGAf showed the high significant sensitivity. The performance of algorithm A, in terms of sensitivity and specificity, was somewhat better than algorithm B.

Conclusion: Our study demonstrated that the sensitivity of different diagnostic algorithms could change the prevalence rate of ABPA. We also found that all of three criteria resulted an adequate specificity for ABPA diagnosis. A consensus patterns combining elements of all three criteria may warrant a better diagnostic algorithm.
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http://dx.doi.org/10.1111/myc.13217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902363PMC
March 2021

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

Inj Prev 2020 10 24;26(Supp 1):i125-i153. Epub 2020 Aug 24.

Department of Pharmacy, Adigrat University, Adigrat, Ethiopia.

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria.

Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced.

Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes.

Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.
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http://dx.doi.org/10.1136/injuryprev-2019-043531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571362PMC
October 2020

Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017.

Inj Prev 2020 10 24;26(Supp 1):i96-i114. Epub 2020 Apr 24.

Faculty of Health Sciences - Health Management and Policy, American University of Beirut, Beirut, Lebanon.

Background: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries.

Methods: We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs).

Findings: In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505).

Interpretation: Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.
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http://dx.doi.org/10.1136/injuryprev-2019-043494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571366PMC
October 2020

Multicenter Cryptococcal Antigen Screening of HIV-Infected Patients in Iran.

Curr Microbiol 2020 Aug 15;77(8):1667-1672. Epub 2020 Apr 15.

Microbiology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.

Early diagnosis and targeted preemptive antifungal treatment are crucial in reducing cryptococcal meningitis (CM)-related mortality in individuals living with human immunodeficiency virus (HIV). The present study was performed to determine cryptococcal antigenemia and outcomes among HIV-infected patients in Iran. This multicenter prospective study was conducted between October 2016 and December 2018. For the purpose of the study, blood samples were randomly collected from 177 profoundly immunosuppressed (CD4+ counts < 200 cells/µL) HIV-positive individuals in six major cities of Iran. The patients were antiretroviral therapy-naive or had received inadequate medication. The stored sera were screened for cryptococcal antigen (CrAg), using point-of-care lateral flow assay (IMMY® diagnostics, Norman, OK, US). Overall, out of the 174 asymptomatic patients, 3 (1.72%) cases were CrAg-positive using the LFA in serum. Accordingly, the prevalence of cryptococcal antigenemia was 7.14%, 0%, and 1.2% in the patients with the CD4+ counts of < 50, 50-100, and 100-200 cells/μL, respectively. The median age of the patients with antigenemia was 36 years (age range 8-55 years). The median CD4+ count of the cohort was 98 cells/μL (range 14-200 cells/μL). Routine screening of Iranian HIV-infected patients with CD4+ count of < 50 cells/µL before initiating antiretroviral therapy is justified. It is suggested to conduct more inclusive research throughout the whole country on more patients to recommend screening cryptococcal antigen strongly.
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http://dx.doi.org/10.1007/s00284-020-01970-zDOI Listing
August 2020

Annotated Genome Sequence of NIH1004.

Microbiol Resour Announc 2020 Jan 16;9(3). Epub 2020 Jan 16.

Department of Infectious Disease, J. Craig Venter Institute, Rockville, Maryland, USA

The annotated genome of , a recently discovered drug-resistant pathogen, was determined by employing the Oxford Nanopore MinION platform and the Funannotate pipeline. The genome size and the number of protein-coding genes are notably larger than those of the most common etiological agent of aspergillosis, .
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http://dx.doi.org/10.1128/MRA.01374-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965580PMC
January 2020

Recovered From Olive Trees () in Turkey Reveal Allopatry With African and South American Lineages.

Front Cell Infect Microbiol 2019 8;9:384. Epub 2019 Nov 8.

Division of Mycology, Department of Microbiology, Faculty of Medicine, University of Çukurova, Adana, Turkey.

species are life-threatening human fungal pathogens that cause cryptococcal meningoencephalitis in both immunocompromised and healthy hosts. The natural environmental niches of include pigeon () guano, soil, and a variety of tree species such as , and spp. Genetic and genomic studies of extensive sample collections have provided insights into the population distribution and composition of different species in geographic regions around the world. However, few such studies examined in Turkey. We sampled 388 (olive) and 132 . trees from seven locations in coastal and inland areas of the Aegean region of Anatolian Turkey in September 2016 to investigate the distribution and genetic diversity present in the natural population. We isolated 84 strains (83 α and 1 ) and 3 strains (all α) from 87 (22.4% of surveyed) . trees; a total of 32 . strains were isolated from 32 (24.2%) of the . trees, all of which were α. A statistically significant difference was observed in the frequency of . isolation between coastal and inland areas ( < 0.05). Interestingly, the . isolate was fertile in laboratory crosses with VNI and VNB α tester strains and produced robust hyphae, basidia, and basidiospores, thus suggesting potential sexual reproduction in the natural population. Sequencing analyses of the gene identified at least five different genotypes among the isolates. Population genetics and genomic analyses revealed that most of the isolates in Turkey belong to the VNBII lineage of . , which is predominantly found in southern Africa; these isolates are part of a distinct minor clade within VNBII that includes several isolates from Zambia and Brazil. Our study provides insights into the geographic distribution of different . lineages in the Mediterranean region and highlights the need for wider geographic sampling to gain a better understanding of the natural habitats, migration, epidemiology, and evolution of this important human fungal pathogen.
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http://dx.doi.org/10.3389/fcimb.2019.00384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856141PMC
August 2020

Molecular epidemiology and antifungal susceptibility profiles of clinical species complex.

J Med Microbiol 2020 Jan;69(1):72-81

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

Limited data regarding the epidemiology and susceptibility profiles of cryptococcosis are available in the Middle East. Our study aimed to evaluate the molecular diversity, mating types and antifungal susceptibility pattern of species (=14) isolated from 320 suspected patients with cryptococcosis. The gene was subjected to restriction fragment length polymorphism and sequence analysis. In addition, antifungal susceptibility testing was performed by Clinical and Laboratory Standards Institute (CLSI) M27-A4 and M59 guidelines. Overall, 14 (4.4 %) patients were confirmed as cryptococcosis. Based on molecular type, 85.7 and 14.3 % of the isolates were VN I and VN II, respectively. Phylogenetic analysis of gene sequences revealed clustering of VN I and VN II isolates into two distinct clades with a substantial difference within each molecular type. Voriconazole and 5-fluorocytosine, respectively, had the lowest (0.031 μg ml) and highest (8 µg ml) MICs. The epidemiological cutoff values (ECVs) for amphotericin B, fluconazole, voriconazole and 5-fluorocytosine encompassed ≥97 % of all 14 . VN I species. However, according to the CLSI document M59, ECVs for itraconazole (7; 50 % of the isolates) and for posaconazole (1; 7.1 % of the isolate), were one log2 dilution higher than the wild type range. Combinations of amphotericin B with 5-fluorocytosine, amphotericin B with fluconazole and fluconazole with 5-fluorocytosine exhibited synergistic effects against 37, 31 and 12.5 % of the isolates, respectively. Our findings may significantly contribute to the development of management strategies for patients at a higher risk of cryptococcosis, particularly HIV-positive individuals.
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http://dx.doi.org/10.1099/jmm.0.001101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137767PMC
January 2020

Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.

Lancet Infect Dis 2019 12 5;19(12):e405-e421. Epub 2019 Nov 5.

InfectiousDisease Research Program, Department of Paediatric Hematology/Oncology and Center for Bone Marrow Transplantation, University Children's Hospital Münster, Münster, Germany.

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
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http://dx.doi.org/10.1016/S1473-3099(19)30312-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559573PMC
December 2019

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.

Nature 2019 10 16;574(7778):353-358. Epub 2019 Oct 16.

School of Health Sciences, Madda Walabu University, Bale Goba, Ethiopia.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.
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http://dx.doi.org/10.1038/s41586-019-1545-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800389PMC
October 2019

Genetic diversity and antifungal susceptibility patterns of Aspergillus nidulans complex obtained from clinical and environmental sources.

Mycoses 2020 Jan 3;63(1):78-88. Epub 2019 Nov 3.

Medical Mycology Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

The molecular epidemiology and antifungal susceptibility of Aspergillus nidulans species complex has not been well studied. To evaluate the genetic diversity and antifungal susceptibility patterns of clinical and environmental isolates of A. nidulans complex. Sixty clinical and environmental isolates of Aspergillus section Nidulantes were collected from five countries (Iran, The Netherlands, Spain, Portugal and Greece). The species were molecularly identified by sequencing of β-tubulin gene. The genetic diversity of A nidulans complex isolates (n = 54) was determined with a microsatellite genotyping assay. Antifungal susceptibility profile was determined using EUCAST method. The isolates were classified as A nidulans (46.7%), A spinulosporus (26.6%), A quadrilineatus (10%), A pachycristatus (3.3%), A rugulosus (3.3%), A unguis (5%), A creber, (1.7%), A olivicola (1.7%) and A sydowii (1.7%). Thirty-four sequence types (STs) were identified among the 54 A nidulans complex isolates. A high level of genetic diversity was found among A nidulans sensu stricto strains but low diversity was found among A spinulosporus strains. Amphotericin B showed high MICs to all species. The most active azole was posaconazole (GM = 0.64 mg/L), while itraconazole showed the highest MICs among azoles (GM = 2.95 mg/L). A spinulosporus showed higher MICs than A nidulans sensu stricto for all antifungals except for micafungin and anidulafungin. Interspecies variations may result in differences in antifungal susceptibility patterns and challenge antifungal therapy in infections caused by A nidulans. Differences in the distribution of STs or persistence of multiple STs might be related to the sources of isolation and niche specialisation.
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http://dx.doi.org/10.1111/myc.13019DOI Listing
January 2020

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study.

JAMA Oncol 2019 12;5(12):1749-1768

Department of Family and Community Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

Conclusions And Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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http://dx.doi.org/10.1001/jamaoncol.2019.2996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777271PMC
December 2019

Discrimination of Aspergillus flavus from Aspergillus oryzae by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry.

Mycoses 2019 Dec 15;62(12):1182-1188. Epub 2019 Oct 15.

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

Background: Aspergillus flavus is a major cause of severe non-invasive fungal infections in the Middle Eastern countries. However, it is difficult to distinguish A flavus from A oryzae.

Objectives: To assess the potential of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in discriminating between A flavus and A oryzae and compare it with β-tubulin gene sequencing.

Methods: We used the Bruker Daltonik MALDI-TOF MS system to analyse 200 clinical and environmental A flavus isolates and one A pseudonomius and one A alliaceus (Aspergillus section Flavi) isolate a priori identified as such by sequencing of the β-tubulin gene.

Results: All 200 A flavus isolates were identified at the genus level and 176 (88%) at the species levels by MALDI-TOF MS based on the spectral log-scores (≥2.0 and 1.7-1.99, respectively); among them, only 18 (10.2%) were confirmed as A flavus, whereas 35 (19.9%) were identified as A oryzae and 123 (69.9%) as A flavus/A oryzae. Aspergillus pseudonomius and A alliaceus were misidentified as A flavus and A parasiticus with log-score values of 1.39 and 1.09, respectively.

Conclusions: The results indicate that the commercially available Bruker Daltonik MALDI-TOF MS score database cannot separate A flavus and A oryzae species. We also showed that establishment of an in-house library is a useful tool to discriminate closely related Aspergillus species, including A flavus and A oryzae.
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http://dx.doi.org/10.1111/myc.13010DOI Listing
December 2019

National trends in incidence, prevalence and disability-adjusted life years of invasive aspergillosis in Iran: a systematic review and meta-analysis.

Expert Rev Respir Med 2019 11 26;13(11):1121-1134. Epub 2019 Aug 26.

The University of Manchester , Manchester , NH , USA.

: We aimed to study the epidemiology, prevalence, incidence, clinical manifestations, underlying diseases, treatments, outcomes, and societal impact through disability-adjusted life years (DALYs) of IA in Iran. : A random-effect meta-analytic model was fitted to estimate the prevalence and incidence of IA in Iran. We also calculated DALYs. : Out of 79 published studies during the past 25 years from Iran, 23 met the inclusion criteria. A total of 2947 patients were included, of whom 396 (13.4%) patients were diagnosed with IA according to EORTC/MSG and ICU criteria. The main underlying condition for IA was hematologic disorders (39.4%). 86 (43%) was the most common isolate. The pooled prevalence and incidence rates were 20.5 (95% CI 12.5 to 29.9) and 4.8 (95% CI 2.3-8.2) per 100,000 population, respectively. Total DALYs was estimated 164.13 per 100,000 population. YLLs constitute the majority of IA burden compared to YLDs (162.80 YLLs/100,000 population vs 1.33 YLDs per 100,000 population). The highest YLL rates were found in people aged 45-49 (62.9 YLLs/100,000 population) and 30-34 years (45.2 YLLs/100,000 population), respectively. : This study indicates an increasing burden of IA in Iran, despite the extensive use of prophylaxis, challenging the public health, especially immunocompromised patients.
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http://dx.doi.org/10.1080/17476348.2019.1657835DOI Listing
November 2019

Identification of clinical dermatophyte isolates obtained from Iran by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Curr Med Mycol 2019 Jun;5(2):22-26

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

Background And Purpose: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used to discriminate among pathogenic microorganisms in clinical laboratories. The aim of this study was to assess the utility of MALDI-TOF MS in the routine identification of clinical dermatophyte isolates obtained from various geographical regions of Iran.

Materials And Methods: A total of 94 isolates, including (n=44), (n=40), (n=4), (n=4), and (=1), were analyzed in this study. The identity of each isolate was determined by polymerase chani reaction amplification and sequencing of the internal transcribed spacer (ITS) region of nuclear-encoded ribosomal DNA and also MALDI-TOF MS. The obtained data by molecular approach were compared with MALDI-TOF MS.

Results: The MALDI-TOF MS led to the identification of 44 (47%) isolates at the species level by generating the spectral score values of ≥ 2.0. However, there was not sufficient agreement between the results of the molecular-based ITS identification methods and MALDI-TOF MS in the species identification of 16 (17%) isolates. The Bruker Daltonics database was also not able to identify protein spectra related to 12 isolates (13%), including . (n=5), . (n=4), . (n=2), and . (n=1).

Conclusion: According to the results, the utility of MALDI-TOF MS as a routine diagnostic tool for the accurate and reliable identification of dermatophytes can be justified whenever the protein spectra of a large set of worldwide clinical isolates are included in the commercial libraries. In addition, MALDI-TOF MS can be alternatively used to construct an in-house reference database.
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http://dx.doi.org/10.18502/cmm.5.2.1157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626716PMC
June 2019

Ochroconis globalis infecting Atlantic salmon (Salmo salar), with a review of Ochroconis species in cold-blooded animals.

J Fish Dis 2019 Jun 12;42(6):947-957. Epub 2019 Apr 12.

Center of Expertise in Mycology of Radboudumc/Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Necropsy examination of an adult Atlantic salmon (Salmo salar) from the Dalälven River in Sweden revealed numerous large, white nodules, with spherical cysts and granulomata in kidney and liver. Histopathology showed dark, septate, thin-walled hyphae. The aetiologic agent was found to be an Ochroconis species (Venturiales) that differed from known fish-associated species of the genus. Molecular phylogenetic studies of the culture (strain UIII09 = CBS 135766) demonstrated that Ochroconis globalis was concerned. The isolate proved to be susceptible to all investigated antifungals, as it is known for another Ochroconis species. The role of Ochroconis in opportunism of cold-blooded animals was discussed, and the diagnostic methods using DNA sequences for routine identification of the fungus were proposed.
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http://dx.doi.org/10.1111/jfd.12999DOI Listing
June 2019

Antifungal Susceptibility Profile of Candida Albicans Isolated from Vulvovaginal Candidiasis in Xinjiang Province of China.

Mycopathologia 2019 Jun 9;184(3):413-422. Epub 2019 Apr 9.

The People's Hospital of Suzhou National New & Hi-Tech Industrial Development Zone, Suzhou, Jiangsu, China.

We investigated the antifungal susceptibility profiles of 207 independent Candida albicans strains isolated from patients with vulvovaginal candidiasis (VVC) in Xinjiang Province of China. Using CLSI M27-A3 and M27-S4 guidelines, anidulafungin and micafungin were the most active drugs against C. albicans showing an MIC/MIC corresponding to 0.016/0.0313 µg/mL, followed by caspofungin (0.25/0.25 µg/mL), posaconazole (0.125/0.5 µg/mL), ravuconazole (0.063/1 µg/mL), itraconazole (0.125/1 µg/mL), amphotericine B (0.5/1 µg/mL), isavuconazole (0.063/2 µg/mL), 5-flucytosine (1/2 µg/mL), voriconazole (0.125/4 µg/mL), and fluconazole (0.5/4 µg/mL). 96.1% (199)-100.0% (207) isolates were sensitive to the three echinocandins tested, amphotericine B and 5-flucytosine. The in vitro activity of triazoles against all isolates tested was variable; itraconazole and voriconazole had reduced the activity to almost half of the isolates (55.1% (114) and 51.2% (106) susceptible, respectively). Fluconazole was active against 76.3% (158) isolates tested. The new triazoles ravuconazole, isavuconazole and posaconazole showed good in vitro potency against 89.9% (186)-95.2% (197) of isolates with the geometric mean MIC (µg/mL) of 0.10, 0.12 and 0.14 µg/mL, respectively. In conclusion, our study indicates that for effective management of systemic candidiasis in Xinjiang Province of China, it is important to determine the susceptibility profiles of isolated C. albicans from patients with VVC.
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http://dx.doi.org/10.1007/s11046-018-0305-2DOI Listing
June 2019

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

Burden of fungal infections in Iran.

J Infect Dev Ctries 2018 10 31;12(10):910-918. Epub 2018 Oct 31.

The University of Manchester, Manchester, United Kingdom.

Introduction: The number of fungal infections occurring each year in Iran is not known. As the burden of fungal disease is a measure used to assess and compare the relative impact of different type of fungal diseases on populations, we have estimated the burden of fungal diseases in Iran.

Methodology: We estimated the burden of human fungal diseases based on the specific populations at risk, existing epidemiological data in both local and international databases, and modelling previously described by the LIFE program (http://www.LIFE-worldwide.org).

Results: Among the population of Iran (79,926,270 in 2016), 6,670,813 (8.3%) individuals are estimated to suffer from a fungal infection each year. A total of 2,791,568 women aged between 15 and 50 years are estimated to suffer from recurrent vulvovaginal candidiasis, annually. In addition, considering the 13.3% prevalence rate of tinea capitis in children, a total of 2,552,624 cases per year are estimated. The estimated burden of invasive aspergillosis in the 3 groups of patients with hematologic malignancy, lung cancer and chronic pulmonary obstructive disease was 6394 (8.0 per 100,000). The estimate for the burden of allergic disease related to fungi including allergic bronchopulmonary aspergillosis, severe asthma with fungal sensitization and allergic fungal rhinosinusitis was 272,095 (340 per 100,000). Based on the 28,663 cases of HIV infection reported, an estimated 900 and 113 cases with pneumocystosis and cryptococcal meningitis are annually anticipated, respectively.

Conclusion: Our estimates indicate that the importance of fungal infections is high but overlooked in Iran, which warrants further actions by health care authorities.
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http://dx.doi.org/10.3855/jidc.10476DOI Listing
October 2018

In-vitro antifungal susceptibility testing of lanoconazole and luliconazole against Aspergillus flavus as an important agent of invasive aspergillosis.

J Infect Chemother 2019 Feb 18;25(2):157-160. Epub 2018 Sep 18.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Middle East Center of Excellence for Infection Biology and Antimicrobial Pharmacology, Tehran, Iran; Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases (LCID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Introduction: The incidence of Aspergillus infections has recently increased remarkably in certain tropical and sub-tropical countries, with Aspergillus flavus being identified as the leading cause of infections after A. fumigatus. Lanoconazole (LAN) and luliconazole (LUL) are currently approved for topical treatment of cutaneous fungal infections. We aimed the in-vitro antifungal susceptibility testing of two imidazole, LAN and LUL against A. flavus.

Methods: One hundred and eighty-seven clinical and environmental A. flavus were tested originating from different climate zones of Iran between 2008 and 2015. The identification of all isolates was confirmed by using PCR-sequencing of β-tubuline ribosomal DNA gene. In-vitro antifungal susceptibility test was performed using CLSI guidelines against LAN, LUL, itraconazole (ITC), voriconazole (VRC), posaconazole (POS), Isavuconazole (ISA), amphotericin B (AMB), 5-flucytosine (5FC), caspofungin (CAS) and anidulafungin (AFG). The minimum inhibitory concentration (MIC) and minimum effect concentration (MEC) values were evaluated according to CLSI M38-A2 guidelines.

Results: The geometric mean MICs for tested antifungals, in increasing order, were: 0.009 μg/mL for LUL (ranging from 0.004 to 0.062), 0.02 μg/mL for LAN (ranging from 0.004 to 0.125), POS (0.10), ISA (0.16), ITC (0.24), VRC (0.27), AMB (1.8) and 5FC (63.06) μg/mL. The mean value of MECs for AFG and CAS were 0.06 and 0.07, respectively.

Conclusion: Overall, LUL and LAN showed the lowest MIC against all isolates of A. flavus. Further studies are required to evaluate the in-vivo efficacy of these agents, and the possibility of using these agents in systemic infections.
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http://dx.doi.org/10.1016/j.jiac.2018.07.018DOI Listing
February 2019

Estimated burden of serious human fungal diseases in Turkey.

Mycoses 2019 Jan 21;62(1):22-31. Epub 2018 Sep 21.

The National Aspergillosis Centre, Wythenshawe Hospital, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological data from 1920 to 2017 and modelling previously described by the LIFE program (http://www.LIFE-worldwide.org). Among the population of Turkey (80.8 million in 2017), approximately 1 785 811 (2.21%) people are estimated to suffer from a serious fungal infection each year. The model used predicts high prevalences of allergic fungal rhinosinusitis episodes (312 994 cases) (392/100 000), of severe asthma with fungal sensitisation (42 989 cases) (53.20 cases/100 000 adults per year), of allergic bronchopulmonary aspergillosis (32 594 cases) (40.33/100 000), of fungal keratitis (26 671 cases) (33/100 000) and of chronic pulmonary aspergillosis (5890 cases) (7.29/100 000). The estimated annual incidence for invasive aspergillosis is lower (3911 cases) (4.84/100 000 annually). Among about 22.5 million women aged 15-50 years, recurrent vulvovaginal candidiasis is estimated to occur in 1 350 371 (3342/100 000) females. The burden of three superficial fungal infections was also estimated: tinea pedis (1.79 million), tinea capitis (43 900) and onychomycosis (1.73 million). Given that the modelling estimates reported in the current study might be substantially under- or overestimated, formal epidemiological and comprehensive surveillance studies are required to validate or modify these estimates.
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http://dx.doi.org/10.1111/myc.12842DOI Listing
January 2019

MGL_3741 gene contributes to pathogenicity of Malassezia globosa in pityriasis versicolor.

Mycoses 2018 Dec 23;61(12):938-944. Epub 2018 Sep 23.

Department of Medical Mycology & Parasitology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Dihydroxyacid dehydratase (DHAD) is a key enzyme in biosynthetic pathway of isoleucine and valine. This pathway is absent in human but exists in various organisms such as fungi. Using RNA-seq analysis in this study, we identified MGL_3741gene which encodes DHAD protein in Malassezia globosa (M. globosa). Furthermore, we found that mentioned gene is homologous to the Ustilago maydis, Saccharomyces cerevisiae, Aspergillus flavus, and Aspergillus fumigatus ILV3P. For understanding the probable role of this gene in pathogenicity of M. globosa, we applied Real-time PCR to investigate the differentially expressed of the MGL_3741 gene in healthy and pathogenic states. Our results indicate a significant difference between two mentioned stats. These results revealed that ILV3-like gene in M. globosa can be related to the pathogenicity of this yeast.
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http://dx.doi.org/10.1111/myc.12840DOI Listing
December 2018

Genetic Diversity and Antifungal Susceptibility of Candida parapsilosis Sensu Stricto Isolated from Bloodstream Infections in Turkish Patients.

Mycopathologia 2018 Aug 3;183(4):701-708. Epub 2018 May 3.

Department of Microbiology and Immunology, Center of Excellence for Infection Biology and Antimicrobial Pharmacology, Tehran, Iran.

Candida parapsilosis sensu stricto is an emerging cause of hospital-acquired Candida infections, predominantly in southern Europe, South America, and Asia. We investigated the genetic diversity and antifungal susceptibility profile of 170 independent C. parapsilosis sensu stricto strains obtained from patients with candidemia who were treated at the Ege University Hospital in Izmir, Turkey, between 2006 and 2014. The identity of each strain was confirmed via PCR amplification and digestion of the secondary alcohol dehydrogenase-encoding gene. The 24-h geometric mean minimum inhibitory concentrations of the antifungal agents, in increasing order, were as follows: posaconazole, 0.10 µg/mL; voriconazole, 0.21 µg/mL; caspofungin, 0.38 µg/mL; amphotericin B, 0.61 µg/mL; anidulafungin, 0.68 µg/mL; and fluconazole, 2.95 µg/mL. Microsatellite genotyping of the isolates (using fluorescently labeled primers and a panel of four different short-nucleotide repeat fragments) identified 25, 17, 17, and 8 different allelic genotypes at the CP6, B5, CP4, and CP1 locus, respectively. Posaconazole, caspofungin, and amphotericin B showed the greatest in vitro activity of the tested systemic azole, echinocandin, and polyene agents, respectively, and the observed antifungal susceptibility of the isolates was shown to be independent of their isolation source. We obtained a combined discriminatory power of 0.99 with a total of 130 genotypes for 170 isolates tested. Finally, microsatellite profiling analysis confirmed the presence of identical genotype between separate isolates, supporting that effective surveillance and infection-prevention programs are essential to limit the impact of C. parapsilosis sensu stricto on hospitalized patients' health.
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http://dx.doi.org/10.1007/s11046-018-0261-xDOI Listing
August 2018

Genetic diversity and antifungal susceptibility of Candida albicans isolated from Iranian patients.

Med Mycol 2019 Jan;57(1):127-131

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

A total of 105 independent Candida albicans strains isolated from patients in Iran were investigated. According to CLSI documents M27-A3 and M27-S4, the 24 h geometric mean MICs of caspofungin, itraconazole, and fluconazole were 0.27, 3.19, and 11.91 μg/ml, respectively. Microsatellites analysis of CEF3, CAIII, LOC4 Loci identified 93 different allelic genotypes clustered apart into six different clades. Antifungal susceptibility was not linked with the source of isolation and the corresponding genotype of C. albicans strains.
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http://dx.doi.org/10.1093/mmy/myy016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506605PMC
January 2019
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