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      High prevalence of mixed infections in global onychomycosis

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          Abstract

          Onychomycosis is estimated at a prevalence of 10% worldwide with the infecting organism most commonly Trichophyton rubrum ( T. rubrum). Traditional culture identification of causative organisms has inherent risks of overestimating dermatophytes, like T. rubrum, by inhibiting the growth of possible nondermatophyte mould (NDM) environmental contaminants which could be causative agents. Recently, molecular methods have revealed that a proportion of onychomycosis cases in North America may be caused by mixed infections of T. rubrum as an agent co-infecting with one or more NDM. Determining the global burden of mixed infections is a necessary step to evaluating the best therapies for this difficult-to-treat disease. To determine the prevalence of mixed infections in a global population, nail samples from onychomycosis patients in Brazil, Canada, and Israel (n = 216) were analyzed by molecular methods for the presence of dermatophytes and five NDMs. If an NDM was detected, repeat sampling was performed to confirm the NDM. T. rubrum was detected in 98% (211/216) of infections with 39% mixed (84/216). The infection type was more likely to be mixed in samples from Brazil, but more likely to be a dermatophyte in samples from Canada and Israel (Χ 2 = 16.92, df = 2, P<0.001). The most common cause of onychomycosis was T. rubrum. In all countries (Brazil, Canada and Israel combined) the prevalence of dermatophyte (Χ 2 = 211.15, df = 3, P<0.001) and mixed (dermatophyte and NDM; Χ 2 = 166.38, df = 3, P<0.001) infection increased with patient age. Our data suggest that mixed infection onychomycosis is more prevalent than previously reported with the aging population being at increased risk for mixed infections.

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          Toenail onychomycosis: an important global disease burden.

          Onychomycosis is a fungal infection of the nail plate or nail bed. It does not usually cure itself and it can trigger more infectious lesions in other parts of the body. The reported prevalence of onychomycosis is increasing in Western countries, presumably due to lifestyle changes and the ageing of the population. Approximately 10% of the general population, 20% of the population aged>60 years, up to 50% of people aged>70 years and up to one-third of diabetic individuals have onychomycosis. Care should be taken for the accurate diagnosis and timely treatment of toenail onychomycosis to prevent complications. Current treatment options have relatively limited therapeutic success, particularly long-term. Oral medications are associated with high recurrence rates and treatment failure, and are not suitable for many cases due to potential adverse effects. Topical medications are recommended only for mild to moderate cases. The cost of therapies may also be prohibitive in some cases. In the light of these issues, more research is warranted for the investigation and development of more effective and economical options for the treatment and prophylaxis of toenail onychomycosis. In patient populations such as diabetic individuals, where onychomycosis can provoke lower extremity complications, professional podiatry care of toenails and feet should be encouraged. Copyright © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.
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            Prevalence and epidemiology of onychomycosis in patients visiting physicians' offices: a multicenter canadian survey of 15,000 patients.

            A prospective, multicenter study to determine the epidemiology of onychomycosis was performed in the offices of 3 dermatologists and 1 family physician in Ontario, Canada. In the sample of 15,000 patients, abnormal-appearing nails were observed in 2505 persons (16. 7%). There were 1199 patients (8%) with toenail or fingernail onychomycosis confirmed on mycologic examination, with 1137 patients (7.6%) who had only pedal onychomycosis, 40 patients with toenail and fingernail onychomycosis (0.27%), and 22 patients (0.15%) with only fingernail onychomycosis. The condition was more common in male patients (P or =75% nail involvement) in 27.6%, 39.9%, and 32.5% of patients, respectively. After adjusting for the age and sex distribution of the general population, the projected rate of onychomycosis in Canada is 6.5% (95% confidence interval [CI], 6. 1%-6.9%). The organisms causing toenail onychomycosis were 90.5% dermatophyte, 7.8% nondermatophyte molds, and 1.7% Candida spp. The corresponding organisms causing fingernail onychomycosis were 70.8%, 0%, and 29.2%, respectively. In a large sample of 15,000 patients, abnormal-appearing nails were present in 17% of the sample with mycologic evidence of toenail or fingernail onychomycosis in 8%. The projected prevalence of onychomycosis in Canada is 6.5% (95% CI, 6. 1%-6.9%).
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              Systematic review of nondermatophyte mold onychomycosis: diagnosis, clinical types, epidemiology, and treatment.

              Nondermatophyte mold (NDM) onychomycosis is difficult to diagnose given that NDMs are common contaminants of the nails and of the mycology laboratory. Diagnostic criteria and definition of cure are inconsistent between studies, which may affect the quality of published data. We identified 6 major criteria used in the literature: identification of the NDM in the nail by microscopy (using potassium hydroxide preparation), isolation in culture, repeated isolation in culture, inoculum counting, failure to isolate a dermatophyte in culture, and histology. Most studies used 3 or more of these (range = 1-5). We recommend using at least 3 of the criteria to rule out contamination; these should include potassium hydroxide preparation for direct microscopy and isolation of the organism in culture. We review geographic distribution and clinical presentations associated with different NDMs. The treatment with the greatest quantity of data and highest reported cure rates is terbinafine, for the treatment of Scopulariopsis brevicaulis and Aspergillus species infections. Topicals such as ciclopirox nail lacquer may also be effective (data originating from Scopulariopsis brevicaulis and Acremonium species infections), especially when combined with chemical or surgical avulsion of the nail. We recommend that future studies use (and clearly indicate) at least 3 of the main criteria for diagnosis, and report the clinical type of onychomycosis and the isolated organism. When evaluating different treatments, we suggest that authors clearly define their efficacy outcomes.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 September 2020
                2020
                : 15
                : 9
                : e0239648
                Affiliations
                [1 ] Department of Medicine, the University of Toronto, Toronto, Ontario, Canada
                [2 ] Mycology Section, Mediprobe Research Inc., London, Ontario, Canada
                [3 ] Cosmetic Dermatology and Laser Center (Delcentro), Bauru, São Paulo, Brazil
                [4 ] Sackler School of Medicine, Chaim Sheba Medical Center, the Tel-Aviv University, Tel-Hashomer, Israel
                [5 ] Sporometrics, Toronto, Ontario, Canada
                [6 ] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
                University of California Riverside, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-8664-7723
                Article
                PONE-D-19-18391
                10.1371/journal.pone.0239648
                7523972
                32991597
                96d97a48-e9f9-49e4-906c-079729485105
                © 2020 Gupta et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 June 2019
                : 10 September 2020
                Page count
                Figures: 0, Tables: 3, Pages: 8
                Funding
                The authors received no specific funding for this work. Mediprobe Research is the research group founded and funded soley by Dr. Gupta. There is no external funding. The study was funded solely by Dr. Gupta in its entirety. In Canada some of the doctors set up Research Groups through which their research is performed. Cosmetic Dermatology and Laser Center (Delcentro) is the name of the clinic that was founded by Dr. Taborda and Dr Taborda. This clinic is self-funded in its entirety by these doctors; there is no external funding.
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                Asia
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                Medicine and Health Sciences
                Medical Conditions
                Skin Diseases
                Skin Infections
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                Dermatology
                Skin Diseases
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                South America
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