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 (Χ2 = 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 (Χ2 = 211.15, df = 3, P<0.001) and mixed (dermatophyte and NDM; Χ2 = 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.

Highlights

  • It is estimated that onychomycosis is at a prevalence of 10% worldwide [1] and that the most common causative agent is Trichophyton rubrum (T. rubrum) [2]

  • In Israel and Brazil, T. rubrum was present as an etiologic agent in all infections seen, serving as the sole agent in 78% (29/37) of cases in Israel and in 39% (21/54) of cases in Brazil

  • T. rubrum was the most common etiological agent of onychomycosis detected in our global study at 98% (211/216) which corroborates all previous molecular-based investigations

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Summary

Introduction

It is estimated that onychomycosis is at a prevalence of 10% worldwide [1] and that the most common causative agent is Trichophyton rubrum (T. rubrum) [2]. Traditional culture-based identification techniques have been compared to molecular identification methods; false negative cultures have been shown to account for most disagreements between methods [3]. The unique challenges of isolating causative NDM(s) may cause underestimation of their clinical prevalence; for example, aggressive outgrowth by one co-infecting microorganism in culture may mask other etiological agents. Repeat sampling with repeat isolation of NDM(s) from culture will increase the likelihood that potentially masked organisms are identified, but will increase the likelihood that the organisms cultured are causative agents and not environmental contaminants [5]. The high sensitivity of molecular identification techniques offers a means of ensuring all causative agents are identified, the spate of identifications obtained may include environmental contaminants that can only be considered clinically significant with a full mycological examination including direct microscopy and repeat sampling. The present study is the first to survey the causal agents of onychomycosis on a global scale with the use of molecular identification techniques

Materials and methods
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