J. Fungi2015, 1(2), 154-167; doi:10.3390/jof1020154 - published 29 July 2015 Show/Hide Abstract
Abstract: The two etiologic agents of cryptococcal meningoencephalitis, Cryptococcus neoformans and C. gattii, have been commonly designated as either an opportunistic pathogen for the first species or as a primary pathogen for the second species. Such a distinction has been based on epidemiological findings that the majority of patients presenting meningoencephalitis caused by C. neoformans are immunocompromised while C. gattii infection has been reported more often in immunocompetent patients. A recent report, however, showed that GM-CSF (granulocyte-macrophage colony-stimulating factor) neutralizing antibodies were prevalent in the plasma of “apparently immunocompetent” C. gattii patients with meningoencephalitis. Because GM-CSF is essential for differentiation of monocytes to macrophages and modulating the immune response, it is not surprising that the lack of GM-CSF function predisposes otherwise healthy individuals to infection via inhalation of environmental pathogens such as C. gattii. Since the test for anti-GM-CSF autoantibodies is not included in routine immunological profiling at most hospitals, healthy patients with GM-CSF neutralizing antibodies are usually categorized as immunocompetent. It is likely that a comprehensive immunological evaluation of patients with C. gattii meningoencephalitis, who had been diagnosed as immunocompetent, would reveal a majority of them had hidden immune dysfunction. This paper reviews the relationship between GM-CSF neutralizing antibodies and the risk for C. gattii infection with CNS involvement.
J. Fungi2015, 1(2), 138-153; doi:10.3390/jof1020138 - published 27 July 2015 Show/Hide Abstract
Abstract: Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment obstacle concerns low nail-plate drug permeability. In vitro antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model. T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on nail pieces at 28 °C (normal air) and 37 °C (6.4% CO2) during 3 to 35 days and PDTs applied to the 37 °C infections. All dermatophytes showed increasingly nail plate invasion at 37 °C between 7 and 35 days; arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans. Using 81 J/cm2 (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%) with 80 µM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%–67%) with 24 h PORTHE (40–80 µM)/40% PG treatment (pH 5). 28 J/cm2 LED light (525 ± 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis.
J. Fungi2015, 1(2), 130-137; doi:10.3390/jof1020130 - published 17 July 2015 Show/Hide Abstract
Abstract: Manifestations of Trichophyton rubrum infestations, such as tinea pedis, tinea cruris, and tinea corporis, are among the most common human skin diseases seen throughout the world. About 80% of patients presenting with acute dermatophytosis respond well to topical antifungal treatment. However, the remaining 20% of patients progress into a chronic state of dermatophytosis, which is resistant to antifungal treatment. Therefore, it is necessary to have a better understanding and appreciation for the diverse immune responses to Trichophyton as this is critical for the development of therapeutic strategies for those individuals who suffer from a chronic manifestation of Trichophyton rubrum (T. rubrum) infection. As a result, a comprehensive literature review was conducted to review and discuss previous studies that evaluated the human body’s defense to T. rubrum infections and to understand why and how these fungal infections invade the host defense system. Our research revealed that a cell-mediated immune response is critical in defending the body against T. rubrum. However, this organism has mechanisms that enable it to evade the immune system. Therefore, a more successful treatment for chronic T. rubrum infection would involve targeting the mechanisms of T. rubrum that diminish the immune response, while restoring the cell-mediated immune response.
J. Fungi2015, 1(2), 115-129; doi:10.3390/jof1020115 - published 14 July 2015 Show/Hide Abstract
Abstract: Cryptococcus has emerged as a significant pathogen in immunocompromised patients. While the diagnostic testing and the antifungal treatment of cryptococcal infections have become firmly established in clinical practice, new developments and areas of ambiguity merit further consideration. These include the potential for donor transmission of Cryptococcus; cirrhosis-associated cryptococcosis, particularly during transplant candidacy; the utility of serum cryptococcal antigen testing of asymptomatic individuals in high-prevalence, poor-resource areas; pathogenesis and treatment of the immune reconstitution syndrome, specifically in relation to antiretroviral therapy and immunosuppressive medications; and new challenges posed by the emerging species of Cryptococcus gatti. In this article, we summarize the literature pertaining to these topics, focusing on recent progress.
J. Fungi2015, 1(2), 107-114; doi:10.3390/jof1020107 - published 3 July 2015 Show/Hide Abstract
Abstract: To provide an adequate therapeutic effect against onychomycosis, it has been suggested that topical drugs should have two properties: drug permeability through the nail plate and into the nail bed, and retention of their antifungal activity in the disease-affected areas. Only recently has the importance of other delivery routes (such as subungual) been discussed. Efinaconazole has been shown to have a more potent antifungal activity in vitro than the most commonly used onychomycosis treatments. The low keratin affinity of efinaconazole contributes to its effective delivery through the nail plate and retention of its antifungal activity. Its unique low surface tension formulation provides good wetting properties affording drug delivery both through and under the nail. High antifungal drug concentrations have been demonstrated in the nail of onychomycosis patients, and effectiveness of efinaconazole topical solution, 10% confirmed in two large well-controlled multicenter Phase 3 clinical studies in patients with mild-to-moderate disease.
J. Fungi2015, 1(2), 94-106; doi:10.3390/jof1020094 - published 30 June 2015 Show/Hide Abstract
Abstract: Histoplasmosis and blastomycosis are geographically restricted dimorphic fungi that cause infection after the conidia produced in the mold phase are inhaled into the lungs. In the lungs, at 37 °C, these organisms undergo transformation into the yeast phase. In transplant recipients, infection can occur by exposure to the mold in the environment, by reactivation of infection that had occurred previously and had been controlled by the host until immunosuppressive medications were given post-transplantation, and finally by transmission from the donor organ in the case of histoplasmosis. In transplant recipients, disseminated infection is common, and pulmonary infection is more likely to be severe than in a non-immunosuppressed person. Diagnosis has been improved, allowing earlier treatment, with the use of rapid antigen tests performed on serum and urine. Initial treatment, for all but the mildest cases of acute pulmonary histoplasmosis, should be with a lipid formulation of amphotericin B. After clinical improvement has occurred, step-down therapy with itraconazole is recommended for a total of 12 months for most transplant recipients, but some patients will require long-term suppressive therapy to prevent relapse of disease.