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      A phenylthiazole derivative demonstrates efficacy on treatment of the cryptococcosis & candidiasis in animal models

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          Abstract

          Aim:

          In this work we test 2-(2-(cyclohexylmethylene)hydrazinyl)-4-phenylthiazole (CHT) against Cryptococcus spp. and Candida albicans.

          Methods:

          The ability of CHT to act in biofilm and also to interfere with C. albicans adhesion was evaluated, as well as the efficiency of the CHT in cryptococcosis and candidiasis invertebrate and murine models.

          Results & conclusion:

          In the present work we verified that CHT is found to inhibit Cryptococcus and C. albicans affecting biofilm in both and inhibited adhesion of Candida to human buccal cells. When we evaluated in vivo, CHT prolonged survival of Galleria mellonella after infections with Cryptococcusgattii, Cryptococcusneoformans or C. albicans and promoted a reduction in the fungal burden to the organs in the murine models. These results demonstrate CHT therapeutic potential.

          Lay abstract

          Candida spp. and Cryptococcus spp. cause thousands of deaths each year. In general, antifungal drugs have several limitations to their use, and there are a limited number of these drugs available to be used in the treatments of fungal diseases. This work contributes to the search for new antifungal drugs for the treatment of candidiasis and cryptococcosis, aiming in the future, after all necessary tests, to serve as a basis for the production of drugs that could be used in the treatment of patients with these fungal diseases.

          Graphical abstract

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          Most cited references 40

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          Hidden killers: human fungal infections.

          Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.
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            Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS.

            Cryptococcal meningitis is one of the most important HIV-related opportunistic infections, especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment, it is important to estimate the burden of cryptococcal meningitis. Global burden of disease estimation using published studies. We used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 United Nations Programme on HIV/AIDS HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths, we assumed a 9% 3-month case-fatality rate among high-income regions, a 55% rate among low-income and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies published in these areas and expert opinion. Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720 000 cases; range, 144 000-1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (
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              Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.

              Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
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                Author and article information

                Journal
                Future Sci OA
                Future Sci OA
                FSOA
                Future Science OA
                Future Science Ltd (London, UK )
                2056-5623
                July 2018
                25 April 2018
                : 4
                : 6
                Affiliations
                Department of Microbiology, Institute of Biological Sciences, Universidade Federal De Minas Gerais, Belo Horizonte, MG, Brazil
                [2 ]Postgraduate Program, Universidade CEUMA (UNICEUMA), São Luís, MA, Brazil
                [3 ]Department of Biosciences & Oral Diagnosis, Institute of Science & Technology, Univ Estadual de São Paulo, São José dos Campos, São Paulo, Brazil
                [4 ]Department of Pharmaceutical Products, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
                [5 ]Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School & Brown University, Providence, RI, 02903, USA
                Author notes
                *Author for correspondence: Tel.: +55 31 3349 7700; Fax: +55 31 3295 3115; sjohann@ 123456icb.ufmg.br
                10.4155/fsoa-2018-0001
                6060395
                © 2018 Susana Johann

                This work is licensed under a Creative Commons Attribution 4.0 License

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