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      Histoplasmosis: a Clinical and Laboratory Update

      Clinical Microbiology Reviews

      American Society for Microbiology

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          Abstract

          SUMMARY

          Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of H. capsulatum within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for Histoplasma antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.

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          Most cited references 150

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          Voriconazole treatment for less-common, emerging, or refractory fungal infections.

          Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections.
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            Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS.

            In patients with moderate to severe histoplasmosis associated with AIDS, the preferred treatment has been the deoxycholate formulation of amphotericin B. However, serious side effects are associated with use of amphotericin B. To compare amphotericin B with liposomal amphotericin B for induction therapy of moderate to severe disseminated histoplasmosis in patients with AIDS. Randomized, double-blind, multicenter clinical trial. 21 sites of the U.S. National Institute of Allergy and Infectious Diseases Mycoses Study Group. 81 patients with AIDS and moderate to severe disseminated histoplasmosis. Clinical success, conversion of baseline blood cultures to negative, and acute toxicities that necessitated discontinuation of treatment. Clinical success was achieved in 14 of 22 patients (64%) treated with amphotericin B compared with 45 of 51 patients (88%) receiving liposomal amphotericin B (difference, 24 percentage points [95% CI, 1 to 52 percentage points]). Culture conversion rates were similar. Three patients treated with amphotericin B and one treated with liposomal amphotericin B died during induction (P = 0.04). Infusion-related side effects were greater with amphotericin B (63%) than with liposomal amphotericin B (25%) (P = 0.002). Nephrotoxicity occurred in 37% of patients treated with amphotericin B and 9% of patients treated with liposomal amphotericin B (P = 0.003). Liposomal amphotericin B seems to be a less toxic alternative to amphotericin B and is associated with improved survival.
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              The epidemiology of histoplasmosis: a review.

               R Hajjeh,  V Cano (2001)
              Histoplasmosis is the most common endemic mycosis in the United States and has recently emerged as an important opportunistic infection among human immunodeficiency virus (HIV)-infected persons living in areas where it is endemic. In this article, we describe the epidemiologic and ecologic features of histoplasmosis, highlighting the implications for prevention. Surveillance and education of the public and health care providers are needed to determine the disease burden of histoplasmosis. Development of better diagnostic tests for detection of disease in humans and of the organism in the environment will help in designing better prevention strategies.
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                Author and article information

                Journal
                Clinical Microbiology Reviews
                CMR
                American Society for Microbiology
                0893-8512
                1098-6618
                January 2007
                January 2007
                : 20
                : 1
                : 115-132
                Article
                10.1128/CMR.00027-06
                1797635
                17223625
                © 2007
                Product
                Self URI (article page): https://CMR.asm.org/content/20/1/115

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