Progressive disseminated histoplasmosis as seen in adults

Reddy, Prathapchandra; Gorelick, David; Brasher, Charles A.; Larsh, Howard W.

doi:10.1016/0002-9343(70)90014-8

Cited by 126 publications

(53 citation statements)

References 22 publications

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“…Chronic progressive disseminated histoplasmosis is a term used to describe the slowly progressive and generally fatal infection due to H. capsulatum that occurs mostly in older adults who are not overtly immunosuppressed (50,104,119). The majority of the cases described by Parsons and Zarafonetis in 1945 in their classic description of disseminated histoplasmosis fall into this category (97).…”

Section: Disseminated Histoplasmosismentioning

confidence: 99%

“…The symptoms of disseminated histoplasmosis include fever, malaise, anorexia, and weight loss. Physical examination will often show hepatosplenomegaly, lymphadenopathy, pallor and petechiae if pancytopenia is present, and, in some patients, mucous membrane ulcerations as well as skin ulcers, nodules, or molluscum-like papules (50,104,119). Laboratory studies reveal elevated alkaline phosphatase levels, pancytopenia, an increased Westergren sedimentation rate, elevated C-reactive protein levels, high lactate dehydrogenase levels, and increased ferritin expression, none of which are specific for disseminated histoplasmosis but all of which are highly suggestive of this diagnosis in the appropriate patient (16,50,68).…”

Section: Disseminated Histoplasmosismentioning

confidence: 99%

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Histoplasmosis: a Clinical and Laboratory Update

2007

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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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Section: Disseminated Histoplasmosismentioning

confidence: 99%

Section: Disseminated Histoplasmosismentioning

confidence: 99%

Histoplasmosis: a Clinical and Laboratory Update

2007

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“…In the United States, Hc is endemic to the Ohio and Mississippi River Valleys, and it has been estimated that 500,000 new infections occur each year (1). Although the course of infection is mild in most immunocompetent individuals, Hc may produce progressive disseminated infections in individuals immunocompromised by hematologic malignancies (2)(3)(4)(5) and cytotoxic therapy (6)(7)(8). More importantly, disseminated histoplasmosis is seen with increasing frequency (5-25% of patients) as a complication of AIDS, particularly in the Ohio and Mississippi River Valleys where Hc is endemic (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Modulation of the effector function of human macrophages for Histoplasma capsulatum by HIV-1. Role of the envelope glycoprotein gp120.

Chaturvedi

Newman²

1997

J. Clin. Invest.

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We have demonstrated that monocyte-derived macrophages (M ) from HIV ϩ individuals are deficient in their capacity to phagocytose Histoplasma capsulatum (Hc) yeasts, and are more permissive for the intracellular growth of Hc. To determine whether these defects in M function were caused by HIV infection of the M and/or by pathological events associated with HIV infection, cultured normal human M were infected with the HIV-1 BaL strain. Virus production, quantified by reverse transcriptase activity and p24 antigen, was evident on day 8 after infection and peaked on day 16. On days 12, 16, and 20 after infection, HIV-1-infected M were deficient in their capacity to recognize and bind Hc yeasts compared with control M , and also were more permissive for the intracellular growth of Hc. Culture of normal M with the envelope glycoprotein gp120 inhibited phagocytosis of Hc yeasts by M in a concentration-dependent manner, but did not cause more rapid intracellular growth of Hc. Normal M cultured in the serum of HIV ϩ individuals with impaired M function subsequently were deficient in their capacity to phagocytose Hc yeasts, and were more permissive for the intracellular growth of yeasts compared with M cultured in normal serum. Conversely, culture of normal M in the serum of HIV ϩ patients with normal M function did not affect the interaction of Hc yeasts with M . Moreover, when M from HIV ϩ individuals that were initially defective in host defense against Hc were cultured in normal HIV Ϫ serum, normal M function was demonstrated. Adsorption of gp120 from the serum of two HIV ϩ patients removed the capacity of the serum to cause a M defect in phagocytosis of Hc, but had no effect on the capacity of the serum to cause accelerated intracellular growth. These data demonstrate that observed defects in M interaction with Hc yeasts may be caused by gp120 and other, as yet unknown serum component(s) probably released into serum by HIV-infected cells. (

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“…The course of H. capsulatum infection is mild in most immunocompetent individuals, but progressive disseminated infections occur in individuals immunocompromised by hematologic malignancies (6,25,30) or cytotoxic therapy (16,32,33) or in individuals infected with human immunodeficiency virus (15,20,31).…”

mentioning

confidence: 99%

Identification of Constituents of Human Neutrophil Azurophil Granules That Mediate Fungistasis againstHistoplasma capsulatum

et al. 2000

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Previously we demonstrated that human neutrophils mediate potent and long-lasting fungistasis against Histoplasma capsulatum yeasts and that all of the fungistatic activity resides in the azurophil granules. In the present study, specific azurophil granule constituents with fungistatic activity were identified by incubation with H. capsulatum yeasts for 24 h and by quantifying the subsequent growth of yeasts via the incorporation of [ 3 H]leucine. Human neutrophil defensins HNP-1, HNP-2, and HNP-3 inhibited the growth of H. capsulatum yeasts in a concentration-dependent manner with maximum inhibition at 8 g/ml. At a concentration of 4 g/ml, all possible paired combinations of defensins exhibited additive fungistatic activity against H. capsulatum yeasts. Cathepsin G and bactericidal-permeability-increasing protein (BPI) also mediated fungistasis against H. capsulatum in a concentration-dependent manner. The fungistatic activities of combinations of cathepsin G and BPI were additive, as were those of combinations of cathepsin G or BPI with HNP-1, HNP-2, and HNP-3. Lysozyme and elastase exhibited modest antifungal activity, and azurocidin and proteinase 3 exhibited no significant fungistasis against H. capsulatum yeasts. Thus, defensins, cathepsin G, and BPI are the major anti-H. capsulatum effector molecules in the azurophil granules of human neutrophils.Histoplasma capsulatum is a dimorphic fungal pathogen of worldwide importance that causes a broad spectrum of disease activity. The course of H. capsulatum infection is mild in most immunocompetent individuals, but progressive disseminated infections occur in individuals immunocompromised by hematologic malignancies (6,25,30) or cytotoxic therapy (16,32,33) or in individuals infected with human immunodeficiency virus (15,20,31).Infection with H. capsulatum is acquired by inhalation of microconidia into the terminal bronchioles and alveoli of the lung. Inhaled microconidia subsequently convert into yeasts that are responsible for the pathogenesis of histoplasmosis (17). H. capsulatum yeasts are phagocytized by alveolar macrophages (M), within which they multiply (2, 7). Dividing yeasts destroy the alveolar M, and subsequently the yeasts are ingested by other resident alveolar M and by inflammatory phagocytes recruited to the locus of infection. Repetition of this cycle results in spread of infection to hilar lymph nodes and to other organs during the acute phase of primary histoplasmosis. Subsequently, the maturation of specific cell-mediated immunity against H. capsulatum activates M to halt yeast proliferation with gradual resolution of the disease process in immunocompetent hosts (7,22).The role of polymorphonuclear neutrophils (PMNs) in the cell-mediated immune response against H. capsulatum is unclear (7). However, even the earliest studies in a murine model of histoplasmosis described PMNs as being the predominant inflammatory cell type in the lungs during the first 36 h after intranasal inoculation with H. capsulatum macroconidia. In these studies the PMNs ...

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Progressive disseminated histoplasmosis as seen in adults

Cited by 126 publications

References 22 publications

Histoplasmosis: a Clinical and Laboratory Update

Histoplasmosis: a Clinical and Laboratory Update

Modulation of the effector function of human macrophages for Histoplasma capsulatum by HIV-1. Role of the envelope glycoprotein gp120.

Identification of Constituents of Human Neutrophil Azurophil Granules That Mediate Fungistasis againstHistoplasma capsulatum

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