Histoplasmosis in immunosuppressed patients

Kauffman, Carol A.; Israel, Karen; Smith, James W.; White, A. Clinton; Schwarz, Jan; Brooks, George F.

doi:10.1016/0002-9343(78)90445-x

Cited by 221 publications

(63 citation statements)

References 61 publications

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“…These organisms are held in check by the immune response but are not completely killed, and thus, reactivation of infection years later is possible. This has been documented to occur in patients who have not returned to the area of endemicity for many years (21,64,80,109). For patients residing in areas of endemicity, it is not possible to ascertain whether disease is due to a new infection or the reactivation of an old infection.…”

Section: Disseminated Histoplasmosismentioning

confidence: 99%

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%

Histoplasmosis: a Clinical and Laboratory Update

2007

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“…Thus, mice congenitally deficient in, or experimentally depleted of T cells are much more susceptible to infection with Histoplasma capsulatum (Hc) 1 as compared to immunocompetent controls (6,7). Similarly, patients with T cell dysfunction caused by immunosuppressive therapy or HIV infection exhibit a higher incidence of disseminated histoplasmosis (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Vbeta4(+) T cells promote clearance of infection in murine pulmonary histoplasmosis.

Gómez¹,

Cain²,

Gibbons³

et al. 1998

J. Clin. Invest.

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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).…”

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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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Histoplasmosis in immunosuppressed patients

Cited by 221 publications

References 61 publications

Histoplasmosis: a Clinical and Laboratory Update

Histoplasmosis: a Clinical and Laboratory Update

Vbeta4(+) T cells promote clearance of infection in murine pulmonary histoplasmosis.

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

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