Disseminated Histoplasmosis in the Acquired Immune Deficiency Syndrome

Wheat, L. Joseph; Connolly‐Stringfield, Patricia; Baker, Robert L.; Curfman, M F; Eads, Micah; Israel, Karen; Norris, Steve; Webb, Douglas; Zeckel, Michael L.

doi:10.1097/00005792-199011000-00004

Cited by 591 publications

(78 citation statements)

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“…Although the mechanism of dissemination of Hc yeasts from the lung is not completely understood, it has been presumed to occur within blood-borne M. However, both patient studies (52,53) and studies with CD4 lymphocytedepleted mice (54) have reported an abundance of extracellular as well as intracellular organisms in the lung. As dissemination of Hc yeasts almost always occurs in AIDS patients, these findings suggest that extracellular Hc may play a role in the pathogenesis of disease in immunocompromised hosts.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The prevalence of histoplasmosis in individuals with AIDS is particularly high, occurring in 2-5% of patients with AIDS from endemic regions of the USA [55,56,58]. In selected US cities, the prevalence of histoplasmosis in individuals with AIDS has reached 25% [55]. In contrast to immunocompetent individuals where dissemination is uncommon, 95% of individuals with AIDS present with disseminated disease [55,56].…”

Section: The Role Of Antibody In Fungal Diseasementioning

confidence: 99%

“…In selected US cities, the prevalence of histoplasmosis in individuals with AIDS has reached 25% [55]. In contrast to immunocompetent individuals where dissemination is uncommon, 95% of individuals with AIDS present with disseminated disease [55,56]. Following acute infection, 85% percent of patients with AIDS develop symptomatic disease requiring hospitalization and these individuals have a fatality rate of 12% [60].…”

Section: The Role Of Antibody In Fungal Diseasementioning

confidence: 99%

Protective Antibodies and Endemic Dimorphic Fungi

Nosanchuk

2005

CMM

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The host response to infection is the outcome of a complex interaction between a microbe and a host's innate and adaptive immune system. In this context, the role of antibody in the endemic mycoses is relatively poorly understood. Recently, a monoclonal antibody to a cell surface protein has been shown to be protective in a murine histoplasmosis model. The findings with Histoplasma capsulatum may provide a paradigm for antibody protection against endemic fungi. This paper reviews the recent data on protective antibody in histoplasmosis and previous data supporting a role for antibody in protective responses in other dimorphic fungi.

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“…Immunocompromised individuals, particularly those with advanced AIDS, are at risk for disseminated histoplasmosis (19,20). A variety of tests are used in the laboratory for the diagnosis of histoplasmosis, but all have limitations.…”

mentioning

confidence: 99%

“…Serologic testing by immunodiffusion and complement fixation also has utility, but both false-positive and false-negative results may occur. False-positive serologic tests may be seen in patients with other disseminated mycoses, while false-negative results may occur in immunocompromised individuals who are unable to produce an antibody response (20,21). Histopathologic analysis of tissue is also useful but is dependent upon adequate sampling, the experience of the observer, and the histochemical stains used (9,15).…”

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confidence: 99%

Identification of Histoplasma capsulatum from Culture Extracts by Real-Time PCR

Shrestha

Sholtis

et al. 2003

J Clin Microbiol

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We designed and tested a real-time LightCycler PCR assay for Histoplasma capsulatum that correctly identified the 34 H. capsulatum isolates in a battery of 107 fungal isolates tested and also detected H. capsulatum in clinical specimens from three patients that were culture positive for this organism.Histoplasma capsulatum is a slow-growing, dimorphic fungus that causes disease that ranges from focal and self-limited to disseminated and rapidly fatal (15,19). Immunocompromised individuals, particularly those with advanced AIDS, are at risk for disseminated histoplasmosis (19,20). A variety of tests are used in the laboratory for the diagnosis of histoplasmosis, but all have limitations. Histoplasma antigen detection in urine and/or serum has a variable range of sensitivity, depending on the clinical pattern, the chronicity of the affliction, and the underlying condition of the patient (6). The sensitivity of the Histoplasma urinary antigen test is as high as 97% in AIDS patients with disseminated histoplasmosis but ranges from 20 to 81% in nonimmunosuppressed patients with acute pulmonary histoplasmosis (6,18,22,23). Serologic testing by immunodiffusion and complement fixation also has utility, but both false-positive and false-negative results may occur. False-positive serologic tests may be seen in patients with other disseminated mycoses, while false-negative results may occur in immunocompromised individuals who are unable to produce an antibody response (20,21). Histopathologic analysis of tissue is also useful but is dependent upon adequate sampling, the experience of the observer, and the histochemical stains used (9, 15). Unfortunately, H. capsulatum may be misidentified in histologic sections because of the variety of morphologically similar small yeast forms, such as Candida glabrata and Sporothrix schenckii. Culture, which is often considered the "gold standard," is limited by the slow growth of the organism, which may take more than 20 days to grow. In addition, confirmatory tests are needed for organisms suspected to be H. capsulatum because saprophytic morphological mimics of the mold phase of the organism exist (3, 7, 15). Confirmatory assays include the H. capsulatum AccuProbe (Gen-Probe, Inc., San Diego, Calif.), exoantigen testing, and temperature-induced mycelium-toyeast conversion. The development of a real-time rapid PCR method that could be used as an alternate method of culture confirmation and potentially to test clinical specimens directly is warranted.The LightCycler PCR system (Roche Molecular Biochemicals, Indianapolis, Ind.) affords nucleic acid amplification and detection in a closed system in a real-time format. We designed a real-time PCR assay for the detection of H. capsulatum that targeted the internal transcribed spacer region of the rRNA gene complex (GenBank accession number AB055231) and used hybridization probes and fluorescent resonance energy transfer technology. We used Hcap-F (5Ј-TTGTCTACCGGA CCTG-3Ј) as the forward primer and Hcap-R (5Ј-TTCTTCA TCGATGTCGGAAC-3Ј) as th...

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Disseminated Histoplasmosis in the Acquired Immune Deficiency Syndrome

Cited by 591 publications

References 0 publications

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

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

Protective Antibodies and Endemic Dimorphic Fungi

Identification of Histoplasma capsulatum from Culture Extracts by Real-Time PCR

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