Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome

Wheat, Joseph; Hafner, Richard; Korzun, Ann H.; Limj, Maria Theresa; Spencer, Patricia; Larsen, Robert A.; Hecht, Frederick M.; Powderly, William G.

doi:10.1016/s0002-9343(99)80311-8

Cited by 225 publications

(123 citation statements)

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“…The clinical samples used in this study were collected from patients with PDH and AIDS who were enrolled in two multicenter trials. In the first study (AIDS Clinical Trials Group 120 [ACTG-120]; 1991 to 1992), patients with mild to moderate PDH were treated with 300 mg itraconazole orally twice daily for 3 days followed by 200 mg twice daily for 12 weeks (7). In the more recent trial (Mycoses Study Group 29 ; 1995 to 1999), patients with moderately severe to severe PDH received 3 mg liposomal amphotericin B/kg body weight/day or 0.7 mg deoxycholate amphotericin B/kg/day for 2 weeks, followed by 200 mg itraconazole twice daily for another 10 weeks (4).…”

Section: Methodsmentioning

confidence: 99%

“…By calculating results using a calibration curve, the interassay variation was markedly reduced, permitting comparison of results from different assays without retesting prior specimens alongside current specimens. The objective of this study using the quantitative assay was to determine the clearance of antigenemia and antigenuria during early successful treatment of PDH in patients with AIDS (1,4,7).…”

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confidence: 99%

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Histoplasma Antigen Clearance during Treatment of Histoplasmosis in Patients with AIDS Determined by a Quantitative Antigen Enzyme Immunoassay

Hage

Kirsch

Stump

et al. 2011

Clin. Vaccine Immunol.

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Clearance of Histoplasma antigen has been used as a marker for response to treatment of progressive disseminated histoplasmosis (PDH) in patients with AIDS. Advancements in Histoplasma antigen detection permit accurate quantification of antigen concentration. We compared the clearance of antigenemia and antigenuria during effective treatment of PDH. Urine and serum specimens were serially collected from patients with AIDS who were successfully treated for PDH as part of two prospective clinical trials. Samples were stored frozen until they were tested in the quantitative Histoplasma antigen enzyme immunoassay. The kinetics of antigen clearance during the first 12 weeks of therapy were assessed in urine and serum during treatment with liposomal or deoxycholate amphotericin B followed by itraconazole and, in a separate analysis, in patients receiving only itraconazole. Latent class growth analysis was performed to define patterns of antigen clearance over time. In patients receiving amphotericin B, antigen levels declined the most during the first 2 weeks of treatment and antigenemia decreased more rapidly than antigenuria (5.90 ng/ml per week versus 4.21 ng/ml per week, respectively; P ‫؍‬ 0.09). Mean reductions of antigen levels from baseline at weeks 2 and 12 were greater in sera than in urine: 11.26 ng/ml versus 7.65 ng/ml (P ‫؍‬ 0.0948) and 18.52 ng/ml versus 14.64 ng/ml (P ‫؍‬ 0.0440), respectively. In patients who received itraconazole alone, most of the decline in antigenuria occurred later during treatment and was overall slower than that seen with amphotericin B (P < 0.0001). Results of latent class growth modeling showed two distinct trajectories for each parameter. With effective therapy, Histoplasma antigenemia decreases more rapidly than antigenuria, providing a more sensitive early laboratory marker for response to treatment. Antigenuria declines earlier with amphotericin B than with itraconazole.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Histoplasma Antigen Clearance during Treatment of Histoplasmosis in Patients with AIDS Determined by a Quantitative Antigen Enzyme Immunoassay

Hage

Kirsch

Stump

et al. 2011

Clin. Vaccine Immunol.

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“…Cases of histoplasmosis with skin lesions have been described among immunocompromised patients with AIDS. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Although rare, patients with AIDS and skin lesions but without lung involvement have also been reported recently. [5][6][7][8] Furthermore, an unusual orofacial case of manifestations of histoplasmosis in immunocompromised renal transplanted patient has also been described.…”

Section: Discussionmentioning

confidence: 99%

Histoplasmosis in the nasal septum without pulmonary involvement in a patient with acquired immunodeficiency syndrome: case report and literature review

et al. 2010

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CONTEXT: Histoplasmosis is a fungal disease caused by inhaling spores of the fungus Histoplasma capsulatum. The spores can be found in soil contaminated with bird, bat or chicken feces. Histoplasmosis occurs worldwide and is one of the most common pulmonary and systemic mycoses. CASE REPORT: We report here the case of a 37-year-old man with acquired immune deficiency syndrome and histoplasmosis in the nasal septum, without pulmonary involvement, that evolved rapidly to disseminated infection, multiple organ failure and death.

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“…Positive cultures or histopathology was the basis for diagnosis in 89% and antigenuria in 11%. Serum and urine specimens had been frozen at Ϫ20°C since 1996 to 1998 in a study conducted by the Mycoses Study Group (4) and since 1991 for an AIDS Clinical Trials Group study (5). For this analysis, specimens obtained before or during antifungal therapy that were negative or Ͻ0.6 ng/ml in the quantitative MVista Histoplasma antigen EIA were evaluated with or without pretreatment at 104°C in EDTA.…”

Section: Methodsmentioning

confidence: 99%

Improved Detection of Histoplasma Antigenemia following Dissociation of Immune Complexes

Swartzentruber¹,

LeMonte²,

Witt³

et al. 2009

Clin Vaccine Immunol

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The sensitivity for detection of Histoplasma antigen is lower in serum than in urine. In other antigen assays, treatment of serum at 104°C in the presence of EDTA was required for detection of antigenemia. Sensitivity and specificity for detection of Histoplasma antigenemia were examined with or without EDTA heat treatment of the serum using the MVista Histoplasma antigen enzyme immunoassay. A total of 94.6% of serum specimens from patients with AIDS and histoplasmosis that were negative untreated were positive after EDTA-heat treatment. Two-thirds of the negative serum specimens from patients with probable histoplasmosis, based upon clinical suspicion and Histoplasma antigenuria, were positive after heat treatment. Specificity was 99.0% in controls, including healthy subjects and patients in whom histoplasmosis or blastomycosis, were excluded. Precision and reproducibility were good and excellent, respectively. These findings demonstrate improvement in sensitivity without reduction in specificity, precision, or reproducibility after heat-EDTA treatment.The sensitivity for detection of Histoplasma antigenemia is lower than for antigenuria. For example, in the quantitative MVista Histoplasma antigen enzyme immunoassay (EIA), among patients with AIDS and progressive disseminated histoplasmosis (PDH), antigenuria was detected in 95 to 100% compared to 92 to 95% for antigenemia (1, 3). Previously, we noted improvement in the sensitivity for detection of antigenuria after ultrafiltration (2). In the Platelia Aspergillus EIA, pretreatment of serum at 104°C in the presence of EDTA is essential for detection of antigenemia. The presumed mechanisms for improvement in sensitivity include dissociation of antigen-antibody complexes and denaturation of the freed antibody.Testing for both antigenemia and antigenuria offers several advantages over testing for antigenuria alone. First, in some cases antigenuria may be undetectable, but antigenemia may be present. Second, urine may not be available in patients with renal failure. Third, antigenuria levels early in the infection often are above the reportable range of the MVista Histoplasma antigen EIA (1, 3). Clearance of antigenemia may provide a better marker for response to therapy in such cases. Fourth, antigenuria is more likely to be affected by hydration status, and consequently urine volume and concentration, than is antigenemia, making it a more accurate marker for fungal burden. The objective of this investigation was to evaluate the effect of preheating serum to 104°C in the presence of EDTA on detection of Histoplasma antigenemia. MATERIALS AND METHODSClinical samples. Serum and urine specimens were obtained from AIDS patients with PDH treated with amphotericin B, followed by itraconazole (4), or with itraconazole alone (5). The criteria for diagnosis included clinical findings of histoplasmosis supported by laboratory confirmation: positive culture, histopathology, or Histoplasma antigen. Positive cultures or histopathology was the basis for diagnosis in 89% and ant...

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Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome

Cited by 225 publications

References 12 publications

Histoplasma Antigen Clearance during Treatment of Histoplasmosis in Patients with AIDS Determined by a Quantitative Antigen Enzyme Immunoassay

Histoplasma Antigen Clearance during Treatment of Histoplasmosis in Patients with AIDS Determined by a Quantitative Antigen Enzyme Immunoassay

Histoplasmosis in the nasal septum without pulmonary involvement in a patient with acquired immunodeficiency syndrome: case report and literature review

Improved Detection of Histoplasma Antigenemia following Dissociation of Immune Complexes

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