Clinical and Laboratory Features of Disseminated Histoplasmosis During Two Large Urban Outbreaks

Sathapatayavongs, Boonmee; Batteiger, Byron E.; Wheat, Joseph; Slama, Thomas G.; Wass, Justin L.

doi:10.1097/00005792-198309000-00001

Cited by 184 publications

(75 citation statements)

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“…Our earlier report with immunocompetent animals did not show fungal burden rebound after discontinuation of therapy (3). These findings are consistent with the experience that treatment is usually curative in nonimmunocompromised human patients (19) but not in those with AIDS (23,24).…”

Section: Fig 3 Quantitativesupporting

confidence: 92%

“…Immunosuppression by a variety of means has been shown to worsen the outcome of infection with H. capsulatum both in humans (19,23,24) and in animals. Immunosuppressed animal models have been established by administration of corticosteroids (15), cyclophosphamide (5,15,16), or antibodies to lymphocytes (1, 9), CD4 cells (8), interleukin 12 (27,28), or gamma interferon (2,27,28).…”

Section: Discussionmentioning

confidence: 99%

“…In persons with AIDS, the course of disseminated histoplasmosis often is more severe than and the response to treatment is inferior (23,24) to that in nonimmunocompromised individuals or those with other immunosuppressive disorders (19). Eighty-five percent of cases in patients with AIDS have occurred in those with CD4 cell counts below 200/l (13,20,22), suggesting that CD4 cells play an important role in defense against Histoplasma capsulatum.…”

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confidence: 99%

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Comparison of a New Triazole, Posaconazole, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in Immunocompromised Mice

Connolly¹,

Wheat

Schnizlein-Bick³

et al. 2000

Antimicrob Agents Chemother

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A murine model of intratracheally induced histoplasmosis in immunocompromised B6C3F 1 mice was used to evaluate a new triazole antifungal agent, posaconazole. This compound was previously shown to be comparable to amphotericin B and superior to itraconazole for the treatment of histoplasmosis in immunocompetent mice. The current study used mice that were depleted of T lymphocytes by intraperitoneal injection of anti-CD4 and anti-CD8 monoclonal antibodies beginning 2 days before infection and continuing at 5-day intervals until completion of the study. Groups of B6C3F 1 mice that were depleted of CD4 and CD8 T cells were infected with an inoculum of 10 4 Histoplasma capsulatum yeasts. All mice receiving posaconazole at 1 or 0.1 mg/kg of body weight/day, amphotericin B at 2 mg/kg every other day (qod), or itraconazole at 75 mg/kg/day survived to day 29. Only 60% of mice receiving itraconazole at 10 mg/kg/day and none receiving amphotericin B at 0.2 mg/kg qod survived to that date. Fungal burdens were determined at day 14 of infection, 1 day after discontinuation of therapy. Quantitative colony counts and Histoplasma antigen levels in lung and spleen tissues declined following treatment with amphotericin B at 2 mg/kg qod, posaconazole at 5 and 1 mg/kg/day, and itraconazole at 75 mg/kg/day but not in mice treated with amphotericin B at 0.2 mg/kg qod or itraconazole at 10 mg/kg/day. Posaconazole at 0.1 mg/kg/day reduced fungal colony counts and antigen levels in spleens but not in lungs. This study shows posaconazole activity for the treatment of histoplasmosis in immunosuppressed animals.Histoplasmosis is an important cause of progressive infection in immunocompromised individuals, including those with AIDS. In persons with AIDS, the course of disseminated histoplasmosis often is more severe than and the response to treatment is inferior (23,24) to that in nonimmunocompromised individuals or those with other immunosuppressive disorders (19). Eighty-five percent of cases in patients with AIDS have occurred in those with CD4 cell counts below 200/l (13, 20, 22), suggesting that CD4 cells play an important role in defense against Histoplasma capsulatum. Recent studies confirm the association of CD4 cell reduction with increased risk for disseminated histoplasmosis in persons with human immunodeficiency virus infection; case rates were 4.6 times higher in persons with CD4 cell counts below 150/l than in those with higher counts (18). CD8 cell counts were below 200/l in 35% of cases in AIDS patients enrolled in clinical trials evaluating the treatment of histoplasmosis (L. J. Wheat, unpublished data).We have shown that dual depletion of CD4 and CD8 cells markedly alters the course of experimental histoplasmosis following pulmonary challenge (6; C. Schnizlein-Bick, M. Durkin, P. Connolly, S. Kohler, and J. Wheat, Program Abstr. 34th Annu. Meet. Infect. Dis. Soc. Am., abstr. 207, p. 74, 1996). While nonimmunosuppressed mice recovered uneventfully following intratracheal inoculation with 10 3 yeasts, CD4-and CD8-depleted m...

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Section: Fig 3 Quantitativesupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Comparison of a New Triazole, Posaconazole, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in Immunocompromised Mice

Connolly¹,

Wheat

Schnizlein-Bick³

et al. 2000

Antimicrob Agents Chemother

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“…However, antibody titers are often negative or equivocal early in infection, and a second specimen, obtained 3 to 4 weeks later, is required for confirmation, thereby delaying diagnosis. Furthermore, immunosuppressed individuals, who are most at risk for the development of disseminated histoplasmosis, may be antibody deficient, leading to falsely negative serology results (27,30,43). For example, it has been reported that complement fixation titers of 1:32 or greater occurred in 83% (25 of 30) of nonimmunocompromised histoplasmosis patients but in only 50% (16 of 32) of immunocompromised patients (P Ͻ 0.05) (27).…”

mentioning

confidence: 99%

“…Furthermore, immunosuppressed individuals, who are most at risk for the development of disseminated histoplasmosis, may be antibody deficient, leading to falsely negative serology results (27,30,43). For example, it has been reported that complement fixation titers of 1:32 or greater occurred in 83% (25 of 30) of nonimmunocompromised histoplasmosis patients but in only 50% (16 of 32) of immunocompromised patients (P Ͻ 0.05) (27). A diagnostic method that does not rely upon an antibody response is therefore especially valuable in such cases.…”

mentioning

confidence: 99%

Production and Evaluation of Reagents for Detection of Histoplasma capsulatum Antigenuria by Enzyme Immunoassay

Lindsley

Holland

Bragg

et al. 2007

Clin Vaccine Immunol

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The detection of urinary Histoplasma capsulatum polysaccharide antigen (HPA) by enzyme immunoassay (EIA) has proven useful for the presumptive diagnosis of histoplasmosis in AIDS patients. Assay limitations include (i) detection of a largely uncharacterized antigen and (ii) difficulty in reproducibly generating antibodies for use in the EIA. To improve antibody production for use in this test and to better understand the antigen being detected, we compared rabbit antibodies elicited using various immunization schedules, routes, and H. capsulatum-derived antigens. Antibodies were evaluated by EIA for their ability to detect purified H. capsulatum C antigen (C-Ag) and antigenuria. Reported as enzyme immunoassay (EI)

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Maculopapular Rash in a Patient With Acquired Immunodeficiency Syndrome

Kalter¹,

Tschen²,

Klima³

1985

Arch Dermatol

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Clinical and Laboratory Features of Disseminated Histoplasmosis During Two Large Urban Outbreaks

Cited by 184 publications

References 0 publications

Comparison of a New Triazole, Posaconazole, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in Immunocompromised Mice

Comparison of a New Triazole, Posaconazole, with Itraconazole and Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in Immunocompromised Mice

Production and Evaluation of Reagents for Detection of Histoplasma capsulatum Antigenuria by Enzyme Immunoassay

Maculopapular Rash in a Patient With Acquired Immunodeficiency Syndrome

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