Further Observations on Histoplasmin Sensitivity in the United States

Edwards, Lydia B.; Acquaviva, Francis A.; Livesay, Verna T.

doi:10.1093/oxfordjournals.aje.a121561

Cited by 36 publications

(32 citation statements)

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“…In areas where the fungus is prevalent, more than 80% of the human population is positive for a Histoplasma antigen skin test, indicating previous exposure or infection (1, 2). Histoplasmosis presents with diverse manifestations, including mild subclinical disease, acute respiratory distress, and systemic dissemination.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Phylogenetically DistinctHistoplasmaStrains Reveals Evolutionarily Divergent Virulence Strategies

Sepúlveda

Williams

Goldman

2014

mBio

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Infection with the dimorphic fungus Histoplasma capsulatum results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the H. capsulatum strain. H. capsulatum is divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized an H. capsulatum isolate (WU24) from the NAm 1 lineage in relation to two other well-characterized Histoplasma isolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall α-(1,3)-glucan for successful in vitro infection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis.

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Section: Introductionmentioning

confidence: 99%

Comparison of Phylogenetically DistinctHistoplasmaStrains Reveals Evolutionarily Divergent Virulence Strategies

Sepúlveda

Williams

Goldman

2014

mBio

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“…Rates of histoplasma exposure are known to be higher in rural settings compared to urban, and are particularly high on farms [27, 28]. As even the Amish who do not self-identify as farmers often have experience with farmwork and an agrarian existence [13], it could be that this common lifestyle conveys increased exposure to histoplasmosis.…”

Section: Discussionmentioning

confidence: 99%

Calcified Granulomatous Disease: Occupational Associations and Lack of Familial Aggregation

Reed

Amoroso

Hashmi

et al. 2014

Lung

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Purpose The acute host response to histoplasma capsulatum infection varies according to exposure and susceptibility. Late sequelae include calcifications in the lung, thoracic lymphatics, and spleen. Determinants of calcified granuloma formation are poorly studied and may differ from those affecting acute response. We examined the occupational associations and familial aggregation of radiographic calcified granulomatous disease to characterize the determinants of calcified granuloma formation. Methods We analyzed prospectively collected cross-sectional data including computed tomograms from 872 adult members of the Old Order Amish of Lancaster County. Results Granulomas were present in 71 % of participants. Granulomas were present in the lung of 57 % of participants, in the hilar or mediastinal lymph nodes of 55 % of participants, and in the spleen of 29 % of participants. No significant differences were observed in the presence of granulomas between men and women. Each year of age was associated with 4 % higher odds of splenic calcifications, and a primary occupation of farming was associated with an 84 % higher odds of splenic calcifications. A compelling pattern of familial aggregation was not observed. Conclusions Calcified granulomatous disease does not appear to aggregate in families. Determinants influencing patterns of granulomatous disease include occupation, age, and geographic location.

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“…Endemic areas of histoplasmosis in the continental US, based on skin testing, and locations of cases reported in this series. Skin reactivity to histoplasmin was assessed among Navy recruits from the continental US from 1958 through 1969 by Edwards et al (9). Light gray shading indicates the approximate geographic areas with at least 10% prevalence of positive histoplasmin skin test reactivity (induration Ն4 mm diameter), and dark gray shading indicates the approximate areas with at least 60% prevalence.…”

Section: Discussionmentioning

confidence: 99%

Life‐threatening histoplasmosis complicating immunotherapy with tumor necrosis factor α antagonists infliximab and etanercept

Lee¹,

Slifman²,

Gershon³

et al. 2002

Arthritis & Rheumatism

423

221

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ObjectiveTwo tumor necrosis factor α (TNFα) antagonists were recently licensed in the US. Infliximab was licensed in 1998 for the treatment of Crohn's disease (CD), and since 1999, it has been licensed in combination with methotrexate for treatment of rheumatoid arthritis (RA). Etanercept was licensed in 1998 for treatment of RA and, more recently, for juvenile RA and psoriatic arthritis. Because of potential immunosuppression related to use of anti‐TNFα agents, we sought to identify postlicensure cases of opportunistic infection, including histoplasmosis, in patients treated with these products.MethodsThe US Food and Drug Administration's (FDA) passive surveillance database for monitoring postlicensure adverse events was reviewed to identify all reports received through July 2001 of histoplasmosis in patients treated with either infliximab or etanercept.ResultsTen cases of Histoplasma capsulatum (HC) infection were reported: 9 associated with infliximab and 1 associated with etanercept. In patients treated with infliximab, manifestations of histoplasmosis occurred within 1 week to 6 months after the first dose and typically included fever, malaise, cough, dyspnea, and interstitial pneumonitis. Of the 10 patients with histoplasmosis, 9 required treatment in an intensive care unit, and 1 died. All patients had received concomitant immunosuppressive medications in addition to infliximab or etanercept, and all resided in HC‐endemic regions.ConclusionPostlicensure surveillance suggests that acute life‐threatening histoplasmosis may complicate immunotherapy with TNFα antagonists, particularly infliximab. Histoplasmosis should be considered early in the evaluation of patients who reside in HC‐endemic areas in whom infectious complications develop during treatment with infliximab or etanercept.

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Further Observations on Histoplasmin Sensitivity in the United States

Cited by 36 publications

References 0 publications

Comparison of Phylogenetically DistinctHistoplasmaStrains Reveals Evolutionarily Divergent Virulence Strategies

Comparison of Phylogenetically DistinctHistoplasmaStrains Reveals Evolutionarily Divergent Virulence Strategies

Calcified Granulomatous Disease: Occupational Associations and Lack of Familial Aggregation

Life‐threatening histoplasmosis complicating immunotherapy with tumor necrosis factor α antagonists infliximab and etanercept

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