Blastomyces Antigen Detection for Monitoring Progression of Blastomycosis in a Pregnant Adolescent

Tarr, Megan E.; Marcinak, John; Mongkolrattanothai, Kanokporn; Burns, Jennifer L.; Wheat, L. Joseph; Durkin, Michelle; Ismail, Mahmoud

doi:10.1155/2007/89059

Cited by 21 publications

(18 citation statements)

References 10 publications

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“…It steadily declined to nondetectable after changing to amphotericin B. This validates previous case reports that have described the use of urine antigen testing in this way (18,21).…”

supporting

confidence: 88%

“…However, a variety of other diagnostic tests, including antigen testing, antibody testing, and PCR, are commercially available (8,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Given that identification from culture may not be evident for 2 to 4 weeks and that it often requires invasive procedures to obtain specimens, there is great interest in using antigen enzyme immunoassays (EIA) for rapid, noninvasive diagnosis and monitoring of disease progression or resolution (2,4,8,19).…”

mentioning

confidence: 99%

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Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis

Frost

Novicki

2015

J Clin Microbiol

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cBlastomyces spp. antigen testing was evaluated over a 10-year period in an area where blastomycosis is endemic. Antigen testing was less sensitive than previously reported, but serial urine testing was useful in monitoring disease resolution or progression. Culture and cytopathology remain the gold standard for diagnosis and exclusion of this infection. Blastomycosis is a serious and potentially fatal fungal infection. Blastomycosis may be asymptomatic or it can present as isolated pulmonary disease, disseminated disease (pulmonary and extrapulmonary infection), or extrapulmonary disease with manifestations in the central nervous system, bone, skin, or other locations (1-11).Culture and cytopathology are the gold standard for the diagnosis of blastomycosis. However, a variety of other diagnostic tests, including antigen testing, antibody testing, and PCR, are commercially available (8,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Given that identification from culture may not be evident for 2 to 4 weeks and that it often requires invasive procedures to obtain specimens, there is great interest in using antigen enzyme immunoassays (EIA) for rapid, noninvasive diagnosis and monitoring of disease progression or resolution (2,4,8,19).We evaluated the use of Blastomyces urine, serum, and bronchoalveolar lavage (BAL) fluid antigen assays for the diagnosis of blastomycosis and the effects of treatment on the clearance of antigenuria at the Marshfield Clinic from 1995 to 2015. Marshfield Clinic is located in Wisconsin where blastomycosis is endemic (1,3,6,9,(23)(24)(25)(26)(27)(28). Research protocols were approved by the Marshfield Clinic Institutional Review Board. Waiver of informed consent was obtained.Patients were included if blastomycosis was confirmed by culture or cytopathology and if urine, serum, or BAL fluid antigen EIA was completed at the time of diagnosis or within 30 days of starting antifungal medication. Blastomycosis was confirmed by culture or cytopathology at Marshfield Labs using conventional techniques. Commercially available blastomycosis antigen EIA was performed at the MiraVista Diagnostics reference laboratory at the time of specimen collection using qualitative EIA prior to March 2011 or quantitative EIA thereafter. EIA results are available within 24 h of sample submission (13,14,16). All specimens were obtained as part of routine clinical evaluations. Retrospective chart review was completed for all patients.Data were abstracted into Excel 2010, and statistical analysis was completed using SAS 9.3. Categorical data were compared using the 2 test or the Fisher exact test. Continuous variables were compared using Wilcoxon rank sum, Kruskal-Wallis, or analysis of variance (ANOVA). Correlation for serial urine antigen testing was measured using Spearman's coefficient. Significance was defined as a P of Ͻ0.05.Patients with quantitative antigen EIA results were reported as negative, positive below the limit of quantification (Ͻ0.2 ng/ml), positive and quantifiable (0.2 to 14.7 ng/ml), or positiv...

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“…It steadily declined to nondetectable after changing to amphotericin B. This validates previous case reports that have described the use of urine antigen testing in this way (18,21).…”

supporting

confidence: 88%

mentioning

confidence: 99%

Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis

Frost

Novicki

2015

J Clin Microbiol

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“…This is consistent with case reports in humans11, 12 and in a retrospective study in dogs, using an older version of the same assay 8. In our study, serum antigen concentrations had a sensitivity of only 18% for active disease during treatment, as assessed 2–4 months into treatment.…”

Section: Discussionsupporting

confidence: 92%

Serum and UrineBlastomycesAntigen Concentrations as Markers of Clinical Remission in Dogs Treated for Systemic Blastomycosis

Foy

Trepanier

Kirsch³

et al. 2014

Veterinary Internal Medicne

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BackgroundSerum and urine Blastomyces antigen concentrations can be used to diagnose blastomycosis in dogs.Objectives Blastomyces antigen concentrations correlate with clinical remission in dogs during antifungal treatment, and detect disease relapse after treatment discontinuation.Animals21 dogs with newly diagnosed blastomycosis monitored until clinical remission (Treatment Phase), and 27 dogs monitored over 1 year from the time of antifungal discontinuation or until clinical relapse (After Treatment Phase).MethodsProspective study. Dogs were monitored monthly during treatment and every 3 months after treatment discontinuation, with a complete history, physical exam, chest radiographs, and ocular exam. Urine and serum Blastomyces antigen concentrations were measured at each visit using a quantitative enzyme immunoassay.ResultsAt enrollment in the Treatment Phase, Blastomyces antigen was positive in all 21 urine samples (100% sensitivity; 95% CI 85–100%), and in 18 of 20 serum samples (90% sensitivity; 95% CI 70–97%). At 2–4 months of treatment, urine antigen was more sensitive for clinically detectable disease (82%; CI 60–94%) than serum antigen (18%; CI 6–41%). The sensitivity of the urine test for clinical relapse was 71% (CI 36–92%), with close to 100% specificity (CI 84–100%) during after treatment surveillance in this population.ConclusionsUrine Blastomyces antigen testing has high sensitivity for active disease at the time of diagnosis and during treatment, and moderate sensitivity but high specificity for clinical relapse. Urine testing should be useful at the time of diagnosis, when treatment discontinuation is being considered, and anytime there is poor clinical response or suspicion of relapse.

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“…To date there is meager evidence for use of the antigen assay for monitoring therapy for blastomycosis. Antigen persistence was reported for a patient who failed itraconazole therapy, compared to steady clearance in two others who responded to therapy (13). Antigenemia and antigenuria steadily declined during itraconazole therapy in dogs with blastomycosis (10).…”

Section: Discussionmentioning

confidence: 99%

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Connolly¹,

Hage

Bariola

et al. 2012

Clin Vaccine Immunol

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100

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The second-generation MVista Blastomyces antigen enzyme immunoassay was not quantitative; therefore, specimens obtained previously were tested in the same assay as new specimens to assess the change in antigen levels. Furthermore, the sensitivity in serum had not been fully evaluated. The purpose of this study was to evaluate a quantitative Blastomyces antigen assay and detection of antigen in serum. Calibrators containing known concentrations of Blastomyces galactomannan were used to quantify antigen in urine and serum from patients with proven blastomycosis and from controls. Paired current and previously obtained urine specimens were tested to determine if quantification eliminated the need for concurrent testing to assess change in antigen. Pretreatment of serum with EDTA at 104°C was evaluated to determine if dissociation of immune complexes improved detection of antigenemia. Antigenuria was detected in 89.9% of patients with culture-or histopathology-proven blastomycosis. Specificity was 99.0% in patients with nonfungal infections and healthy subjects, but cross-reactions occurred in 95.6% of patients with histoplasmosis. Change in antigen level categorized as increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in ng/ml determined from different assays. Pretreatment increased the sensitivity of detection of antigenemia from 35.7% to 57.1%. Quantification eliminated the need for concurrent testing of current and previously obtained specimens for assessment of changes in antigen concentration. Pretreatment increased the sensitivity for detection of antigenemia. Differentiation of histoplasmosis and blastomycosis is not possible by antigen detection.A ntigen detection is a useful method for diagnosis of blastomycosis. The sensitivity has been reported to be over 90% and specificity has been reported to be 100% in healthy subjects, but cross-reactions occur in most patients with histoplasmosis (6). In a recent report of 59 patients with proven blastomycosis (4), culture was positive in 86%, histopathology in 81%, antigen in 74%, cytopathology in 38%, and immunodiffusion for antibody in 32% (4). Antigen detection was considered to be a "reliable method to make an accurate and rapid diagnosis of blastomycosis, particularly when a large burden of disease is present, and when cytological analysis is performed at less-experienced centers" (4). Blastomyces antigen detection was also reported to be useful for diagnosis of blastomycosis in solid organ transplant patients (7).Because of interassay variability, specimens obtained earlier have been tested simultaneously with current specimens to assess the change in antigen levels. In a Histoplasma antigen assay, quantification of galactomannan antigen eliminated the need to test the previously obtained specimen with the current specimen to determine change in antigen level (5). In a recent study, quantification and improved detection of antigen in serum following EDTA treatment at 104°C in the t...

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Blastomyces Antigen Detection for Monitoring Progression of Blastomycosis in a Pregnant Adolescent

Cited by 21 publications

References 10 publications

Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis

Blastomyces Antigen Detection for Diagnosis and Management of Blastomycosis

Serum and UrineBlastomycesAntigen Concentrations as Markers of Clinical Remission in Dogs Treated for Systemic Blastomycosis

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

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