Urine Antigen Detection of Blastomycosis in Pediatric Patients

Mongkolrattanothai, Kanokporn; Peev, Milen; Wheat, L. Joseph; Marcinak, John

doi:10.1097/01.inf.0000241144.89426.2a

Cited by 51 publications

(29 citation statements)

References 11 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: 74%

“…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: 74%

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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“…However, in that study, assay specificity was a problem; B. dermatitidis antigen also was detected in the urine of 26 (96.3%) of 27 of patients with histoplasmosis, all 10 patients with paracoccidioidomycosis, and 7 (70%) of 10 patients with penicilliosis. A few case reports describing the usefulness of repeated antigen testing during therapy to monitor response have been published (84,116); however, additional data are needed to confirm these results. The urine of patients with blastomycosis may contain cross-reactive or shared antigens with H. capsulatum var.…”

Section: Antigen Detectionmentioning

confidence: 90%

Clinical and Laboratory Update on Blastomycosis

2010

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SUMMARY Blastomycosis is endemic in regions of North America that border the Great Lakes and the St. Lawrence River, as well as in the Mississippi River and Ohio River basins. Men are affected more often than women and children because men are more likely to participate in activities that put them at risk for exposure to Blastomyces dermatitidis. Human infection occurs when soil containing microfoci of mycelia is disturbed and airborne conidia are inhaled. If natural defenses in the alveoli fail to contain the infection, lymphohematogenous dissemination ensues. Normal host responses generate a characteristic pyogranulomatous reaction. The most common sites of clinical disease are the lung and skin; osseous, genitourinary, and central nervous system manifestations follow in decreasing order of frequency. Blastomycosis is one of the great mimickers in medicine; verrucous cutaneous blastomycosis resembles malignancy, and mass-like lung opacities due to B. dermatitidis often are confused with cancer. Blastomycosis may be clinically indistinguishable from tuberculosis. Diagnosis is based on culture and direct visualization of round, multinucleated yeast forms that produce daughter cells from a single broad-based bud. Although a long course of amphotericin B is usually curative, itraconazole is also highly effective and is the mainstay of therapy for most patients with blastomycosis.

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Urine Antigen Detection of Blastomycosis in Pediatric Patients

Cited by 51 publications

References 11 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

Clinical and Laboratory Update on Blastomycosis

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