Urine Antigen Detection as an Aid to Diagnose Invasive Aspergillosis

Kieren Marr, Kausik Datta, Seema Mehta, Darin Bruce Ostrander, Michelle Rock, Jesse Francis, Marta Feldmesser

Research output: Contribution to journalArticle

Abstract

Background: Establishing rapid diagnoses of invasive aspergillosis (IA) is a priority tests that detect galactomannan and β-d-glucan are available, but are technically cumbersome and rely on invasive sampling (blood or bronchoalveolar lavage). Methods: We optimized a lateral flow dipstick assay using the galactofuranose-specific monoclonal antibody (mAb476), which recognizes urine antigens after Aspergillus fumigatus pulmonary infection in animals. Urine samples were obtained from a cohort of 78 subjects undergoing evaluation for suspected invasive fungal infections, and stored frozen until testing. Urine was processed by centrifugation through desalting columns and exposed to dipsticks. Reviewers blinded to clinical diagnoses graded results. Western blots were performed on urine samples from 2 subjects to characterize mAb476-reactive antigens. Results: Per-patient sensitivity and specificity for diagnosis of proven or probable IA in the overall cohort was 80% (95% confidence interval [CI], 61.4%-92.3%) and 92% (95% CI, 74%-99%), respectively. In the subgroup with cancer, sensitivity was 89.5% (95% CI, 66.7%-98.7%) and specificity was 90.9% (95% CI, 58.7%-99.8%); among all others, sensitivity and specificity were 63.6% (95% CI, 30.8%-89.1%) and 92.9% (95% CI, 66.1%-99.8%), respectively. Eliminating lung transplant recipients with airway disease increased sensitivity in the noncancer cohort (85.7% [95% CI, 42.1%-99.6%]). Semiquantitative urine assay results correlated with serum galactomannan indices. Western blots demonstrated mAb476-reactive antigens in urine from cases, ranging between 26 kDa and 35 kDa in size. Conclusions: Urine testing using mAb476 may be used as an aid to diagnose IA in high-risk patients.

Original languageEnglish (US)
Pages (from-to)1705-1711
Number of pages7
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume67
Issue number11
DOIs
StatePublished - Nov 13 2018

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Aspergillosis
Urine
Confidence Intervals
Antigens
Western Blotting
Sensitivity and Specificity
Lung
Aspergillus fumigatus
Glucans
Bronchoalveolar Lavage
Centrifugation
Monoclonal Antibodies
Infection
Serum
Neoplasms

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Urine Antigen Detection as an Aid to Diagnose Invasive Aspergillosis. / Marr, Kieren; Datta, Kausik; Mehta, Seema; Ostrander, Darin Bruce; Rock, Michelle; Francis, Jesse; Feldmesser, Marta.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 67, No. 11, 13.11.2018, p. 1705-1711.

Research output: Contribution to journalArticle

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abstract = "Background: Establishing rapid diagnoses of invasive aspergillosis (IA) is a priority tests that detect galactomannan and β-d-glucan are available, but are technically cumbersome and rely on invasive sampling (blood or bronchoalveolar lavage). Methods: We optimized a lateral flow dipstick assay using the galactofuranose-specific monoclonal antibody (mAb476), which recognizes urine antigens after Aspergillus fumigatus pulmonary infection in animals. Urine samples were obtained from a cohort of 78 subjects undergoing evaluation for suspected invasive fungal infections, and stored frozen until testing. Urine was processed by centrifugation through desalting columns and exposed to dipsticks. Reviewers blinded to clinical diagnoses graded results. Western blots were performed on urine samples from 2 subjects to characterize mAb476-reactive antigens. Results: Per-patient sensitivity and specificity for diagnosis of proven or probable IA in the overall cohort was 80{\%} (95{\%} confidence interval [CI], 61.4{\%}-92.3{\%}) and 92{\%} (95{\%} CI, 74{\%}-99{\%}), respectively. In the subgroup with cancer, sensitivity was 89.5{\%} (95{\%} CI, 66.7{\%}-98.7{\%}) and specificity was 90.9{\%} (95{\%} CI, 58.7{\%}-99.8{\%}); among all others, sensitivity and specificity were 63.6{\%} (95{\%} CI, 30.8{\%}-89.1{\%}) and 92.9{\%} (95{\%} CI, 66.1{\%}-99.8{\%}), respectively. Eliminating lung transplant recipients with airway disease increased sensitivity in the noncancer cohort (85.7{\%} [95{\%} CI, 42.1{\%}-99.6{\%}]). Semiquantitative urine assay results correlated with serum galactomannan indices. Western blots demonstrated mAb476-reactive antigens in urine from cases, ranging between 26 kDa and 35 kDa in size. Conclusions: Urine testing using mAb476 may be used as an aid to diagnose IA in high-risk patients.",
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AU - Datta, Kausik

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AU - Rock, Michelle

AU - Francis, Jesse

AU - Feldmesser, Marta

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