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Antibody Testing Can Differentiate Histoplasmosis from Blastomycosis.

A 6-year-old Labrador retriever from Kentucky presented with sudden onset of coughing, lethargy and inappetence. Thoracic radiographs revealed diffuse nodular interstitial pulmonary infiltrates and tracheobronchial lymphadenopathy, suggestive of a systemic mycosis. The veterinarian submitted urine for both Blastomyces and Histoplasma antigen tests, with results of 4.5 ng/mL and 6.8 ng/mL, respectively.

QUESTION:
What diagnostic tests can distinguish histoplasmosis from blastomycosis?

ANSWER:
Antibody testing can differentiate histoplasmosis from blastomycosis.

Case Presentation:

  • MVista® Histoplasma Canine IgG Antibody EIA and MVista® Blastomyces Canine IgG Antibody EIA have fast turnaround times and are semi-quantitative (results reported in EIA units [EU] from 10-80+ EU)
  • Nearly complete cross reactivity is observed between the Blastomyces and Histoplasma antigen tests. Comparison of the quantitative results from both assays will NOT help to differentiate the two infections. For patients living in the area of overlapping endemic ranges, it is typically not recommended to test their urine in both assays.
  • Both fungi are endemic in states such KY, IN, IL, TN, OH, WV, LA, MS, MO, AR and surrounding areas. This case demonstrates the ability of the antibody EIA tests to differentiate the infections
  • Definitive diagnosis by identification of the Blastomyces or Histoplasma yeasts is not always possible; therefore, antibody testing is beneficial to assist in diagnosis
  • Occasionally cross reactivity is observed with the antibody assays; however, histoplasmosis cases usually display higher quantitative results in the Histoplasma antibody EIA

Current Challenge

Highly endemic
Moderately endemic
Mildly endemic
Suspected endemic
Areas Endemic for Histoplasmosis USA Areas Endemic for Blastomycosis USA

Hc Histoplasma
MVista® Histoplasma Canine IgG Antibody EIA

TEST CODE: 327

CPT CODE: N/A

CLINICAL SIGNIFICANCE:

IgG antibodies to Histoplasma antigen appear to be associated with active infection, especially in dogs with moderate to high positive (20 EU or greater) results. Antibodies may also be detected in a small percentage of healthy dogs from the endemic area as a result of sub-clinical infection within the last 2 years. IgG may be detected in histoplasmosis cases with falsely-negative antigen results (especially with localized disease or chronic infection) and combined antibody and antigen testing increases the overall sensitivity. Intermediate results (8-9.9 EU) typically reflect either rising or falling IgG, and retesting the patient in several weeks may be beneficial.

SPECIMEN COLLECTION:

Serum: Collect serum specimens in a serum separator or red top tube. Allow blood to clot for 30 minutes, then centrifuge. Pipette serum into a plastic screw cap vial for shipment, is preferred. If plastic screw cap vial is not available, ship in specimen collection tube.

CSF: Sterile transport tube

MINIMUM SPECIMEN REQUIREMENTS

Serum: 0.25ml

SPECIMEN STABILITY:

  • Refrigerated: 14 Days
  • Frozen: 14 Days

SPECIMEN REJECTION: Any specimen type >14 days old other than serum or CSF. For specimen submissions that do not meet these criteria, please call Customer Service.

TRANSPORT TEMPERATURE: Refrigerated/Frozen

SHIPPING: Ship on dry ice for Monday – Friday, next day delivery. Frozen ice packs may be substituted if specimen is shipped the day of collection.

TURNAROUND: Testing is performed on Mondays & Thursdays

Serum or CSF: Next Day

REFERENCE RANGE: Negative

INTERPRETATIVE INFORMATION:

  • Negative: <8.0 EU
  • Indeterminate: 8.0 – 9.9 EU
  • Positive: 10.0 EU – 80.0 EU
  • ALQ: >80.0 EU

METHODOLOGY: Semi-Quantitative Indirect Enzyme Immunoassay

LIMITATIONS:~1/3 of patients with blastomycosis or coccidioidomycosis will exhibit cross reactivity. The reference range and other method performance specifications have not been established for this test in CSF. The test results should be integrated into the clinical context for interpretation.

Bd Blastomyces
MVista® Blastomyces Canine IgG Antibody EIA

TEST CODE: 330

CPT CODE: N/A

CLINICAL SIGNIFICANCE:

IgG antibodies to Blastomyces antigen appear to be associated with active infection, especially in dogs with moderate to high positive

(20 EU or greater) results. Antibodies may also be detected in a small percentage of healthy dogs as a result of sub-clinical infection within the last 2 years; however, results of preliminary studies show high specificity of the assay (>90%) in healthy animals from Blastomyces-endemic areas. IgG may be detected in blastomycosis cases with falsely-negative antigen results (especially with localized disease; e.g., ocular or bone infections) and combined antibody and antigen testing increases the overall sensitivity. Intermediate results (8-9.9 EU)

typically reflect either rising or falling IgG, and retesting the patient in several weeks may be beneficial.

SPECIMEN COLLECTION:

Serum: Collect serum specimens in a serum separator or red top tube. Allow blood to clot for 30 minutes, then centrifuge. Pipette serum into a plastic screw cap vial for shipment, is preferred. If plastic screw cap vial is not available, ship in specimen collection tube.

CSF: Sterile transport tube

MINIMUM SPECIMEN REQUIREMENTS

Serum: 0.25ml

SPECIMEN STABILITY:

  • Refrigerated: 14 Days
  • Frozen: 14 Days

SPECIMEN REJECTION: Any specimen type >14 days old other than serum or CSF. For specimen submissions that do not meet these criteria, please call Customer Service.

TRANSPORT TEMPERATURE: Refrigerated/Frozen

SHIPPING: Ship on dry ice for Monday – Friday, next day delivery. Frozen ice packs may be substituted if specimen is shipped the day of collection.

TURNAROUND: Testing is performed on Mondays & Thursdays

Serum or CSF: Next Day

REFERENCE RANGE: Negative

INTERPRETATIVE INFORMATION:

  • Negative: <8.0 EU
  • Indeterminate: 8.0 – 9.9 EU
  • Positive: 10.0 EU – 80.0 EU
  • ALQ: >80.0 EU

METHODOLOGY: Semi-Quantitative Indirect Enzyme Immunoassay

LIMITATIONS: May cross-react with other fungi. The reference range and other method performance specifications have not been established for this test in CSF. The test results should be integrated into the clinical context for interpretation.

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REFERENCE LIST

(1) Mourning AC, Patterson EE, Kirsch EJ, Renschler JS, Wolf LA, Paris JK, Durkin MM and Wheat LJ. Evaluation of an enzyme immunoassay for antibodies to a recombinant Blastomyces adhesin-1 repeat antigen as an aid in the diagnosis of blastomycosis in dogs. J Am Vet Med Assoc 2015 Nov:247(10):1133-38.
(2) Spector D, Legendre AM, Wheat J, et al. Antigen and antibody testing for the diagnosis of blastomycosis in dogs. J Vet Intern Med 2008 Jul;22(4):839-43.

CREDENTIALS:
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