When to Stop Antifungal Treatment in Dogs and Cats with Blastomycosis

At a Glance – Crucial Information

1. MVista® Blasto Antigen test can be used for diagnosis, treatment monitoring, and detection of disease relapse [1Motschenbacher LO, Furrow E, Rendahl AK, et al. Retrospective analysis of the effects of Blastomyces antigen concentration in urine and radiographic findings on survival in dogs with blastomycosis. J Vet Intern Med 2021., 2Mourning AC, Patterson EE, Kirsch EJ, et al. 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;247:1133-1138., 3Spector D, Legendre AM, Wheat J, et al. Antigen and antibody testing for the diagnosis of blastomycosis in dogs. J Vet Intern Med 2008;22:839-843., 4Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014;28:305-310.].

2. Treatment monitoring includes following clinical signs, physical exam findings, imaging study results, and antigen concentrations.

3. Antigen concentrations decrease with effective treatment and increase with disease relapse [4Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014;28:305-310.].

4. MVista® Blasto Antigen test should be performed at diagnosis, every 3 months during treatment, and at 6 months then every 12 months after treatment.

 

The MVista® Blastomyces Antigen test has revolutionized diagnosis and treatment monitoring of blastomycosis. It provides a non-invasive option with high diagnostic performance (sensitivity = 93%, specificity = 98%) [1Motschenbacher LO, Furrow E, Rendahl AK, et al. Retrospective analysis of the effects of Blastomyces antigen concentration in urine and radiographic findings on survival in dogs with blastomycosis. J Vet Intern Med 2021., 2Mourning AC, Patterson EE, Kirsch EJ, et al. 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;247:1133-1138., 3Spector D, Legendre AM, Wheat J, et al. Antigen and antibody testing for the diagnosis of blastomycosis in dogs. J Vet Intern Med 2008;22:839-843., 4Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014;28:305-310.]. With effective treatment, antigen concentrations decrease. With ineffective treatment or disease relapse, antigen concentrations remain static or increase over time. Many dogs and most cats have no detectable antigen at the time of disease remission. Less frequently, a very low concentration of antigen is present, even after remission. In these cases, it might be appropriate to stop treatment even when the antigen test is still positive (described below).

Urine is the ideal sample when using the MVista® Blasto Antigen test for treatment monitoring. It commonly contains a higher antigen concentration, as compared with serum, and thus is a better marker for remission and relapse. When urine antigen concentration is too high to be quantified (above the limit of quantification), serum can often be used instead until urine concentrations are quantifiable. In these cases, antigen is often quantifiable in urine at the 6 months recheck.

Disease relapse has been reported in approximately 20% of dogs treated for blastomycosis [5Legendre AM, Rohrbach BW, Toal RL, et al. Treatment of blastomycosis with itraconazole in 112 dogs. J Vet Intern Med 1996;10:365-371., 6Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980-1995). J Am Vet Med Assoc 1998;213:658-664., 7Mazepa AS, Trepanier LA, Foy DS. Retrospective comparison of the efficacy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs. J Vet Intern Med 2011;25:440-445., 8Krawiec DR, McKiernan BC, Twardock AR, et al. Use of an amphotericin B lipid complex for treatment of blastomycosis in dogs. J Am Vet Med Assoc.]. Intuitively, a treatment duration that is too short increases the chance of disease relapse. Using a multimodal monitoring approach helps identify the appropriate treatment duration (Table 1). In addition to treatment duration, appropriate drug and dosage are also vital. Itraconazole is the first-choice treatment for animals not hospitalized. Due to variability in absorption, itraconazole blood levels should be monitored to determine the ideal individualized dose. This can be achieved with the MVista® Itraconazole Bioassay, which accounts for parent drug and all active metabolites. It has the additional advantage of being significantly less expensive than chromatography/spectrometry testing available from pharmacology labs.

Table 1. All of the following criteria should be met before stopping antifungal treatment in dogs and cats with blastomycosis.
Monitoring Tool Criteria Notes
Treatment Duration Minimum of 6 months Required duration is often much longer.
History ≥1-month past resolution of clinical signs Mild exercise intolerance might persist, most notable in working or performance animals.

Persistent tracheobronchial lymphadenopathy can cause cough, requiring concurrent corticosteroid treatment.
Physical Examination ≥1-month past resolution of physical exam abnormalities Differentiating active ocular disease from permanent inactive change is important.
Imaging Studies ≥1-month past resolution of imaging abnormalities Pulmonary scarring can be permanent and can cause static focal unstructured interstitial lung disease.

Radiographic bone lesions should improve but might never return to normal.
MVista® Blasto Antigen EIA (urine) ≥1-month past no detectable antigen
OR
Antigen ≤0.4 ng/ml on 2 consecutive rechecks at least 3 months apart		 Most dogs, and essentially all cats, have no detectable antigen at the time of remission.

Submit antigen test at diagnosis, every 3 months during treatment, and at 6 months then every 12 months after treatment.

 

References

  1. Motschenbacher LO, Furrow E, Rendahl AK, et al. Retrospective analysis of the effects of Blastomyces antigen concentration in urine and radiographic findings on survival in dogs with blastomycosis. J Vet Intern Med 2021.
  2. Mourning AC, Patterson EE, Kirsch EJ, et al. 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;247:1133-1138.
  3. Spector D, Legendre AM, Wheat J, et al. Antigen and antibody testing for the diagnosis of blastomycosis in dogs. J Vet Intern Med 2008;22:839-843.
  4. Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014;28:305-310.
  5. Legendre AM, Rohrbach BW, Toal RL, et al. Treatment of blastomycosis with itraconazole in 112 dogs. J Vet Intern Med 1996;10:365-371.
  6. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980-1995). J Am Vet Med Assoc 1998;213:658-664.
  7. Mazepa AS, Trepanier LA, Foy DS. Retrospective comparison of the efficacy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs. J Vet Intern Med 2011;25:440-445.
  8. Krawiec DR, McKiernan BC, Twardock AR, et al. Use of an amphotericin B lipid complex for treatment of blastomycosis in dogs. J Am Vet Med Assoc.