False negative antigen tests in dogs infected with heartworm and placed on macrocyclic lactone preventives
Open accessAbstract
BACKGROUND: Dogs with chronic inflammation, including those with heartworm being managed with macrocyclic lactones and doxycycline (slow kill, SK), may develop immune complexes that block detection of Dirofilaria immitis antigen on commercial tests. METHODS: To determine if SK could result in development of false-negative antigen tests, we collected serum samples from dogs that had been diagnosed with heartworm by antigen detection, with or without confirmation by detection of D. immitis microfilariae, placed on monthly macrocyclic lactones and doxycycline, and that later tested negative on an antigen test, and then tested them for antigen of D. immitis before and after treatment to disrupt immune complexes. RESULTS: Serum samples from a total of 15 dogs managed with SK were negative for antigen prior to heating on commercial assay (DiroCHEK, Zoetis) by colorimetric detection and spectrophotometry, but after heat treatment, 8/15 (53.3%) samples converted to positive. Review of the medical records of each dog indicated that, after the heartworm diagnosis, only 7/15 (46.7%) dogs appeared to receive preventive monthly as prescribed, including 3 dogs that had detectable antigen after heating the sample and 4 dogs that did not have detectable antigen after heating. Whole blood was available from 9 dogs; microfilariae of D. immitis were detected in 1 sample. CONCLUSIONS: These data suggest that immune complex formation in dogs infected with heartworm and managed with SK can induce false negative antigen test results, misleading veterinarians and owners about the efficacy of this approach. Moreover, compliance with preventive administration appears poor, even after a heartworm diagnosis. The presence of persistent microfilaremia in at least one dog has implications for resistance selection.
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Treatment with macrocyclic lactones can lead to the formation of antigen-antibody complexes in some patients, masking the antigen and resulting in false-negative test results.
“As treatment with macrocyclic lactones can lead to the formation of antigen-antibody complexes in some patients, masking the antigen and resulting in false-negative test results, ELISA antigen-testing was repeated in negative samples, using heated serum [41,42].”
From The Incidence of Dirofilaria immitis in Shelter Dogs and Mosquitoes in Austria (2021) · cites this paper as [41]
Pre-treatment with macrocyclic lactones can lead to the formation of antigen-antibody complexes masking the antigen, which can no longer be detected by commercial test kits.
“Another factor for inconsistency is the pre-treatment with macrocyclic lactones, which can lead to the formation of antigen–antibody-complexes masking the antigen, which could then no longer be detected by commercial test kits (Drake et al. 2015).”
From Current trends in canine dirofilariosis in Austria-do we face a pre-endemic status? (2020) · cites this paper as Drake et al. 2015
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References 20 · Cited by 60
Research works printed but not linked: 4
- [3]European Scientific Councel Companion Animal Parasites. Control of Vector-Borne Diseases in Dogs and Cats. ESCCAP Guideline 05 Second Edition – October 2012. http://www.esccap.org, accessed December 1, 2014.
- [11]McCall JW Ryan WG Roberts RE Dzimianski MT Heartworm adulticidal activity of prophylactic doses of ivermectin (6 μg/kg) plus pyrantel administered monthly to dogs 1998 Batavia, IL, USA Recent Advances in Heartworm Disease: Symposium’98, American Heartworm Society 209 15
- [12]McCall JW Guerrero J Roberts RE Supakorndej N Mansour AE Dzimianski MT Further evidence of clinical prophylactic, retro-active (reach-back) and adulticidal activity of monthly administrations of ivermectin (Heartgard Plus™) in dogs experimentally infected with heartworms 2001 Batavia, IL, USA Recent Advances in Heartworm Disease: Symposium’01, American Heartworm Society 189 200
- [26]Tonelli QJ Seward RL Factors affecting the accuracy of enzyme immunoassays for Dirofilaria immitis adult antigen Proceedings of the American Heartworm Symposium 1989 Batavia, IL, USA American Heartworm Society 161 5
- Authors
- Drake, J., Gruntmeir, J., Merritt, H., Allen, L., & Little, S. E.
- Affiliations
- Oklahoma State University (US)
- Oklahoma Department of Transportation (US)
- Corresponding author
- Little, Susan E
- Venue
- Parasites & Vectors
- Published
- 2015-02-04
- Volume
- 8
- Issue
- 1
- Pages
- 68-68
- ISSN
- 1756-3305 (ISSN-L)
- PMC
- PMC4336501
- OpenAlex
- W2107101788
- Cited by
- 60
- References
- 20
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 12 · 2018: 5 · 2017: 7 · 2016: 5
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Parasites & Vectors (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
- Health Sciences › Veterinary › Small Animals › Helminth infection and control
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Keywords
- canine heartworm disease, Dirofilaria immitis, immune complexes, doxycycline, microfilariae, treatment response monitoring
- MeSH terms
- Animals, Antigens, Helminth, Dirofilaria immitis, Dirofilariasis, Dog Diseases, Dogs, Doxycycline, False Negative Reactions, Filaricides, Lactones, Macrocyclic Compounds
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