title: False negative antigen tests in dogs infected with heartworm and placed on macrocyclic lactone preventives.
abstract: 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.
authors: Novartis Animal Health, Greensboro, NC, USA. jason.drake@novartis.com.
authors: Jason
authors: J
authors: Drake
authors: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Room 250 74078 McElroy Hall, Stillwater, OK, USA. jeff.gruntmeir@okstate.edu.
authors: Jeff
authors: J
authors: Gruntmeir
authors: Swaim Serum Company, Oklahoma City, OK, USA. hdavvy@hotmail.com.
authors: Hannah
authors: H
authors: Merritt
authors: Novartis Animal Health, Greensboro, NC, USA. lynn.allen@novartis.com.
authors: Lynn
authors: L
authors: Allen
authors: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Room 250 74078 McElroy Hall, Stillwater, OK, USA. susan.little@okstate.edu.
authors: Susan E
authors: SE
authors: Little
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000097:blood*; D004183:Dirofilaria immitis / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D004184:Dirofilariasis / Q000097:blood / Q000175:diagnosis / Q000469:parasitology / Q000517:prevention & control*; D004283:Dog Diseases / Q000097:blood / Q000175:diagnosis / Q000469:parasitology / Q000517:prevention & control*; D004285:Dogs; D004318:Doxycycline / Q000008:administration & dosage / Q000009:adverse effects; D005188:False Negative Reactions; D005369:Filaricides / Q000008:administration & dosage / Q000009:adverse effects*; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects*; D047028:Macrocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000947:Antigens, Helminth; D005369:Filaricides; D007783:Lactones; D047028:Macrocyclic Compounds; D004318:Doxycycline
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