title: Moxidectin steady state prior to inoculation protects cats from subsequent, repeated infection with Dirofilaria immitis.
abstract: BACKGROUND
  Infection of cats with Dirofilaria immitis causes seroconversion on antibody tests and pulmonary pathology, often without subsequent development of adult heartworms. Consistent administration of topical 10% imidacloprid-1% moxidectin has been shown to result in sustained plasma levels of moxidectin in cats after three to five treatments, a pharmacokinetic behavior known as "steady state".
  
  
  METHODS
  To evaluate the ability of moxidectin at "steady state" to protect cats from subsequent infection with D. immitis, cats (n = 10) were treated with the labeled dose of topical 10% imidacloprid-1% moxidectin for four monthly treatments. Each cat was inoculated with 25 third-stage larvae of D. immitis 7, 14, 21, and 28 days after the last treatment; non-treated cats (n = 9) were inoculated on the same days, serving as infection controls. Blood samples were collected from each cat from 1 month prior to treatment until 7 months after the final inoculation and tested for antibody to, and antigen and microfilaria of, D. immitis.
  
  
  RESULTS
  Measurement of serum levels of moxidectin confirmed steady state in treated cats. Cats treated with topical 10% imidacloprid-1% moxidectin prior to trickle inoculation of D. immitis L3 larvae throughout the 28 day post-treatment period remained negative on antibody and antigen tests throughout the study and did not develop gross or histologic lesions characteristic of heartworm infection. A majority of non-treated cats tested antibody positive by 3-4 months post infection (6/9) and, after heat treatment, tested antigen positive by 6-7 months post-infection (5/9). Histologic lesions characteristic of D. immitis infection, including intimal and medial thickening of the pulmonary artery, were present in every cat with D. immitis antibodies (6/6), although adult D. immitis were confirmed in only 5/6 antibody-positive cats at necropsy. Microfilariae were not detected at any time.
  
  
  CONCLUSIONS
  Taken together, these data indicate that prior treatment with 10% imidacloprid-1% moxidectin protected cats from subsequent infection with D. immitis for 28 days, preventing both formation of a detectable antibody response and development of pulmonary lesions by either immature stages of D. immitis or young adult heartworms.
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. susan.little@okstate.edu.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Little
authors.affiliation: Bayer HealthCare, Animal Health, Shawnee, KS, USA. joe.hostetler@bayer.com.
authors.forename: Joe A
authors.initials: JA
authors.lastname: Hostetler
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. jennifer.e.thomas@okstate.edu.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Thomas
authors.affiliation: Oklahoma Animal Disease Diagnostic Laboratory, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. keith.bailey@okstate.edu.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Bailey
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. anne.barrett@okstate.edu.
authors.forename: Anne W
authors.initials: AW
authors.lastname: Barrett
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. kaylynn@okstate.edu.
authors.forename: Kaylynn
authors.initials: K
authors.lastname: Gruntmeir
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. jeff.gruntmeir@okstate.edu.
authors.forename: Jeff
authors.initials: J
authors.lastname: Gruntmeir
authors.affiliation: Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA. lindsay.starkey@okstate.edu.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Starkey
authors.affiliation: Bayer HealthCare, Animal Health, Shawnee, KS, USA. chris.basel@bayer.com.
authors.forename: Chris
authors.initials: C
authors.lastname: Basel
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. blagbbl@auburn.edu.
authors.forename: Byron L
authors.initials: BL
authors.lastname: Blagburn
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000097:blood; D002371:Cat Diseases / Q000469:parasitology / Q000517:prevention & control*; D002415:Cats; D018890:Chemoprevention / Q000379:methods*; D004183:Dirofilaria immitis / Q000302:isolation & purification*; D004184:Dirofilariasis / Q000469:parasitology / Q000517:prevention & control*; D018942:Macrolides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000871:Anthelmintics; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018942:Macrolides; C027837:moxidectin