The efficacy of a topical formulation of selamectin plus sarolaner in preventing the development of a macrocyclic lactone-resistant strain of Dirofilaria immitis in cats

Vet Parasitol. 2020 Jun:282:109122. doi: 10.1016/j.vetpar.2020.109122. Epub 2020 May 11.

Abstract

Revolution®/Stronghold® Plus, a topical endectocide incorporating 6 mg/kg selamectin plus 1 mg/kg sarolaner, is approved for use in cats to prevent heartworm disease. The efficacy of selamectin has not previously been evaluated against any macrocyclic lactone (ML)-resistant heartworm strains in cats for prevention of heartworm disease. In this study, an experimental combination formulation of selamectin (6 mg/kg) plus sarolaner (2 mg/kg) was assessed for preventing the development of a ML-resistant strain of Dirofilaria immitis in cats. Forty purpose-bred domestic shorted-haired cats (20 males; 20 females) from 7-9 months of age and negative for heartworm antigen prior to study inclusion were used. On Day -30, cats were inoculated with 100 D. immitis L3 (ZoeMO strain) subcutaneously in the inguinal area. Cats were randomly allocated to one of the following four treatments with associated dosing regimens: T01 (vehicle-treated control on Days 0, 28, and 56), T02 (single dose of selamectin plus sarolaner combination on Day 0 only), T03 (selamectin plus sarolaner combination on Days 0, 28, and 56) or T04 (single dose of selamectin on Day 0 only). All treatments were administered topically in an isopropyl alcohol-based formulation. Selamectin was administered at 6 mg/kg in both standalone and combination formulations. Sarolaner was administered at 2 mg/kg. Cats were necropsied on Day ∼145 (∼175 days post infection) and adult worms were counted. Nine of ten cats in the control group (T01) were infected with adult worms (range, 1-23; geometric mean, 3.5). In contrast, all cats in T03 had zero heartworms. Only two cats in T02 (0-3; 0.2) and a single cat in the T04 (0-1; 0.1) had heartworms. Compared to T01 (control cats), all treated cats had significantly (p < 0.0001) reduced worm burdens, with treatment efficacies of 100% (T03), 93.5% (T02) and 98% (T04). A topical combination of selamectin (6 mg/kg) plus sarolaner (2 mg/kg) was 100% efficacious in preventing the development of an ML-resistant strain of D. immitis (ZoeMO) in cats when administered as three consecutive monthly treatments. A single dose was highly (93.5%) but incompletely effective.

Keywords: Cat; Dirofilaria immitis; Heartworm; Macrocyclic Lactone; Prevention; Resistance; Sarolaner; Selamectin.

MeSH terms

  • Administration, Topical
  • Animals
  • Antinematodal Agents / pharmacology*
  • Azetidines / pharmacology*
  • Cat Diseases / parasitology
  • Cat Diseases / prevention & control*
  • Cats
  • Dirofilaria immitis / drug effects*
  • Dirofilariasis / parasitology
  • Dirofilariasis / prevention & control*
  • Female
  • Ivermectin / analogs & derivatives*
  • Ivermectin / pharmacology
  • Male
  • Spiro Compounds / pharmacology*

Substances

  • Antinematodal Agents
  • Azetidines
  • Spiro Compounds
  • sarolaner
  • Ivermectin
  • selamectin