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.

Figure 1

Mean levels of moxidectin (μg/L) prior to and during repeated infection with Dirofilaria immitis . Cats were treated with 10% imidacloprid-1% moxidectin on study days −84, −56, −28, and 0. Third-stage larvae of D. immitis (n = 25) were inoculated on days 7, 14, 21, and 28, 1 – 4 weeks after the final treatment was administered.

Figure 2

Photomicrograph of hematoxylin & eosin-stained sections of lung. (a) Intimal thickening, villous proliferation and leukocyte infiltration of the pulmonary artery (arrow) associated with Dirofilaria immitis infection in a non-treated control cat (10× magnification). (b) Medial thickening of pulmonary artery branches (arrowheads) associated with Dirofilaria immitis infection in a non-treated control cat (20× magnification). (c, d) In cats treated with 10% imidacloprid-1% moxidectin prior to repeated inoculation with D. immitis, pulmonary lesions did not develop (10× and 20× magnification, respectively).