Topical Fipronil/Permethrin Combination Repels Visceral Leishmaniasis Vector

Visceral leishmaniasis, also known as black fever, is a zoonotic infection with the protozoan parasite Leishmania infantum. The disease is endemic in portions of South America, with 3690 human deaths reported in Brazil from 2000 to 2015.

The main vector for L infantum is the phlebotomine sand fly, namely Lutzomyia longipalpis in the New World. Most human infections with L infantum occur from the bite of a female sand fly that acquired the parasite while feeding on an infected reservoir. The domestic dog is considered an important reservoir for visceral leishmaniasis in endemic areas.

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Researchers in Brazil recently tested the efficacy of a new topical combination drug (Frontline Tri-Act, Merial, now part of Boehringer Ingelheim) against Lu longipalpis parasitism in canine subjects.

Study Design

Eight male and 8 female beagles aged 2 to 4 years and weighing 8.4 to 14.4 kg were enrolled in the study. Each dog had received no ectoparasiticides for at least 3 months before the study and received no medications during the study other than the treatment drugs and injectable anesthesia before sand fly exposures. Dogs were housed individually for the duration of the study.

Investigators randomly allocated the dogs into 2 treatment groups, taking care to match groups as closely as possible by weight. On day 0 of the study, dogs in the experimental group received a topical application on the dorsal midline containing a minimum dose of 50.48 mg/kg permethrin and 6.76 mg/kg fipronil.

Lu longipalpis used for exposures were obtained from an established laboratory colony. Exposures occurred during the nighttime on days 1, 14, 21, and 30 of the study. Before exposure, each dog was administered either intramuscular acepromazine (0.1 mg/kg), ketamine (11 mg/kg), and midazolam (0.5 mg/kg) or ketamine (22 mg/kg) and xylazine (1.1 mg/kg). An average of 79 female and 58.2 male Lu longipalpis were released into each dog’s exposure cage for 65 (+/-15) minutes, then recovered and classified as engorged or nonengorged. The authors calculated repellency of each treatment based on proportion of engorged sand flies.

Results

All dogs remained healthy throughout the study, although 1 dog was replaced by a backup dog on day 1 due to anesthesia intolerance.

The percentage of engorged Lu longipalpis collected from untreated control dogs on days 1, 14, 21, and 30 was 84.6, 98.8, 98.7 and 99.4%, respectively, thus confirming aggressive feeding by the sand fly population. Compared with the untreated group, the calculated percent repellency against sand flies in the treated group was 95.7, 94.3, 81.7 and 72.2% on days 1, 14, 21, and 30, respectively.

Major Finding

The combination of fipronil and permethrin demonstrated a strong repellent effect against the sand fly Lu longipalpis. Topical application resulted in a rapid onset of action and protection that lasted 30 days for most dogs, making it an effective prophylactic option against the primary vector for L infantum.

Dr. Stilwell received her DVM from Auburn University, followed by an MS in Fisheries and Aquatic Sciences and a PhD in Veterinary Medical Sciences from the University of Florida. She provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting.