A single oral dose of fluralaner (Bravecto®) in dogs rapidly kills 100% of blood‐fed Phlebotomus perniciosus, a main visceral leishmaniasis vector, for at least 1 month after treatment

Abstract

Dogs are the reservoir host of zoonotic visceral leishmaniasis (VL) caused by Leishmania infantum (Kinetoplastida: Trypanosomatidae). Both subclinically-infected and sick animals can be infectious to competent phlebotomine vectors. The degree and duration of insecticidal efficacy of an oral dose of fluralaner (Bravecto ® ; Merck Animal Health) was determined in dogs exposed to bites of Phlebotomus perniciosus (Diptera: Psychodidae), a main Mediterranean vector of VL. Twelve dogs allocated to two groups of six animals each were included in a parallel-group designed, negative-controlled, randomized, blinded, single-centre efficacy study. Group 2 was treated with fluralaner on day 0, and sand-fly exposure of both groups was performed on days 1, 28 and 84. Viability of blood-fed females was assessed up to 96 h after exposure and efficacy was measured as the survival rate of specimens fed on Group 2 versus those fed on Group 1. A mortality of 100% was recorded at 24 h in females fed on Group 2 at both days 1 and 28. Significant insecticidal efficacy was still observed on day 84, with > 50% mortality recorded by 48 h post blood meal in Group 2. Fluralaner treatment of dogs represents a promising and affordable method for reducing the pool of infected vectors in endemic settings of zoonotic VL.

Fluralaner (Bravecto®) induces long-term mortality of Lutzomyia longipalpis after a blood meal in treated dogs

“…longipalpis, with observed mortality of 100, 91.2, 48.7 and 37.5 on post-treatment days 1, 30, 60 and 90, respectively. Furthermore, a study with P. perniciosus showed that 96 h after blood meal, there was 100, 100 and 68.6% mortality on days 1, 28 and 84 post-fluralaner treatment, respectively [27]. In our study, 96 h after a blood meal, 100% mortality was recorded in Lu.…”

“…longipalpis 96 h after a blood meal. On the other hand, fluralaner efficacy against sand fly P. perniciosus was 100, 100 and 52.7 on days 1, 28 and 84 post-treatment, respectively [27]. The prolonged efficacy of fluralaner against Lu.…”

“…longipalpis within 120 h post-blood meal on fluralaner-treated dogs for up to 150 days post-treatment. Susceptibility to fluralaner has been determined in other sand fly species, such as Phlebotomus papatasi and P. perniciosus [25,27]. A survey by Gomez and co-workers noted mortality of 100, 96, 89 and 42% in P. papatasi (24 h post-blood meal directly on dogs) on post-treatment days 3, 31, 45 and 73, respectively [25].…”

“…Fluralaner has been shown to be safe in dogs [22] and has a significant selectivity for insects over mammalian receptors [23]. Experimental studies with fluralaner have shown insecticide activity within short periods of time against Triatoma infestans, the vector of Trypanosoma cruzi (the etiologic agent of Chagas disease [24]) and against some species of phlebotome sand flies, such as Phlebotomus papatasi [25,26] and P. perniciosus [27]. However, to date, there has been no study demonstrating fluralaner action on Lu.…”

Insecticidal efficacy of fluralaner (Bravecto®) against Triatoma brasiliensis, a major vector of Trypanosoma cruzi in Brazil

“…Fluralaner (Bravecto ® ) belongs to the isoxazoline compound class and acts as an antagonist of γ-aminobutyric acid (GABA)-gated chloride ion (Cl − ) channels, preventing the entrance of Cl − into the postsynaptic neuron, leading to hyperexcitability of the insect central nervous system [ 15 ]. Fluralaner (Bravecto ® ) has potent acaricidal activity against ticks and mites, as well as insecticide activity against infestations of phlebotomine sand flies, such as Phlebotomus papatasi [ 34 , 35 ], Phlebotomus perniciosus [ 36 ] and Lutzomyia longipalpis [ 37 ], in dogs, cats and poultry [ 38 – 42 ]. Dogs treated with fluralaner (Bravecto ® ) do not experience any side effects [ 43 ], and the compound has significant selectivity for insects over mammalian neurons [ 44 ].…”