Autor/a:
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Ares Gómez, Sonia; Lucientes Curdi, Javier; Castillo Hernández, Juan Antonio; Peris Peris, Paz; Esteban Gil, Adriana; Oropeza Velasquez, Ronald Vladimir; Ortega Hernández, Paula; Picado, Albert
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Abstract:
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BACKGROUND: Zoonotic visceral leishmaniasis (ZVL) caused by
Leishmania (Leishmania) infantum is an important disease in
humans and dogs. Different mammal species are reservoirs but
dogs are considered to be the main one. Phlebotomine sand flies
are the proven vector. Four systemic insecticides approved for
their use in dogs were previously selected based on their
potential to be used in endemic countries as part of the control
programs of ZVL. These insecticides are proved to be safe and
effective against the on-label insects and parasites, but there
is no information about their activity against phlebotomine sand
flies. METHODS: The phlebotomine mortality of four systemic
insecticides in dogs was evaluated using two randomized clinical
trials. For the first trial, thirty dogs were randomly allocated
into five groups: four treatments and one control, of equal
size. The treatments evaluated were: Guardian(R)SR, Elanco
(moxidectin); Comfortis(R), Elanco (spinosad); Bravecto(R),
Merck Animal Health (fluralaner); and NexGard(R), Merial
(afoxolaner). Blood from dogs was taken at days 2, 4, 21 and 31
post-treatment (trial 1). The compound that showed the highest
efficacy was selected for a second trial (trial 2) with 20 dogs
sampled at days 0, 2, 4, 7, 14, 18, 32, 39, 51 and 84
post-treatment. Membrane feeding bioassays with Phlebotomus
papatasi were used to evaluate the phlebotomine mortality
efficacy of the different treatments. Phlebotomine mortality was
observed every 24 h following the membrane feeding during 5
days. A mixed model for a negative binomial logistic regression,
and a Cox proportional hazard mixed model were used to estimate
phlebotomine mortality due to different treatments. RESULTS:
Fluralaner was the only compound that showed significant
phlebotomine mortality. Fluralaner maintained the phlebotomine
mortality between 60-80% for 30 days after treatment. In trial 1
we found that fluralaner increased the risk of death by 1.9
times (95% CI: 1.02-3.6) and 1.7 times (95% CI: 1.09-2.6) at
days 2 and 4 after treatment. The Cox model resulted in an
increase of 1.47 (95% CI: 1.1-1.96) times in hazard risk at day
2 and 1.89 (95% CI: 1.35-2.45) at day 4 after treatment. In
trial 2 we found that fluralaner increased the risk of death by
1.64 times (95% CI: 1.16-2.54) and 1.97 times (95% CI:
1.23-3.17) at days 14 and 32. The hazard risk was also increased
by 1.92 (95% CI: 1.4-2.64) times at day 14 after treatment.
Phlebotomine survival including all experimental days was
significantly lower in the fluralaner group in both trials.
CONCLUSIONS: A single oral treatment of fluralaner in dogs
induces phlebotomine mortality. Systemic insecticides in dogs
should be considered as a potential preventive measure of ZVL. |