Prevention of Canine Leishmaniosis in a Hyper-Endemic Area Using a Combination of 10% Imidacloprid/4.5% Flumethrin

et al. (2013) Prevention of Canine Leishmaniosis in a Hyper-Endemic Area Using a Combination of 10% Imidacloprid/4.5% Flumethrin. PLoS ONE 8(2): e56374. doi:10.1371/journal.pone.0056374 Prevention of Canine Leishmaniosis in a Hyper-Endemic Area Using a Combination of 10% Imidacloprid/4.5% Flumethrin Domenico Otranto 0 Filipe Dantas-Torres 0 Donato de Caprariis 0 Giancarlo Di Paola 0 Viviana D. Tarallo 0 Maria S. Latrofa 0 Riccardo P. Lia 0 Giada Annoscia 0 Edward B. Breitshwerdt 0 Cinzia Cantacessi 0 Gioia Capelli 0 Dorothee Stanneck 0 Stuart Alexander Ralph, University of Melbourne, Australia 0 1 Dipartimento di Medicina Veterinaria, Universita` degli Studi di Bari , Valenzano , Italy , 2 Departamento de Imunologia, Centro de Pesquisas Aggeu Magalha es (Fiocruz-PE) , Recife, Pernambuco , Brazil , 3 Intracellular Pathogens Research Laboratory, College of Veterinary Medicine, North Carolina State University , Raleigh , North Carolina, United States of America, 4 Center for Biodiscovery and Molecular Development of Therapeutics, James Cook University , Cairns , Australia , 5 Istituto Zooprofilattico Sperimentale delle Venezie, Laboratory of Parasitology , Legnaro, Italy, 6 Bayer Animal Health GmbH, Leverkusen , Germany Background: Dogs are the main reservoir hosts of Leishmania infantum, the agent of human zoonotic visceral leishmaniosis. This study investigated the efficacy of a polymer matrix collar containing a combination of 10% imidacloprid and 4.5% flumethrin as a novel prophylactic measure to prevent L. infantum infections in young dogs from a hyper-endemic area of southern Italy, with a view towards enhancing current control strategies against both human and canine leishmaniosis. Methodology/Principal Findings: The study was carried out on 124 young dogs, of which 63 were collared (Group A) while 61 were left untreated (Group B), from March-April 2011 until March 2012. Blood and skin samples were collected at baseline (April 2011) and at the first, second, third and fourth follow-up time points (July, September 2011 and November 2011, and March 2012, respectively). Bone marrow and conjunctiva were sampled at baseline and at the fourth follow-up. Serological, cytological and molecular tests were performed to detect the presence of L. infantum in the different tissues collected. At the end of the trial, no dog from Group A proved positive for L. infantum at any follow-up, whereas 22 dogs from Group B were infected (incidence density rate = 45.1%); therefore, the combination of 10% imidacloprid and 4.5% flumethrin was 100% efficacious for the prevention of L. infantum infection in young dogs prior to their first exposure to the parasite in a hyper-endemic area for CanL. Conclusions: The use of collars containing 10% imidacloprid and 4.5% flumethrin conferred long-term protection against infection by L. infantum to dogs located in a hyper-endemic area, thus representing a reliable and sustainable strategy to decrease the frequency and spread of this disease among the canine population which will ultimately result in the reduction of associated risks to human health. - Funding: This project was funded by Bayer Animal Health GmbH (Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The study was supported by Bayer Animal Health GmbH (Germany) and Dr. Dorothee Stanneck is an employee of Bayer Animal Health GmbH, Leverkusen, Germany. There are no patents, products in development or marketed products to declare. This does not alter the authors adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. Leishmania infantum is a major protozoan parasite transmitted by arthropod vectors causing visceral and cutaneous leishmaniosis in dogs and humans in southern Europe, Africa, Middle and Far Eastern countries and Central and South America, with approximately 500,000 new infections recorded each year [1,2]. In southern Europe (including Turkey), leishmaniosis caused by L. infantum is endemic, with a total of 3,950 new human cases reported each year [3]. Dogs play a major role as the main reservoir hosts of zoonotic visceral leishmaniosis [4]. Indeed, canine leishmaniosis (CanL) is amongst the most widespread vector-borne parasitic diseases affecting dogs from all continents, except Oceania [5]. In areas where the competent vectors, i.e. phlebotomine sand flies of the genus Phlebotomus (in the Old World) and Lutzomyia (in the Americas), are widespread, human and canine infections are closely associated [6,7] and hotspots of infection correspond to areas whose environmental and climatic conditions are ideal for the development of the arthropod vectors [8,9]. Therefore, over the last decades, considerable efforts have been directed towards monitoring the prevalence and incidence of CanL in both endemic and non-endemic areas, as well as developing novel and cost-effective control strategies against this devastating disease. Recent studies have reported the diffusion of CanL by L. infantum in previously non-endemic areas (e.g., from northern Argentina to northern United States and some provinces of southern Canada) [4,10]. Also, the disease has spread from southern Mediterranean regions to northern Europe [11,12]. CanL is highly prevalent in dogs in South America and in the Mediterranean regions, with up to 60% of infected dogs being asymptomatic, making current estimations of prevalence of infection based on the detection of clinical signs unreliable in both non-endemic and hyper-endemic areas [13,14]. As a consequence of the eco-epidemiological complexities involved in the route of transmission of L. infantum, the control of CanL has proven challenging, and none of the proposed strategies (e.g., dog culling in Brazil, environmental spraying with insecticides) have yielded satisfactory results thus far [4]. For instance, the use of dichlorodiphenyltrichloroethane (DDT) house spraying against phlebotomine sand flies in Brazil has been unsuccessful [15], probably due to failure to apply the insecticide at the right time of year [16] and to the impracticability to reach the natural breeding sites of these insects [17]. Also, due to environmental side effects and human health hazards, organochlorides [e.g., DDT and benzene hexachloride (BHC)] have gradually been substituted by synthetic pyrethroids [1618]. The use of pyrethroids with repellent properties in spot-on formulations [19] or as impregnated collars [20] has represented a useful and cost-effective approach to reduce the risk of L. infantum infection in dogs in endemic areas. In a previous study [21], the use of deltamethrin-impregnated dog collars resulted in a protection rate against canine infections by L. infantum of 50% and 86%, respectively, over two consecutive transmission seasons in Europe [22]. A combination of imidacloprid 10% and permethrin 50% in (...truncated)