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The prevention of canine leishmaniasis and its impact on public health

2013; Elsevier BV; Volume: 29; Issue: 7 Linguagem: Inglês

10.1016/j.pt.2013.05.003

1471-5007

Domenico Otranto, Filipe Dantas‐Torres,

Leptospirosis research and findings

•Dogs should be subjected to periodical clinical and laboratory check-ups towards an early detection of infection.•Each dog (healthy, infected, or diseased) should be protected with pyrethroids to reduce contact with sand flies.•Vaccines against canine leishmaniosis are now available in some countries.•Each of the currently available tools may have advantages and disadvantages. Their combined use may represent the next frontier in canine leishmaniosis prevention.•The dog culling strategy recommended in Brazil is an unethical and ineffective measure. Canine leishmaniasis (CanL) caused by Leishmania infantum is a vector-borne disease of great veterinary and medical significance. Prevention of CanL requires a combined approach including measures focused on dogs and the environment where the vectors perpetuate. Over past decades, considerable effort has been put towards developing novel and cost-effective strategies against CanL. Vaccination is considered among the most promising tools for controlling CanL, and synthetic pyrethroids are useful and cost-effective in reducing risk of L. infantum infection in dogs. The effectiveness of the use of vaccines plus repellents in preventing L. infantum infection and subsequent disease development should be assessed by means of large-scale, randomized controlled field trials because this combined strategy may become the next frontier in the control of CanL. Canine leishmaniasis (CanL) caused by Leishmania infantum is a vector-borne disease of great veterinary and medical significance. Prevention of CanL requires a combined approach including measures focused on dogs and the environment where the vectors perpetuate. Over past decades, considerable effort has been put towards developing novel and cost-effective strategies against CanL. Vaccination is considered among the most promising tools for controlling CanL, and synthetic pyrethroids are useful and cost-effective in reducing risk of L. infantum infection in dogs. The effectiveness of the use of vaccines plus repellents in preventing L. infantum infection and subsequent disease development should be assessed by means of large-scale, randomized controlled field trials because this combined strategy may become the next frontier in the control of CanL. Canine leishmaniasis (CanL) caused by Leishmania infantum is among the most important vector-borne parasitic diseases of dogs, occurring on all continents, except Oceania [1Dantas-Torres F. et al.Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences.Trends Parasitol. 2012; 28: 531-538Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. In dogs, the infection may be asymptomatic (over 80% of cases in some areas) or may evolve to life-threatening overt disease, with a wide range of clinical signs (from localized skin alterations to severe loss of weight and generalized lymphadenomegaly). For its potential severity in dogs and its zoonotic nature, the prevention of this infection is not only desirable but also a must for both dog and human health (Figure 1). Because the infection to a receptive host occurs through the bite of sand flies of the genus Phlebotomus (in the Old World) and genus Lutzomyia (in the Americas) [2Maroli M. et al.Phlebotomine sand flies and the spreading of leishmaniases and other diseases of public health concern.Med. Vet. Entomol. 2013; 27: 123-147Crossref PubMed Scopus (489) Google Scholar], the management of this disease is extremely complex [1Dantas-Torres F. et al.Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences.Trends Parasitol. 2012; 28: 531-538Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar, 3Otranto D. et al.Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.Vet. Parasitol. 2010; 172: 323-332Crossref PubMed Scopus (83) Google Scholar]. In this regard, the prevention of CanL should include measures targeting animals (at individual and population level) and the environment. However, the adoption and transportation of dogs from areas of CanL endemicity has resulted in the introduction and spread of disease to regions where infections were not previously found [4Maroli M. et al.The northward spread of leishmaniasis in Italy: evidence from retrospective and ongoing studies on the canine reservoir and phlebotomine vectors.Trop. Med. Int. Health. 2008; 13: 256-264Crossref PubMed Scopus (249) Google Scholar, 5Petersen C.A. Barr S.C. Canine leishmaniasis in North America: emerging or newly recognized?.Vet. Clin. North Am. Small Anim. Pract. 2009; 39: 1065-1074Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 6Otranto D. et al.Toward diagnosing Leishmania infantum infection in asymptomatic dogs in an area where leishmaniasis is endemic.Clin. Vaccine Immunol. 2009; 16: 337-343Crossref PubMed Scopus (68) Google Scholar], which may create new epidemiological scenarios, further complicating the zoonotic potential. This often occurs in combination with emerging immunosuppressive conditions in humans (e.g., HIV/AIDS) that may increase the risk of zoonotic diseases such as visceral leishmaniasis (VL) [7Fernandéz-Guerrero M.L. et al.Visceral leishmaniasis in immunocompromised patients with and without AIDS: a comparison of clinical features and prognosis.Acta Trop. 2004; 90: 11-16Crossref PubMed Scopus (66) Google Scholar]. Although the risk of CanL transmission is reputed to be low in the absence of sand flies, other ways of transmission, such as venereal and transplacental transmission, should be seriously considered [8Naucke T.J. Lorentz S. First report of venereal and vertical transmission of canine leishmaniosis from naturally infected dogs in Germany.Parasit. Vectors. 2012; 5: 67Crossref PubMed Scopus (75) Google Scholar]. Here, we summarize the main difficulties in setting control plans as well as current knowledge on the prevention and control of CanL, with emphasis on currently available tools and future research needs. Dogs are regarded as the principal reservoirs of L. infantum, and for this reason they are the target of control programs in some countries, such as in Brazil, where approximately 3500 human cases of zoonotic VL are reported each year [1Dantas-Torres F. et al.Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences.Trends Parasitol. 2012; 28: 531-538Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. This figure is significantly different from the Mediterranean region, where approximately 875 human cases are reported annually [9Alvar J. et al.Leishmaniasis worldwide and global estimates of its incidence.PLoS ONE. 2012; 7: e35671Crossref PubMed Scopus (3617) Google Scholar]. However, although CanL is thought to be highly prevalent in several countries, mainly in South America and in the Mediterranean region (Figure 1), a precise account of its actual distribution and frequency is currently unavailable. Based on serological surveys, it has been estimated in the past that over 2.5 million L. infantum-infected dogs are present in southern Europe [10Moreno J. Alvar J. Canine leishmaniasis: epidemiological risk and the experimental model.Trends Parasitol. 2002; 18: 399-405Abstract Full Text Full Text PDF PubMed Scopus (355) Google Scholar]; from these numbers, pervasive infection of dogs with L. infantum does not necessarily imply a higher incidence of the disease in humans. Importantly, stray dogs that are not treated with proper preventatives (e.g., insecticide-impregnated collars) may potentially play a role in maintaining CanL, in areas where the disease is endemic. In some European countries, the existence of municipal kennels, where dogs are kept throughout their life, may represent a major barrier to the control of CanL (Figure 1). Under these conditions, focal spots of CanL may easily occur with infection of up to 35% of dogs exposed to sand fly bites over a single season [11Otranto D. et al.Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.PLoS ONE. 2013; 8: e56374Crossref PubMed Scopus (49) Google Scholar]. This picture highlights how pivotal it is to control CanL by different approaches according to the epidemiology of the disease in a given area and the difficulties inherent to local conditions [1Dantas-Torres F. et al.Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences.Trends Parasitol. 2012; 28: 531-538Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar]. The control of CanL is a difficult task because of the complex transmission cycle of L. infantum. Based on current knowledge and considering the tools available, the environmental control of immature sand flies is unfeasible because the microhabitats of larvae and pupae are extremely variable, including, for example, tree roots, animal burrows, decaying foliage, and tree holes [2Maroli M. et al.Phlebotomine sand flies and the spreading of leishmaniases and other diseases of public health concern.Med. Vet. Entomol. 2013; 27: 123-147Crossref PubMed Scopus (489) Google Scholar]. Similarly, evidence indicates that spatial fogging for adult sand fly control is useless and that the residual effect of house wall spraying is very short [12Romero G.A. Boelaert M. Control of visceral leishmaniasis in Latin America – a systematic review.PLoS Negl. Trop. Dis. 2010; 4: e584Crossref PubMed Scopus (263) Google Scholar], making the residual spraying of houses impractical and ineffective, particularly in rural areas [13Alexander B. Maroli M. Control of phlebotomine sandflies.Med. Vet. Entomol. 2003; 17: 1-18Crossref PubMed Scopus (234) Google Scholar]. A proper assessment of the infection status of dogs is fundamental for a better determination of actions to be taken, to start the treatment in the initial stages of the disease, and to monitor the effectiveness of control measures. In areas where L. infantum is prevalent, most of the dogs and people exposed to sand flies will come into contact with the parasite, but remain asymptomatic [14Dantas-Torres F. et al.Seroepidemiological survey on canine leishmaniasis among dogs from an urban area of Brazil.Vet. Parasitol. 2006; 310: 54-60Crossref Scopus (90) Google Scholar, 15Costa C.H. et al.Asymptomatic human carriers of Leishmania chagasi.Am. J. Trop. Med. Hyg. 2002; 66: 334-337PubMed Google Scholar]. Although asymptomatic dogs may potentially be infectious to sand flies [16Molina R. et al.Infectivity of dogs naturally infected with Leishmania infantum to colonized Phlebotomus perniciosus.Trans. R. Soc. Trop. Med. Hyg. 1994; 88: 491-493Abstract Full Text PDF PubMed Scopus (272) Google Scholar, 17Michalsky E.M. et al.Infectivity of seropositive dogs, showing different clinical forms of leishmaniasis, to Lutzomyia longipalpis phlebotomine sand flies.Vet. Parasitol. 2007; 147: 67-76Crossref PubMed Scopus (124) Google Scholar], the role of asymptomatic humans in the epidemiology of VL has yet to be ascertained [15Costa C.H. et al.Asymptomatic human carriers of Leishmania chagasi.Am. J. Trop. Med. Hyg. 2002; 66: 334-337PubMed Google Scholar]. It is worth noting that the definitive diagnosis of L. infantum infection in asymptomatic dogs and people is often troublesome due to the inherent limitations of serological and parasitological methods [15Costa C.H. et al.Asymptomatic human carriers of Leishmania chagasi.Am. J. Trop. Med. Hyg. 2002; 66: 334-337PubMed Google Scholar, 18Miró G. et al.Canine leishmaniosis – new concepts and insights on an expanding zoonosis: part two.Trends Parasitol. 2008; 8: 371-377Abstract Full Text Full Text PDF Scopus (186) Google Scholar]. For example, serology may not be a good indicator of infection due to the variable time in seroconversion. Additionally, the costs attached to the systematic serological testing of dogs may be difficult to handle by local public health authorities, especially in large countries such as Brazil where the number of dogs living in areas with a high rate of infection might be huge [1Dantas-Torres F. et al.Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences.Trends Parasitol. 2012; 28: 531-538Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar, 6Otranto D. et al.Toward diagnosing Leishmania infantum infection in asymptomatic dogs in an area where leishmaniasis is endemic.Clin. Vaccine Immunol. 2009; 16: 337-343Crossref PubMed Scopus (68) Google Scholar, 14Dantas-Torres F. et al.Seroepidemiological survey on canine leishmaniasis among dogs from an urban area of Brazil.Vet. Parasitol. 2006; 310: 54-60Crossref Scopus (90) Google Scholar, 19Baneth G. Leishmaniases.in: Greene C.E. Infectious Diseases of the Dog and Cat. 3rd edn. Saunders/Elsevier, 2006: 685-698Google Scholar]. Conversely, microscopic examination of stained smears (e.g., lymph node and bone marrow) is a simple method, but has a low sensitivity, particularly in asymptomatic dogs [6Otranto D. et al.Toward diagnosing Leishmania infantum infection in asymptomatic dogs in an area where leishmaniasis is endemic.Clin. Vaccine Immunol. 2009; 16: 337-343Crossref PubMed Scopus (68) Google Scholar], whereas molecular tools, although the most sensitive and specific, often have prohibitive costs [6Otranto D. et al.Toward diagnosing Leishmania infantum infection in asymptomatic dogs in an area where leishmaniasis is endemic.Clin. Vaccine Immunol. 2009; 16: 337-343Crossref PubMed Scopus (68) Google Scholar, 20Paiva Cavalcanti M. et al.The development of a real-time PCR assay for the quantification of Leishmania infantum DNA in canine blood.Vet. J. 2009; 182: 356-358Crossref PubMed Scopus (50) Google Scholar]. Available data clearly show that there is no gold standard to detect Leishmania infections in asymptomatic dogs [6Otranto D. et al.Toward diagnosing Leishmania infantum infection in asymptomatic dogs in an area where leishmaniasis is endemic.Clin. Vaccine Immunol. 2009; 16: 337-343Crossref PubMed Scopus (68) Google Scholar], indicating that improved diagnostic tests are needed. In spite of the major concerns related to the complex ecology of vectors, control measures aimed at reducing vector populations in the environment have also been employed. The application of insecticides may eventually have a transitory effect but is typically unsustainable in the long term for several technical and economic reasons. For example, a variety of sand fly species may be potentially involved in the transmission of L. infantum [2Maroli M. et al.Phlebotomine sand flies and the spreading of leishmaniases and other diseases of public health concern.Med. Vet. Entomol. 2013; 27: 123-147Crossref PubMed Scopus (489) Google Scholar], and the ecology and behavior of each species may vary widely. Similarly, the size of the area to be treated in countries such as Brazil where leishmaniasis is endemic may be vast and make environmental control economically unaffordable. The application of insecticides on the walls and roofs of human habitations (indoor residual spraying; IRS) and in animal shelters (e.g., chicken pens and corrals) was shown to be effective in reducing the population of sand flies [13Alexander B. Maroli M. Control of phlebotomine sandflies.Med. Vet. Entomol. 2003; 17: 1-18Crossref PubMed Scopus (234) Google Scholar, 21Maroli M. et al.Guidelines for prevention of leishmaniasis in dogs.J. Am. Vet. Med. Assoc. 2010; 236: 1200-1206Crossref PubMed Scopus (63) Google Scholar]. Environmental and human health hazard concerns around the employment of organochlorides and other chemical groups (e.g., organophosphates and carbamates) have progressively led to their substitution by synthetic pyrethroids (e.g., α-cypermethrin, cypermethrin, deltamethrin, and λ-cyhalothrin), which are currently used by public health authorities in several countries. Another major constraint in employing insecticides in the environment for sand fly control relies on the fact that their natural resting and breeding sites are difficult to find [13Alexander B. Maroli M. Control of phlebotomine sandflies.Med. Vet. Entomol. 2003; 17: 1-18Crossref PubMed Scopus (234) Google Scholar]. However, IRS may be useful in particular situations, such as when a high density of sand flies is found near or in human habitations. Similarly, chicken coops, pigsties, corrals, and dog shelters may represent a 'natural lure' for the vectors [22Tarallo V.D. et al.Phlebotomine sand fly population dynamics in a leishmaniasis endemic peri-urban area in southern Italy.Acta Trop. 2010; 116: 227-234Crossref PubMed Scopus (57) Google Scholar, 23Costa P.L. et al.Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil.Acta Trop. 2013; 26: 99-102Crossref Scopus (40) Google Scholar] and should be targeted by control activities. In any case, information on sand fly population dynamics is fundamental to optimize timing and modalities of insecticide applications. Microhabitats favorable to their development, for example, in crevices and cracks on the walls and humid soil in shaded areas, should also be removed [13Alexander B. Maroli M. Control of phlebotomine sandflies.Med. Vet. Entomol. 2003; 17: 1-18Crossref PubMed Scopus (234) Google Scholar]. Furthermore, the destruction of these microhabitats has been considered as one of the few examples of effective noninsecticidal control of sand flies [13Alexander B. Maroli M. Control of phlebotomine sandflies.Med. Vet. Entomol. 2003; 17: 1-18Crossref PubMed Scopus (234) Google Scholar], but such a measure is difficult to apply; there is no convincing scientific evidence showing that cleaning microhabitats may have an impact on the incidence of VL in humans and dogs. The use of repellents such as synthetic pyrethroids on dogs has become the most effective tool for prevention of L. infantum infection in these animals. Their mode of action, a toxic and irritating effect on sand flies, causes insect disorientation and sudden abandonment of the host followed by death soon after the landing of an insect on the coat of a treated animal. Hence, bloodfeeding usually does not occur and infection is usually prevented (Table 1). The effect of synthetic pyrethroids in spot-on formulations or collars (Figure 2) may last from 1 to approximately 8 months, respectively [3Otranto D. et al.Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.Vet. Parasitol. 2010; 172: 323-332Crossref PubMed Scopus (83) Google Scholar, 11Otranto D. et al.Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.PLoS ONE. 2013; 8: e56374Crossref PubMed Scopus (49) Google Scholar, 24Killick-Kendrick R. The biology and control of phlebotomine sand flies.Clin. Dermatol. 1999; 17: 279-289Abstract Full Text Full Text PDF PubMed Scopus (521) Google Scholar].Table 1Efficacy of pyrethroids to prevent CanL under field conditionsPharmaceutical compoundFormulationStudy siteStudy durationTreated dogsUntreated animals (incidence)Efficacy (%)RefsImidacloprid 10% and permethrin 50%Spot-onItaly12 months209aDogs treated once a month.; 204bDogs treated twice a month.218 (9.8%)89%aDogs treated once a month.; 90.3%bDogs treated twice a month.37Otranto D. et al.Efficacy of a combination of 10% imidacloprid/50% permethrin for the prevention of leishmaniasis in kennelled dogs in an endemic area.Vet. Parasitol. 2007; 144: 270-278Crossref PubMed Scopus (76) Google ScholarPermethrin 65%Spot-onBrazil4 months230160 (7.4%)50%71Giffoni J.H. et al.Evaluation of 65% permethrin spot-on for prevention of canine visceral leishmaniasis: effect on disease prevalence and the vectors (Diptera: Psychodidae) in a hyperendemic area.Vet. Ther. 2002; 3: 485-492PubMed Google ScholarPermethrin 65%Spot-onItaly2 seasons120188 (15%)84%72Ferroglio E. et al.Evaluation of 65% permethrin spot-on and deltamethrin-impregnated collars for canine Leishmania infantum infection prevention.Zoonoses Public Health. 2008; 55: 145-148Crossref PubMed Scopus (58) Google ScholarDeltamethrin 4%CollarsItaly2 seasons119188 (15%)84%72Ferroglio E. et al.Evaluation of 65% permethrin spot-on and deltamethrin-impregnated collars for canine Leishmania infantum infection prevention.Zoonoses Public Health. 2008; 55: 145-148Crossref PubMed Scopus (58) Google ScholarImidacloprid 10% and permethrin 50%Spot-onItaly24 months7156 (47.6%)100%3Otranto D. et al.Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.Vet. Parasitol. 2010; 172: 323-332Crossref PubMed Scopus (83) Google ScholarDeltamethrin 4%CollarsItaly2 seasons354371 (25.8%)50–86%34Maroli M. et al.Evidence for an impact on the incidence of canine leishmaniasis by the use of deltamethrin-impregnated dog collars in southern Italy.Med. Vet. Entomol. 2001; 15: 358-363Crossref PubMed Scopus (130) Google ScholarDeltamethrin 4%CollarsItaly2 seasons6060 (41.2%)51%73Foglia Manzillo V. et al.Deltamethrin-impregnated collars for the control of canine leishmaniasis: evaluation of the protective effect and influence on the clinical outcome of Leishmania infection in kennelled stray dogs.Vet. Parasitol. 2006; 142: 142-145Crossref PubMed Scopus (73) Google ScholarDeltamethrin 4%CollarsTunisia2 seasons4238 (15.8%)100%74Aoun K. et al.[Efficacy of deltamethrine-impregnated collars Scalibor in the prevention of canine leishmaniasis in the area of Tunis].Arch. Inst. Pasteur Tunis. 2008; 85 (in French): 63-68PubMed Google ScholarDeltamethrin 4%CollarsIran6 months354466 (6.6%)54%cThis is an estimation of reduction in dog seroconversion during a transmission season.71Giffoni J.H. et al.Evaluation of 65% permethrin spot-on for prevention of canine visceral leishmaniasis: effect on disease prevalence and the vectors (Diptera: Psychodidae) in a hyperendemic area.Vet. Ther. 2002; 3: 485-492PubMed Google ScholarDeltamethrin 4%CollarsBrazil12 months13697 (17.6%)50%33Reithinger R. et al.Are insecticide-impregnated dog collars a feasible alternative to dog culling as a strategy for controlling canine visceral leishmaniasis in Brazil?.Int. J. Parasitol. 2004; 34: 55-62Crossref PubMed Scopus (102) Google ScholarImidacloprid 10% and flumethrin 4.5%CollarsItaly24 months6361 (35.3%)100%11Otranto D. et al.Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.PLoS ONE. 2013; 8: e56374Crossref PubMed Scopus (49) Google Scholara Dogs treated once a month.b Dogs treated twice a month.c This is an estimation of reduction in dog seroconversion during a transmission season. Open table in a new tab When a spot-on formulation is applied, it usually takes 24 h for the insecticide to spread throughout the stratum corneum. It is recommended to apply the first treatment 1 month before the sand fly season occurs in order to achieve the highest level of protection [3Otranto D. et al.Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.Vet. Parasitol. 2010; 172: 323-332Crossref PubMed Scopus (83) Google Scholar]. On the contrary, powders and sprays have an immediate effect but a short residual activity. Moreover, the use of a slow-release collar matrix system with a combination of 10% imidacloprid and 4.5% flumethrin (Seresto®, Bayer Animal Health) has resulted in an increased period of efficacy against ticks and fleas [25Stanneck D. et al.The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats.Parasit. Vectors. 2012; 5: 73Crossref PubMed Scopus (41) Google Scholar, 26Stanneck D. et al.Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe.Parasit. Vectors. 2012; 5: 66Crossref PubMed Scopus (48) Google Scholar]. The efficacy of several repellents against sand flies has been evaluated under laboratory and field conditions with encouraging results. For example, the insecticidal effect of deltamethrin and permethrin, alone or in combination with other insecticides (e.g., imidacloprid), was experimentally tested against different sand fly vectors by evaluating the number of unfed female sand flies collected soon after contact with a treated animal and their mortality within 24 h after exposure to treated dogs [27Halbig P. et al.Further evidence that deltamethrin-impregnated collars protect domestic dogs from sandfly bites.Med. Vet. Entomol. 2000; 14: 223-226Crossref PubMed Scopus (35) Google Scholar, 28David J.R. et al.Deltamethrin-impregnated dog collars have a potent anti-feeding and insecticidal effect on Lutzomyia longipalpis and Lutzomyia migonei.Mem. Inst. Oswaldo Cruz. 2001; 96: 839-847Crossref PubMed Scopus (58) Google Scholar, 29Reithinger R. et al.Topical insecticide treatments to protect dogs from sand fly vectors of leishmaniasis.Emerg. Infect. Dis. 2001; 7: 872-876PubMed Google Scholar, 30Mencke N. et al.Repellent efficacy of a combination containing imidacloprid and permethrin against sand flies (Phlebotomus papatasi) on dogs.Parasitol. Res. 2003; 90: 108-111Crossref Scopus (60) Google Scholar, 31Molina R. et al.Evaluation of a spray of permethrin and pyriproxyfen for the protection of dogs against Phlebotomus perniciosus.Vet. Rec. 2006; 159: 206-209Crossref PubMed Scopus (21) Google Scholar, 32Mirò G. et al.Evaluation of the efficacy of a topically administered combination of imidacloprid and permethrin against Phlebotomus perniciosus in dog.Vet. Parasitol. 2007; 143: 375-379Crossref PubMed Scopus (41) Google Scholar]. The results of laboratory studies were generally positive, with an antifeeding effect ranging from 84% to 96% of sand flies and an insecticidal activity of near 100% in the few fed females. These results fostered field investigations in the Old and the New Worlds with the ultimate goal of finding an effective product to protect dogs. The use of pyrethroids with repellent properties in impregnated collars [33Reithinger R. et al.Are insecticide-impregnated dog collars a feasible alternative to dog culling as a strategy for controlling canine visceral leishmaniasis in Brazil?.Int. J. Parasitol. 2004; 34: 55-62Crossref PubMed Scopus (102) Google Scholar] and spot-on formulations [3Otranto D. et al.Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.Vet. Parasitol. 2010; 172: 323-332Crossref PubMed Scopus (83) Google Scholar] was demonstrated to be a suitable approach to reduce the risk of L. infantum infection in dogs. Specifically, collars containing 4% deltamethrin (Scalibor®, Intervet) [34Maroli M. et al.Evidence for an impact on the incidence of canine leishmaniasis by the use of deltamethrin-impregnated dog collars in southern Italy.Med. Vet. Entomol. 2001; 15: 358-363Crossref PubMed Scopus (130) Google Scholar, 35Killick-Kendrick R. et al.Protection of dogs from the bites of phlebotomine sandflies by deltamethrin collars for the control of canine leishmaniasis.Med. Vet. Entomol. 1997; 11: 105-111Crossref PubMed Scopus (123) Google Scholar] or 10% imidacloprid and 4.5% flumethrin [11Otranto D. et al.Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.PLoS ONE. 2013; 8: e56374Crossref PubMed Scopus (49) Google Scholar], and a spot-on formulation containing 10% imidacloprid and 50% permethrin (Advantix®, Bayer) [3Otranto D. et al.Prevention of endemic canine vector-borne diseases using imidacloprid 10% and permethrin 50% in young dogs: a longitudinal field study.Vet. Parasitol. 2010; 172: 323-332Crossref PubMed Scopus (83) Google Scholar] have been used for reducing the biting rate of sand fly vectors, exhibiting protection rates ranging from 50% to 100% over two consecutive transmission seasons (Table 1). Based on current knowledge, topical insecticides used on dogs represent a promising tool for reducing the transmission of infection to dogs [11Otranto D. et al.Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.PLoS ONE. 2013; 8: e56374Crossref PubMed Scopus (49) Google Scholar, 34Maroli M. et al.Evidence for an impact on the incidence of canine leishmaniasis by the use of deltamethrin-impregnated dog collars in southern Italy.Med. Vet. Entomol. 2001; 15: 358-363Crossref PubMed Scopus (130) Google Scholar, 35Killick-Kendrick R. et al.Protection of dogs from the bites of phlebotomine sandflies by deltamethrin collars for the control of canine leishmaniasis.Med. Vet. Entomol. 1997; 11: 105-111Crossref PubMed Scopus (123) Google Scholar, 36Gavgani A.S. et al.Domestic dog ownership in Iran is a risk factor for human infection with Leishmania infantum.Am. J. Trop. Med. Hyg. 2002; 67: 511-515PubMed Google Scholar, 37Otranto D. et al.Efficacy of a combination of 10% imidacloprid/50% permethrin for the prevention of leishmaniasis in kennelled dogs in an endemic area.Vet. Parasitol. 2007; 144: 270-278Crossref PubMed Scopus (76) Google Scholar]. Large-scale studies in Brazil would be needed to assess whether the massive use of collars in dogs living in a given community would impact on the incidence of the disease in humans. Over the past decades, considerable effort has been made towards selecting potential Leishmania antigens as vaccine candidates as well as the best adjuvant for such vaccines [38Palatnik-de-Sousa C.B. Vaccines for leishmaniasis in the