Update on therapy and prevention of canine leishmaniasis

Summary

Canine leishmaniasis is an emerging infection with increasing importance because the main vector also exists in Germany and autochthonous infections have been described. In this article we present the latest information available regarding therapy and prevention of this disease. Allopurinol-resistant Leishmania infantum strains were isolated from dogs which experienced recurrent disease while being treated with allopurinol, highlighting the need for alternative treatment options. Differing results of long-term studies on the efficacy of miltefosine in combination with allopurinol in comparison to meglumine antimoniate and allopurinol can affect the selection of the treatment protocol. A high number of repellents with distinctive characteristics is available for the prevention of infection in dogs. In Europe, two vaccines are licensed for dogs which aim at reducing the risk of an active infection and the severity clinical disease.

Keywords

Dietary nucleotides - AHCC - resistance - vaccination - LetiFend® - Cani-Leish®

• Literatur

• 1 Baneth G, Koutinas AF, Solano-Gallego L, Bourdeau P, Ferrer L. Canine leishmaniosis – new concepts and insights on an expanding zoonosis: part one. Trends Parasitol 2008; 24 (07) 324-330.
• 2 Bizikova P, Moriello KA, Linder KE, Sauber L. Dinotefuran/pyriproxyfen/ permethrin pemphigus-like drug reaction in three dogs. Vet Dermatol 2015; 26 (03) 206-208 e45–46.
• 3 Brianti E, Gaglio G, Napoli E, Falsone L, Prudente C, Solari FBasano, Latrofa MS, Tarallo VD, Dantas-Torres F, Capelli G, Stanneck D, Giannetto S, Otranto D. Efficacy of a slow-release imidacloprid (10 %)/flumethrin (4.5 %) collar for the prevention of canine leishmaniosis. Parasit Vectors 2014; 07: 327.
• 4 Brianti E, Napoli E, Gaglio G, Falsone L, Giannetto S, Solari FBasano, Nazzari R, Latrofa MS, Annoscia G, Tarallo VD, Stanneck D, Dantas-Torres F, Otranto D. Field evaluation of two different treatment approaches and their ability to control fleas and prevent canine leishmaniosis in a highly endemic area. PLoS neglected tropical diseases 2016; 10 (09) e0004987.
• 5 Carcelen J, Iniesta V, Fernandez-Cotrina J, Serrano F, Parejo JC, Corraliza I, Gallardo-Soler A, Maranon F, Soto M, Alonso C, Gomez-Nieto C. The chimerical multi-component Q protein from Leishmania in the absence of adjuvant protects dogs against an experimental Leishmania infantum infection. Vaccine 2009; 27 (43) 5964-5973.
• 6 Denerolle P, Bourdoiseau G. Combination allopurinol and antimony treatment versus antimony alone and allopurinol alone in the treatment of canine leishmaniasis (96 cases). J Vet Intern Med 1999; 13 (05) 413-415.
• 7 Dorlo TPC, Balasegaram M, Beijnen JH, Vries de PJ. Miltefosine. A review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother 2012; 67 (11) 2576-2597.
• 8 Dumont P, Fankhauser B, Bouhsira E, Lienard E, Jacquiet P, Beugnet F, Franc M. Repellent and insecticidal efficacy of a new combination of fipronil and permethrin against the main vector of canine leishmaniosis in Europe (Phlebotomus perniciosus). Parasit Vectors 2015; 08: 49.
• 9 European Scientific Counsel Companion Animal Parasites (ESCCAP) &. Bauer C, Brahm R, Daugschies A, Kietzmann M, Kohn B, Moritz A, Schnieder T, Wendland B. Control of Vector-Borne Diseases Dogs and Cats. Deutsche Adaption der ESCCAP-Empfehlung Nr.. 5, April 2011
• 10 Farca AM, Miniscalco B, Badino P, Odore R, Monticelli P, Trisciuoglio A, Ferroglio E. Canine leishmaniosis. In vitro efficacy of miltefosine and marbofloxacin alone or in combination with allopurinol against clinical strains of Leishmania infantum. Parasitol Res 2012; 110 (06) 2509-2513.
• 11 Fernandes CB, Junior JTM, Jesus de C, Souza BMPdS, Larangeira DF, Fraga DBM, Tavares PSVeras, Barrouin-Melo SM. Comparison of two commercial vaccines against visceral leishmaniasis in dogs from endemic areas. IgG, and subclasses, parasitism, and parasite transmission by xenodiagnosis. Vaccine 2014; 32 (11) 1287-1295.
• 12 Ferroglio E, Poggi M, Trisciuoglio A. Evaluation of 65 % permethrin spoton and deltamethrin-impregnated collars for canine Leishmania infantum infection prevention. Zoonoses Public Health 2008; 55 (03) 145-148.
• 13 Franc M, Lienard E, Jacquiet P, Bonneau S, Navarro C, Bouhsira E. Efficacy of a new combination of fipronil and permethrin (Effitix®) against Phlebotomus perniciosus in dogs. Vet Parasitol 2015; 212 (3–4): 156-160.
• 14 Furlanello T, Trotta M. Retriebal of leishmanial DNA in a commercially available LiESP/QA-21 vaccine. International SCIVAC Congress, Canine Leishmaniosis and other vector-borne diseases: our current state of knowledge. 2013
• 15 Gomez SA, Picado A. Systemic insecticides used in dogs: potential candidates for phlebotomine vector control?. Trop Med Int Health 2017; 22 (06) 755-764.
• 16 Gramiccia M, Gradoni L. The current status of zoonotic leishmaniases and approaches to disease control. Int J Parasitol 2005; 35 (11–12): 1169-1180.
• 17 Hosein S, Blake DP, Solano-Gallego L. Insights on adaptive and innate immunity in canine leishmaniosis. Parasitology 2017; 144 (01) 95-115.
• 18 Iniesta V, Fernández-Cotrina J, Solano-Gallego L, Isabel IMonroy, Gomez-Luque A, Muñoz-Madrid R, Luis JBarneto, Gómez-Nieto LC, Fabra M, Balsa D, Brazis P. Vaccination with Letifend®, a novel canine leishmaniosis vaccine, does not interfere with serological diagnostic tests. Abstract SEVC, Granada, Spain. 2016
• 19 Jain K, Jain NK. Vaccines for visceral leishmaniasis: A review. J Immunol Methods 2015; 422: 1-12.
• 20 Killick-Kendrick R, Killick-Kendrick M, Focheux C, Dereure J, Pueck M-P, Cadiergues M. Protection of dogs from bites of phlebotomine sandflies by deltamethrin collars for control of canine leishmaniasis. Med Vet Entomol 1997; 11 (02) 105-111.
• 21 Klinman DM, Currie D, Gursel I, Verthelyi D. Use of CpG oligodeoxynucleotides as immune adjuvants. Immunol Rev 2004; 199: 201-216.
• 22 Laurenti MD, Rossi CN, Matta Vânia Lúcia Ribeiro da, Tomokane TY, Corbett CEP, Secundino NFC, Pimenta PFP, Marcondes M. Asymptomatic dogs are highly competent to transmit Leishmania (Leishmania) infantum chagasi to the natural vector. Vet Parasitol 2013; 196 (3–4): 296-300.
• 23 Leontides LS, Saridomichelakis MN, Billinis C, Kontos V, Koutinas AF, Galatos AD, Mylonakis ME. A cross-sectional study of Leishmania spp. infection in clinically healthy dogs with polymerase chain reaction and serology in Greece. Vet Parasitol 2002; 109 (1–2): 19-27.
• 24 Lienard E, Bouhsira E, Jacquiet P, Warin S, Kaltsatos V, Franc M. Efficacy of dinotefuran, permethrin and pyriproxyfen combination spot-on on dogs against Phlebotomus perniciosus and Ctenocephalides canis. Parasitol Res 2013; 112 (11) 3799-3805.
• 25 Lladro S, Picado A, Ballart C, Portus M, Gallego M. Management, prevention and treatment of canine leishmaniosis in north-eastern Spain: an online questionnaire-based survey in the province of Girona with special emphasis on new preventive methods (CaniLeish vaccine and domperidone). Vet Rec 2017; 180 (02) 47.
• 26 Manna L, Corso R, Galiero G, Cerrone A, Muzj P, Gravino AE. Long-term follow-up of dogs with leishmaniosis treated with meglumine antimoniate plus allopurinol versus miltefosine plus allopurinol. Parasit Vectors 2015; 08: 289.
• 27 Manna L, Vitale F, Reale S, Picillo E, Neglia G, Vescio F, Gravino AE. Study of efficacy of miltefosine and allopurinol in dogs with leishmaniosis. Vet J 2009; 182 (03) 441-445.
• 28 Mateo M, Maynard L, Vischer C, Bianciardi P, Miro G. Comparative study on the short term efficacy and adverse effects of miltefosine and meglumine antimoniate in dogs with natural leishmaniosis. Parasitol Res 2009; 105 (01) 155-162.
• 29 Maurício IL, Stothard JR, Miles MA. The strange case of Leishmania chagasi. Parasitol Today 2000; 16 (05) 188-189.
• 30 Miro G, Galvez R, Mateo M, Montoya A, Descalzo MA, Molina R. Evaluation of the efficacy of a topically administered combination of imidacloprid and permethrin against Phlebotomus perniciosus in dog. Vet Parasitol 2007; 143 (3–4): 375-379.
• 31 Miró G, Cardoso L, Pennisi MG, Oliva G, Baneth G. Canine leishmaniosis– new concepts and insights on an expanding zoonosis. Part two. Trends Parasitol 2008; 24 (08) 371-377.
• 32 Miró G, Oliva G, Cruz I, Cañavate C, Mortarino M, Vischer C, Bianciardi P. Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis. Vet Dermatol 2009; 20 (5–6): 397-404.
• 33 Molano I, Alonso MG, Mirón C, Redondo E, Requena JM, Soto M, Nieto CG, Alonso C. A Leishmania infantum multi-component antigenic protein mixed with live BCG confers protection to dogs experimentally infected with L. infantum. Vet Immunol Immunopathol 2003; 92 (1–2): 1-13.
• 34 Molina R, Espinosa-Gongora C, Galvez R, Montoya A, Descalzo MA, Jimenez MI, Dado D, Miro G. Efficacy of 65 % permethrin applied to dogs as a spot-on against Phlebotomus perniciosus. Vet Parasitol 2012; 187 (3–4): 529-533.
• 35 Moreno J, Vouldoukis I, Martin V, McGahie D, Cuisinier A-M, Gueguen S. Use of a LiESP/QA-21 vaccine (CaniLeish) stimulates an appropriate Th1dominated cell-mediated immune response in dogs. PLoS neglected tropical diseases 2012; 06 (06) e1683.
• 36 Moreno J, Vouldoukis I, Schreiber P, Martin V, McGahie D, Gueguen S, Cuisinier A-M. Primary vaccination with the LiESP/QA-21 vaccine (Cani-Leish) produces a cell-mediated immune response which is still present 1 year later. Vet Immunol Immunopathol 2014; 158 (3–4): 199-207.
• 37 Naucke TJ, Lorentz S. Non-sandfly transmission of canine leishmaniasis in Germany. Tierärztl Umsch 2013; 68: 121-125.
• 38 Noli C, Auxilia ST. Treatment of canine Old World visceral leishmaniasis. A systematic review. Vet Dermatol 2005; 16 (04) 213-232.
• 39 Noli C, Saridomichelakis MN. An update on the diagnosis and treatment of canine leishmaniosis caused by Leishmania infantum (syn. L. chagasi). Vet J 2014; 202 (03) 425-435.
• 40 Oliva G, Nieto J, Foglia VManzillo, Cappiello S, Fiorentino E, Di Muccio T, Scalone A, Moreno J, Chicharro C, Carrillo E, Butaud T, Guegand L, Martin V, Cuisinier A-M, McGahie D, Gueguen S, Canavate C, Gradoni L. A randomised, double-blind, controlled efficacy trial of the LiESP/QA-21 vaccine in naive dogs exposed to two leishmania infantum transmission seasons. PLoS neglected tropical diseases 2014; 08 (10) e3213.
• 41 Otranto D, Caprariis de D, Lia RP, Tarallo V, Lorusso V, Testini G, Dantas-Torres F, Latrofa S, Diniz PPVP, Mencke N, Maggi RG, Breitschwerdt E, Capelli G, Stanneck D. Prevention of endemic canine vector-borne diseases using imidacloprid 10 % and permethrin 50 % in young dogs: a longitudinal field study. Vet Parasitol 2010; 172 (3–4): 323-332.
• 42 Otranto D, Dantas-Torres F. The prevention of canine leishmaniasis and its impact on public health. Trends Parasitol 2013; 29 (07) 339-345.
• 43 Papadopoulos E, Angelou A, Diakou A, Halos L, Beugnet F. Five-month serological monitoring to assess the effectiveness of permethrin/fipronil (Frontline Tri-Act®) spot-on in reducing the transmission of Leishmania infantum in dogs. Veterinary Parasitology: Regional Studies and Reports 2017; 07: 48-53.
• 44 Parody N, Soto M, Requena JM, Alonso C. Adjuvant guided polarization of the immune humoral response against a protective multicomponent antigenic protein (Q) from Leishmania infantum. A CpG + Q mix protects Balb/c mice from infection. Parasite Immunol 2004; 26 (6–7): 283-293.
• 45 Pinto-Martinez AK, Rodriguez-Durán J, Serrano-Martin X, Hernandez-Rodriguez V, Benaim G. Mechanism of action of miltefosine on Leishmania donovani involves the impairment of acidocalcisomes function and the activation of the sphingosine-dependent plasma membrane Ca2+ channel. Antimicrob Agents Chemother. 2018 62. (1).
• 46 Podaliri MVulpiani, Iannetti L, Paganico D, Iannino F, Ferri N. Methods of control of the Leishmania infantum dog reservoir: state of the art. Vet Med Int 2011; 2011: 215964.
• 47 Poot J, Janssen LHM, van Kasteren-Westerneng TJ, van der Heijden-Liefkens KHA, Schijns VEJC, Heckeroth A. Vaccination of dogs with six different candidate leishmaniasis vaccines composed of a chimerical recombinant protein containing ribosomal and histone protein epitopes in combination with different adjuvants. Vaccine 2009; 27 (33) 4439-4446.
• 48 Prakash A, Wagstaff AJ. Domperidone. A review of its use in diabetic gastropathy. Drugs 1998; 56 (03) 429-445.
• 49 Reguera RM, Moran M, Perez-Pertejo Y, Garcia-Estrada C, Balana-Fouce R. Current status on prevention and treatment of canine leishmaniasis. Vet Parasitol 2016; 227: 98-114.
• 50 Sabaté D, Llinás J, Homedes J, Sust M, Ferrer L. A single-centre, open-label, controlled, randomized clinical trial to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis in a high prevalence area. Prev Vet Med 2014; 115 (1–2): 56-63.
• 51 Saridomichelakis MN. Advances in the pathogenesis of canine leishmaniosis: epidemiologic and diagnostic implications. Vet Dermatol 2009; 20 (5–6): 471-489.
• 52 Segarra S, Miró G, Montoya A, Pardo-Marín L, Boqué N, Ferrer L, Cerón J. Randomized, allopurinol-controlled trial of the effects of dietary nucleotides and active hexose correlated compound in the treatment of canine leishmaniosis. Vet Parasitol 2017; 239: 50-56.
• 53 Solano-Gallego L, Miro G, Koutinas A, Cardoso L, Pennisi MG, Ferrer L, Bourdeau P, Oliva G, Baneth G, The LG. LeishVet guidelines for the practical management of canine leishmaniosis. Parasit Vectors 2011; 04: 86.
• 54 Soto M, Requena JM, Quijada L, Alonso C. Multicomponent chimeric antigen for serodiagnosis of canine visceral leishmaniasis. J Clin Microbiol 1998; 36 (01) 58-63.
• 55 Starita C, Gavazza A, Lubas G. Hematological, biochemical, and serological findings in healthy canine blood donors after the administration of Cani-Leish(R) vaccine. Vet Med Int 2016; 10: 1-6.
• 56 Torres M, Bardagí M, Roura X, Zanna G, Ravera I, Ferrer L. Long term follow-up of dogs diagnosed with leishmaniosis (clinical stage II) and treated with meglumine antimoniate and allopurinol. Vet J 2011; 188 (03) 346-351.
• 57 Travi BL, Cordeiro-da-Silva A, Dantas-Torres F, Miró G. Canine visceral leishmaniasis. Diagnosis and management of the reservoir living among us. PLoS neglected tropical diseases 2018; 12 (01) e0006082.
• 58 Vetidata Veterinärmedizinischer Informationsdienst für Arzneimittelanwendung, Toxikologie und Arzneimittelrecht. http://www.vetidata.de/ Zugriff am 25. Juli 2018
• 59 Walker SE, Allen SH, Hoffman RW, McMurray RW. Review. Prolactin: a stimulator of disease activity in systemic lupus erythematosus. Lupus 1995; 04 (01) 3-9.
• 60 Walther FM, Fisara P, Allan MJ, Roepke RKA, Nuernberger MC. Safety of the concurrent treatment of dogs with Bravecto (fluralaner) and Scalibor protectorband (deltamethrin). Parasit Vectors 2014; 07: 105.
• 61 Wengenmayer C, Williams H, Zschiesche E, Moritz A, Langenstein J, Roepke RKA, Heckeroth AR. The speed of kill of fluralaner (Bravecto™) against Ixodes ricinus ticks on dogs. Parasit Vectors 2014; 07: 525.
• 62 Yasur-Landau D, Jaffe CL, David L, Baneth G. Allopurinol resistance in Leishmania infantum from dogs with disease relapse. PLoS neglected tropical diseases 2016; 10 (01) e0004341.