Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M; WHO Leishmaniasis Control Team, 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7: e35671.
Coura-Vital W et al. 2014. Evaluation of change in canine diagnosis protocol adopted by the visceral leishmaniasis control program in Brazil and a new proposal for diagnosis. PLoS One 9: e91009.
Millan J, Ferroglio E, Solano-Gallego L, 2014. Role of wildlife in the epidemiology of Leishmania infantum infection in Europe. Parasitol Res 113: 2005–2014.
Dantas-Torres F, Solano-Gallego L, Baneth G, Ribeiro VM, de Paiva-Cavalcanti M, Otranto D, 2012. Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences. Trends Parasitol 28: 531–538.
Rock KS, Quinnell RJ, Medley GF, Courtenay O, 2016. Progress in the mathematical modelling of visceral leishmaniasis. Adv Parasitol 94: 49–131.
Courtenay O, Quinnell RJ, Garcez LM, Shaw JJ, Dye C, 2002. Infectiousness in a cohort of Brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission. J Infect Dis 186: 1314–1320.
Dye C, 1996. The logic of visceral leishmaniasis control. Am J Trop Med Hyg 55: 125–130.
Esch KJ, Juelsgaard R, Martinez PA, Jones DE, Petersen CA, 2013. Programmed death 1-mediated T cell exhaustion during visceral leishmaniasis impairs phagocyte function. J Immunol 191: 5542–5550.
Boggiatto PM, Ramer-Tait AE, Metz K, Kramer EE, Gibson-Corley K, Mullin K, Hostetter JM, Gallup JM, Jones DE, Petersen CA, 2010. Immunologic indicators of clinical progression during canine Leishmania infantum infection. Clin Vaccine Immunol 17: 267–273.
Schantz PM, Steurer FJ, Duprey ZH, Kurpel KP, Barr SC, Jackson JE, Breitschwerdt EB, Levy MG, Fox JC, 2005. Autochthonous visceral leishmaniasis in dogs in North America. J Am Vet Med Assoc 226: 1316–1322.
Gaskin AA et al. 2002. Visceral leishmaniasis in a New York foxhound kennel. J Vet Intern Med 16: 34–44.
Schaut RG, Robles-Murguia M, Juelsgaard R, Esch KJ, Bartholomay LC, Ramalho-Ortigao M, Petersen CA, 2015. Vectorborne transmission of Leishmania infantum from hounds, United States. Emerg Infect Dis 21: 2209–2212.
Petersen CA, 2009. New means of canine leishmaniasis transmission in North America: the possibility of transmission to humans still unknown. Interdiscip Perspect Infect Dis 2009: 802712.
Drahota J, Martin-Martin I, Sumova P, Rohousova I, Jimenez M, Molina R, Volf P, 2014. Recombinant antigens from Phlebotomus perniciosus saliva as markers of canine exposure to visceral leishmaniases vector. PLoS Negl Trop Dis 8: e2597.
Grinnage-Pulley T, Scott B, Petersen CA, 2016. A mother’s gift: congenital transmission of Trypanosoma and Leishmania species. PLoS Pathog 12: e1005302.
Palatnik-de-Sousa CB, 2012. Vaccines for canine leishmaniasis. Front Immunol 3: 69.
Palatnik-de-Sousa CB, 2008. Vaccines for leishmaniasis in the fore coming 25 years. Vaccine 26: 1709–1724.
Vida B, Toepp A, Schaut RG, Esch KJ, Juelsgaard R, Shimak RM, Petersen CA, 2016. Immunologic progression of canine leishmaniosis following vertical transmission in United States dogs. Vet Immunol Immunopathol 169: 34–38.
Schaut RG, Grinnage-Pulley TL, Esch KJ, Toepp AJ, Duthie MS, Howard RF, Reed SG, Petersen CA, 2016. Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant. Vaccine 34: 5225–5234.
Regina-Silva S, Feres AM, Franca-Silva JC, Dias ES, Michalsky EM, de Andrade HM, Coelho EA, Ribeiro GM, Fernandes AP, Machado-Coelho GL, 2016. Field randomized trial to evaluate the efficacy of the Leish-Tec® vaccine against canine visceral leishmaniasis in an endemic area of Brazil. Vaccine 34: 2233–2239.
Testasicca MC et al. 2014. Antibody responses induced by Leish-Tec®, an A2-based vaccine for visceral leishmaniasis, in a heterogeneous canine population. Vet Parasitol 204: 169–176.
Fernandes AP et al. 2008. Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein. Vaccine 26: 5888–5895.
Starita C, Gavazza A, Lubas G, 2016. Hematological, biochemical, and serological findings in healthy canine blood donors after the administration of CaniLeish® vaccine. Vet Med Int 2016: 4601893.
Oliva G et al. 2014. A randomised, double-blind, controlled efficacy trial of the LiESP/QA-21 vaccine in naive dogs exposed to two Leishmania infantum transmission seasons. PLoS Negl Trop Dis 8: e3213.
Martin V, Vouldoukis I, Moreno J, McGahie D, Gueguen S, Cuisinier AM, 2014. The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later. Vet Res (Faisalabad) 45: 69.
European Commission, 2016. Community Register of Veterinary Medicinal Products. Available at: http://ec.europa.eu/health/documents/community-register/html/alfvreg.htm. Accessed April 5, 2017.
Fernandes CB, Junior JT, de Jesus C, Souza BM, Larangeira DF, Fraga DB, Tavares Veras PS, Barrouin-Melo SM, 2014. Comparison of two commercial vaccines against visceral leishmaniasis in dogs from endemic areas: IgG, and subclasses, parasitism, and parasite transmission by xenodiagnosis. Vaccine 32: 1287–1295.
Moore GE, Guptill LF, Ward MP, Glickman NW, Faunt KK, Lewis HB, Glickman LT, 2005. Adverse events diagnosed within three days of vaccine administration in dogs. J Am Vet Med Assoc 227: 1102–1108.
Yao PJ, Stephenson N, Foley JE, Toussieng CR, Farver TB, Sykes JE, Fleer KA, 2015. Incidence rates and risk factors for owner-reported adverse events following vaccination of dogs that did or did not receive a Leptospira vaccine. J Am Vet Med Assoc 247: 1139–1145.
Reis AB, Martins-Filho OA, Teixeira-Carvalho A, Giunchetti RC, Carneiro CM, Mayrink W, Tafuri WL, Correa-Oliveira R, 2009. Systemic and compartmentalized immune response in canine visceral leishmaniasis. Vet Immunol Immunopathol 128: 87–95.
Ciaramella P, Oliva G, Luna RD, Gradoni L, Ambrosio R, Cortese L, Scalone A, Persechino A, 1997. A retrospective clinical study of canine leishmaniasis in 150 dogs naturally infected by Leishmania infantum. Vet Rec 141: 539–543.
Pattabhi S et al. 2010. Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. PLoS Negl Trop Dis 4: pii: e822.
Grimaldi G Jr., Teva A, Ferreira AL, dos Santos CB, Pinto I, de-Azevedo CT, Falqueto A, 2012. Evaluation of a novel chromatographic immunoassay based on Dual-Path Platform technology (DPP® CVL rapid test) for the serodiagnosis of canine visceral leishmaniasis. Trans R Soc Trop Med Hyg 106: 54–59.
Costa CH, 2011. How effective is dog culling in controlling zoonotic visceral leishmaniasis? A critical evaluation of the science, politics and ethics behind this public health policy. Rev Soc Bras Med Trop 44: 232–242.
Costa DN, Codeco CT, Silva MA, Werneck GL, 2013. Culling dogs in scenarios of imperfect control: realistic impact on the prevalence of canine visceral leishmaniasis. PLoS Negl Trop Dis 7: e2355.
Croft SL, Sundar S, Fairlamb AH, 2006. Drug resistance in leishmaniasis. Clin Microbiol Rev 19: 111–126.
Werneck GL, 2014. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control. Rev Saude Publica 48: 851–856.
Werneck GL, Costa CH, de Carvalho FA, Pires e Cruz Mdo S, Maguire JH, Castro MC, 2014. Effectiveness of insecticide spraying and culling of dogs on the incidence of Leishmania infantum infection in humans: a cluster randomized trial in Teresina, Brazil. PLoS Negl Trop Dis 8: e3172.
Miro G, Cardoso L, Pennisi MG, Oliva G, Baneth G, 2008. Canine leishmaniosis–new concepts and insights on an expanding zoonosis: part two. Trends Parasitol 24: 371–377.
Manna L, Reale S, Vitale F, Picillo E, Pavone LM, Gravino AE, 2008. Real-time PCR assay in Leishmania-infected dogs treated with meglumine antimoniate and allopurinol. Vet J 177: 279–282.
Noli C, Auxilia ST, 2005. Treatment of canine Old World visceral leishmaniasis: a systematic review. Vet Dermatol 16: 213–232.
Costa PL, Dantas-Torres F, da Silva FJ, Guimaraes VC, Gaudencio K, Brandao-Filho SP, 2013. Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil. Acta Trop 126: 99–102.
Sundar S, Chakravarty J, 2015. An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother 16: 237–252.
Murray HW, 2001. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob Agents Chemother 45: 2185–2197.
Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, Kumar PC, Murray HW, 2000. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31: 1104–1107.
Rijal S, Chappuis F, Singh R, Bovier PA, Acharya P, Karki BM, Das ML, Desjeux P, Loutan L, Koirala S, 2003. Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline. Trans R Soc Trop Med Hyg 97: 350–354.
Musa A et al. 2012. Sodium stibogluconate (SSG) and paromomycin combination compared to SSG for visceral leishmaniasis in east Africa: a randomised controlled trial. PLoS Negl Trop Dis 6: e1674.
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In Leishmania infantum–endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
Authors’ addresses: Angela Toepp, Mandy Larson, Molly Parrish, and Geneva Wilson, College of Public Health, University of Iowa, Iowa City, IA, E-mails: angela-schneider@uiowa.edu, maklarson@gmail.com, molly-parrish@uiowa.edu, and geneva-wilson@uiowa.edu. Tara Grinnage-Pulley, National Cancer Institute, Frederick, MD, E-mail: tara.grinnage-pulley@nih.gov. Carolyne Bennett and Caitlin Cotter, Centers for Disease Control and Prevention, Decatur, GA, E-mails: nuw8@cdc.gov and caitlincotter@gmail.com. Michael Anderson, Center for State and Territorial Epidemiologists, Atlanta, GA, E-mail: manderson@cste.org. Hailie Fowler, Integrated DNA Technologies, Coralville, IA, E-mail: hflowler@idtdna.com. Radhika Gharpure, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, E-mail: radhika.gharpure@gmail.com. Christine Petersen, Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, and Center for Emerging Infectious Diseases, University of Iowa Research Park, Coralville, IA, E-mail: christine-petersen@uiowa.edu.
These authors contributed equally to this work.
Alvar J, Vélez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M; WHO Leishmaniasis Control Team, 2012. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 7: e35671.
Coura-Vital W et al. 2014. Evaluation of change in canine diagnosis protocol adopted by the visceral leishmaniasis control program in Brazil and a new proposal for diagnosis. PLoS One 9: e91009.
Millan J, Ferroglio E, Solano-Gallego L, 2014. Role of wildlife in the epidemiology of Leishmania infantum infection in Europe. Parasitol Res 113: 2005–2014.
Dantas-Torres F, Solano-Gallego L, Baneth G, Ribeiro VM, de Paiva-Cavalcanti M, Otranto D, 2012. Canine leishmaniosis in the Old and New Worlds: unveiled similarities and differences. Trends Parasitol 28: 531–538.
Rock KS, Quinnell RJ, Medley GF, Courtenay O, 2016. Progress in the mathematical modelling of visceral leishmaniasis. Adv Parasitol 94: 49–131.
Courtenay O, Quinnell RJ, Garcez LM, Shaw JJ, Dye C, 2002. Infectiousness in a cohort of Brazilian dogs: why culling fails to control visceral leishmaniasis in areas of high transmission. J Infect Dis 186: 1314–1320.
Dye C, 1996. The logic of visceral leishmaniasis control. Am J Trop Med Hyg 55: 125–130.
Esch KJ, Juelsgaard R, Martinez PA, Jones DE, Petersen CA, 2013. Programmed death 1-mediated T cell exhaustion during visceral leishmaniasis impairs phagocyte function. J Immunol 191: 5542–5550.
Boggiatto PM, Ramer-Tait AE, Metz K, Kramer EE, Gibson-Corley K, Mullin K, Hostetter JM, Gallup JM, Jones DE, Petersen CA, 2010. Immunologic indicators of clinical progression during canine Leishmania infantum infection. Clin Vaccine Immunol 17: 267–273.
Schantz PM, Steurer FJ, Duprey ZH, Kurpel KP, Barr SC, Jackson JE, Breitschwerdt EB, Levy MG, Fox JC, 2005. Autochthonous visceral leishmaniasis in dogs in North America. J Am Vet Med Assoc 226: 1316–1322.
Gaskin AA et al. 2002. Visceral leishmaniasis in a New York foxhound kennel. J Vet Intern Med 16: 34–44.
Schaut RG, Robles-Murguia M, Juelsgaard R, Esch KJ, Bartholomay LC, Ramalho-Ortigao M, Petersen CA, 2015. Vectorborne transmission of Leishmania infantum from hounds, United States. Emerg Infect Dis 21: 2209–2212.
Petersen CA, 2009. New means of canine leishmaniasis transmission in North America: the possibility of transmission to humans still unknown. Interdiscip Perspect Infect Dis 2009: 802712.
Drahota J, Martin-Martin I, Sumova P, Rohousova I, Jimenez M, Molina R, Volf P, 2014. Recombinant antigens from Phlebotomus perniciosus saliva as markers of canine exposure to visceral leishmaniases vector. PLoS Negl Trop Dis 8: e2597.
Grinnage-Pulley T, Scott B, Petersen CA, 2016. A mother’s gift: congenital transmission of Trypanosoma and Leishmania species. PLoS Pathog 12: e1005302.
Palatnik-de-Sousa CB, 2012. Vaccines for canine leishmaniasis. Front Immunol 3: 69.
Palatnik-de-Sousa CB, 2008. Vaccines for leishmaniasis in the fore coming 25 years. Vaccine 26: 1709–1724.
Vida B, Toepp A, Schaut RG, Esch KJ, Juelsgaard R, Shimak RM, Petersen CA, 2016. Immunologic progression of canine leishmaniosis following vertical transmission in United States dogs. Vet Immunol Immunopathol 169: 34–38.
Schaut RG, Grinnage-Pulley TL, Esch KJ, Toepp AJ, Duthie MS, Howard RF, Reed SG, Petersen CA, 2016. Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant. Vaccine 34: 5225–5234.
Regina-Silva S, Feres AM, Franca-Silva JC, Dias ES, Michalsky EM, de Andrade HM, Coelho EA, Ribeiro GM, Fernandes AP, Machado-Coelho GL, 2016. Field randomized trial to evaluate the efficacy of the Leish-Tec® vaccine against canine visceral leishmaniasis in an endemic area of Brazil. Vaccine 34: 2233–2239.
Testasicca MC et al. 2014. Antibody responses induced by Leish-Tec®, an A2-based vaccine for visceral leishmaniasis, in a heterogeneous canine population. Vet Parasitol 204: 169–176.
Fernandes AP et al. 2008. Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein. Vaccine 26: 5888–5895.
Starita C, Gavazza A, Lubas G, 2016. Hematological, biochemical, and serological findings in healthy canine blood donors after the administration of CaniLeish® vaccine. Vet Med Int 2016: 4601893.
Oliva G et al. 2014. A randomised, double-blind, controlled efficacy trial of the LiESP/QA-21 vaccine in naive dogs exposed to two Leishmania infantum transmission seasons. PLoS Negl Trop Dis 8: e3213.
Martin V, Vouldoukis I, Moreno J, McGahie D, Gueguen S, Cuisinier AM, 2014. The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later. Vet Res (Faisalabad) 45: 69.
European Commission, 2016. Community Register of Veterinary Medicinal Products. Available at: http://ec.europa.eu/health/documents/community-register/html/alfvreg.htm. Accessed April 5, 2017.
Fernandes CB, Junior JT, de Jesus C, Souza BM, Larangeira DF, Fraga DB, Tavares Veras PS, Barrouin-Melo SM, 2014. Comparison of two commercial vaccines against visceral leishmaniasis in dogs from endemic areas: IgG, and subclasses, parasitism, and parasite transmission by xenodiagnosis. Vaccine 32: 1287–1295.
Moore GE, Guptill LF, Ward MP, Glickman NW, Faunt KK, Lewis HB, Glickman LT, 2005. Adverse events diagnosed within three days of vaccine administration in dogs. J Am Vet Med Assoc 227: 1102–1108.
Yao PJ, Stephenson N, Foley JE, Toussieng CR, Farver TB, Sykes JE, Fleer KA, 2015. Incidence rates and risk factors for owner-reported adverse events following vaccination of dogs that did or did not receive a Leptospira vaccine. J Am Vet Med Assoc 247: 1139–1145.
Reis AB, Martins-Filho OA, Teixeira-Carvalho A, Giunchetti RC, Carneiro CM, Mayrink W, Tafuri WL, Correa-Oliveira R, 2009. Systemic and compartmentalized immune response in canine visceral leishmaniasis. Vet Immunol Immunopathol 128: 87–95.
Ciaramella P, Oliva G, Luna RD, Gradoni L, Ambrosio R, Cortese L, Scalone A, Persechino A, 1997. A retrospective clinical study of canine leishmaniasis in 150 dogs naturally infected by Leishmania infantum. Vet Rec 141: 539–543.
Pattabhi S et al. 2010. Design, development and evaluation of rK28-based point-of-care tests for improving rapid diagnosis of visceral leishmaniasis. PLoS Negl Trop Dis 4: pii: e822.
Grimaldi G Jr., Teva A, Ferreira AL, dos Santos CB, Pinto I, de-Azevedo CT, Falqueto A, 2012. Evaluation of a novel chromatographic immunoassay based on Dual-Path Platform technology (DPP® CVL rapid test) for the serodiagnosis of canine visceral leishmaniasis. Trans R Soc Trop Med Hyg 106: 54–59.
Costa CH, 2011. How effective is dog culling in controlling zoonotic visceral leishmaniasis? A critical evaluation of the science, politics and ethics behind this public health policy. Rev Soc Bras Med Trop 44: 232–242.
Costa DN, Codeco CT, Silva MA, Werneck GL, 2013. Culling dogs in scenarios of imperfect control: realistic impact on the prevalence of canine visceral leishmaniasis. PLoS Negl Trop Dis 7: e2355.
Croft SL, Sundar S, Fairlamb AH, 2006. Drug resistance in leishmaniasis. Clin Microbiol Rev 19: 111–126.
Werneck GL, 2014. Visceral leishmaniasis in Brazil: rationale and concerns related to reservoir control. Rev Saude Publica 48: 851–856.
Werneck GL, Costa CH, de Carvalho FA, Pires e Cruz Mdo S, Maguire JH, Castro MC, 2014. Effectiveness of insecticide spraying and culling of dogs on the incidence of Leishmania infantum infection in humans: a cluster randomized trial in Teresina, Brazil. PLoS Negl Trop Dis 8: e3172.
Miro G, Cardoso L, Pennisi MG, Oliva G, Baneth G, 2008. Canine leishmaniosis–new concepts and insights on an expanding zoonosis: part two. Trends Parasitol 24: 371–377.
Manna L, Reale S, Vitale F, Picillo E, Pavone LM, Gravino AE, 2008. Real-time PCR assay in Leishmania-infected dogs treated with meglumine antimoniate and allopurinol. Vet J 177: 279–282.
Noli C, Auxilia ST, 2005. Treatment of canine Old World visceral leishmaniasis: a systematic review. Vet Dermatol 16: 213–232.
Costa PL, Dantas-Torres F, da Silva FJ, Guimaraes VC, Gaudencio K, Brandao-Filho SP, 2013. Ecology of Lutzomyia longipalpis in an area of visceral leishmaniasis transmission in north-eastern Brazil. Acta Trop 126: 99–102.
Sundar S, Chakravarty J, 2015. An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother 16: 237–252.
Murray HW, 2001. Clinical and experimental advances in treatment of visceral leishmaniasis. Antimicrob Agents Chemother 45: 2185–2197.
Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, Kumar PC, Murray HW, 2000. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31: 1104–1107.
Rijal S, Chappuis F, Singh R, Bovier PA, Acharya P, Karki BM, Das ML, Desjeux P, Loutan L, Koirala S, 2003. Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline. Trans R Soc Trop Med Hyg 97: 350–354.
Musa A et al. 2012. Sodium stibogluconate (SSG) and paromomycin combination compared to SSG for visceral leishmaniasis in east Africa: a randomised controlled trial. PLoS Negl Trop Dis 6: e1674.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 561 | 381 | 103 |
Full Text Views | 947 | 18 | 2 |
PDF Downloads | 321 | 20 | 2 |