Particle and Fibre Toxicology | |
Field clinical study evaluating the efficacy and safety of an oral formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of the zoonotic canine infection by Dirofilaria repens | |
Donato Traversa4  Stefania Avolio6  Federico Pandolfi5  Jason Drake1  Silvana Meloni4  Francesco La Torre3  Roberto Bartolini4  Vincenzo Aquilino4  Barbara Paoletti4  Emanuela Di Giulio6  Gabriele Braun2  Angela Di Cesare4  | |
[1] Novartis Animal Health, 3200 Northline Ave., Suite 300, Greensboro, NC 27408, USA;Klifovet AG, Munich, Geyerspergerstrasse 27, 80689 Munich, Germany;Novartis Animal Health S.p.A., Largo Umberto Boccioni 1, Origgio 21040, Varese, Italy;Faculty of Veterinary Medicine, University of Teramo, Piazza A. Moro, 45, 64100 Teramo, Italy;Canile Federico I°, Via San Giovanni 12/A, 60010 Ostra Vetere Ancona, Italy;Veterinary Practice James Herriot, Via Nazionale 2/g, 64026, Roseto degli Abruzzi Teramo, Italy | |
关键词: Italy; Dog; Prevention; Milbemycin oxime; Dirofilaria repens; | |
Others : 1181889 DOI : 10.1186/1756-3305-7-347 |
|
received in 2014-05-15, accepted in 2014-07-18, 发布年份 2014 | |
【 摘 要 】
Background
Dirofilaria repens is the causative agent of subcutaneous dirofilariosis of dogs, other animals and humans. This nematode is transmitted by mosquitoes of Aedes, Anopheles and Culex genera. In dogs, the parasite may cause subclinical infection or cutaneous signs. Recently, D. repens has emerged and spread in different geographical areas, with an increase of cases in dogs and humans. Chemoprevention in dogs in endemic areas is the most reliable approach for controlling this infection. This paper describes a randomized, blocked and multicentric clinical field study investigating the efficacy of an oral, chewable formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of subcutaneous dirofilariosis in dogs.
Methods
This study was conducted in endemic areas of Italy. A total of 249 dogs, at two sites, negative for D. repens, were allocated into two groups (i.e. Treated -T1 vs Untreated-T2) with a ratio of 1:1, and subjected to clinical visits and blood sampling once monthly until the end of the study. All blood samples were microscopically and genetically examined. Animals belonging to T1 group received a minimum target dose of 0.5 mg/kg bodyweight of milbemycin oxime and 5 mg/kg of praziquantel in commercial tablets (Milbemax®) according body weight once every 4 weeks. Animals of group T2 were not treated with Milbemax® but received, when necessary, specific parasiticide treatments. The study duration was 336 ± 2 days for each dog.
Results
A total of 219 dogs completed the study (i.e. 111 in T1 and 108 in T2), while 30 dogs (i.e. 13 in T1, 17 in T2) were withdrawn for a variety of reasons unrelated to administration of Milbemax®. The percentages of animals not showing microfilariae of D. repens were 100% (111 animals) in T1 and 94.7% (108 animals out of 114) in group T2. Milbemax® was shown to be safe in treated dogs.
Conclusions
The results of this study confirm that the monthly use of Milbemax® in dogs is effective and safe for the prevention of subcutaneous dirofilariosis in endemic areas.
【 授权许可】
2014 Di Cesare et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150515085144613.pdf | 649KB | download | |
Figure 2. | 122KB | Image | download |
Figure 1. | 74KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Otranto D, Capelli G, Genchi C: Changing distribution patterns of canine vector borne diseases in Italy: leishmaniosis vs. dirofilariosis. Parasit Vectors 2009, 2(Suppl 1):S2.
- [2]Otranto D, Dantas-Torres F, Brianti E, Traversa D, Petrić D, Genchi C, Capelli G: Vector-borne helminths of dogs and humans in Europe. Parasit Vectors 2013, 6:16.
- [3]McCall JW, Genchi C, Kramer LH, Guerrero J, Venco L: Heartworm disease in animals and humans. Adv Parasitol 2008, 66:193-285.
- [4]Bredal WP, Gjerde B, Eberhard ML, Aleksandersen M, Wilhelmsen DK, Mansfield LS: Adult Dirofilaria repens in a subcutaneous granuloma on the chest of a dog. J Small Anim Pract 1998, 39:595-597.
- [5]Hargis AM, Lewis TP, Duclos DD, Loeffler DG, Raush RL: Dermatitis associated with microfilariae (Filarioidea) in 10 dogs. Vet Dermat 1999, 10:95-107.
- [6]Rocconi F, Di Tommaso M, Traversa D, Palmieri C, Pampurini F, Boari A: Allergic dermatitis by Dirofilaria repens in a dog: clinical picture and treatment. Parasitol Res 2012, 111:493-496.
- [7]Pampiglione S, Rivasi F, Gustinelli A: Dirofilarial human cases in the Old World, attributed to Dirofilaria immitis: a critical analysis. Histopathology 2009, 54:192-204.
- [8]Otranto D, Brianti E, Gaglio G, Dantas-Torres F, Azzaro S, Giannetto S: Human ocular infection with Dirofilaria repens (Railliet and Henry, 1911) in an area endemic for canine dirofilariasis. Am J Trop Med Hyg 2011, 84:1002-1004.
- [9]Svobodova Z, Svobodova V, Genchi C, Forejtek P: The first report of authochthonous dirofilariosis in dogs in the Czech Republic. Helminthologica 2006, 43:242-245.
- [10]Genchi C, Rinaldi L, Mortarino M, Genchi M, Cringoli G: Climate and Dirofilaria infection in Europe. Vet Parasitol 2009, 163:286-292.
- [11]Genchi C, Poglayen G, Kramer L, Casiraghi M, Venco L, Brianti E: Efficacy of selamectin in the prophylaxis of Dirofilaria repens infestations in dogs. Veterinaria 2002, 16:69-71. In Italian
- [12]Traversa D, Aste G, Di Cesare A, Paoletti B, Di Tommaso M, Di Giulio E, Pampurini F, Tunesi C, Boari A: Efficacy of a single administration of a spot-on solution containing imidacloprid 10%/moxidectin 2.5% in eliminating Dirofilaria repens microfilariae in naturally infected dogs. Vet Parasitol 2011, 179:107-112.
- [13]Duscher G, Feiler A, Wille-Piazzai W, Bakonyi T, Leschnik M, Miterpáková M, Kolodziejek J, Nowotny N, Joachim A: Detection of Dirofilaria in Austrian dogs. Berl Munch Tierarztl Wochenschr 2009, 122:199-203.
- [14]Silbermayr K, Eigner B, Joachim A, Duscher GG, Seidel B, Allerberger F, Indra A, Hufnagl P, Fuehrer HP: Autochthonous Dirofilaria repens in Austria. Parasit Vectors 2014, 7:226.
- [15]Svobodová Z, Svobodova V, Genchi C, Forejtek P: The first report of autochthonous dirofilariosis in dogs in the Czech Republic. Helminthologia 2006, 43:242-245.
- [16]Kershaw O, Dyachenko V, Gruber AD: Kutane Dirofilariose beim Hund in Deutschland. Dtsch Tierarztl Wochenschr 2009, 116:273.
- [17]Sassnau R, Kohn M, Demeler J, Kohn B, Müller E, Krücken J, von Samson-Himmelstjerna G: Is Dirofilaria repens endemic in the Havelland district in Brandenburg, Germany? Vector Borne Zoonotic Dis 2013, 13:888-891.
- [18]Pantchev N, Norden N, Lorentzen L, Reif M, Rossi U, Brand B, Dyachenko V: Current surveys on the prevalence and distribution of Dirofilaria spp. in dogs in Germany. Parasitol Res 2009, 105:63-74.
- [19]Fok É, Jascó O, Szebeni Z, Györffy A, Südkösd l, Lukács Z, Schaper R: Elimination of Dirofilaria (syn. Nochtiella) repens microfilariae in dogs with monthly treatments of moxidectin 2.5%/imidacloprid 10% (Advocate®, Bayer) spot-on. Parasitol Res 2010, 106:1141-1149.
- [20]Svobodova V, Svobodova Z, Beladicova V, Valentova D: First cases of canine dirofilariosis in Slovakia, a case report. Vet Med Czech 2005, 50:510-512.
- [21]Hamel D, Silaghi C, Zapadynska S, Kudrin A, Pfister K: Vector-borne pathogens in ticks and EDTA-blood samples collected from client-owned dogs, Kiev, Ukraine. Ticks Tick Borne Dis 2013, 4:152-155.
- [22]Aiello A, Aiello P, Aiello F: A case of palpebral dirofilariasis. Eur J Ophthalmol 2005, 15:407-408.
- [23]Babal P, Kobzova D, Novak I, Dubinsky P, Jalili N: First case of cutaneous human dirofilariosis in Slovak Republic. Bratisl Lek List 2008, 109:486-488.
- [24]Szénási Z, Kovács AH, Pampiglione S, Fioravanti ML, Kucsera I, Tánczos B, Tiszlavicz L: Human dirofilariosis in Hungary: an emerging zoonosis in central Europe. Wien Klin Wochenschr 2008, 120:96-102.
- [25]Zarnowska-Prymek H, Cielecka D, Salamatin R: Dirofilariasis -Dirofilaria repens-first time described in Polish patients. Przegl Epidemiol 2008, 62:547-551.
- [26]Cancrini G, di Regalbono A, Ricci I, Tessarin C, Gabrielli S, Pietrobelli M: Aedes albopictus is a natural vector of Dirofilaria immitis in Italy. Vet Parasitol 2003, 118:195-202.
- [27]Gratz NG: Critical review of the vector status of Aedes albopictus. Med Vet Entomol 2004, 18:215-227.
- [28]Knols BGJ, Takken W: Alarm bells ringing: more of the same, and new and novel diseases and pests. In Emerging Pests and Vector-Borne Diseases in Europe. Edited by Takken W, Knols BGJ. The Netherlands: Wageningen Academic Publishers; 2007:13-19.
- [29]Paran RD, Svobodová V: Effect of therapy by using advocate spot-on combination (imidacloprid 10% and moxidectin 2.5%) on subcutaneous dirofilariosis in dogs. Vet Med Int 2011, 2011:482746.
- [30]Genchi C, Genchi M, Petry G, Kruedewagen EM, Schaper R: Evaluation of the efficacy of imidacloprid 10% / moxidectin 2.5% (Advocate®, Advantage® Multi, Bayer) for the prevention of Dirofilaria repens infection in dogs. Parasitol Res 2013, 112(Suppl 1):81-89.
- [31]Traversa D, Di Cesare A, Conboy G: Canine and feline cardiopulmonary parasitic nematodes in Europe: emerging and underestimated. Parasit Vectors 2010, 3:62.
- [32]Snyder DE, Wiseman S, Cruthers LR, Slone RL: Ivermectin and milbemycin oxime in experimental adult heartworm (Dirofilaria immitis) infection of dogs. J Vet Intern Med 2011, 25:61-64.
- [33]Nolan TJ, Lok JB: Macrocyclic lactones in the treatment and control of parasitism in small companion animals. Curr Pharm Biotechnol 2012, 13:1078-1094.
- [34]Di Cesare A, Otranto D, Di Giulio E, Simonato G, Latrofa MS, La Torre F, Coccia G, Traversa D: Microfilarial periodicity of Dirofilaria repens in naturally infested dogs. Parasitol Res 2013, 112:4273-4279.
- [35]Sloss MW, Kemp RL, Zajac AM: Veterinary Clinical Parasitology. 6th edition. Ames, IA: Iowa State University Press; 1994.
- [36]Taylor MA, Coop RL, Wall RL: Veterinary Parasitology. 3rd edition. Oxford UK: Blackwell Publishing; 2007.
- [37]Lindsey LR: Identification of canine microfilariae. J Am Vet Med Assoc 1965, 146:1106-1114.
- [38]Euzeby J: Diagnostic experimental des helminthoses animales. Travaux pratiques d’helminthologie veterinaire, Livre 1. Paris, France: Informations Techniques des Services Veterinaires, Ministry of Agriculture; 1981:302.
- [39]Casiraghi M, Bazzocchi C, Mortarino M, Ottina E, Genchi C: A simple molecular method for discriminating common filarial nematodes of dogs (Canis familiaris). Vet Parasitol 2006, 141:368-372.
- [40]Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
- [41]Traversa D, Aste G, Milillo P, Capelli G, Pampurini F, Tunesi C, Santori D, Paoletti B, Boari A: Autochthonous foci of canine and feline infections by Dirofilaria immitis and Dirofilaria repens in central Italy. Vet Parasitol 2010, 169:128-132.
- [42]Marconcini A, Magi M, Hecht Contin B: The value of ivermectin in the prophylaxis of Dirofilaria repens infestation in naturally infected dogs. Parassitologia 1993, 35:67-71.
- [43]Pollono F, Pollmeier M, Rossi L: The prevention of Dirofilaria repens infection with ivermectin/pyrantel chewables. Parassitologia 1998, 40:457-459.
- [44]Rossi L, Ferroglio E, Agostini A: Use of moxidectin tablets in the control of canine subcutaneous dirofilariosis. Vet Rec 2002, 150:383.
- [45]Rossi L, Ferroglio E, Agostini A: Use of an injectable, sustained-release formulation of moxidectin to prevent canine subcutaneous dirofilariosis. Vet Rec 2004, 154:26-27.
- [46]Genchi M, Pengo G, Genchi C: Efficacy of moxidectin microsphere sustained release formulation for the prevention of subcutaneous filarial (Dirofilaria repens) infection in dogs. Vet Parasitol 2010, 170:167-189.
- [47]Traversa D, Mazzi A, Di Cesare A, Famigli Bergamini P, Fracassi F, Fanini G, Aste G, Pampurini F, Boari A: Potential efficacy of monthly administrations of spot-on moxidectin 2.5%/imidacloprid 10% in the simultaneous prevention of major canine filarioses. Parasitol Res 2013, 112:3753-3756.
- [48]Traversa D: Pet roundworms and hookworms: a continuing need for global worming. Parasit Vectors 2012, 5:91.
- [49]Kelly PJ, Fisher M, Lucas H, Krecek RC: Treatment of esophageal spirocercosis with milbemycin oxime. Vet Parasitol 2008, 156:358-360.
- [50]Ferroglio E, Rossi L, Tomio E, Schenker R, Bianciardi P: Therapeutic and prophylactic efficacy of milbemycin oxime (Interceptor) against Thelazia callipaeda in naturally exposed dogs. Vet Parasitol 2008, 154:351-353.
- [51]Motta B, Schnyder M, Basano FS, Nägeli F, Nägeli C, Schiessl B, Mallia E, Lia RP, Dantas-Torres F, Otranto D: Therapeutic efficacy of milbemycin oxime/praziquantel oral formulation (Milbemax®) against Thelazia callipaeda in naturally infested dogs and cats. Parasit Vectors 2012, 5:85.
- [52]Conboy G: Natural infections of Crenosoma vulpis and Angiostrongylus vasorum in dogs in Atlantic Canada and their treatment with milbemycin oxime. Vet Rec 2004, 155:16-18.
- [53]Conboy G, Bourque A, Miller L, Seewald W, Schenker R: Efficacy of Milbemax (milbemycin oxime + praziquantel) in the treatment of dogs experimentally infected with Crenosoma vulpis. Vet Parasitol 2013, 198:319-324.
- [54]Traversa D: Are we paying too much attention to cardio-pulmonary nematodes and neglecting old-fashioned worms like Trichuris vulpis? Parasit Vectors 2011, 4:32.