Efficacy of topical application of carvacrol, amitraz, and combination of carvacrol-amitraz for the treatment of dogs with generalized demodicosis

Subject Areas : Parasitology

Sina  Fereydooni ¹ (Department of Clinical Sciences, Veterinary Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran Department of Clinical Sciences, Veterinary Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran)
Farnoosh  Arfaee ² (Department of Clinical Sciences, Veterinary Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran Department of Clinical Sciences, Veterinary Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran )
Mohammad Reza  Youssefi ³ (Department of Parasitology, Veterinary Faculty, Babol Branch, Islamic Azad University, Babol, Iran)
Fatemeh Zahra  Gharib ⁴ (Department of Clinical Sciences, Veterinary Faculty, Babol Branch, Islamic Azad University, Babol, Iran)
Mohaddeseh  Abouhosseini-Tabari ⁵ (Veterinary Faculty, Amol University of Special Modern Technologies, Amol, Iran)

Received: 2023-11-22 Accepted : 2023-12-23 Published : 2024-03-03

Keywords: Demodicosis, Carvacrol, Amitraz, Skin, Pour-on,

Abstract :

Canine demodicosis is an inflammatory parasitic skin disease caused by an increasing population of Demodex spp. mite. Thus, there will be an urgent need for effective, safe, and available treatment for demodicosis. This study aimed to evaluate the activity of Carvacrol %5, Amitraz %0.05, and Carvacrol-Amitraz combination on killing Demodex canis mites after topical pour-on use and analyzing the improvement in associated dermatologic signs. Fifteen dogs with naturally acquired generalized demodicosis were randomly allocated to 3 equal study groups. The dogs were selected from the animal shelter in Mazandaran province. Treatment groups included a pour-on solution of 50 ml of Carvacrol %5, 50 ml of Amitraz %0.05, and the combined Carvacrol and Amitraz 1:1 mixture at the same concentrations. Evaluation of clinical factors consisted of mite count by skin scraping, hair re-growth, comedones, erythema, crusts, and scales during seven-day intervals over four weeks. Mite counts significantly decreased in all groups during the study, especially in Carvacrol %5 (p0.05). The highest decrease in mite population was associated with Carvacrol %5 from day 14 up to %90 in demodicosis treatment. This clinical field study demonstrated that pour-on administration of Carvacrol %5 is highly effective in the reduction of mite numbers and improvement in associated dermatologic signs of demodicosis

References:

[1] Miller WH, Griffin CE, Campbell KL. Neoplastic and non-neoplastic tumors. Muller and kirk’s small animal dermatology. 2013; 7: 774-843.
[2] Patra G, Behera P, Ghosh S, Mohanta D, Borthakur SK, Biswas P. et al. Molecular characterization of chitin synthase gene of Demodex canis from Mizoram, India. Acta Parasitologica. 2019; 64: 57-62.
doi:10.2478/s11686-018-00008-6
[3] Mueller RS. An update on the therapy of canine demodicosis. Compendium (Yardley, PA). 2012; 34(4): E1-4.
doi:10.1111/j.1365-3164.2011.01026.x
[4] Shrestha D, Thapa B, Rawal G, Dhakal S, Sharma B. Prevalence of demodectic mange in canines of Kathmandu Valley having skin disorder and its associated risk factors. International Journal of Applied Sciences and Biotechnology. 2015; 3(3): 459-63. doi:10.3126/ijasbt.v3i3.13218
[5] Ionică AM, Deak G, D’ Amico G, Stan GF, Chișamera GB, Constantinescu IC. et al. Thelazia callipaeda in mustelids from Romania with the European badger, Meles meles, as a new host for this parasite. Parasites & Vectors. 2019; 12(1): 1-6.
doi:10.1186/s13071-019-3631-4
[6] Plant JD, Lund EM, Yang MA. Case–control study of the risk factors for canine juvenile‐onset generalized demodicosis in the USA. Veterinary dermatology. 2011; 22(1): 95-9. doi:10.1111/j.1365-3164.2010.00922.x
[7] Mueller RS, Meyer D, Bensignor E, Sauter‐Louis C. Treatment of canine generalized demodicosis with a ‘spot‐on’ formulation containing 10% moxidectin and 2.5% imidacloprid (Advocate®, Bayer Healthcare). Veterinary Dermatology. 2009; 20(5‐6):441-446.
doi:10.1111/j.1365-3164.2009.00790.x
[8] Mueller RS, Rosenkrantz W, Bensignor E, Karaś‐Tęcza J, Paterson T, Shipstone MA. Diagnosis and treatment of demodicosis in dogs and cats: Clinical consensus guidelines of the World Association for Veterinary Dermatology. Veterinary dermatology. 2020; 31(1): 4-e2. doi:10.1111/vde.12806
[9] Ferrer L, Ravera I, Silbermayr K. Immunology and pathogenesis of canine demodicosis. Veterinary Dermatology. 2014; 25(5): 427-e65. doi:10.1111/vde.12136
[10] Guaguere E, Prélaud P. A practical guide to canine dermatology. Merial; 2008. pp: 187-347.
[11] Mueller RS, Bettenay SV. Scraping, fine-needle aspiration and biopsy of skin and subcutaneous tissues. Textbook of veterinary internal medicine, 8th edition. St Louis, MO: Elsevier. 2017; 342-45.
[12] Marepally S, Boakye CH, Shah PP, Etukala JR, Vemuri A, Singh M. Design, synthesis of novel lipids as chemical permeation enhancers and development of nanoparticle system for transdermal drug delivery. PloS one. 2013; 8(12); e82581.
doi:10.1371/journal.pone.0082581
[13] Hugnet C, Bruchon‐Hugnet C, Royer H, Bourdoiseau G. Efficacy of 1.25% amitraz solution in the treatment of generalized demodicosis (eight cases) and sarcoptic mange (five cases) in dogs. Veterinary Dermatology. 2001; 12(2): 89-92.
doi:10.1046/j.1365-3164.2001.00231.x
[14] Mueller RS. Treatment protocols for demodicosis: an evidence‐based review. Veterinary dermatology. 2004; 15(2): 75-89. doi:10.1111/j.1365-3164.2004.00344.x
[15] Paterson TE, Halliwell RE, Fields PJ, Louw ML, Louw JP, Ball GS. et al. Treatment of canine‐generalized demodicosis: a blind, randomized clinical trial comparing the efficacy of Advocate® (Bayer Animal Health) with ivermectin. Veterinary Dermatology. 2009; 20(5‐6): 447-55.
doi:10.1111/j.1365-3164.2009.00803.x
[16] Holm BR. Efficacy of milbemycin oxime in the treatment of canine generalized demodicosis: a retrospective study of 99 dogs (1995–2000). Veterinary Dermatology. 2003; 14(4): 189-95.
doi:10.1046/j.1365- 3164.2003.00339.x
[17] Barbet JL, Snook T, Gay JM, Mealey KL. ABCB1‐1Delta (MDR1‐1Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis. Veterinary dermatology. 2009; 20(2): 111-14.
doi:10.1111/j.1365-3164.2008.00725.x
[18] Fourie LJ, Kok DJ, Du Plessis A, Rugg D. Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of demodectic mange in dogs. Veterinary Parasitology. 2007; 150(3): 268-74.
doi:10.1016/j.vetpar.2007.08.047
[19] Heine J, Krieger K, Dumont P, Hellmann, K. Evaluation of the efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot–on in the treatment of generalized demodicosis in dogs: results of a European field study. Parasitology research. 2005; 97: S89-S96. doi:10.1007/s00436-005-1450-3
[20] Fourie JJ, Liebenberg JE, Horak IG, Taenzler J, Heckeroth AR Frénais R. Efficacy of orally administered fluralaner (BravectoTM) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs. Parasites & vectors. 2015; 8: 187.
doi:10.1186/s13071-015-0775-8
[21] Beugnet F, Halos L, Larsen D, de Vos C. Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis. Parasite. 2016; 23. doi:10.1051/parasite/2016014
[22] Mueller RS, Bensignor E, Ferrer L, Holm B, Lemarie S, Paradis M. Treatment of demodicosis in dogs: 2011 clinical practice guidelines. Veterinary dermatology. 2012; 23(2); 86-e21.
doi:10.1111/j.1365-3164.2011.01026.x
[23] Snyder DE, Wiseman S, Liebenberg JE. Efficacy of lotilaner (Credelio™), a novel oral isoxazoline against naturally occurring mange mite infestations in dogs caused by Demodex spp. Parasites & vectors. 2017; 10(1): 532.
doi:10.1186/s13071-017-2472-2
[24] Rohdich N, Roepke RK, Zschiesche EA. Randomized, blinded, controlled, and multi-centered field study comparing the efficacy and safety of Bravecto™ (fluralaner) against Frontline™ (fipronil) in flea-and tick-infested dogs. Parasites & vectors. 2014; 7(1): 83.
doi:10.1186/1756-3305-7-83
[25] Gaens D, Rummel C, Schmidt M, Hamann M, Geyer J. Suspected neurological toxicity after oral application of fluralaner (Bravecto®) in a Kooikerhondje dog. BMC Veterinary Research. 2019; 15: 283.
doi:10.1186/s12917-019-2016-4
[26] Castro KNDC, Canuto KM, Brito EDS, Costa-Júnior LM, Andrade IMD, Magalhães JA. et al. In vitro efficacy of essential oils with different concentrations of 1, 8-cineole against Rhipicephalus (Boophilus) microplus. Revista Brasileira de Parasitologia Veterinária. 2018; 27: 203-210.
doi:10.1590/S1984-296120180015
[27] Etewa SE, Abaza SM. Herbal medicine and parasitic diseases. Parasitology United Journal. 2011; 4(1): 3-14.
doi:10.29252/mlj.16.4.26
[28] Sapra B, Jain S, Tiwary AK. Percutaneous permeation enhancement by terpenes: mechanistic view. The AAPS journal. 2008; 10: 120-132.
doi:10.1208/s12248-397008-9012-0
[29] Shokri J, Nokhodchi A, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Jalali MB. The effect of surfactants on the skin penetration of diazepam. International Journal of Pharmaceutics. 2001; 228(1-2): 99-107.
doi:10.1016/s0378-5173(01)00805-5
[30] de Souza CP, Correia TR, Melo RM, Verocai GG, Cavalcanti MC, Scott FB. Miticidal efficacy of thiabendazole against Otodectes cynotis (Hering, 1838) in dogs. Brazilian journal of veterinary parasitology. 2006; 15(4): 143-6.
doi:10.1053/j.ctsap.2006.05.006
[31] Okabe H, Suzuki E, Saitoh T, Takayama K, Nagai T. Development of novel transdermal system containing d-limonene and ethanol as absorption enhancers. Journal of controlled release. 1994; 32(3): 243-7.
doi:10.1016/0168-3659(94)90234-8
[32] Lane ME. Skin penetration enhancers. International journal of pharmaceutics. 2013; 447(1-2): 12-21.
doi:10.1016/j.ijpharm.2013.02.040
[33] Jayakumar S, Madankumar A, Asokkumar S, Raghunandhakumar S, Gokula dhas K, Kamaraj S. et al. Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats. Molecular and cellular biochemistry. 2012; 360: 51-60. doi:10.1007/s11010-011-1043-7
[34] Sajed H, Sahebkar A, Iranshahi M. Zataria multiflora Boiss. (Shirazi thyme) an ancient condiment with modern pharmaceutical uses. Journal of ethnopharmacology. 2013; 145(3): 686-98. doi:10.1016/j.jep.2012.12.018
[35] Baranauskaite J, Kubiliene A, Marksa M, Petrikaite V, Vitkevičius K, Baranauskas A. et al. The influence of different oregano species on the antioxidant activity determined using HPLC postcolumn DPPH method and anticancer activity of carvacrol and rosmarinic acid. BioMed Research International. 2017. doi:10.1155/2017/1681392
[36] Barnwal P, Vafa A, Afzal SM, Shahid A, Hasan SK, Alpashree. et al. Benzo (a) pyrene induces lung toxicity and inflammation in mice: prevention by carvacrol. Human & Experimental Toxicology. 2018; 37(7): 752-61. doi:10.1177/0960327117735572
[37] Allaoua M, Etienne P, Noirot V, Carayon JL, Tene N, Bonnafé E. et al. Pharmacokinetic and antimicrobial activity of a new carvacrol‐based product against a human pathogen, Campylobacter jejuni. Journal of applied microbiology. 2018; 125(4): 1162-74.
doi:10.1111/jam.139151
[38] Ahn YJ, Lee SB, Lee HS, Kim GH. Insecticidal and acaricidal activity of carvacrol and β-thujaplicine derived from Thujopsis dolabrata var. hondai sawdust. Journal of Chemical Ecology. 1998; 24: 81-90.
doi:10.1023/a:1022388829078
[39] Marchese A, Arciola CR, Coppo E, Barbieri R, Barreca D, Chebaibi S. et al. The natural plant compound carvacrol as an antimicrobial and anti-biofilm agent: Mechanisms, synergies and bio-inspired anti-infective materials. Biofouling. 2018; 34(6): 630-56. doi:10.1080/08927014.2018.1480756
[40] Sharifi‐Rad M, Varoni EM, Iriti M, Martorell M, Setzer WN, del Mar Contreras M. et al. Carvacrol and human health: A comprehensive review. Phytotherapy Research. 2018; 32(9): 1675-87.
doi:10.1002/ptr.6103
[41] APA American Psychological Association. National center for biotechnology information. pubchem compound summary for CID 12699, N-Nitroso-N-methylurea. retrieved 24. 2020. https://pubchem.ncbi.nlm.nih.gov/compound/N-Nitroso-N-methylurea
[42] Savla K, Le JT, Pucker AD. Tea tree oil for Demodex blepharitis. Cochrane Database of Systematic Reviews. 2020; (6).
doi:10.1002/14651858.CD013333.pub2
[43] Akkucuk S, Kaya OM. Can thyme oil be an alternative treatment for human demodicosis?. 2022.
doi:10.21203/rs.3.rs-1530942/v1
[44] Neves RDCDSM, Barros LA, Mendes SMC, Amorim TIDSWDA, Ferraz VP, Mateus LADF et al. The sensitivity of Demodex canis (Acari: Demodicidae) to the essential oil of Melaleuca alternifolia–an in vitro study. Brazilian Journal of Veterinary Parasitology. 2020; 29: e005220.
doi:10.1590/S1984-29612020059
[45] Perego R, Spada E, Foppa C, Proverbio D. Critically appraised topic for the most effective and safe treatment for canine generalised demodicosis. BMC Veterinary Research. 2019; 15(1): 17.
doi:10.1186/s12917-018-1767-7
[46] Dhooria S, Agarwal R. Amitraz, an underrecognized poison: A systematic review. The Indian Journal of Medical Research. 2016; 144(3): 348.
doi:10.4103/0971- 5916.198723
[47] Fourie J, Dumont P, Halos L, Beugnet F, Pollmeier M. Efficacy of a topical application of Certifect® (fipronil 6.26% w/v, amitraz 7.48% w/v, (S)-methoprene 5.63% w/v) for the treatment of canine generalized demodicosis. Parasite. 2013; 20.
doi:10.1051/parasite/2013046