DOI QR코드

DOI QR Code

Therapeutic Effects of Atovaquone/Proguanil in Combination with Azithromycin in Dogs Naturally Infected with Babesia gibsoni

Babesia gibsoni 자연 감염개에서의 Atovaquone/Proguanil 합제와 Azithromycin 병용투여에 따른 치료효과

  • Lee, Dae-Keun (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Kim, Yun-Gi (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Yun, Young-Min (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University) ;
  • Lee, Kyoung-Kap (College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University)
  • 이대근 (제주대학교 수의과대학.제주대학교 수의과학 연구소) ;
  • 김윤기 (제주대학교 수의과대학.제주대학교 수의과학 연구소) ;
  • 윤영민 (제주대학교 수의과대학.제주대학교 수의과학 연구소) ;
  • 이경갑 (제주대학교 수의과대학.제주대학교 수의과학 연구소)
  • Accepted : 2016.02.20
  • Published : 2016.02.29

Abstract

This study was performed to estimate the clinical use of combination therapy with atovaquone/proguanil and azithromycin as a effective treatment in dogs infected with Babesia gibsoni. Eight mixed-breed dogs that were infected naturally with B. gibsoni were used in this study. Four dogs (No. 1-4) as experimental group received atovaquone/proguanil and azithromycin therapy. As for the other four dogs as the control group (No. 5-8) were administered diminazene aceturate and tetracycline/clindamycin. All the dogs in this study showed mild to severe anemia and thrombocytopenia. After initiating the treatment B. gibsoni in blood smears disappeared. PCR analysis of the experimental group showed negative results during the observation period, but more than one dog from the control groups showed continuous positive results. Atovaquone/proguanil and azithromycin combination therapy can significantly lower the B. gibsoni parasitemia levels and the results suggested that this combination therapy should be a new protocol for an effective treatment in dogs infected with B. gibsoni.

Keywords

References

  1. Baggish AL, Hill DR. Antiparasitic agent atovaquone. Antimicrob Agents Chemother 2002; 46: 1163-1173. https://doi.org/10.1128/AAC.46.5.1163-1173.2002
  2. Birkenheuer AJ, Levy MG, Breitschwerdt EB. Efficacy of combined atovaquone and azithromycin for therpy of chronic Babesia gibsoni (asian genotype) infections in dogs. J Vet Intern Med 2004; 18: 494-498. https://doi.org/10.1111/j.1939-1676.2004.tb02573.x
  3. Conrad P, Thomford J, Tamane I, Whiting J, Bosma L, Uno T, Holshuh HJ, Shelly S. Hemolytic anemia caused by Babesia gibsoni infection in dogs. J Am Vet Med Assoc 1991; 199: 601-605.
  4. Farwell GE, LeGrand EK, Cobb CC. Clinical observations on Babesia gibsoni and Babesia canis infection in dogs. J AM Vet Med Assoc 1982; 180: 507-511.
  5. Fukumoto S, Xuan X, Shigeno S, Kimbita E, Igarashi I, Nagasawa H, Fujisaki K, Mikami T. Development of a polymerase chain reaction method for diagnosing Babesia gibsoni infection in dogs. J Vet Med Sci 2001; 63: 977-981. https://doi.org/10.1292/jvms.63.977
  6. Groves MG, Dennis GL. Babesia gibsoni; field and laboratory studies of canine infections. Exp Parasitol 1972; 31: 153-159. https://doi.org/10.1016/0014-4894(72)90057-4
  7. Hwang MJ, Lee HS, Lee KW, Hematological and serum chemical findings following repeated medication of diminazene aceturate in canine babesiosis. Korean J Vet Clin Med 2000; 17: 349-358.
  8. Iguchi A, Matsuu A, Fujii Y, Ikadai H, Hikasa Y. The in vitro interactions and in vivo efficacy of atovaquone and proguanil against Babesia gibsoni infection in dogs. Vet Parasitol 2013; 197: 527-533. https://doi.org/10.1016/j.vetpar.2013.06.006
  9. Iguchi A, Shiranaga N, Matsuu A, Hikasa Y. Efficacy of $Malarone(^{(R)})$ in dogs naturally infected with Babesia gibsoni. J Vet Med Sci 2014; 76: 1291-1295. https://doi.org/10.1292/jvms.14-0139
  10. Inokuma H, Yoshizaki Y, Matsumoto K, Onishi T, Nakagome K, Kosugi R, Hirakawa M. Molecular survey of Babesia infection in dogs in Okinawa, Japan. Vet Parasitol 2004; 121: 341-346. https://doi.org/10.1016/j.vetpar.2004.03.012
  11. Jefferies R, Ryan UM, Jardine J, Robertson ID, Irwin PJ. Babesia gibsoni: Detection during experimental infections and after combined atovaquone and azithromycin therapy. Exp Parasitol 2007; 117: 115-123. https://doi.org/10.1016/j.exppara.2007.03.016
  12. Korsinczky M, Chen N, Kotecha B, Saul A, Rieckmann K, Cheng Q. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother 2000; 44: 2100-2108. https://doi.org/10.1128/AAC.44.8.2100-2108.2000
  13. Lee MJ, Yu DH, Yoon JS, Li YH, Lee JH, Chae JS, Park J., Epidemiologic and clinical surveys in dogs infected with Babesia gibsoni in South Korea, Vector Borne Zoonotic Dis. 2009.
  14. Lin EC, Chueh LL, Lin CN, Hsieh LE, Su BL. The therapeutic efficacy of two antibabesial strategies against Babesia gibsoni. Vet Parasitol 2012; 186: 159-164. https://doi.org/10.1016/j.vetpar.2011.11.073
  15. Lin MY, Huang HP. Use of a doxycycline-enrofloxacinmetronidazole combanation with/without diminazene diaceturate to treat naturally occuring canine babesiosis caused by Babesia gibsoni. Acta Vet Scand 2010; 52: 27. https://doi.org/10.1186/1751-0147-52-27
  16. Matsuu A, Koshida Y, Kawahara M, Inoue K, Ikadai H, Hikasa Y, Okano S, Hifuchi S. Efficacy of atovaquone against Babesia gibsoni in vivo and in vitro. Vet Parasitol 2004; 124: 9-18. https://doi.org/10.1016/j.vetpar.2004.07.005
  17. Matsuu A, Ono S, Ikadai H, Uchide T, Imamura S, Onuma M, Okano S, Hifuchi S. Development of a SYBR green real-time polymerase chain reaction assay for quantitative detection of Babesia gibsoni (Asian genotype) DNA. J Vet Diagn Invest 2005; 17: 569-573. https://doi.org/10.1177/104063870501700608
  18. Matsuu A, Miyamoto K, Ikadai H, Okano S, Higuchi S. Cloning of the Babesia gibsoni cytochrome b gene and isolation of three single nucleotide polymorphisms from parasites present after atovaquone treatment. Am J Trop Med Hyg 2006; 74: 593-597.
  19. Matsuu A, Yamasaki M, Xuan X, Ikadai H, Hikasa Y. In vitro evaluation of the growth inhibitory activities of 15 drugs against Babesia gibsoni (Aomori strain). Vet Prasitol 2008; 157: 1-8. https://doi.org/10.1016/j.vetpar.2008.07.023
  20. Miller DB, Swan GM, Lobetti RG, Jacobson LS. The pharmacokinetics of diminazene aceturate after intramuscular administration in healthy dogs. J S Afr Vet Assoc 2005; 76: 146-150.
  21. Sakuma M, Setoguchi A, Endo Y. Possible emergence of drug-resistant variants of Babesia gibsoni in clinical cases treated with atovaquone and azithromycin. J Vet Intern Med 2009; 23: 493-498. https://doi.org/10.1111/j.1939-1676.2009.0300.x
  22. Suzuki K, Wakabayashi H, Takahashi M, Fukushima K, Yabuki A, Endo, Y. A possible treatment strategy and clinical factors to estimate the treatment response in Babesia gibsoni infection. J Vet Med Sci 2007; 69: 563-568. https://doi.org/10.1292/jvms.69.563
  23. Wickramasekara Rajapakshage BK, Yamasaki M, Hwang SJ, Sasaki N, Murakami M, Tamura Y, Lim SY, Nakamura K, Ohta H, Takiguchi M. Involvement of mitochondrial genes of Babesia gibsoni in resistance to diminazene aceturate. J Vet Med Sci 2012; 74: 1139-1148. https://doi.org/10.1292/jvms.12-0056
  24. Wulansari R, Wijaya A, Ano H, Horii Y, Nasu T, Yamane S, Makimura S. Clindamycin in the treatment of Babesia gibsoni infections in dogs. J Am Anim Hosp Assoc 2003; 39: 558-562. https://doi.org/10.5326/0390558