Interpretation of doxycycline+chloroquine dual therapy for A. phagocytophilum infection in dogs

Interpretation of doxycycline+chloroquine dual therapy for A. phagocytophilum infection in dogs

ABSTRACT

Objective. A. phagocytophilum, an obligate intracellular pathogen, is a well-known agent causing granulocytic infections in both animals and humans. The purpose of the present study was to describe clinical course and consequences of Canine Granulocyctic Anaplasmosis among dogs in Aydin province, Turkey with special reference to hematological alterations and possible interpretations of doxycycline+chloroquine dual therapy. Materials and methods. A controlled clinical trial was carried out on 14 dogs referred and diagnosed as Canine Granulocyctic Anaplasmosis within Snap 4dx test. Relevant haematological data were recorded before (day 0) and after treatment (day 30) in both groups. Group I (n=7) were adminestered doxycycline (10 mg/kg q 12 h via oral route for 14 days) and chloroquine (2.5 mg/kg q 12 h for 14 days) and group II (n=7) received only doxycycline (10 mg/kg q 12 h for 14 days via oral route) therapy. Results. Doxycycline treatment hasten resolution of clinical signs in all dogs in about 2 to 7 days. There was no statistically significant differences among hematological variances detected (p>0.05). Conclusions. It may suggest that in conjunction with doxycycline chloroquine may have helped to speed up relevant clinical signs of CGA.

RESUMEN

Objetivo. A. phagocytophilum, un patógeno intracelular obligado, es un agente ampliamente conocido que causa infecciones granulocíticas tanto en animales como en humanos. El propósito del presente estudio fue describir la evolución clínica y las consecuencias de la Anaplasmosis Granulocítica Canina en perros de la provincia de Aydin, Turquía, con especial referencia a las alteraciones hematológicas y a las posibles interpretaciones de una terapia dual de doxicilina+cloroquina. Materiales y métodos. Se realizó un estudio clínico controlado en 14 perros remitidos y diagnosticados con Anaplasmosis Granulocítica Canina usando de una prueba Snap 4dx. Se registraron datos hematológicos pertinentes antes (día 0) y después del tratamiento (día 30) en ambos grupos. Al Grupo I (n=7) se le administró doxicilina (10 mg/kg q 12 h por vía oral durante 14 días) y cloroquina (2.5 mg/kg q 12 h durante 14 días), mientras que el Grupo II (n=7) recibió una terapia únicamente con doxicilina (10 mg/kg q 12 h por vía oral durante 14 días). Resultados. La doxicilina aceleró la resolución de los signos clínicos en todos los perros en un periodo de aproximadamente 2 a 7 días. No se detectaron diferencias estadísticas significativas entre las variaciones hematológicas (p>0.05). Conclusiones. Lo anterior puede sugerir que, conjuntamente con la doxicilina, la cloroquina puede haber ayudado a acelerar los signos clínicos pertinentes de la Anaplasmosis Granulocítica Canina (AGC).

1. Carrade D, Foley J, Sullivan M, Foley CW, Sykes JE. Spatial distribution of seroprevalence for Anaplasma phagocytophilum, Borrelia burgdorferi, Ehrlichia canis, and Dirofilaria immitis in dogs in Washington, Oregon, and California. Vet Clin Pathol 2011; 40(3):293-302. http://dx.doi.org/10.1111/j.1939-165X.2011.00334.x
3. Dumler JS, Barbet AF, Bekker CP. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila. Int J Syst Evol Microbiol 2001;5:2145–2165.
4. http://dx.doi.org/10.1099/00207713-51-6-2145
6. Bakken JS, Dumler S. Human granulocytic anaplasmosis. Infect Dis Clin N Am 2008; 22:443–448. http://dx.doi.org/10.1016/j.idc.2008.03.011
8. Bakken JS, Dumler JS. Clinical diagnosis and treatment of human granulocytotropic anaplasmosis. Ann N Y Acad Sci 2006; 1078:236–247. http://dx.doi.org/10.1196/annals.1374.042
10. Bjöersdorff A. Ehrlichiosis and anaplasmosis, Part II: Anaplasma phagocytophilum comb. nov. infection. . Arthropod borne Infectious Diseases of the Dog and Cat. Manson Publishing, London; 2005.
12. Courtney JW, Kostelnik LM, Zeidner NS, Massung RF. Multiplex real time PCR for detection of Anaplasma phagocytophilum and Borrelia burgdorferi. J Clin Microbiol 2004; 42:3164–3168.
13. http://dx.doi.org/10.1128/JCM.42.7.3164-3168.2004
15. Carrade DD, Foley JE, Borjesson DL, Sykes JE. Canine granulocytic anaplasmosis: a review. J Vet Intern Med 2009; 23(6):1129-1141. http://dx.doi.org/10.1111/j.1939-1676.2009.0384.x
17. Bjoersdorff A. Canine granulocytic ehrlichiosis due to Anaplasma phagocytophila. Guide to Major Vector-borne Diseases of Pets, Merial, France. 2002.
19. McQuiston JH, McCall CL, Nicholson WL. Ehrlichiosis and related infections. J Am Vet Med Assoc 2003; 223(12):1750–1756.
20. http://dx.doi.org/10.2460/javma.2003.223.1750
22. Eberts MD, Vissotto de Paiva Diniz PP, Beall MJ, Stillman BA, Chandrashekar R, Breitschwerdt EB. Typical and atypical manifestations of Anaplasma phagocytophilum infection in dogs. J Am Anim Hosp Assoc 2011; 47(6):86-94. http://dx.doi.org/10.5326/JAAHA-MS-5578
24. Kohn B, Silaghi C, Galkea D, Arndt G, Pfister K. Infections with Anaplasma phagocytophilum in dogs in Germany. Res Vet Sci 2011; 91:71-76. http://dx.doi.org/10.1016/j.rvsc.2010.08.008
26. Granick JL, Armstrong PJ, Bender JB. Anaplasma phagocytophilum infection in dogs: 34 cases (2000-2007). J Am Vet Med Assoc 2009; 234(12):1559–65. http://dx.doi.org/10.2460/javma.234.12.1559
28. Aysul N, Ural K, Cetinkaya H, Kuşkucu M, Toros G, Eren H, Durum C. Doxycycline-Chloroquine Combination for the Treatment of Canine Monocytic Ehrlichiosis. Acta Sci Vet 2012; 40(2):1031.
30. Faria JL, Munhoz TD, João CF, Vargas-Hernández G, André MR, Pereira WA, Machado RZ, Tinucci Costa M. Ehrlichia canis (Jaboticabal strain) induces the expression of TNF-a in leukocytes and splenocytes of experimentally infected dogs. Braz J Vet Parasitol 2011; 20(1):71-74. http://dx.doi.org/10.1590/S1984-29612011000100015
32. Park J, Kwon D, Choi C, Oh JW, Benveniste EN. Chloroquine induces activation of nuclear factor kappa B and subsequent expression of pro-inflammatory cytokines by human astroglial cells. J Neurochem 2003; 84(6):1266-1274. http://dx.doi.org/10.1046/j.1471-4159.2003.01623.x
34. Weber S, Levitz SM. Chloroquine antagonizes the proinflammatory cytokine response to oppurtunistic fungi by alkalizing the fungal phagolysosome. J Infect Dis 2001; 183(6):935-942. http://dx.doi.org/10.1086/319259
36. Wozniacka A, Lesiak A, Narbutt J, McCauliff DP, Sysa-Jedrzejowska A. Chloroquine treatment influences proinflammatory cytokine levels in systemic lupus erythematosus patients. Lupus 2006; 15(5):268-275. http://dx.doi.org/10.1191/0961203306lu2299oa
38. Lester SJ, Breitschwerdt EB, Hegarty BC. Anaplasma phagocytophilum infection (granulocytic anaplasmosis) in a dog from Vancouver Island. Can Vet J 2005; 46(9):825-827.
40. O Melter, I Stehlik, H Kinska, I Volfova, V Ticha, D Hulinska. Infection with Anaplasma phagocytophilum in a young dog: a case report Vet Med 2007; 52(5):207–212.
42. AlKadi HO. Antimalarial drug toxicity: a review. Chemotherapy 2007; 53(6):385-391. http://dx.doi.org/10.1159/000109767
44. Petersen I, Eastman R, Lanzer M. Drug-resistant malaria: molecular mechanisms and implications for public health. FEBS Lett 2011; 585(11):1551-1562. http://dx.doi.org/10.1016/j.febslet.2011.04.042
46. Stepniewska K, White NJ. Pharmacokinetic determinants of the window of selection for antimalarial drug resistance. Antimicrob Agents Chemother 2008; 52:1589-1596.
47. http://dx.doi.org/10.1128/AAC.00903-07