Effectiveness of doxycycline/ivermectin therapy for heartworm disease in regards to Wolbachia status in dogs


Published: Apr 22, 2024
Keywords:
Heartworm disease Wolbachia alternative therapy
L Spasojević Kosić
V Lalošević
https://orcid.org/0000-0002-4813-8370
G Kozoderović
V Vračar
https://orcid.org/0000-0002-7369-9946
S Simin
https://orcid.org/0000-0002-2655-5325
A Potkonjak
https://orcid.org/0000-0003-3410-6842
Abstract

Heartworm disease (HWD), a highly important canine disease in veterinary medicine, is caused by Dirofilaria immitis (D. immitis). A therapeutic approach (the standard treatment or an alternative one, or even surgical intervention) in dogs naturally infected with D. immitis should be individually adjusted. The goal of this research was to test the effectiveness of an alternative therapeutic protocol for D.immitis and Wolbachia in 30 naturally infected dogs. Clinical and parasitological examinations (modified Knott test and SNAP Test IDEXX) were used for diagnosing Dirofilaria spp. Blood and urine laboratory, and radiographic examinations were used for the determination of HWD classes. An alternative therapy consisted of oral doxycycline and ivermectin administrations until microfilaremic and antigenic negativization, and was not longer than 9 months. Polymerase chain reaction (PCR) for wsp and 16S rRNA genes at the beginning and at the end of the therapy in 15 dogs was used for Wolbachia detection. The effectiveness of the alternative therapy for D. immitis and Wolbachia was 83.33% and 75% respectively. Neither the number of cured dogs nor the duration of the alternative therapy depended on the presence of Wolbachia. Thus, the alternative therapy with doxycycline and ivermectin is not based solely on targeting Wolbachia.

Article Details
  • Section
  • Research Articles
Downloads
Download data is not yet available.
Author Biographies
L Spasojević Kosić, Faculty of agriculture, University of Novi Sad

Department of veterinary medicine, full professor

V Lalošević, Faculty of agriculture, University of Novi Sad

Department of veterinary medicine, full professor

V Vračar, Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia

Department of veterinary medicine, assistant professor

S Simin, Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia

Department of veterinary medicine, assistant professor

A Potkonjak, Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Novi Sad, Serbia

Department of veterinary medicine, full professor

References
American heartworm society (AHS) (2020) https://d3ft8sckhnqim2. loudfront.net/images/pdf/2020_AHS_Canine_Guidelines.
pdf?1580934824 [accessed 20 September 2022]
Bandi C, McCall JW, Genchi C, Corona S, Venco L, Sacchi L (1999) Effects of tetracycline on the filarial worms Brugia pahangi and Dirofilaria immitis and their bacterial endosymbionts Wolbachia. Int J Parasitol 29: 357-364.
Bazzocchi C, Jamnongluk W, O’Neill SL, Anderson TJC, Genchi C, Bandi C (2000) wsp Gene Sequences from the Wolbachia of Filarial Nematodes. Curr Microbiol 41: 96-100.
Bazzocchi C, Genchi C, Paltrimieri S, Lecchi C, Mortarino M, Bandi C (2003) Immunological role of the endosymbiont of Dirofilaria immitis: the Wolbachia surface protein activates neutrophils with production of IL-8. Vet Parasitol 117: 73-83.
Bazzocchi C, Mortarino M, Grandi G, Kramer LH, Genchi C, Bandi C, Genchi M, Sacchi L, McCall JW (2008) Combined ivermectin and doxycycline treatment has microfilaricidal and adulticidal activity against Dirofilaria immitis in experimantally infected dogs. Int J Parasitol 38: 1401-1410. https://doi.org/10.1016/j.ijpara.2008.03.002
Carretón E, Morchón R, Falcón-Cordón Y, Falcón-Cordón S, Matos JI, Montoya-Alonso JA (2020) Evaluation of different dosages of doxycycline during the adulticide treatment of heartworm (Dirofilaria immitis) in dogs. Vet Parasitol 283: 109-141. https://doi.org/10.1016/j.vetpar.2020.109141
Dunn JK (2000) Textbook of small animal medicine. W. B. Saunders, London.
European Scientific Councel Companion Animal Parasites (ESCCAP) (2019) https://www.esccap.org/uploads/docs/t2kkcbgl_0775_ESCCAP_Guideline_GL5_v9_1p.pdf [accessed 20 September 2022]
Foster JM, Kumar S, Ford L, Johnston KL, Ben R, Graeff-Teixeira C, Taylor MJ (2008) Absence of Wolbachia endobacteria in the non-filarid nematodes Angiostrongylus cantonensis and A. costaricensis. Parasit Vectors 1: 31. https://doi.org/10.1186/1756-3305-1-31
Genchi G, Venco L, Genchi M. (2007) Guideline for the laboratory diagnosis of canine and feline Dirofilaria infections. In: Mappe Parassitologiche 8 - Dirofilaria immitis and D. repens in dog and cat and human infections. Rolando Editore, Naples: pp 137-145.
Genchi M, Vismarra A, Lucchetti C, Viglietti A, Crosara S, Gnudi G, Quintavalla C, Schaper R, Kramer L (2019) Efficacy of imidacloprid 10%/moxidectin 2.5% spot on (Advocate®,Advantage Multi®) and doxycycline for the treatment of natural Dirofilaria immitis infectionsin dogs. Vet Parasitol 273: 11-16. https://doi.org/10.1016/j.vetpar.2019.07.011
Grandi G, Quintavalla C, Mavropoulou A, Genchi M, Gnudi G, Bertoni G, Kramer L (2010) Combination of doxycycline and ivermectin is adulticidal in dogs with naturally acquired heartworm disease (Dirofilaria immitis). Vet Parasitol 169(3-4): 347-351. https://doi.org/10.1016/j.vetpar.2010.01.025
Janda JM, Abbott SL (2007) 16SrRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J Clin Microbiol 45(9): 2761-2764. https://doi.org/10.1128/JCM.01228-07
Kramer L, Grandi G, Passeri B, Gianelli P, Genchi M, Dzimianski MT, Supakorndej P, Mansour AM, Supakorndej N, McCall SD, McCall JW (2011) Evaluation of lung pathology in Dirofilaria immitis-experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of melarsomine dihydrochloride. Vet Parasitol 176: 357-360. https://doi.org/10.1016/j.vetpar.2011.01.021
Landum M, Ferreira CC, Calado M, Alho MA, Maurício IL, Meireles JS, de Carvalho LM, Cunha C, Belo S (2014) Detection of Wolbachia in Dirofilaria infected dogs in Portugal. Vet Parasitol 29 (3-4): 407-410. https://doi.org/10.1016/j.vetpar.2014.05.027
Maia C, Altet L, Serrano L, Cristovao JM, Tabar MD, Francino O, Cardoso L, Campino L, Roura X (2016) Molecular detection of Leishmania infantum, filariae and Wolbachia spp., in dogs from southern Portugal. Parasit Vectors 9: 170-176. https://doi.org/10.1186/s13071-016-1452-2
Martin C, Gavotte L. (2010) The bacteria Wolbachia in filariae, a biological Russian dolls’ system: new trends in antifilarial treatments. Parasite 17: 79-89. https://doi.org/10.1051/parasite/2010172079
McCall JW, Genchi C, Kramer L, Guerrero J, Dzimianski MT, Supakorndej P, Mansour AM, McCall SD, Supakorndej N, Grandi G, Carson B (2008) Heartworm and Wolbachia: therapeutic implications. Vet Parasitol 158: 204-214.
Milojković N, Aranđelović M, Ćurčin Lj (2016) In field retrospective study of „slow-kill “treatment efficiency on heartworm positive dogs in general practises in Serbia. Parasit Vectors 10 (Suppl 1): 5 A13.
Nelson T, Myrick ES, Nelson TA (2017) Clinical benefits of incorporating doxycycline into a canine heartworm treatment protocol. Parasit Vectors 10 (suppl 2): 515. https://doi.org/10.1186/s13071-017-2446-4
Potkonjak A, Savić S, Spasojević Kosić Lj, Tasić-Otašević S, Tomanović S, Kovačević Filipović M (2020) Consensus statement on the epidemiological situation and expected frequency of canine vector-borne diseases in Serbia. Vet Glasnik 74 (2): 211-215. https://doi.org/10.2298/VETGL201124016P
Rajan TV (2004) Relationship of anti-microbial activity of tetracyclines to their ability to block the L3 to L4 molt of the human filarial parasite Brugia malayi. Am J Trop Med Hyg 71(1): 24-28. https://doi.org/10.4269/ajtmh.2004.71.24
Ren W, Wei H, Yang Y, Shao S, Wu H, Chen X, Yang Z (2020) Molecular detection and phylogenetic analyses of Wolbachia in natural populations of nine galling Aphid species. Sci Rep 10: 12025. https://doi.org/10.1038/s41598-020-68925-z
Rossi MID, Paiva J, Bendas A, Mendes-de-Almeidac F, Knackfuss F, Miranda M, Guerrero J, Fernandes O, Labarthe N (2010) Effects of doxycycline on the endosymbiont Wolbachia in Dirofilaria immitis (Leidy, 1856)-Naturally infected dogs. Vet Parasitol 174: 119-123. https://doi.org/10.1016/j.vetpar.2010.07.019
Sarwar MS, Jahan N, Shahbaz F (2018) Molecular detection and characterization of Wolbachia pipientis from Culex quinquefasciatus collected from Lahore, Pakistan. Am J Trop Med Hyg 98 (1): 154-161.
Savadelis MD, Day KM, Bradner JL, Wolstenholme AJ, Dzimianski MT, Moorhead AR (2018) Efficacy and side effects of doxycycline versus minocycline in the three-dose melarsomine canine adulticidal heartworm treatment protocol. Parasit Vectors 11: 671. https://pubmed ncbi.nlm.nih.gov/30587225
Simón F, González-Miguel J, Diosdado A, Gómez PJ, Morchón R, Kartashev V (2017) The Complexity of Zoonotic Filariasis Episystem and Its Consequences: A Multidisciplinary View. BioMed Res Int 6436130. https://doi.org/10.1155/2017/6436130
Simsek S, Turkan Ciftci A (2016) Serological and molecular detection of Dirofilaria species in stray dogs and investigation of Wolbachia DNA by PCR in Turkey. J Arthropod Borne Dis 10 (4): 445-453.
Spasojević Kosić Lj, Lalosević V, Simin S, Kuruca Lj, Naglić A, Vasić I (2014) Microfilaraemia and antigenemia in dogs with natural heartworm infection treated with combination of doxycyclin and ivermectin - preliminary results. In: Proceedings of Fourth European Dirofilaria and Angiostrongylus Days (FEDAD), Budapest, Hungary: pp 62. https://www.esda.vet/wp-content/uploads/2017/10/Meetings-FEDAD.pdf
Spasojević Kosić Lj, Lalošević V, Potkonjak A, Simin S, Kuruca Lj, Vračar V (2020) Severe heartworm disease in two dogs cured by an alternative therapy. Vet Glasnik 74(2): 202-210. https://doi.org/10.2298/VETGL190717002S
Stepanović P, Ilić T, Krstić N, Dimitrijević S (2015) Efficiency of modified therapeutic protocol in the treatment of some varieties of canine cardiovascular dirofilariasis. Bull Vet Inst Pulawy 59: 505-509.
Ware W (2011) Heartworm disease. In: Ware W. Cardiovascular disease in small animal disese. Manson Publishing/The veterinary press, London: pp 351-371.