Dog heartworm disease is here to stay: the most important aspects of clinical relevance
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Abstract
Heartworm disease (HWD) is a clinically important parasitic disease of the cardiovascular system in dogs, and is caused by Dirofilaria immitis (D. immitis), which resides in pulmonary arteries. Infected domestic and wild canids as hosts, and mosquitoes as intermediate hosts, are the main reservoirs of D. immitis. Because D. immitis does not reach complete development in humans, HWD is considered to be a disease with zoonotic potential. In addition to its veterinary relevance and zoonotic potential, the disease is distributed worldwide, and thus, a multidisciplinary approach is necessary to control this disease on the global level. The life cycle of D. immitis explains the pathogenesis and clinical signs of HWD in dogs, and determines its diagnosis, therapy and prophylactic measures. In this review, the most important aspects of HWD in canine patients are emphasized: establishment of correct diagnosis of the disease, proper diagnostic procedures for monitoring the clinical condition of an infected dog, different therapeutic protocols and how efficient they are and finally, recommendations for adequate prophylactic measures. Dogs with and without clinical signs of HWD should be tested for both microfilariae and adults of D. immitis at appropriate times. If positive for heartworm, the pathological changes in relevant organs, mainly lungs and heart, should be assessed in the dog. Their extent and severity determine therapeutic protocol. For dogs cured from HWD and non-infected ones, adequate preventive measures should be applied.
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References
AHS 2020, American Heartworm Society 2020: Current canine guidelines for the prevention, diagnosis and management of heartworm infection in dogs. https://d3ft8sckhnqim2.cloudfront.net/images/pdf/2020_AHS_Canine_Guidelines.pdf?1580934824
Ames M. K. and Atkins C. (2020). Treatment of dogs with severe heartworm disease. Veterinary Parasitology, 283: 109131. https://doi.org/10.1016/j.vetpar.2020.109131.
Anvari D., Naroue E., Daryani A., Sarvi S., Moosazadeh M., Hezarjaribi H.Z., Narouei M. R., Gholami S. 2020. The global status of Dirofilaria immitis in dogs: a systematic review and metaanalysis based on published articles. Research in Veterinary Science, 131: 104–116.
Atkins C.E. 2003. Comparison of results of three commercial heartworm antigen test kits in dogs with low heartworm burdens. Journal of the American Veterinary Medical Association, 222 (9): 1221-1223. https://doi.org/10.2460/javma.2003.222.1221
Badertscher R. R. 2nd , Losonsky J. M., Paul A. J., Kneller S. K. 1988. Two-dimensional echocardiography for diagnosis of dirofilariasis in nine dogs. Journal of the American Veterinary Medical Association, 193(7):843- 846.
Bahr R. 2018. Canine and Feline Cardiovascular System. In Textbook of veterinary diagnostic radiology. Ed. D. E. Trall, Elsevier Inc., St. Louis, pp. 684.
Bandi C., McCall J. W., 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. International Journal for Parasitology 29: 357–364.
Bartges J. W. 2012. Chronic kidney disease in dogs and cats. Veterinary Clinic of North America (Small Animal Practice) 42:669–692.
Bazzocchi C., Mortarino M., Grandi G., Kramer L.H., Genchi C., Bandi C., Genchi M., Sacchi L., McCall J. W. 2008. Combined ivermectin and doxycycline treatment has microfilaricidal and adulticidal activity against Dirofilaria immitis in experimentally infected dogs. International Journal for Parasitology, 38:1401-1410.
Bowman D. D. and Atkins C. E. 2009. Heartworm biology, treatment, and control. Veterinary Clinic of North America (Small Animal Practice), 39(6):1127–1158.
Buchanan J. W. and Bücheler J. 1995. Vertebral scale system to measure canine heart size in radiographs. Journal of American Veterinary Medical Association, 206: 194-199.
Carretón E., Corbera J. A., Juste M. C., Morchón R., Simón F., Montoya-Alonso J. A. 2011. Dirofilaria immitis infection in dogs: cardiopulmonary biomarker levels. Veterinary Parasitology, 176:313–316.
Carretón E., Morchón R., Montoya-Alonso J. A. 2017. Cardiopulmonary and inflammatory biomarkers in heartworm disease. Parasites & Vectors, 10(Suppl 2):534. DOI 10.1186/s13071-017-2448-2
Carretón E., Falcón-Cordón Y, Rodon J., Matos J. I., Morchón R., Montoya-Alonso J. A. 2020a. Evaluation of serum biomarkers and proteinuria for the early detection of renal damage in dogs with heartworm (Dirofilaria immitis). Veterinary Parasitology, 283:109-144.
Carretón E., Morchón R., Falcón-Cordón Y., Falcón-Cordón S., Matos J. I., Montoya-Alonso J. A. 2020b. Evaluation of different dosages of doxycycline during the adulticide treatment of heartworm (Dirofilaria immitis) in dogs. Veterinary Parasitology 283:109-141. https://doi.org/10.1016/j.vetpar.2020.109141
Dunn J. K. 2000. Textbook of small animal medicine, London: W. B. Saunders.
ESCCAP 2019, European Scientific Council Companion Animal Parasites: Control of Vector-Borne Diseases in Dogs and Cats, ESCCAP Guideline 05 Third Edition – March 2019.
ESDA 2017, European Society of Dirofilariosis and Angiostrongylosis, 2017: Guidelines for Clinical Management of Canine Heartworm Disease. http://www.esda.vet
Gabrieli S., Tasić A., Miladinović-Tasić N., Tasić-Otašević S., Cancrini G. 2012. Seroprevalence of dirofilarioses in Serbia. Proceedings of the 3rd European Dirofilaria days, 21-22 June, Parma, Italy, 2012, p38.
Gavrilović P., Blitva-Robertson G., Özvegy J., Kiskároly F., Becskei Z. 2015. Case Report of dirofilariasis in grey wolf in Serbia. Acta Parasitologica, 60 (1): 000–000. DOI: 10.1515/ap-2015-0025
Gavrilović P., Dobrosavljević I., Vasković N., Todorović I., Živulj A., Kureljušić B., Pavlović I. 2019. Cardiopulmonary parasitic nematodes of the red fox (Vulpes vulpes) in Serbia. Acta Veterinaria Hungarica, 67 (1):60–69. DOI: 10.1556/004.2019.007
Genchi G., Venco L., Genchi M. 2007. Guideline for the laboratory diagnosis of canine and feline Dirofilaria infections. Mappe Parassitologighe 8, Dirofilaria, 137-145.
Genchi G., Kramer L. H., Rivasi, F. 2011. Dirofilarial Infections in Europe. Vector Borne and Zoonotic Diseases, 11(10):1307-1317.
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 infections in dogs. Veterinary Parasitology, 273:11–16.
https://doi.org/10.1016/j.vetpar.2019.07.011
Goggs R., Benigni L., Fuentes V. L., Chan D. L. 2009. Pulmonary thromboembolism. Journal of Veterinary Emergency and Critical Care, 19(1):30–52. doi:10.1111/j.1476-4431.2009.00388.x
Goodwin J.-K. 1998. The Serologic Diagnosis of Heartworm Infection in Dogs and Cats. Clinical Techniques in Small Animal Practice, 13 (2):83-87.
Grandi G., Quintavalla C., Mavropoulou A., Genchi M., Gnudi G., Bertoni G., Kramer L. A. 2010. Combination of doxycycline and ivermectin is adulticidal in dogs with naturally acquired heartworm disease (Dirofilaria immitis). Veterinary Parasitology, 169(3-4):347-351. https://doi.org/10.1016/j.vetpar.2010.01.025.
Hayasaki, M. 1996. Re-migration of fifth-stage juvenile Dirofilaria immitis into pulmonary arteries after subcutaneous transplantation in dogs, cats, and rabbits. The Journal of Parasitology, 82, (5):835-837. doi:10.2307/3283901.
Hoh C. and McMichael M. 2009. Thromboembolism. Standards of care: Emergency and Critical Care Medicine, 11 (4):7-11.
Jones S.L. 2016. Canine Caval Syndrome Series Part 2: A practical approach to diagnosing caval syndrome. Today’s Veterinary Practice, January/February:63-67.
Kartman L. 1953. Factors influencing infection of the mosquito with Dirofilaria immitis (Leidy, 1856). Experimental Parasitology, 2:27-78.
Kitagawa H., Kitoh K., Inoue H., Ohba Y., Suzuki F., Sasaki Y. 2000. Plasma rennin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease. Journal of Veterinary Medical Science, 62(4):453–455.
Kitoh K., Watoh K., Kitagawa H., Sasaki Y. 1994. Blood coagulopathy in dogs with shock induced by injection of heartworm extract. American Journal of Veterinary Research, 55(11):1542-1547.
Kitoh K., Katoh H., Kitagawa H., Nagase M., Sasaki N., Sasaki Y. 2001. Role of histamine in heartworm extract-induced shock in dogs. American Journal of Veterinary Research, 62 (5): 770-774. https://doi.org/10.2460/ajvr.2001.62.770.
Kotani T. and Powers K.G. 1982. Developmental stages of Dirofilaria immitis in the dog. American Journal of Veterinary Research, 43(12):2199-2206.
Kramer, L., Grandi, G., Passeri, B., Gianelli, P., Genchi, M., Dzimianski, M. T., Supakorndej, P., Mansour, A. M., Supakorndej, N., McCall, S. D., McCall, J. W. 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. Veterinary Parasitology, 176:357–360.
Kramer L.H., Passeri B., Corona S., Simoncini L., Casiraghi M. 2003. Immunohistochemical/ immunogold detection and distribution of the endosymbiont Wolbachia of Dirofilaria immitis and Brugia pahangi using a polyclonal antiserum raised against WSP (Wolbachia surface protein). Parasitology Research, 89:381–386.
Kramer, L. H., Tamarozzi, F., Morchón, R., López-Belmonte, J., Marcos-Atxutegi, C., Martín-Pacho, J. R., Simón, F. 2005. Immune response to and tissue localization of the Wolbachia spp. Surface protein (WSP) in dogs with natural heartworm (Dirofilaria immitis) infection. Veterinary Immunology and Immunopathology, 106:303–308.
Krstić M., Gabrielli S., Ignjatovic M., Savic S., Cancrini G., RanCelovic G., Momcilovic S., Stojnev S., Otasevic S. 2017. An appraisal of canine and human cases reveals an endemic status of dirofilariosis in parts of Serbia. Molecular and Cellular Probes, 31: 37-41.
Kurucz K. Kepner A., Krtinic B., Zana B., Földes F., Bányai K., Oldal M., Jakab F., Kemenesi G. 2016. First molecular identification of Dirofilaria spp. (Onchocercidae) in mosquitoes from Serbia. Parasitology Research, 115:3257–3260. DOI 10.1007/s00436-016-5126-y.
Lichtenfels J. R., Pilitt P. A., Kotani T., Powers K. G. 1985. Morphogenesis of developmental stages of Dirofilaria immitis (Nematoda) in the dog. Proceedings of the Helminothological Society of Washington, 52:98-113.
Ludders, J. W., Grauer, G. F., Dubielzig, R. R., Ribble, G. A., Wilson, J. W. 1988. Renal microcirculatory and correlated histologic changes associated with dirofilariasis in dogs. American Journal of Veterinary Research. 49:826–830.
McCall, J. W., Genchi, C., Kramer, L., Guerrero, J., Dzimianski, M. T., Supakorndej P., Mansour, A. M., McCall, S. D., Supakorndej, N., Grandi, G., Carson, B. 2008b. Heartworm and Wolbachia: therapeutic implications. Veterinary Parasitology, 158:204–214.
McCall J. W., Genchi C., Kramer L. H., Guerrero J., Venco L. 2008a. Heartworm disease in animals and humans. Advances in Parasitology, 66:193–285.
McCall J. W., Hodgkins E., Varloud M., Mansour A., DiCosty U. 2017a. Blocking the transmission of heartworm (Dirofilaria immitis) to mosquitoes (Aedes aegypti) by weekly exposure for one month to microfilaremic dogs treated once topically with dinotefuran-permethrinpyriproxyfen. Parasites & Vectors, 10(Suppl 2):511. DOI 10.1186/s13071-017-2439-3.
McCall J. W., Varloud M., Hodgkins E., Mansour A., DiCosty U., McCall S., Carmichael J., Carson B., Carter J. 2017b. Shifting the paradigm in Dirofilaria immitis prevention: blocking transmission from mosquitoes to dogs using repellents/insecticides and macrocyclic lactone prevention as part of a multimodal approach. Parasites & Vectors, 10(Suppl 2):525. DOI 10.1186/s13071-017-2438-4.
McGreevy P. B., Theis J. H., Lavoipierre M. M. J., Clark J. 1974. Studies on filariasis. III. Dirofilaria immitis: emergence of infective larvae from the mouthparts of Aedes aegypti. Journal of Helminthology, 48 (4):221-228. DOI: https://doi.org/10.1017/S0022149X00022896.
Menozzi A., Bertini S., Turin L., Serventi P., Kramer L., Bazzocchi C. 2015. Doxycycline levels and anti-Wolbachia antibodies in sera from dogs experimentally infected with Dirofilaria immitis and treated with a combination of ivermectin/doxycycline. Veterinary Parasitology, 209:281–284.
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. Parasites & Vectors, 10(Suppl 1):5 (A13). DOI 10.1186/s13071-016-1902-x. https://parasitesandvectors.biomedcentral.com/track/pdf/10.1186/s13071-016-1902-x
Milosavljević P, Kulišić Z. 1989. Prvi slučajevi dirofilariaze kod pasa u Jugoslaviji.Veterinarski Glasnik, 43:71 –76.
Newton W.L. 1968. Longevity of an experimental infection with Dirofilaria immitis in a dog. Journal of Parasitology, 54: 187-188.
Onyango E. M. 2011. Electrocardiography may be a useful tool in the diagnosis of early mild canine heartworm disease. Acta Veterinaria Brno, 80:081–085. doi:10.2754/avb201180010081
Pajković D., Savić S., Veljković P., Grgić Ž. 2010. Praćenje pojave dirofilarioze kod radnih pasa u službi Vojske Srbije. Arhiv Veterinarske Medicine. 3(2):53-58.
Pavlović I., Terzin V., Ćurčin Lj., Petković D., Terzin D., Ćurčin K. 2009. Dirofilariosis – prevalence at stray and pets dogs at Belgrade area in period 2007-2008. Second European Dirofilaria Days 2009, Salamanca, Spain, Program and Abstracts P 17. https://www.esda.vet/wp-content/uploads/2017/10/Meetings-SEDD.pdf
Pavlović I., Milojković N., Ćurčin L., Kovacevic M., Novak N., Ivanovic O. 2012. Prevalence of Dirofilaria immitis in Serbia. Proceedings of the 3rd European Dirofilaria Days, 21-22 June, Parma, Italy, 2012, p53.
Pavlović I., Terzin V., Stanković B., Petković D., Ćurčin Lj., Antić V., Terzin D., Ćurčin K. 2014. Prevalence of Dirofilaria immitis at pets and stray dogs at Belgrade area in period 2012-2013. Fourth European Dirofilaria and Angiostrongylus Days (FEDAD), Budapest, Hungary, Final Program and Abstracts, 77. https://www.esda.vet/wp-content/uploads/2017/10/Meetings-FEDAD.pdf
Penezić A., Selaković S., Pavlović I., Ćirović D. 2014. First findings and prevalence of adult heartworms (Dirofilaria immitis) in wild carnivores from Serbia. Parasitology Research, 113(9):3281-3285 DOI 10.1007/s00436-014-3991-9.
Potkonjak A., Rojas A., Gutiérrez R., Nachum-Biala Y., Kleinerman G., Savić S., Polaček V., Pušić I., Harrus S., Baneth G. 2020. Molecular survey of Dirofilaria species in stray dogs, red foxes and golden jackals from Vojvodina, Serbia. Comparative Immunology, Microbiology and Infectious Diseases, 68. https://doi.org/10.1016/j.cimid.2019.101409
Rajan, T.V. 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. Amercian Journal of Tropical Medicine and Hygiene, 71,24–28.
Rawlings C.A., Dawe D.L., McCall J.W., Keith J.C., Prestwood A. K. 1982. Four types of occult Dirofilaria immitis infection in dogs. Journal of the American Veterinary Medical Association, 180(11):1323-1326.
Rossi M. I. D., 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. Veterinary Parasitology, 174:119–123.
Savadelis, M. D., Day, K. M., Bradner, J. L., Wolstenholme, A. J., Dzimianski, M. T., Moorhead, A. R. 2018. Efficacy and side effects of doxycycline versus minocycline in the three-dose melarsomine canine adulticidal heartworm treatment protocol. Parasites & Vectors, 11, 671. https://pubmed.ncbi.nlm.nih.gov/30587225.
Savić S., Vidić B., Grgić Ž., Jurišić A., Ćurčić V., Ružić M., Lolić Z. 2012. Vektorske zoonoze pasa u Vojvodini / Canine vector borne zoonoses in Vojvodina. Archive of Veterinary Medicine, 5:77-87.
Savić S., Vidić B., Grgić Ž., Potkonjak A., Spasojević Lj. 2014. Emerging vector borne diseases – incidence through vectors. Frontiers in Public Health, doi:10.3389/fpubh.2014.00267.https://www.frontiersin.org/articles/10.3389/fpubh.2014.00267/full
Serrano-Parreño B., Carretón E., Caro-Vadillo A., Falcón-Cordón Y., Falcón-Cordón S., Montoya-Alonso J. A. 2017. Evaluation of pulmonary hypertension and clinical status in dogs with heartworm by Right Pulmonary Artery Distensibility Index and other echocardiographic parameters. Parasites & Vectors (2017) 10:106. DOI 10.1186/s13071-017-2047-2
Simin S., Spasojević Kosić Lj., Kuruca Lj., Pavlović I., Savović M., Lalošević V. 2014. Moving the boundaries to the south-east: first record of autochthonous Angiostrongylus vasorum in a dog in Vojvodina province, northern Serbia. Parasites & Vectors, 7:396.
Simón F., Siles-Lucas M., Morchón R., González-Miguel J., Mellado I., Carretón E., Montoya-Alonso J. A. 2012. Human and animal dirofilariasis: the emergence of a zoonotic mosaic. Clinical Microbiology Reviews, 25 (3):507–544.
Simón F., González-Miguel J., Diosdado A., Gómez P. J., Morchón R., Kartashev V. 2017. The complexity of zoonotic filariasis episystem and its consequences: A multidisciplinary view. BioMedical Research International, Volume 2017, Article ID 6436130, 10 pages. https://doi.org/10.1155/2017/6436130
So-Young K., Park H.-Y., Lee J.-Y., Lee Y.-W., Choi H.-J. 2019. Comparison of radiographic and echocardiographic features between small and large dogs with heartworm disease. Journal of Veterinary Clinics, 36(4):207-211. http://dx.doi.org/10.17555/jvc.2019.08.36.4.207
Spasojević Kosić Lj., Krstić N., Trailović D. R. 2007. Comparison of three methods of measuring vertebral heart size in German shepherd dogs, Acta Veterinaria (Beograd), 57 (2-3):133 – 141. http://www.doiserbia.nb.rs/img/doi/0567-8315/2007/0567-83150703133S.pdf.
Spasojević Kosić Lj., Lalošević V., Lalošević D., Naglić A. 2011. Bolest srčanog crva: prikaz slučaja kod psa. Veterinarski Glasnik, 65 (3-4):257 – 267.
Spasojević Kosić Lj., Lalošević V., Lalošević D., Simin S., Vasić I., Kuruca Lj. 2012a. Prevalence of dirofilariosis in pet dogs in Novi Sad. Contemporary Agriculture/ Savremena poljoprivreda, 61 (3-4): 247 – 254.
Spasojević Kosić Lj., Trailović D. R., Matunović R. 2012b. Resting and dobutamine stress test induced serum concentrations of brain natriuretic peptide in German Shepherd dogs. Research in Veterinary Science, 93 (3):1446 – 1453.
Spasojević Kosić Lj., Simin S., Lalosević V., Kuruca Lj., Nikolić S., Nerac D. 2014a. Updating the prevalence of canine dirofilariosis in pet dogs in Novi Sad, Vojvodina Serbia. Proceedings of FEDAD 2014, 47, Budapest, Hungary. https://www.esda.vet/wp-content/uploads/2017/10/Meetings-FEDAD.pdf
Spasojević Kosić Lj., Lalosević V., Simin S., Kuruca Lj., Naglić A., Vasić I. 2014b. Microfilaraemia and antigenemia in dogs with natural heartworm infection treated with combination of doxycyclin and ivermectin – preliminary results. Proceedings of FEDAD 2014, 62, Budapest, Hungary.https://www.esda.vet/wp-content/uploads/2017/10/Meetings-FEDAD.pdf
Spasojević Kosić Lj., Simin S., Lalosević V., Lalošević D., Kuruca Lj., Nikolić S., Nerac D. 2014c. Updating the prevalence of canine dirofilariosis in pet dogs in Novi Sad, Vojvodina, Serbia. Savremena poljoprivreda/Contemporary agriculture 63 (4-5):487–493.
Spasojević Kosić Lj., Lalošević V., Simin S., Kuruca Lj. 2016a. Dirofilariosis and angiostrongilosis in Novi Sad, Vojvodina, Serbia. Archive vet med, 9 (2):53–62.
Spasojević Kosić Lj., Lalošević V., Naglić A., Simin S., Kuruca Lj., Spasović A. 2016b. Subjective and objective assessment of radiographic findings in dogs with heartworm disease. Parasites & Vectors 2016, 10(Suppl 1):5 (A26) 10.1186/s13071-016-1902-x.
Spasojević Kosić Lj., Trailović D. R., Krstić N. 2017. Age-dependent electrocardiographic and echocardiographic changes in German Shepherd dogs. Iranian Journal of Veterinary Research, 18 (1):43 - 48.
Spasojević Kosić Lj., Potkonjak A., Vidanovic D., Kozoderovic G., Vračar V., Laloševic V. 2018. The first report of Wolbachia spp. in dogs naturally infected with Dirofilaria spp. in Serbia – preliminary results. Parasite & Vectors, 11(Suppl 1):623.
https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-018-3183-z
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. Veterinarski Glasnik 2020, 00, 1-9. 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. Bulletin of the Veterinary Institute in Pulawy, 59:505-509. DOI:10.1515/bvip-2015-0075.
Tai T.C. and Huang H.P. 2013. Echocardiographic assessment of right heart indices in dogs with elevated pulmonary artery pressure associated with chronic respiratory disorders, heartworm disease, and chronic degenerative mitral valvular disease. Veterinarni Medicina, 58 (12):613–620.
Takemura N., Koyama H., Sako T., Ando K., Motoyoshi S., Marumo F. 1991. Plasma atrial natriuretic peptide (ANP) in dogs with mild heartworm infection. Journal of Veterinary Medical Science. 53(2):323–325.
Tasić A., Rosi L., Tasić S., Miladinović-Tasić N., Ilić T., Dimitrijević S. 2008. Survey of canine dirofilariasis in Vojvodina, Serbia. Parasitology Research, 103:1297-1302.
Taylor A.E. 1960. The development of Dirofilaria immitis in the mosquito Aedes aegypti. Journal of Helminthology, 34:27-38.
Tudor N., Ionita L., Tapaloaga D., Tudor P., Ionita C., Vlagioiu C. 2014. Radiographic cardiopulmonary changes in dogs with heartworm disease. Romanian Biotechnological Letters, 19 (6):9918-9924.
Uchide T. and Saida K. 2005. Elevated endothelin-1 expression in dogs with heartworm disease. Journal of Veterinary Medical Science, 67(11):1155–1161.
Venco L., Bertazzolo W., Giordano G., Paltrinieri S. 2014. Evaluation of C-reactive protein as a clinical biomarker in naturally heartworm-infected dogs: a field study. Veterinary Parasitology, 206(1–2):48–54.
Wang J.S., Tung K.C., Huang C.C., Lai C.H. 2005. Alteration of extracellular collagen matrix in the myocardium of canines infected with Dirofilaria immitis. Veterinary Parasitology, 131(3–4):261–265.
Ware W.: 2011. Heartworm disease. In Cardiovascular disease in small animal disease. Ed. W. Wandy, Manson Publishing/ The Veterinary Press, London, pp. 351.