Heartworm disease

From Dog
Jump to: navigation, search
HWD01.jpg
Dirofilaria immitis microfilaria (L3) under light microscopy
Angiogram of a dog with heartworm disease, showing cardiomegaly and pulmonary arterial distension[1]

Heartworm disease (cardiopulmonary dirofilariosis) is a mosquito-borne zoonotic[2] parasitic disease caused by Dirofilaria immitis that affects canines worldwide.

Although dogs are considered the definitive hosts, this parasite also affects other carnivores such as wolves, coyotes, foxes, horses[3], cats[4], rabbits[5] and rarely, humans[6].

Heartworm disease should be considered a dual parasitism since the endosymbiont Wolbachia pipientis, which is essential to L3 growth to adulthood within the canine host[7], contributes significantly to the inflammatory pathology of heartworm disease[8]. More than 30% of dogs are infected by this proteobacteria[9] and D. immitis-infected animals can have circulating Wolbachia antibodies and pro-inflammatory Wolbachia antigens deposited in tissues[10].

Epidemiology

Since its first detection in 1969[11], the disease has been reported in every continent, with a worldwide incidence of heartworm in dogs worldwide varies from 5 - 30% depending on geographical location, season (higher prevalence in warmer months due to mosquito-populations[12]), exposure rates (outdoor roaming versus indoor activity)[13] and use of preventative therapy in the general dog population[14]. The disease, although increasingly reported, even in geographically-isolated communities, is likely to have been extant within stray dog populations for millenia[15], and increasing due to interstate and intercontinental movements of dogs[16].

Genetic analysis has shown at least 4 different genetic clusters with the D. immitis species, allowing for the emerging spread of drug resistance alleles[17].

While avermectin-class drugs are widely used for prevention, the American Heartworm Society estimated that 27 million dogs remain untreated in the United States alone[18].

Adult Dirofilaria maintain homeostasis with the canine host immune system by proffering over 600 antigenic protein secretomes to the host's immune system[19] due to single nucleotide polymorphism[20], which activates over 14 immune-system pathways during the evasive process of modulating the host immune response[21].

Coinfections with Dirofilaria spp and other hemoparasites such as Leishmania spp[22], Anaplasma phagocytophilum, Babesia vogeli[23], Borrelia burgdorferi and Ehrlichia canis[24] is common in some countries and exacerbates both clinical signs and eventual therapy.

Prior to the widespread use of drugs such as selamectin, the incidence of heartworm in tropical and subtropical regions was high, approaching 80% of urban dogs. Over the last twenty years, these monthly topical and yearly injectable agents have markedly reduced the risk of endemic heartworm disease to the dog population.

The prepatent period of this parasite is approximately 6 months from time of infection to detection of circulating microfilariae, and by this time, pathological changes are already evident within the pulmonary parenchyma[25]. Clinical signs usually develop 1 - 5 years post-infection.

Clinical signs

D. immitis infection is primarily a cardiovascular disease and symptoms relate to right-sided congestive heart failure, endarteritis, pulmonary hypertension, pulmonary effusion, pneumonitis, bronchitis and alveolitis, and is directly related to worm burden. Although up to 100 or more adult worms have been found on necropsy in some dogs, commonly reported infestations show an average infestation with 10 - 20 worms associated with clinical disease[26].

Worms can be found in the portal vein, vena cava, right atrium and ventricle and pulmonary veins. Microfilariae circulate thorughout the cardiovascular system and can be found in the lungs, kidneys, liver, heart, brain, and spleen[27]. Chronic glomerulonephritis due to immune-complex deposition is a long-term complication of this disease in older dogs[28].

Aberrant migrations of adult worms can also result in translocation to organs such as the brain, eye, peritoneum and chest cavity, leading to meningitis, chorioretinitis, peritonitis and spontaneous pneumothorax respectively [29].

Affected dogs are usually over 5 years of age[30] and present with exercise intolerance, varying amounts of coughing, and in heavy infestations, dyspnea, epistaxis and ascites due to cor pulmonale. Early symptoms of intermittent coughing are commonly due to heartworm-associated respiratory disease.

Blood tests usually reveal microfilaremia, varying degrees of leucocytosis, eosinophilia, thrombocytopenia and elevated levels of myoglobin, D-dimer[31] and cardiac troponin I[32]. Significant reduction in circulating minerals and antioxidants, particularly zinc, copper, iron, glutathione peroxidase and glutathione-S-transferase, have also been noted in infected dogs[33].

In younger dogs or dogs recently acquiring infection, migration of adult worms to the vena cava can trigger a thrombotic embolic episode within the anterior vena cava known as caval syndrome, which has high mortality.

Diagnosis

A presumptive diagnosis is based on exposure to mosquitoes in heartworm endemic regions and presenting clinical signs, which may be absent in low worm-burden dogs.

Determining parasitism by D. immitis requires use of available Knott's filtration, in-house ELISA assays or laboratory IFAT, ELISA and when required PCR assays[34], and exclusion of less pathogenic filariids such as Acanthocheilonema dracunculoides and A. reconditum[35].

The use of the Knott's test should be interpreted with caution to exclude unisex infections ('occult' infections)[36] and confusion with other dermal filariids such as Dirofilaria repens, Acanthocheilonema spp, Onchocerca spp, Brugia pahangi[37], and Cercopithifilaria spp[38].

Supportive diagnostic and prognostic tests include thoracic radiographs and ultrasonography to determine the severity of lung and heart disease due to adult worms.

Fecal copromicroscopical flotations and Baermann technique should be employed to help exclusion of lungworm[39].

A differential diagnosis would include respiratory diseases such as kennel cough and lungworms (e.g. Angiostrongylus spp, Capillaria aerophila[40] and Filaroides osleri)[41].

Infections with other dirofilariids such as Dirofilaria repens are usually less pathogenic, resulting in self-limiting cutaneous nodular panniculitis[42] but should be excluded in areas where this parasite is endemic, usually by using PCR assays[43].

Treatment

Treatment is usually dictated by the age of patient (old dogs and heavy-burden dogs are usually treated more conservatively) and severity of symptoms.

Conservative microfilaricidal, antimicrobial and anti-inflammatory therapy is usually appropriate in older dogs or dogs with severe filariid loads and secondary congestive heart failure, pneumonia and circulatory disorders.

Instigation of preventative therapy in prepatent infections may result in persistent microfilaremia for months or years>, and diagnosis of infections should therefore be conducted prior to dogs starting heartworm prevention[44].

Surgical intervention involves percutaneous removal of adult worms from the heart via the vena cava and has been routinely used in severe heartworm loads[45].

Adulticidal drugs are effective but come with elevated risks of mortality associated with dead and dying adult worms being washed into the pulmonary tree as a result of pulmonary thromboembolism[46]. Doxycycline treatment alone or combined with ivermectin-based drugs have less pathological reactions than patients receiving melarsomine-based adulticidals[47].

Patients with clinical signs associated with pneumonitis benefit from short-term therapy with anti-inflammatory doses of corticosteroids before and after adulticide treatment.

Strict cage rest is recommended for 4 - 6 weeks after adulticide administration[48] to minimize the potentially fatal risk of secondary pneumonia and thromboembolism[49] as adult worms die and are pumped into the pulmonary tree.

Medications indicated in the treatment of D. immitis infection include:

The use of daily diethycarbamazine medication has become less commonly used due to reactions associated with microfilaremic dogs[50] and the ease of monthly macrycylic lactone administration.

Use of antihistamines such as diphenhydramine have shown to be ineffective at minimizing post-adulticidal complications[51].

Failure of owner compliance to maintain regular monthly preventative therapy[52] is estimated at 10 - 20%[53]. Adding further to this problem is the growing resistance of fourth- and fifth-stage larvae to milbemycin[54][55] are two common causes of recrudescence of canine heartworm disease.

Prevention

Prevention of heartworm disease remains the mainstay of effective control of the disease in dog populations, and despite extensive genomic sequencing of this parasite[56], vaccine development have as yet remained elusive.

A large number of oral medications, primarily avermectin-based have shown 100% efficacy at halting L3 development and migration in dogs.

As well, the use of preventative doxycycline, given at 10mg/kg orally twice daily has efficacy against migrating L3 - L5 and will delay or restrict microfilarial production[57], growth and development within the new canine host[58].

However, despite aggressive veterinary and pharmaceutical marketing to clients about the serious and prevalence of this disease, satellite sentinel populations of urban, free-roaming dogs, wolves and foxes remain at risk and are responsible for maintaining the parasite's prevalence, particularly in indigenous and impoverished communities[59][60].

References

  1. Blue Valley
  2. Fuehrer HP et al (2013) Indigenous Dirofilaria immitis in Bangladesh. Parasitol Res Jan 29
  3. Thurman JD et al (1984) Dirofilariasis with arteriosclerosis in a horse. J Am Vet Med Assoc 185(5):532-533
  4. Dunn KF et al (2011) Diagnostic, treatment, and prevention protocols for feline heartworm infection in animal sheltering agencies. Vet Parasitol 176(4):342-349
  5. Nakagaki K et al (1997) Dirofilaria immitis: experimental infection of rabbits with immature fifth-stage worms. Am J Trop Med Hyg 57(6):667-671
  6. Montoya-Alonso JA et al (2011) Current prevalence of Dirofilaria immitis in dogs, cats and humans from the island of Gran Canaria, Spain. Vet Parasitol 176(4):291-294
  7. Pers Comm, Dr Jim Euclid, 2013
  8. Rossi MI et al (2010) Detection of Wolbachia DNA in blood from dogs infected with Dirofilaria immitis. Exp Parasitol 126(2):270-272
  9. McHaffie J (2012) Dirofilaria immitis and Wolbachia pipientis: a thorough investigation of the symbiosis responsible for canine heartworm disease. Parasitol Res 110(2):499-502
  10. Dingman P et al (2010) Association of Wolbachia with heartworm disease in cats and dogs. Vet Parasitol 170(1-2):50-60
  11. Sadighian A (1969) Helminth parasites of stray dogs and jackals in Shahsavar area, Caspian region, Iran. J Helminth '2:372–4
  12. Genchi C et al (2011) Changing climate and changing vector-borne disease distribution: the example of Dirofilaria in Europe. Vet Parasitol 176(4):295-299
  13. Tasić A et al (2012) Canine dirofilaria infections in two uninvestigated areas of serbia: epidemiological and genetic aspects. Vector Borne Zoonotic Dis 12(12):1031-1035
  14. Brown HE et al (2012) Key factors influencing canine heartworm, Dirofilaria immitis, in the United States. Parasit Vectors 5:245
  15. Ranjbar-Bahadori Sh et al (2011) Epidemiological aspects of canine dirofilariasis in the north of iran. Iran J Parasitol 6(1):73-80
  16. Hamel D et al (2011) Canine vector-borne disease in travelled dogs in Germany - a retrospective evaluation of laboratory data from the years 2004-2008. Vet Parasitol 181(1):31-36
  17. Belanger DH et al (2011) Inference of population structure and patterns of gene flow in canine heartworm (Dirofilaria immitis). J Parasitol 97(4):602-609
  18. Martin J et al (2012) Nematode.net update 2011: addition of data sets and tools featuring next-generation sequencing data. Nucleic Acids Res 40:D720–D728
  19. Geary J et al (2012) First analysis of the secretome of the canine heartworm, Dirofilaria immitis. Parasit Vectors 5:140
  20. Bourguinat C et al (2011) Genetic polymorphism in Dirofilaria immitis. Vet Parasitol 176(4):368-373
  21. Fu Y et al (2012) Novel insights into the transcriptome of Dirofilaria immitis. PLoS One 7(7):e41639
  22. Tabar MD et al (2013) Wolbachia, filariae and Leishmania coinfection in dogs from a Mediterranean area. J Small Anim Pract Feb 20
  23. Barker EN et al (2012) Haemoparasites of free-roaming dogs associated with several remote Aboriginal communities in Australia. BMC Vet Res 8:55
  24. Mircean V et al (2012) Seroprevalence and geographic distribution of Dirofilaria immitis and tick-borne infections (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, and Ehrlichia canis) in dogs from Romania. Vector Borne Zoonotic Dis 12(7):595-604
  25. Seiler GS et al (2010) Computed tomographic changes associated with the prepatent and early patent phase of dirofilariasis in an experimentally infected dog. Vet Radiol Ultrasound '51(2):136-140
  26. Rishniw M et al (2012) Sex ratios of Dirofilaria immitis in naturally infected dogs show female bias at low worm intensities. Res Vet Sci 93(3):1324-1328
  27. Ceribasi A & Simsek S (2012) Histopathologic Effects of Dirofilaria immitis Microfilaria on Internal Organs of Dog Confirming by PCR Technique. Iran J Parasitol 7(2):103-107
  28. Morchón R et al (2012) Anti-Wolbachia Surface Protein antibodies are present in the urine of dogs naturally infected with Dirofilaria immitis with circulating microfilariae but not in dogs with occult infections. Vector Borne Zoonotic Dis 12(1):17-20
  29. Oliveira C et al (2010) Spontaneous pneumothorax in a dog secondary to Dirofilaria immitis infection. J Vet Diagn Invest 22(6):991-994
  30. Köse M & Erdoğan M (2012) Serological screening of canine heartworm (Dirofilaria immitis) infections in Turkey. Berl Munch Tierarztl Wochenschr 125(11-12):503-508
  31. Carretón E et al (2011) Dirofilaria immitis infection in dogs: cardiopulmonary biomarker levels. Vet Parasitol 176(4):313-316
  32. Carretón E et al (2012) Myocardial damage in dogs affected by heartworm disease (Dirofilaria immitis): immunohistochemical study of cardiac myoglobin and troponin I in naturally infected dogs. Vet Parasitol '189(2-4):390-393
  33. Dimri U et al (2012) Oxidant/antioxidant balance, minerals status and apoptosis in peripheral blood of dogs naturally infected with Dirofilaria immitis. Res Vet Sci 93(1):296-299
  34. Latrofa MS et al (2012) A duplex real-time polymerase chain reaction assay for the detection of and differentiation between Dirofilaria immitis and Dirofilaria repens in dogs and mosquitoes. Vet Parasitol 185(2-4):181-185
  35. Magnis J et al (2013) Morphometric analyses of canine blood microfilariae isolated by the Knott's test enables Dirofilaria immitis and D. repens species-specific and Acanthocheilonema (syn. Dipetalonema) genus-specific diagnosis. Parasit Vectors 6(1):48
  36. Rishniw M et al (2012) Sex ratios of Dirofilaria immitis in naturally infected dogs show female bias at low worm intensities. Res Vet Sci 93(3):1324-1328
  37. Wongkamchai S et al (2013) Rapid detection and identification of Brugia malayi, B. pahangi, and Dirofilaria immitis by high-resolution melting assay. Vector Borne Zoonotic Dis 13(1):31-36
  38. Otranto D et al (2013) Vector-borne helminths of dogs and humans in Europe. Parasit Vectors 6:16
  39. Di Cesare A et al (2011) Canine and feline infections by cardiopulmonary nematodes in central and southern Italy. Parasitol Res 109(1):S87-S96
  40. Guardone L et al (2013) Serological detection of circulating Angiostrongylus vasorum antigen and specific antibodies in dogs from central and northern Italy. Vet Parasitol 192(1-3):192-198
  41. Boersema JH et al (1989) A persistent case of kennel cough caused by Filaroides osleri. Tijdschr Diergeneeskd 114(1):10-13
  42. Albanese F et al (2013) Nodular lesions due to infestation by Dirofilaria repens in dogs from Italy. Vet Dermatol 24(2):255-256
  43. Gioia G et al (2010) Highly sensitive multiplex PCR for simultaneous detection and discrimination of Dirofilaria immitis and Dirofilaria repens in canine peripheral blood. Vet Parasitol 172(1-2):160-163
  44. Bowman DD & Mannella C (2011) Macrocyclic lactones and Dirofilaria immitis microfilariae. Top Companion Anim Med 26(4):160-172
  45. Lee SG et al (2008) Percutaneous heartworm removal from dogs with severe heart worm (Dirofilaria immitis) infestation. J Vet Sci 9(2):197-202
  46. Kramer L et al (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(4):357-360
  47. Kramer L et al (2008) Wolbachia and its influence on the pathology and immunology of Dirofilaria immitis infection. Vet Parasitol 158(3):191-195
  48. Hoch H & Strickland K (2008) Canine and feline dirofilariasis: prophylaxis, treatment, and complications of treatment. Compend Contin Educ Vet 30(3):146-151
  49. Carretón E et al (2013) Variation of d-dimer values as assessment of pulmonary thromboembolism during adulticide treatment of heartworm disease in dogs. Vet Parasitol Jan 16
  50. Boreham PF et al (1985) Studies on the mechanism of the DEC reaction in dogs infected with Dirofilaria immitis. Int J Parasitol 15(5):543-549
  51. Rawlings CA & Tackett RL (1990) Postadulticide pulmonary hypertension of canine heartworm disease: successful treatment with oxygen and failure of antihistamines. Am J Vet Res 51(10):1565-1569
  52. Gyles C (2011) Heartworm resistance. Can Vet J 52(12):1279-1280
  53. Rohrbach BW et al (2011) Survey of heartworm prevention practices among members of a national hunting dog club. J Am Anim Hosp Assoc 47(3):161-169
  54. Bourguinat C et al (2011) Macrocyclic lactone resistance in Dirofilaria immitis. Vet Parasitol 181:388–392
  55. Geary TG et al (2011) Evidence for macrocyclic lactone anthelmintic resistance in Dirofilaria immitis. Top Companion Anim Med 26(4):186-192
  56. Godel C et al (2012) The genome of the heartworm, Dirofilaria immitis, reveals drug and vaccine targets. FASEB J 26(11):4650-4661
  57. McCall JW et al (2011) Effects of doxycycline on early infections of Dirofilaria immitis in dogs. Vet Parasitol 176(4):361-367
  58. Rossi MI et al (2010) Effects of doxycycline on the endosymbiont Wolbachia in Dirofilaria immitis (Leidy, 1856)--naturally infected dogs. Vet Parasitol 174(1-2):119-123
  59. Theis JH et al (2011) Dirofilaria immitis infection in dogs from underserved, Native American reservations in the United States. J Am Anim Hosp Assoc 47(3):179-184
  60. Bryan HM et al (2011) Exposure to infectious agents in dogs in remote coastal British Columbia: Possible sentinels of diseases in wildlife and humans. Can J Vet Res 75(1):11-17