Heartworm
Dr. Andrew Peregrine, Associate Professor, Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON
Dirofilaria immitis
Host range: Dogs, cats, ferrets and wild canids serve as definitive hosts. Once established in wild canids, the parasite is essentially endemic in that area (e.g. parts of Ontario).
Geographic range: The parasite is focally distributed across Canada; dependent on the presence of definitive hosts and the duration of activity of mosquito vectors. Approximately one half of the mosquitoes found in North America are possible vectors. However, to date, significant vector roles have only been demonstrated for a few. In the most recent review of heartworm cases diagnosed in dogs in Canada (2013-2014), 79.4% were diagnosed in Ontario, 14.6% in Quebec, 5.4% in Manitoba, 0.4% in New Brunswick and 0.2% in Nova Scotia. Usually there are also a few cases in the greater Vancouver area. Cases diagnosed elsewhere (e.g. Alberta) are travel associated. Furthermore, across the country, at least one third of all cases appear to be travel associated. Within the USA, heartworm has been diagnosed in all States, however, the risk is greatest in the eastern half of the USA, especially the southeastern USA, where practices may diagnose more than 100 canine cases a year.
Life cycle: Adult parasites reside within the arterial blood vessels of the lungs. In low burdens, the caudal lobar artery may be the only place that parasites are found. When moderate/high burdens are present, the parasites will also be found in the pulmonary artery and the right side of the heart. When fully mature, adult female and male parasites mate. Subsequently, microfilariae (early first-stage larvae) are released by female parasites into the bloodstream. If ingested by mosquitoes, the microfilariae mature to
third-stage larvae over a period of 1-4 weeks, depending on temperature. Only when third-stage larvae are present can parasites be transferred to a definitive host during a blood meal; larvae enter the animal via the mosquito’s bite wound on the skin. Within a few days the parasites moult to fourth-stage larvae; after 2-3 months they moult to immature adult parasites. Throughout this time they reside within connective tissue. After the final moult to immature adults, the parasites migrate to the pulmonary arteries via the venous circulation. Once at this location, the parasites mature to adults then release microfilariae and antigen in to the bloodstream. Typically, this begins 6-7 months following infection. In dogs, adult parasites live 5-7 years. In cats, the life span is typically 2-3 years.
On the basis of 30 years of climate data from southern Ontario, the heartworm transmission season conservatively lasts from the first week of June to the second week in October (i.e. 4.5 months). These dates are used across Canada where transmission occurs but are likely over- estimates for many places. At the moment, there is no evidence that the transmission season has lengthened. However, climate change will very likely result in lengthening of the transmission season and an increase in the geographic area of endemic transmission.
Diagnosis: In Canada, approximately 88% of heartworm infections in dogs are subclinical, due to low parasite burdens. Clinical signs include exercise intolerance, coughing, dyspnea, loss of condition, hemoptysis, ascites and hydrothorax. Heartworm antigen tests are the primary diagnostic and screening tests for heartworm. All detect a uterine antigen produced by reproductively active female parasites. Thus, since the pre-patent period (i.e. the time from infection to presence in blood) for antigen and microfilariae is 6-7 months, antigen tests for the purposes of detecting heartworm antigens should never be performed on animals under 6 months of age. Whenever a positive test result is obtained, the test should always be repeated using a different blood sample, ideally with a different antigen test, to ensure the test was carried out correctly.
In general, heartworm antigen tests are extremely good tests with very high levels of sensitivity and specificity. However, in low prevalence areas (i.e. almost all of Canada) one has to be careful to interpret the result correctly. For example, the most recent data on heartworm in Canada (Herrin et al 2017) indicated that the nationwide proportion of dogs testing positive for heartworm using 4Dx Plus Tests (Idexx Laboratories) was 0.42% (485/115,636 dogs tested); in no province was the proportion of positive dogs greater than 0.5%. How does one interpret a positive or a negative result when the prevalence of infection is this low?
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Routine testing for heartworm: The American Heartworm Society recommends annual testing for heartworm. Likewise, the licensed used of heartworm preventives in Canada requires annual testing. However, the problem with annual testing in low risk areas is that little is gained by carrying out the test. For example, in the above example, when the prevalence of infection is 0.42%, there is a 99.58% chance a dog is not infected before a test is carried out. If one then obtains a negative antigen test result, one is now 99.99% sure the dog is not infected. Likewise, if a positive antigen test result is obtained, there is a low likelihood the dog is genuinely infected; multiple additional diagnostic tests are required to determine whether or not this is the case. One alternative approach to annual testing, once baseline data have been obtained, is to carry out a risk-based assessment on all dogs every year, e.g. (i) has the dog traveled to a higher risk area since last year? (ii) was the dog on heartworm preventives last year? (iii) what was compliance with use of heartworm preventives like over the past year? If any of these issues are a concern, the dog should be tested. This risk-based approach focuses on dogs most likely to be infected with heartworm. For example, heartworm surveys in Canada have consistently shown that 85-90% of dogs diagnosed with heartworm were not on heartworm prevention in the year prior to testing; risk-based assessment would identify all these dogs. Testing less frequently than once a year is off-label testing and requires informed consent from owners.
Management: Dogs diagnosed with heartworm, whether clinical or subclinical, should be treated with melarsomine using the protocol described by the American Heartworm Society. This involves pre-treating with doxycycline for 28 days, then administering three doses of melarsomine. In dogs where immature parasites may be present, it is also recommended that animals should be pretreated for 60 days with a heartworm preventive before beginning melarsomine treatment. Pre-treatment with doxycycline, treatment with prednisone at the time of melarsomine treatment, and strict cage rest, all reduce the risk of post-adulticide complications. Sedation of dogs for the melarsomine injections reduces the risk of pain at the intramuscular injection sites. The American Heartworm Society advises against the use of the slow-kill protocol (i.e. monthly treatment with a heartworm preventive) for treating heartworm infections in dogs. While infections have been eliminated in some dogs after 6 monthly treatments, in other dogs monthly treatment for 5 years has failed to eliminate the infection! In addition, such treatment likely selects for drug-resistant parasites. Furthermore, dogs should remain on strict cage rest throughout this treatment protocol.
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Key references
American Heartworm Society: www.heartwormsociety.org
Bourguinat, C., Keller, K., Bhan, A., Peregrine, A., Geary, T., Prichard, R. (2011) Macrocyclic lactone resistance in Dirofilaria immitis. Veterinary Parasitology 181, 388-392.
Canadian heartworm surveys (1996-2010)
Herrin, B.H., Peregrine, A.S., Goring, J., Beall, M.J., Little, S.E. (2017) Canine infection with Borrelia burgdorferi, Dirofilaria immitis, Anaplasma spp. and Ehrlichia spp. in Canada, 2013-2014. Parasites and Vectors 10:244. DOI 10.1186/s13071-017-2184-7