Canine Heartworm: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Canine Heartworm (CHW)

Agent type

Parasite

Taxonomy

Family

Onchocercidae^{Footnote 1}

Genus

Dirofilaria

Species

immitis

Synonym or cross-reference

The parasite Dirofilaria immitis is known as Dog Heartworm or Canine Heartworm (CHW)^{Footnote 2}. It is also referred to as Heartworm (HW)^{Footnote 3}, or as the diseases it causes: Animal or Human cardiopulmonary/pulmonary Dirofilarisis^{Footnote 4} and Heartworm disease^{Footnote 3}. HW was known in the past as the inexorable dreaded threadworm^{Footnote 5}.

Characteristics

Brief description

Dirofilaria immitis is a eukaryotic endoparasite, specifically a filarial nematode parasite, that causes heartworm disease^{Footnote 3} or cardiopulmonary/pulmonary dirofilariasis^{Footnote 4}. They are thread-like round worms, that appear pale white in colour with a transversal striation on the body surface^{Footnote 6}, and can grow up to 30cm^{Footnote 5}. Male worms are generally smaller, from 12 to 20cm, while females range from 25 to 31cm long^{Footnote 5Footnote 7}. The parasites have a slightly thin and rounded cephalic extremity (head end), and a terminal circular oral opening with two lateral amphids and 8 cephalic papillae surrounding it^{Footnote 6}. Their genome has been reported to be approximately 84.2 to 87.9 Mb with a GC content from 27.5% to 28.3% and encodes approximately 10,000 genes^{Footnote 7Footnote 8Footnote 9}.

Properties

D. immitis have four definitive stages in their life cycle (L1 to L4)^{Footnote 4}. L1 is the first life stage, and refers to the microfilariae, L2 and L3 refer to immature larvae, and the final life stage, L4, are mature worms. The microfilariae (L1) are ingested by mosquitos during a blood meal on an infected host, and within the mosquito, they molt to the L2 larval form within approximately 8 to 10 days postinfection. Subsequently, the L2 larvae molt into L3 approximately 3 days afterwards. When the parasites are around 1-1.5mm in length, the L3 larvae penetrate the host's skin via mosquito vector. 3 to 12 days postinfection the larvae molt from L3 to L4 and then the subsequently molt into preadult worms 50 to 70 days postinfection. Between 70 to 85 days postinfection, the first preadult worms arrive in the pulmonary artery and right ventricle of the host's heart^{Footnote 4}. At 120 days post infection, the worms are considered adults, and have reached sexual maturity. The adult females begin to produce offspring, microfilariae (L1), between 6 and 9 months post-infection, which measure between 230-330 μm in length. Microfilariae live in the bloodstream up to 2 years, while the adult worms can live up to 7 years^{Footnote 4}.

The heat shock protein p27 has been found to play an important role in the host-parasite relationship, repairing functions during development^{Footnote 4}.

D. immitis rely on rickettsia-like endosymbionts from the genus Wolbachia for embryogenesis, development, and survival. The genome of these endosymbionts encode for enzymes missing in the D. immitis genome, including those responsible for the biosynthesis of heme, purine, and pyrimidines^{Footnote 3}.

Section II – Hazard identification

Pathogenicity and toxicity

Humans may become infected, however, they often present asymptomatically as the worms rarely reach adult stage and microfilaremia are absent^{Footnote 3Footnote 10}. Even though humans may present no clinical manifestations, an infection will progress and reach the pulmonary vasculature^{Footnote 3}. As the young adult worms die, pulmonary nodules encompassing the dead worms develop^{Footnote 3Footnote 4}. In some cases this can cause clinical nonspecific manifestations such as cough with thoracic pain, purulent or hemoptoic sputum, dyspnea, fever, malaise, myalgia, chills, and wheezing^{Footnote 4}. While D. immitis is associated with pulmonary infections, the parasitic infection has also been reported to cause conjunctival dirofilariasis^{Footnote 11Footnote 12Footnote 13}. Additionally, children with acute dirofilariasis may exhibit cranial manifestations including epileptiform seizures and/or eosinophilic meningitis^{Footnote 11}.

In canines, CHW begins as vascular disease that can cause impaired blood flow, eventually affecting the vascular and pulmonary systems, and in severe cases the right heart chambers^{Footnote 3}. Symptoms include a mild to persistent or unproductive cough, decreased appetite, reluctance to exercise, fatigue, hemoptysis (coughing up blood due to pulmonary hemorrhage), moderate to severe dyspnea, tachypnea, and epistaxis^{Footnote 3Footnote 4}. Eventually, damage to the pulmonary epithelium along with the vascular occlusion/blockage due to parasitic presence will cause reduced cardiac output and pulmonary hypertension, which may lead to compensatory right-side heart enlargement^{Footnote 3Footnote 4}. The enlargement may further progress and lead to right heart failure^{Footnote 3Footnote 4}. Worms have also been found in cranial, hepatic, intraocular, conjunctival, and mesenteric adipose tissues, as well as testicular arteries^{Footnote 4}. CHW may also cause severe renal dysfunction due to glomerulonephritis, which may further progress to severe nephrosis. At the hepatic level, venous congestion can also cause hepatomegaly, which can further lead to liver failure. Less commonly, sudden obstruction of blood flow through the lungs caused by occlusion in the pulmonary arteries, reduces the flow to the point where worms migrate and become aberrantly located in the right atrium, ventricle, and often in the vena cava^{Footnote 3}. Blockage of the vena cava is referred to as caval or vena cava syndrome, and will cause a life-threatening form of heart failure^{Footnote 3Footnote 4}. Sudden death is rare but can occur as a consequence of cardiorespiratory insufficiency, cachexia, or severe thromboembolic pneumonia^{Footnote 4}.

Ferrets are also susceptible to CHW infection, and their clinical manifestation is similar to those in dogs, however, the symptoms progress faster^{Footnote 4}. Symptoms specific to ferrets include lethargy, poor appetite, exercise intolerance, pleural effusion, cyanosis, dyspnea, monocytosis, and anemia. When death occurs, it is typically caused by pulmonary embolisms.

Felines exhibit more severe symptoms in comparison to canines^{Footnote 3}, however, they can also be asymptomatic carriers of the parasite^{Footnote 4}. In felines, the death of immature worms in the pulmonary arteries can cause severe pulmonary symptoms, and this condition has been named Heartworm Associated Respiratory Disease (HARD)^{Footnote 3}. Clinical symptoms manifest as chronic coughing, labored breathing, vomiting, dyspnea, tachypnea^{Footnote 3Footnote 4}. Larvae has also been found in body cavities and the nervous system, potentially resulting in ataxia, syncope, blindness, or vestibular disorders^{Footnote 4}. In nonfatal cases of acute infection, cats can transition to the chronic stage or become fully asymptomatic but later revert to the chronic form of the disease^{Footnote 4}.

Epidemiology

CHW disease affects humans along with domestic and wild canines and felines in tropical and temperate regions of the world^{Footnote 3Footnote 4}. The prevalence of D. immitis is linked to the prevalence of mosquito vectors. There are as many as 60 mosquito species that allow the successful development of microfilariae into the infective L3 stage and subsequent migration to the proboscis and therefore can be competent vectors of D. immitis. CHW infections appear to be increasing worldwide mainly due to climate changes and the accompanying spread of these mosquitos species^{Footnote 3}.

CHW is not geographically restricted, however, prevalence varies between countries^{Footnote 3Footnote 4}. Up until 2012, approximately 1,800 cases of human cases of dirofilariasis had been reported with 372 being pulmonary cases and 1410 subcutaneous/ocular^{Footnote 4}. Approximately 116 of these occurred in the North America (specifically in Southern Canada^{Footnote 14}, South-Western America^{Footnote 3Footnote 11}, and Mexico^{Footnote 3}); 50 in South America (specifically in Brazil^{Footnote 3Footnote 15} and Argentina^{Footnote 3}); 619 occurred in Europe (Eastern and central Europe such as Germany, Spain, Portugal, and Italy^{Footnote 3Footnote 16}), 20 in Australia, 145 in Asia, and 622 in Russia. In Canada, with an overall estimated prevalence in dogs of 0.16% from 2007 to 2016, CHW is considered a rare disease^{Footnote 14}.

Host range

Natural host(s)

Natural hosts of D. immitis include canines such as domestic dogs, racoon dogs, coyotes, wolves, foxes, and jackals; felines such as domestic cats, ocelots, jaguars, lions, tigers, cougars, and leopards; humans; ferrets; pinnipeds; black bears; otters; lemurs and seas lions^{Footnote 3Footnote 4Footnote 17Footnote 18}.

Other host(s)

Experimentally infected hosts with D. immitis include rodents such as mice and rats^{Footnote 19Footnote 20}.

Infectious dose

Unknown.

Incubation period

The incubation period for the CHW infection varies from months to years depending on various factors such as parasitic load, animal exertion, and individual reactivity^{Footnote 4}.

Communicability

The preferred route of transmission for CHW is via arthropod-mediated transmission, specifically, through injection via a bite of an infected mosquito^{Footnote 4}. For both human and animal hosts, during a blood meal, mosquitos deposit hemolymph on the wound, which carries the infectious worms, and the worms later penetrate the host's skin.

Section III – Dissemination

Reservoir

Animals such as domestic cats and dogs can have asymptomatic infection of CHW which consequently increases the prevalence of CHW^{Footnote 4}. Additionally, unprotected canines can act as reservoir hosts that maintain CHW prevalence^{Footnote 3Footnote 4Footnote 5}.

Zoonosis

None.

Vectors

Mosquitos act as the vector to transmit the CHW infection^{Footnote 4}. However, species of mosquitos that are possible vectors for CHW differ based on geographical location^{Footnote 4}. Specific mosquito species that are proposed candidates as vectors for CHW include Culex species such as C. annulirostris, C. pipiens, C. quinquefasciatus, and C. theileri; Aedes species such as A. aegypi, A. albopictus, A. caspius, A. crucians, A. notosciptus, A. ochlerotatus, A. punctipennis, A. punctor, A. scapularis, A. sierrensis, A. taeniorhynchus, A. triseriatus, and A. vexaus; as well as Cuiliseta incidens; and Anopheles maculipennis^{Footnote 4}.

Section IV – Stability and viability

Drug susceptibility/resistance

CHW is susceptible to macrocyclic lactones (MLs)^{Footnote 21}, commercially known as ivermectin^{Footnote 3Footnote 4Footnote 17Footnote 21}, moxidectin^{Footnote 3Footnote 4}, eprinomectin^{Footnote 3}, selamectin^{Footnote 3Footnote 4}, milbemycin oxime^{Footnote 3Footnote 4}, or abamectin^{Footnote 3}. However, strains of ML-resistant CHW have recently been emerging^{Footnote 17Footnote 22}.

In addition to MLs, other drugs that have shown efficacy against CHW include melarsomine^{Footnote 3Footnote 4Footnote 21Footnote 22Footnote 23}, oxycycline^{Footnote 3Footnote 21Footnote 23Footnote 24}, a combination of moxidectin, afoxolaner, and pyrantel pamoate^{Footnote 25}, diethylcarbamazine citrate^{Footnote 3}, and minocycline^{Footnote 25}.

New and emerging strains of D. immitis that are macrocyclic lactone (ML)-resistant (such as JYD-34^{Footnote 26}) have been described in the Southern USA (mainly in the southern Mississippi Delta region^{Footnote 27}), and are now a cause for concern in other areas of the world susceptible to CHW^{Footnote 28}.

Susceptibility to disinfectants

Unknown.

Physical inactivation

Parasitic worms have been 100% inactivated by heating at 50^oC for 5 minutes and D. immitis microfilariae survival was reduced by up to 40% upon thawing, when frozen at -70^oC^{Footnote 29Footnote 30}.

Survival outside host

In experimental settings, CHW microfilariae has been reported to survive in culture for 6 days and 7 days for adult worms^{Footnote 31}.

Section V – First aid/medical

Surveillance

Animals, specifically dogs, should be tested annually using both antigen and microfilarial tests^{Footnote 3}. Microscopic diagnosis for microfilariae can be performed using the Knott test^{Footnote 3Footnote 4}. Several serological tests based on enzyme-linked immunosorbent assays (ELISA) or immunochromatographic tests (ICT) can be used for the detection of CHW antigens in mature infections, approximately 7 months post infection^{Footnote 3Footnote 4}. In addition, polymerase chain reaction (PCR) assays can be used to detect CHW infection^{Footnote 3Footnote 4}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

Medicinal treatment of human dirofilariasis is not recommended^{Footnote 4}. Treatment, when required, is usually surgical to remove granulomas resulting from dead heartworm buildup in the arteries. The removal of subcutaneous nodules or worms from the ocular conjunctiva is a simple procedure, but surgical intervention is much more complex for pulmonary, ocular, retro-ocular, or other internal tissues.

The established CHW treatment for cats and dogs relies on the use of the arsenical drug melarsomine^{Footnote 21Footnote 24}, which is considered an adulticide, and often preceded by the administration of doxycycline to remove symbiotic bacteria Wolbachia spp.^{Footnote 21}. Efficacy has also been shown for both ivermectin and doxycycline^{Footnote 23}. Supportive care such as corticosteroids, diuretics, and oxygen therapy may also be necessary to control symptoms^{Footnote 4}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

There is no vaccine available for CHW.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

There is no known pre- or post-exposure prophylaxis for humans. In dogs prophylactic treatment consists of the administration of macrocyclic lactones such as ivermectin, milbemycin oxime, moxidectin, or selamectin^{Footnote 3Footnote 4}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

There have been no reported cases of laboratory-acquired infections for CHW.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

The primary specimen that contains CHW is blood samples^{Footnote 3Footnote 4}.

Primary hazards

Autoinoculation with infectious material, and being bitten by infected mosquitos, are the primary hazard associated with CHW^{Footnote 4}.

Special hazards

Work with either experimentally or naturally infected mosquitos^{Footnote 4} or mammals^{Footnote 3Footnote 4Footnote 18Footnote 19Footnote 26} could present a special hazard.

Section VII – Exposure controls/personal protection

Risk group classification

Dirofilaria immitis is a Risk Group 2 Human Pathogen and Risk Group 2 Animal Pathogen^{Footnote 2}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures are required.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, post mortem rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes are to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

Proper precautions should be considered when working with infected arthropods. This might include implementing a program to prevent escapes and monitor any escaped arthropods, as well as using suitable personal protective equipment (PPE), among other measures^{Footnote 32Footnote 33}.

For diagnostic laboratories handling primary specimens that may contain Canine Heartworm, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time between the surface and the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the regulated materials to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with D. immitis require a Pathogen and Toxin licence issued by the Public Health Agency of Canada. D. immitis is a terrestrial animal pathogen in Canada; therefore, importation of D. immitis requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence which includes a Human Pathogen and Toxin Licence and an HAR importation permit.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations

Last file update

July, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, directives and standards applicable to the import, transport, and use of pathogens and toxins in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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