The short answer
Canine heartworm disease is caused by the mosquito-borne filarial nematode Dirofilaria immitis, which damages the pulmonary arteries and can progress to pulmonary hypertension and right-sided heart failure. The sources describe year-round macrocyclic lactone preventives as the core of prevention and antigen testing, paired with a microfilaria test, as the main diagnostic approach. For treatment, the American Heartworm Society (AHS) protocol, as described by Merck and the AHS, combines doxycycline, a preventive, a three-dose melarsomine course, corticosteroids and strict exercise restriction. Antigen retesting after treatment confirms whether adult worms have been cleared.
Key takeaways
- Merck reports that most infected dogs show no clinical signs, and that cough is the most common sign when signs appear [1].
- Merck reports that antigenemia and microfilaremia appear no earlier than about 5 and 6.5 months after infection, so testing before about 7 months of age has no value [1].
- CAPC recommends testing all dogs annually for both antigen and microfilariae, including dogs on prevention [2].
- Merck's protocol table lists the three-dose melarsomine plus doxycycline protocol as killing 99% of heartworms, compared with 90% for the two-dose protocol in studies run without doxycycline [1].
- An AHS article reports that following the AHS protocol lowers respiratory complications from about 22% to about 6%, with mortality under 1% [4].
- Merck describes macrocyclic lactone resistance as rare and geographically limited, citing the Mississippi Delta as an example [1].
Doses on this pageEvery dose below is quoted from the cited source. Verify against the current label/formulary and the patient's full clinical picture.
Cause, transmission and risk
Merck describes D. immitis as primarily a parasite of dogs, with dogs and coyotes as the main reservoirs, and states that at least 70 mosquito species can act as intermediate hosts [1]. In the mosquito, microfilariae develop to the infective third larval stage (L3) in roughly 1 to 4 weeks depending on temperature, per Merck [1]. After a bite, larvae migrate through tissues and reach the heart and pulmonary arteries about 70 to 120 days after infection [1]. CAPC gives an adult lifespan in the dog of about 5 to 7 years [2].
According to Merck, transmission runs year-round in tropical and subtropical latitudes and is seasonal but hard to predict in temperate ones. Merck also reports that outdoor-housed dogs carry the greatest risk, although indoor animals can also be infected [1]. CAPC reports that case numbers and range continue to grow, with the most cases in the southeastern US and the Mississippi River Valley and rising frequency in states such as California, Oregon, Washington and Colorado. CAPC attributes part of that spread to relocation and rehoming of dogs [2].
Merck explains that live worms injure the pulmonary endothelium and drive inflammation, and that dead worms provoke more severe vascular reactions and thromboembolism [1]. Merck also notes that active dogs develop pulmonary hypertension more often than inactive dogs carrying a similar worm burden [1]. The endosymbiotic bacterium Wolbachia pipientis is required for worm maturation and reproduction, which is the rationale for doxycycline in treatment [1][2].
Clinical presentation and classification
Merck lists signs of advancing disease as exercise intolerance, labored breathing, abdominal distention from right-sided heart failure, syncope and cachexia [1]. Caval syndrome, in which worms move back into the right atrium and venae cavae, produces hemolysis with pigmenturia, poor perfusion and a right-sided systolic murmur from tricuspid insufficiency [1]. CAPC calls caval syndrome "a peracute life-threatening condition" [2].
Merck classifies severity in four classes [1]:
| Class | Merck description [1] |
|---|
| I (mild) | "No clinical signs or cough" |
| II (moderate) | "Cough, exercise intolerance, abnormal lung sounds" |
| III (severe) | Cough, exercise intolerance, abnormal heart or lung sounds, dyspnea, hepatomegaly, syncope, ascites, death |
| IV (caval syndrome) | "Hemoglobinuria, anemia, low-output heart failure" |
CAPC uses a three-stage scheme: asymptomatic or mild (stage 1), moderate (stage 2) and severe (stage 3) [2].
Diagnosis and testing pitfalls
Merck calls antigen testing "the most sensitive and specific diagnostic method available to veterinary practitioners" [1]. CAPC explains that antigen tests detect a glycoprotein found mainly in the female reproductive tract, so low burdens and male-only infections may be missed [2]. Merck suggests testing about 7 months after the last possible exposure, and testing young dogs 6 to 7 months after starting prophylaxis [1].
Microfilaria testing has limits of its own. Merck reports that roughly 20% of infected dogs are amicrofilaremic, a share that rises in dogs on macrolide preventives, but notes that a small percentage of infected dogs test antigen-negative and microfilaria-positive [1]. Merck also considers a microfilaria check critical after a positive antigen result, since microfilarial burden affects the risk of reaction to the first macrocyclic lactone dose [1]. CAPC notes that D. immitis microfilariae must be told apart from those of Acanthocheilonema reconditum. CAPC gives a modified Knott length of 300 to 322 microm for D. immitis versus 250 to 288 microm for A. reconditum [2].
Merck's guidance on confirmation is that a positive antigen result with positive microfilariae confirms infection. When microfilariae are negative, Merck states that "a second antigen test, ideally using a different type of assay, should be performed for confirmation before adulticide therapy" [1].
Heat treatment of serum frees antigen bound in antigen-antibody complexes. CAPC reports that in the southern US, samples from as many as 5 to 10% of dogs gave false-negative antigen results that became positive after heat treatment [2]. Both CAPC and Merck reserve heat treatment for dogs where infection is suspected but antigen is not detected, rather than routine screening [1][2]. Merck adds that heat treatment invalidates antibody-based tests on combination kits, such as tickborne disease panels [1].
The 2021 industry-perspective review in the International Journal for Parasitology: Drugs and Drug Resistance cites one evaluation (Liu et al. 2018) of two in-clinic multiplex assays [3]. In that evaluation, the assays had 98% to 100% specificity but D. immitis sensitivity of 88.2% and 94.1% [3]. The review does not report that study's sample size.
Merck describes thoracic radiography as giving the most information on disease severity in dogs [1]. Merck describes echocardiography as relatively unimportant for diagnosis, except to assess pulmonary hypertension or confirm intracardiac worms in suspected caval syndrome [1].
Prevention
Merck states that year-round macrocyclic lactone administration "is the only way to reliably prevent heartworm infection," and CAPC recommends year-round prevention for all dogs regardless of lifestyle [1][2]. The drug class includes ivermectin, milbemycin oxime, moxidectin and selamectin, available in monthly oral or topical forms and as long-acting injectable moxidectin [1][2]. Merck states that all macrocyclic lactone preventives are considered safe in dogs with the MDR1 (ABCB1) mutation at approved dosages [1].
On resistance, Merck reports that resistant isolates exist but remain rare and geographically limited [1]. Merck also reports that moxidectin-containing formulations appear more effective against some known resistant isolates [1]. The industry review reports that moxidectin resistance has also been described in four resistant isolates [3].
Merck states that repellents and ectoparasiticides should not be used as a stand-alone prevention program but can be part of a dual defense strategy alongside a preventive, and CAPC notes that mosquito-repellent products further reduce the risk of infection [1][2]. The review cites two controlled laboratory studies in which a topical dinotefuran-permethrin-pyriproxyfen product was 95% effective at blocking transmission, and notes that the findings still need verification under field conditions [3].
Treatment
Pretreatment and the AHS protocol
Merck describes starting a macrocyclic lactone preventive and doxycycline at diagnosis in all dogs, at "10 mg/kg, PO, every 12 hours for 4 weeks," followed by a 30-day wait before melarsomine [1]. Dr. Tom Nelson, writing for the AHS, explains that doxycycline depletes Wolbachia and its surface proteins, which reduces inflammation after worm death [4]. Merck describes a tapering prednisone or prednisolone course in dogs with clinical signs and after melarsomine injections [1].
Under the three-dose protocol, Merck describes a single melarsomine injection followed 30 days later by two injections 24 hours apart [1]. Merck gives melarsomine at "2.5 mg/kg, deep IM" in the epaxial lumbar muscles [1]. Nelson writes that the first injection kills about 50% of adult worms [4]. He also writes that lowering any dose or lengthening the gap between the second and third injections "significantly decreases treatment efficacy" [4]. Merck calls for crate rest for 6 to 8 weeks after the final injection, and the AHS article cites activity restriction for about four to five months across adulticide therapy [1][4].
Comparing protocols
Merck's protocol table reports efficacy as follows [1]:
| Protocol | Reported efficacy [1] | Merck's stated use [1] |
|---|
| Three-dose melarsomine plus doxycycline | Kills 99% of heartworms | Recommended by AHS for all stages |
| Two-dose melarsomine plus doxycycline | 90% kill in studies without doxycycline | Rescue or shelter settings with time or financial constraints; mild to moderate disease |
| Ivermectin or moxidectin plus doxycycline | About 95% "no antigen detected" within 1 year | When melarsomine is unavailable or contraindicated |
| Preventive-dose macrocyclic lactone alone | Likely over 2 years to a negative test | Not recommended |
CAPC also names the three-injection regimen as the treatment of choice for all heartworm-infected dogs [2]. CAPC recommends treating as soon as medically practical, warning that delay on preventives alone may allow disease to progress [2]. CAPC notes an alternative opinion that the pre-melarsomine delay can be cut to one month without loss of efficacy [2]. Merck describes the evidence for macrolide-doxycycline protocols as several small studies and says larger prospective studies are still needed [1]. The AHS article reports respiratory complication rates of 25% to 36% for slow-kill protocols [4].
Advanced disease and caval syndrome
Merck describes stabilizing right-sided heart failure before melarsomine and calls sildenafil a reasonable empirical choice for presumed severe pulmonary hypertension [1]. In caval syndrome, Merck states that removing worms from the right atrium and tricuspid orifice through a jugular venotomy "is typically necessary to save the dog's life" [1]. The AHS article states that when right-sided heart failure cannot be controlled medically, surgical worm extraction should be considered the preferred option [4].
Monitoring and prognosis
Merck recommends antigen testing 9 months after the final melarsomine dose, while CAPC says treated dogs may be tested 6 to 7 months after therapy or after 1 year [1][2]. For nonarsenical protocols, Merck describes retesting at 10 months and confirming any negative result with a heat-treated test, since doxycycline and macrolides make complexed antigen more likely [1]. Merck recommends a microfilaria test at diagnosis and 1 to 3 months after microfilaricide treatment begins [1].
Merck notes that pulmonary thromboembolism usually occurs 1 to 3 weeks after a melarsomine injection [1]. Nelson cautions that much of the vascular and pulmonary damage is irreversible even after worms are eliminated [4]. Merck describes the prognosis as guarded when right-sided heart failure is refractory to medical therapy [1].
The sources stress months of exercise restriction, a preventive continued for the rest of the dog's life, and common adverse effects [1][4]. Merck reports injection-site pain or swelling in about one-third of dogs [1]. Nelson reports elevated liver enzymes in about 40% of dogs on doxycycline, which he describes as generally not clinically significant if the dog stays well [4].
