Canine Heartworm Adulticide Treatment When Melarsomine is Unavailable

Treatment of mature Dirofilaria immitis infection can be challenging for veterinarians, particularly in tropical regions where melarsomine, the first-line heartworm adulticide, is unavailable. Treatment is also demanding because of its cost, potential complications and the need for exercise restriction^1,2. 

The American Heartworm Society (AHS), European Scientific Counsel Companion Animal Parasites (ESCCAP), Tropical Council for Companion Animal Parasites (TroCCAP), European Society of Dirofilariosis and Angiostrongylosis (ESDA) and Companion Animal Parasite Council (CAPC) all recognise melarsomine as the preferred adulticide. The AHS-recommended approach combines doxycycline, a macrocyclic lactone and melarsomine in a three-injection regimen¹. However, when melarsomine is unavailable or contraindicated, a non-arsenical approach may need to be considered. 

Why Melarsomine Availability Matters 

Melarsomine is not registered in most countries where heartworm disease is endemic, and temporary shortages can also occur in countries where it is registered^1,2. Limited availability may result from commercial factors, lengthy registration procedures, or restrictions on veterinary products containing arsenic or arsenical compounds. 

This creates a practical treatment dilemma in areas where heartworm transmission is common. Simply leaving infection untreated is not an appropriate solution because heartworm disease can progress and become life-threatening. 

Advanced disease may include heart failure and caval syndrome. In Grenada, heartworm infection was identified in 249 of 1,617 dogs necropsied between 2001 and 2013; 33 of the infected dogs (13.2%) had caval syndrome³. 

The Slow-Kill Approach 

When melarsomine cannot be used, the so-called slow-kill protocol combines doxycycline or minocycline for 28–30 days with a monthly heartworm preventive such as ivermectin or moxidectin^4,5,6. 

Doxycycline targets Wolbachia, an endosymbiotic bacterium important for heartworm development, reproduction, and adult survival⁷. It also helps reduce pulmonary pathology and post-treatment complications^4,7. 

Macrocyclic lactones act against different developmental stages of D. immitis, including microfilariae, L3, and young L4 stages. When combined with doxycycline, they also contribute to adulticidal activity^1,7. 

Evidence summarised in the provided content indicates that moxidectin has greater adulticidal efficacy than ivermectin in slow-kill protocols. Differences may relate to moxidectin's greater lipophilicity, larger volume of distribution, longer half-life, and slower elimination compared with ivermectin¹. 

A combination of topical moxidectin at the recommended dose, administered monthly until no antigen is detected, with doxycycline at 10 mg/kg PO q 12 or 24 h for 28 days has been identified as an accessible alternative when melarsomine is unavailable or contraindicated¹. 

Monitoring Treatment Response 

Slow-kill treatment requires prolonged monitoring rather than assuming rapid elimination of adult worms. Dogs should be tested at 6 and/or 12 months after treatment begins. Treatment success is presumed when both heartworm antigen and microfilariae are no longer detected⁴. 

If antigen remains positive after 12 months, doxycycline therapy should be repeated. Treatment failure should be considered when antigen positivity persists beyond 24 months⁴. Detection of Wolbachia DNA may provide an additional method for assessing therapeutic response¹. 

Exercise should be restricted as much as possible during treatment until adult heartworm antigen is no longer detected. However, there is insufficient evidence to define a specific duration of exercise restriction for non-arsenical treatment, and clinical pulmonary thromboembolism appears to be uncommon⁴. 

Important Limitations and Safety Considerations 

Slow-kill treatment should not be presented as equivalent to the standard melarsomine regimen. Concerns include prolonged pulmonary pathology, the requirement for sustained monthly preventive administration, maintenance of an infection reservoir, potential selection for microfilarial resistance, and overall treatment costs⁴. 

Doxycycline or minocycline may also cause gastrointestinal adverse effects. Dogs receiving 10 mg/kg q 12 h experienced more frequent and severe gastrointestinal effects than those receiving 5 mg/kg q 12 h. In cases of severe gastrointestinal effects, reducing doxycycline to 5 mg/kg q 12 h was recommended. Once-daily doxycycline administration (10–20 mg/kg q 24 h) may also improve owner compliance⁶. 

Practical Clinical Approach 

Where melarsomine is available and indicated, the three-injection melarsomine regimen remains the first-line approach. When it is unavailable, contraindicated or financially inaccessible, slow-kill treatment may provide an alternative. 

The key is to pair treatment with long-term monitoring, exercise restriction, preventive administration, and realistic owner counselling. Slow-kill treatment requires commitment because adult worms take longer to eliminate, but it can reduce the harm associated with leaving heartworm infection untreated. 

References 

1. Dantas-Torres F, Ketzis J, Pérez Tort G, Mihalca AD, Baneth G, Otranto D, Watanabe M, Linh BK, Inpankaew T, Borrás P, Arumugam S. Heartworm adulticide treatment: a tropical perspective. Parasites & vectors. 2023 Apr 28;16(1):148. https://link.springer.com/content/pdf/10.1186/s13071-023-05690-8.pdf 

2. Jacobson LS, DiGangi BA. An accessible alternative to melarsomine:“Moxi-Doxy” for treatment of adult heartworm infection in dogs. Frontiers in Veterinary Science. 2021 Jul 27;8:702018. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2021.702018/pdf 

3. Chikweto A, Bhaiyat MI, Lanza-Perea M, Veytsman S, Tiwari K, De Allie C, Sharma RN. Retrospective study of canine heartworm disease with caval syndrome in Grenada, West Indies. Veterinary Parasitology. 2014 Oct 15;205(3-4):721-4. https://www.academia.edu/download/45135649/Retrospective_study_of_canine_heartworm_20160427-2818-uh4io8.pdf 

4. Jacobson LS, DiGangi BA. An accessible alternative to melarsomine:“Moxi-Doxy” for treatment of adult heartworm infection in dogs. Frontiers in Veterinary Science. 2021 Jul 27;8:702018. https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2021.702018/pdf 

5. Savadelis MD, Ohmes CM, Hostetler JA, Settje TL, Zolynas R, Dzimianski MT, Moorhead AR. Assessment of parasitological findings in heartworm-infected beagles treated with Advantage Multi® for dogs (10% imidacloprid+ 2.5% moxidectin) and doxycycline. Parasites & Vectors. 2017 May 19;10(1):245. https://link.springer.com/content/pdf/10.1186/s13071-017-2190-9.pdf 

6. Savadelis MD, Day KM, Bradner JL, Wolstenholme AJ, Dzimianski MT, Moorhead AR. Efficacy and side effects of doxycycline versus minocycline in the three-dose melarsomine canine adulticidal heartworm treatment protocol. Parasites & Vectors. 2018 Dec 27;11(1):671. https://link.springer.com/content/pdf/10.1186/s13071-018-3264-z.pdf 

7. Kramer L, Crosara S, Gnudi G, Genchi M, Mangia C, Viglietti A, Quintavalla C. Wolbachia, doxycycline and macrocyclic lactones: new prospects in the treatment of canine heartworm disease. Veterinary parasitology. 2018 Apr 30;254:95-7. https://www.sciencedirect.com/science/article/pii/S0304401718301055