New approaches in the battle against heartworm disease

Causes and spread of the disease

Heartworm disease is caused by the parasitic worm Dirofilaria immitis (D. immitis) transmitted by mosquitos. In dogs, heartworm disease affects the circulatory and respiratory systems. It can start with a mild persistent cough and reluctance to exercise and can progress to heart failure. In cats, it begins with chronic coughing and labored breathing or vomiting and can cause sudden death. 

Heartworm disease is endemic in countries on every continent except Antarctica. Climate change is increasing the spread of mosquitos and therefore heartworm disease. Prof. Dr. Paul M. Selzer, Head of New Mechanisms Parasitology, and Dr. Douglas S. Carithers, Senior Associate Director, Applied Research and Publications at Boehringer Ingelheim Animal Health, are among the experts leading research to improve understanding of the disease and develop new approaches.

Current approaches to prevention and treatment

Currently, Immiticide® is recommended as the first line adulticide treatment to kill adult heartworms¹. It should, however, only be used at the direction and under the close supervision of a veterinarian. “If a dog’s heart is infected with too many worms, there is a high risk that the dog will suffer and may even die as the parasites die,” says Prof. Selzer. “From the time of the mosquito bite we have a window of 60 days for preventive intervention by macrocyclic lactones (MLs) before the parasite develops to pre-adults and adults, which move towards the heart. The trouble is, you usually don’t know when the bite occurs.” 

The current practice therefore focuses on controlling the disease through the use of the MLs as preventives targeting the larvae before they become adults. Since the introduction of the ML ivermectin in 1987, heartworm prevention has been achieved primarily by continuous administration of MLs.

“Preventive treatments using these drugs are highly effective against heartworm larvae when they are administered correctly,” says Dr. Carithers. “However, improper use has led to an increase in the percentage of resistance in various heartworm populations, particularly in the Mississippi River areas in the US.”

New preventives could be resistance breakers

It is not yet clear how much resistance is present in heartworm populations or how likely it is that resistance will spread to new regions. However, research is needed to develop new drug classes or other therapeutic interventions to manage or delay this spread. 

Fortunately, we have a wide array of new tools for drug discovery, and rapid improvements in molecular biology, biochemistry and related technologies allow detailed insights in the parasite and molecular mechanisms of drug action. Automated screening processes substantially increase the number of compounds that can be evaluated. Omics technologies, extensively used in research of human diseases, have only just begun to be applied in addressing parasitic diseases. The mapping of the D. immitis heartworm genome is not yet complete but new, more refined omics, molecular biology and biochemistry approaches will foster the discovery of novel drug targets and subsequent novel drugs.

Our scientists at Boehringer Ingelheim Animal Health are exploring opportunities to target heartworms by affecting their metabolism, attacking their internal organ systems, or making them even more recognizable to the dog’s or cat’s immune system. In addition, advances in the broad understanding of the various biological molecules that translate into the structure, function, and dynamics of an organism, together with mRNA or microRNA technologies, may even lead to development of next-generation vaccines for the treatment of heartworm disease.

“If we learn more about host-parasite interaction we might discover new ways to intervene,” says Prof. Selzer. “Along with developing novel resistance-breaking drugs and effective vaccines, we also have a need for safe and effective long-lasting repellents.”

Combining innovation and proper drug use

Boehringer Ingelheim is at the forefront of developing innovative approaches to manage heartworm disease, but more education is needed too. “Heartworms have likely been around as long as dogs and wolves have existed, so we are unlikely to eliminate them completely. All we can hope to do is manage the disease in our pets,” says Dr. Carithers. 

The lifecycle of heartworms (D. immitis) and potential new areas for intervention

This diagram represents the complex life cycle of a heartworm within the host (the dog) and the vector (the mosquito) as it grows from the early microfilariae stage (mf). Within the mosquito it develops to the infective larval stage (L3). These larvae can then be transmitted back to the dog, where they develop further. Adult worms appear in the pulmonary arteries approximately six months after infection.
 
The outer circle shows points at which prevention and treatment options may be effective. Macrocyclic lactones are used as preventive treatment up to 60 days (d) after infection against the parasite in its L3 and L4 larval stages. Developing new safe and long-lasting repellents is another important area for intervention.

D. immitis is a worldwide problem for dog owners

Presence of D. immitis and D. repens (a close relative of D. immitis) infections throughout the world. According to Boehringer Ingelheim internal marketing analysis, the number of dogs at risk of Dirofilaria infection is approximately 148 million in Asia, 98 million each in Latin America and Europe, 80 million in North America, 50 million in Africa, and 6 million in Oceania.

Further reading

Sandra Noack, John Harrington, Douglas S. Carithers, Ronald Kaminsky, Paul M. Selzer. 2021. “Heartworm disease – Overview, intervention, and industry perspective”, in International Journal for Parasitology: Drugs and Drug Resistance 16: 65–89. https://doi.org/10.1016/j.ijpddr.2021.03.004

The American Heartworm Society https://www.heartwormsociety.org/

References

¹ https://www.heartwormsociety.org/images/pdf/Canine-Guidelines-Summary.pdf