Canine Leishmaniasis (animal health)

Health Burden

Canine leishmaniasis is prevalent in over 50 countries spread over 4 continents and is most frequent in tropical and subtropical zones, expanding to new area’s because of climate change.

135 million dogs are yearly infected worldwide. The health burden for dogs with canine leishmaniasis can be severe and multifaceted, impacting their quality of life, longevity, and ability to thrive. Dogs with leishmaniasis often experience:

  • Chronic Pain and Discomfort: skin lesions, arthritis, and systemic inflammation);
  • Reduced Physical Activity (due to fatigue, weakness, and organ dysfunction and
  • Behavioral Changes (Irritability or depression due to chronic illness).

If the disease is not treated, the health burden of canine leishmaniasis is significant, encompassing chronic physical, systemic, and immune-mediated challenges, that can lead to death.

Last but not least, canine leishmaniasis imposes a significant economic burden on dog owners and public health systems, especially in rural and economically disadvantaged regions where the disease is endemic.

 

Disease

Canine leishmaniasis is a serious disease in dogs caused by parasites of the genus Leishmania which is primarily transmitted through the bites of infected female sandflies (Phlebotomus species in the Old World and Lutzomyia species in the New World).

DOI: 10.26717/BJSTR.2022.42.006815

It is a zoonotic disease, meaning it can also infect humans, though the transmission between dogs and humans typically requires sandfly vectors. The dog (Canis familiaris) is considered as the main reservoir in the domestic and peridomestic environment, contributing to the maintenance of the disease cycle of leishmaniasis. The parasite will alternate between the mammalian host and the insect vector (Ribeiro et al. 2018). Transmission also occurs between dogs, either sexually, vertically or during treatment such as blood transfusion, needle sharing or organ donation.

In the dog, canine visceral leishmaniasis has a slow evolution and an insidious onset. There is a correlation between the spatial distribution of positive dogs and the occurrence of human cases of VL in several regions, which suggests that human infection is preceded by a rise in the prevalence of canine visceral leishmaniasis (CVL) in the same area.

Generally, this disease is found in tropical and sub-tropical regions, however global warming may increase the prevalence of leishmaniasis due to expansion in the distribution of sandflies (Morales-Yuste, Martín-Sánchez, and Corpas- Lopez 2022) to areas that were previously unsuitable for the vectors due to cooler temperatures. Some of these new areas include southern parts of Europe, Mediterranean bassin, parts of Central Asia, new areas in South America, southwestern USA, parts of Middle East and Northen Africa.

The dog (Canis familiaris) is considered as the main reservoir in the domestic and peridomestic environment, due to its close relationship with humans, and because it houses parasites on the skin, favoring the infection of sandflies. The dog contributes to the maintenance of the disease cycle of leishmaniasis.

Canine leishmaniasis causes chronic suffering in dogs. The disease can affect internal organs of the dog such as the liver, the spleen. The infections also involves skin lesions, ulcers, or nodules, often in areas like the ears, muzzle, or other exposed parts. Typical symptoms are hair loss, especially around the eyes, ears and nose, ulcers and scaling. Other systemic symptoms are lethargy, weight loss, anemia and swollen lymph nodes.

 

Treatment

The treatment protocol for canine leishmaniasis differs between the clinical manifestations and degree of severity.

Canine leishmaniasis is challenging to treat because the parasite Leishmania integrates deeply into the dog’s immune system, and complete elimination is rare.

Currently, the existing treatments used for canine leishmaniasis present several problems, including high toxicity and many adverse effects that require careful monitoring and additional medications. Side effects of treatment may further compromise the dog’s health. Injection-only treatments require intramuscular or subcutaneous injections which can be very stressful for the dog as well as the dog owner.

Some of the treatments are expensive, especially for endemic regions. This applies definitely to large dogs that require more medication to achieve the desired effect. Treatments gets even more expensive, when medication needs to be administered for a long time.

With most current treatments we see a relapse when the treatment is discontinued leading to long term management of the disease, thus even more expenses for veterinary consult and prolonged treatment periods.

Overuse of all existing drugs to treat canine leishmaniasis has led to emerging drug-resistant parasite strains. Nowadays one tries to overcome with combination therapies, but that increases the treatment expenses for dog owners, as well as the likelihood and severity of side effects. A strict adherence to dosing regimens for combination therapies can be very challenging for dog owners.

The market needs for drugs against canine leishmaniasis are manifold:

  1. affordable drugs;
  2. drugs with less side effects;
  3. drugs that lead to longer periods without relapse (less veterinary consults/guidance ; less costs/year);
  4. drugs that can be easily orally administered and are very palatable for the dog;
  5. drugs that are efficient against resistant strains.

 

D121

The only orally bioavailable parasiticidal drug with acceptable efficacy against leishmaniasis is the chemical cousin of D121. The latter is known to have a narrow therapeutic window, mainly due to its side effect profile which may reduce compliance to treatment. As sub-optimal dosage can lead to drug resistance, high compliance is a very important criterion to ensure the longevity of an anti-infective agent.

Oblita Therapeutics intends to further develop and commercialize D121 as it shows a significant competitive advantage to alleviate suffering of the dog and improve his quality of life:

  • higher efficacy, also against drug resistant strains
  • longer periods without relapse
  • palatable and easy administration of the drug
  • stable pharmaceutical product for the highest climate zones

A good new treatment for canine leishmaniasis would significantly advance One Health goals by breaking the disease’s transmission cycle, improving animal and human health, reducing environmental impacts, and fostering collaboration across disciplines. It exemplifies how veterinary medicine can play a critical role in global health challenges.