World Leishmaniasis Day: the potential of Artemisia annua

01-06-2024

In the context of World Leishmaniasis Day, we take a closer look at the important role of Artemisia annua in the therapeutic approach to this disease.

Epidemiology and cycle of canine leishmaniasis

Canine leishmaniasis is an endemic disease in Spain and it is estimated that around 30% of dogs in the country are affected by Leishmania infantum, an intracellular protozoan parasite, of which dogs are considered the main reservoir. This protozoan is transmitted by the bite of female sandflies and alternates its life cycle between the amastigote form in the vertebrate host and the promastigote form in the gut of the vector.

Clinical manifestations of canine leishmaniasis

The clinical manifestations of canine leishmaniasis are related to the host immune response, which is responsible for some animals infected with L. infantum not developing clinical disease. Dogs are considered to have clinical leishmaniasis when, in addition to having a confirmed L. infantum infection, they show clinical signs and/or alterations in routine laboratory tests. Conversely, if they have no clinical signs or abnormalities, they are considered to be subclinically infected or clinically healthy infected dogs. The LeishVet clinical disease staging system is recommended for treatment and prognosis.

Challenges of conventional disease management

Treatment of canine leishmaniasis is challenging due to the intracellular localisation of the parasite. Currently, the drugs used reduce the parasite load and improve quality of life, but they rarely achieve total parasite elimination. Clinical relapses often occur after treatment has been completed. Moreover, drugs have often adverse effects, such as lethargy, vomiting, diarrhoea, nephrotoxicity or xanthine crystal formation. Moreover resistant strains have already emerged.

Due to the adverse effects and the emergence of strains resistant to the drugs used, new therapeutic alternatives need to be evaluated.

The potential of medicinal plants

Medicinal plants represent a promising therapeutic integration to the treatments recommended in the LeishVet protocol, according to the clinical staging system of the disease. A clear example is Artemisia annua plant, which thanks to its properties has been used since ancient times for the treatment of various diseases. This medicinal plant is the only natural source of artemisinin, a molecule recommended by the WHO to treat malaria. Many studies have positioned Artemisia annua as a great candidate for combating canine leishmaniasis.

Efficacy of Artemisia annua in the treatment of leishmaniasis

The leishmanicidal activity of artemisinin appears to be mediated by the production of reactive oxygen species secondary to the cleavage of the endoperoxide ring and subsequent depolarisation of the mitochondrial membrane, triggering parasite death by programmed cell death. In vitro and in vivo studies have demonstrated the leishmanicidal effect of artemisinin and other derived compounds, which appear to be safer and more effective in controlling and reducing the clinical signs, parasite load and antibody level of leishmaniasis compared to some conventional treatments. On the other hand, artemisinin and other derived compounds also demonstrate immunomodulatory activity.

It has been shown that the dried leaves of Artemisia annua provide greater efficacy of artemisinin in its anti-parasitic and immunomodulatory activity, increasing its bioavailability by 40 times compared to when pure artemisinin is administered. This is possible thanks to the more than 200 molecules contained in the plant and the pharmacological synergy between them. Other active ingredients of therapeutic interest in the plant include casticin, eupatorin and quercetin, for their anti-inflammatory and anticarcinogenic properties, among others.

In short, scientific evidence shows that the active principles of medicinal plants, and especially Artemisia annua, can be an effective and safe integration or alternative to traditional medicine, with artemisinin being a potential candidate for stimulating the body’s natural defences against Leishmania infantum and maintaining the homeostasis of the immune system.