Leishmania, the parasites causing leishmaniases, are transmitted to humans when the insect vector (the female sandfly) feeds on their blood. Sandflies inject the parasites into mammal hosts, including humans, in the "promastigote" stage (i.e. when they possess a flagellum). In the dermis, these leishmania are captured by macrophages and transform into "amastigotes" (a purely intracellular development stage in which they have no flagellum). Host cells may subsequently be located in different tissues or organs, causing various symptoms characteristic of the disease, depending on factors specific to the host and Leishmania species.
Leishmaniases may present in various clinical forms, which are broadly classified into two categories:
Cutaneous leishmaniasis, which is mild in most cases, and is characterized by ulcerated or ulcerated-crusted lesions, sometimes occurring in very high numbers on uncovered parts of the body, and generally healing spontaneously, although sometimes leaving highly disfiguring scars. Depending on the infecting species, cutaneous leishmaniasis may progress to a mucocutaneous or diffuse cutaneous form.
Visceral leishmaniasis is the most severe form of the disease, with symptoms including fever, anemia, weight loss, and swelling of the liver, spleen, and lymph nodes. It is fatal if left untreated.
In 2018, visceral and cutaneous leishmaniases were endemic in 92 and 83 countries respectively. Over a billion people now live in endemic areas, and are therefore at risk of contracting the parasite and developing the disease.
In mainland France, leishmaniasis, and particularly visceral leishmaniasis, is present in the Mediterranean departments (Eastern Pyrenees, Cévennes, Provence, Côte d’Azur, and Corsica) where the causative species is Leishmania infantum, which also causes canine leishmaniasis. Travelers may also be infected with other species when traveling to endemic countries.
Prevention and treatments
No vaccine or prophylactic drug is currently available. The WHO and French experts (technical report on controlling leishmaniasis) recommend a therapeutic approach addressing the various clinical and parasitological aspects of the disease, which leads to recovery in the vast majority of cases.
At the Institut Pasteur
The Molecular Parasitology and Signaling Unit led by Gerald Spaeth conducts research on the biology and mechanisms of interaction between mammal hosts and Leishmania, one of the world's main parasites causing severe human diseases classified as emerging parasitic diseases in the EU. Through a combination of cutting-edge molecular, genetic, pharmacological, and immunological approaches, the team has made major contributions to our understanding of the way in which these intracellular parasites adapt to host cells, namely macrophages, and how they alter the functions of these host cells to increase their chances of survival and multiplication, ultimately causing disease. The results of this fundamental research are fed into a pipeline for the discovery of new drug candidates and the validation of new therapeutic targets. This key area of research is essential, since currently available anti-Leishmania treatments are toxic for some people or are losing efficacy due to the emergence of resistant parasites. This research is conducted in close collaboration with partner teams in the Institut Pasteur International Network based in regions where Leishmania is endemic (www.leishriip.org) and in partnership with the Institut Pasteur of Shanghai. It relies on coordination between major national and international networks including the FP7-Leishdrug, ANR-TransLeish, and H2020-LeiSHield consortia.
The Institut Pasteur teams working on leishmaniasis
Molecular Parasitology and Signaling laboratory led by Gérald Spaeth