Abstract
Leishmaniases are a group of vector-borne diseases caused by infection with the protozoan parasites Leishmania spp. Some of them, such as Mediterranean visceral leishmaniasis, are zoonotic diseases transmitted from vertebrate to vertebrate by a hematophagous insect, the sand fly. As there is an endemic in more than 90 countries worldwide, this complex and major health problem has different clinical forms depending on the parasite species involved, with the visceral form being the most worrying since it is fatal when left untreated. Nevertheless, currently available antileishmanial therapies are significantly limited (low efficacy, toxicity, adverse side effects, drug-resistance, length of treatment, and cost), so there is an urgent need to discover new compounds with antileishmanial activity, which are ideally inexpensive and orally administrable with few side effects and a novel mechanism of action. Therefore, various powerful approaches were recently applied in many interesting antileishmanial drug development programs. The objective of this review is to focus on the very first step in developing a potential drug and to identify the exploratory methods currently used to screen in vitro hit compounds and the challenges involved, particularly in terms of harmonizing the results of work carried out by different research teams. This review also aims to identify innovative screening tools and methods for more extensive use in the drug development process.
Highlights
The leishmaniases are a group of vector-borne diseases common to humans and certain mammals, mainly the dog, for zoonotic visceral forms
Medicine donation programs are multiplying to support the burden of neglected tropical diseases [150] such as leishmaniases, the pharmaceutical industry seems to increasingly restrict its research and development investment to new drug candidates [151]
Alternative options consist of repurposing drugs [152,153,154] or improving existing drugs, such as the gold standard amphotericin B [155]
Summary
The leishmaniases are a group of vector-borne diseases common to humans and certain mammals, mainly the dog, for zoonotic visceral forms. There was an endemic in 98 countries and territories in 2020 [1], and the geographic distribution of these diseases evolved according to the movements of the insect vector driven by climatic and environmental changes (such as deforestation and urbanization) [2] These diseases mainly affect poor people in Africa, Asia, and South America and are associated with malnutrition, population displacement, poor housing, weak immune system, and a lack of resources [1,2]. The main epidemiological type around the Mediterranean basin involves L. infantum and is represented by zoonotic visceral leishmaniasis This type is clinically characterized by the triad of mad fever, anemia, and splenomegaly and is transmitted from dogs to humans. In 2020, about 87% of global visceral leishmaniasis cases were reported from eight countries (Brazil, Eritrea, Ethiopia, India, Kenya, Somalia, South Sudan, and Sudan) [1]
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