Leishmaniases belong to a group of diseases considered to be neglected by the World Organization of Health (WHO) since these diseases disproportionately affect marginalized communities with limited healthcare access [1]. The etiological agents are transmitted through the bite of infected female Phlebotomus spp. (in the Old World) and Lutzomyia spp. (in the New World) sandflies. Clinical outcomes range from the self-healing cutaneous form (CL) to the visceral (VL) one that can be fatal in the absence of treatment. The leishmaniases are endemic in 98 countries in the tropics, subtropics, and Southern Europe, where 3 million new cases and more than 50,000 deaths are recorded yearly [1]. The measures aimed to reduce such burden still rely on sandfly and reservoir (for zoonotic infections) control.
A number of contributions have appeared in Parasitologia, over the last few years, which open up new possibilities for the reduction in the impact of these diseases in public health.
In particular, Yona et al. [2] gave an overview of the different vaccination strategies described in the international literature, starting with the historical use of live-attenuated or whole-killed parasites (first generation vaccines) followed by those of the second generation, represented by two molecules, i.e., gp63 and lipophosphoglycan, which play a relevant role in immune response escape mechanisms of the parasite.
Third generation vaccines are based on DNA, protein subunits, peptides and chimeric/multiepitopes as well as mRNA. The obtained results with these tools are encouraging but the path to obtaining long-lasting effects of a multi-specific vaccine is still a very long way off.
The Authors warn about the risk of simply translating preclinical data obtained with animal models to human applications because of the substantial differences in the immune response to the parasite, which occur in the different hosts.
According to the Authors, many factors can affect the success of a vaccine for leishmaniasis like immunomodulation by factors present in the sandfly saliva, host immune complexity, and variable clinical manifestations.
Furthermore, emerging strategies including mRNA platforms, nanoparticle delivery, reverse vaccinology, and immunoinformatics offer promising avenues for advancing the development of novel as well as effective human vaccines.
The possibility of identifying more effective adjuvants which might stimulate macrophage function [3] also represents a new interesting approach.
The solution to obtain definite control over leishmaniasis is not only based on vaccines, but also on the discovery of new drugs.
Henne et al. [4] studied the activity of new thiol organic compounds against the etiological agent of human cutaneous leishmaniasis (CL), i.e., Leishmania major.
These Authors studied a great number of functionalized thiols (like enethiols and amidothiols) for their effects against the parasite, and they identified 13 products active against promastigotes of Leishmania major using an anti-Leishmania test, based on the reduction in resazurin [5]. In particular, they identified the amidothiol 13 which showed similar efficacy of that of Amphotericin B, the drug of choice for CL.
Structure analysis revealed that the activity of these compounds is prevalently due to the presence of the free thiol group.
While identifying phytochemical products against parasites responsible for neglected diseases, the study by Schou et al. [6] analyzed the activity of an ethanolic extract from leaves of Ptilostemon chamaepeuce subsp. cyprius (Pcc, Asteraceae), an endemic plant species of Cyprus, against promastigotes and amastigotes of Leishmania infantum, which is responsible for most of cases of VL in the Mediterranean region.
The Authors isolated the main sesquiterpene lactone (STL), deacylcynaropicrin, along with a minor derivative, 13-hydroxy-11β,13-dihydro-deacylcynaropicrin which resulted in being active against the parasite.
Effective parasite culture is critical for the evaluation of the effects of potentially active new drugs. Alves de Oliveira et al. [7] reviewed all the methods described in the international literature over the past ten years to identify the best conditions to cultivate the promastigotes of Leishmania spp. in vitro.
According to published data, the Authors concluded that different factors such as culture media composition, pH, supplementation, and temperature can lead to varied drug responses in in vitro activity assays against promastigotes which are still used in many research laboratories, although the use of amastigotes is essential for testing new drug candidates, since the correlation between data of efficacy obtained with the two stages is not always present [8].
Control of leishmaniasis requires an interdisciplinary one health approach, according to WHO [9].
It is based on a relatively few key control strategies: (i) early diagnosis and (ii) case management. The latter is the most important, not only for the patients but also for the limitation of transmission (at least in the anthroponotic form of the disease). Additionally, sandfly control measures (i.e., insecticide spraying, insecticide-treated materials, environmental management, and personal protection) can reduce transmission.
When the infection has a zoonotic transmission, the control of reservoirs is needed.
Unfortunately, no human vaccine is available yet, but many putative molecules are under study, although the formulations present in the market against canine leishmaniasis have not shown good efficacy in reducing the transmission to humans.
New drugs which might represent efficacious alternatives to amphotericin and meltefosine are still needed and the research in this field should certainly be prioritized.
Acknowledgments
The Author is grateful to N. Basilico for helpful suggestions.
Conflicts of Interest
The author declares no conflict of interest.
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