Chemotherapy of Leishmania and Trypanosoma Infections: Lost in Translation?—2nd Edition

Dear Colleagues,

Infections by the kinetoplastids Trypanosoma and Leishmania are widespread, causing debilitating or deadly processes and affecting a variety of hosts, including humans. Some species are zoonotic, and both domestic and wild hosts can be infected; this provides uncontrolled infection reservoirs. Naturally occurring vectoral transmission makes the environmental control of these infections virtually unfeasible in most cases; vaccination is unavailable or very limited, and the reduction in the infection level and its extension relies mainly on chemotherapy. The therapeutic arsenal is very limited and of variable efficacy depending on the kinetoplastid species involved or even the developmental stage. Most of the available drugs have toxicity issues and, with few exceptions, were synthesized over 50 years ago. Very few new chemical entities (NCE) are foreseen, and resistance to the commonly used drugs has been increasingly reported. Exploratory studies are largely carried out by academia given the low revenues expected by industry. Strategies to cope with the shortage of NCE include the development of drug delivery systems, the combination of available drugs, and target-based exploration combined with high-throughput drug screening. Insofar, current therapeutics involve, as a rule, the same compounds that were available within the second half of the 20^th century.

Reports on the identification of new targets in the parasites and new molecules of potential value are abundant. However, the effective progress of these molecules along the drug pipeline has been negligible. Several causes for the scarcity of NCE and the high attrition rate of the candidates could be invoked. Among them, the inherent difficulty involved, the complexity of life cycles or the inadequate surrogate models for drug screening have been incriminated. There are other issues receiving lower consideration that could be relevant to reducing the high numbers of molecules with potential value that have never been tested in adequate models or “drug killing” in the so-called Valley of Death in drug discovery.

Potential topics for this Special Issue include, but are not restricted to, research papers or reviews on the pharmacology-driven selection of molecules for the treatment of Leishmania and Trypanosoma infections, knowledge of the pathophysiology of these diseases and its effect on drug availability and efficacy, improvements in the identification of the predictive markers of efficacy, drug delivery systems and their value beyond the laboratory, the standardization of efficacy trials, the relative value of in vitro, ex vivo and in vivo models for drug exploration, the impact of the microbiome on efficacy, immune modulation to improve drug efficacy, and strategies to minimize the emergence and extension and drug resistance.

The therapy of these life-threatening human and animal diseases is challenging, but the reward is high. I hope you find this topic attractive and that your contribution is able to facilitate the development of effective and affordable drugs.

Prof. Dr. José María Alunda
Prof. Dr. Juan Torrado
Guest Editors

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• Leishmania
• Trypanosoma
• pharmacology
• therapeutics
• screening
• drugs
• molecules
• high-throughput systems
• target-based drug selection
• in vitro
• in vivo
• ex vivo
• animal models
• dogs
• cattle
• humans
• resistance

• Chemotherapy of Leishmania and Trypanosoma Infections: Lost in Translation? in Microorganisms (8 articles)