Leishmaniasis: Recent epidemiological studies in the Middle East

Knight, Chinyere A.; Harris, David R.; Alshammari, Shifaa O.; Gugssa, Ayele; Young, Todd; Lee, Clarence M.

doi:10.3389/fmicb.2022.1052478

Cited by 26 publications

(19 citation statements)

References 107 publications

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“…Cutaneous leishmaniasis (CL) is a worldwide spread vector-borne parasitic disease caused by various members of the Leishmania genus and transmitted by sand flies ( 1 ). The World Health Organization estimates 600,000 to 1 million new cases worldwide, occurring mainly in the Americas, Middle East, and Central Asia; however, some factors such as rapid urbanization, human migration, and climate change lead to the risk of transmission and emergence of CL in non-endemic zones ( 2 ). This disease manifests in multiple clinical forms, influenced by both the pathogen species and the host’s immune response.…”

Section: Introductionmentioning

confidence: 99%

Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms

Morales-Primo,

Becker,

Pedraza-Zamora

et al. 2024

Immune Netw

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The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4 + T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8 + T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8 + T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4 + T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

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Section: Introductionmentioning

confidence: 99%

Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms

Morales-Primo,

Becker,

Pedraza-Zamora

et al. 2024

Immune Netw

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“…Protozoan parasites of the Leishmania genus (Kinetoplastida: Trypanosomatidae) are responsible for human and animal leishmaniasis, pathologies that are found to be endemic in Asia, the Middle East, North Africa, East Africa, the Mediterranean, and South and Central America [ 1 , 2 ]. Leishmaniasis affects more than 12 million people worldwide [ 2 ], with almost 250,000 new cases of both cutaneous and visceral leishmaniosis reported in 2021 (data source: World Health Organization, accessed on 8 March 2023, last updated on 6 February 2023; ).…”

Section: Introductionmentioning

confidence: 99%

A Calcium- and GTP-Dependent Transglutaminase in Leishmania infantum

Almugadam

Trentini

Maritati

et al. 2023

Veterinary Sciences

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While human and animal leishmaniasis affect several millions of people worldwide, L. infantum is the species responsible for visceral leishmaniasis in Europe, Middle East, and America. Antileishmanial drugs present issues associated with drug toxicity and increasing parasite resistance. Therefore, the study of this parasite with a focus on new potential drug targets is extremely useful. Accordingly, we purified and characterized a transglutaminase (TGase) from L. infantum promastigotes. While Tgases are known to be involved in cell death and autophagy, it appears that these functions are very important for parasites’ virulence. For the first time, we showed a Ca2+- and GTP-dependent TGase in Leishmania corresponding to a 54 kDa protein, which was purified by two chromatographic steps: DEAE-Sepharose and Heparin-Sepharose. Using polyclonal antibodies against a 50-amino-acid conserved region of the catalytic core of human TGase 2, we revealed two other bands of 66 and 75 kDa. The 54 kDa band appears to be different from the previously reported TGase, which was shown to be Ca2+- independent. Future research should address the identification of the purified enzyme sequence and, subsequently, its cloning to more comprehensively investigate its pathophysiological function and possible differences from mammal enzymes.

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“…Current drugs for the treatment of leishmaniasis are pentavalent antimonials (sodium stibogluconate and meglumine antimoniate), amphotericin B (amphotericin B deoxycholate and liposomal amphotericin B), miltefosine, paromomycin and pentamidine. However, in general, they are limited by one or more of the following issues: toxicity, variable e cacy, parasite resistance, parenteral administration, lack of availability and cost of treatment and hospitalization (Knight et al, 2023). Consequently, for years there has been a call to prioritize the search for better new drugs for the treatment of leishmaniasis.…”

Section: Introductionmentioning

confidence: 99%

PubChem BioAssays 1063: A poorly exploited source of new antileishmanial compounds

Sifontes-Rodríguez,

Meneses-Gómez,

Escalona-Montaño

et al. 2023

Preprint

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PubChem Bioassays (AID 1063) reported the in vitro testing of 196 441 compounds against Leishmania major promastigotes. Although these results have been publicly available since 2008, limited efforts on further testing of some of these compounds has been published. The aim of the present work was selecting a small set of compounds that were highly active in that primary assay and assessing their antileishmanial activity in vitro and in vivo. Selected compounds were 100 % active in the primary assay at 10 μM, were not theoretically toxic, did not have structural features of pan assay interfering substances, had positive druglikeness, were not cytotoxic and their activity rate in previous assays reported in PubChem Bioassays was under 5 %. Seven commercially available compounds were purchased and tested against L. major, Leishmania mexicana, Leishmania amazonensis and Leishmania infantum promastigotes; in mouse peritoneal macrophages (cytotoxicity); and against L. mexicana intracellular amastigotes. Eventually, four compounds with appropriate selectivity and high activity against L. mexicana amastigotes were tested by intralesional route (1 %, 20 μL) in a mouse model of cutaneous leishmaniasis. Four compounds were active (IC50<10 μM) against the promastigote stage of the four Leishmania species tested. These four compounds were also active (IC50< 10 μM) in vitro against intracellular amastigotes and in vivo in mice experimentally infected with L. mexicana. Results demonstrated the potential of these compounds as antileishmanials and the high, unexploited potential of AID 1063 as a source of new antileishmanial agents.

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Leishmaniasis: Recent epidemiological studies in the Middle East

Cited by 26 publications

References 107 publications

Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms

Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms

A Calcium- and GTP-Dependent Transglutaminase in Leishmania infantum

PubChem BioAssays 1063: A poorly exploited source of new antileishmanial compounds

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