Transmission patterns of Leishmania tropica around the Mediterranean basin: Could Morocco be impacted by a zoonotic spillover?

Cutaneous leishmaniasis (CL) due to Leishmania tropica is a neglected tropical disease characterized by a wide geographical distribution in the Mediterranean basin and is endemic in several of its countries. In addition, the vector Phlebotomus sergenti is abundantly present all around the basin. Its transmission cycle is still subject to debate. In some countries, the presence of an animal reservoir has been confirmed. In Morocco, CL due to L. tropica has risen since the 1980s and has spread widely to become the most abundant form of leishmaniasis in the territory. However, the anthroponotic transmission is so far the only recognized mode, despite recordings of L. tropica infection in animal hosts. In this review article, we assess the situation of CL due to L. tropica in the Mediterranean basin with a focus on Morocco and gather knowledge about any potential zoonotic transmission in the country. A concomitant zoonotic transmission could explain the persistence of the disease in areas where human protective measures combined with vector management did not help reduce the disease burden.

Case Report: Local Treatment of a Leishmania tropica Infection in a Syrian Child with a Novel Filmogenic Preparation of Pharmaceutical Sodium Chlorite (LeiProtect®)

Cutaneous leishmaniasis (CL) frequently entails chronic skin lesions that heal only slowly. Until now, the available therapeutic options are very limited. Here, we present a case of a 5½-year-old Syrian refugee with two progressive lower-leg skin ulcers caused by Leishmania tropica. The patient received topical treatment with LeiProtect®, a newly developed, hydroxypropylcellulose-based, filmogenic gel containing nontoxic concentrations of pharmaceutical sodium chlorite. The skin lesions completely healed within 8 weeks and did not relapse during 1 year of follow-up, underlining the efficacy of this novel local therapy of CL.

High genome plasticity and frequent genetic exchange in Leishmania tropica isolates from Afghanistan, Iran and Syria

Background The kinetoplastid protozoan Leishmania tropica mainly causes cutaneous leishmaniasis in humans in the Middle East, and relapse or treatment failure after treatment are common in this area. L. tropica’s digenic life cycle includes distinct stages in the vector sandfly and the mammalian host. Sexual reproduction and genetic exchange appear to occur more frequently than in other Leishmania species. Understanding these processes is complicated by chromosome instability during cell division that yields aneuploidy, recombination and heterozygosity. This combination of rare recombination and aneuploid permits may reveal signs of hypothetical parasexual mating, where diploid cells fuse to form a transient tetraploid that undergoes chromosomal recombination and gradual chromosomal loss. Methodology/principal findings The genome-wide SNP diversity from 22 L. tropica isolates showed chromosome-specific runs of patchy heterozygosity and extensive chromosome copy number variation. All these isolates were collected during 2007–2017 in Sweden from patients infected in the Middle East and included isolates from a patient possessing two genetically distinct leishmaniasis infections three years apart with no evidence of re-infection. We found differing ancestries on the same chromosome (chr36) across multiple samples: matching the reference genome with few derived alleles, followed by blocks of heterozygous SNPs, and then by clusters of homozygous SNPs with specific recombination breakpoints at an inferred origin of replication. Other chromosomes had similar marked changes in heterozygosity at strand-switch regions separating polycistronic transcriptional units. Conclusion/significance These large-scale intra- and inter-chromosomal changes in diversity driven by recombination and aneuploidy suggest multiple mechanisms of cell reproduction and diversification in L. tropica, including mitotic, meiotic and parasexual processes. It underpins the need for more genomic surveillance of Leishmania, to detect emerging hybrids that could spread more widely and to better understand the association between genetic variation and treatment outcome. Furthering our understanding of Leishmania genome evolution and ancestry will aid better diagnostics and treatment for cutaneous leishmaniasis caused by L.tropica in the Middle East.

Spectral, Anti-Inflammatory, Anti-Pyretic, Leishmanicidal, and Molecular Docking Studies, Against Selected Protein Targets, of a New Bisbenzylisoquinoline Alkaloid

A new bisbenzylisoquinoline named as chondrofolinol (1) and four reported compounds (2–5) were isolated and characterized from the roots of Berberis glaucocarpa Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of Leishmania tropica, respectively. The new compound significantly reduced the paw volume in carrageenan-induced paw edema and rectal temperature in yeast-induced pyrexia at 10 and 20 mg/ kg of body weight. Chondrofolinol caused almost 100% inhibition of the promastigotes of Leishmania tropica. All the compounds displayed minimal cytotoxicity against THP-1 monocytic cells. In order to ascertain the potential macromolecular targets of chondrofolinol responsible for the observed anti-inflammatory and anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and Leishmania. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of N-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for Leishmania major were selected after thorough literature search about protein targets responsible for inflammation and Leishmania major. Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The Leishmania major protein targets with the most favorable docking scores to chondrofolinol were NMT, TyrRS, and UGPase. The study indicated that bisbenzylisoquinoline and isoquinoline alkaloids possess anti-pyretic, anti-inflammatory, and anti-leishmanial properties with minimal cytotoxicity and therefore, need to be further explored for their therapeutic potential.

Wings’ Descriptive and Geometric Morphometry Analyses Support Distinct Phlebotomus sergenti Parrot Populations in Central Morocco

Phlebotomus (Paraphlebotomus) sergenti Parrot, 1917, the proven vector of Leishmania tropica Wright, 1903, the causative agent of anthroponotic cutaneous leishmaniasis, is widely distributed in Morocco. Previous works using molecular markers (ITS2 rDNA and Cyt b mtDNA) have hy-pothesized the existence of multiple closely related populations of sandfly species (cryptic species) that would exhibit distinct vectorial capacities. In this work, descriptive characteristics of wings (size and shape of the right and left wings) were measured in samples collected from fourteen sta-tions in central Morocco. These analyses support the existence of distinct P. sergenti populations, enlightening significant phenotypic variations of P. sergenti’s wings, regarding their size and shape, depending on geographic origin. In addition, geomorphometric analyses of wing’s length, centroid size, alpha, and beta distances allowed clear discrimination of P. sergenti sub-populations. These data pinpoint the adaptative ability of P. sergenti to local environmental conditions. Additional studies are now required to further shed light on the genetic structure of P. sergenti populations in Morocco.

Cutaneous Leishmaniasis in Suspected Patients Referred to the Health Centers of Abarkouh, Ardakan, Bafgh and Khatam, Yazd Province, Iran

Background and Aims: Cutaneous Leishmaniasis is a significant health problem in many parts of Iran. Management of the disease and its treatment is a global dilemma. In this study, the status and the proportions of Cutaneous Leishmaniasis induced by Leishmania major and tropica among suspected patients referred to the Health Centers of Abarkouh, Ardakan, Bafgh, and Khatam cities, Yazd Province, Iran were investigated. Materials and Methods: The lesion was diagnosed using direct smear microscopy and conventional polymerase chain reaction. Results: A total of 90 samples were prepared of which 64 (71.1%) were male and 26 (27.9%) were female. Also, 30 (33.3%) samples came from Ardakan, 29 (32.2%) samples from Bafgh, 21 (23.3%) samples from Abarkouh, and 10 (11.1%) samples from Khatam city. Ninety samples with 112 lesions were recruited and parasitologically examined. The results showed that, in macroscopic examination, 90 of the patients had 59 lesions: patients with lesion(s) induced by Leishmania major = 52 (M=35, 67.3%, F=17, 32.7%), lesion(s) induced by Leishmania tropica =4 (M=2, 50.0%, F=2, 50.0%), and lesion(s) induced by false positive =33 (36.4%). Basides, in microscopic method, 90 of the patients had 59 lesions: patients with lesion(s) induced by Leishmania major =44 (M=29, 65.9%, F=15, 34.09%), lesion(s) induced by Leishmania tropica =9 (M=8, 88.8%, F=1, 11.2%), and lesion(s) induced by false positive =37 (M=28, 75.7%, F=9, 24.3%). Conclusion: Although travel history to an endemic area is important for diagnosis, parasitological confirmation is necessary to initiate treatment.