Evolution of the genus Leishmania revealed by comparison of DNA and RNA polymerase gene sequences1Note: Nucleotide sequence data reported in this paper have been submitted to the GenBank™ data base with the accession numbers: POLA/RPOIILS (AF009134/AF009153, Leishmania adleri); (AF009135/NS, Leishmania aethiopica); (AF009136/AF009154, Leishmania amazonensis); (AF009137/NS, Leishmania arabica); (AF009138/AF009155, Leishmania braziliensis); (AF009139/NS, Leishmania chagasi); (AF009140/AF009156, Leishmania deanei); (AF009141/AF009157, Leishmania donovani); (AF009142/AF009158, Endotrypanum monterogeii); (AF009143/AF009159, Leishmania gymnodactyli); (AF009144/AF009160, Leishmania herreri); (AF009145/AF009161, Leishmania hertigi); (AF009146/AF009162, Leishmania hoogstraali); (AF009147/NS, Leishmania infantum); (AF009148/AF009163, Leishmania major); (AF009149/AF009164, Leishmania mexicana); (AF009150/AF009165, Leishmania panamensis); (AF009151/AF009166, Leishmania tarentolae); (AF009152/AF009167, Leishmania tropica).1

1997 ◽  
Vol 89 (2) ◽  
pp. 149-159 ◽  
Author(s):  
David G Croan ◽  
David A Morrison ◽  
John T Ellis
Author(s):  
Ravinder Sharma ◽  
Vikas Gupta ◽  
Viney Chawla ◽  
Pooja Chawla

Background: Communicable diseases have always been a threat to mankind since times immemorial. Leishmaniasis, an infectious disease caused by protozoan of various species of leishmania, is a major health problem spreading across 98 countries and about 350 million people stand the risk of this infection worldwide. Medical research has struggled a lot to combat this disease. Objective: Among the various approaches available for treatment of Leishmaniasis, many are costly so there is a need to develop effective but economical and easily available antileishmanial agents. Methods: Natural products are important source of various new medicaments and their derivatives can be used for synthetic modification and bioactivity optimization. Therefore, in order to fulfil the need for novel, economical, more effective and safer chemotherapeutic agents, scientists have explored Mother Nature in detail. Results: A number of plant species possess inhibitory activity against certain types of parasites such as Leishmania major, Leishmania amazonensis, Leishmania aethiopica, Leishmania braziliensis, Leishmania mexicana, Leishmania infantum, Leishmania chagasi and Leishmania donovani. Moreover natural products are economical, safer, more effective and without considerable side effects. Conclusion: The present review highlights the leishmanicidal activity of various natural products with an insight in to their possible mechanism.


Author(s):  
JeanAnne M Ware ◽  
Elise M O’Connell ◽  
Thomas Brown ◽  
Lauren Wetzler ◽  
Kawsar R Talaat ◽  
...  

Abstract Background Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited. Methods Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed. Results Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment. Conclusions Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use.


2015 ◽  
Vol 57 (5) ◽  
pp. 377-383 ◽  
Author(s):  
Kézia Peres GUALDA ◽  
Lílian Mathias MARCUSSI ◽  
Herintha Coeto NEITZKE-ABREU ◽  
Sandra Mara Alessi ARISTIDES ◽  
Maria Valdrinez Campana LONARDONI ◽  
...  

SUMMARY Leishmania infantum causes visceral leishmaniasis (VL) in the New World. The diagnosis of VL is confirmed by parasitological and serological tests, which are not always sensitive or specific. Our aim was to design new primers to perform a Polymerase Chain Reaction (PCR) for detecting L. infantum. Sequences of the minicircle kinetoplast DNA (kDNA) were obtained from GenBank, and the FLC2/RLC2 primers were designed. Samples of DNA from L. infantum, Leishmania amazonensis, Leishmania braziliensis, Leishmania guyanensis, Leishmania naiffi, Leishmania lainsoni, Leishmania panamensis, Leishmania major and Trypanosoma cruzi were used to standardize the PCR. PCR with FLC2/RLC2 primers amplified a fragment of 230 bp and the detection limit was 0.2 fg of L. infantum DNA. Of the parasite species assayed, only L. infantum DNA was amplified. After sequencing, the fragment was aligned to GenBank sequences, and showed (99%) homology with L. infantum. In the analysis of blood samples and lesion biopsy from a dog clinically suspected to have VL, the PCR detected DNA from L. infantum. In biopsy lesions from humans and dogs with cutaneous leishmaniasis, the PCR was negative. The PCR with FLC2/RLC2 primers showed high sensitivity and specificity, and constitutes a promising technique for the diagnosis of VL.


2007 ◽  
Vol 56 (5) ◽  
pp. 629-636 ◽  
Author(s):  
Avijit Dutta ◽  
Suman Bandyopadhyay ◽  
Chitra Mandal ◽  
Mitali Chatterjee

Leishmaniasis constitutes a complex of diseases with clinical and epidemiological diversity and includes visceral leishmaniasis, a disease that is fatal when left untreated. In earlier studies, the authors reported that Aloe vera leaf exudate (AVL) is a potent antileishmanial agent effective in promastigotes of Leishmania braziliensis, Leishmania mexicana, Leishmania tropica, Leishmania major and Leishmania infantum and also in axenic amastigotes of Leishmania donovani. In the present study, it has been demonstrated that, in promastigotes of L. donovani (IC50=110 μg ml−1), AVL mediates this leishmanicidal effect by triggering a programmed cell death. Incubation of promastigotes with AVL caused translocation of phosphatidylserine to the outer leaflet of the plasma membrane as measured by annexin V binding, which was accompanied by loss of mitochondrial membrane potential, release of cytochrome c into the cytosol and concomitant nuclear alterations that included chromatin condensation, deoxynucleotidyltransferase-mediated dUTP end labelling and DNA laddering. As this AVL-induced leishmanicidal effect could not be inhibited by protease inhibitors including Z-Val-Ala-dl-Asp (methoxy)-fluoromethylketone, a broad-spectrum caspase inhibitor, non-involvement of caspases and major proteases was suggested. Additionally, AVL treatment caused no increase in cytosolic Ca2+ or generation of reactive oxygen species, indicating that although promastigote death was induced by an apoptotic-like mechanism similar to metazoan apoptosis, the pathways of induction and/or execution differed at the molecular level.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nesrine Aissaoui ◽  
Samia Hamane ◽  
Maud Gits-Muselli ◽  
Antoine Petit ◽  
Mazouz Benderdouche ◽  
...  

Abstract Background Leishmaniases are regularly seen in non-endemic areas due to the increase of international travels. They include cutaneous leishmaniases (CL) and mucocutaneous (MC) caused by different Leishmania species, and visceral leishmaniases (VL) which present with non-specific symptoms. Methods We reviewed all consecutive leishmaniasis cases seen between September 2012 and May 2020. The diagnostic strategy included microscopy after May-Grünwald-Giemsa staining, a diagnostic quantitative PCR (qPCR) assay, and species identification based on sequencing of the cytochrome b gene. Results Eighty-nine patients had a definitive leishmaniasis diagnosis. Nine patients had VL with Leishmania infantum. Eighty patients had CL. Twelve patients acquired CL after trips in Latin America (7 Leishmania guyanensis, 2 Leishmania braziliensis, 2 Leishmania mexicana, and 1 Leishmania panamensis). Species could be identified in 63 of the 68 CLs mainly after travel in North Africa (59%) with Leishmania major (65%), Leishmania tropica/killicki (24%), and L. infantum (11%), or in West Sub-Saharan Africa (32%), all due to L. major. The median day between appearance of the lesions and diagnosis was 90 [range 60–127]. Conclusions Our diagnostic strategy allows both positive diagnoses and species identifications. Travelers in West Sub-Saharan Africa and North Africa should be better aware of the risk of contracting leishmananiasis.


Parasitology ◽  
2008 ◽  
Vol 135 (5) ◽  
pp. 567-574 ◽  
Author(s):  
M. FAKHAR ◽  
M. H. MOTAZEDIAN ◽  
D. DALY ◽  
C. D. LOWE ◽  
S. J. KEMP ◽  
...  

SUMMARYA panel of microsatellites mapped to the Leishmania genome might make it possible to find associations between specific loci and phenotypic traits. To identify such loci, a Perl programme was written that scans the sequence of a genome and writes all loci containing microsatellites to a MySQL database. The programme was applied to the sequences of the L. braziliensis, L. infantum and L. major genomes. The database is publicly available over the internet: http://www.genomics.liv.ac.uk/tryps/resources.html ‘Microsatellite Locus Extractor’, and allows the selection of mapped microsatellites that meet user-defined criteria from a specified region of the selected genome. The website also incorporates a primer design pipeline that will design primers to amplify the selected loci. Using this pipeline 12 out of 17 primer sets designed against the L. infantum genome generated polymorphic PCR products. A tailed primer protocol was used to label all microsatellite primers with a single set of labelled primers. To avoid the culture of parasites prior to genotyping, sets of nested PCR primers were developed to amplify parasite DNA eluted from microscope slides. The limit of detection was approximately 1·6 parasite equivalents. However, only 6/56 DNA from slides stored at ambient temperature for over 6 months gave positive PCR results.


2014 ◽  
Vol 58 (6) ◽  
pp. 3379-3388 ◽  
Author(s):  
Iris L. K. Wong ◽  
Kin-Fai Chan ◽  
Yun-Fu Chen ◽  
Zhao-Rong Lun ◽  
Tak Hang Chan ◽  
...  

ABSTRACTTreatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. We previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity againstLeishmania donovani, the causative agent of visceral leishmaniasis. Here, we further investigate their leishmanicidal activities against cutaneousLeishmaniaspecies. One of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhibitory concentrations [IC50s], 0.19 to 0.69 μM) and antiamastigote (IC50s, 0.17 to 2.2 μM) activities toward different species ofLeishmaniathat cause cutaneous leishmaniasis, includingLeishmania amazonensis,Leishmania braziliensis,Leishmania tropica, andLeishmania major. Compound 39 is not toxic to peritoneal elicited macrophages, with IC50values higher than 88 μM. In the mouse model of cutaneous leishmaniasis induced by subcutaneous inoculation ofL. amazonensisin mouse footpads, intralesional administration of 2.5 mg/kg of body weight of compound 39.HCl can reduce footpad thickness by 36%, compared with that of controls values. The amastigote load in the lesions was reduced 20-fold. The present study suggests that flavonoid dimer 39 represents a new class of safe and effective leishmanicidal agent against visceral and cutaneous leishmaniasis.


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