Dataset Information

Super Infection of Cutaneous Leishmaniasis Caused by Leishmania major and L. tropica to Crithidia fasciculata in Shiraz, Iran.

ABSTRACT: Background:The aims of the current study were to determined present status of CL in Shiraz City, identify the causative species of Leishmania and conduct phylogenetic evaluations in detected parasites. Methods:This study was conducted on 70 individuals with suspected CL that referred to the major health centers of Shiraz (Valfajr), Fars province, Iran, from Sep 2016 to Jul 2017. DNA was extracted from cultured Leishmania promastigotes and PCR-RFLP were performed using ITS1-rDNA gene. Results:Overall, 39 male (55.70%) and 31 (44.30%) female were found to be positive microscopically. All of direct examined positive samples were confirmed to be positive for Leishmania spp. DNA. Based upon the PCRRFLP patterns and phylogenetic analysis, 46 (65.72%), 17 (24.28%) and 7 (10%) isolates were clearly identified as L. major, L. tropica and C. fasciculata, respectively. Conclusion:The dominat detected species in Shiraz City was L. major and L. tropica, respectively. CL has high prevalence in Shiraz City; therefore, more studies on leishmaniasis in the natural vectors and also reservoirs infection in this region is exceedingly recommended. Skin leisons due to C. fasciculata, was described for the first time in Iran (Shiraz City).

SUBMITTER: Mirzapour A

PROVIDER: S-EPMC6974865 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Super Infection of Cutaneous Leishmaniasis Caused by <i>Leishmania major</i> and <i>L. tropica</i> to <i>Crithidia fasciculata</i> in Shiraz, Iran.

Mirzapour Aliyar A Badirzadeh Alireza A Ashrafmansouri Marzieh M Behniafar Hamed H Norouzi Maryam M Azizi Hakim H Behravan Mahmoodreza M Seyyed Tabaei Seyyed Javad SJ

Iranian journal of public health 20191201 12

<h4>Background</h4>The aims of the current study were to determined present status of CL in Shiraz City, identify the causative species of <i>Leishmania</i> and conduct phylogenetic evaluations in detected parasites.<h4>Methods</h4>This study was conducted on 70 individuals with suspected CL that referred to the major health centers of Shiraz (Valfajr), Fars province, Iran, from Sep 2016 to Jul 2017. DNA was extracted from cultured <i>Leishmania</i> promastigotes and PCR-RFLP were performed usin ...[more]

PMID: 31993398

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Project description:Cutaneous Leishmaniasis (CL) is a parasitic infection classified by the WHO as one of the most uncontrolled spreading neglected diseases. Syria is endemic for Leishmania tropica and Leishmania major, causing CL in the Eastern Mediterranean. The large-scale displacement of Syrian refugees exacerbated the spread of CL into neighboring countries. Therapeutic interventions against CL include local, systemic and physical treatments. The high risk for drug-resistance to current treatments stresses the need for new therapies. Imiquimod is an immunomodulatory drug with a tested efficacy against L. major species. Yet, Imiquimod efficacy against L. tropica and the molecular mechanisms dictating its potency are still underexplored. In this study, we characterized the effect of Imiquimod against L. tropica and L. major, and characterized the molecular mechanisms dictating its anti-leishmanial efficacy against both strains. We also investigated the potency and molecular mechanisms of an Imiquimod analog, EAPB0503, against these two strains. We have tested the effect of Imiquimod and EAPB0503 on macrophages infected with either L. major, L. tropica strains, or patient-derived freshly isolated L. tropica parasites. The anti-amastigote activity of either drugs was assessed by quantitative real time PCR (RT-PCR) using kinetoplast specific primers, confocal microscopy using the Glycoprotein 63 (Gp63) Leishmania amastigote antibody or by histology staining. The mechanism of action of either drugs on the canonical nuclear factor kappa- B (NF-?B) pathway was determined by western blot, and confocal microscopy. The immune production of cytokines upon treatment of infected macrophages with either drugs was assessed by ELISA. Both drugs reduced amastigote replication. EAPB0503 proved more potent, particularly on the wild type L. tropica amastigotes. Toll-Like Receptor-7 was upregulated, mainly by Imiquimod, and to a lesser extent by EAPB0503. Both drugs activated the NF-?B canonical pathway triggering an immune response and i-NOS upregulation in infected macrophages. Our findings establish Imiquimod as a strong candidate for treating L. tropica and show the higher potency of its analog EAPB0503 against CL.

Project description:Leishmaniasis may occur in three different clinical forms, namely, visceral, mucocutaneous and cutaneous, which are caused by different species of trypanosomatid protozoans of the genus Leishmania. Pentavalent antimonials are the leading treatment for cutaneous leishmaniasis despite the hepatic, renal, and cardiac toxicity. In addition, the response of some Leishmania species to pentavalent antimonials is increasingly poorer, and therefore new and more potent therapeutic alternatives are needed. Arnica montana L., Asteraceae, is a traditional medicinal plant of Europe and preparations of its flowers are commonly used externally to treat disorders of the musculoskeletal system as well as superficial inflammatory conditions. Previous studies have shown that Arnica tincture (AT), an ethanolic extract prepared from the flowerheads of Arnica montana as well as isolated Arnica sesquiterpene lactones (STLs) have antileishmanial activity in vitro against L. donovani and L. infantum, as well as in vivo against L. braziliensis. In this work, we studied the in vitro cytotoxicity and antileishmanial activity of AT and STLs against both L. braziliensis and L. tropica. The in vivo therapeutic effect of AT was studied in hamsters with cutaneous Leishmaniasis (CL) caused by experimental infection with L. braziliensis and L. tropica. Furthermore, various semisolid Arnica preparations were also evaluated against L. braziliensis. The STLs and the AT possess a very high in vitro activity against both Leishmania species with median effective concentrations (EC50) ranging from 1.9 to 5.9 μg/mL. The AT was not cytotoxic for human tissue macrophages, skin fibroblasts, and hepatic cells. The therapeutic response of hamsters infected with L. braziliensis to the topical treatment with AT was 87.5% at a dose of 19.2 μg STL/2× day/60 d, 72.7% at doses of 19.2 μg STL/1× d/60 d and 67% at a dose of 38.4 μg STL/2× d/60 d. In turn, the therapeutic response in hamsters infected with L. tropica was 100% when treated at a dose of 19.2 μg STL/2× day/60 d and 71% at a dose of 38.4 μg STL/2× d/60 d. On the other hand, the effectiveness of treatment with glucantime administered intralesionally at a dose of 200 mg/every three days for 30 days was 62.5% for L. braziliensis and 37.5% for L. tropica infection. These results are promising and encourage the implementation of clinical trials with AT in CL patients as a first step to using AT as a drug against CL.

Dataset Information

Super Infection of Cutaneous Leishmaniasis Caused by Leishmania major and L. tropica to Crithidia fasciculata in Shiraz, Iran.

Publications

Super Infection of Cutaneous Leishmaniasis Caused by <i>Leishmania major</i> and <i>L. tropica</i> to <i>Crithidia fasciculata</i> in Shiraz, Iran.

Similar Datasets

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