Treatment Failure in Cutaneous Leishmaniasis Patients Referred to the School of Public Health, Tehran University of Medical Sciences During 2008-2017

Background: Cutaneous leishmaniasis (CL) is a vector borne disease predominantly found in tropical and subtropical countries, including Iran. For more than 6 decades, pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis, but over the past few years, clinical resistance to these medications has increased. In this study, we evaluated CL patients who did not show any desirable responses to the anti-leishmanial treatment within a 10-year period (2008 to 2017). Methods: All patients from different parts of Iran suspected of having cutaneous leishmaniasis, who were referred to the laboratory of leishmaniosis in Tehran University of Medical Sciences from 2008-2017 were parasitological examined. Results: During this period, a total of 1480 suspected CL patients were referred to the laboratory of leishmaniosis. Samples from 655 patients (70.8) suspected of having CL were positive microscopically. The failure rate in patients treated with anti-leishmaniasis medications for a minimum of three complete treatment periods was 1.83 (12 cases). There was no association between the number and size of skin lesions and patient characteristics. Also, the route of drug administration had no significant effect on the number and size of lesions. Conclusion: In the present study, treatment failure was found in some confirmed CL patients treated with meglumine antimoniate. Over the past few years, it seems that had been increased in resistance to these medications. So, a review of the correct implementation of the treatment protocol and/or a combination therapy may be helpful in preventing an increase in the rate of treatment failure

A Survey on the Adjuvant Role of Naloxone Alone or Combined with Alum in Vaccination Against Fasciolosis in BALB/c Mice.

BACKGROUND: Fasciolosis is a zoonotic parasitic disease imposing a heavy load of livestock losses worldwide. PURPOSE: We aimed to evaluate immune-stimulatory effects of naloxone (NLX), an opioid receptor antagonist, in combination with alum in mice vaccinated with excretory-secretory antigens (E/S) of Fasciola hepatica. METHODS: 8-week-old female BALB/c mice were subcutaneously vaccinated using E/S antigens of F. hepatica. Experimental groups (14 mice per group) included: vaccine (E/S antigen), alum vaccine (E/S antigen plus alum), NLX vaccine (E/S antigen plus NLX), and alum-NLX vaccine (E/S antigen plus a mixture of alum-NLX). The control group was infused with PBS. Lymphocyte proliferation and the levels of IFN-γ, IL-4, IgG2a, IgG1, and total IgG were measured. RESULTS: Mice vaccinated with NLX or alum-NLX adjuvants showed significantly higher rates of lymphocyte proliferation, IFN-γ, total IgG, and IgG2a levels. The mice that were injected with alum showed a significantly higher concentration of IL-4. Ratios of IFN-γ/Il-4 and IgG2a/IgG1 were significantly higher in the NLX and alum-NLX groups in comparison with the groups vaccinated either with alum or without any adjuvant. A significantly higher protection rate (62.5%) was seen in mice vaccinated with the alum-NLX adjuvant compared to the other groups. CONCLUSION: NLX can be effective in conferring cellular immunity and protection against F. hepatica. It is recommended to consider this agent as a potential adjuvant in vaccines against fasciolosis

Antileishmanial activity of Allium hirtifolium on promastigote and amastigote developmental stages of the parasite, Leishmania major

Cutaneous leishmaniasis is one of the most common parasitic diseases with great public health concern. The aim of this study is to investigate the effect of Allium hirtifolium on promastigote and amastigote developmental stages of Leishmania major. L. major promastigote was cultured in RPMI-1640 medium. The viability of promastigote stage after 24, 48, and 72 hr-IP incubation using alcoholic extracts of A. hirtifolium and Meglumine evaluated by MTT Assay and IC50 values (50 inhibitory concentrations) were calculated. Amastigote growth in mouse macrophages was evaluated. The efficacy of different doses ofDownloaded the A. hirtifolium and Meglumine were calculated as 24, 48, and 72 hr after addition. The promastigote growth stage of L. major was inhibited by A. hirtifolium extracts after 24, 48 and 72 hours. The IC50 of Allium hirtifolium extracts on amastigote growth of L. major were µg /ml,70.1 µg/ml and 51.4 µg/ml after 24, 48, and 72 hr respectively. Alcoholic extract of A. hirtifolium was reported to have anti-parasite effect in vitro on both the promastigote and amastigote development stages. © 2020, IndianJournals.com. All rights reserved

Curcumin nanoemulsion as a novel chemical for the treatment of acute and chronic toxoplasmosis in mice

Background: The aim of this study was to prepare curcumin nanoemulsion (CR-NE) to solve the problems associated with poor water solubility and low bioavailability of CR and to test its efficiency in the treatment of acute and chronic toxoplasmosis in mouse models. Materials and methods: CR-NE 1 was prepared using spontaneous emulsification by soybean as oil phase; a mixture of Tween 80 and Tween 85 as surfactant; ethanol as cosurfactant and distilled water. Particle size and zeta potential of NE were assessed using Nano-ZS90 dynamic light scattering. Stability testing of NE was assessed after storage for 2 months at room temperature. In vivo experiments were carried out using 50 BALB/c mice inoculated with virulent RH strain (type I) and 50 BALB/c mice inoculated with avirulent Tehran strain (type II) of Toxoplasma gondii and treated with CR-NE (1 w/v), CR suspension (CR-S, 1 w/v), and NE without CR (NE-no CR). Results: The mean particle size and zeta potential of CR-NE included 215.66+/-16.8 nm and -29.46+/-2.65 mV, respectively, and were stable in particle size after a three freeze-thaw cycle. In acute phase experiment, the survival time of mice infected with RH strain of T. gondii and treated with CR-NE extended from 8 to 10 days postinoculation. The differences were statistically significant between the survival time of mice in CR-NE-treated group compared with negative control group (P<0.001). Furthermore, CR-NE significantly decreased the mean counts of peritoneum tachyzoites from 5,962.5+/-666 in negative control group to 627.5+/-73 in CR-NE-treated mice (P<0.001). Growth inhibition rates of tachyzoites in peritoneum of mice receiving CR-NE, CR-S, and NE-no CR included 90, 21, and 11, respectively, compared with negative control group. In chronic phase experiment, the average number and size of tissue cysts significantly decreased to 17.2+/-15.6 and 31.5+/-6.26 microm, respectively, in mice inoculated with bradyzoites of T. gondii Tehran strain and treated with CR-NE compared with that in negative control group (P<0.001). Decrease of cyst numbers was verified by downregulation of BAG1 in treatment groups compared with negative control group with a minimum relative expression in CR-NE (1.12+/-0.28), CR-S (11.76+/-0.87), and NE-no CR (14.67+/-0.77), respectively, (P<0.001). Conclusion: Results from the current study showed the potential of CR-S and CR-NE in treatment of acute and chronic toxoplasmosis in mouse models for the first time. However, CR-NE was more efficient than CR-S, and it seems that CR-NE has a potential formula for the treatment of acute and chronic toxoplasmosis, especially in those with latent bradyzoites in brain

A comparative evaluation of regulatory T cells profile among acute and chronic cutaneous leishmaniasis using flow cytometry

Background: Cutaneous leishmaniasis (CL) is described as a major health problem in many countries of the world. Regulatory T cells (Tregs) are characterized as one of immunologic indexes. One of the best methods to determine of Tregs percentage is flow cytometry. The aim of this study was determination of the role of Tregs profile among acute and chronic forms of human CL using flow cytometry analysis. Methods: This study was conducted on 24 patients referred to Laboratory of Leishmaniasis, Tehran University of Medical Sciences, Tehran, Iran with acute and 14 patients with chronic phases of CL as well as 15 healthy individuals as control group in 2015-2016. After microscopic examination, 2 ml of peripheral blood samples were collected for determining percentage of CD4 + CD25+ CD127 low Tregs by using flow cytometry method. Results: Using flow cytometry analysis, the average percentage of Tregs were calculated 5.73, 6.71 and 6.61 for acute, chronic and healthy individuals, respectively. With SPSS software and Scheffe multiple comparison tests, the differences within in these groups are statistically significant (P=0.04) and between the acute and chronic group, there was marginally significant with approximately 91 of confidence level (P=0.088). Conclusion: Marginally differences were found significantly among averages of Regulatory T cells, acute and chronic phases of CL. Further comprehensive studies can be needed to verify the role of Tregs in both phases of CL cases. © 2019, Tehran University of Medical Sciences (TUMS). All rights reserved

Polyamine Metabolism in Leishmania Parasites: A Promising Therapeutic Target

Parasites of the genus Leishmania cause a variety of devastating and often fatal diseases in humans and domestic animals worldwide. The need for new therapeutic strategies is urgent because no vaccine is available, and treatment options are limited due to a lack of specificity and the emergence of drug resistance. Polyamines are metabolites that play a central role in rapidly proliferating cells, and recent studies have highlighted their critical nature in Leishmania. Numerous studies using a variety of inhibitors as well as gene deletion mutants have elucidated the pathway and routes of transport, revealing unique aspects of polyamine metabolism in Leishmania parasites. These studies have also shed light on the significance of polyamines for parasite proliferation, infectivity, and host&ndash;parasite interactions. This comprehensive review article focuses on the main polyamine biosynthetic enzymes: ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase, and it emphasizes recent discoveries that advance these enzymes as potential therapeutic targets against Leishmania parasites