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Pentavalent antimonials are the mainstay treatment against different clinical forms of leishmaniasis. The emergence of resistant isolates in endemic areas has led to treatment failure. Unraveling the underlying resistance mechanism would assist in improving the treatment strategies against resistant isolates. This study aimed to investigate the RNA expression level of glutathione synthetase (GS), Spermidine synthetase (SpS), trypanothione synthetase (TryS) genes involved in trypanothione synthesis, and thiol-dependent reductase (TDR) implicated in drug reduction, in antimony-sensitive and -resistant Leishmania tropica isolates. We investigated 11 antimony-resistant and 11 antimony-sensitive L. tropica clinical isolates from ACL patients. Drug sensitivity of amastigotes was determined in mouse macrophage cell line J774A.1. The RNA expression level in the promastigote forms was analyzed by quantitative real-time PCR. The results revealed a significant increase in the average expression of GS, SpS, and TrpS genes by 2.19, 1.56, and 2.33-fold in resistant isolates compared to sensitive ones. The average expression of TDR was 1.24-fold higher in resistant isolates, which was insignificant. The highest correlation coefficient between inhibitory concentration (IC 50 ) values and gene expression belonged to the TryS, GS, SpS, and TDR genes. Moreover, the intracellular thiol content was increased 2.17-fold in resistant isolates compared to sensitive ones and positively correlated with IC 50 values. Our findings suggest that overexpression of trypanothione biosynthesis genes and increased thiol content might play a key role in the antimony resistance of L. tropica clinical isolates. In addition, the diversity of gene expression in the trypanothione system and thiol content among L. tropica clinical isolates highlighted the phenotypic heterogeneity of antimony resistance among the parasite population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Acanthamoeba keratitis (AK) is an eye disease often occurring in contact lens wearers. AK treatment is prolonged and requires multiple drugs, which can lead to adverse effects. Our study aimed to compare the in vitro activities and safety of Miltefosine with that of conventional antimicrobial agents used to treat AK. Acanthamoeba castellanii genotype T4 was obtained from a patient with keratitis and subjected to in vitro susceptibility testing with various antimicrobial agents, including Chlorhexidine (CHX), Pentamidine isethionate (PI)Polyhexamethylene biguanide (PHMB), and Miltefosine to assess their efficacy against Acanthamoeba trophozoites and cyst. The cytotoxicity of the agents was evaluated in Vero cells, and their selectivity indexes (SI) were calculated. Chlorhexidine exhibited the highest amoebicidal activity with the highest selectivity index against the trophozoite and cyst, ranging from 1.17 to 8.35. The selectivity index of PHMB is slightly comparable to Chlorhexidine, exhibiting significant anti-Acanthamoeba activity. On the other hand, Pentamidine isethionate and Miltefosine displayed low SI among the compounds. Pentamidine isethionate was effective at high concentrations, which was toxic. Miltefosine exhibited the lowest cytotoxicity; nevertheless, due to the lowest anti-Acanthamoeba activity presented a low selectivity against the parasite. Further studies on more clinical samples and prolonged incubation time should be done to investigate the effectiveness and toxicity of drugs in both in vitro and in vivo conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rodents from the subfamily Gerbillinae are the principal reservoir of cutaneous leishmaniasis (CL) caused by Leishmania major in the center and northeast of Iran. This study was conducted to determine both naturally occurring Leishmania infection rates and the distribution of Leishmania species in the central parts of Iran during 2019-2020. In this regard, presence of Leishmania parasites were confirmed by microscopic examination and the species were identified by nested-PCR using the Internal Transcribed Spacer2- Ribosomal DNA (ITS2-rDNA). Finally, some samples were sequenced and, the blast analysis of L. major samples, showed a 92.45-100% homology to the L. major sequence. Of the 181 wild gerbils collected (Rhombomys opimus=157 and Meriones lybicus=24), 88 (48.6%) tested positive for Leishmania sp. by microscopic examination whereas 162 (89.5%) were positive by nested-PCR. Of the 162 infected gerbils, 103 showed single strain infections (30 L. major, 28 L. gerbilli and 45 L. turanica), 43 showed dual infections with only the non-human species (L. gerbilli and L. turanica), and 16 were mixed infections of L. major and L. turanica (n = 14) or L. gerbilli (n = 2). All single or mixed L. major infections were detected in gerbils from areas with reports of human CL during the last decade. These findings suggest that Rhombomys opimus and Meriones libycus have a potential role in the maintenance of human and non-human transmission of Leishmania species in the CL foci., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Leishmanization (LZ) is an intradermal inoculation of live Leishmania to induce an artificial cutaneous leishmaniasis (CL) lesion in a covered part of the body to protect against further natural CL lesion development. Leishmanization has been used from ancient times and when NNN medium was developed continued with using Leishmania from culture media. The objective of this study was to review LZ published experiences. This article is a review of LZ experiences and historical studies initiated since 1910 when Leishmania promastigotes were harvested from culture media and used for LZ. This review includes LZ experiences in Israel, some countries of Former Soviet Union and Iran. The results of LZ in Israel, some countries of Former Soviet Union and Iran showed that despite limitations, using this method significantly reduced the incidence rate of CL among leishmanized individuals in endemic areas. In conclusion, leishmanization using Leishmania major produced under GMP guideline is a valuable tool to protect against CL, there are limitations which need further study., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Cutaneous Leshmaniasis (CL), a parasitic skin infection caused by Leishmania species, is endemic in some regions of Iran. In this study, the effect of location on the incidence and distribution of CL in Iran was studied., Methods: We collected datas including the number of Cutaneous Leishmaniasis cases and populations at-risk of disease in Iran's different provinces reported by the Iranian ministry of health and the National Bureau of Statistics, respectively. Spatial modeling was performed using Arc GIS software. Descriptive maps, hotspot analysis, and high/low clustering analysis were used to demonstrate distribution of the cutaneous leishmaniasis, to determine regions at risk of disease's incidence, and to reach the most appropriate method for clustering of disease., Results: The total number of cases of cutaneous leishmaniasis reported through the study period was 589,913. The annual incidence of CL was estimated to be 30.9 per 100,000 in Iranian population. We also demonstrated that Cutaneous leishmaniasis most prominently occurs in regions with dry and desert climates as well as in central parts of Iran. It affected the southwest of Iran between 1983 and 1997, and subsequently developed towards the center and the eastern between 1998 and 2013. Disease hotspots were focused in the provinces of Yazd, Khozestan and Kohgiloyeh-Boyer-Ahmad (p<0.05). No pattern of spatial clustering was observed., Conclusion: Cutaneous leishmaniasis is a major health problem which could be a serious threat for inhabitants who live in high-risk provinces of Iran; much more resources need to be allocated in these areas, to warrant the prevention as well as effectively management of this disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Cutaneous Leshmaniasis (CL), a parasitic skin infection caused by Leishmania species, is endemic in some regions of Iran. In this study, the effect of location on the incidence and distribution of CL in Iran was studied., Methods: We collected datas including the number of Cutaneous Leishmaniasis cases and populations at-risk of disease in Iran's different provinces reported by the Iranian ministry of health and the National Bureau of Statistics, respectively. Spatial modeling was performed using Arc GIS software. Descriptive maps, hotspot analysis, and high/low clustering analysis were used to demonstrate distribution of the cutaneous leishmaniasis, to determine regions at risk of disease's incidence, and to reach the most appropriate method for clustering of disease., Results: The total number of cases of cutaneous leishmaniasis reported through the study period was 589,913. The annual incidence of CL was estimated to be 30.9 per 100,000 in Iranian population. We also demonstrated that Cutaneous leishmaniasis most prominently occurs in regions with dry and desert climates as well as in central parts of Iran. It affected the southwest of Iran between 1983 and 1997, and subsequently developed towards the center and the eastern between 1998 and 2013. Disease hotspots were focused in the provinces of Yazd, Khozestan and Kohgiloyeh-Boyer-Ahmad (p<0.05). No pattern of spatial clustering was observed., Conclusion: Cutaneous leishmaniasis is a major health problem which could be a serious threat for inhabitants who live in high-risk provinces of Iran; much more resources need to be allocated in these areas, to warrant the prevention as well as effectively management of this disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Zoonotic cutaneous leishmaniasis (ZCL), caused by Leishmania major, is a common zoonotic vector-borne disease in Iran. Close contact with infected reservoir hosts increases the probability of transmission of Leishmania parasite infections to susceptible humans. Four gerbil species (Rodentia: Gerbillidae) serve as the main reservoir hosts for ZCL in different endemic foci of Iran. These species include Rhombomys opimus, Meriones libycus, Meriones hurrianae and Tatera indica; while notable infection has been reported in Nesokia indica as well. The purpose of this study is to model the distribution of these reservoirs to identify the risk areas of ZCL. A data bank was developed including all published data during the period of 1970-2015. Maximum entropy model was used to find the most appropriate ecological niches for each species. The areas under curve obtained were 0.961, 0.927, 0.922, 0.997 and 0.899, instead of 1, for training test in R. opimus, M. libycus, T. indica, M. hurrianae and N. indica, respectively. The environmental variable with the highest gain when used in isolation was slope for R. opimus and N. indica, annual mean temperature for M. libycus, and seasonal precipitation for T. indica and M. hurrianae. Summation of presence probabilities for three main species, i.e., R. opimus, M. libycus and T. indica revealed favorable ecological niches in wide areas of 16 provinces. This is the first study to predict the distribution of ZCL reservoir hosts in Iran. Climatology and topography variables had high contributions toward the prediction of potential distribution of the main reservoir species; therefore, as climate changes, the models should be updated periodically with novel data, and the results should be used in disease-monitoring programs., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Clinically infected dogs have been identified as the main reservoir hosts of visceral leishmaniasis (VL) caused by Leishmania infantum in the Mediterranean region. The objective of this study was to determine the potential of asymptomatic infected dogs compared with symptomatic ones as a source of L. infantum infection to golden hamster. For this purpose, anti-Leishmania antibodies were detected with direct agglutination test (DAT) in 13 symptomatic (7 seropositive =>or=1:320) and 53 asymptomatic (9 seropositive =>or=1:320 and 44 seronegative =<1:320) ownership dogs. DNA of Leishmania sp. was extracted from skin and peripheral blood tissues of each dog and tested by PCR. Sixty-six Syrian golden hamsters (Mesocricetus auratus) were used for the determination of infectivity and pathogenicity of L. infantum, isolated from the dogs. We used the internal transcribed spacer 2 (ITS 2) rDNA sequence analysis. The results showed that 22 and 11 out of 66 inoculated golden hamsters were positive by PCR and parasitological examinations, respectively. From 22 PCR positive hamsters, 17 were related to asymptomatic dogs and 5 were from symptomatic ones. There was no significant difference between symptomatic and asymptomatic dogs in producing Leishmania infection in the susceptible animal model (P=0.66). Smears and cultures of 5 dogs from 13 symptomatic dogs (38.5%) and 6 dogs from 53 asymptomatic ones (11.3%) were found to be positive at parasitological examination. All the L. infantum isolates from symptomatic and asymptomatic dogs were similar in sequencing. In conclusion, asymptomatic infected dogs as well as symptomatic ones can harbor L. infantum in their blood and skins which are virulent and infectious for inoculated golden hamster.