Forms Of Leishmaniasis Research Articles

Molecular Identification of Leishmania Species in Phlebotomus alexandri (Diptera: Psychodidae) in Western Iran

Background:Visceral and cutaneous leishmaniasis are common in some areas of Iran and consider as health problems. Phlebotomus alexandri has been incriminated as a suspected vector for the both form of leishmaniasis.Methods:This study was carried out in 4 western provinces of Iran. Sand flies were collected using sticky traps and light traps from indoor and outdoor resting places. Nested PCR was employed to detect Leishmania parasites among collected sand flies.Results:Seven hundred and twenty two P. alexandri females were collected and pooled in 179 batches. Results of nested PCR showed, out of 9 samples from East Azerbaijan Province, only one sample was infected by Leishmania infantum. Of 34 individual and pooled samples from Kermanshah Province, only one pooled sample was infected with Leishmania major and among 30 individual and pooled samples in Fars Province, five specimens were infected by L. major, L. infantum, Leishmania donovani and Leishmania tropica. Furthermore, out of 108 individual and pooled samples from Khuzestan Province, 10 samples showed infection with L. major and L. infantum.Conclusion:The results of this study showed that P. alexandri is more active in hot zones than in moderate zones and this species may be considered as a permissive species.

Leishmania spp. seropositivity in Austrian soldiers returning from the Kosovo.

SummaryLeishmaniasis is a severe vector-borne disease with two main clinical forms, visceral leishmaniasis and cutaneous leishmaniasis. Both forms of leishmaniasis are also endemic in Mediterranean countries including the Balkan region from where mainly visceral leishmaniasis is reported. Austrian soldiers returning from Kosovo were screened for anti-Leishmania antibodies to assess the risk of infection during operations. Anti-Leishmania antibodies were detected in more than 20% of the soldiers investigated, which indicates a considerable risk of infection during missions in this area and thus suggests the application of protective measures.Electronic supplementary materialThe online version of this article (10.1007/s00508-019-01598-5) contains supplementary material, which is available to authorized users.

In vitro Assessment of Camphor Hydrazone Derivatives as an Agent Against Leishmania amazonensis

Due to serious problems with the treatment of leishmaniasis all around the world, here is an urgent need in the search for new drugs that are more effective and safer for the treatment of the various forms of leishmaniasis. Actual therapy is limited and lacks sufficient efficacy due to incomplete elimination of the parasites form of patients. In this sense, we decided to evaluate, by first-time, a series of seventeen camphor hydrazone derivatives (2a-2p) against Leishmania amazonensis. The compounds previously synthesized from camphor, an abundant natural compound, were evaluated in vitro against the extra and intracellular forms of Leishmania amazonensis, and murine macrophages. The majority of compounds, fourteen, displayed activity against the intracellular form of the parasite (amastigote) with IC50 values ranging from 21.78 to 58.23µM, being six compounds active for both forms of the parasite. The compound 2i exhibited higher activity against the amastigote form with the value of IC50 (21.78µM) close to standard utilized miltefosine (12.74µM) and selectivity index of at least 6.9. Six compounds displayed activity against promastigote form of Leishmania amazonensis 2g, 2j-2n (41.17-69.59µM), with the compound 2m being the more active with IC50 = 41.17µM, 1.9 times less active than the reference drug (IC50 = 21.39µM). The compound 2m was the more selective to this form, with a selectivity index of at least 3.6. All the compounds were non-cytotoxic to macrophages. Most compounds showed activity against amastigote form of Leishmania amazonensis, being that they were not cytotoxic to macrophage at the maximum tested concentration, showing the selective property of these compounds. Since amastigotes are the parasite stages that cause the disease in humans, these results highlight the antileishmanial effect of the compounds. This study indicates the possible development of candidates to leishmanicidal drugs from an abundant natural compound of easy access.

Imported cutaneous leishmaniasis: molecular investigation unveils Leishmania major in Bangladesh

BackgroundThe main clinical forms of leishmaniasis in Bangladesh are visceral leishmaniasis and post-kala-azar dermal leishmaniasis, which are caused by Leishmania donovani. Imported cutaneous leishmaniasis (CL) is emerging globally due mainly to increased human mobility. In recent years, several imported CL cases have also been reported in Bangladesh. Sporadic atypical cases of CL can be challenging for diagnosis and clinical management, while occurrence of infection on a frequent basis can be alarming. We report of a case of a Bangladeshi temporary-migrant worker who, upon return, presented development of skin lesions that are characteristic of CL.MethodsA serum sample was collected and tested with an rK39 immunochromatographic test. Nucleic acid from skin biopsy derived culture sample was extracted and screened with a real-time PCR assay which targets the conserved REPL repeat region of L. donovani complex. The internal transcribed spacer 2 region of the ribosomal RNA gene cluster was amplified and sequenced.ResultsThe suspect had a history of travel in both CL and VL endemic areas and had a positive rK39 test result. Based on clinical presentation, travel history and demonstration of the parasite in the skin biopsy, CL was diagnosed and the patient underwent a combination therapy with Miltefosine and liposomal amphotericin B. While typical endemic species were not detected, we identified Leishmania major, a species that, to our knowledge, has never been reported in Bangladesh.ConclusionsProper monitoring and reporting of imported cases should be given careful consideration for both clinical and epidemiological reasons. Molecular tests should be performed in diagnosis to avoid dilemma, and identification of causative species should be prioritized.

A highly sensitive modified nested PCR to enhance case detection in leishmaniasis

BackgroundHuman leishmaniasis is one of the major parasitic diseases with worldwide distribution. Sri Lanka is a recently established focus of leishmaniasis caused by a variant Leishmania donovani. Early case detection and management is a main approach identified for L. donovani control in the regional leishmaniasis elimination drive. Usefulness of light microscopy and in-vitro culture are limited in chronic, atypical or treated lesions though timely and accurate detection of all light microscopy/in-vitro culture negative cases of all forms of leishmaniasis is necessary for treatment. Timely treatment is important to minimize risk for death in visceral disease and undesired sequelae of long standing infection and illness on both patients and community. We described a 100% sensitive, Leishmania spp. specific modified version of a nested PCR (Mo-STNPCR) that also minimizes carry over and cross contaminations while facilitate investigation of light microscopy and in-vitro culture negative clinically suggestive cases of leishmaniasis.MethodsLeishmania DNA was amplified using previously published P221: 5′-GGTTCCTTTCCTGATTTACG-3′ and P332: 5′-GGCCGGTAAAGGCCGAATAG-3’outer primers followed by a nested reaction using P223: 5′-TCCCATCGCAACCTCGGTT-3′ and P333: 5′-AAGCGGGCGCGGTGCTG-3′ inner primers that by passes the requirement of tube handling between the two steps of the conventional nested PCR. Leishmania DNA was detected in a range of infected tissue material. Infected material from patients with cutaneous leishmaniasis (n = 30), visceral leishmaniasis (n = 10) and from a control group including patients with non-leishmanial skin diseases (n = 10), other systemic diseases (n = 10) and healthy individuals (n = 10) were examined with Mo-STNPCR. Results were further compared with those of light microscopy and in-vitro culture.ResultsMo-STNPCR method was 100% sensitive and 100% specific for diagnosis of leishmaniasis. Light microscopy and in-vitro culture were positive in 75.0% (n = 30/40) and 72.5% (n = 29/40) samples respectively where combined results of them gave 87.5% (n = 35/40) sensitivity. Mo-STNPCR did not cross react with control samples. Furthermore, Mo-STNPCR reduces the risk of cross-contaminations and carry over contaminations since the full reaction is carried out without opening the tubes. Per patient cost was calculated as 22 USD while the same was 3 and 6 USD for light microscopy and in-vitro culture respectively.ConclusionMo-STNPCR method is a useful tool in detecting leishmaniasis in minority of cases that go undetected by first line investigations.

Effectiveness of Paromomycin on Cutaneous Leishmaniasis in Iran: A Systematic Review and Meta-Analysis.

Some treatment reported for cutaneous leishmaniasis. The studies examined the impact of the paromomycin has different characteristics and results. The aim of the present study was to conduct a systematic review and meta-analysis of all randomized clinical trials evaluating the effectiveness of paromomycin in the treatment of cutaneous leishmaniasis in Iran. Literature search was conducted using MEDLINE, Web of Science, Scopus, Scientific Information Database, IranMedex, Magiran, Iranian Registry of Clinical Trials (from February 2000 to May 2016), and references cited in the text of selected studies. Search terms used were "paromomycin", "cutaneous leishmaniasis", "randomized"," aminosidine", "controlled trial", and "clinical trial". Random effects models were used to calculate the measure of association, with 95% confidence intervals, to analyze the efficacy of paromomycin in the treatment of cutaneous leishmaniasis. Initial search yielded 76 citations. Of these original results, 9 met our specific selection criteria. Four of the randomized controlled trials compared the efficacy of paromomycin in the treatment of cutaneous leishmaniasis with that of a placebo; they were included in the meta-analysis. The success rate of treatment with paromomycin was higher than that with the placebo (pooled RR=4.50, 95% CI: 2.54 to 8.02; P=0.001 and I2=26.7%), whereas the difference with the non-placebo treatments was nonsignificant (pooled RR=0.79, 95% CI: 0.58 to 1.073; P=0.131 and I2=83.3%). No significant difference was observed between paromomycin and the other treatments in their effectiveness in the treatment of cutaneous leishmaniasis. Because no single drug is effective against all the forms of leishmaniasis, we suggest multidrug therapy.

Prevalence of Leishmania species among patients with cutaneous leishmaniasis in Qassim province of Saudi Arabia

BackgroundLeishmaniasis is a parasitic infection endemic in more than ninety countries of the world. The cutaneous leishmaniasis (CL) is a most common form of leishmaniasis and it remains to be a major public health issue in Saudi Arabia. This study was undertaken to investigate the Leishmania species responsible for CL infection in different provinces of Qassim, Saudi Arabia.MethodsSkin biopsies were obtained from CL patients and DNA was extracted using the Magna pure system. Leishmania species were identified by highly specific/sensitive quantitative and qualitative PCR.ResultsOut of total 206 CL biopsies, 49.5% biopsies were found to be positive for Leishmania major (L. major), 28.6% biopsies were positive for Leishmania tropica (L. tropica), 3.9% were found to be positive for Leishmania infantum/donovani (L. infantum/donovani). Not only have these, all tested CL biopsies showed negative test for Leishmania mexicana (L. mexicana) and Leishmania viannia (L. viannia).ConclusionsThis is the first comprehensive study that shows the majority of CL in Qassim was caused by L. major and L. tropica. To the best of our knowledge, this is the very first report that shows the occurrence of L. infantum/donovani in Saudi Arabia. This requires higher alert to the Ministry of Health of Saudi Arabia to take proactive actions in preventing the onset of L. major, L. tropica, L. infantum and L. donovani infections.

Environmental risk factors of leishmaniasis in Bahia State, Brazil using NASA Earth observation satellites

NASA’s Earth Observing Satellites (EOS) were used to calculate three vegetation indices, extract precipitation and elevation data, and then evaluate their applicability for assessing risk of visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) in Bahia State, Brazil. Regression models showed that either form of leishmaniasis can be predicted by NDVI, NDMI, NDWI data products and TRMM) precipitation data (R2= 0.370; p<0.001). Elevation was not significantly associated with the distribution of either VL or CL. In areas of high annual precipitation, CL was 3.6 times more likely to occur than VL. For vegetative moisture (NDMI), CL was 2.11 times more likely to occur than VL. Odds of CL occurrence increased to 5.5 times when vegetation (NDVI) and 13.5 times when liquid water content of vegetation canopies (NDWI) was considered. Areas at risk of CL and VL were mapped based on the selected explanatory variables. Accuracy of models were assessed using area under the receiver operating characteristic curve (AUC=0.72). We propose that statewide scale risk models based on use of EOS products will be a useful tool at 1 km2 spatial resolution to enable health workers to identify and target high risk areas to prevent transmission of leishmaniasis.

Ethnopharmacology Study of Plants from Atlantic Forest with Leishmanicidal Activity.

Leishmaniasis is an infectious disease caused by a protozoan belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and patient's health condition. The outcomes can range from single cutaneous lesions to lethal visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and, in some cases, the second-line drug, amphotericin B, is used. Beside the toxicity of both classes of drugs, in some areas of the world, parasites are resistant to antimonial. These detrimental features make fundamental the discovery and characterization of new drugs or plant extracts with leishmanicidal effects. Brazil is a well-known country for its biodiversity. Additionally, the common knowledge inherited for generations in small villages makes Brazil a source of new information and resources for the discovery and development of new drugs. Based on ethnopharmacology, elderlies were interviewed about plants they commonly used for skin diseases and infections. Five native plants from Atlantic forest were indicated; EtOH and n-hexane extracts were prepared with the vegetative organs of the plants and assayed against promastigote and amastigote forms of L. (L.) amazonensis. The major molecules of each extract were detected using qualitative nuclear magnetic resonance. Among all tested extracts, the n-hexane extract from the leave of Eugenia uniflora (Myrtaceae), enriched in myricitrin and quercitrin flavonoids, was the most effective against L. (L.) amazonensis amastigotes. This data supports the ethnopharmacology approach as a successful tool for the discovery of new drugs with leishmanicidal effects.

A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica.

There is no effective treatment modality available against different forms of leishmaniasis. Therefore, the aim of this study was to improve the penetration and efficacy of selenium and glucantime coupled with niosomes and compared them with their simple forms alone on in vitro susceptibility assays. In this study, the niosomal formulations of selenium and in combination with glucantime were prepared. The size and morphology of the niosomal formulations were characterized and the effectivity of the new formulation was also evaluated using in vitro MTT assay, intra-macrophage model, and gene expression profile. From the results obtained, no cytotoxicity effect was observed for niosomal and simple forms of drugs, as alone or in combination. Niosomal formulations of the drugs significantly showed more inhibitory effects (P≤0.001) than the simple drugs when the selectivity index was considered. The gene expression levels of Interleukin (IL-10) significantly decreased, while the level of IL-12 and metacaspase significantly increased (P≤0.001). The results of the present study showed that selenium plus glucantime niosome possess a potent anti-leishmanial effect and enhanced their lethal activity as evidenced by the in vitro experiments.

Activity of Fenticonazole, Tioconazole and Nystatin on New World Leishmania Species.

Leishmaniasis is an infectious disease caused by protozoal parasites belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and health condition of patients. It can range from single cutaneous lesion until deadly visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and in some cases, the second-line drug, amphotericin B is used. Beside the toxicity of both drugs, parasites can be resistant to antimonial in some areas of the world. This makes fundamental the characterization of new drugs with leishmanicidal effect. Thus, the aim of the present work was to study the leishmanicidal activity of drugs able to interfere with ergosterol pathway (fenticonazole, tioconazole, nystatin, rosuvastatin and voriconazole) against promastigote and amastigote forms of L.(L.) amazonensis, L.(V.) braziliensis and L.(L.) infantum, and its impact on morphological and physiological changes in L.(L.) amazonensis or in host macrophages. We observed that fenticonazole, tioconazole and nystatin drugs eliminated promastigote and intracellular amastigotes, being fenticonazole and nystatin the most selective towards amastigote forms. Rosuvastatin and voriconazole did not present activity against amastigote forms of Leishmania sp. In addition, the drugs with leishmanicidal activity interfered with parasite mitochondrion. Although drugs did not stimulate NO and H2O2, specially fenticonazole was able to alkalize infected host macrophages. These results suggest well established and non-toxic antifungal drugs can be repurposed and used in leishmaniasis.

Chronic Skin Lesions as the Presentation of Diffuse Cutaneous Leishmaniasis in the HIV-infected Woman: A Case Report and Review of Literatures

Background: Cutaneous leishmaniasis (CL) is the most form of leishmaniasis that caused by intracellular parasites, Leishmania. Case Report: A 39-year-old woman, known case of HIV infection, presented with a 6-month history of skin lesions initially on her face, then extending onto the chest, abdomen, and extremities. Laboratory examinations revealed leukopenia and a CD4 cell count of 280 cells / mm3. A biopsy was taken from skin lesions, and histopathological studies showed aggregates of macrophages filled with numerous Leishman bodies, the diagnosis of diffuse CL was confirmed. Consequently, she received liposomal amphotericin B (total dose of 40 mg/kg) as a case of diffuse CL. The skin lesions showed significant improvement after completion of treatment. Conclusion: Diffuse CL should be considered as a differential diagnosis in all patients with diffuse skin lesions mainly in the cases that suffer from disorders of cell-mediated immunity. [GMJ.2019;inpress:e1297]

Chronic Skin Lesions as the Presentation of Diffuse Cutaneous Leishmaniasis in the HIV-Infected Woman: A Case Report and Review of Literatures

Background: Cutaneous leishmaniasis (CL) is the most form of leishmaniasis that caused by intracellular parasites, Leishmania. Case Report: A 39-year-old woman, known case of HIV infection, presented with a 6-month history of skin lesions initially on her face, then extending onto the chest, abdomen, and extremities. Laboratory examinations revealed leukopenia and a CD4 cell count of 280 cells / mm3. A biopsy was taken from skin lesions, and histopathological studies showed aggregates of macrophages filled with numerous Leishman bodies, the diagnosis of diffuse CL was confirmed. Consequently, she received liposomal amphotericin B (total dose of 40 mg/kg) as a case of diffuse CL. The skin lesions showed significant improvement after completion of treatment. Conclusion: Diffuse CL should be considered as a differential diagnosis in all patients with diffuse skin lesions mainly in the cases that suffer from disorders of cell-mediated immunity.[GMJ.2019;8:e1294]

Leishmania tropica: What we know from its experimental models.

Leishmania tropica causes different forms of leishmaniasis in many parts of the world. Animal models can help to clarify the issues of pathology and immune response in L. tropica infections and can be applied to the control, prevention and treatment of the disease. The aim of this article is to summarize published data related to experimental models of this parasite, presenting an overview of the subject. We also present in brief the epidemiology, transmission and human manifestation of L. tropica infection. Mice, rats and hamsters have been used for experimental models of L. tropica infection. Main findings of the published studies show that: (1) Hamsters are the best animal model for L. tropica infection, with the drawback of being outbred hence not suitable for many studies. (2) L. tropica infection causes a non-ulcerative and chronic pathology as cutaneous form in mice and usually visceral form in hamsters. (3) L. tropica infection in mice results in a weaker immune response in comparison to Leishmania major. (4) While the Th1 responses are evoked against L. tropica, Th2 responses do not explain the outcomes of this infection, and IL-10 and TGF-β are two main suppressive cytokines. (5) The host genotype affects the immune response and disease outcome of L. tropica infection and the dose, strain, routes of inoculation, and sex of the host are among the factors affecting disease outcome of this species.

IN VITRO ANTI-LEISHMANIAL ACTIVITY AGAINST CUTANEOUS LEISHMANIA PARASITES AND PRELIMINARY PHYTOCHEMICAL ANALYSIS OF FOUR YEMENI MEDICINAL PLANTS

Cutaneous leishmaniasis is one form of leishmaniasis that chiefly infected the poor sections of the society. The prototypical therapeutic interventions in vogue are handicapped due to toxicity and an alarming increase in drug resistance. Furthermore, the absence of vaccines has raised the quest for alternative therapies. So, the aim of our study was to assess the anti-leishmanial activity of Euphorbia cactus Ehrenb, Euphorbia ammak Forssk, Euphorbia inarticulate Schweinf, and Pergularia tomentosa L. The extracts of plants were prepared by maceration method and by Soxhlet extractor. The extracts were dried and re-dissolved in 2% dimethyl sulfoxide (DMSO) 1% solvent. Leishmania spp. cells were then tested with serial concentrations (15.6 μgml-1 to 500 μg ml-1 ) of the extracts, using the 3-(4,5-dimethylthazolk-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. All experiments were performed in triplicate and analyzed by ANOVA test. The optical density values as measured by Enzyme-Linked Immunosorbent Assay (ELISA) were used to calculate the IC50 values. The results indicated that the methanolic latex extract of Euphorbia cactus Ehrenb, Euphorbia ammak Forssk had potent anti-leishmanial activity against the promastigotes of Leishmania spp. based on a dose-dependent response analysis. The IC50 values for Euphorbia cactus Ehrenb and Euphorbia ammak Forssk after 24h incubation against Leishmania spp. promastigotes were less than <15.6 μgml-1. Furthermore, the phytochemical analysis of methanolic extracts showed the presence of alkaloids, phytosterols, phenols, saponins, and flavonoids in which these components have been proven previously to be the active compounds against Leishmania parasite. In conclusion, the present study reveals that latex extract of Euphorbia cactus Ehrenb and Euphorbia ammak Forssk contain active compounds that have anti-leishmanial activity, which could serve as an alternative agent in the treatment of Cutaneous leishmaniasis, but further studies would, therefore, be needed to assess the activity of these materials of this plants in vivo clinical response and study their toxicity on cell lines.

Imported cutaneous leishmaniasis cases detected in truck drivers in Hatay

Leishmaniasis, seen in tropical and subtropical regions, is an infectious disease caused by the protozoan parasite Leishmania species. There are three main forms of leishmaniasis: cutaneous, mucocutaneous and visceral leishmaniasis. Cutaneous leishmaniasis (CL) has become an increasing problem as the number of travels around the world increases and people go to work in endemic areas. Turkey has received great numbers of immigrants in recent years, from its neighboring countries like Iraq, Islamic Republic of Iran, Afghanistan, Turkmenistan and the Syrian Arab Republic because of the political instabilities in these countries as well as the job opportunities caused by large-scale development projects undertaken by Turkey. In this report, imported CL cases detected in five truck drivers transporting from Hatay to Turkmenistan, Syria, Saudi Arabia, Iran and Georgia, Uzbekistan and Azarbaijan countries were presented. The patients admitted to Mustafa Kemal University, Faculty of Medicine Dermatology Policlinic, with wound complaints on their bodies were directed to the Department of Parasitology to obtain smear samples from their wounds. The age range of the patients were 38 to 43 years. Patients with wound trail for a period ranging from one month to one year had a number of lesions varying between 2-7 and in all cases, a smear preparation was prepared from the lesions for diagnostic purposes. Clinical material obtained from five patients with pre-diagnosis of CL was firstly examined with Giemsa stain. Samples taken from the patients were inoculated into modified NNN (Novy-MacNeal-Nicolle) medium for the evaluation of the presence of the promastigotes. Promastigotes obtained from the inoculated medium were also genotyped using the ITS1 region. In all of the slides prepared from the clinical material taken from the patients amastigotes were determined. The growth of promastigotes were observed in only three of the clinical specimen inoculated media. The genotyped three species were Leishmania tropica, Leishmania infantum/donovani and Leishmania major. In this study, the importance of support for the diagnosis of different microbiological methods used in the diagnosis of leishmaniasis infection which occurred during the outbreaks of the disease has been put forward. In addition, it was aimed to draw attention to the importance of imported CL cases in our country diagnosed in five truck drivers making transportation from Hatay to Turkmenistan, Syria, Saudi Arabia, Iran, Georgia, Uzbekistan and Azerbaijan.

Biological Evaluation and X-ray Co-crystal Structures of Cyclohexylpyrrolidine Ligands for Trypanothione Reductase, an Enzyme from the Redox Metabolism of Trypanosoma.

The tropical diseases human African trypanosomiasis, Chagas disease, and the various forms of leishmaniasis are caused by parasites of the family of trypanosomatids. These protozoa possess a unique redox metabolism based on trypanothione and trypanothione reductase (TR), making TR a promising drug target. We report the optimization of properties and potency of cyclohexylpyrrolidine inhibitors of TR by structure-based design. The best inhibitors were freely soluble and showed competitive inhibition constants (Ki ) against Trypanosoma (T.) brucei TR and T. cruzi TR and in vitro activities (half-maximal inhibitory concentration, IC50 ) against these parasites in the low micromolar range, with high selectivity against human glutathione reductase. X-ray co-crystal structures confirmed the binding of the ligands to the hydrophobic wall of the "mepacrine binding site" with the new, solubility-providing vectors oriented toward the surface of the large active site.

Infection of Human Monocytes with Leishmania infantum Strains Induces a Downmodulated Response when Compared with Infection with Leishmania braziliensis.

Human infection with different species of Leishmania leads to distinct clinical manifestations, ranging from relatively mild cutaneous (Leishmania braziliensis) to severe visceral (Leishmania infantum) forms of leishmaniasis. Here, we asked whether in vitro infection of human monocytes by Leishmania strains responsible for distinct clinical manifestations leads to early changes in immunological characteristics and ability of the host cells to control Leishmania. We evaluated the expression of toll-like receptors and MHC class II molecules, cytokines, and Leishmania control by human monocytes following short-term infection with L. braziliensis (M2904), a reference strain of L. infantum (BH46), and a wild strain of L. infantum (wild). The induction of TLR2, TLR9, and HLA-DR were all lower in L. infantum when compared with L. braziliensis-infected cells. Moreover, L. infantum-infected monocytes (both strains) produced lower TNF-alpha and a lower TNF-alpha/IL-10 ratio, resulting in a weaker inflammatory profile and a 100-fold less effective control of Leishmania than cells infected with L. braziliensis. Our results show that L. infantum strains fail to induce a strong inflammatory response, less activation, and less control of Leishmania from human monocytes, when compared with that induced by L. braziliensis infection. This functional profile may help explain the distinct clinical course observed in patients infected with the different Leishmania species.

Potent antileishmanial activity of chitosan against Iranian strain of Leishmania major (MRHO/IR/75/ER): In vitro and in vivo assay.

Leishmaniasis is one of the major neglected zoonotic parasitic diseases whose treatment and control is very complex. Pentavalent antimonials remain the primary drugs against different forms of leishmaniasis, however, resistance to antimony and its toxic effects has necessitated the development of alternative medications such as use of medicinal plants and natural compounds. The aim of the current study was to assess the in vitro and in vivo activities of chitosan as a natural resource against Leishmania major. Low molecular weight chitosan, with 95% degree of deacetylation was melted in normal saline to a final concentration of 50, 100, 200 and 400 μg/ml. Then, the promastigotes of L. major (Iranian strain) were added to the wells of 96-well plate and 20 μl of each concentration was added to the RPMI 1640 medium. Live and dead promastigotes were counted after adding 0.1% eosin stain. The efficacy of the chitosan was also examined in BALB/c mice infected with Iranian strain of L. major. All in vitro experiments were performed in triplicate and the results of in vitro and in vivo tests were compared to the acetic acid and NaOH as negative control and glucantime as positive control. The low molecular weight chitosan was completely effective at concentrations of 100, 200 and 400 μg/ml on promastigotes of L. major after 180 min of application. Moreover, in the in vivo study, the mean size of dermal lesions significantly decreased in the groups treated with the chitosan compared to the control group. According to the results of the study, it can be concluded that chitosan is a potent active compound against L. major and could be evaluated as a new antileishmanial drug in the future.

Immune Checkpoint Targets for Host-Directed Therapy to Prevent and Treat Leishmaniasis.

Leishmaniasis encompasses a group of diseases caused by protozoan parasites belonging to the genus Leishmania. These diseases range from life threatening visceral forms to self-healing cutaneous lesions, and each disease manifestations can progress to complications involving dissemination of parasites to skin or mucosal tissue. A feature of leishmaniasis is the key role host immune responses play in disease outcome. T cells are critical for controlling parasite growth. However, they can also contribute to disease onset and progression. For example, potent regulatory T cell responses can develop that suppress antiparasitic immunity. Alternatively, hyperactivated CD4+ or CD8+ T cells can be generated that cause damage to host tissues. There is no licensed human vaccine and drug treatment options are often limited and problematic. Hence, there is an urgent need for new strategies to improve the efficacy of current vaccine candidates and/or enhance both antiparasitic drug effectiveness and subsequent immunity in treated individuals. Here, we describe our current understanding about host immune responses contributing to disease protection and progression in the various forms of leishmaniasis. We also discuss how this knowledge may be used to develop new strategies for host-directed immune therapy to prevent or treat leishmaniasis. Given the major advances made in immune therapy in the cancer and autoimmune fields in recent years, there are significant opportunities to ride on the back of these successes in the infectious disease domain. Conversely, the rapid progress in our understanding about host immune responses during leishmaniasis is also providing opportunities to develop novel immunotherapy strategies that could have broad applications in diseases characterized by inflammation or immune dysfunction.