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1
Kostygov, Alexei Y., Danyil Grybchuk, Yulia Kleschenko, Daniil S. Chistyakov, Alexander N. Lukashev, Evgeny S. Gerasimov, and Vyacheslav Yurchenko. "Analyses of Leishmania-LRV Co-Phylogenetic Patterns and Evolutionary Variability of Viral Proteins." Viruses 13, no. 11 (November 19, 2021): 2305. http://dx.doi.org/10.3390/v13112305.
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Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins.
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Soni, Mohini, and J. Venkatesh Pratap. "Development of Novel Anti-Leishmanials: The Case for Structure-Based Approaches." Pathogens 11, no. 8 (August 22, 2022): 950. http://dx.doi.org/10.3390/pathogens11080950.
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The neglected tropical disease (NTD) leishmaniasis is the collective name given to a diverse group of illnesses caused by ~20 species belonging to the genus Leishmania, a majority of which are vector borne and associated with complex life cycles that cause immense health, social, and economic burdens locally, but individually are not a major global health priority. Therapeutic approaches against leishmaniasis have various inadequacies including drug resistance and a lack of effective control and eradication of the disease spread. Therefore, the development of a rationale-driven, target based approaches towards novel therapeutics against leishmaniasis is an emergent need. The utilization of Artificial Intelligence/Machine Learning methods, which have made significant advances in drug discovery applications, would benefit the discovery process. In this review, following a summary of the disease epidemiology and available therapies, we consider three important leishmanial metabolic pathways that can be attractive targets for a structure-based drug discovery approach towards the development of novel anti-leishmanials. The folate biosynthesis pathway is critical, as Leishmania is auxotrophic for folates that are essential in many metabolic pathways. Leishmania can not synthesize purines de novo, and salvage them from the host, making the purine salvage pathway an attractive target for novel therapeutics. Leishmania also possesses an organelle glycosome, evolutionarily related to peroxisomes of higher eukaryotes, which is essential for the survival of the parasite. Research towards therapeutics is underway against enzymes from the first two pathways, while the third is as yet unexplored.
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Jain, Surbhi, Utkarsha Sahu, Awanish Kumar, and Prashant Khare. "Metabolic Pathways of Leishmania Parasite: Source of Pertinent Drug Targets and Potent Drug Candidates." Pharmaceutics 14, no. 8 (July 30, 2022): 1590. http://dx.doi.org/10.3390/pharmaceutics14081590.
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Leishmaniasis is a tropical disease caused by a protozoan parasite Leishmania that is transmitted via infected female sandflies. At present, leishmaniasis treatment mainly counts on chemotherapy. The currently available drugs against leishmaniasis are costly, toxic, with multiple side effects, and limitations in the administration route. The rapid emergence of drug resistance has severely reduced the potency of anti-leishmanial drugs. As a result, there is a pressing need for the development of novel anti-leishmanial drugs with high potency, low cost, acceptable toxicity, and good pharmacokinetics features. Due to the availability of preclinical data, drug repurposing is a valuable approach for speeding up the development of effective anti-leishmanial through pointing to new drug targets in less time, having low costs and risk. Metabolic pathways of this parasite play a crucial role in the growth and proliferation of Leishmania species during the various stages of their life cycle. Based on available genomics/proteomics information, known pathways-based (sterol biosynthetic pathway, purine salvage pathway, glycolysis, GPI biosynthesis, hypusine, polyamine biosynthesis) Leishmania-specific proteins could be targeted with known drugs that were used in other diseases, resulting in finding new promising anti-leishmanial therapeutics. The present review discusses various metabolic pathways of the Leishmania parasite and some drug candidates targeting these pathways effectively that could be potent drugs against leishmaniasis in the future.
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Carstens-Kass, Jessica, Kayla Paulini, Patrick Lypaczewski, and Greg Matlashewski. "A review of the leishmanin skin test: A neglected test for a neglected disease." PLOS Neglected Tropical Diseases 15, no. 7 (July 22, 2021): e0009531. http://dx.doi.org/10.1371/journal.pntd.0009531.
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The leishmanin skin test (LST) has been used for decades to detect exposure and immunity to the parasite Leishmania, the causative agent of the neglected tropical disease leishmaniasis. In the LST, Leishmania antigen (leishmanin) is intradermally injected into the forearm. In an individual who has been previously infected, a delayed-type hypersensitivity (DTH) reaction results in a measurable induration at the site of the injection, indicating that previous exposure to Leishmania has resulted in the development of cell-mediated immunity. LST positivity is associated with long-lasting protective immunity against reinfection, most notably as reported for visceral leishmaniasis (VL). Despite efforts over the past few decades, leishmanin antigen is no longer produced under good manufacturing practice (GMP) conditions anywhere in the world. Consequently, the use of the LST in epidemiological studies has declined in favor of serological and molecular tests. In this review, we provide a historical overview of the LST and justification for the reintroduction of leishmanin. A GMP-grade leishmanin can be used to detect immunity in vivo by the LST and can be investigated for use in an interferon-γ release assay (IGRA), which may serve as an in vitro version of the LST. The LST will be a valuable tool for surveillance and epidemiological studies in support of the VL elimination programs and as a surrogate marker of immunity in vaccine clinical trials. Methods A review of the literature was conducted using PubMed as the primary database, with MeSH terms “leishmanin skin test” OR “Montenegro test” OR “Montenegro skin test.” Articles written in English that describe the history or standardization of leishmanin, the use of leishmanin in an IGRA, or the use of the LST in epidemiological studies or vaccine trials were prioritized in our appraisal of the literature.
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Kurkjian, K. M., L. E. Vaz, R. Haque, C. Cetre-Sossah, S. Akhter, S. Roy, F. Steurer, et al. "Application of an Improved Method for the Recombinant K39 Enzyme-Linked Immunosorbent Assay To Detect Visceral Leishmaniasis Disease and Infection in Bangladesh." Clinical Diagnostic Laboratory Immunology 12, no. 12 (December 2005): 1410–15. http://dx.doi.org/10.1128/cdli.12.12.1410-1415.2005.
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ABSTRACT Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement = 0.970) and more reliable compared to the original method (kappa = 0.587, P < 0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kala-azar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.
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Khademvatan, Shahram, Kaveh Eskandari, Batool Sadeghi Nejad, and Sedigheh Yusef Naanaie. "Cytotoxic Effects of Artemisia Dracunculus L. and Heracleum Persicum Desf. Extracts on Leishmania major and Leishmania infantum Promastigotes Using MTT Assay." International Journal of Enteric Pathogens 9, no. 2 (May 29, 2021): 59–63. http://dx.doi.org/10.34172/ijep.2021.12.
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Background: Leishmaniasis is a parasitic disease that occurs in subtropical and tropical regions with approximately 350 million people worldwide and 2 million new cases annually. The annual increase in cutaneous leishmaniasis (CL) is observed, especially in endemic areas such as Iran. Since there is no effective vaccine, the detection of natural anti-leishmanial products is essential. Objective: The purpose of this study was to evaluate the in vitro anti-leishmanial activity of two herbal medicine including Artemisia dracunculus L. and Heracleum persicum Desf. (Golpar). Materials and Methods: The extracts of selected plants were obtained by maceration, and in vitro anti-leishmanial activity was assayed on Leishmania major and Leishmania infantum promastigotes using colorimetric MTT [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] assay in comparison with glucantime as a reference. Results: Based on the results, 50% inhibitory concentration (IC50) values of selected plants and glucantime solutions were determined at 24, 48, and 72 hours incubation. Further, the anti-leishmanial activity of the leaf extract of A. dracunculus with IC50 values of 1.85 and 3.5 µg/mL and the fruit extract of H. persicum with values of 31.32 and 11.7 µg/mL were evaluated against L. major and L. infantum promastigotes, respectively. Conclusion: These results revealed anti-leishmania properties of the above-mentioned plants and the need to study the effects of these extracts on the Leishmania genus in animal models and in vivo assay in the future.
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Maciej-Hulme, Marissa L., Mark A. Skidmore, and Helen P. Price. "The role of heparan sulfate in host macrophage infection by Leishmania species." Biochemical Society Transactions 46, no. 4 (June 22, 2018): 789–96. http://dx.doi.org/10.1042/bst20170398.
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The leishmaniases are a group of neglected tropical diseases caused by parasites from the Leishmania genus. More than 20 Leishmania species are responsible for human disease, causing a broad spectrum of symptoms ranging from cutaneous lesions to a fatal visceral infection. There is no single safe and effective approach to treat these diseases and resistance to current anti-leishmanial drugs is emerging. New drug targets need to be identified and validated to generate novel treatments. Host heparan sulfates (HSs) are abundant, heterogeneous polysaccharides displayed on proteoglycans that bind various ligands, including cell surface proteins expressed on Leishmania promastigote and amastigote parasites. The fine chemical structure of HS is formed by a plethora of specific enzymes during biosynthesis, with various positions (N-, 2-O-, 6-O- and 3-O-) on the carbon sugar backbone modified with sulfate groups. Post-biosynthesis mechanisms can further modify the sulfation pattern or size of the polysaccharide, altering ligand affinity to moderate biological functions. Chemically modified heparins used to mimic the heterogeneous nature of HS influence the affinity of different Leishmania species, demonstrating the importance of specific HS chemical sequences in parasite interaction. However, the endogenous structures of host HSs that might interact with Leishmania parasites during host invasion have not been elucidated, nor has the role of HSs in host–parasite biology. Decoding the structure of HSs on target host cells will increase understanding of HS/parasite interactions in leishmaniasis, potentiating identification of new opportunities for the development of novel treatments.
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McDowell, Mary Ann, Mary Marovich, Rosalia Lira, Michael Braun, and David Sacks. "Leishmania Priming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent." Infection and Immunity 70, no. 8 (August 2002): 3994–4001. http://dx.doi.org/10.1128/iai.70.8.3994-4001.2002.
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ABSTRACT A major question in the study of leishmaniasis is what dictates clinical disease expression produced by different Leishmania species, i.e., cutaneous versus systemic and healing versus nonhealing. Animal models using a Leishmania species associated with self-limiting cutaneous disease (L. major) have revealed that protective immunity requires CD40/CD40 ligand (CD40L)-dependent, interleukin-12 (IL-12)-driven Th1 responses. We recently showed that L. major can prime human dendritic cells (DCs) for CD40L-triggered IL-12p70 secretion and that these cells can drive a Th1 response in autologous T cells from sensitized individuals. Here we show that in contrast to L. major, Leishmania species responsible for visceral disease (L. donovani), as well as species associated with persistent, cutaneous lesions and occasional systemic disease (L. tropica), did not induce CD40L-dependent IL-12p70 production, despite comparable levels of uptake by DCs. Up-regulated surface expression of CD40 did not correlate with IL-12p70 production, and appreciable CD40L-induced IL-12p40 secretion was observed in uninfected as well as infected DCs, regardless of species. Reverse transcription-PCR analysis confirmed that the production of heterodimeric IL-12 was limited by expression of IL-12p35 mRNA, which was dependent on both a microbial priming signal and CD40 engagement for its high-level induction. The intrinsic differences in the ability of Leishmania species to prime DCs for CD40L-dependent IL-12p70 secretion may account, at least in part, for the evolution of healing and nonhealing forms of leishmanial disease.
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Gogou, Georgia, Olga S. Koutsoni, Panagiotis Stathopoulos, Leandros A. Skaltsounis, Maria Halabalaki, and Eleni Dotsika. "Direct In Vitro Comparison of the Anti-Leishmanial Activity of Different Olive Oil Total Polyphenolic Fractions and Assessment of Their Combined Effects with Miltefosine." Molecules 27, no. 19 (September 21, 2022): 6176. http://dx.doi.org/10.3390/molecules27196176.
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The bioactive compounds present in the edible products of the olive tree have been extensively studied and their favorable effects on various disease risk factors have been demonstrated. The aim of this study was to perform a comparative analysis of the anti-leishmanial effects of total phenolic fractions (TPFs) derived from extra virgin olive oil with different phenolic contents and diverse quantitative patterns. Moreover, the present study investigated their association with miltefosine, a standard anti-leishmanial drug, against both extracellular promastigotes and intracellular amastigotes of a viscerotropic and a dermotropic Leishmania strain. The chemical compositions of TPFs were determined by high performance liquid chromatography with diode array detection (HPLC-DAD). Analysis of parasite growth kinetics, reactive oxygen species production and apoptotic events were determined by microscopy and flow cytometry. Our results revealed that the presence of oleacein (OLEA) and oleocanthal (OLEO) secoiridoids enhances the anti-leishmanial effect of TPF. The association between TPFs and miltefosine was suggested as being additive in Leishmania infantum and Leishmania major promastigotes, and as antagonistic in intracellular amastigotes, as was evaluated with the modified isobologram method. The obtained data verified that TPFs are bioactive dietary extracts with a strong anti-leishmanial activity and highlighted that fractions that are richer in OLEA and OLEO phenolic compounds possess stronger inhibitory effects against parasites. This study may contribute to improving the therapeutic approaches against leishmaniasis.
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Jalaj Kumar Gour and Manoj Kumar Singh. "Leishmanial Excretory-Secretory proteins: A potent vaccine candidate." International Journal of Fundamental and Applied Sciences (IJFAS) 7, no. 1 (March 30, 2018): 18–22. http://dx.doi.org/10.59415/ijfas.v7i1.118.
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Leishmaniasis is caused by the intracellular parasite of the genus Leishmania. It now becomes a major public health problem in many countries all over the world. It is always better to prevent the disease than to treat it. The vaccine prevents disease in the people who receive them and protect those who come into contact with an unvaccinated individual. Because of the large genome and complex biology, developing a vaccine for this pathogen has proved to be a challenging task. Leishmania promastigotes are successfully cultivated incompletely defined medium and their excretory-secretory proteins/factors which may act as antigens are easily purified form culture supernatant of cultured Leishmania species. These leishmanial excretory-secretory antigens serve as a candidate for vaccine development in formulation with muramyl dipeptide (MDP) as an adjuvant. However, currently, there is not a single vaccine is available against any form of leishmaniasis for general human use. According to the estimate of the World Health Organization (WHO), 90% of visceral leishmaniasis (VL) occurs in just five countries (Bangladesh, Brazil, India, Nepal, and Sudan). Those in need are amongst the poorest people in these countries to develop a vaccine. The main purpose of this review is to present only the use of Leishmania excretory-secretory antigens (LESAs) as a candidate for the formulation of a potent vaccine against the severe disease leishmaniasis
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Coler, Rhea N., Yasir A. W. Skeiky, Karen Bernards, Kay Greeson, Darrick Carter, Charisa D. Cornellison, Farrokh Modabber, Antonio Campos-Neto, and Steven G. Reed. "Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens Thiol-Specific Antioxidant, Leishmania major Stress-Inducible Protein 1, and Leishmania Elongation Initiation Factor Protects against Leishmaniasis." Infection and Immunity 70, no. 8 (August 2002): 4215–25. http://dx.doi.org/10.1128/iai.70.8.4215-4225.2002.
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ABSTRACT Development of an effective vaccine against Leishmania infection is a priority of tropical disease research. We have recently demonstrated protection against Leishmania major in the murine and nonhuman primate models with individual or combinations of purified leishmanial recombinant antigens delivered as plasmid DNA constructs or formulated with recombinant interleukin-12 (IL-12) as adjuvant. In the present study, we immunized BALB/c mice with a recombinant polyprotein comprising a tandem fusion of the leishmanial antigens thiol-specific antioxidant, L. major stress-inducible protein 1 (LmSTI1), and Leishmania elongation initiation factor (LeIF) delivered with adjuvants suitable for human use. Aspects of the safety, immunogenicity, and vaccine efficacy of formulations with each individual component, as well as the polyprotein referred to as Leish-111f, were assessed by using the L. major challenge model with BALB/c mice. No adverse reactions were observed when three subcutaneous injections of the Leish-111f polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were given to BALB/c mice. A predominant Th1 immune response characterized by in vitro lymphocyte proliferation, gamma interferon production, and immunoglobulin G2A antibodies was observed with little, if any, IL-4. Moreover, Leish-111f formulated with MPL-SE conferred immunity to leishmaniasis for at least 3 months. These data demonstrate success at designing and developing a prophylactic leishmaniasis vaccine that proved effective in a preclinical model using multiple leishmanial antigens produced as a single protein delivered with a powerful Th1 adjuvant suitable for human use.
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Akuffo, Richard, Michael Wilson, Bismark Sarfo, Naiki Attram, Mba-Tihssommah Mosore, Clara Yeboah, Israel Cruz, et al. "Prevalence of Leishmania infection in three communities of Oti Region, Ghana." PLOS Neglected Tropical Diseases 15, no. 5 (May 27, 2021): e0009413. http://dx.doi.org/10.1371/journal.pntd.0009413.
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Background Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania and is transmitted by various species of female phlebotomine sand flies. The first report of cutaneous leishmaniasis (CL) in Ghana refer to a cluster of cases in 1999–2003 in the Ho municipality of the Volta Region. We conducted an epidemiological assessment in the Oti Region, encouraged by recent reports of potential cases of CL. Methodology/Principal findings Using a cross-sectional study design, the exposure to Leishmania was investigated in three communities of the Oti Region based on the leishmanin skin test (LST). LST results for 3,071 participants comprising 1091, 848, and 1132 persons from the communities of Ashiabre, Keri, and Sibi Hilltop, indicated an overall prevalence of exposure to Leishmania infection of 41.8% and individual community prevalence of 39.4%, 55.1%, and 34.2% respectively. Being male [AOR = 1.27; CI: 1.09, 1.49], and living in Keri [AOR = 1.83; CI: 1.43, 2.34] were associated with an increase in the odds of exposure to Leishmania. Being 5–10 years old [AOR = 1.48; CI: 1.06, 2.05], 11–17 years old [AOR = 2.03; CI: 1.45, 2.85], 18–40 years old [AORR = 2.83; CI: 1.81, 4.43] and 41–65 years old [AOR = 5.08; CI: 2.98, 8.68] were also significantly associated with increased odds of being exposed to Leishmania. Conclusions/Significance This study demonstrated exposure to Leishmania in the study communities and also identified associated factors. Future efforts aimed at reducing exposure to Leishmania infection in the study area should take the associated factors into consideration.
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Sato, Camila Massae, Maria Carmen Arroyo Sanchez, Beatriz Julieta Celeste, Malcolm S. Duthie, Jeffrey Guderian, Steven G. Reed, Maria Edileuza Felinto de Brito, et al. "Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different Leishmania Species." Journal of Clinical Microbiology 55, no. 2 (December 7, 2016): 495–503. http://dx.doi.org/10.1128/jcm.01904-16.
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ABSTRACTAmerican tegumentary leishmaniasis (ATL) (also known as cutaneous leishmaniasis [CL]) is caused by various species of protozoa of the genusLeishmania. The diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayed-type hypersensitivity. Serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particularLeishmaniaspecies causing the disease can lead to variable performance. In the present study, we generated recombinant versions of two highly conservedLeishmaniaproteins,Leishmania(Viannia)braziliensis-derived Lb8E and Lb6H, and evaluated both in enzyme-linked immunosorbent assays (ELISA). Recombinant Lb6H (rLb6H) had better performance and reacted with 100.0% of the ATL and 89.4% of the VL samples. These reactions with rLb6H were highly specific (98.5%) when compared against those for samples from healthy control individuals. We then assessed rLb6H against sera from ATL patients infected with different species ofLeishmaniaprevalent in Brazil [Leishmania(Leishmania)amazonensis,L. (Viannia)braziliensis, andL. (V.)guyanensis] and samples from patients with other infectious diseases. In analyses of 500 sera, ELISA using rLb6H detected all 219 ATL samples (sensitivity of 100.0%) with an overall specificity of 93.9% (considering healthy individuals and other infectious diseases patients). Only a minority of samples from Chagas disease patients possessed antibodies against rLb6H, and all of these responses were low (with a highest reactivity index of 2.2). Taken together, our data support further evaluation of rLb6H and the potential for its routine use in the serological diagnosis of ATL.
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Cao, Lili, Weina Jiang, Songgao Cao, Panpan Zhao, Juan Liu, Hang Dong, Yanbing Guo, Quan Liu, and Pengtao Gong. "In vitro leishmanicidal activity of antimicrobial peptide KDEL against Leishmania tarentolae." Acta Biochimica et Biophysica Sinica 51, no. 12 (November 22, 2019): 1286–92. http://dx.doi.org/10.1093/abbs/gmz128.
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Abstract Leishmaniasis, caused by the intracellular protozoan parasite Leishmania, remains an important neglected tropical infectious disease. Infection may be lethal if untreated. Currently, the available drugs for the disease are limited by high toxicity and drug resistance. There is an urgent need to develop novel anti-leishmanial strategies. Antimicrobial peptides (AMPs) have been described as the first-line immune defense against pathogenic microbes and are being developed as emerging anti-parasitic therapies. In the present study, we showed the anti-leishmanial activity of the synthetic 4-amino acid peptide lysine, aspartic acid, glutamic acid, and leucine (KDEL), the endoplasmic reticulum retention sequence, against Leishmania tarentolae promastigote and amastigote. Different concentrations of KDEL peptides were incubated with promastigotes, MTT viability assay, and promastigote assay were carried out. Macrophages infected with GFP-transfected L. tarentolae promastigotes were incubated with KDEL peptides, and the anti-amastigote activity of the KDEL peptides was measured by fluorescence microscopy. The damage of L. tarentolae was observed by light microscopy and electron microscopy. The cell apoptosis was analyzed using the Annexin V-FITC/PI apoptosis detection kit and mitochondrial membrane potential assay kit and by flow cytometry. Results showed that L. tarentolae was susceptible to KDEL peptides in a dose-dependent manner, and KDEL peptides disrupted the surface membrane integrity and caused cell apoptosis. In our study, we found for the first time an AMP KDEL from Pseudomonas aeruginosa and proved its significant therapeutic potential as a novel anti-leishmanial drug.
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Joshi, Jyoti, Chetna Bandral, Raj Kumar Manchanda, Anil Khurana, Debadatta Nayak, and Sukhbir Kaur. "The Effect of Iodium 30c on Experimental Visceral Leishmaniasis." Homeopathy 109, no. 04 (August 21, 2020): 213–23. http://dx.doi.org/10.1055/s-0040-1713361.
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Abstract Background Leishmaniasis is one of several neglected tropical diseases that warrant serious attention. A disease of socio-economically poor people, it demands safer and cheaper drugs that help to overcome the limitations faced by the existing anti-leishmanials. Complementary or traditional medicines might be a good option, with an added advantage that resistance may not develop against these drugs. Thus, the present investigation was performed to evaluate the anti-leishmanial efficacy of an ultra-diluted homeopathic medicine (Iodium 30c) in experimental visceral leishmaniasis (VL). Methods Compliant with strict ethical standards in animal experimentation, the study was performed in-vivo in inbred BALB/c mice which were injected intravenously with 1 × 107 promastigotes of Leishmania donovani before (therapeutic) or after (prophylactic) treatment with Iodium 30c for 30 days. In other groups of mice (n = 6 per group), amphotericin B served as positive control, infected animals as the disease control, while the naïve controls included normal animals; animals receiving only Iodium 30c or Alcohol 30c served as sham controls. The anti-leishmanial efficacy was assessed by determining the hepatic parasite load and analysing percentages of CD4+ and CD8+ T cells. Biochemical analysis and histological studies were performed to check any toxicities. Results Iodium-treated animals showed a significantly reduced parasite load (to 1503 ± 39 Leishman Donovan Units, LDU) as compared with the infected controls (4489 ± 256 LDU) (p < 0.05): thus, the mean therapeutic efficacy of Iodium 30c was 66.5%. In addition, the population of CD4+ and CD8+ T cells was significantly increased (p < 0.05) after treatment. No toxicity was observed, as evidenced from biochemical and histopathological studies of the liver and kidneys. Efficacy of Iodium 30c prophylaxis was 58.3%, while the therapeutic efficacy of amphotericin B was 85.9%. Conclusion This original study has shown that Iodium 30c had significant impact in controlling parasite replication in experimental VL, though the effect was less than that using standard pharmaceutical treatment.
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Brito, Maria Edileuza Felinto de, Maria Sandra Andrade, Filipe Dantas-Torres, Eduardo Henrique Gomes Rodrigues, Milena de Paiva Cavalcanti, Alzira Maria Paiva de Almeida, and Sinval Pinto Brandão-Filho. "Cutaneous leishmaniasis in northeastern Brazil: a critical appraisal of studies conducted in State of Pernambuco." Revista da Sociedade Brasileira de Medicina Tropical 45, no. 4 (July 26, 2012): 425–29. http://dx.doi.org/10.1590/s0037-86822012005000006.
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American cutaneous leishmaniasis (ACL) is a complex disease with clinical and epidemiological features that may vary from region to region. In fact, at least seven different Leishmania species, including Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis, Leishmania (Viannia) lainsoni, Leishmania (Viannia) naiffi, Leishmania (Viannia) shawi, Leishmania (Viannia) lindenbergi, and Leishmania (Leishmania) amazonensis, have been implicated in the etiology of ACL in Brazil, and numerous phlebotomine sandfly species of the genus Lutzomyia have been regarded as putative or proven vectors. Because ACL is a focal disease, understanding the disease dynamics at the local level is essential for the implementation of more effective control measures. The present paper is a narrative review about the ACL epidemiology in Pernambuco, northeastern Brazil. Furthermore, the need for more effective diagnosis, treatment, control and prevention strategies for the affected populations is highlighted. This paper will provide researchers with a critical appraisal of ACL in Pernambuco. Hopefully, it will also be helpful for public health authorities to improve current control strategies against ACL at the state and country levels.
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Mukkala, Avinash Naraiah, Ruwandi Kariyawasam, Rachel Lau, Braulio M. Valencia, Alejandro Llanos-Cuentas, and Andrea K. Boggild. "Elevated baseline expression of seven virulence factor RNA transcripts in visceralizing species of Leishmania: a preliminary quantitative PCR study." Therapeutic Advances in Infectious Disease 9 (January 2022): 204993612211026. http://dx.doi.org/10.1177/20499361221102665.
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Introduction: Leishmaniasis is a neglected tropical disease that manifests as three major disease phenotypes: cutaneous, mucocutaneous, and visceral. In this preliminary study, we quantified virulence factor (VF) RNA transcript expression in Leishmania species, stratified by geographic origin and propensity for specific disease phenotypes. Methods: Cultured promastigotes of 19 Leishmania clinical and ATCC isolates were extracted for total cellular RNA, cDNA was reverse transcribed, and qPCR assays were performed to quantify VF RNA transcript expression for hsp23, hsp70, hsp83, hsp100, mpi, cpb, and gp63. Results: Comparison of visceralizing species (Leishmania donovani, Leishmania chagasi, and Leishmania infantum) versus non-visceralizing species [Leishmania (Viannia) spp., Leishmania tropica, Leishmania major, Leishmania mexicana, and Leishmania amazonensis] revealed a significantly greater pooled transcript expression for visceralizing species (p = 0.0032). Similarly, Old World species demonstrated significantly higher VF RNA transcript expression than New World species (p = 0.0015). On a per-gene basis, species with a propensity to visceralize ubiquitously expressed higher levels of gp63 (p = 0.005), cpb (p = 0.0032), mpi (p = 0.0032), hsp23 (p = 0.0039), hsp70 (p = 0.0032), hsp83 (p = 0.0032), and hsp100 (p = 0.0032). Conclusion: Here, we provide quantitative, preliminary evidence of elevated VF RNA transcript expression driven largely by the visceralizing causative species of Leishmania. This work highlights the extensive heterogeneity in pathogenicity mechanisms between Leishmania species, which may partly underpin the fatal progression of visceral leishmaniasis.
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Brannigan, James A., and Anthony J. Wilkinson. "Drug discovery in leishmaniasis using protein lipidation as a target." Biophysical Reviews 13, no. 6 (November 4, 2021): 1139–46. http://dx.doi.org/10.1007/s12551-021-00855-0.
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AbstractThe leishmaniases are infectious diseases caused by a number of species of obligate intracellular protozoa of the genus Leishmania with disease manifesting as cutaneous, mucocutaneous and visceral forms. Despite being endemic in more than 80 countries and its being the cause of high morbidity and mortality, leishmaniasis remains a neglected tropical disease. Chemotherapy is the frontline treatment, but drugs in current use suffer from toxic side effects, difficulties in administration and extended treatment times — moreover, resistance is emerging. New anti-leishmanial drugs are a recognised international priority. Here, we review investigations into N-myristoyltransferase (NMT) as a potential drug target. NMT catalyses the co-translational transfer of a C14 fatty acid from myristoyl-CoA onto the N-terminal glycine residue of a significant subset of proteins in eukaryotic cells. This covalent modification influences the stability and interactions of substrate proteins with lipids and partner proteins. Structure-guided development of new lead compounds emerging from high-throughput screening campaigns targeting Leishmania donovani NMT has led to the discovery of potent inhibitors which have been used to gain insights into the role of protein myristoylation in these parasites and to validate NMT as a drug target.
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Wong, Alexander Kin-Choi. "Molecular genetics of the parasitic protozoan Leishmania." Biochemistry and Cell Biology 73, no. 5-6 (May 1, 1995): 235–40. http://dx.doi.org/10.1139/o95-028.
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Leishmania is a member of the family Trypanosomatidae, which causes debilitating diseases in humans. Over the past several years, researchers have applied molecular genetic techniques to study extensively the biology of this parasitic protozoan. Many aspects of Leishmania biology are found to be unique when compared with the higher eukaryotes. This minireview highlights some recent developments in the molecular genetic analysis of this fascinating organism.Key words: Leishmania, protozoan, molecular genetics, disease.
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Nascimento, Katia Fialho, Jenifer Pendiuk Gonçalves, MaurÃcio Baum, Izanara Pritsch, Magda Clara Vieira da Costa Ribeiro, Edilene Alcântara de Castro, Carolina Camargo de Oliveira, and Dorly de Freitas Buchi. "Highly diluted natural complex (M2) effects on leishmanias." International Journal of High Dilution Research - ISSN 1982-6206 13, no. 47 (November 30, 2021): 115–16. http://dx.doi.org/10.51910/ijhdr.v13i47.729.
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Introduction: Leishmaniosis is regarded as a serious public health issue either by its magnitude, morbidity or mortality. Depending on Leishmania species disease ranges from cutaneous, which is relatively confined and controlled, until a progressive and fatal visceral disease [4]. In order to complete their lifecycle Leishmania undergo transformations in the vector digestive tract to get to metacyclic infective form [3,5]. Those include secretion of the “promastigote secretory gel†(PSG) that protect parasites from digestive enzymes. PSG acts on survival and colonization of parasites inside the vector, on transmission and infection development in mammals, and also facilitates and increases transmission [1,2]. Drugs used for leishmaniosis treatment show high toxicity and several side effects, leading patients to quit the treatment and consequently generating resistant strains. The search for new therapeutic approaches is considered a strategic research priority by the World Health Organization. Highly diluted natural products show efficacy in modifying immunological response by stimulating the immune system through macrophages activation, then favoring the organism in many pathological conditions. Aim: To assess the direct action of M2 treatment on promastigotes of different Leishmania species. Methods: 3x106 were cultured in the presence of 20% of M2 plus booster 1% doses every 24h for up to 96h at 25ºC in humidified incubator and then submitted to assays for determining mitochondrial activity by MTT (5mg/mL), cell proliferation trough cell counting on Neubauer chamber and rosettes formation (around PSG) by light microscopy. Results of 3 independent experiments were statistically analyzed using t-test. Results: M2 treatment changed mitochondrial metabolic activity in all tested Leishmania strains. L. amazonensis proliferation decreased after 96h treatment and likewise the rosettes formation (total, closed and open ones). Discussion: Our data show that Leishmania cultures treated with M2 present decreased number of rosettes and these rosettes may be slowing the production of PSG, that is typically synthesized by Leishmania during metacyclic infective phase. Rosettes are also a place for fusion between 2 or more leishmanias, a process that involves nuclear and kinetoplast genetic material exchange. Conclusion: M2 acts on L. amazonensis promastigote forms by reducing the total number of rosettes (the same for open and closed rosettes) that are related to infective form of promastigotes, which produce PSG while on rosettes. This result suggests that M2 treatment is capable of decreasing Leishmania infectivity. Although our results are preliminary, these changes open new perspectives for the disease treatment and/or prevention using M2.
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Soto, Manuel, Laura Ramírez, José Carlos Solana, Emma C. L. Cook, Elena Hernández-García, José María Requena, and Salvador Iborra. "Inoculation of the Leishmania infantum HSP70-II Null Mutant Induces Long-Term Protection against L. amazonensis Infection in BALB/c Mice." Microorganisms 9, no. 2 (February 12, 2021): 363. http://dx.doi.org/10.3390/microorganisms9020363.
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Leishmania amazonensis parasites are etiological agents of cutaneous leishmaniasis in the New World. BALB/c mice are highly susceptible to L. amazonensis challenge due to their inability to mount parasite-dependent IFN-γ-mediated responses. Here, we analyzed the capacity of a single administration of the LiΔHSP70-II genetically-modified attenuated L. infantum line in preventing cutaneous leishmaniasis in mice challenged with L. amazonensis virulent parasites. In previous studies, this live attenuated vaccine has demonstrated to induce long-protection against murine leishmaniasis due to Old World Leishmania species. Vaccinated mice showed a reduction in the disease evolution due to L. amazonensis challenge, namely reduction in cutaneous lesions and parasite burdens. In contrast to control animals, after the challenge, protected mice showed anti-Leishmania IgG2a circulating antibodies accompanied to the induction of Leishmania-driven specific IFN-γ systemic response. An analysis performed in the lymph node draining the site of infection revealed an increase of the parasite-specific IFN-ϒ production by CD4+ and CD8+ T cells and a decrease in the secretion of IL-10 against leishmanial antigens. Since the immunity caused by the inoculation of this live vaccine generates protection against different forms of murine leishmaniasis, we postulate LiΔHSP70-II as a candidate for the development of human vaccines.
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Hassan, Ghuffran Muhammed. "Antiparasitic activity of Artemether and combination Artemether with Artemisinin against Leishmaniasis, in vitro." Journal of University of Shanghai for Science and Technology 24, no. 02 (February 24, 2022): 327–34. http://dx.doi.org/10.51201/jusst/22/0255.
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The Leishmania donovani parasite causes visceral leishmaniasis (VL), an acute and fatal form of leishmaniasis. Because traditional therapy alternatives, such as glucantime and other pentavalent medicines, are toxic and have side effects, new treatments with fewer negative effects are needed. Only a handful of drugs are clinically beneficial to treatments of the disease, but considerable limitations threaten their very usage. Novel, safe, and efficient drugs, including those against antimalaria and leishmaniasis co-infections, are so essential. Artemether (ATM) is an Artemisinin derivative that has been demonstrated to be useful in the treatment of malaria and, more recently, leishmaniasis. The current research was carried out to evaluate the anti-leishmanial effects of Artemether (ART) and combination of Artemether- Artemisinin (ART- ATM) against procyclic promastigotes of Leishmania donovani. In this fundamental-applied research, we compared the effect of (ATM) and combination of (ART- ATM) on Leishmania donovani procyclic promastigotes, at different concentrations by using the MTT assay method after 24 ,48 and 72 h of treatment. The results prove ATM and combination (ART- ATM) efficiency against the procyclic promastigotes viability with IC50 measured after 24, 48- and 72hours treatment. The combination of (ART- ATM) could be used in the treatment of leishmaniasis to improve the therapeutic outcome for Leishmania species.
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Oliveira, Trícia Maria Ferreira de Sousa, Elton José Rosas de Vasconcelos, Andréa Cristina Higa Nakaghi, Tânia Paula Aquino Defina, Márcia Mariza Gomes Jusi, Cristiane Divan Baldani, Ângela Kaysel Cruz, and Rosangela Zacarias Machado. "A novel A2 allele found in Leishmania (Leishmania) infantum chagasi." Revista Brasileira de Parasitologia Veterinária 20, no. 1 (March 2011): 42–48. http://dx.doi.org/10.1590/s1984-29612011000100009.
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Visceral leishmaniasis (VL) is a widely spread zoonotic disease. In Brazil the disease is caused by Leishmania (Leishmania) infantum chagasi. Peridomestic sandflies acquire the etiological agent by feeding on blood of infected reservoir animals, such as dogs or wildlife. The disease is endemic in Brazil and epidemic foci have been reported in densely populated cities all over the country. Many clinical features of Leishmania infection are related to the host-parasite relationship, and many candidate virulence factors in parasites that cause VL have been studied such as A2 genes. The A2 gene was first isolated in 1994 and then in 2005 three new alleles were described in Leishmania (Leishmania) infantum. In the present study we amplified by polymerase chain reaction (PCR) and sequenced the A2 gene from the genome of a clonal population of L. (L.) infantum chagasi VL parasites. The L. (L.) infantum chagasi A2 gene was amplified, cloned, and sequenced in. The amplified fragment showed approximately 90% similarity with another A2 allele amplified in Leishmania (Leishmania) donovani and in L.(L.) infantum described in literature. However, nucleotide translation shows differences in protein amino acid sequence, which may be essential to determine the variability of A2 genes in the species of the L. (L.) donovani complex and represents an additional tool to help understanding the role this gene family may have in establishing virulence and immunity in visceral leishmaniasis. This knowledge is important for the development of more accurate diagnostic tests and effective tools for disease control.
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Ayala, Ignacio, Luis Jesus Bernal, Juan Diego Garcia-Martinez, Miguel Angel Gomez, Jose Antonio Navarro, and Antonio Bernabe. "An Atypical Case of Leishmaniasis Associated with Chronic Duodenitis in a Dog." Journal of the American Animal Hospital Association 53, no. 2 (March 1, 2017): 101–6. http://dx.doi.org/10.5326/jaaha-ms-6401.
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ABSTRACT We describe an atypical case of duodenal leishmaniasis in a boxer dog presenting with chronic diarrhea and poor general condition. Antidiarrheic therapy was previously administered without success and inflammatory bowel disease localized to the small intestine was suspected, given the chronic clinical signs and by ruling out other known causes of gastrointestinal inflammation. Endoscopic biopsy of duodenum showed a moderate increase in lamina propria lymphocytes, plasma cells, and macrophages. Basophilic bodies were seen in the cytoplasm of numerous macrophages, suggestive of Leishmania spp, confirmed by immunostaining, and a diagnosis of granulomatous duodenitis associated to Leishmania infection was made. After 7 mo of therapy, a significant clinical improvement and weight gain were observed, and endoscopic histology showed no evidence of Leishmania. A progressive decline of anti-leishmanial antibody titer was also observed during follow-up. This report emphasizes the importance of atypical symptoms and the unusual location of visceral leishmaniasis, suggesting the need to consider leishmaniasis in the differential diagnosis of canine chronic enteritis, especially in endemic areas.
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Mursalin, S. M. "Leishmania disease gap analysis study - Pakistan." International Journal of Infectious Diseases 45 (April 2016): 185. http://dx.doi.org/10.1016/j.ijid.2016.02.431.
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Limeira, Clécio Henrique, Clebert José Alves, Sérgio Santos de Azevedo, Carolina de Souza Américo Batista Santos, Marcia Almeida de Melo, Rafael Rodrigues Soares, Nathanael Natércio da Costa Barnabé, and Gabriel de Queiroz Rodrigues. "Clinical aspects and diagnosis of leishmaniasis in equids: a systematic review and meta-analysis." Revista Brasileira de Parasitologia Veterinária 28, no. 4 (December 2019): 574–81. http://dx.doi.org/10.1590/s1984-29612019074.
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Abstract Leishmaniases are a group of diseases of zoonotic importance caused by over 20 species of protozoa of the genus Leishmania, in which domestic dogs are considered to be the main reservoir for the disease. However, the involvement of other vertebrates as reservoirs for these parasites has also been investigated. Therefore, the objective of the present study was to carry out a systematic review with meta-analysis on occurrences of leishmaniasis in equids. The case reports described animals with cutaneous symptoms of leishmaniasis (papules, nodules, ulcers or crusts) that regressed spontaneously, located mainly on the head and limbs, from which three species of protozoa were identified in the lesions: Leishmania braziliensis, Leishmania infantum and Leishmania siamensis. In turn, the meta-analysis showed a combined prevalence of 25%, although with high heterogeneity among the studies, which was attributed to the use of different methods for diagnosing the disease. Leishmaniasis in equids is a benign disease but it should be included in the differential diagnosis of cutaneous diseases among these species. Seroepidemiological studies are important in investigating and monitoring suspected exposure of these hosts to the parasite, especially in endemic areas. However, there is also a need to standardize diagnostic methods.
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Jusi, Márcia Mariza Gomes, Wilma Aparecida Starke-Buzetti, Trícia Maria Ferreira de Sousa Oliveira, Michely da Silva Tenório, Lúcio de Oliveira de Sousa, and Rosangela Zacarias Machado. "Molecular and serological detection of Leishmania spp. in captive wild animals from Ilha Solteira, SP, Brazil." Revista Brasileira de Parasitologia Veterinária 20, no. 3 (September 2011): 219–22. http://dx.doi.org/10.1590/s1984-29612011000300008.
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Leishmaniasis is a zoonotic disease that affects 12 million people worldwide. Several mammalian species can serve as a reservoir for this disease. Dogs are the main reservoir for visceral leishmaniasis in urban areas, which has become a serious public health concern in Brazil. The aim of this study was to evaluate the presence of Leishmania spp. in captive wild animals from Ilha Solteira, São Paulo, Brazil. Blood and various tissues samples were collected from animals of five different species: Speothos venaticus, Chrysocyon brachyurus, Cerdocyon thous, Pseudalopex vetulus, and Procyon cancrivorus. Antibodies against Leishmania spp. were detected in three wild canids by indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). PCR analyses of blood and bone marrow from all animals were negative, but Leishmania DNA was found in the tissues and skin of seropositive animals. Positive PCR samples were also positive for Leishmania donovani complex. Analysis of sequenced PCR products showed similarities with different regions of Leishmania (Leishmania) infantum and Leishmania (Leishmania) chagasi kinetoplastids. Measures to control visceral leishmaniasis in wild animals kept in Brazilian zoos should be established, as no disease control programs are currently available.
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GÓMEZ-HERNÁNDEZ, CÉSAR, ELAINE C. BENTO, KARINE REZENDE-OLIVEIRA, GABRIEL A. N. NASCENTES, CECILIA G. BARBOSA, LARA R. BATISTA, MONIQUE G. S. TIBURCIO, et al. "Leishmania infection in bats from a non-endemic region of Leishmaniasis in Brazil." Parasitology 144, no. 14 (August 23, 2017): 1980–86. http://dx.doi.org/10.1017/s0031182017001500.
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SUMMARYLeishmaniasis is a complex of zoonotic diseases caused by parasites of the genus Leishmania, which can develop in domestic as well as wild animals and humans throughout the world. Currently, this disease is spreading in rural and urban areas of non-endemic regions in Brazil. Recently, bats have gained epidemiological significance in leishmaniasis due to its close relationship with human settlements. In this study, we investigated the presence of Leishmania spp. DNA in blood samples from 448 bats belonging to four families representing 20 species that were captured in the Triangulo Mineiro and Alto Paranaiba areas of Minas Gerais State (non-endemic areas for leishmaniasis), Brazil. Leishmania spp. DNA was detected in 8·0% of the blood samples, 41·6% of which were Leishmania infantum, 38·9% Leishmania amazonensis and 19·4% Leishmania braziliensis. No positive correlation was found between Leishmania spp. and bat food source. The species with more infection rates were the insectivorous bats Eumops perotis; 22·2% (4/18) of which tested positive for Leishmania DNA. The presence of Leishmania in the bat blood samples, as observed in this study, represents epidemiological importance due to the absence of Leishmaniasis cases in the region.
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Rub, Abdur, Kamal Shaker, Mohammad Kashif, Mohd Arish, Abdul Aziz Bin Dukhyil, Bader Mohammed Alshehri, Mohammed A. Alaidarous, Saeed Banawas, and Khwaja Amir. "Repurposing Glyburide as Antileishmanial Agent to Fight Against Leishmaniasis." Protein & Peptide Letters 26, no. 5 (May 29, 2019): 371–76. http://dx.doi.org/10.2174/0929866526666190301114012.
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Background: Leishmaniasis is caused by a protozoan parasite, Leishmania. It is common in more than 98 countries throughout the world. Due to insufficient availability of antileishmanial chemotherapeutics, it is an urgent need to search for new molecules which have better efficacy, low toxicity and are available at low cost. Objectives: There is a high rate of diabetic cases throughout the world that is why we planned to test the antileishmanial activity of glyburide, an effective sugar lowering drug used for the treatment of diabetes. In this study, glyburide showed a significant decrease in the parasite growth and survival in vitro in a dose-dependent manner. Methods: Anti-leishmanial activity of glyburide was checked by culturing Leishmania donovani promastigotes in the presence of glyburide in a dose and time dependent manner. Docking study against Leishmania donovani-Trypanothione synthetase (LdTrySyn) protein was performed using Autodock Vina tool. Results: Growth reversibility assay shows that growth of treated parasite was not reversed when transferred to fresh culture media after 7 days. Moreover, docking studies show efficient interactions of glyburide with key residues in the catalytic site of Leishmania donovani- Trypanothione synthetase (LdTrySyn), a very important leishmanial enzyme involved in parasite’s survival by detoxification of Nitric Oxide (NO) species, generated by the mammalian host as a defense molecule. Thus this study proves that the drug-repurposing is a beneficial strategy for identification of new and potent antileishmanial molecules. Conclusion: The results suggest that glyburide binds to LdTrySyn and inhibits its activity which further leads to the altered parasite morphology and inhibition of parasite growth. Glyburide may also be used in combination with other anti-leishmanial drugs to potentiate the response of the chemotherapy. Overall this study provides information about combination therapy as well as a single drug treatment for the infected patients suffering from diabetes. This study also provides raw information for further in vivo disease model studies to confirm the hypothesis.
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Valigurová, Andrea, and Iva Kolářová. "Unrevealing the Mystery of Latent Leishmaniasis: What Cells Can Host Leishmania?" Pathogens 12, no. 2 (February 3, 2023): 246. http://dx.doi.org/10.3390/pathogens12020246.
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Leishmania spp. (Kinetoplastida) are unicellular parasites causing leishmaniases, neglected tropical diseases of medical and veterinary importance. In the vertebrate host, Leishmania parasites multiply intracellularly in professional phagocytes, such as monocytes and macrophages. However, their close relative with intracellular development—Trypanosoma cruzi—can unlock even non-professional phagocytes. Since Leishmania and T. cruzi have similar organelle equipment, is it possible that Leishmania can invade and even proliferate in cells other than the professional phagocytes? Additionally, could these cells play a role in the long-term persistence of Leishmania in the host, even in cured individuals? In this review, we provide (i) an overview of non-canonical Leishmania host cells and (ii) an insight into the strategies that Leishmania may use to enter them. Many studies point to fibroblasts as already established host cells that are important in latent leishmaniasis and disease epidemiology, as they support Leishmania transformation into amastigotes and even their multiplication. To invade them, Leishmania causes damage to their plasma membrane and exploits the subsequent repair mechanism via lysosome-triggered endocytosis. Unrevealing the interactions between Leishmania and its non-canonical host cells may shed light on the persistence of these parasites in vertebrate hosts, a way to control latent leishmaniasis.
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Solomon, Michal, Inbal Fuchs, Yael Glazer, and Eli Schwartz. "Gender and Cutaneous Leishmaniasis in Israel." Tropical Medicine and Infectious Disease 7, no. 8 (August 12, 2022): 179. http://dx.doi.org/10.3390/tropicalmed7080179.
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Leishmaniasis is estimated to be more common in males than in females. Our purpose was to evaluate differences in preponderance in relation to sex and gender across cutaneous and mucocutaneous leishmaniasis in Israel. An observational study was performed, including cases of endemic CL (cutaneous leishmaniasis) in Israel, and imported MCL (mucocutaneous leishmaniasis). CL is a notifiable disease and is supposed to be reported to the Ministry of Health (MOH). The MOH database shows that males as more likely to be infected by leishmania, with an incidence of 5/100,000 in males vs. 3.5/100,000 in females. However, while conducting a demographic house-to-house survey in several locations in Israel where CL is highly endemic, among 608 people who were screened only 49% were males in Leishmania major (L. major) endemic regions and 41% were males in Leishmania tropica (L. tropica) endemic regions, while among 165 cases of imported New-World cutaneous leishmaniasis in Israeli travelers freturning from abroad, 142 (86%) were males. It may be postulated that there is no real gender difference in leishmanial infection, but, perhaps, infections are more commonly seen in men because of referral/reported bias, due to more risk-taking behaviors by men or, perhaps, men are less likely to strictly adhere to recommended preventive measures and thus increase their risk of contracting the disease.
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Pacheco-Fernandez, Thalia, Greta Volpedo, Chaitenya Verma, and Abhay R. Satoskar. "Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis." Biochemical Society Transactions 49, no. 1 (January 15, 2021): 297–311. http://dx.doi.org/10.1042/bst20200606.
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Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.
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Norouzi, Roghayeh, Abolghasem Siadatpanah, Ruhollah Fateh, Fariba Sohrabi, and Seyed Jafar Adnani Sadati. "In-vitro Study on the Anti-leishmania Effects of Silver Nanoparticles on Leishmanaia Major Promastigotes." Qom Univ Med Sci J 16, no. 5 (August 1, 2022): 414–29. http://dx.doi.org/10.32598/qums.16.5.377.1.
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Background and Objectives: Cutaneous leishmaniasis is one of the most important health-threatening diseases in Iran and other countries. Glucantime is currently used to treat this disease, but due to its side effects and high resistance, alternative therapies such as the use of nanoparticles have been considered by researchers. This study aims to investigate the anti-leishmania activity of silver nanoparticles on Leishmania major in vitro. Methods: This is an experimental study on the anti-leishmania activities of silver nanoparticles at different concentrations of 0.75-0.96 µg/ml after 24, 48 and 72 hours of exposure to 106 live Leishmania major promastigotes. The numbers of live parasites were counted by Trypan Blue on a neobar slide using optical microscope (Hemocytometer method). Glucantime and distilled water were considered as positive and negative controls, respectively. The half-maximal inhibitory concentration (IC50) was calculated by SigmaPlot™ software, version 13. All reactions were done three times and their average was considered as final result. Results: All concentrations of silver nanoparticles had anti-leishmania activity, where the concentration of 96 µg/ml had the highest effect (100%) 72 hours after exposure. The IC50 was obtained 36.67, 27.2 and 21.08 µg/ml after 24, 48 and 72 hours of exposure, respectively. Conclusion: Silver nanoparticles have an inhibitory effect on the growth of Leishmania major in different concentrations. However, further in-vivo studies are needed to determine the effictivness of silver nanoparticles.
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Gomes-Silva, Adriano, Maria Aparecida Souza, Sandra Regina Afonso-Cardoso, Lívia Resende Andrade, Reynaldo Dietze, Elenice Lemos, Alejandro Belli, Silvio Favoreto Júnior, and Marcelo Simão Ferreira. "Serological reactivity of different antigenic preparations of Leishmania (Leishmania) amazonensis and the Leishmania braziliensis complex." Revista da Sociedade Brasileira de Medicina Tropical 41, no. 2 (April 2008): 135–41. http://dx.doi.org/10.1590/s0037-86822008000200001.
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Total antigen from Leishmania (Leishmania) amazonensis and isolates from the Leishmania braziliensis complex, along with their respective antigenic fractions obtained by affinity chromatography on concanavalin-A-Sepharose and jacalin-agarose columns evaluated using immunoenzymatic ELISA assay. For this, serum samples from 229 patients were used, grouped as American tegmental leishmaniasis (nº=58), visceral leishmaniasis (nº=28), Chagas disease (nº=49), malaria (nº=32), tuberculosis (nº=13) and healthy volunteers (nº=49). Samples from American tegmentary leishmaniasis showed higher reactivity with antigens isolated from the Leishmania braziliensis complex than with antigens from Leishmania amazonensis (p<0.001). ELISA assays showed a sensitivity range from 60% to 95% with antigens isolated from the Leishmania braziliensis complex. There was marked nonspecific reactivity among serum samples with the use of antigenic fractions binding with concanavalin-A and jacalin from both Leishmania complexes, in comparison with other antigens (p<0.001). The results presented in this study suggest that the use of homologous antigens increases the efficiency of anti-Leishmania immunoglobulin detection, which may be very valuable for diagnostic purposes.
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Badirzadeh, Alireza, Mehdi Najm, Andrew Hemphill, Maryam Alipour, Hamid Hasanpour, Leila Masoori, and Poorya Karimi. "Effects of negative air ions (NAIs) on Leishmania major: A novel tool for treatment of zoonotic cutaneous leishmaniasis (ZCL)." PLOS ONE 17, no. 9 (September 8, 2022): e0274124. http://dx.doi.org/10.1371/journal.pone.0274124.
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Background Cutaneous leishmaniasis (CL) is a Neglected Tropical Disease (NTD) that causes high morbidity in the tropics and sub-tropics. Despite the remarkable advancements in the treatment of CL, the available therapeutics are far from ideal and also cause serious adverse side effects. Negative air ions (NAIs) generators are widely available for domestic and industrial uses. Several studies have reported on positive effects of NAIs therapy on human health as a non-pharmaceutical treatment for respiratory disease, allergy, or stress-related health conditions, including infectious diseases. To our knowledge, no studies have examined the effectiveness of the NAIs therapy against Leishmania parasites. The aims of this study were to investigate the effect of NAIs therapy on Leishmania major (L. major) the causative agent of CL in in vitro and in a murine model. Methodology/Principal findings In vitro anti-leishmanial effects of NAIs therapy were measured by parasitological methods. NAIs therapy was assessed in vivo in L. major infected BALB/c mice by measuring the footpad (FP) lesion size and parasite load using metric caliper tool and qPCR, respectively. Immune responses in treated and non-treated mice were assessed by measuring the levels of IFN-γ, IL-4, NO and arginase activity. In vitro NAIs therapy significantly decreased the viability of Leishmania promastigotes and of amastigotes cultured in macrophages, but did not affect the host cells. NAIs therapy of L. major infected BALB/c mice resulted in reduced FP lesion size, diminished parasite burden, and importantly decreased induction of IL-4 and arginase activity in the presence of NAIs. In contrast IFN-γ and NO levels were significantly enhanced. NAIs therapy significantly diminished the progression of disease compared to the control group, but was less effective than amphotericin B treatment. Conclusions Our study shows that NAIs treatment was effective in vitro and in Leishmania-infected mice, elicited a T-helper 1 (Th1) response and increased efficient cellular immunity, resulting in a diminished parasite load. Therefore, NAIs therapy can be considered as a useful and safe tool that can contribute to clearing L. major infections without inducing toxicity in host cells. The applications and mechanisms of NAIs therapy warrant further investigation especially in humans suffering from CL.
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Eldbouni, Oussaima, Pierre Abihanna, Mona Beaini, Afaf Minari, Ibrahim Khalife, and Gladys Gemayel. "Visceral leishmaniasis in Lebanon a report of four cases: case series and review." Journal of Infection in Developing Countries 12, no. 02.1 (February 22, 2018): 31S. http://dx.doi.org/10.3855/jidc.10157.
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Introduction: Leishmaniasis comprises a complex of vector-borne diseases, caused by more than 20 species of the protozoan genus Leishmania, and ranging from localized skin ulcers to lethal systemic disease. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. In the Middle East countries like Syria reports high incidence of the disease. In addition to the endemicity of the region for leishmaniasis, the Middle East has seen a great deal of human migration either for earning of livelihood or due to political upheaval in the region. Cutaneous form can be disfiguring but visceral form can be lethal.
Methodology: In this article we report the clinical presentation of 4 cases of visceral leishmaniasis; 3 cases were pediatrics and one immunosuppressed adult patient all of them were from Syria from different regions. The diagnosis was made by bone marrow aspirate; PCR was made for 2 of them and was positive for leishmania infantum. All of them were treated with Amphotericn B lipid formulation (ABELCET) with complete response (definite cure).
Results: We report in this article 4 cases of visceral leishmaniasis treated with amphotericin B lipid complex (Abelcet) following the guidelines with complete remission.
Conclusion: Visceral leishmaniasis is a serious disease and if not treated can lead to death. Lebanon is not known to be endemic for leishmania but since the war the ministry of health reported an outbreak of leishmania and mainly cutaneous leishmania. Here we present 4 cases of visceral leishmania and a review of the latest guidelines on the treatment modalities and protocols.
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Ikeogu, Nnamdi M., Gloria N. Akaluka, Chidalu A. Edechi, Enitan S. Salako, Chukwunonso Onyilagha, Aida F. Barazandeh, and Jude E. Uzonna. "Leishmania Immunity: Advancing Immunotherapy and Vaccine Development." Microorganisms 8, no. 8 (August 7, 2020): 1201. http://dx.doi.org/10.3390/microorganisms8081201.
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Parasitic diseases still constitute a major global health problem affecting billions of people around the world. These diseases are capable of becoming chronic and result in high morbidity and mortality. Worldwide, millions of people die each year from parasitic diseases, with the bulk of those deaths resulting from parasitic protozoan infections. Leishmaniasis, which is a disease caused by over 20 species of the protozoan parasite belonging to the genus Leishmania, is an important neglected disease. According to the World Health Organization (WHO), an estimated 12 million people are currently infected in about 98 countries and about 2 million new cases occur yearly, resulting in about 50,000 deaths each year. Current treatment methods for leishmaniasis are not very effective and often have significant side effects. In this review, we discussed host immunity to leishmaniasis, various treatment options currently being utilized, and the progress of both immunotherapy and vaccine development strategies used so far in leishmaniasis. We concluded with insights into what the future holds toward the fight against this debilitating parasitic disease.
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Monteiro, JS. "A Zoonosis without Fever." Clinical Studies and Medical Case Reports 9, no. 1 (April 6, 2022): 1–3. http://dx.doi.org/10.24966/csmc-8801/1000130.
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Introdution: Zoonosis are infectious diseases transmissible from vertebrate animals to humans under natural conditions. The infectious agents involved include bacteria, viruses, parasites, fungi and rickettsia, among others. Case Presentation:A 13 year-old female teenager, presented with frequent epistaxis, pale mucosae and palpable hepatosplenomegaly on examination and history of contact with a neighbor's sick dog. Laboratory tests showed anemia, thrombocytopenia, mild hepatic dysfunction and negative serologies. Abdominal ultrasound showed moderate hepatosplenomegaly.Normal myelogram, bone marrow aspirate with positive leishmania PCR and peripheral blood positive leishmania IgM/IgG (ELISA), with negative leishmania PCR.Therapy with liposomal amphotericin B was iniciated, with progressive clinical and analytical improvement. Conclusion: Visceral Leishmaniasis is a parasitic disease, caused by infection with Leishmania parasites. Human and animal reservoirs are key elements in the transmission chain.
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Binhazim, Awadh A., Willie L. Chapman, Kenneth S. Latimer, Martha Styles, and Karen Comer. "Canine Leishmaniasis Caused by Leishmania Leishmania Infantum in Two Labrador Retrievers." Journal of Veterinary Diagnostic Investigation 4, no. 3 (July 1992): 299–305. http://dx.doi.org/10.1177/104063879200400312.
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Canine leishmaniasis, a generally fatal parasitic disease, was diagnosed in 2 dogs with a medical history of foreign travel, lymphadenopathy, emaciation, anorexia, intermittent fever, and cutaneous lesions. Clinically, hyperproteinemia, proteinuria, azotemia, and glomerulopathy were evident. Isolation of Leishmania species was done using Schneider's Drosophila medium. Syrian hamsters were used for infectivity studies. Clear taxonomic identification was done biochemically by isoenzyme analysis and comparison of zymogram banding patterns with 6 World Health Organization reference strains. Based on the geographic origin of affected dogs, clinicopathologic presentation, visceralization with hepatosplenomegaly in hamsters, and isoenzyme analysis, a diagnosis of Leishmania leishmania infantum was made. This study, representing the first taxonomic identification of an isolate from canine leishmaniasis, demonstrates the Zoonotic and epidemiologic implications of this disease.
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Podešvová, Lucie, Tereza Leštinová, Eva Horáková, Julius Lukeš, Petr Volf, and Vyacheslav Yurchenko. "Suicidal Leishmania." Pathogens 9, no. 2 (January 25, 2020): 79. http://dx.doi.org/10.3390/pathogens9020079.
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Leishmania are obligate intracellular parasites known to have developed successful ways of efficient immunity evasion. Because of this, leishmaniasis, a disease caused by these flagellated protists, is ranked as one of the most serious tropical infections worldwide. Neither prophylactic medication, nor vaccination has been developed thus far, even though the infection has usually led to strong and long-lasting immunity. In this paper, we describe a “suicidal” system established in Leishmania mexicana, a human pathogen causing cutaneous leishmaniasis. This system is based on the expression and (de)stabilization of a basic phospholipase A2 toxin from the Bothrops pauloensis snake venom, which leads to the inducible cell death of the parasites in vitro. Furthermore, the suicidal strain was highly attenuated during macrophage infection, regardless of the toxin stabilization. Such a deliberately weakened parasite could be used to vaccinate the host, as its viability is regulated by the toxin stabilization, causing a profoundly reduced pathogenesis.
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Suffia, Isabelle, Bernard Ferrua, Xavier Stien, Baharia Mograbi, Pierre Marty, Deborah Rousseau, Konstantina Fragaki, and Joanna Kubar. "A Novel Leishmania infantum Recombinant Antigen Which Elicits Interleukin 10 Production by Peripheral Blood Mononuclear Cells of Patients with Visceral Leishmaniasis." Infection and Immunity 68, no. 2 (February 1, 2000): 630–36. http://dx.doi.org/10.1128/iai.68.2.630-636.2000.
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ABSTRACT We report here the characterization of a novel Leishmania infantum protein termed papLe22 (22-kDa potentially aggravating protein of Leishmania). A positive clone from a cDNA library was identified by serum of a visceral leishmaniasis (VL) patient. Full-length cDNA obtained using rapid amplification of cDNA ends-PCR codes for a 22-kDa protein. In L. infantumpromastigotes an endogenous nuclear protein of 14-kDa electrophoretic mobility was found by using an antiserum prepared against the fusion protein glutathione S-transferase–papLe22. Its expression was also shown in L. infantum amastigotes and inLeishmania major and Leishmania guyanensispromastigotes. VL patients' sera showed anti-papLe22 immunoglobulin M (IgM) and IgG reactivities, indicating that a primary response against the leishmanial protein papLe22 accompanied acute VL manifestations. Specific IgG levels were correlated with patients' clinical status. The presence of IgG1, IgG2, and IgG3 subclasses suggested a mixed Th1- and Th2-type response; there was no correlation between subclass reactivity and the disease course. The recombinant papLe22 specifically activated interleukin-10 production by VL patients' peripheral blood mononuclear cells collected at diagnosis and after treatment-induced cure, indicating its contribution to VL pathogenesis and concomitant immunosuppression and its potential role in the reactivation of latent parasites. As a dominant immunogen, papLe22 might be used as a vaccine component, provided that the vaccination protocol directs the response toward the Th1 pattern.
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Sarfraz, Muhammad, Chenxi Wang, Nargis Sultana, Humna Ellahi, Muhammad Fayyaz ur Rehman, Muhammad Jameel, Shahzaib Akhter, Fariha Kanwal, Muhammad Ilyas Tariq, and Song Xue. "2,3-Dihydroquinazolin-4(1H)-one as a New Class of Anti-Leishmanial Agents: A Combined Experimental and Computational Study." Crystals 12, no. 1 (December 29, 2021): 44. http://dx.doi.org/10.3390/cryst12010044.
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Leishmaniasis is a neglected parasitic disease caused by various Leishmania species. The discovery of new protozoa drugs makes it easier to treat the disease; but, conventional clinical issues like drug resistance, cumulative toxicity, and target selectivity are also getting attention. So, there is always a need for new therapeutics to treat Leishmaniasis. Here, we have reported 2,3-dihydroquinazolin-4(1H)-one derivative as a new class of anti-leishmanial agents. Two derivatives, 3a (6,8-dinitro-2,2-disubstituted-2,3-dihydroquinazolin-4(1H)-ones) and 3b (2-(4-chloro-3-nitro-phenyl)-2-methyl-6,8-dinitro-2,3-dihydro-1H-quinazolin-4-one) were prepared that show promising in silico anti-leishmanial activities. Molecular docking was performed against the Leishmanial key proteins including Pyridoxal Kinase and Trypanothione Reductase. The stability of the ligand-protein complexes was further studied by 100 ns MD simulations and MM/PBSA calculations for both compounds. 3b has been shown to be a better anti-leishmanial candidate. In vitro studies also agree with the in-silico results where IC50 for 3a and 3b was 1.61 and 0.05 µg/mL, respectively.
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Santrich, Cecilia, Alba Lucia Arias, Iris Segura, and Nancy G. Saravia. "Mucosal Disease Caused by Leishmania Braziliensis Guyanensis." American Journal of Tropical Medicine and Hygiene 42, no. 1 (January 1, 1990): 51–55. http://dx.doi.org/10.4269/ajtmh.1990.42.51.
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Cardeñosa, N., C. Muñoz, G. Prats, I. Badell, J. Querol, R. Bordes, and M. Cuatrecasas. "False-positive leishmania serology in castleman's disease." Clinical Microbiology Newsletter 16, no. 11 (June 1994): 86. http://dx.doi.org/10.1016/0196-4399(94)90061-2.
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Saleem, Kiran, Zainab Khursheed, Christophe Hano, Iram Anjum, and Sumaira Anjum. "Applications of Nanomaterials in Leishmaniasis: A Focus on Recent Advances and Challenges." Nanomaterials 9, no. 12 (December 9, 2019): 1749. http://dx.doi.org/10.3390/nano9121749.
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Leishmaniasis is a widely distributed protozoan vector-born disease affecting almost 350 million people. Initially, chemotherapeutic drugs were employed for leishmania treatment but they had toxic side effects. Various nanotechnology-based techniques and products have emerged as anti-leishmanial drugs, including liposomes, lipid nano-capsules, metal and metallic oxide nanoparticles, polymeric nanoparticles, nanotubes and nanovaccines, due to their unique properties, such as bioavailability, lowered toxicity, targeted drug delivery, and biodegradability. Many new studies have emerged with nanoparticles serving as promising therapeutic agent for anti-leishmanial disease treatment. Liposomal Amphotericin B (AmB) is one of the successful nano-based drugs with high efficacy and negligible toxicity. A new nanovaccine concept has been studied as a carrier for targeted delivery. This review discusses different nanotechnology-based techniques, materials, and their efficacies in leishmaniasis treatment and their futuristic improvements.
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Zhdanova, Olga, O. V. Rudneva, J. K. Akulinina, and L. A. Napisanova. "Evaluation of the effectiveness of different immunostimulatory medicine at the experimental trichinosis and leishmaniosis on white mice." International Journal of High Dilution Research - ISSN 1982-6206 18, no. 02 (June 30, 2021): 12. http://dx.doi.org/10.51910/ijhdr.v18i02.998.
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Immunostimulatory drugs in recent years are widely used in Parasitology. Also, homeopathic drugs such as Cina have anti-helmintic and immunostimulation properties. We studied the possibility of using immunostimulating and high dilutions drugs during parasitological disease treatment. Two experimental parasitological disease models (trichinelosis and cutaneous leishmaniosis) were used. Trichinellosis caused by gastrointestinal nematode Trichinella spiralis occurs in humans, domestic and wild animals. Leishmaniasis is a disease caused by parasites of Leishmania genus. It is spread by certain sandflies types bite. The disease can present in three main ways. We used 2 leishmania in vitro models and experimental mice cutaneous model. The cutaneous form presents skin ulcers, while the mucocutaneous form presents skin, mouth, and nose ulcers. For estimation of immunostimulatory efficacy, size of leishmanioma, presence of leishmania in the ulcer, and treatment time were analyzed. This study aimed at to assess the protective efficiency of homeopathic drug such as Cina C6cH and interferon 2 and inductors of interferons of types 1 and 2 interferon, against experimental trichinosis and leichmaniosis. An assay was carried out on 50 white outbred mice. These were divided into three groups of ten mice each. Group 1 was injected with interferon inductors (2.16 mg/mouse in 0.2 ml sterile saline, intramuscularly); group 2 - desoldering dissolved in water Cina C6cH one time a day per os. The group 3 received interferone-a2b; and the group 4 was injected 0.2 ml of sterile 0.9% NaCl. The group 5 was only for leishmaniasis. After a 48 hours regimen, the groups 1-3 were inoculated with a dose of 80 ± 5 units of T. spiralis larva per mouse. After 90 days of trichinellosis incubation, and during one year of leishmaniasis process the mice were euthanized and dissected for evaluation. Maximum protection was obtained in mice immunized with interferon-a2b and its stimulatory, as T. spiralis detected larvae in animals was 733.5±25.1 larva/animal. Cina C6cH immunized group presented 2840.5±183.3 larva/animal. This was less than control group (4485±430.6 larva/mouse). Also mice with leishmaniasis had fewer ulcers during treatment with immune stimulating. Ulcers sizes were 0.46+0.05 (group 3); 2.2 +0.5 (group 2), and 3.2+0.8 (group 5). Leishmanial amount in the ulcer was 3.1 +0.7(group 3), 3.6 +0.4 (group 2), and 3.7+0.3(goup 5). The time of the treatment in the 3-d group was 19.2+0.9 and more than 40 days in all group (2,4,5). So, based on this, we consider it advantageous to continue the study of immunostimulatory drugs in the complex treatment of trichinelosis and leishmaniosis.
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Alexander, J., A. R. Satoskar, and D. G. Russell. "Leishmania species: models of intracellular parasitism." Journal of Cell Science 112, no. 18 (September 15, 1999): 2993–3002. http://dx.doi.org/10.1242/jcs.112.18.2993.
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Leishmania species are obligate intracellular parasites of cells of the macrophage-dendritic cell lineage. Indeed, the ability to survive and multiply within macrophages is a feature of a surprising number of infectious agents of major importance to public health, including Mycobacterium tuberculosis, Mycobacterium leprae, Listeria monocytogenes, Salmonella typhimurium, Toxoplasma gondii and Trypanosoma cruzi. The relationship between such organisms and their host cells is particularly intriguing because, not only are macrophages capable of potent microbicidal activity, but in their antigen-presenting capacity they can orchestrate the developing immune response. Thus, to initiate a successful infection parasites must gain entry into macrophages, and also withstand or circumvent their killing and degradative functions. However, to sustain a chronic infection, parasites must also subvert macrophage-accessory-cell activities and ablate the development of protective immunity. The leishmanias produce a wide spectrum of disease in mice, and as such they have provided excellent models for studying problems associated with intracellular parasitism. In recent years, largely using these organisms, we have made enormous progress in elucidating the mechanisms by which successful intracellular infection occurs. Furthermore, characterization of immunological pathways that are responsible for resistance or susceptibility to Leishmania has given rise to the Th1/Th2 paradigm of cellular/humoral dominance of the immune response.
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Rodríguez-Chaves, Daniela, Vanessa Bagnarello-Madrigal, Javier Alpizar-Cordero, Alonso Calvo-Vargas, Maribel Cordero-Villalobos, Misael Chinchilla-Carmona, Idalia Valerio-Campos, and Ronald Sánchez Porras. "Actividad in vitro anti-Leishmania (Trypanosomatidae) del epóxido trans-Z-α-bisaboleno y del Safrol, en frutos de Piper auritum (Piperaceae)." Revista de Biología Tropical 66, no. 2 (May 24, 2018): 826. http://dx.doi.org/10.15517/rbt.v66i2.33412.
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Anti-Leishmania (Trypanosomatidae) activity of trans-Z-α-bisabolene epoxide and isolation of safrole, in fruits of Piper auritum (Piperaceae). The leishmaniosis disease incidence is high in tropical regions, and its current treatment has shown severe secondary effects. Considering this problem, many studies have focused on plants, looking for chemical components that have anti-leishmanial activity, and are free of adverse effects for human beings. The purpose of this work was to find a chemical component with this kind of activity in Piper auritum. In a phytochemical screening of this plant, we found some cumarins, terpens, triterpens and reducing sugars; and later, we identified the components trans-Z-α-bisabolene epoxide and Safrol. The first component presented a CI50 of 50.0 µg/mL of anti-Leishmania activity. The Safrol, which is the major component of the essential oils of this plant, did not show antiparasitic activity. These results are discussed considering treatment of leishmaniasis. Rev. Biol. Trop. 66(2): 826-835. Epub 2018 June 01.
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Vojtkova, Barbora, Tatiana Spitzova, Jan Votypka, Tereza Lestinova, Iveta Kominkova, Michaela Hajkova, David Santos-Mateus, Michael A. Miles, Petr Volf, and Jovana Sadlova. "Central Asian Rodents as Model Animals for Leishmania major and Leishmania donovani Research." Microorganisms 8, no. 9 (September 20, 2020): 1440. http://dx.doi.org/10.3390/microorganisms8091440.
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The clinical manifestation of leishmaniases depends on parasite species, host genetic background, and immune response. Manifestations of human leishmaniases are highly variable, ranging from self-healing skin lesions to fatal visceral disease. The scope of standard model hosts is insufficient to mimic well the wide disease spectrum, which compels the introduction of new model animals for leishmaniasis research. In this article, we study the susceptibility of three Asian rodent species (Cricetulus griseus, Lagurus lagurus, and Phodopus sungorus) to Leishmania major and L. donovani. The external manifestation of the disease, distribution, as well as load of parasites and infectiousness to natural sand fly vectors, were compared with standard models, BALB/c mice and Mesocricetus auratus. No significant differences were found in disease outcomes in animals inoculated with sand fly- or culture-derived parasites. All Asian rodent species were highly susceptible to L. major. Phodopus sungorus showed the non-healing phenotype with the progressive growth of ulcerative lesions and massive parasite loads. Lagurus lagurus and C. griseus represented the healing phenotype, the latter with high infectiousness to vectors, mimicking best the character of natural reservoir hosts. Both, L. lagurus and C. griseus were also highly susceptible to L. donovani, having wider parasite distribution and higher parasite loads and infectiousness than standard model animals.
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Noorpisheh Ghadimi, Shamsi, Negin Sharifi, and Mahmoud Osanloo. "The leishmanicidal activity of essential oils: A systematic review." Journal of Herbmed Pharmacology 9, no. 4 (July 1, 2020): 300–308. http://dx.doi.org/10.34172/jhp.2020.38.
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Leishmaniasis is the neglected disease among parasitic diseases with an increasing rate of infections. Recently, numerous studies have been conducted on the leishmanicidal properties of various essential oils (EOs). In this research, literature have been systematically reviewed, from 20 years ago, and required information have been extracted. Overally, leishmanicidal effects of ~180 EOs against promastigotes of nine species of Leishmania havebeen documented. Inhibitory concentrations 50% (IC50) of around 30 EOs were less than 10 μg.mL-1. EOs of Tetradenia riparia, Nectandra hihua, and Thymus hirtus with IC50s of 0.01,0.20, and 0.25 μg.mL-1 against Leishmania amazonensis, Leishmania infantum, and Leishmania major respectively, were identified as the most effective EOs. Furthermore, IC50 of Thymus hirtus on Leishmania infantum was 0.43 μg.mL-1. Frequently, substantial differences were found between the observed IC50s of one EO against promastigotes of different species of Leishmania. It can be concluded that the leishmanicidal activity of EOs is selective. Turning to the results,the combination of EOs for the design of multifunctional drugs can lead to excellent outcomes.Interestingly, the results have been classified by promastigote species, so this would be a valuablebenchmark for researchers.