MedWorm: HIV-Leishmania Co-infection

Extracellular matrix alterations in experimental Leishmania amazonensis infection in susceptible and resistant mice

BioMed Central — Wed, 08 Feb 2012 05:00:00 +0100

Leishmania is inoculated, by the bite of an infected sandfly, into the skin of the host, where the promastigotes are phagocyted by dermal macrophages. The dermal region comprises cells and abundant extracellular matrix. Studies show that matrix metalloproteinases play an important role in host defense responses against pathogens in mammals and that their activities lead to the production of antimicrobial peptides. The aim of this study is to evaluate the changes in the distribution of fibronectin and laminin as well as in the elastic system fibres during the course of infection caused by Leishmania amazonensis in mice with distinct genetic backgrounds of susceptibility to this parasite. The results showed that BALB/c presented an enhancement of fibronectin during the course of infection wh...

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Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation

European Journal of Immunology — Mon, 06 Feb 2012 05:00:00 +0100

In conclusion, we propose that A2B receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response. (Source: European Journal of Immunology)

Genome sequencing of the lizard parasite Leishmania tarentolae reveals loss of genes associated to the intracellular stage of human pathogenic species

Nucleic Acids Research — Mon, 06 Feb 2012 05:00:00 +0100

The Leishmania tarentolae Parrot-TarII strain genome sequence was resolved to an average 16-fold mean coverage by next-generation DNA sequencing technologies. This is the first non-pathogenic to humans kinetoplastid protozoan genome to be described thus providing an opportunity for comparison with the completed genomes of pathogenic Leishmania species. A high synteny was observed between all sequenced Leishmania species. A limited number of chromosomal regions diverged between L. tarentolae and L. infantum, while remaining syntenic to L. major. Globally, >90% of the L. tarentolae gene content was shared with the other Leishmania species. We identified 95 predicted coding sequences unique to L. tarentolae and 250 genes that were absent from L. tarentolae. Interestingly, many of the latte...

Multifunctional CD4(+) T cells in patients with American cutaneous leishmaniasis.

Clinical and Developmental Immunology — Sun, 05 Feb 2012 16:25:05 +0100

Authors: Macedo AB, Sánchez-Arcila JC, Schubach AO, Mendonça SC, Marins-Dos-Santos A, de Fatima Madeira M, Gagini T, Pimentel MI, De Luca PM Abstract Leishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)-γ-producing CD4(+) T cells induced by both an...

Multifunctional CD4+T cells in patients with American cutaneous leishmaniasis

Clinical and Experimental Immunology — Thu, 02 Feb 2012 11:18:45 +0100

SummaryLeishmaniasis is a group of important parasitic diseases affecting millions worldwide. To understand more clearly the quality of T helper type 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total interferon (IFN)‐γ‐producing CD4+T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of mult...

Comparative Analysis of Different DNA Binding Drugs for Leishmaniasis Cure: A Pharmacoinformatics Approach

Chemical Biology and Drug Design — Wed, 01 Feb 2012 05:00:00 +0100

AbstractSeveral experiments have been performed to test DNA binding drugs to cure Leishmania infection. However, there are no details of pharmacoinformatics study. Herein, we have selected a good number of compounds from experimentally verified studies and performed a comparative analysis based on Pharmacoinformatics techniques. In silico docking study were performed to observe the molecular level interactions of these known ligands with the DNA receptor by automated computational docking using Glide. A comparison between the calculated interaction energies and in silico ADME/T study was made. In agreement of drug likeness rules, our study suggests that, Seco‐hydroxy‐aza‐CBI‐TMI (compound 4b; GScore: ‐12.058) is a potential molecule for targeting the DNA to cure Leishmaniasis.© ...

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Parasite-specific aptamers as biosynthetic reagents and potential pharmaceuticals.

Trends in Parasitology — Tue, 31 Jan 2012 05:00:00 +0100

Authors: Göringer HU Abstract Aptamers are short, synthetic nucleic acid molecules. They are generated by a Darwinian-type in vitro evolution method known as 'systematic evolution of ligands by exponential enrichment' (SELEX). SELEX represents an experimental platform to identify rare ligands with predetermined functionality from combinatorial nucleic acid libraries. Since its discovery about 20 years ago the method has been instrumental in identifying a large number of aptamers that recognize targets of very different chemistry and molecular complexity. Although aptamers have been converted into sophisticated biomolecular tools for a diverse set of technologies, only a limited number of aptamers have been selected as binding reagents for parasites or parasite-derived molecules. H...

Methodology optimizing SAGE library tag-to-gene mapping: application to Leishmania

BMC Research Notes — Fri, 27 Jan 2012 05:00:00 +0100

Conclusion: The developed method optimizes the assignment of SAGE tags in trypanosomatidae genomes as well as in any genome having polycistronic transcription and small intergenic regions. (Source: BMC Research Notes)

Horizontal gene transfer confers fermentative metabolism in the respiratory-deficient plant trypanosomatid Phytomonas serpens.

Infection, Genetics and Evolution — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Ienne S, Pappas G, Benabdellah K, González A, Zingales B Abstract Among trypanosomatids, the genus Phytomonas is the only one specifically adapted to infect plants. These hosts provide a particular habitat with a plentiful supply of carbohydrates. Phytomonas sp. lacks a cytochrome-mediated respiratory chain and Krebs cycle, and ATP production relies predominantly on glycolysis. We have characterised the complete gene encoding a putative pyruvate/indolepyruvate decarboxylase (PDC/IPDC) (548 amino acids) of P. serpens, that displays high amino acid sequence similarity with phytobacteria and Leishmania enzymes. No orthologous PDC/IPDC genes were found in Trypanosoma cruzi or T. brucei. Conservation of the PDC/IPDC gene sequence was verified in 14 Phytomonas isolates. A phylo...

Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis [Medical Sciences]

Proceedings of the National Academy of Sciences — Tue, 24 Jan 2012 05:00:00 +0100

In this study, we demonstrate that class IB PI3K, PI3Kγ, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by L. mexicana. Using the isoform-selective PI3Kγ inhibitor, AS-605240 and PI3Kγ gene-deficient mice, we show that selective blockade or deficiency of PI3Kγ significantly enhances resistance against L. mexicana that is associated with a significant suppression of parasite entry into phagocytes and reduction in recruitment of host phagocytes as well as regulatory T cells to the site of infection. Furthermore, we demonstrate that AS-605240 is as effective as the standard antileishmanial drug sodium stibogluconate in treatment of cutaneous leishmaniasis caused by L. mexicana. These findings reveal a unique role for PI3Kγ in Leishmania invasion and estab...

Trafficking and release of the metacyclic HASPB protein in the kinetoplastid parasite Leishmania

Cellular Microbiology — Sun, 22 Jan 2012 02:11:11 +0100

SummaryProteins of the Leishmania HASPB family are only expressed in infective parasites (both extra‐ and intracellular stages) and, together with the peripheral membrane protein SHERP, are essential for parasite differentiation (metacyclogenesis) in the sand fly vector. HASPB is a “non‐classically” secreted protein, requiring N‐terminal acylation for trafficking to and exposure on the plasma membrane. Here, we use live cell imaging methods to further explore this pathway to the membrane and flagellum. Unlike HASPB trafficking in transfected mammalian cells, we find no evidence for a phosphorylation‐regulated recycling pathway in metacyclic parasites. Once at the plasma membrane, HASPB18‐GFP can undergo bidirectional movement within the inner leaflet of the membrane and on th...

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Bone marrow cytomorphological changes in patients co-infected with visceral leishmaniasis and human immunodeficiency virus

Revista Brasileira de Hematologia e Hemoterapia — Fri, 20 Jan 2012 22:10:14 +0100

Visceral leishmaniasis (VL) is a severe systemic infectious disease.(1) It has been recognized as an opportunistic disease in patients infected with human immunodeficiency virus (HIV).(2,3) The analysis of the bone marrow of patients co-infected with VL and HIV showed dysplasia of erythroid, granulocytic and megakaryocytic lineages (Figure 1), besides the presence of plasmacytosis, cytoplasmic bodies, hemophagocytosis, granuloma and intracellular and extracellular leishmania amastigotes (Figure 2). These findings are found in the analysis of bone marrow of patients co-infected with HIV and VL; knowledge of these findings may be useful for the diagnosis and prognosis of patients (Source: Revista Brasileira de Hematologia e Hemoterapia)

Synthesis of lipophilic tyrosyl esters derivatives and assessment of their antimicrobial and antileishmania activities

Lipids in Health and Disease — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: These results open up potential applications to use medium tyrosyl derivatives surfactants, antioxidants, antimicrobial and antileishmanial compounds in cosmetic, food and pharmaceutical industries. (Source: Lipids in Health and Disease)

Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi.

Experimental Parasitology — Fri, 20 Jan 2012 05:00:00 +0100

The objective of this study was to develop a novel liposomal formulation, containing phosphatidylserine (PS), of buparvaquone (BPQ) and to evaluate its in vivo effectiveness in Leishmania (L.) infantum chagasi-infected hamsters. The activity of BPQ was evaluated against both the promastigote forms of different Leishmania species and the intracellular amastigotes of L. (L.) infantum chagasi. Buparvaquone was entrapped in PS-liposomes (BPQ-PS-LP), and the drug was quantified by ultra-high-performance liquid chromatography. The treatment was quantified by detecting the RNA of the living amastigotes in the spleen and the liver by real-time PCR. In vitro assays with L. (L.) infantum chagasi intracellular amastigotes were performed in peritoneal macrophages for the evaluation of the 50% inhibito...

The transmission of Leishmania infantum chagasi by the bite of the Lutzomyia longipalpis to two different vertebrates

Parasites and Vectors — Thu, 19 Jan 2012 05:00:00 +0100

We established a transmission model of Leishmania infantum chagasi by the bite of Lutzomyia longipalpis, the vector of American visceral leishmaniasis. The parasites were successfully transmitted to mice and hamsters indicating that both animals are good experimental models.Image: An infected sandfly biting a mouse ear (transmission experiment). Inset: The mouse ear after bite (red dot). (Source: Parasites and Vectors)

Anti-Trypanosoma cruzi activity of nicotinamide.

Acta Tropica — Wed, 18 Jan 2012 05:00:00 +0100

Authors: Soares MB, Silva CV, Bastos TM, Guimarães ET, Figueira CP, Smirlis D, Azevedo WF Abstract Inhibition of Trypanosoma brucei and Leishmania spp. sirtuins has shown promising antiparasitic activity, indicating that these enzymes may be used as targets for drug discovery against trypanosomatid infections. In the present work we carried out a virtual screening focused on the C pocket of Sir2 from Trypanosoma cruzi. Using this approach, the best ligand found was nicotinamide. In vitro tests confirmed the anti-T. cruzi activity of nicotinamide on epimastigote and trypomastigote forms. Moreover, treatment of T. cruzi-infected macrophages with nicotinamide caused a significant reduction in the number of amastigotes. In addition, alterations in the mitochondria and an increase in t...

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SYBR Green-based Real-Time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniases

Parasites and Vectors — Thu, 12 Jan 2012 05:00:00 +0100

SYBR Green-based real-time PCR targeting kDNA minicircles can differentiate between Leishmania subgenera through the amplicons dissociation kinetic. This methodology was further validated with human clinical specimens and field sandflies from Brazil. Image: Characteristic SYBR Green dissociation curve profiles of kDNA conserved regions amplicons from both Leishmania subgenera. (Source: Parasites and Vectors)

Acute New World cutaneous leishmaniasis presenting as tuberculoid granulomatous dermatitis

Journal of Cutaneous Pathology — Wed, 11 Jan 2012 05:00:00 +0100

Acute primary cutaneous leishmaniasis typically presents microscopically with a lymphohistiocytic infiltrate containing admixed plasma cells, parasitized macrophages and abundant organisms. Tuberculoid granulomatous changes may occur in the later phases of primary infection. A 23‐year‐old male presented 1 month after visiting Peru with classic clinical findings of acute primary cutaneous leishmaniasis, while histopathology showed a tuberculoid granulomatous process that lacked any organisms in hematoxylin–eosin and fungal stains. Polymerase chain reaction (PCR) analysis and tissue cultures confirmed the diagnosis of cutaneous leishmaniasis with Leishmania (Viannia) panamensis infection. A pauci‐organism tuberculoid granulomatous process may uncommonly be the presenting histopatholo...

A dysflagellar mutant of Leishmania (Viannia) braziliensis isolated from a cutaneous leishmaniasis patient

Parasites and Vectors — Wed, 11 Jan 2012 05:00:00 +0100

We describe a morphologically atypical Leishmania isolate, obtained from a cutaneous leishmaniasis patient in Brazil. In axenic cultures, atypical promastigotes grow as round cells with very short or absent flagella. We show that, in spite of the defective flagella, they can infect macrophages and are able to establish infections in mice and sand flies. Image: Atypical promastigote of a L. (V.) braziliensis isolate. (Source: Parasites and Vectors)

Acylation-dependent and independent membrane targeting and distinct functions of small myristoylated proteins (SMPs) in Leishmania major.

International Journal for Parasitology — Wed, 11 Jan 2012 05:00:00 +0100

Authors: Tull D, Heng J, Gooley PR, Naderer T, McConville MJ Abstract Trypanosomatid parasites express a number of mono- and diacylated proteins that are targeted to distinct regions of the plasma membrane including the cell body, the flagellum and the flagellar pocket. The extent to which the acylation status and other protein motifs regulate the targeting and/or retention of these proteins to the distinct membrane domains is poorly defined. We have previously described a family of small myristoylated proteins (SMPs) that are either monoacylated (myristoylated) or diacylated (myristoylated and palmitoylated) and targeted to distinct plasma membrane domains. Diacylated SMP-1 is a major constituent of the flagellar membrane, whereas monoacylated SMP-2 resides in the flagellar pocket...

In vitro leishmanicidal activity of imidazole- or pyrazole-based benzo[g]phthalazine derivatives against Leishmania infantum and Leishmania braziliensis species

Journal of Antimicrobial Chemotherapy — Tue, 10 Jan 2012 05:00:00 +0100

Conclusions All the compounds assayed were active in vitro against the two Leishmania species and were less toxic against mammalian cells than the reference drug, but the monosubstituted compounds were significantly more effective and less toxic than their disubstituted counterparts. (Source: Journal of Antimicrobial Chemotherapy)

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Treatment of Leishmania donovani-infected hamsters with miltefosine: analysis of cytokine mRNA expression by real-time PCR, lymphoproliferation, nitrite production and antibody responses

Journal of Antimicrobial Chemotherapy — Tue, 10 Jan 2012 05:00:00 +0100

Conclusions Treatment of Leishmania-infected hamsters with miltefosine reverses the Th2-type response into a strong Th1-type immune response. (Source: Journal of Antimicrobial Chemotherapy)

Structural complex of sterol 14{alpha}-demethylase (CYP51) with 14{alpha}-methylenecyclopropyl-{Delta}7-24, 25-dihydrolanosterol [Research Articles]

The Journal of Lipid Research — Mon, 09 Jan 2012 05:00:00 +0100

Sterol 14α-demethylase (CYP51) that catalyzes the removal of the 14α-methyl group from the sterol nucleus is an essential enzyme in sterol biosynthesis, a primary target for clinical and agricultural antifungal azoles and an emerging target for antitrypanosomal chemotherapy. Here, we present the crystal structure of Trypanosoma (T) brucei CYP51 in complex with the substrate analog 14α-methylenecyclopropyl-7-24,25-dihydrolanosterol (MCP). This sterol binds tightly to all protozoan CYP51s and acts as a competitive inhibitor of F105-containing (plant-like) T. brucei and Leishmania (L) infantum orthologs, but it has a much stronger, mechanism-based inhibitory effect on I105-containing (animal/fungi-like) T. cruzi CYP51. Depicting substrate orientation in the conserved CYP51 b...

Antiparasitic antioxidant phenylpropanoids and iridoid glycosides from Tecoma mollis.

Fitoterapia — Sun, 08 Jan 2012 05:00:00 +0100

Authors: Abdel-Mageed WM, Backheet EY, Khalifa AA, Ibraheim ZZ, Ross SA Abstract A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed ...

Modelling of leishmaniasis infection dynamics: novel application to the design of effective therapies

BMC Systems Biology - Latest articles — Thu, 05 Jan 2012 05:00:00 +0100

Conclusions: Our model can be used to identify the biological factors that must be changed to minimize parasite load in the host body, and contributes to the design of effective therapies. (Source: BMC Systems Biology - Latest articles)

Natural Infection of Leishmania (Viannia) braziliensis in Mus musculus Captured in Mato Grosso, Brazil

Vector-Borne and Zoonotic Diseases — Wed, 04 Jan 2012 15:58:54 +0100

Vector-Borne and Zoonotic Diseases Jan 2012, Vol. 12, No. 1: 81-83. (Source: Vector-Borne and Zoonotic Diseases)

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Molecular Diagnosis of Leishmania mexicana in a Cutaneous Leishmaniasis Case in Sinaloa, Mexico

Vector-Borne and Zoonotic Diseases — Wed, 04 Jan 2012 15:58:46 +0100

Vector-Borne and Zoonotic Diseases Jan 2012, Vol. 12, No. 1: 78-80. (Source: Vector-Borne and Zoonotic Diseases)

Prevalence of Sand Flies and Leishmania donovani Infection in a Natural Population of Female Phlebotomus argentipes in Bihar State, India

Vector-Borne and Zoonotic Diseases — Wed, 04 Jan 2012 14:16:21 +0100

Vector-Borne and Zoonotic Diseases , Vol. 0, No. 0. (Source: Vector-Borne and Zoonotic Diseases)

Detailed interrogation of trypanosome cell biology via differential organelle staining and automated image analysis

BMC Biology - Latest articles — Tue, 03 Jan 2012 05:00:00 +0100

Conclusions: Our approach to DNA staining and automated quantitative analysis of trypanosomatid morphology accelerated analysis of trypanosomatid protozoa. We have validated this approach using Leishmania mexicana, Crithidia fasciculata and wild-type and mutant Trypanosoma brucei. Automated analysis of T. brucei morphology was of comparable quality to manual analysis while being faster and less susceptible to experimentalist bias. The complete data set from each cell and all analysis parameters used can be recorded ensuring repeatability and allowing complete data archiving and reanalysis. (Source: BMC Biology - Latest articles)

Cellular and Subcellular Imaging in Live Mice Using Fluorescent Proteins.

Current Pharmaceutical Biotechnology — Mon, 02 Jan 2012 05:00:00 +0100

Authors: Hoffman RM Abstract Fluorescent proteins have revolutionized in vivo biology. Due to their intrinsic brightness, multiple colors, and ease of generic manipulation, fluorescent proteins are the genetic reporters of choice for in vivo imaging. The present report reviews applications of fluorescent protein for imaging cancer progression, gene expression, angiogenesis, stem cells, bacterial infection, Leishmania, and asthma at the cellular level in live mice. With fluorescent protein-expressing cells and a highly sensitive small animal imaging system, cellular and subcellular dynamics can now be observed in live mice in real time. Fluorescent proteins thus enable both micro as well as macro imaging technology and thereby provide the basis for the new field of in vivo cell biol...

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Aldheides monoterpenes as potential anti-Leishmania agents: Activity of Cymbopongon citratus and citral on L. infantum, L. tropica and L. major.

Experimental Parasitology — Mon, 02 Jan 2012 05:00:00 +0100

Authors: Machado M, Pires P, Dinis AM, Santos-Rosa M, Alves V, Salgueiro L, Cavaleiro C, Sousa MC Abstract In order to contribute for the search of new drugs for leishmaniasis, we study the susceptibility of Leishmania infantum, Leishmania tropica and Leishmania major to Cymbopogon citratus essential oil and major compounds, mrycene and citral. C. citratus and citral were the most active inhibiting L. infantum, L. tropica and L. major growth at IC(50) concentrations ranging from 25 to 52μg/ml and from 34 to 42μg/ml, respectively. L. infantum promastigotes exposed to essential oil and citral underwent considerable ultrastructural alterations, namely mitochondrial and kinetoplast swelling, autophagosomal structures, disruption of nuclear membrane and nuclear chromatin condensation....

Epidemiology of imported cutaneous leishmaniasis at the hospital for tropical diseases, london, United kingdom: use of polymerase chain reaction to identify the species.

The American Journal of Tropical Medicine and Hygiene — Sun, 01 Jan 2012 05:00:00 +0100

This study reviewed all patients diagnosed with imported cutaneous leishmaniasis (CL) at the Hospital for Tropical Diseases in London, United Kingdom, over an 11-year period. Diagnostic and epidemiologic information was collected prospectively for all patients with imported CL to this hospital during 1998-2009. A total of 223 patients were given a diagnosis of CL. Ninety patients were diagnosed with Old World CL, which was caused most commonly by Leishmania donovani complex (n = 20). A total of 71% were tourists to the Mediterranean region, 36% were migrants or visiting friends and relatives, and 17% were soldiers. One hundred thirty-three patients were given a diagnosis of New World CL. The Leishmania subgenus Viannia caused 97 of these cases; 44% of these were in backpackers and 29% were...

American visceral leishmaniasis in chiapas, Mexico.

The American Journal of Tropical Medicine and Hygiene — Sun, 01 Jan 2012 05:00:00 +0100

We report the results of a study conducted during 1990-2006 with 89 cases of American visceral leishmaniasis in Chiapas State in southeastern Mexico and a seroprevalence study performed with 726 persons and 224 dogs that lived near cases of American visceral leishmaniasis. Clinical aspects, epidemiologic profiles, and risk factors are described. Most cases were in children ≤ 5 years of age, the prevalence of seropositive persons was 77%. The main risk factors associated with this disease were having 1-3 rooms in a house compared with ≥ 4 rooms, having a roof that was not made of cement, and having domestic animals. In contrast, only 19% of dogs were seropositive, suggesting that this species is not important in the transmission cycle of Leishmania. These data indicate that active trans...

Leishmania infantum chagasi in Northeastern Brazil: Asymptomatic Infection at the Urban Perimeter.

The American Journal of Tropical Medicine and Hygiene — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Lima ID, Queiroz JW, Lacerda HG, Queiroz PV, Pontes NN, Barbosa JD, Martins DR, Weirather JL, Pearson RD, Wilson ME, Jeronimo SM Abstract Abstract. Visceral leishmaniasis (VL) is endemic in large cities in Brazil, including Natal. We determined the prevalence of asymptomatic human infection with Leishmania infantum chagasi and associated environmental risks around Natal. Infection was detected by Leishmania skin test (LST) and anti-leishmanial antibodies in humans and anti-leishmanial antibodies in dogs. Amongst 345 humans, 24.6% were seropositive, and 38.6% were LST-positive. Prevalence of positive serology was similar in both sexes and across all ages. However, positive LST responses increased with age, suggesting that LST is long-lasting and cumulative. Multinomial logi...

Visceral Leishmaniasis during Italian Renaissance, 1522-1562.

Emerging Infectious Diseases — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Nerlich AG, Bianucci R, Trisciuoglio A, Schönian G, Ball M, Giuffra V, Bachmeier B, Pusch CM, Ferroglio E, Fornaciari G Abstract TO THE EDITOR: Leishmaniasis, an infectious disease caused by parasites of the genus Leishmania, is transmitted to humans through the bite of a female sandfly. The 3 forms of leishmaniasis are visceral (VL) and cutaneous (CL), which are typical of the Old World, and mucocutaneous leishmaniasis, which occurs primarily in Central and South America. VL (also called kala-azar) is caused by species of the L. donovani complex (including L. infantum), and CL is mainly caused by L. major or L. tropica (1). In Italy, VL and CL are caused by L. infantum. The origin and spread of leishmaniasis are a matter of debate. Widespread in antiquity, visceral leish...

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Leishmania (Viannia) braziliensis antigenic fractions: the immune response characterization of patients at the initial phase of disease

Parasite Immunology — Wed, 28 Dec 2011 05:00:00 +0100

AbstractAmerican cutaneous leishmaniasis (ACL) has different clinical manifestations and those are dependent on the immunological status of the host. Since CD4+ and CD8+ T cells and its mediators play a fundamental role in the host response to Leishmania and that there is also a search for antigenic molecules to be used as future vaccines and tools for prognostic tests, this study characterized ACL patients immune response after stimulation with soluble and insoluble fractions of L. (V.) braziliensis. We demonstrated a prevailing production of the Th2 cytokines, IL‐4 and IL‐10, and a specific production of IFN‐γ and TNF‐α in patients before treatment. There was also a predominance of CD4+ T cells and a small percentage CD8+ T cells. The insoluble antigenic fraction primarily stim...

Trypanosoma rangeli expresses a β-galactofuranosyl transferase.

Experimental Parasitology — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Stoco PH, Aresi C, Lückemeyer DD, Sperandio MM, Sincero TC, Steindel M, Miletti LC, Grisard EC Abstract Glycoconjugates play essential roles in cell recognition, infectivity and survival of protozoan parasites within their insect vectors and mammalian hosts. β-Galactofuranose is a component of several glycoconjugates in many organisms, including a variety of trypanosomatids, but is absent in mammalian and African trypanosomes. Herein, we describe the presence of a β(1-3) galactofuranosyl transferase (GALFT), an important enzyme of the galactofuranose biosynthetic pathway, in Trypanosoma rangeli. The T. rangeli GALFT gene (TrGALFT) has an ORF of 1.2Kb and is organized in two copies in the T. rangeli genome. Antibodies raised against an internal fragment of the transferas...

Genome-wide SNP and microsatellite variation illuminate population-level epidemiology in the Leishmania donovani species complex.

Infection, Genetics and Evolution — Wed, 21 Dec 2011 22:43:54 +0100

This study demonstrates the power of genomic data for exploring parasite population structure. Furthermore, markers defining different genetic groups have been discovered that could potentially be applied to investigate drug resistance in clinical Leishmania strains. PMID: 22119748 [PubMed - in process] (Source: Infection, Genetics and Evolution)

A possible role for Phlebotmus (Anaphlebotmous) rodhaini (Parrot 1930) in transmission of Leishmania donovani

Parasites and Vectors — Wed, 21 Dec 2011 05:00:00 +0100

Evidence is presented that in zoonotic foci of visceral leishmaniasis in eastern Sudan, Phlebotomus rodhaini is a possible vector of Leishmania donovani that plays a role in transmission of the parasite between reservoir animals. Image: Proposed transmission cycles of Leishmania donovani in zoonotic foci of visceral leishmaniasis in eastern Sudan. (Source: Parasites and Vectors)

PhosTryp: a phosphorylation site predictor specific for parasitic protozoa of the family trypanosomatidae.

BMC Genomics - Latest articles — Mon, 19 Dec 2011 05:00:00 +0100

Conclusions: Our work demonstrates that training on organism-specific data results in an improvement that extends to related species. PhosTryp is freely available at http://phostryp.bio.uniroma2.it (Source: BMC Genomics - Latest articles)

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Evaluation of an ELISA for canine leishmaniasis immunodiagnostic using recombinant proteins

Parasite Immunology — Wed, 14 Dec 2011 19:38:35 +0100

SummaryThe present work describes the isolation and purification of two Leishmania chagasi (= syn. Leishmania infantum) recombinant proteins, rLci2B and rLci1A, and their use in the development of an immunoassay for the diagnostic of canine leishmaniasis. After protein expression and cell disruption, rLci2B was purified by immobilized metal affinity chromatography followed by size exclusion chromatography, whereas rLci1A, expressed as an inclusion body, was treated with urea and purified by anion‐exchange chromatography. Homogeneities were ascertained by denaturing gel electrophoresis (MW rLci2B = 46 370; MWrLci1A = 88 400), isoelectric focusing (pI rLci2B = 5·91; pI rLci1A = 6·01) and Western blot. An indirect ELISA was developed using the purified antigens rLci2B ...

Identification of a protein kinase A regulatory subunit from Leishmania having importance in metacyclogenesis through induction of autophagy

Molecular Microbiology — Wed, 14 Dec 2011 05:00:00 +0100

In this study, a regulatory subunit of cAMP‐dependent protein kinase (Ldpkar1), homologous to mammalian class I cAMP‐dependent protein kinase regulatory subunit, has been identified from L. donovani. Further characterization suggested possible interaction of LdPKAR1 with PKA catalytic subunits and inhibition of PKA activity. This PKA regulatory subunit is expressed in all lifecycle stages and its expression attained maximum level in stationary phase promastigotes, which are biochemically similar to the infective metacyclic promastigotes. Starvation condition, the trigger for metacyclogenesis in the parasite, elevates LdPKAR1 expression and under starvation condition promastigotes overexpressing Ldpkar1 attained metacyclic features earlier than normal cells. Furthermore, Ldpkar1 over ex...

Leishmania (Viannia) shawi purified antigens confer protection against murine cutaneous leishmaniasis

Inflammation Research — Tue, 13 Dec 2011 17:03:32 +0100

Conclusion The capability of antigens to restrain IL-4 levels and increase IFN-γ was associated with protection, such as in immunization using F1 antigen. Content Type Journal ArticleCategory Original Research PaperPages 1-9DOI 10.1007/s00011-011-0407-5Authors Luiz Felipe Domingues Passero, Laboratório de Patologia de Moléstias Infecciosas (LIM-50), Departmento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, São Paulo, SP 01246-903, BrazilAna Kely Carvalho, Laboratório de Patologia de Moléstias Infecciosas (LIM-50), Departmento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, São Paulo, SP 01246-903, BrazilMaria Luiza A. C. Bordon, Laboratório de Patologia de Moléstias Infeccios...

Histopathological and parasitological study of the gastrointestinal tract of dogs naturally infected with Leishmania infantum

Acta Veterinaria Scandinavica — Tue, 13 Dec 2011 05:00:00 +0100

Conclusion: The high parasite burden evident throughout the GIT mucosa with only mild pathological alterations led us to consider whether Leishmania gains an advantage from the intestinal immunoregulatory response (immunological tolerance). (Source: Acta Veterinaria Scandinavica)

Glial reactivity in dogs with visceral leishmaniasis: correlation with T lymphocyte infiltration and with cerebrospinal fluid anti-Leishmania antibody titres

Cell and Tissue Research — Mon, 12 Dec 2011 06:33:16 +0100

Abstract Visceral leishmaniasis is a multisystemic zoonotic disease that can manifest with several symptoms, including neurological disorders. Because glial cells are extensively associated with the immune response within the brain, we evaluated the morphology of astrocytes and microglia of dogs naturally infected with Leishmania chagasi. We used immunohistochemical and lectin-histochemical techniques for morphological analyses and we also examined the glial correlation with lymphocyte infiltration of the brain and with the presence of anti-Leishmania antibodies within the cerebrospinal fluid of the dogs. Although we did not detect a shared morphological pattern in the astrocytes or microglia in the brain tissue, these cells were more intensely labelled in infected dogs than...

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The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis

Journal of Antimicrobial Chemotherapy — Mon, 12 Dec 2011 05:00:00 +0100

Conclusions Upon comparison of each MI compound, MI-4-NO2 was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested. (Source: Journal of Antimicrobial Chemotherapy)

Coinfection of schistosoma (trematoda) with bacteria, protozoa and helminths.

Advances in Parasitology — Sun, 11 Dec 2011 19:12:02 +0100

Authors: Abruzzi A, Fried B Abstract This review examines coinfection of selected species of Schistosoma with bacteria, protozoa and helminths and focuses on the effects of the coinfection on the hosts. The review is based mainly on tables that contain the salient information on the coinfecting organisms in vertebrate hosts. Further explanation and clarification of the tables are given in the text. A table is also provided that gives synoptic information on the 37 species in the 19 genera considered in this review. Coinfection studies with Schistosoma species and the other organisms were considered in six tables plus the accompanying text. Considerations of the Schistosoma interactions with another species of organism include studies on coinfection with Plasmodium, with protozoa ot...

Human African Trypanosomiasis in Non‐Endemic Countries (2000–2010)

Journal of Travel Medicine — Thu, 08 Dec 2011 05:00:00 +0100

Conclusions. The risk of HAT in travelers and migrants, albeit low, cannot be overlooked. In non‐DECs, rarity, nonspecific symptoms, and lack of knowledge and awareness in health staff make diagnosis difficult. Misdiagnosis is frequent, thus leading to invasive diagnosis methods, unnecessary treatments, and increased risk of fatality. Centralized distribution of drugs for HAT by WHO enables an HAT surveillance system for non‐DECs to be maintained. This system provides valuable information on disease transmission and complements data collected in DECs. (Source: Journal of Travel Medicine)

Successful Treatment of Imported Mucosal Leishmania infantum Leishmaniasis With Miltefosine After Severe Hypokalemia Under Meglumine Antimoniate Treatment

Journal of Travel Medicine — Thu, 08 Dec 2011 05:00:00 +0100

We report the case of a 64‐year‐old woman who developed severe hypokalemia under meglumine antimoniate treatment and was successfully treated under second line therapy with miltefosine. (Source: Journal of Travel Medicine)

In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents.

Bioorganic and Medicinal Chemistry Letters — Thu, 08 Dec 2011 05:00:00 +0100

Authors: Almerico AM, Tutone M, Guarcello A, Lauria A Abstract Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei, and Trypanosoma cruzi, resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds. PMID: 22197138 [PubMed - as supplied by publisher] (Source: Bioorganic and Medicinal Chemistry Letters)

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Immunomodulatory Activities of Chitin Microparticles on Leishmania major-infected Murine Macrophages

Archives of Medical Research — Wed, 07 Dec 2011 05:00:00 +0100

Conclusions: These findings show that chitin microparticles have immunomodulatory effects on L. major-infected macrophages and further provide motivations for future studies on their in vivo effects. (Source: Archives of Medical Research)

Improvement of the green fluorescent protein reporter system in Leishmania spp. for the in vitro and in vivo screening of antileishmanial drugs.

Acta Tropica — Tue, 06 Dec 2011 05:00:00 +0100

Authors: Pulido SA, Muñoz DL, Restrepo AM, Mesa CV, Alzate JF, Velez ID, Robledo SM Abstract Development of new therapeutic approaches for leishmaniasis treatment requires new high throughput screening methodologies for the antileishmanial activity of the new compounds both in vitro and in vivo. Reporter genes as the GFP have become one of the most promissory and widely used tools for drug screening in several models, since it offers live imaging, high sensibility, specificity and flexibility; additionally, the use of GFP as a reporter gene in screening assays eliminates all the drawbacks presented in conventional assays and also those technical problems found using other reporter genes. The utility of the GFP as a reporter gene in drug screening assays with Leishmania parasites d...

In vitro growth kinetics, differentiation and morphological characterisation of Tunisian Leishmania infantum parasites

Transactions of the Royal Society of Tropical Medicine and Hygiene — Mon, 05 Dec 2011 22:39:33 +0100

In this study, a negative peanut agglutinin (PNA) selection was used as a marker for promastigote differentiation to compare the in vitro growth and differentiation kinetics of two visceral and two cutaneous Leishmania (Leishmania) infantum parasites. All parasites had different growth and differentiation kinetics. Cultures initiated with PNA+ parasites purified during the early stationary phase (Day 4), when PNA− (non-agglutinating) parasites peaked, yielded a high PNA− percent. Further morphological analysis at this time point showed that 60–86% of PNA+ forms were procyclics, whilst PNA− forms were composed of 53–71% leptomonads. Nectomonads were present both in PNA− and PNA+ promastigote fractions at nearly equivalent proportions, suggesting that they constitute a transition...

Evaluation of a novel chromatographic immunoassay based on Dual-Path Platform technology (DPP® CVL rapid test) for the serodiagnosis of canine visceral leishmaniasis

Transactions of the Royal Society of Tropical Medicine and Hygiene — Mon, 05 Dec 2011 22:39:33 +0100

Abstract: Canine visceral leishmaniasis (CVL) is the major source of human visceral leishmaniasis (VL) and is transmitted from dogs to sand flies to humans. To control the spread of this disease, early and accurate detection of infected dogs is critical but challenging. Here we demonstrate the potential of the Dual-Path Platform (DPP®) CVL rapid test for detecting K26/K39-reactive antibodies in sera from clinically symptomatic (n=60) and asymptomatic (n=60) Leishmania infantum-infected dogs. For the specificity evaluation, assays were performed using known negative diagnostic serum samples (n=59) and cross-reaction control sera (n=11) from animals born in a VL-free area of Brazil. The diagnostic kit displayed high specificity (96%) but low sensitivity (47%) in identifying parasite-positiv...

Myeloid Cell IL-10 Production in Response to Leishmania Involves Inactivation of Glycogen Synthase Kinase-3β Downstream of Phosphatidylinositol-3 Kinase.

Journal of Immunology — Fri, 02 Dec 2011 05:00:00 +0100

In this study, we investigated the regulation of IL-10 production by macrophages infected with Leishmania donovani. Infection of either murine or human macrophages brought about selective phosphorylation of Akt-2 in a PI3K-dependent manner. These events were linked to phosphorylation and inactivation of glycogen synthase kinase-3β (GSK-3β) at serine 9, as the latter was abrogated by inhibition of either PI3K or Akt. One of the transcription factors that is negatively regulated by GSK-3β is CREB, which itself positively regulates IL-10 expression. Infection of macrophages with leishmania induced phosphorylation of CREB at serine 133, and this was associated with enhanced CREB DNA binding activity and induction of IL-10. Similar to phosphorylation of GSK-3β, both phosphorylation of CREB ...

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Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania [RESEARCH]

Genome Research — Thu, 01 Dec 2011 05:00:00 +0100

Leishmania parasites cause a spectrum of clinical pathology in humans ranging from disfiguring cutaneous lesions to fatal visceral leishmaniasis. We have generated a reference genome for Leishmania mexicana and refined the reference genomes for Leishmania major, Leishmania infantum, and Leishmania braziliensis. This has allowed the identification of a remarkably low number of genes or paralog groups (2, 14, 19, and 67, respectively) unique to one species. These were found to be conserved in additional isolates of the same species. We have predicted allelic variation and find that in these isolates, L. major and L. infantum have a surprisingly low number of predicted heterozygous SNPs compared with L. braziliensis and L. mexicana. We used short read coverage to infer ploidy and gene copy nu...

Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance [RESEARCH]

Genome Research — Thu, 01 Dec 2011 05:00:00 +0100

This study provides a basis for more powerful molecular profiling of visceral leishmaniasis, providing additional power to track the drug resistance and epidemiology of an important human pathogen. (Source: Genome Research)

Functional Genomics of Trypanosomatids

Parasite Immunology — Thu, 01 Dec 2011 05:00:00 +0100

AbstractThe decoding of the Tritryp reference genomes nearly seven years ago provided a first peek into the biology of pathogenic trypanosomatids and a blueprint that has paved the way for genome‐wide studies. Although 60‐70% of the predicted protein coding genes in Trypanosoma brucei, Trypanosoma cruzi and Leishmania major remain unannotated, the functional genomics landscape is rapidly changing. Facilitated by the advent of next‐generation sequencing technologies, improved structural and functional annotation and genes and their products are emerging. Information is also growing for interactions between cellular components as transcriptomes, regulatory networks and metabolomes are characterized, ushering in a new era of systems biology. Simultaneously, the launch of comparative seq...

Acute renal injury as a result of liposomal amphotericin B treatment in sodium stibogluconate unresponsive visceral leishmaniasis.

The American Journal of Tropical Medicine and Hygiene — Thu, 01 Dec 2011 05:00:00 +0100

We report an unusual case of visceral leishmaniasis occurring in a patient from Sichuan China. The patient presented with a remitting fever, anemia, and pancytopenia. The case was confirmed as visceral leishmaniasis by microscopical detection of the Leishmania species amastigote in bone marrow aspirate. The patient was treated with 10 mg/kg/day of sodium stibogluconate for 5 days, with no therapeutic response. As a result, the patient was treated with liposomal amphotericin B (LAB) at 10 mg/day as an initial dosage. After treatment with an increasing drug dosage for 7 days, acute renal injury was evident as indicated by increased serum creatinine and urea nitrogen. LAB administration was discontinued until serum creatinine and serum urea nitrogen regressed on Day 15. Two maintenance treatm...

Characterization of Novel Leishmania infantum Recombinant Proteins Encoded by Genes from Five Families with Distinct Capacities for Serodiagnosis of Canine and Human Visceral Leishmaniasis.

The American Journal of Tropical Medicine and Hygiene — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Oliveira GG, Magalhães FB, Teixeira MC, Pereira AM, Pinheiro CG, Santos LR, Nascimento MB, Bedor CN, Albuquerque AL, Dos-Santos WL, Gomes YM, Moreira ED, Brito ME, Pontes de Carvalho LC, de Melo Neto OP Abstract Abstract. To expand the available panel of recombinant proteins that can be useful for identifying Leishmania-infected dogs and for diagnosing human visceral leishmaniasis (VL), we selected recombinant antigens from L. infantum, cDNA, and genomic libraries by using pools of serum samples from infected dogs and humans. The selected DNA fragments encoded homologs of a cytoplasmic heat-shock protein 70, a kinesin, a polyubiquitin, and two novel hypothetical proteins. Histidine-tagged recombinant proteins were produced after subcloning these DNA fragments and evaluate...

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Terpenoids from Maytenus Species and Assessment of Their Reversal Activity against a Multidrug-Resistant Leishmania tropica Line.

Chemistry and Biodiversity — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Kennedy ML, Llanos GG, Castanys S, Gamarro F, Bazzocchi IL, Jiménez IA Abstract The phytochemical analysis of the root bark extracts of the Chilean Maytenus, M. chubutensis, and M. magellanica (Celastraceae), led to the isolation of one phenolic nortriterpene, 1, and one diterpene with a nor-ent-kaurene skeleton, 2. In addition, four known compounds were isolated, among which compound 3 has been isolated for the first time from a natural source. Their structures were elucidated by spectroscopic methods, including 1D- and 2D-NMR (COSY, ROESY, HSQC, and HMBC) experiments, comparison with data reported in the literature, and chemical correlations. The isolated compounds were assayed for their reversal activity against a multidrug-resistant Leishmania tropica line, overexpres...

Potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime.

Revista do Instituto de Medicina Tropical de Sao Paulo — Thu, 01 Dec 2011 05:00:00 +0100

In this study we investigated the efficacy of hyperbaric oxygen (HBO) therapy, alone or combined with the pentavalent antimonial glucantime on Leishmania amazonensis infection. In parallel, the effect of Brazilian red propolis gel (propain) alone or combined with glucantime on L. amazonensis infection was evaluated. The inhibition of the infection in macrophages treated with glucantime in combination with HBO exposition was greater than that of macrophages treated with glucantime alone or HBO alone. The susceptible mouse strain BALB/c infected in the shaved rump with L. amazonensis treated with glucantime and exposed to HBO showed: time points in the course of the disease in which lesions were smaller than those of mice treated with glucantime alone and revascularization of the skin in the...

Distribution of phlebotomine fauna (Diptera: Psychodidae) across an urban-rural gradient in an area of endemic visceral leishmaniasis in northern Brazil.

Memorias do Instituto Oswaldo Cruz — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Oliveira DM, Saraiva EM, Ishikawa EA, Sousa AA, Silva EO, Silva IM Abstract The number of visceral leishmaniasis (VL) cases has increased over the past 10 years in Brazil, especially in the North and Northeast regions of the country. The aim of this study was to evaluate the urbanisation of VL vectors in Barcarena, Pará, an area in northern Brazil where VL is endemic. Sandflies were captured using Centers for Disease Control (CDC) light traps along an urban-rural gradient. The CDC traps were installed inside hen houses at a height of 150 cm. A total of 5,089 sandflies were collected and 11 species were identified. The predominant species was Lutzomyia longipalpis (rate of 95.15%), which suggests its participation in the transmission of VL. A total of 1,451 Lu. longipalpis...

Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs.

Memorias do Instituto Oswaldo Cruz — Thu, 01 Dec 2011 05:00:00 +0100

Authors: Reimão JQ, Tempone AG Abstract The need for drug combinations to treat visceral leishmaniasis (VL) arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs) have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania) chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs), sum of ...

Phlebotominae fauna in a recent deforested area with American Tegumentary Leishmaniasis transmission (Puerto Iguazú, Misiones, Argentina): Seasonal distribution in domestic and peridomestic environments.

Acta Tropica — Tue, 29 Nov 2011 05:00:00 +0100

Authors: Fernández MS, Lestani EA, Cavia R, Salomón OD Abstract Phlebotominae sand flies have been involved as vectors of Leishmania. In Argentina, Nyssomyia neivai and Nyssomyia whitmani are involved as the main vectors of American Tegumentary Leishmaniasis (ATL). In the northeastern border of the country, an outbreak of ATL during 2004-2005 was associated with deforestation and subsequent settlement of farmers close to the edge of the forest. The aim of this work was to study the community composition of sand flies along time in farms located near primary and secondary forest in two environments: houses and pigsties. The association of abundance with temperature and precipitation was also evaluated for the most prevalent species. A total of 23,659 Phlebotominae belonging to the...

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Comparative proteomics profiling of a gentamicin-attenuated Leishmania infantum cell line identifies key changes in parasite thiol-redox metabolism.

Journal of Proteomics — Mon, 28 Nov 2011 05:00:00 +0100

Authors: Daneshvar H, Wyllie S, Phillips S, Hagan P, Burchmore R Abstract We have previously described an attenuated line of Leishmania infantum (H-line), selected by culturing promastigotes in vitro in the presence of gentamicin. To elucidate the molecular basis for this attenuation, we undertook a comparative proteomic analysis using multiplex 2-dimensional (2D) difference gel electrophoresis. Eighteen proteins that showed significant and reproducible changes in expression were identified. Many of these were components of the thiol-redox control system in Leishmania and this observation, validated by Western blot, prompted us to investigate the sensitivity of the attenuated line to oxidative stress. The attenuated line was found to be significantly more susceptible to hydrogen pe...

In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae).

Experimental Parasitology — Mon, 28 Nov 2011 05:00:00 +0100

Authors: Grecco SD, Reimão JQ, Tempone AG, Sartorelli P, Cunha RL, Romoff P, Ferreira MJ, Fávero OA, Lago JH Abstract Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, novel, safe and more efficacious drugs are essential. In this work, the CH(2)Cl(2) phase from MeOH extract from the leaves of Baccharis retusa DC. (Asteraceae) was fractioned to afford two flavonoids: naringenin (1) and sakuranetin (2). These compounds were in vitro tested against Leishmania spp. promastigotes and amastigotes and Trypanosoma cruzi trypomastigotes and amastigotes. Compound 2 presented activity against Leishmania (L.) amazonensis, Leishmania (V.) braz...

Anti-citrullinated peptide antibodies and rheumatoid factor in Sudanese patients with Leishmania donovani infection

Revista Brasileira de Reumatologia — Fri, 25 Nov 2011 22:38:28 +0100

CONCLUSION: The finding that CCP reactivity was not restricted to citrulline argues that this is more an effect of extensive inflammation and immune activation than a sign of shared pathogenic characteristics with anti-CCP arthritis. Our fi ndings stress the importance to interpret a positive CCP test carefully when evaluated in non-rheumatic conditions or in areas where such infections predominate. (Source: Revista Brasileira de Reumatologia)

“Look back in giemsa”

Journal of Infection — Fri, 25 Nov 2011 11:05:45 +0100

Visceral leishmaniasis (VL) is a parasitic disease endemic in the Mediterranean basin, East Africa, Asia and South America characterized by fever, weight loss and hepatosplenomegaly. It is caused by protozoa of the genus Leishmania which are transmitted by the bite of the sandfly, and asymptomatic infection is common. There is a clear association between Visceral leishmaniasis and immunosupression, most notable in the HIV infected population but also now recognized in other immunosupressed states including organ transplant recipients. In such cases the protozoa may have been acquired months to years previously, only causing disease when the host immune system is compromised. It is a serious disease, uniformly fatal if untreated, and with a mortality of 20% with optimal therapy in the immun...

Multifunctional CD4+T cells in patients with American cutaneous leishmaniasis*

Clinical and Experimental Immunology — Fri, 25 Nov 2011 05:00:00 +0100

ABSTRACTLeishmaniasis is a group of important parasitic diseases affecting millions worldwide. To better understand the quality of T helper 1 (Th1) response stimulated after Leishmania infection, we applied a multiparametric flow cytometry protocol to evaluate multifunctional T cells induced by crude antigen extracts obtained from promastigotes of Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg), in peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients. Although no significant difference was detected in the percentage of total gamma interferon (IFN‐γ) producing CD4+T cells induced by both antigens, multiparametric flow cytometry analysis revealed clear differences in the quality of Th1 responses. LbAg induced an important proportion of multifunc...

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Development of Cutaneous Leishmaniasis after Leishmania Skin Test

Clinical and Developmental Immunology — Thu, 24 Nov 2011 23:55:40 +0100

Thirty-year-old female with a previous history of a cutaneous ulcer suspicious of leishmaniasis 20 years ago presented with a new complaint of a depressed papular lesion 8×7 mm in the right lower extremity. The lesion was of 10-day duration. Because early cutaneous leishmaniasis (CL) lesions may have a non-ulcerated appearance, a Leishmania skin test (LST) was performed on the forearm with a strong positive result (38×32 mm). After 8 days, the lesion in the leg, which was diagnosed as folliculitis, completely healed. However, a typical CL ulcer (26×24 mm) developed at the LST site. Histopathology of the new lesion did not identifiy parasites, but the findings were consistent with a diagnosis of CL. Further analysis identified amastigotes by immunohistoc...

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Blood — Thu, 24 Nov 2011 05:00:00 +0100

HIV infection is characterized by immune system dysregulation, including depletion of CD4+ T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. F...

T. vaginalis Surface Lipoglycan Structure [Microbiology]

Journal of Biological Chemistry — Fri, 18 Nov 2011 05:00:00 +0100

The extracellular parasite Trichomonas vaginalis contains a surface glycoconjugate that appears to mediate parasite-host cell interaction via binding to human galectin-1. This glycoconjugate also elicits cytokine production from human vaginal epithelial cells, implicating its role in modulation of host immune responses. We have analyzed the structure of this glycoconjugate, previously described to contain the sugars rhamnose (Rha), N-acetylglucosamine (GlcNAc), galactose (Gal), xylose (Xyl), N-acetylgalactosamine (GalNAc), and glucose (Glc), using gas chromatograph mass spectrometry (GC-MS), matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF), electrospray MS/MS, and nuclear magnetic resonance (NMR), combined with chemical and enzymatic digestions. Our ...

Antimony Resistance in Leishmania, Focusing on Experimental Research

Journal of Cancer Epidemiology — Thu, 17 Nov 2011 19:11:07 +0100

Leishmaniases are parasitic diseases that spread in many countries with a prevalence of 12 million cases. There are few available treatments and antimonials are still of major importance in the therapeutic strategies used in most endemic regions. However, resistance toward these compounds has recently emerged in areas where the replacement of these drugs is mainly limited by the cost of alternative molecules. In this paper, we reviewed the studies carried out on antimonial resistance in Leishmania. Several common limitations of these works are presented before prevalent approaches to evidence antimonial resistance are related. Afterwards, phenotypic determination of resistance is described, then confronted to clinical outcome. Finally, we detail molecular mechanisms and targets involved in...

Evolutionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1 in secretion

BMC Evolutionary Biology - Latest articles — Thu, 17 Nov 2011 05:00:00 +0100

Conclusions: Overall, this work uses an evolutionary biology approach, 3D-modeling and site-directed mutagenesis to arrive at new insights into functions of Leishmania META1. (Source: BMC Evolutionary Biology - Latest articles)

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Three new sensitive and specific heat-shock protein 70 PCRs for global Leishmania species identification

European Journal of Clinical Microbiology and Infectious Diseases — Tue, 15 Nov 2011 06:47:33 +0100

Abstract The heat-shock protein 70 gene (hsp70) has been exploited for Leishmania species identification in the New and Old World, using PCR followed by restriction fragment length polymorphism (RFLP) analysis. Current PCR presents limitations in terms of sensitivity, which hampers its use for analyzing clinical and biological samples, and specificity, which makes it inappropriate to discriminate between Leishmania and other trypanosomatids. The aim of the study was to improve the sensitivity and specificity of a previously reported hsp70 PCR using alternative PCR primers and RFLPs. Following in silico analysis of available sequences, three new PCR primer sets and restriction digest schemes were tested on a globally representative panel of 114 Leishmania strains, various othe...

Lulo cell line derived from Lutzomyia longipalpis (Diptera: Psychodidae): a novel model to assay Leishmania spp. and vector interaction.

Parasites and Vectors — Mon, 14 Nov 2011 05:00:00 +0100

The interaction of Leishmania sp with an insect cell line from Lutzomyia longipalpis (Lulo) was assessed. These findings indicate that Lulo cells can be useful in studies of insect-parasite interactions for Leishmania sp. Image: Scanning electron microscopy image showing Leishmania sp promastigotes adhering to Lulo cells by the flagellum. (Source: Parasites and Vectors)

Antimicrobial and antiprotozoal activities of secondary metabolites from the fungus Eurotium repens

Medicinal Chemistry Research — Thu, 10 Nov 2011 16:53:15 +0100

In this study, we examined in vitro antibacterial, antifungal, antimalarial, and antileishmanial activities of secondary metabolites (1–8) isolated from the fungus Eurotium repens. All compounds showed mild to moderate antibacterial or antifungal or both activities except 7. The activity of compound 6 was the best of the group tested. The in vitro antimalarial evaluation of these compounds revealed that compounds 1–3, 5, and 6 showed antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC50 values in the range of 1.1–3.0 μg/ml without showing any cytotoxicity to the mammalian cells. Compound 5 displayed the highest antimalarial activity. Antileishmanial activity against Leishmania donovani promastigotes was ...

A novel mechanism for an old drug: Amphotericin B in the treatment of visceral leishmaniasis.

Biochemical and Biophysical Research communications — Thu, 10 Nov 2011 05:00:00 +0100

Authors: Chattopadhyay A, Jafurulla M Abstract Visceral leishmaniasis (VL) is caused by various species of the genus Leishmania. Internalization of Leishmania into host cells is facilitated by a large number of receptors, and therefore no panacea is available for the treatment of leishmaniasis. We previously demonstrated the requirement of host membrane cholesterol in the entry of Leishmania into macrophages by cholesterol depletion using methyl-β-cyclodextrin (MβCD). We recently showed that leishmanial infection is inhibited upon sequestration of host membrane cholesterol using amphotericin B (AmB), considered as the best existing drug against VL. The reason for the antileishmanial activity of AmB is generally believed to be its ability to bind ergosterol in parasite membranes. ...

The influence of natural rubber/Au nanoparticle membranes on the physiology of Leishmania brasiliensis.

Experimental Parasitology — Thu, 10 Nov 2011 05:00:00 +0100

Authors: Barboza-Filho CG, Cabrera FC, Dos Santos RJ, De Saja Saez JA, Job AE Abstract The development of nanotechnology has generated new means of disease diagnosis and treatment. Infectious diseases, including leishmaniasis, malaria, etc., have benefited from the advent of new nanomaterials and/or nanodevices capable of detecting specific antigens and antibodies with high specificity and low cost. In this paper, we present an investigation on a single-celled protozoan Leishmaniasis parasite, a disease considered of standard infectivity, given the high degree of immunological specificity. Natural rubber (NR) membranes incorporating gold nanoparticles (GNPs) were placed in the culture medium and the physiological behavior of Leishmania brasiliensis promastigotes was evaluated. The ...

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Identification of phospholipid species affected by miltefosine action in Leishmania donovani cultures using LC-ELSD, LC-ESI/MS, and multivariate data analysis.

Analytical and Bioanalytical Chemistry — Tue, 08 Nov 2011 05:00:00 +0100

Authors: Imbert L, Ramos RG, Libong D, Abreu S, Loiseau PM, Chaminade P Abstract Leishmaniasis is a widespread parasitic disease principally treated by intravenous drugs. Hexadecylphosphocholine (miltefosine) has recently proved its efficacy by oral route. Although its mechanism of action has been investigated, and principally relies on perturbations of the metabolism of lipids and especially phospholipids, further studies need to be conducted to detect precisely which metabolic pathways are impacted. For this purpose, the present work proposes a complete lipidomic study focused on membrane phospholipids of clones of Leishmania donovani non-treated (NT), treated (T) and resistant (R) to miltefosine. Firstly, a separation of phospholipids in normal phase high-performance liquid chro...

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

Beilstein Journal of Organic Chemistry — Mon, 07 Nov 2011 15:43:00 +0100

Abstract An improved total synthesis of (−)-julocrotine in three steps from Cbz-glutamine, in 51% overall yield, is presented. To demonstrate the potential of the heterocyclic moiety for diversity oriented synthesis, a series of (−)-julocrotine analogues was synthesized by employing the heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) . Beilstein J. Org. Chem. 2011, 7, 1504–1507. doi:10.3762/bjoc.7.175 (Source: Beilstein Journal of Organic Chemistry)

Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance [RESEARCH]

Genome Research — Mon, 07 Nov 2011 05:00:00 +0100

MAP Kinase1 of Leishmania Donovani: Down Regulation Associates With Antimony Resistance in Field Isolates.

Antimicrobial Agents and Chemotherapy — Mon, 07 Nov 2011 05:00:00 +0100

Authors: Ashutosh , Garg M, Sundar S, Duncan R, Nakhasi HL, Goyal N Abstract Emergence of resistance to pentavalent antimonials has become a severe obstacle in treatment of visceral leishmaniasis (VL) in the Indian subcontinent. The mechanisms operating in laboratory generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan Leishmania donovani (LdMAPK1) that was consistently down-regulated in antimony-resistant field isolates. The expression level of the gene was validated by real time polymerase chain reaction). Furthermore, decreased expression of LdMAPK1 was al...

Pterocarpanquinones, aza-pterocarpanquinone and derivatives: Synthesis, antineoplasic activity on human malignant cell lines and antileishmanial activity on Leishmania amazonensis.

Bioorganic and Medicinal Chemistry — Sat, 05 Nov 2011 07:36:58 +0100

Authors: Buarque CD, Militão GC, Lima DJ, Costa-Lotufo LV, Pessoa C, de Moraes MO, Cunha-Junior EF, Torres-Santos EC, Netto CD, Costa PR Abstract Pterocarpanquinones (1a-e) and the aza-pterocarpanquinone (2) were synthesized through palladium catalyzed oxyarylation and azaarylation of conjugate olefins, and showed antineoplasic effect on leukemic cell lines (K562 and HL-60) as well as colon cancer (HCT-8), gliobastoma (SF-295) and melanoma (MDA-MB435) cell lines. Some derivatives were prepared (3-8) and evaluated, allowing establishing the structural requirements for the antineoplasic activity in each series. Compound 1a showed the best selectivity index in special for leukemic cells while 2 showed to be more bioselective for HCT-8, SF-295 and MDA-MB435 cells. Pterocarpanquinones ...

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Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani

Biological Chemistry — Fri, 04 Nov 2011 16:47:06 +0100

Biological Chemistry 392 (12): 1113-1122 Abstract Trypanothione synthetase, a validated drug target, synthesizes trypanothione from glutathione and spermidine. Here we report the gene cloning, expression, characterization and inhibition studies of trypanothione synthetase from Leishmania donovani (LdTryS). The purified recombinant LdTryS enzyme obeyed Michaelis-Menten kinetics. High substrate inhibition was observed with glutathione (Km=33.24 μm, kcat=1.3 s-1, Ki=866 μm). The enzyme shows simple hyperbolic kinetics with fixed glutathione concentration and with other substrates limiting Km values for Mg. ATP and spermidine of 14.2 μm and 139.6 μm, respectively. LdTryS was also screened for inhibitors. Tomatine, conessine, uvaol and betulin were identified as inhibitors of the enzyme and...

Successful treatment of multifocal cutaneous leishmaniasis with miltefosine

Indian Journal of Dermatology — Fri, 04 Nov 2011 04:00:00 +0100

We report a 48-year-old immunocompetent male, resident of Central India, who presented with slowly progressive asymptomatic multiple red lesions on different parts of body. On enquiry, the patient gave history of travel to Middle East 6 months back. Examination showed 10 crusted erythematous indurated plaques and nodules over forearms, left leg, right index finger, left wrist and dorsa of both feet. Histopathological examination of tissue biopsy showed multiple intracellular as well as extracellular leishmania donovan bodies. Keeping in mind the higher rate of side effects to pentavalent antimony, we treated this patient with oral miltefosine 50 mg bid and the lesions showed complete resolution over 4 months of therapy. (Source: Indian Journal of Dermatology)

Short Communication: Evaluation of a New Rapid Diagnostic Test for Quality Assurance by Kala Azar Elimination Programme in Bangladesh

Infectious Diseases in Obstetrics and Gynecology — Fri, 04 Nov 2011 01:31:20 +0100

This study showed that the performance of the “Onsite Leishmania Ab Rapid Test” strip tests was up to the recommended level. (Source: Infectious Diseases in Obstetrics and Gynecology)

Deadly Parasite Juggles The Number Of Its Chromosomes

Health News from Medical News Today — Tue, 01 Nov 2011 07:00:00 +0100

Scientists found a deadly parasite with some of its chromosomes in duplicate, others in triplicate, while still others are present four or even five times. Moreover, the copy number varies between individuals. Such a bizarre occurrence has never before been found in nature, in any organism. As a rule, chromosomes should come in couples. The scientists, from the Institute of Tropical Medicine (ITG) and the Wellcome Trust Sanger Institute, made the striking discovery while deciphering the genetic code of a series of Leishmania-parasites... (Source: Health News from Medical News Today)

A Cutaneous Ulcer Resulting from Mycobacterium ulcerans--Leishmania braziliensis Coinfection in South America.

The American Journal of Tropical Medicine and Hygiene — Tue, 01 Nov 2011 04:00:00 +0100

We report here a cutaneous ulcer in a European traveler in South America resulting from a coinfection detected specifically for Mycobacterium ulcerans and Leishmania braziliensis DNA with real-time polymerase chain reaction. This observation of a unique cutaneous ulcer raises the issue about possible modes of transmission of those two pathogens by the same vector. PMID: 22049045 [PubMed - as supplied by publisher] (Source: The American Journal of Tropical Medicine and Hygiene)

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Phlebotomine vector ecology in the domestic transmission of american cutaneous leishmaniasis in chaparral, Colombia.

The American Journal of Tropical Medicine and Hygiene — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Ferro C, Marín D, Góngora R, Carrasquilla MC, Trujillo JE, Rueda NK, Marín J, Valderrama-Ardila C, Alexander N, Pérez M, Munstermann LE, Ocampo CB Abstract Abstract. Phlebotomine vector ecology was studied in the largest recorded outbreak of American cutaneous leishmaniasis in Colombia in 2004. In two rural townships that had experienced contrasting patterns of case incidence, this study evaluated phlebotomine species composition, seasonal abundance, nocturnal activity, blood source, prevalence of Leishmania infection, and species identification. CDC miniature light traps were used to trap the phlebotomines. Traps were set indoors, peridomestically, and in woodlands. Natural infection was determined in pools by polymerase chain reaction-Southern blot, and blood sources...

Current Knowledge of Leishmania Vectors in Mexico: How Geographic Distributions of Species Relate to Transmission Areas.

The American Journal of Tropical Medicine and Hygiene — Tue, 01 Nov 2011 04:00:00 +0100

Authors: González C, Rebollar-Téllez EA, Ibáñez-Bernal S, Becker-Fauser I, Martínez-Meyer E, Peterson AT, Sánchez-Cordero V Abstract Abstract. Leishmaniases are a group of vector-borne diseases with different clinical manifestations caused by parasites transmitted by sand fly vectors. In Mexico, the sand fly Lutzomyia olmeca olmeca is the only vector proven to transmit the parasite Leishmania mexicana to humans, which causes leishmaniasis. Other vector species with potential medical importance have been obtained, but their geographic distributions and relation to transmission areas have never been assessed. We modeled the ecological niches of nine sand fly species and projected niches to estimate potential distributions by using known occurrences, environmental coverages, and...

Schistosoma mansoni antigens alter the cytokine response in vitro during cutaneous leishmaniasis.

Memorias do Instituto Oswaldo Cruz — Tue, 01 Nov 2011 04:00:00 +0100

In this study, we evaluated how S. mansoni antigens altered the immune response that was induced by the soluble Leishmania antigen (SLA) from cutaneous leishmaniasis (CL) patients. Cytokines were measured from the supernatants of peripheral blood mononuclear cell cultures stimulated with SLA. This was performed using the sandwich enzyme linked immunosorbent assay technique in the presence or absence of S. mansoni recombinant antigens Sm29, SmTSP-2 and PIII. The addition of S. mansoni antigens to the cultures resulted in the reduction of interferon gamma (IFN-γ) levels in 37-50% of patients. Although to a lesser extent, the antigens were also able to decrease the production of tumour necrosis factor-alpha (TNF-α). We compared patients that either had or did not have reduction in IFN-γ an...

Antiparasitic activity of plumericin & isoplumericin isolated from Plumeria bicolor against Leishmania donovani.

The Indian Journal of Medical Research — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Sharma U, Singh D, Kumar P, Dobhal MP, Singh S Abstract Background & objectives: The severe toxicity, exorbitant cost and emerging resistance of Leishmania species against most of the currently used drugs underscores the urgent need for the alternative drugs. The present study evaluates in vitro anti-leishmanial activity of Plumeria bicolor and its isolated compounds. Methods: The in vitro anti-parasitic activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested alongwith appropriate controls against promastigote and amastigote forms of Leishmania donovani using 96 well microtiter plate. The concentration used for assessing the anti-leishmanial activity of extract of Plumeria bicolor and both isolated compounds were 100 μg/ml and 15 ...

New Therapeutic Target Against Leishmaniasis

Health News from Medical News Today — Mon, 31 Oct 2011 09:00:00 +0100

Leishmaniasis is a serious parasitic disease with several forms, cutaneous mucocutaneous or visceral, respectively causing skin sores, ulceration and internal damage. The visceral form can be fatal if no treatment is given. These diseases are endemic in more than 98 countries across the world, most of them developing countries, and 350 million people are exposed to them. The protozoan pathogens, responsible, from the genus Leishmania, are transmitted to humans or other mammals by the bite of a sand fly, Phlebotomus... (Source: Health News from Medical News Today)

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Different Paths To Drug Resistance In Leishmania

Health News from Medical News Today — Mon, 31 Oct 2011 07:00:00 +0100

Two remarkable discoveries were revealed by researchers into genome analysis of Leishmania parasites. These results uncovered a surprising level of variation at the genome structure level. First, they found that the DNA sequence of individual strains of each species populations is almost completely identical. It appears that only a small number of genes may cause different symptoms of infection. Second, the parasite's evolutionary development and success may be driven by a genetic abnormality leading to multiple copies of chromosomes that would kill most organisms... (Source: Health News from Medical News Today)

Chromosome chaos in serial killer

EurekAlert! - Medicine and Health — Fri, 28 Oct 2011 04:00:00 +0100

(Institute of Tropical Medicine Antwerp) Scientists found a deadly parasite with some of its chromosomes in duplicate, others in triplicate, while still others are present four or even five times. Moreover, the copy number varies between individuals. Such a bizarre occurrence has never before been found in nature, in any organism. As a rule, chromosomes should come in couples. The scientists, from the Institute of Tropical Medicine and the Wellcome Trust Sanger Institute, made the striking discovery while deciphering the genetic code of a series of Leishmania-parasites. (Source: EurekAlert! - Medicine and Health)

Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance [RESEARCH]

Genome Research — Fri, 28 Oct 2011 04:00:00 +0100

Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania [RESEARCH]

Genome Research — Fri, 28 Oct 2011 04:00:00 +0100

Different paths to drug resistance in Leishmania

EurekAlert! - Social and Behavioral Science — Thu, 27 Oct 2011 04:00:00 +0100

(Wellcome Trust Sanger Institute) This release describes two papers on Leishmania, a disfiguring and potentially fatal disease. The first study suggests that only a few genes are involved in causing the variety of symptoms associated with the different strains of this parasite. The researchers found that the DNA sequence of individual strains of each species populations is almost completely identical. Second, the parasite's evolutionary development and success may be driven by a genetic abnormality that would kill most organisms - having multiple copies of chromosomes. (Source: EurekAlert! - Social and Behavioral Science)

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A novel 4E-interacting protein in Leishmania is involved in stage-specific translation pathways

Nucleic Acids Research — Tue, 25 Oct 2011 04:00:00 +0100

In eukaryotes, exposure to stress conditions causes a shift from cap-dependent to cap-independent translation. In trypanosomatids, environmental switches are the driving force of a developmental program of gene expression, but it is yet unclear how their translation machinery copes with their constantly changing environment. Trypanosomatids have a unique cap structure (cap-4) and encode four highly diverged paralogs of the cap-binding protein, eIF4E; none were found to genetically complement a yeast mutant failing to express eIF4E. Here we show that in promastigotes, a typical cap-binding complex is anchored through LeishIF4E-4, which associates with components of the cap-binding pre-initiation complex. In axenic amastigotes, expression of LeishIF4E-4 decreases and the protein does not bin...

Discovery of Safe and Orally Effective 4-Aminoquinaldine Analogues as Apoptotic Inducers with Activity against Experimental Visceral Leishmaniasis.

Antimicrobial Agents and Chemotherapy — Mon, 24 Oct 2011 04:00:00 +0100

Authors: Palit P, Hazra A, Maity A, Vijayan RS, Manoharan P, Banerjee S, Mondal NB, Ghoshal N, Ali N Abstract Novel antileishmanials are urgently required to overcome emergence of drug resistance, cytotoxic effects, and difficulties in oral delivery. Towards this, we investigated a series of novel 4-aminoquinaldine derivatives, a new class of molecules as potential antileishmanials. 4-amino quinaldine derivatives presented inhibitory effects on L. donovani promatigotes and amastigotes (IC(50) ranging from 0.94 to 127 μM). Of these PP-9 and PP-10 were most effective in vitro and demonstrated strong efficacies in vivo through intraperitoneal route. They were also found to be effective against both sodium antimony gluconate sensitive and resistant Leishmania donovani strains in BALB/...

Effect of ethyl acetate extract from husk fiber water of Cocos nucifera in Leishmania braziliensis infected hamsters

Revista Brasileira de Farmacognosia — Sat, 22 Oct 2011 05:55:24 +0100

The objective of this study was to evaluate the treatment with ethyl acetate extract (EAE) from husk fiber water of Cocos nucifera L., Arecaceae, in L. braziliensis (Lb) infected hamsters. Twelve male hamsters were randomly allocated in three groups (n=4): G1 received only EAE; G2 was infected with Lb only and G3 received EAE after Lb infection. The infection was carried 28 days prior to the treatment with EAE, which was administrated (0.2 mL, 300 mg.kg-1) for 21 consecutive days. Infection was evaluated through skin lesions and infected footpad edema. Haematological evaluation was done on -28th, 0 and 21st days. Imprint footpad and lymph node weight were evaluated on 21st day. Lb infection significantly inhibited the peripheral leukocytes blood. However, neutrophils and lymphocytes values...

Treatment of imported New World cutaneous leishmaniasis in Germany

International Journal of Dermatology — Sat, 22 Oct 2011 04:52:15 +0100

Conclusions In this outcome evaluation of treatment of imported L. (V.) braziliensis infections, liposomal amphotericin B, miltefosine, and meglumine antimoniate proved to be effective. Conventional meglumine antimoniate showed high efficacy as a first‐line treatment and cured lesions that failed to respond to the other two drugs. A multi‐country study using standardized treatment protocols is needed to establish a definitive regimen. (Source: International Journal of Dermatology)

Diverse viscerotropic isolates of Leishmania all express a highly conserved secretory nuclease during human infections.

Molecular and Cellular Biochemistry — Sat, 22 Oct 2011 04:00:00 +0100

Authors: Joshi MB, Hernandez Y, Owings JP, Dwyer DM Abstract Previously, we characterized a gene encoding the unique nuclease (LdNuc(s)) from a Sudanese isolate of the human pathogen Leishmania donovani. This parasite secretory enzyme is involved in the salvage of host-derived purines and is constitutively expressed by both developmental forms of the parasite. Currently, we assessed whether an LdNuc(s)-like nuclease was conserved among other geographically disparate isolates of L. donovani and whether this enzyme was produced by intracellular amastigotes during human infections. Using RT-PCR and Southern blotting, we showed that LdNuc (s) gene homologs were present in each of the viscerotropic Leishmania tested (i.e., L. donovani isolates from the Sudan, Ethiopia and Indi...

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Identification of Novel Inhibitors of Dipeptidylcarboxypeptidase of Leishmania donovani via Ligand Based Virtual Screening and Biological Evaluation

Chemical Biology and Drug Design — Thu, 20 Oct 2011 04:00:00 +0100

AbstractCurrent treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity and lack of efficacy in endemic regions. Therefore, development of new, effective and affordable anti‐leishmanial drugs is a global health priority. Dipeptidylcarboxypeptidase has been characterized and established as a drug target for antileishmanial drug discovery. We virtually screened a large chemical library of 15,452 compounds against a 3D model of dipeptidylcarboxypeptidase to identify novel inhibitors. The initial virtual screening using a ligand‐based pharmacophore model identified 103 compounds. Forty‐six compounds were short listed based on the docking scores and other scoring functions. Further, these compounds were s...

The histone H4 lysine 14 acetylation in Leishmania donovani is mediated by the MYST family protein HAT4.

Microbiology — Thu, 20 Oct 2011 04:00:00 +0100

This report presents results of the first study of a histone acetyltransferase in a Leishmania species. The HAT4 gene of Leishmania donovani, the causative pathogen of Visceral Leishmaniasis, has been cloned and expressed in fusion with GFP in Leishmania promastigotes. We find that HAT4-GFP behaves differently from typical eukaryotic MYST family HATs that are usually constitutively nuclear, in that it is cytosolic throughout the cell cycle, though the protein is also present in the nucleus in post-mitotic cells. Substrate specificity analyses reveal that LdHAT4 acetylates the N-terminus of histone H4, but not of H2A, H2B or H3. Nor does it acetylate the C-terminus of H2A. The primary target of HAT4-mediated acetylation is the K14 residue of H4, though K2 might be a minor site as well. H4K1...

Identification of Novel Inhibitors of Dipeptidylcarboxypeptidase of Leishmania donovani via Ligand‐Based Virtual Screening and Biological Evaluation

Chemical Biology and Drug Design — Thu, 20 Oct 2011 04:00:00 +0100

Current treatment of leishmaniasis is based on chemotherapy, which relies on a handful of drugs with serious limitations, such as high cost, toxicity, and lack of efficacy in endemic regions. Therefore, development of new, effective, and affordable anti‐leishmanial drugs is a global health priority. Dipeptidylcarboxypeptidase has been characterized and established as a drug target for antileishmanial drug discovery. We virtually screened a large chemical library of 15 452 compounds against a 3D model of dipeptidylcarboxypeptidase to identify novel inhibitors. The initial virtual screening using a ligand‐based pharmacophore model identified 103 compounds. Forty‐six compounds were shortlisted based on the docking scores and other scoring functions. Further, these compounds were subje...

Protective Therapy with Novel Chromone Derivative against Leishmania donovani Infection Induces Th1 Response in vivo

Chemotherapy — Mon, 17 Oct 2011 23:00:00 +0100

Chemotherapy 2011;57:388–393 (DOI:10.1159/000330856) (Source: Chemotherapy)

Uptake of the antileishmania drug tafenoquine follows a sterol-dependent diffusion process in Leishmania

Journal of Antimicrobial Chemotherapy — Wed, 12 Oct 2011 04:00:00 +0100

Conclusions These findings suggest that Leishmania takes up tafenoquine by a diffusion process and that decreases in membrane sterol content may induce a decrease in drug uptake. (Source: Journal of Antimicrobial Chemotherapy)

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Lack of signaling by IL-4 or by IL-4/IL-13 has more attenuating effects on Leishmania amazonensis dorsal skin - than on footpad-infected mice.

Experimental Parasitology — Wed, 12 Oct 2011 04:00:00 +0100

Authors: Felizardo TC, Gaspar-Elsas MI, Lima GM, Abrahamsohn IA Abstract Lesion development in tegumentary leishmaniasis is markedly influenced by the inoculation site and the type and number of injected infective forms. This and the yet unclear contribution of Th2 cytokines as susceptibility factors to Leishmania amazonensis infection prompted us to investigate the roles of IL-4, IL-13 and IL-10 on C57BL/6 and BALB/c mice infected in the footpad (paw) or rump with low-dose L. amazonensis purified-metacyclics. Wild-type (WT) mice of either strain developed, in the rump, a single large ulcerated lesion whereas paw lesions never ulcerated and were much smaller in C57BL/6 than in BALB/c mice. However, rump-inoculated IL-4-deficient (IL-4(-/-)) C57BL/6 mice did not develop any visible ...

Radio-attenuated leishmanial parasites as immunoprophylactic agent against experimental murine visceral leishmaniasis.

Experimental Parasitology — Wed, 12 Oct 2011 04:00:00 +0100

Authors: Datta S, Adak R, Chakraborty P, Haldar AK, Bhattacharjee S, Chakraborty A, Roy S, Manna M Abstract The present study intends to evaluate the role of radio-attenuated leishmania parasites as immunoprophylactic agents for experimental murine visceral leishmaniasis. BALB/c mice were immunized with gamma (γ)-irradiated Leishmania donovani. A second immunization was given after 15days of first immunization. After two immunizations, mice were infected with virulent L. donovani promastigotes. Protection against Kala-azar (KA) was estimated from spleen and liver parasitic burden along with the measurement of nitrite and superoxide anion generation by isolation of splenocytes and also by T-lymphocyte helper 1(Th1) and T-lymphocyte helper 2(Th2) cytokines release from the experimen...

The opioid antagonist naloxone inhibits Leishmania major infection in BALB/c mice.

Experimental Parasitology — Wed, 12 Oct 2011 04:00:00 +0100

This study demonstrates that administration of high dose of naloxone could improve protection against L. major infection in BALB/c mice, presumably by modulation in Th1/Th2 balance or by affecting macrophages through binding to Toll-like receptors. PMID: 22019408 [PubMed - as supplied by publisher] (Source: Experimental Parasitology)

Expression plasticity of Phlebotomus papatasi salivary gland genes in distinct ecotopes through the sand fly season

BMC Ecology - Latest articles — Mon, 10 Oct 2011 04:00:00 +0100

Conclusion: Expression plasticity of genes involved with vectorial capacity in disease vectors may play an important epidemiological role in the establishment of diseases in natural habitats. (Source: BMC Ecology - Latest articles)

Antileishmanial activity of nerolidol-rich essential oil from Piper claussenianum

Revista Brasileira de Farmacognosia — Mon, 03 Oct 2011 06:01:14 +0100

In this study, the nerolidol-rich essential oil from Piper claussenianum (Miq.) C. DC., Piperaceae, was assayed on arginase activity of Leishmania amazonensis. The effect of this essential oil on arginase activity levels showed an enzyme inhibition of 62.2%. This result stimulates the scientific interest about the potential value of this plant species on neglected diseases as potential new natural product source of pharmacological interest for the treatment of leishmaniasis. (Source: Revista Brasileira de Farmacognosia)

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Th1/Th2 Cytokine Profile in Patients Coinfected with HIV and Leishmania in Brazil.

Clinical and Vaccine Immunology — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Rodrigues MZ, Grassi MF, Mehta S, Zhang XQ, Gois LL, Schooley RT, Badaro R Abstract To evaluate the effects of HIV on immune responses in cutaneous leishmaniasis (CL), we quantified cytokine levels from plasma and stimulated peripheral blood mononuclear cells (PBMCs) from individuals infected with HIV and/or CL. Gamma interferon (IFN-γ) and interleukin 13 (IL-13) levels and the ratio of IFN-γ to IL-10 produced in response to stimulation with soluble Leishmania antigens were significantly lower in HIV-Leishmania-coinfected patients than in CL-monoinfected patients. PMID: 21832098 [PubMed - in process] (Source: Clinical and Vaccine Immunology)

Feline cutaneous leishmaniasis

Advances in Small Animal Medicine and Surgery — Sat, 01 Oct 2011 04:00:00 +0100

Leishmaniasis is caused by an intracellular protozoa of the genus Leishmania that can infect humans and a wide variety of domestic mammals. These parasites are usually transmitted by the bite of various species of female sandflies and occasionally by blood transfusion, sharing of needles, and congenital transmission. Numerous Leishmania species are geographically widespread, with the highest prevalence in parts of Latin America, southern Europe, and the Middle East. In humans, there are 3 recognized forms of clinical leishmaniasis: cutaneous, mucocutaneous, and visceral. (Source: Advances in Small Animal Medicine and Surgery)

First Report on Natural Infection of Phlebotomus sergenti with Leishmania Promastigotes in the Cutaneous Leishmaniasis Focus in Southeastern Tunisia.

The American Journal of Tropical Medicine and Hygiene — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Tabbabi A, Bousslimi N, Rhim A, Aoun K, Bouratbine A Abstract Abstract. During September 2010, 133 female sand flies were caught inside houses of patients with cutaneous leishmaniasis in the focus for this disease in southeastern Tunisia and subsequently dissected. One specimen was positive for Leishmania protozoa. This sand fly species was identified as Phlebotomus sergenti, and the parasite was identified as L. tropica. This is the first report of P. sergenti involvement in transmission of L. tropica in Tunisia. PMID: 21976566 [PubMed - in process] (Source: The American Journal of Tropical Medicine and Hygiene)

First Report on Ambisome-Associated Allergic Reaction in Two Sudanese Leishmaniasis Patients.

The American Journal of Tropical Medicine and Hygiene — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Mukhtar M, Aboud M, Kheir M, Bakhiet S, Abdullah N, Ali A, Hassan N, Elamin E, Elagib A Abstract Abstract. Post kala-azar dermal leishmaniasis (PKDL) and mucosal leishmaniasis (ML) are serious clinical forms of leishmaniasis caused by Leishmania donovani parasites in Sudan. Although pentavalent antimonys are used as the first line of treatment of all clinical forms of leishmaniasis, persistent PKDL and ML patients are treated with liposomal amphotericin B (Ambisome) as a second-line drug. In this work, we report the development of allergic reactions by a PKDL and a ML Sudanese patient to Ambisome. The findings warrant future close supervision of patients to be treated with the drug. PMID: 21976565 [PubMed - as supplied by publisher] (Source: The American Journal of Tro...

Effect of human urine on cell cycle and infectivity of leismania species promastigotes in vitro.

The American Journal of Tropical Medicine and Hygiene — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Allahverdiyev AM, Bagirova M, Elcicek S, Koc RC, Oztel ON Abstract Abstract. In vitro cultivation of Leishmania parasites plays an important role in diagnosis and treatment of leishmaniasis and in vaccine and drug development studies. Conversely, long-term cultivation of Leishmania parasites usually results in decreased infectivity potential. Some studies reported a stimulatory effect of human urine in Leishmania promastigotes. However, there is no information about the effects of urine within culture on the infectivity of Leishmania parasites. Analysis of the effect of urine have showed that proliferation indexes were significantly increased in culture medium supplemented with human urine (L. tropica = 38.17 ± 5.12, L. donovani = 34.74 ± 5.6, L. major = 34.22 ± 4.66, a...

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Use of elisa employing homologous and heterologous antigens for the detection of IgG and subclasses (IgG1 and IgG2) in the diagnosis of Canine visceral leishmaniasis.

Revista do Instituto de Medicina Tropical de Sao Paulo — Sat, 01 Oct 2011 04:00:00 +0100

Authors: Ribeiro FC, Schubach Ade O, Mouta-Confort E, Pacheco TM, Madeira Mde F, Abboud LC, Honse Cde O, Alves AS, Marzochi MC Abstract Indirect immunofluorescence is the method recommended for the diagnosis of visceral leishmanisis in dogs, however, the accuracy of this technique is low and its use on a large scale is limited. Since ELISA does not present these limitations, this technique might be an option for the detection of IgG or specific IgG1 and IgG2 subclasses. Canine ehrlichiosis is an important differential diagnosis of American Visceral Leishmaniasis (AVL). The present study compared ELISA using Leishmania chagasi and Leishmania braziliensis antigen for the detection of anti-Leishmania IgG and subclasses in serum samples from 37 dogs naturally infected with L. chagasi (...

Sandfly fauna (Diptera: Psychodidae) in Parque do Sabiá complex, Uberlândia, Minas Gerais, Brazil.

Revista do Instituto de Medicina Tropical de Sao Paulo — Sat, 01 Oct 2011 04:00:00 +0100

The objective was to associate the sandfly species captured to the risk of the transmission of leishmaniasis in the municipality. The 126 captured specimens belonging to six species of phlebotomine, among which Lutzomyia (Psychodopygus) davisi (Root, 1934) predominated with 113 specimens (89.7%). The remaining captured species were Lutzomyia (Pintomyia) mamedei Oliveira, Afonso, Dias & Brazil, 1994 - five specimens (3.9%); Lutzomyia (Nyssomyia) flaviscutellata (Mangabeira, 1942) - four specimens (3.2%); Lutzomyia lenti (Mangabeira, 1938) - two specimens (1.6%); Brumptomyia avellari (Costa Lima, 1932) - one specimen (0.8%); and Lutzomyia (Nyssomyia) whitmani (Antunes & Coutinho, 1939) - one specimen (0.8%). The collection of species that may be involved in the transmission of Leishm...

Chronic cutaneous leishmaniasis, a great mimicker with various clinical presentations: 12 years experience from Aleppo

Journal of the European Academy of Dermatology and Venereology — Thu, 29 Sep 2011 04:00:00 +0100

Conclusions CCL due to Leishmania tropica can mimic many other dermatological conditions which might lead to a delay in making the correct diagnosis resulting in increased resistance to treatment. We have illustrated eight different clinical presentations of CCL and their differential diagnoses to make physicians more aware of the atypical presentations of CCL. A new treatment plan is suggested for the high‐risk group of acute cutaneous leishmaniasis patients to decrease the likelihood of progressing to chronicity. (Source: Journal of the European Academy of Dermatology and Venereology)

Expression of a Leishmaniadonovani nucleotide sugar transporter in Leishmaniamajor enhances survival in visceral organs.

Experimental Parasitology — Thu, 29 Sep 2011 04:00:00 +0100

In this study we report that Ld1590 potentially encodes a nucleotide sugar transporter (NST) which localizes in the L.donovani Golgi apparatus. Surprisingly, although transgenic expression of the Ld1590 NST increased L.major survival in visceral organs, deletion of Ld1590 NST in L.donovani had no significant effect on L.donovani survival in mice. These observations suggest that loss of the functional Ld1590 gene in L.major may have been associated with reduced virulence in visceral organs in its animal reservoir and could have contributed to L.major's tropism for cutaneous infections. PMID: 21978449 [PubMed - as supplied by publisher] (Source: Experimental Parasitology)

Transmission of Leishmania infantum MON-98 to hamsters by the bite of Phlebotomus langeroni Nitzulescu (Diptera: Psychodidae).

Acta Tropica — Thu, 22 Sep 2011 04:00:00 +0100

Authors: El Sawaf BM, Doha SA, Imam MI Abstract The ability of Phlebotomus langeroni to successfully acquire and transmit Leishmania infantum MON-98 to hamsters was demonstrated. Sand flies and Leishmania both originated from an infantile visceral leishmaniasis focus in El Agamy Egypt. P. langeroni females were infected by feeding on lesions of needle-inoculated hamster and on infected blood suspension using a chick-skin membrane apparatus. Infection rate of sand flies fed on membrane was 88% compared to 7.8% for flies fed on leishmanial lesion. The transmission to hamster took place by the bites of infective flies taking a second blood meal, on the 8th to 10th day post-feeding. Furthermore, successful transmission was by the bites of flies that took no blood or that took partial b...

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Leishmania species identification using FTA card sampling directly from patients’ cutaneous lesions in the state of Lara, Venezuela

Transactions of the Royal Society of Tropical Medicine and Hygiene — Tue, 20 Sep 2011 17:25:25 +0100

Abstract: A molecular epidemiological study was performed using FTA card materials directly sampled from lesions of patients with cutaneous leishmaniasis (CL) in the state of Lara, Venezuela, where causative agents have been identified as Leishmania (Viannia) braziliensis and L. (Leishmania) venezuelensis in previous studies. Of the 17 patients diagnosed with CL, Leishmania spp. were successfully identified in 16 patients based on analysis of the cytochrome b gene and rRNA internal transcribed spacer sequences. Consistent with previous findings, seven of the patients were infected with L. (V.) braziliensis. However, parasites from the other nine patients were genetically identified as L. (L.) mexicana, which differed from results of previous enzymatic and antigenic analyses. These results ...

Wild, synanthropic and domestic hosts of Leishmania in an endemic area of cutaneous leishmaniasis in Minas Gerais State, Brazil

Transactions of the Royal Society of Tropical Medicine and Hygiene — Tue, 20 Sep 2011 17:25:25 +0100

This study evaluated 72 rodents, 25 marsupials and 98 domestic dogs found in two villages of the Xakriabá Indigenous Territory, an area of intense ATL transmission. A total of 23 dogs (23.47%) were shown to be positive according to at least one test; 8 dogs (8.16%) tested positive in a single serological test and 15 dogs (15.31%) tested positive by IFAT and ELISA. Eleven dogs were euthanised to allow for molecular diagnosis, of which nine (81.8%) tested positive by PCR for Leishmania in at least one tissue. Seven animals were infected only with L. (L.) infantum, whilst two displayed a mixed infection of L. (L.) infantum and L. (V.) braziliensis. Isoenzymatic characterisation identified L. (L.) infantum parasites isolated from the bone marrow of two dogs. Of the 97 small mammals captured, ...

Evaluation of an ELISA assay for canine leishmaniasis immunodiagnostic using recombinant proteins

Parasite Immunology — Tue, 20 Sep 2011 08:18:04 +0100

SummaryThe present work describes the isolation and purification of two Leishmania chagasi (= syn. Leishmania infantum) recombinant proteins, rLci2B and rLci1A, and their use in the development of an immunoassay for the diagnostic of canine leismaniasis. After protein expression and cell disruption, rLci2B was purified by immobilized metal affinity chromatography followed by size exclusion chromatography, whereas rLci1A, expressed as an inclusion body, was treated with urea and purified by anion exchange chromatography. Homogeneities were ascertained by denaturing gel electrophoresis (MW rLci2B = 46370; MWrLci1A= 88400), isoelectric focusing (pI rLci2B = 5.91; pI rLci1A= 6.01) and western blot. An indirect ELISA assay was developed using the purified antigens rLci2B and rLci1A and a leisma...

Intrachromosomal tandem duplication and repeat expansion during attempts to inactivate the subtelomeric essential gene GSH1 in Leishmania

Nucleic Acids Research — Tue, 20 Sep 2011 04:00:00 +0100

Gamma-glutamylcysteine synthetase encoded by GSH1 is the rate-limiting enzyme in the biosynthesis of glutathione and trypanothione in Leishmania. Attempts to generate GSH1 null mutants by gene disruption failed in Leishmania infantum. Removal of even a single allele invariably led to the generation of an extra copy of GSH1, maintaining two intact wild-type alleles. In the second and even third round of inactivation, the markers integrated at the homologous locus but always preserved two intact copies of GSH1. We probed into the mechanism of GSH1 duplication. GSH1 is subtelomeric on chromosome 18 and Southern blot analysis indicated that a 10-kb fragment flanked by 466-bp direct repeated sequences was duplicated in tandem on the same chromosomal allele each time GSH1 was targeted. Polymeras...

Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses.

Journal of Leukocyte Biology — Tue, 20 Sep 2011 04:00:00 +0100

Authors: Pereira WF, Ribeiro-Gomes FL, Guillermo LV, Vellozo NS, Montalvão F, Dosreis GA, Lopes MF Abstract Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1(hi)(Ly6C(hi)) CD11b(hi) MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate in...

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Natural Infection of Leishmania (Viannia) braziliensis in Mus musculus Captured in Mato Grosso, Brazil

Vector-Borne and Zoonotic Diseases — Fri, 16 Sep 2011 14:43:53 +0100

Vector-Borne and Zoonotic Diseases , Vol. 0, No. 0. (Source: Vector-Borne and Zoonotic Diseases)

A Novel 12.6-kDa Protein of Leishmania donovani for the Diagnosis of Indian Visceral Leishmaniasis

Vector-Borne and Zoonotic Diseases — Fri, 16 Sep 2011 14:43:51 +0100

Vector-Borne and Zoonotic Diseases , Vol. 0, No. 0. (Source: Vector-Borne and Zoonotic Diseases)

Molecular Diagnosis of Leishmania mexicana in a Cutaneous Leishmaniasis Case in Sinaloa, Mexico

Vector-Borne and Zoonotic Diseases — Fri, 16 Sep 2011 14:43:36 +0100

Vector-Borne and Zoonotic Diseases , Vol. 0, No. 0. (Source: Vector-Borne and Zoonotic Diseases)

Flagellar Membrane Determinants of FCaBP [Microbiology]

Journal of Biological Chemistry — Fri, 16 Sep 2011 04:00:00 +0100

The flagellar calcium-binding protein (FCaBP) of Trypanosoma cruzi is localized to the flagellar membrane in all life cycle stages of the parasite. Myristoylation and palmitoylation of the N terminus of FCaBP are necessary for flagellar membrane targeting. Not all dually acylated proteins in T. cruzi are flagellar, however. Other determinants of FCaBP therefore likely contribute to flagellar specificity. We generated T. cruzi transfectants expressing the N-terminal 24 or 12 amino acids of FCaBP fused to GFP. Analysis of these mutants revealed that although amino acids 1–12 are sufficient for dual acylation and membrane binding, amino acids 13–24 are required for flagellar specificity and lipid raft association. Mutagenesis of several conserved lysine residues in the latter peptide demo...

Lutzomyia (Pintomyia) fischeri (Diptera: Psychodidae: Phlebotominae), a probable vector of American Cutaneous Leishmaniasis: Detection of natural infection by Leishmania (Viannia) DNA in specimens from the municipality of Porto Alegre (RS), Brazil, using multiplex PCR assay.

Acta Tropica — Fri, 16 Sep 2011 04:00:00 +0100

Authors: Pereira DD, Souza GD, Pereira TD, Zwetsch A, Britto C, Rangel EF Abstract In order to determine natural Leishmania (Viannia) infection in Lutzomyia (Pintomyia) fischeri, a multiplex PCR methodology coupled to non-isotopic hybridization was adopted for the analysis of sand fly samples collected by CDC light traps in an endemic area of American Cutaneous Leishmaniasis (ACL) in the periurban region of the municipality of Porto Alegre, Rio Grande do Sul State, Brazil. We analyzed by PCR methodology 560 specimens of Lutzomyia (Pintomyia) fischeri (520 females and 40 males). The wild sand flies were grouped into 56 pools (52 females and 4 males) of 10 each, and positive results were detected in 2 of the 52 female pools, representing a minimum infection rate of 0.38% based on the...

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Isolation and detection of Leishmania species among naturally infected Rhombomis opimus, a reservoir host of zoonotic cutaneous leishmaniasis in Turkemen Sahara, North East of Iran.

Experimental Parasitology — Fri, 16 Sep 2011 04:00:00 +0100

Authors: Mirzaei A, Rouhani S, Taherkhani H, Farahmand M, Kazemi B, Hedayati M, Baghaei A, Davari B, Parvizi P Abstract In Iran, three species of Leishmania have been incriminated as the causative agents of human leishmaniasis, Leishmania (L.) major, Leishmania tropica, and Leishmania infantum.Rhombomis opimus have been incriminated as a principal reservoirs of the parasitic protozoan Leishmania major, the causative agent of rural zoonotic cutaneous leishmaniasis (ZCL) in Iran. Rodents captured and examined to find Leishmania species using conventional methods including direct impression smear and microscopic observation inoculation samples to Balb/c and culture in NNN medium. Also molecular method was employed to detect Leishmania in rodents by amplifying a region of the ribosomal...

Use of Parasitological Culture to Detect Leishmania (Leishmania) chagasi in Naturally Infected Dogs

Vector-Borne and Zoonotic Diseases — Thu, 15 Sep 2011 18:44:17 +0100

Vector-Borne and Zoonotic Diseases , Vol. 0, No. 0. (Source: Vector-Borne and Zoonotic Diseases)

Leishmania Major Infection Among Psammomys Obesus and Meriones Shawi: Reservoirs of Zoonotic Cutaneous Leishmaniasis in Sidi Bouzid (Central Tunisia)

Vector-Borne and Zoonotic Diseases — Thu, 15 Sep 2011 18:44:07 +0100

Vector-Borne and Zoonotic Diseases , Vol. 0, No. 0. (Source: Vector-Borne and Zoonotic Diseases)

Leishmania infantum LeIF and its recombinant polypeptides modulate interleukin IL‐12p70, IL‐10 and tumour necrosis factor‐α production by human monocytes

Parasite Immunology — Thu, 15 Sep 2011 11:06:57 +0100

This study aimed at characterizing the cytokine‐inducing activity of Leishmania infantum LeIF [Leishmania (L.) infantum (LieIF)] and at defining the fragments necessary for inducing cytokine secretion. Eleven rationally designed recombinant polypeptides, corresponding to the entire LeIF protein or parts of it, were expressed and used to stimulate monocytes from healthy individuals. Leishmania (L.) infantum was able to induce IL‐12p70, IL‐10 and TNF‐α secretion in human monocytes. In addition, both amino‐ (1–226) and carboxyl‐terminal (196–403) parts of the protein were shown to induce significant levels of the three cytokines analysed. However, IL‐12p70‐inducing activity was not significant when monocytes were stimulated with the fragments 129–226 and 129–261, infe...

Co‐administration of rectal BCG and autoclaved Leishmania major induce protection in susceptible BALB/c mice

Parasite Immunology — Thu, 15 Sep 2011 11:06:53 +0100

In conclusion, the results of our study indicated that co‐administration of rectal BCG and ALM induced protective type 1 immune responses against L. major infection. This safe and effective mucosal vaccine could be useful in prevention of human leishmaniasis infections. (Source: Parasite Immunology)

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Identification of Inhibitors of the Leishmania cdc-Related Protein Kinase CRK3.

ChemMedChem — Tue, 13 Sep 2011 04:00:00 +0100

Authors: Cleghorn LA, Woodland A, Collie IT, Torrie LS, Norcross N, Luksch T, Mpamhanga C, Walker RG, Mottram JC, Brenk R, Frearson JA, Gilbert IH, Wyatt PG Abstract New drugs are urgently needed for the treatment of tropical parasitic diseases such as leishmaniasis and human African trypanosomiasis (HAT). This work involved a high-throughput screen of a focussed kinase set of ~3400 compounds to identify potent and parasite-selective inhibitors of an enzymatic Leishmania CRK3-cyclin 6 complex. The aim of this study is to provide chemical validation that Leishmania CRK3-CYC6 is a drug target. Eight hit series were identified, of which four were followed up. The optimisation of these series using classical SAR studies afforded low-nanomolar CRK3 inhibitors with significant selectiv...

Conjunctival Squamous Cell Carcinoma Harboring Leishmania Amastigotes in a Human Immunodeficiency Virus-Positive Patient [Research Letters]

Archives of Opthalmology — Mon, 12 Sep 2011 04:00:00 +0100

(Source: Archives of Opthalmology)

The prevalence of canine Leishmania infantum infection in Sichuan Province, southwestern China detected by real time PCR

Parasites and Vectors — Mon, 12 Sep 2011 04:00:00 +0100

The paper investigated the prevalence of Leishmania infantum infection in dogs from Wenchuan, Heishui and Jiuzhaigou County in Sichuan Province, southwestern China by real time PCR. A higher prevalence was found in older dogs and those showing external symptoms. Image: Infected dogs are major reservoirs for Leishmania infantum. (Source: Parasites and Vectors)

Synthesis, cytotoxicity, and in vitro antileishmanial activity of mono-t-butyloxycarbonyl-protected diamines

Diagnostic Microbiology and Infectious Disease — Mon, 12 Sep 2011 04:00:00 +0100

In this study, using the in vitro traditional drug screening test, we have analyzed the effects of a series of diaminoalkanes monoprotected with t-butyloxycarbonyl (BOC) against L. amazonensis. Among the 18 tested compounds, 6 exhibited antileishmanial activity (2, 7–9, 17, and 18). Best IC50 values (10.39 ± 0.27 and 3.8 ± 0.42 μg/mL) were observed for compounds 17 and 18 (H2N(CH2)nNHBoc, n = 10 and 12), respectively. Although those compounds had higher lipophilicity as indicated by their cLog P values, compound 17 was very toxic. Determination of the selective indexes indicated that 50% of the active compounds were very toxic for HepG2 cells. However, compounds 2, 8, and 18 had good lipophilicity and were less toxic among all polyamine derivatives tested. The chemical properties of a...

Auricular enlargement: An atypical presentation of old world cutaneous leishmaniasis

Indian Journal of Dermatology — Sat, 10 Sep 2011 04:00:00 +0100

Reza Mahmoud Robati, Mehdi Qeisari, Marjan Saeedi, Mona KarimiIndian Journal of Dermatology 2011 56(4):428-429The auricle is an extremely rare site for cutaneous leishmaniasis (CL) in Old World, which tends to be a benign disease with self-healing small nodules such as the "oriental sore". However, in the New World, there is a type of CL of the ear, named as "chiclero's ulcer" which is caused by Leishmania mexicana. Herein, we describe a case of massive auricular enlargement due to Old World CL. (Source: Indian Journal of Dermatology)

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Structure and Function of a Protective Protein [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 09 Sep 2011 04:00:00 +0100

In this study, we immunized mice with 17 plasmids encoding L. longiplapis salivary proteins and demonstrated that LJM11 confers protective immunity against Leishmania major infection. This protection correlates with a strong induction of a delayed type hypersensitivity (DTH) response following exposure to L. longipalpis saliva. Additionally, splenocytes of exposed mice produce IFN-γ upon stimulation with LJM11, demonstrating the systemic induction of Th1 immunity by this protein. In contrast to LJM11, LJM111, another yellow protein from L. longipalpis saliva, does not produce a DTH response in these mice, suggesting that structural or functional features specific to LJM11 are important for the induction of a robust DTH response. To examine these features, we used calorimetric analysis to ...

Expression of Recombinant Human Coagulation Factor VII by the Lizard Leishmania Expression System

International Journal of Biomedical Imaging — Thu, 08 Sep 2011 11:11:37 +0100

Conclusion, this study has demonstrated, for the first time, that Leishmania cells can be used as an expression system for producing recombinant FVII. (Source: International Journal of Biomedical Imaging)

Synthesis and evaluation of the anti parasitic activity of aromatic nitro compounds.

European Journal of Medicinal Chemistry — Thu, 08 Sep 2011 04:00:00 +0100

Authors: Lopes MS, de Souza Pietra RC, Borgati TF, Romeiro CF, Júnior PA, Romanha AJ, Alves RJ, Souza-Fagundes EM, Fernandes AP, de Oliveira RB Abstract A series of nitroaromatic compounds was synthesized and evaluated as potential antileishmanial and trypanocidal agents. Five compounds exerted significant anti-leishmanial activity in vitro against promastigotes forms of Leishmania (L.) amazonensis, with IC(50) in the range of 23-59 μmol L(-1), but none were active against amastigotes intracellular forms of Trypanosoma cruzi. In vitro cytotoxicity on the proliferation of human peripheral blood mononuclear cells (PBMC) stimulated with phytohemaglutinin (PHA) was also evaluated. Two compounds, 6 and 7, were found to present a promising anti-leishmanial activity with IC(50) valu...

Characterisation of antimony-resistant Leishmania donovani isolates: Biochemical and biophysical studies and interaction with host cells.

International Journal for Parasitology — Wed, 07 Sep 2011 04:00:00 +0100

Authors: Mukhopadhyay R, Mukherjee S, Mukherjee B, Naskar K, Mandal D, Decuypere S, Ostyn B, Prajapati VK, Sundar S, Dujardin JC, Roy S Abstract Recent clinical isolates of Leishmania donovani from the hyperendemic zone of Bihar were characterised in vitro in terms of their sensitivity towards sodium stibogluconate (SSG) in a macrophage (MΦ) culture system. The resulting half maximal effective concentration (EC(50)) values were compared with those of known sensitive isolates. Fifteen of the isolates showed decreased sensitivity towards SSG with an average EC(50) of 25.7±4.5μg/ml pentavalent antimony (SbV) (defined as antimony resistant (Sb-R)), whereas nine showed considerable sensitivity with an average EC(50) of 4.6±1.7μg/ml (defined as antimony sensitive (Sb-S)). Out of tho...