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immunization with leishmania vaccine-alum-bcg and montanide isa 720 adjuvants induces low-grade type 2 cytokines and high levels of igg2 subclass antibodies in the vervet monkey (chlorocebus aethiops) model.the availability of hundreds of adjuvants has prompted a need for identifying rational standards for the selection of adjuvant formulation based on sound immunological principles for human vaccines. as cytokines elaborated by activated t cells are required for the regulation of isotype switch during b-cell development, a study of th2 cytokines and subclass distribution of the antibodies may shed new light on the processes involved in the polarization of the immune responses during vaccination st ...201222862788
the narrow active-site cleft of o-acetylserine sulfhydrylase from leishmania donovani allows complex formation with serine acetyltransferases with a range of c-terminal sequences.cysteine is a crucial substrate for the synthesis of glutathione and trypanothione, which in turn maintain intracellular redox homeostasis and defend against oxidative stress in the pathogen leishmania donovani. here, the identification, sequencing, characterization and crystal structure at 1.79 å resolution of o-acetylserine sulfhydrylase (oass), a cysteine-biosynthetic pathway enzyme from l. donovani (ldoass), are reported. it shows binding to the serine acetyltransferase (sat) c-terminal pept ...201222868756
development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis.the purpose of this study was to explore the applicability, targeting potential and drug delivery to specialized phagocytes via phosphatidylserine (ps)-specific ligand-anchored nanocapsules (ncs) bearing doxorubicin.201222872448
pcr-based detection of leishmania donovani dna in a stray dog from a visceral leishmaniasis endemic focus in bangladesh.although phlebotomus argentipes as the only known vector of visceral leishmaniasis (vl) is zoophilic in nature, vl is considered to be anthroponotic in the indian subcontinent. peripheral blood samples from 85 stray dogs were examined for any molecular evidence of leishmania infection in vl endemic areas of bangladesh. parasite dna was detected in a blood sample from 1 of 85 (1.2%) stray dogs using its1-pcr, and pcr sequencing of the rrna-its and cytochrome b gene confirmed that the parasitic dn ...201322878541
post-kala-azar dermal leishmaniasis in visceral leishmaniasis-endemic communities in bihar, india.we assessed the prevalence of post-kala-azar dermal leishmaniasis (pkdl), a late cutaneous manifestation of visceral leishmaniasis (vl), in 16 vl-endemic communities in bihar, india. the prevalence of confirmed pkdl cases was 4.4 per 10 000 individuals and 7.8 if probable cases were also considered. the clinical history and treatment of the post-kala-azar dermal leishmaniasis cases are discussed.201222882665
the histone acetyl transferase ldhat1 from leishmania donovani is regulated by s-phase cell cycle kinase.histone acetyl transferases (hats) are important histone modifiers that affect critical cellular processes like transcription, dna replication and repairs through highly dynamic chromatin remodelling. our earlier studies recognized ldhat1 as a substrate of the s-phase cell cycle kinase ldcyc1-crk3 from leishmania donovani. here, we confirm through site-directed mutagenesis that rxl-like cyclin-binding (cy) motif dependent interaction of ldhat1 with ldcyc1 is essential for its phosphorylation at ...201222889278
deletion of mitochondrial associated ubiquitin fold modifier protein ufm1 in leishmania donovani results in loss of β-oxidation of fatty acids and blocks cell division in the amastigote stage.recently, we described the existence of the ubiquitin fold modifier 1 (ufm1) and its conjugation pathway in leishmania donovani. we demonstrated the conjugation of ufm1 to proteins such as mitochondrial trifunctional protein (mtp) that catalyses β-oxidation of fatty acids in l. donovani. to elucidate the biological roles of the ufm1-mediated modifications, we made an l. donovani ufm1 null mutant (ufm1(-/-)). loss of ufm1 and consequently absence of ufm1 conjugation with mtp resulted in diminishe ...201222897198
leishmanicidal and anticandidal activity of constituents of indian edible mushroom astraeus hygrometricus.two new lanostane-type triterpenes, 1 and 2, were isolated from astraeus hygrometricus. the structures were established by ir, (1)h- and (13)c-nmr, ms, and x-ray crystallographic experiments. the triterpenes exhibited excellent in vitro toxicities against candida albicans, comparable to standard antifungal antibiotics. the triterpene 2 significantly inhibited the growth of leishmania donovani promastigotes in vitro. the triterpene skeleton may be considered a template structure in search for new ...201222899612
the role of nf-κb activation during protection against leishmania infection.members of the nuclear factor-κb (nf-κb) family of transcription factors regulate a variety of molecules involved in host defense against pathogens. a prominent role of nf-κb in innate and adoptive immunity is based on the regulation of inducible transcription of various genes whose products are essential components of the immune response such as cytokines, chemokines, and adhesion molecules. since the discovery of the five members of the nf-κb transcription factor family, rela, c-rel, relb, p50 ...201222901377
pentacyclic ingamine alkaloids, a new antiplasmodial pharmacophore from the marine sponge petrosid ng5 sp5.two new pentacyclic ingamine alkaloids, namely 22(s)-hydroxyingamine a (2) and dihydroingenamine d (3), together with the known ingamine a (1), have been isolated from marine sponge petrosid ng5 sp5 (family petrosiidae) obtained from the open repository of the national cancer institute, usa. the structures of compounds 1-3 were determined using 1d and 2d nmr, and hresims techniques. the absolute configuration of both the c9 and c22 of 2 was determined as (s) using a modified mosher esterificatio ...201222903383
visceral leishmaniasis: a case report.although leishmaniasis is widely prevalent in the eastern states of india namely bihar, jharkhand, uttar pradesh and west bengal, diagnosing the illness is still difficult. we present a case of a 20-year-old agricultural labourer with a history of recurrent fever, progressive weakness and abdominal discomfort associated with loss of appetite for six months followed by petechial hemorrhages over body.on examination there was hepato-splenomegaly. a diagnosis of visceral leishmaniasis (kala-azar) w ...201222905054
il-10-producing th1 cells and disease progression are regulated by distinct cd11c⁺ cell populations during visceral leishmaniasis.il-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of cd4⁺ ifnγ⁺ t cells committed to il-10 production. here, combining conditional cell-specific depletion with adoptive transfer, we demonstrate that only conventional cd11c(hi) dcs that produce both il-10 and il-27 are capable of inducing il-10-producing th1 cells in vi ...201222911108
immunobiology of visceral leishmaniasis.visceral leishmaniasis (vl), commonly known as kala-azar, is caused by leishmania donovani and leishmania infantum (leishmania chagasi in the americas). these leishmania species infect macrophages throughout the viscera, and parasites are typically found in the spleen, liver, and bone marrow. patients with active disease typically exhibit marked immunosuppression, lack reactivity to the leishmania skin test (lst), a delayed type hypersensitivity test, and their peripheral blood mononuclear cells ...201222912637
kdna genetic signatures obtained by lssp-pcr analysis of leishmania (leishmania) infantum isolated from the new and the old world.visceral leishmaniasis (vl) caused by species from the leishmania donovani complex is the most severe form of the disease, lethal if untreated. vl caused by leishmania infantum is a zoonosis with an increasing number of human cases and millions of dogs infected in the old and the new world. in this study, l. infantum (syn. l.chagasi) strains were isolated from human and canine vl cases. the strains were obtained from endemic areas from brazil and portugal and their genetic polymorphism was ascer ...201222912862
real-time pcr to quantify leishmania donovani in hamsters.visceral leishmaniasis, a vector-borne disease caused by leishmania donovani and leishmania infantum , currently affects 12 million individuals in 88 countries. in the present study, a real-time pcr (rt-pcr) assay has been optimized and validated against 2 other routine methods, i.e., microscopy and limiting dilution culture assay, to estimate parasite load in the liver of infected syrian hamsters (mesocricetus auratus). a set of specific primers amplified a 116-bp target template of the kinetop ...201322924923
in vitro antileishmanial drug susceptibility of clinical isolates from patients with indian visceral leishmaniasis--status of newly introduced drugs.regional variations in susceptibility of leishmania donovani clinical isolates have been reported to antimonials but not other antileishmanial drugs. therefore, we evaluated the susceptibility of four antileishmanial drugs in clinical use in 28 clinical isolates from endemic and non-endemic regions in the j774a.1 macrophage cell line, and we found increased tolerance of miltefosine and paromomycin in isolates from a patient from a high endemic region. effective dose for 90% killing (ed(90)) valu ...201222927497
involvement of cd4⁺ foxp3⁺ regulatory t cells in persistence of leishmania donovani in the liver of alymphoplastic aly/aly mice.visceral leishmaniasis (vl) is a chronic and fatal disease in humans and dogs caused by the intracellular protozoan parasites, leishmania donovani and l. infantum (l. chagasi). relapse of disease is frequent in immunocompromised patients, in which the number of vl cases has been increasing recently. the present study is aimed to improve the understanding of mechanisms of l. donovani persistence in immunocompromised conditions using alymphoplastic aly/aly mice. hepatic parasite burden, granuloma ...201222928057
2-alkynoic fatty acids inhibit topoisomerase ib from leishmania donovani.2-alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. in this work we synthesized the 2-octadecynoic acid (2-oda), 2-hexadecynoic acid (2-hda), and 2-tetradecynoic acid (2-tda) and show that 2-oda is the best inhibitor of the leishmania donovani dna topoisomerase ib enzyme (ldtopib) with an ec(50)=5.3±0.7μm. the potency of ldtopib inhibition follows the trend 2-oda>2-hda>2-tda, indicating that the e ...201222932312
development of luciferase expressing leishmania donovani axenic amastigotes as primary model for in vitro screening of antileishmanial compounds.the development of new therapeutic leads against leishmaniasis relies primarily on screening of a large number of compounds on multiplication of clinically irrelevant transgenic promastigotes. the advent of the successful in vitro culture of axenic amastigotes allows the development of transgenic axenic amastigotes as a primary screen which can test compounds in a high throughput mode like promastigotes, still representative of the clinically relevant mammalian amastigotes stage. the present stu ...201222945482
kinetics and docking studies of two potential new inhibitors of the nucleoside hydrolase from leishmania donovani.in this study the recombinant enzyme nucleoside hydrolase of leishmania donovani (rldnh) was expressed in escherichia coli in connection with maltose binding protein (mbp). the rldnh-mbp showed efficient a significant in vitro activity with inosine as substrate. from the coupled reaction with xanthine oxidase (xo) it was possible to determine the kinetic constants of rldnh-mbp as k(m) (434 ± 109 μm) and v(max) (0.20 ± 0.02 μm). in addition, two nucleoside analogs (compounds 1 and 2) were tested ...201222947894
drug-resistant microorganisms with a higher fitness--can medicines boost pathogens?drug-resistant microorganisms (drms) are generally thought to suffer from a fitness cost associated with their drug-resistant trait, inflicting them a disadvantage when the drug pressure reduces. however, leishmania resistant to pentavalent antimonies shows traits of a higher fitness compared to its sensitive counterparts. this is likely due the combination of an intracellular pathogen and a drug that targets the parasite's general defense mechanisms while at the same time stimulating the host's ...201322950457
marchantin a, a macrocyclic bisbibenzyl ether, isolated from the liverwort marchantia polymorpha, inhibits protozoal growth in vitro.in vitro anti-plasmodial activity-guided fractionation of a diethyl ether extract of the liverwort species marchantia polymorpha, collected in iceland, led to isolation of the bisbibenzyl ether, marchantin a. the structure of marchantin a (1) was confirmed by nmr and hreims. marchantin a inhibited proliferation of the plasmodium falciparum strains, nf54 (ic(50)=3.41μm) and k1 (ic(50)=2.02μm) and showed activity against other protozoan species trypanosoma brucei rhodesiense, t. cruzi and leishman ...201222951393
identification of th1-responsive leishmanial excretory-secretory antigens (lesas).the objective of this study was to evaluate the immunomodulatory role of leishmanial excretory-secretory antigens (lesas) released by in vitro cultured protozoan parasite leishmania donovani promastigotes. a total of seventeen excretory-secretory proteins of relative molecular weights 11, 13, 16, 18, 21, 23, 26, 29, 33, 35, 42, 51, 54, 58, 64, 70 and 80 kda were identified. the proteins were divided into five fractions (f1-f5) along with the whole lesas, these fractions were evaluated for their ...201222955114
extracts of artemisia annua leaves and seeds mediate programmed cell death in leishmania donovani.leishmaniasis is one of the major tropical parasitic diseases, and the condition ranges in severity from self-healing cutaneous lesions to fatal visceral manifestations. there is no vaccine available against visceral leishmaniasis (vl) (also known as kala-azar in india), and current antileishmanial drugs face major drawbacks, including drug resistance, variable efficacy, toxicity and parenteral administration. we report here that n-hexane fractions of artemisia annua leaves (aal) and seeds (aas) ...201222956747
retraction: human recombinant migration inhibitory factor activates human macrophages to kill leishmania donovani. 201222956762
rflps of its, its1 and hsp70 amplicons and sequencing of its1 of recent clinical isolates of kala-azar from india and bangladesh confirms the association of l. tropica with the disease.visceral leishmaniasis or kala-azar (ka) is a serious health concern in india. in the present study, restriction fragment length polymorphism (rflp) of three genetic markers viz., internal transcribed spacer (its), its1 and heat shock protein 70 (hsp70) have been employed for typing the clinical isolates [n=15] of ka and post kala-azar dermal leishmaniosis (pkdl) collected from india and bangladesh in the period of 2006-2010. experimentally, its, its1 and hsp70 regions of genomes of all the clin ...201222960646
antineoplastic drug, carboplatin, protects mice against visceral leishmaniasis.in the present study, the leishmanicidal effect of two doses (5 and 10 mg/kg body weight) of the carboplatin was studied in leishmania donovani-infected balb/c mice. mice were infected intracardially with promastigotes of l. donovani, and a month after infection, they were treated intraperitoneally with the two doses of the drug (5 and 10 mg/kg body weight) for five continuous days. animals were sacrificed on 1 and 15 posttreatment days. hepatic parasite load was assessed on geimsa-stained impri ...201322961311
atypical mucocutaneous involvement with leishmania donovani.mucocutaneous leishmaniasis has rarely been reported from india. the usual causative organisms of this infection are leishmania braziliensis and l. tropica. another species, l. donovani, which usually causes visceral leishmaniasis, has recently been reported to cause mucocutaneous disease in a few patients from sri lanka. we report two patients who had undiagnosed chronic skin lesions for several years. skin biopsies revealed leishmania and the species was characterized as l. donovani in both pa ...201322963292
laryngeal leishmaniasis: case report of a rare infection.we report a case of laryngeal leishmaniasis in a united kingdom (uk) resident who lived in spain for 5 years.201322972594
highlights on molecular identification of closely related species.the term "complex" emerged in the literature at the beginning of the genomic era associated to taxonomy and grouping organisms that belong to different species but exhibited similar patterns according to their morphological, physiological and/or other phenotypic features. dna-dna hybridization values ~70% and high identity on 16s rrna gene sequences were recommended for species delineation. electrophoretic methods showed in some cases to be useful for species identification and population struct ...201322982158
synthesis and structure-activity relationships of lansine analogues as antileishmanial agents.clear and rational thinking: a series of rationally designed, lansine-derived carbazoles was synthesized and evaluated for activity against promastigotes and amastigotes of leishmania donovani, the causative agent of leishmaniasis. some structural modifications gave rise to compounds with enhanced activity and selectivity over lansine, allowing structure-activity relationships to be elucidated and providing a foundation for the further development of this pharmacophore.201222987791
antitrypanosomal alkaloids from the marine bacterium bacillus pumilus.fractionation of the ethyl acetate extract of the marine bacterium bacillus pumilus isolated from the black coral antipathes sp. led to the isolation of five compounds: cyclo-(l-leu-l-pro) (1), 3-hydroxyacetylindole (2), n-acetyl-β-oxotryptamine (3), cyclo-(l-phe-l-pro) (4), and 3-formylindole (5). the structures of compounds 1-5 were established by spectroscopic analyses, including hresitof-ms and nmr (1h, 13c, hsqc, hmbc and cosy). compounds 2, 3 and 5 caused the inhibition on the growth of tr ...201222990456
a versatile proline/alanine transporter in the unicellular pathogen leishmania donovani regulates amino acid homoeostasis and osmotic stress responses.unlike all other organisms, parasitic protozoa of the family trypanosomatidae maintain a large cellular pool of proline that, together with the alanine pool, serve as alternative carbon sources as well as reservoirs of organic osmolytes. these reflect adaptation to their insect vectors whose haemolymphs are exceptionally rich in the two amino acids. in the present study we identify and characterize a new neutral amino acid transporter, ldaap24, that translocates proline and alanine across the le ...201322994895
effect of allicin on promastigotes and intracellular amastigotes of leishmania donovani and l. infantum.anti-leishmanial activity of allicin (=diallyl thiosulphinate) has been tested in vitro against promastigotes and intracellular amastigotes of leishmania donovani and leishmania infantum. macrophage infections have been carried out in vitro in the murine cell line j774 and ex vivo with peritoneal macrophages from balb/c mice with a modified method to isolate metacyclic promastigotes. the compound has shown a significant in vitro effect on the multiplication of promastigotes of l. donovani and l. ...201222995646
a pentapeptide signature motif plays a pivotal role in leishmania dna topoisomerase ib activity and camptothecin sensitivity.leishmania donovani - the causative agent of visceral leishmaniasis - has several evolutionary characteristics that make the disease difficult to combat. among these differences, a rare heterodimeric dna topoisomerase ib has been reported thus opening a new promising field in the therapy of leishmaniasis. several studies of the human enzyme have pointed to the importance of the linker domain in respect to camptothecin sensitivity. at present, it has been impossible to pinpoint the regions that m ...201223000572
a rapid method to assess the stage differentiation in leishmania donovani by flow cytometry.in this study we describe a rapid and novel method to assess the morphological stage differentiation in leishmania donovani by flow cytometry (fcm). fcm is fast, accurate, and inexpensive to study the stage differentiation of promastigote into l. donovani axenic amastigote (ldaxam). the non-flourimetric fcm method is easy to perform; with requirement of little expertise, and provides unambiguous results. it is an advanced tool, requires minimal time, and no fluorescent dyes. the gradual increase ...201223022521
testing urine samples with rk39 strip as the simplest non-invasive field diagnosis for visceral leishmaniasis: an early report from eastern india.diagnosis of visceral leishmaniasis (vl) is a major obstacle in the control of this disease. the rk39 strip-test using patient's blood is a breakthrough; however, it still requires a blood sample, which is a concern for safety in the field. we tried to simplify the test using the patient's urine instead of blood.201523023349
characterization of the recent clinical isolates of indian kala-azar patients by rapd-pcr method.leishmaniasis is one of the most important vector borne diseases caused by kinetoplastid protozoa leishmania sp. among all forms of leishmaniasis, visceral leishmaniasis (vl) or kala-azar is the severest form of the illness. vl is characterized by fever, hepatosplenomegaly, anaemia, edema, weight loss and invariably fatal if left untreated. characterization of leishmania sp. is extremely necessary to understand the epidemiology, taxonomy and population genetics of the parasites which ultimately ...201123024491
antimicrobial and antiprotozoal activities of secondary metabolites from the fungus eurotium repens.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 ...201123024574
the lignan niranthin poisons leishmania donovani topoisomerase ib and favours a th1 immune response in mice.niranthin, a lignan isolated from the aerial parts of the plant phyllanthus amarus, exhibits a wide spectrum of pharmacological activities. in the present study, we have shown for the first time that niranthin is a potent anti-leishmanial agent. the compound induces topoisomerase i-mediated dna-protein adduct formation inside leishmania cells and triggers apoptosis by activation of cellular nucleases. we also show that niranthin inhibits the relaxation activity of heterodimeric type ib topoisome ...201223027614
chemotherapy of leishmaniasis. part ix: synthesis and bioevaluation of aryl substituted ketene dithioacetals as antileishmanial agents.a new series of aryl substituted ketene dithioacetals 6a-h was synthesized and evaluated for their in vitro and in vivo antileishmanial activity against leishmania donovani. two compounds exhibited significant in vitro activity against intracellular amastigotes of l. donovani with ic(50) values 3.56 and 5.12 μm and were found promising as compared with reference drug, miltefosine. on the basis of good selectivity indices (s.i.), they were further tested for their in vivo response against l. dono ...201223031588
chemotherapy of leishmaniasis. part xi: synthesis and bioevaluation of novel isoxazole containing heteroretinoid and its amide derivatives.novel isoxazole containing heteroretinoid (4) and its amide derivatives (5a-j) have been synthesized and evaluated for their in vivo antileishmanial activity against leishmania donovani in hamsters. compounds 3, 5a, 5d, 5k and 5l inhibited 70-76% parasite growth at 50 mg kg(-1) ×5 days. the present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent.201223031597
leishmanicidal activity of two naphthoquinones against leishmania donovani.here we studied ability of two naphthoquinones to inhibit leishmania growth (2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (tr 001) and 2,3-dibromo-1,4-naphthoquinone (tr 002). tr 001 was more efficient than tr 002 in inducing killing of promastigotes and intracellular amastigotes. these values compare well to those obtained with the standard first-line antileishmanial agent sodium stibogluconate (ssg). tr 001 also induced significantly more nitric oxide (no) production than tr 002 or ssg. taken ...201223037165
leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis.visceral leishmaniasis (vl) is one of the most important parasitic diseases with approximately 350 million people at risk. due to the non availability of an ideal drug, development of a safe, effective, and affordable vaccine could be a solution for control and prevention of this disease. in this study, a potential th1 stimulatory protein- triose phosphate isomerase (tpi), a glycolytic enzyme, identified through proteomics from a fraction of leishmania donovani soluble antigen ranging from 89.9- ...201223049855
leishmania promastigotes: building a safe niche within macrophages.upon their internalization by macrophages, leishmania promastigotes inhibit phagolysosome biogenesis. the main factor responsible for this inhibition is the promastigote surface glycolipid lipophosphoglycan (lpg). this glycolipid has a profound impact on the phagosome, causing periphagosomal accumulation of f-actin and disruption of phagosomal lipid microdomains. functionally, this lpg-mediated inhibition of phagosome maturation is characterized by an impaired assembly of the nadph oxidase and t ...201223050244
immunopathogenesis of non-healing american cutaneous leishmaniasis and progressive visceral leishmaniasis.the outcomes of leishmania infection are determined by host immune and nutrition status, parasite species, and co-infection with other pathogens. while subclinical infection and self-healing cutaneous leishmaniasis (cl) are common, uncontrolled parasite replication can lead to non-healing local lesions or visceral leishmaniasis (vl). it is known that infection control requires th1-differentiation cytokines (il-12, il-18, and il-27) and th1 cell and macrophage activation. however, there is no gen ...201223053396
hyperlipidemia offers protection against leishmania donovani infection: role of membrane cholesterol.leishmania donovani (ld), the causative agent of visceral leishmaniasis (vl), extracts membrane cholesterol from macrophages and disrupts lipid rafts, leading to their inability to stimulate t cells. restoration of membrane cholesterol by liposomal delivery corrects the above defects and offers protection in infected hamsters. to reinforce further the protective role of cholesterol in vl, mice were either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. subsequent ld ...201223060454
[kala azar - lethal course of visceral leishmaniasis. synchronous infection with leishmania donovani/infantum complex and leishmania major in a patient after mediterranean vacation].infections with leishmania spp. are endemic in areas of the tropics and subtropics. an increased incidence of human infections has been reported in southern europe, where zoonotic leishmaniasis is common. the systemic, visceral infection is caused by the leishmania donovani/infantum complex and may be fatal when untreated.201223064668
molecular and parasitological detection of leishmania spp. in dogs caught in palmas, to, brazil.this study evaluated occurrences of leishmania infantum in dogs in the municipality of palmas, tocantins, comparing diagnostic data obtained using the polymerase chain reaction (pcr) and parasitological diagnosis. blood samples and lymph node aspirates were collected from 63 dogs of males and females and various ages and races, with or without owners, between august 2009 and june 2010. slides containing smears of lymph node aspirates were stained with giemsa stained. in pcr, the 145 bp target se ...201223070439
expression of concern: ahlin e et al.,"anti-citrullinated peptide antibodies and rheumatoid factor in sudanese patients with leishmania donovani infection", rev bras reumatol 2011; 51(6):572-86. 201223090367
leishmania donovani argininosuccinate synthase is an active enzyme associated with parasite pathogenesis.gene expression analysis in leishmania donovani (ld) identified an orthologue of the urea cycle enzyme, argininosuccinate synthase (ldass), that was more abundantly expressed in amastigotes than in promastigotes. in order to characterize in detail this newly identified protein in leishmania, we determined its enzymatic activity, subcellular localization in the parasite and affect on virulence in vivo.201223094117
erythrocyte glutathione status in human visceral leishmaniasis.a glutathione redox cycle is a major antioxidant defense system for the detoxification of reactive oxygen species within erythrocytes. reactive oxygen species such as superoxide anions, hydrogen peroxide and hydroxyl radicals are generated as a host defense mechanism for killing of engulfed leishmania donovani, a causative agent of visceral leishmaniasis, are capable of damaging lipids and other biomolecules when produced in excess. erythrocytes are most vulnerable to reactive oxygen species. in ...200823105731
the hsp90-sti1 interaction is critical for leishmania donovani proliferation in both life cycle stages.the heat shock protein 90 plays a pivotal role in the life cycle control of leishmania donovani promoting the fast-growing insect stage of this parasite. equally important for insect stage growth is the co-chaperone sti1. we show that replacement of sti1 is only feasible in the presence of additional sti1 transgenes indicating an essential role. to better understand the impact of sti1 and its interaction with hsp90, we performed a mutational analysis of hsp90. we established that a single amino ...201323107115
first total synthesis of the (±)-2-methoxy-6-heptadecynoic acid and related 2-methoxylated analogs as effective inhibitors of the leishmania topoisomerase ib enzyme.the fatty acids (±)-2-methoxy-6z-heptadecenoic acid (1), (±)-2-methoxy-6-heptadecynoic acid (2) and (±)-2-methoxyheptadecanoic acid (3) were synthesized and their inhibitory activity against the leishmania dna topoisomerase ib enzyme (ldtopib) determined. acids 1 and 2 were synthesized from 4-bromo-1-pentanol, the former in ten steps and in 7% overall yield, while the latter in seven steps and in 14% overall yield. acid 3 was prepared in six steps and in 42% yield from 1-hexadecanol. acids 1-3 i ...201223118491
role of cytosolic glyceraldehyde-3-phosphate dehydrogenase in visceral organ infection by leishmania donovani.the initial 7 steps of the glycolytic pathway from glucose to 3-phosphoglycerate are localized in the glycosomes in leishmania, including step 6, catalyzed by the enzyme glyceraldehyde-3-phosphate dehydrogenase (gapdh). in l. donovani and l. mexicana, there exists a second gapdh enzyme present in the cytosol that is absent in l. braziliensis and that has become a pseudogene in l. major. to investigate the role of the cytosolic gapdh (cgapdh), an l. donovani cgapdh-null mutant was generated, and ...201323125352
cloning, characterization and sub-cellular localization of gamma subunit of t-complex protein-1 (chaperonin) from leishmania donovani.t-complex protein-1 (tcp1) complex, a chaperonin class of protein, ubiquitous in all genera of life, is involved in intracellular assembly and folding of various proteins. the gamma subunit of tcp1 complex (tcp1γ), plays a pivotal role in the folding and assembly of cytoskeleton protein(s) as an individual or complexed with other subunits. here, we report for the first time cloning, characterization and expression of the tcp1γ of leishmania donovani (ldtcp1γ), the causative agent of indian kala- ...201223137535
cxcl10 is critical for the generation of protective cd8 t cell response induced by antigen pulsed cpg-odn activated dendritic cells.the visceral form of leishmaniasis is the most severe form of the disease and of particular concern due to the emerging problem of hiv/visceral leishmaniasis (vl) co-infection in the tropics. till date miltefosine, amphotericin b and pentavalent antimony compounds remain the main treatment regimens for leishmaniasis. however, because of severe side effects, there is an urgent need for alternative improved therapies to combat this dreaded disease. in the present study, we have used the murine mod ...201223144947
geographical distribution and epidemiological features of old world leishmania infantum and leishmania donovani foci, based on the isoenzyme analysis of 2277 strains.a series of 2277 leishmania strains from old world visceral leishmaniasis foci, isolated between 1973 and 2008, were studied by isoenzyme analysis. the strains were obtained from humans, domestic and wild carnivores, rodents and phlebotomine sandflies, and came from 36 countries. in all, 60 different zymodemes were identified and clustered by a phenetic analysis into 3 different groups corresponding to the typically visceralizing species l. donovani (20 zymodemes, 169 strains), l. archibaldi (3 ...201323146283
cysteine cross-linking defines the extracellular gate for the leishmania donovani nucleoside transporter 1.1 (ldnt1.1).equilibrative nucleoside transporters are a unique family of proteins that enable uptake of nucleosides/nucleobases into a wide range of eukaryotes and internalize a myriad of drugs used in the treatment of cancer, heart disease, aids, and parasitic infections. in previous work we generated a structural model for such a transporter, the ldnt1.1 nucleoside permease from the parasitic protozoan leishmania donovani, using ab initio computation. the model suggested that aromatic residues present in ...201223150661
conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile.a combinatorial library of quinone-polyamine conjugates designed to optimize the antitrypanosomatid profile of hit compounds 1 and 2 has been prepared by a solid-phase approach. the conjugates were evaluated against the three most important human trypanosomatid pathogens (trypanosoma brucei rhodesiense, trypanosoma cruzi, and leishmania donovani), and several showed promising activity. a subset also inhibited trypanothione reductase in vitro and induced oxidase activity of the enzyme. a highly p ...201223153330
8,8-dialkyldihydroberberines with potent antiprotozoal activity.semisynthetic 8,8-dialkyldihydroberberines (8,8-ddbs) were found to possess mid- to low-nanomolar potency against plasmodium falciparum blood-stage parasites, leishmania donovani intracellular amastigotes, and trypanosoma brucei brucei bloodstream forms. for example, 8,8-diethyldihydroberberine chloride (5b) exhibited in vitro ic50 values of 77, 100, and 5.3 nm against these three parasites, respectively. in turn, two 8,8-dialkylcanadines, obtained by reduction of the corresponding 8,8-ddbs, wer ...201323167812
chemotherapy of leishmaniasis part x: synthesis and bioevaluation of novel terpenyl heterocycles.some novel α and β ionone based chalcones and their dihydropyrazolidines/pyrazolidines have been synthesized and evaluated for their in vitro and in vivo antileishmanial activities against leishmania donovani. amongest all, one compound (4d) exhibited significant in vitro activity against intracellular amastigotes of leishmania donovani with ic(50) values of 7.49 μm and was found promising as compared to reference drug, miltefosine. on the basis of good selectivity index (s.i.), the compound was ...201323177254
chemical stress does not induce heat shock protein synthesis in leishmania donovani.the cellular heat shock response in kinetoplastid protozoa is regulated exclusively at a post-transcriptional level. the heat-inducibility of heat shock protein synthesis is retained under actinomycin c(1) which indicates an inducible translation of heat shock mrnas. we have also assessed the ability of various chemicals known to be effective triggers of the heat shock response in higher eukaryotes to induce heat shock protein synthesis in leishmania donovani. none of the tested chemicals elicit ...199823196166
assessing the essentiality of leishmania donovani nitroreductase and its role in nitro drug activation.the nitroimidazole fexinidazole has potential as a safe and effective oral drug therapy for the treatment of visceral leishmaniasis. to date, nitroheterocyclics have not been used in the treatment of leishmaniasis, and relatively little is known about their mechanism of action. in african trypanosomes, nitro drugs are reductively activated by a type i nitroreductase (ntr), absent in mammalian cells. modulation of nitroreductase levels in trypanosoma brucei directly affected sensitivity to nitro ...201323208716
leishmanization revisited: immunization with a naturally attenuated cutaneous leishmania donovani isolate from sri lanka protects against visceral leishmaniasis.leishmaniasis is a neglected tropical disease caused by leishmania protozoa and associated with three main clinical presentations: cutaneous, mucocutaneous and visceral leishmaniasis. visceral leishmaniasis is the second most lethal parasitic disease after malaria and there is so far no human vaccine. leishmania donovani is a causative agent of visceral leishmaniasis in south east asia and eastern africa. however, in sri lanka, l. donovani causes mainly cutaneous leishmaniasis, while visceral le ...201323219435
identification of tunisian leishmania spp. by pcr amplification of cysteine proteinase b (cpb) genes and phylogenetic analysis.discrimination of the old world leishmania parasites is important for diagnosis and epidemiological studies of leishmaniasis. we have developed pcr assays that allow the discrimination between leishmania major, leishmania tropica and leishmania infantum tunisian species. the identification was performed by a simple pcr targeting cysteine protease b (cpb) gene copies. these pcr can be a routine molecular biology tools for discrimination of leishmania spp. from different geographical origins and d ...201323228525
different susceptibilities of leishmania spp. promastigotes to the annona muricata acetogenins annonacinone and corossolone, and the platymiscium floribundum coumarin scoparone.leishmaniasis is a zoonotic disease that can manifest itself in visceral and cutaneous form. the aim of this study was to search for new leishmanicidal compounds. preliminarily, artemia salina assay was applied to compounds from two plants found in northeastern brazil, platymiscium floribundum and annona muricata. then these compounds were tested against three leishmania species (leishmania donovani, leishmania mexicana and leishmania major). a screening assay using luciferase-expressing promast ...201323232251
noncovalent complexation of amphotericin-b with poly(α-glutamic acid).a noncovalent complex of amphotericin b (amb) and poly(α-glutamic acid) (pga) was prepared to develop a safe and stable formulation for the treatment of leishmaniasis. the loading of amb in the complex was in the range of ∼20-50%. amb was in a highly aggregated state with an aggregation ratio often above 2.0. this complex (amb-pga) was shown to be stable and to have reduced toxicity to human red blood cells and kb cells compared to the parent compound; cell viability was not affected at an amb c ...201323234235
validation of a simple resazurin-based promastigote assay for the routine monitoring of miltefosine susceptibility in clinical isolates of leishmania donovani.simple, cost-effective approach for routine surveillance of parasite susceptibility to antileishmanial drug miltefosine (mil) is highly desirable for controlling emergence of drug resistance in visceral leishmaniasis (vl). we validated a simple resazurin-based fluorimetric assay using promastigotes to track natural mil tolerance in leishmania donovani parasites from vl cases (n = 17) against standard amastigote assay, in two different labs in india. the inter-stage mil susceptibility correlated ...201323239091
visceral and post-kala-azar dermal leishmaniasis isolates show significant difference in their in vitro drug susceptibility pattern.visceral leishmaniasis (vl) remains a major health problem in old world, and india accounts for half of the world burden. the widespread emergence of resistance to standard drug in india poses a major obstacle in the control of leishmaniasis. post-kala-azar dermal leishmaniasis (pkdl) is considered as main source of drug resistance. experimental data indicate that resistance against newer drugs is also imminent. therefore, in vitro studies were carried out to test minimum parasiticidal concentra ...201323242321
unresponsiveness of mycobacterium w vaccine in managing acute and chronic leishmania donovani infections in mouse and hamster.the role of mycobacterium w (mw) vaccine as an immunomodulator and immunoprophylactant in the treatment of mycobacterial diseases (leprosy and pulmonary tuberculosis) is well established. the fact that it shares common antigens with leishmanial parasites prompted its assessment as an immunostimulant and as an adjunct to known anti-leishmanials that may help in stimulating the suppressed immune status of leishmania donovani-infected individuals. the efficacy of mw vaccine was assessed as an immun ...201323253783
human hepatic stellate cells in primary culture are safe targets for leishmania donovani.leishmania parasites can escape the immune response by invading cell types lacking leishmanicidal mechanisms. silent persistence of leishmania parasites in the host organism is responsible for asymptomatic carriage and relapses after cured leishmaniasis. here, we studied the interaction between hepatic stellate cells (hsc) and leishmania. an original model of human hsc in primary culture infected with l. donovani was developed. the presence of intracellular parasites was studied and quantified u ...201323253952
leishmaniasis: an update of current pharmacotherapy.leishmaniasis broadly manifests as visceral leishmaniasis (vl), cutaneous leishmaniasis (cl) and mucocutaneous leishmaniasis (mcl). the treatment of vl is challenging. the duration of treatment is long, and drugs are toxic thereby needing monitoring and hospitalization.201323256501
apoptotic marker expression in the absence of cell death in staurosporine-treated leishmania donovani.the protozoan parasite leishmania donovani undergoes several developmental transitions in its insect and vertebrate hosts that are induced by environmental changes. the roles of protein kinases in these adaptive differentiation steps and their potential as targets for antiparasitic intervention are only poorly characterized. here, we used the generic protein kinase inhibitor staurosporine to gain insight into how interference with phosphotransferase activities affects the viability, growth, and ...201223263009
leishmania donovani zymodeme mon-37 isolated from an autochthonous visceral leishmaniasis patient in sri lanka.although the strain causing cutaneous leishmaniasis (cl) in sri lanka was first identified in 2003, the strain causing visceral leishmaniasis (vl) has not yet been identified. we report the first isoenzyme typing of a strain causing vl in sri lanka at an early stage of emergence of vl in the country. the parasite was isolated from a 57-year-old civil soldier who had been in the jungle in the vavuniya district in the northern province of sri lanka for a period of nearly 6 months immediately befor ...201223265615
identification of drosophila gene products required for phagocytosis of leishmania donovani.the identity and function of host factors required for efficient phagocytosis and intracellular maintenance of the protozoan parasite leishmania donovani are poorly understood. utilising the phagocytic capability of drosophila s2 cells, together with available tools for modulating gene expression by rnai, we have developed an experimental system in which to identify host proteins of this type on a genome-wide scale. we have shown that l. donovani amastigotes can be phagocytosed by s2 cells, in w ...201223272175
leishmania donovani develops resistance to drug combinations.drug combinations for the treatment of leishmaniasis represent a promising and challenging chemotherapeutic strategy that has recently been implemented in different endemic areas. however, the vast majority of studies undertaken to date have ignored the potential risk that leishmania parasites could develop resistance to the different drugs used in such combinations. as a result, this study was designed to elucidate the ability of leishmania donovani to develop experimental resistance to anti-le ...201223285310
a new model of progressive visceral leishmaniasis in hamsters by natural transmission via bites of vector sand flies.visceral leishmaniasis (vl) is transmitted by sand flies. protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for vl.201323288926
synthesis of perspicamide a and related diverse analogues: their bioevaluation as potent antileishmanial agents.the first protocol for the synthesis of perspicamide a and related diverse analogues has been developed from economical and readily available starting materials. furthermore, a few synthesized analogues, 24a, 24b, 24c, 24d, and 24l, exhibited potent activity against leishmania donovani with ic(50) values ranging from 3.75 to 10.37 μm and a selectivity index (si) ranging from 9.58 to 53.12, which is improved compared to the standard drug miltefosine (ic(50) 12.4 μm and si 4.1).201323289499
a parasite rescue and transformation assay for antileishmanial screening against intracellular leishmania donovani amastigotes in thp1 human acute monocytic leukemia cell line.leishmaniasis is one of the world's most neglected diseases, largely affecting the poorest of the poor, mainly in developing countries. over 350 million people are considered at risk of contracting leishmaniasis, and approximately 2 million new cases occur yearly(1). leishmania donovani is the causative agent for visceral leishmaniasis (vl), the most fatal form of the disease. the choice of drugs available to treat leishmaniasis is limited (2);current treatments provide limited efficacy and many ...201223299097
imipramine is an orally active drug against both antimony sensitive and resistant leishmania donovani clinical isolates in experimental infection.in an endeavor to find an orally active and affordable antileishmanial drug, we tested the efficacy of a cationic amphiphilic drug, imipramine, commonly used for the treatment of depression in humans. the only available orally active antileishmanial drug is miltefosine with long half life and teratogenic potential limits patient compliance. thus there is a genuine need for an orally active antileishmanial drug. previously it was shown that imipramine, a tricyclic antidepressant alters the proton ...201223301108
asymmetric synthesis and anti-protozoal activity of the 8,4'-oxyneolignans virolin, surinamensin and analogues.the asymmetric synthesis of 8,4'-oxyneolignans (-)-virolin, (-)-surinamensin and a number of analogues has been achieved. a divergent synthesis was used, with all compounds being elaborated from a single chiral aldehyde derived from ethyl lactate. in the 15 compounds that were tested, the level of substitution on the a-ring was found to directly influence the activity against leishmania donovani whilst the activity against plasmodium falciparum was influenced by numerous substitution and stereoc ...201223313632
human visceral leishmaniasis in kermanshah province, western iran, during 2011-2012.visceral leishmaniasis (vl) or kala-azar is a parasitic disease caused by the species of leishmania donovani complex. it is endemic in some parts of provinces of iran. according to the reported cases of vl in kermanshah province in recent years, this study was conducted to determine the seroprevalence of vl in high risk villages of the province.201223323091
potential antileishmanial effect of three medicinal plants.the antileishmanial activity of three organic solvent extracts and water residue of the plants: acacia nilotica (mimosaceae) (husk), ambrosia miratima (astraceae) (aerial shoot) and azadarichta indica (meliaceae) (leaves) were tested in vitro against leishmania donovani promastigotes. the study revealed that the extracts of a. nilotica and a. miratima have effectious antileishmanial activity at concentrations (ic(50)) less than 8 μg/ml, while the extracts of a. indica lack antileishmanial activi ...201223326001
identification and functional characterization of leishmania donovani secretory peroxidase: delineating its role in nramp1 regulation.leishmania silently evades host immune system and establish in the hostile environment of host macrophage phagolysosomes. for differentiation, growth and division parasite acquires divalent cations especially iron from the host nutritive pool. natural resistance associated with macrophage protein1 (nramp1), a cation transporter that effluxes out divalent cations specifically iron from phagosomal milieu to the cytosol, to create ions deprived status for pathogenic microorganisms. the mechanisms o ...201323326430
an outbreak investigation of visceral leishmaniasis among residents of dharan town, eastern nepal, evidence for urban transmission of leishmania donovani.visceral leishmaniasis (vl) is a predominantly rural disease, common in the low lands of eastern nepal. since 1997 vl cases have also been reported among residents of the city of dharan. our main research objective was to find out whether there had been local transmission of vl inside the city.201323327548
leishmania donovani-specific 25- and 28-kda urinary proteins activate macrophage effector functions, lymphocyte proliferation and th1 cytokines production.growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. in this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation. a total four proteins of molecular mass 25, 28, 54 and 60 kda we ...201323334693
live attenuated leishmania donovani p27 gene knockout parasites are nonpathogenic and elicit long-term protective immunity in balb/c mice.leishmaniasis causes significant morbidity and mortality worldwide, and no vaccines against this disease are available. previously, we had shown that the amastigote-specific protein p27 (ldp27) is a component of an active cytochrome c oxidase complex in leishmania donovani and that upon deletion of its gene the parasite had reduced virulence in vivo. in this study, we have shown that ldp27(-/-) parasites do not survive beyond 20 wk in balb/c mice and hence are safe as an immunogen. upon virulent ...201323338240
antimony-resistant but not antimony-sensitive leishmania donovani up-regulates host il-10 to overexpress multidrug-resistant protein 1.the molecular mechanism of antimony-resistant leishmania donovani (sb(r)ld)-driven up-regulation of il-10 and multidrug-resistant protein 1 (mdr1) in infected macrophages (ms) has been investigated. this study showed that both promastigote and amastigote forms of sb(r)ld, but not the antimony-sensitive form of ld, express a unique glycan with n-acetylgalactosamine as a terminal sugar. removal of it either by enzyme treatment or by knocking down the relevant enzyme, galactosyltransferase in sb(r) ...201323341611
immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin b-encapsulated nanoemulsion template-based chitosan nanocapsules.the accessible treatment options for life-threatening neglected visceral leishmaniasis (vl) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. here we formulated nanometric amphotericin b (amb)-encapsulated chitosan nanocapsules (cnc-amb) using a polymer deposition technique mediated by nanoemulsion template fabrication. cnc-amb exhibited good steric stability in vitro, where the chitosan content was found to be efficient at preventing de ...201323357762
polymorphism in the haspb repeat region of east african leishmania donovani strains.visceral leishmaniasis (vl) caused by leishmania donovani is a major health problem in ethiopia. parasites in disparate regions are transmitted by different vectors, and cluster in distinctive genotypes. recently isolated strains from vl and hiv-vl co-infected patients in north and south ethiopia were characterized as part of a longitudinal study on vl transmission.201323358849
low prevalence of leishmania donovani infection among the blood donors in kala-azar endemic areas of bangladesh.visceral leishmaniasis (vl) is a major public health problem in bangladesh with the highest disease burden in the mymensingh district. the disease is transmitted by sand fly bites, but it may also be transmitted through blood transfusions. no information is available about the prevalence of leishmania infection among blood donors in bangladesh; therefore we aimed to investigate this question.201323375008
proteome changes associated with leishmania donovani promastigote adaptation to oxidative and nitrosative stresses.phagocytic cells produce reactive oxygen and nitrogen species (ros & rns) as the most common arsenal to kill intracellular pathogens. leishmania, an obligate intracellular pathogen also confronts this antimicrobial assault during the early phase of infection but nevertheless is able to survive these attacks and proliferate in macrophage. adaptation of leishmania to the toxic effects of ros and rns, involves a rapid change in the parasite proteome to combat the host defense response that macropha ...201323376486
analysis of kinetoplast cytochrome b gene of 16 leishmania isolates from different foci of china: different species of leishmania in china and their phylogenetic inference.leishmania species belong to the family trypanosomatidae and cause leishmaniasis, a geographically widespread disease that infects humans and other vertebrates. this disease remains endemic in china. due to the large geographic area and complex ecological environment, the taxonomic position and phylogenetic relationship of chinese leishmania isolates remain uncertain. a recent internal transcribed spacer 1 and cytochrome oxidase ii phylogeny of chinese leishmania isolates has challenged some asp ...201323383990
induction of immunogenicity by live attenuated leishmania donovani centrin deleted parasites in dogs.zoonotic visceral leishmaniasis, caused by the intracellular protozoan parasite leishmania infantum, is a neglected tropical disease that is often fatal when untreated. dogs are considered the main reservoir of l. infantum in zoonotic vl as the presence of infected dogs may increase the risk for human infection. canine visceral leishmaniasis (cvl) is a major veterinary and public health problem in southern europe, middle east and south america. control of animal reservoirs relies on elimination ...201323398933
adenylosuccinate synthetase and adenylosuccinate lyase deficiencies trigger growth and infectivity deficits in leishmania donovani.leishmania are auxotrophic for purines, and consequently purine acquisition from the host is a requisite nutritional function for the parasite. both adenylosuccinate synthetase (adss) and adenylosuccinate lyase (asl) have been identified as vital components of purine salvage in leishmania donovani, and therefore δadss and δasl null mutants were constructed to test this hypothesis. unlike wild type l. donovani, δadss and δasl parasites in culture exhibited a profoundly restricted growth phenotype ...201323404497
an in vitro study of apoptotic like death in leishmania donovani promastigotes by withanolides.the aim of this study was to isolate and evaluate the withanolides in inducing apoptotic like death in leishmania donovani in vitro. withanolides were fractionated and isolated from the leaves of withania somnifera and lc-ms/ms analysis of two fractions namely, f5 and f6 of ethanolic extracts, obtained through column chromatography with silica gel, was performed. the antileishmanial effect of withanolides on l. donovani promastigotes was assessed in vitro using pi dye exclusion test. the effect ...201323416156
solid™ sequencing of genomes of clinical isolates of leishmania donovani from india confirm leptomonas co-infection and raise some key questions.known as 'neglected disease' because relatively little effort has been applied to finding cures, leishmaniasis kills more than 150,000 people every year and debilitates millions more. visceral leishmaniasis (vl), also called kala azar (ka) or black fever in india, claims around 20,000 lives every year. whole genome analysis presents an excellent means to identify new targets for drugs, vaccine and diagnostics development, and also provide an avenue into the biological basis of parasite virulence ...201323418454
identifying salivary antigens of phlebotomus argentipes by a 2de approach.in the indian subcontinent visceral leishmaniasis, also known as kala-azar, is caused by the protozoa leishmania donovani and is transmitted to humans by the bite of infected female sand flies phlebotomus argentipes in an anthroponotic cycle. sand fly saliva is known to play an important role in host infection outcome after an infective bite. immunogenicity of p. argentipes saliva has already been described. however, specific antigens that can contribute to these immunogenic properties are unkno ...201323422341
functional complexity of the leishmania granuloma and the potential of in silico modeling.in human and canine visceral leishmaniasis and in various experimental models of this disease, host resistance is strongly linked to efficient granuloma development. however, it is unknown exactly how the granuloma microenvironment executes an effective antileishmanial response. recent studies, including using advanced imaging techniques, have improved our understanding of granuloma biology at the cellular level, highlighting heterogeneity in granuloma development and function, and hinting at co ...201323423646
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