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Sent on Tuesday, 2011 Dec 06Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | PLoS Negl Trop Dis. 2011 Nov;5(11):e1407. Epub 2011 Nov 29.Combining climatic projections and dispersal ability: a method for estimating the responses of sandfly vector species to climate change.Fischer D, Moeller P, Thomas SM, Naucke TJ, Beierkuhnlein C.SourceDepartment of Biogeography, University of Bayreuth, Bayreuth, Germany. AbstractBACKGROUND:In the Old World, sandfly species of the genus Phlebotomus are known vectors of Leishmania, Bartonella and several viruses. Recent sandfly catches and autochthonous cases of leishmaniasis hint on spreading tendencies of the vectors towards Central Europe. However, studies addressing potential future distribution of sandflies in the light of a changing European climate are missing. METHODOLOGY:Here, we modelled bioclimatic envelopes using MaxEnt for five species with proven or assumed vector competence for Leishmania infantum, which are either predominantly located in (south-) western (Phlebotomus ariasi, P. mascittii and P. perniciosus) or south-eastern Europe (P. neglectus and P. perfiliewi). The determined bioclimatic envelopes were transferred to two climate change scenarios (A1B and B1) for Central Europe (Austria, Germany and Switzerland) using data of the regional climate model COSMO-CLM. We detected the most likely way of natural dispersal ("least-cost path") for each species and hence determined the accessibility of potential future climatically suitable habitats by integrating landscape features, projected changes in climatic suitability and wind speed. RESULTS AND RELEVANCE:Results indicate that the Central European climate will become increasingly suitable especially for those vector species with a current south-western focus of distribution. In general, the highest suitability of Central Europe is projected for all species in the second half of the 21st century, except for P. perfiliewi. Nevertheless, we show that sandflies will hardly be able to occupy their climatically suitable habitats entirely, due to their limited natural dispersal ability. A northward spread of species with south-eastern focus of distribution may be constrained but not completely avoided by the Alps. Our results can be used to install specific monitoring systems to the projected risk zones of potential sandfly establishment. This is urgently needed for adaptation and coping strategies against the emerging spread of sandfly-borne diseases. |
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2. | PLoS Negl Trop Dis. 2011 Nov;5(11):e1405. Epub 2011 Nov 29.Visceral leishmaniasis in the Indian subcontinent: modelling epidemiology and control.Stauch A, Sarkar RR, Picado A, Ostyn B, Sundar S, Rijal S, Boelaert M, Dujardin JC, Duerr HP.SourceDepartment of Medical Biometry, University of Tübingen, Tübingen, Germany. AbstractBACKGROUND:In the Indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies. METHODS AND FINDINGS:Parameters on the natural history of Leishmania infection were estimated based on a literature review and expert opinion or drawn from a community intervention trial (the KALANET project). The transmission dynamic of Leishmania donovani is rather slow, mainly due to its long incubation period and the potentially long persistence of parasites in infected humans. Cellular immunity as measured by the Leishmanin skin test (LST) lasts on average for roughly one year, and re-infection occurs in intervals of about two years, with variation not specified. The model suggests that transmission of L. donovani is predominantly maintained by asymptomatically infected hosts. Only patients with symptomatic disease were eligible for treatment; thus, in contrast to vector control, the treatment of cases had almost no effect on the overall intensity of transmission. CONCLUSIONS:Treatment of Kala-azar is necessary on the level of the individual patient but may have little effect on transmission of parasites. In contrast, vector control or exposure prophylaxis has the potential to efficiently reduce transmission of parasites. Based on these findings, control of VL should pay more attention to vector-related interventions. Cases of PKDL may appear after years and may initiate a new outbreak of disease; interventions should therefore be long enough, combined with an active case detection and include effective treatment. |
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3. | PLoS One. 2011;6(11):e27679. Epub 2011 Nov 30.Toll Receptors Type-2 and CR3 Expression of Canine Monocytes and Its Correlation with Immunohistochemistry and Xenodiagnosis in Visceral Leishmaniasis.de Amorim IF, da Silva SM, Figueiredo MM, Moura EP, de Castro RS, de Souza Lima TK, de Figueiredo Gontijo N, Michalick MS, Gollob KJ, Tafuri WL.SourceDepartamento de Patologia Geral, Escola de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brasil. AbstractThe aim of the present study was to investigate TLR2 expression in peripheral blood monocytes from dogs naturally infected with Leishmania (Leishmania) infantum to determine whether it correlates with CD11b/CD18 (CR3) expression, and to evaluate the potential of dogs as sources of infection using phlebotomine xenodiagnosis. Forty eight dogs were serologically diagnosed with L. infantum infection by indirect immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA). Parasitological exams from bone-marrow aspirates were positive by PCR analysis. All dogs were clinical defined as symptomatic. Ear skin tissue samples were obtained for immunohistochemistry (IHQ) analysis. The potential of these dogs as a source of infection using phlebotomine xenodiagnosis (XENO) was evaluated. Flow cytometry was carried out on peripheral blood mononuclear cells using superficial receptors including CD14, CD11b, TLR2 and MHCII. IHQ ear skin tissue parasite load and XENO where done where we found a strict correlation (r = 0.5373). Dogs with higher expression of MFI of CD11b inside CD14 monocytes were represented by dogs without parasite ear tissue load that were unable to infect phlebotomines (IHQ(-)/XENO(-)). Dogs with lower expression of MFI of CD11b inside CD14 monocytes were represented by dogs with parasite ear tissue load and able to infect phlebotomines (IHQ(+)/XENO(+)) (p = 0,0032). Comparable results were obtained for MFI of MHCII (p = 0.0054). In addition, considering the population frequency of CD11b(+)TLR2(+) and CD11b(+)MHCII(+), higher values were obtained from dogs with IHQ(-)/XENO(-) than dogs with IHQ(+)/XENO(+) (p = 0.01; p = 0.0048, respectively). These data, together with the TLR2 and NO assays results (CD11b(+)TLR2(+) and NO with higher values for dogs with IHQ(-)/XENO(-) than dogs with IHQ(+)/XENO(+)), led to the conclusion that IHQ(-)/XENO(-) dogs are more resistant or could modulate the cellular immune response essential for Leishmania tissue clearance. |
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4. | J Immunol. 2011 Dec 2. [Epub ahead of print]Myeloid Cell IL-10 Production in Response to Leishmania Involves Inactivation of Glycogen Synthase Kinase-3β Downstream of Phosphatidylinositol-3 Kinase.Nandan D, Camargo de Oliveira C, Moeenrezakhanlou A, Lopez M, Silverman JM, Subek J, Reiner NE.SourceDivision of Infectious Diseases, Department of Medicine, Faculties of Medicine and Science, University of British Columbia, Vancouver, British Columbia V5Z 3J5, Canada; AbstractLeishmania disease expression has been linked to IL-10. 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 at serine 133 and CREB DNA binding activity were abrogated in cells treated with inhibitors of either PI3K or Akt prior to infection. Furthermore, disruption of this pathway either by inhibition of Akt or by overexpression of GSK-3β markedly attenuated IL-10 production in response to leishmania. Thus, GSK-3β negatively regulates myeloid cell IL-10 production in response to leishmania. Switching off GSK-3β promotes disease pathogenesis. |
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5. | Nucleic Acids Res. 2011 Dec 2. [Epub ahead of print]The post-transcriptional trans-acting regulator, TbZFP3, co-ordinates transmission-stage enriched mRNAs in Trypanosoma brucei.Walrad PB, Capewell P, Fenn K, Matthews KR.SourceCentre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, King's Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK. AbstractPost-transcriptional gene regulation is essential to eukaryotic development. This is particularly emphasized in trypanosome parasites where genes are co-transcribed in polycistronic arrays but not necessarily co-regulated. The small CCCH protein, TbZFP3, has been identified as a trans-acting post-transcriptional regulator of Procyclin surface antigen expression in Trypanosoma brucei. To investigate the wider role of TbZFP3 in parasite transmission, a global analysis of associating transcripts was carried out. Examination of a subset of the selected transcripts revealed their increased abundance through mRNA stabilization upon TbZFP3 ectopic overexpression, dependent upon the integrity of the CCCH zinc finger domain. Reporter assays demonstrated that this regulation was mediated through 3'-UTR sequences for two target transcripts. Global developmental expression profiling of the cohort of TbZFP3-selected transcripts revealed their significant enrichment in transmissible stumpy forms of the parasite. This analysis of the specific mRNAs selected by the TbZFP3mRNP provides evidence for a developmental regulon with the potential to co-ordinate genes important in parasite transmission. |
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6. | Dalton Trans. 2011 Dec 2. [Epub ahead of print]New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents.Demoro B, Sarniguet C, Sánchez-Delgado R, Rossi M, Liebowitz D, Caruso F, Olea-Azar C, Moreno V, Medeiros A, Comini MA, Otero L, Gambino D.SourceCátedra de Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República (UdelaR), Gral. Flores 2124, 11800, Montevideo, Uruguay. dgambino@fq.edu.uy luotero@fq.edu.uy. AbstractIn the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(ii) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X = Cl or PF(6), were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs. |
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7. | Pharmacol Ther. 2011 Nov 28. [Epub ahead of print]Matrix metalloproteinases as therapeutic targets in protozoan parasitic infections.Geurts N, Opdenakker G, den Steen PE.AbstractMatrix metalloproteinases (MMPs) are associated with processes of tissue remodeling and are expressed in all infections with protozoan parasites. We here report the status of MMP research in malaria, trypanosomiasis, leishmaniasis and toxoplasmosis. In all these infections, the balances between MMPs and endogenous MMP inhibitors are disturbed, mostly in favor of active proteolysis. When the infection is associated with leukocyte influx into specific organs, immunopathology and collateral tissue damage may occur. These pathologies include cerebral malaria, sleeping sickness (human African trypanosomiasis), Chagas disease (human American trypanosomiasis), leishmaniasis, and toxoplasmic encephalitis in immunocompromised hosts. Destruction of the integrity of the blood-brain barrier (BBB) is a common denominator that may be executed by leukocytic MMPs under the control of host cytokines and chemokines as well as influenced by parasite products. Mechanisms by which parasite-derived products alter host expression of MMP and endogenous MMP inhibitors, have only been described for hemozoin (Hz) in malaria. Hence, understanding these interactions in other parasitic infections remains an important challenge. Furthermore, the involved parasites are also known to produce their own metalloproteinases, and this forms an extra stimulus to investigate MMP inhibitory drugs as therapeutics. MMP inhibitors (MMPIs) may dampen collateral tissue damage, as is anecdotically reported for tetracyclines as MMP regulators in parasite infections. Copyright © 2011 Elsevier Inc. All rights reserved. |
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8. | Adv Parasitol. 2011;77:1-85.Coinfection of schistosoma (trematoda) with bacteria, protozoa and helminths.Abruzzi A, Fried B.SourceSkillman Library, Lafayette College, Easton, Pennsylvania, USA; Epidemiology, University of Medicine and Dentistry of New Jersey (UMDNJ), Piscataway, New Jersey, USA. AbstractThis 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 other than Plasmodium; with Salmonella, with bacteria other than Salmonella; and with Fasciola, with helminths other than Fasciola. Numerous factors were found to influence the effects of coinfection on the vertebrate host, including organisms and hosts used in the studies, order and time interval between the first and the second infection, studies on natural versus experimental hosts, dosage of the infectious agents, strains and pedigrees of the parasites, age of hosts at time of exposure to the infectious agents and age of hosts at the time of necropsy. Overall, a prior infection with Schistosoma, particularly a patent infection, often has an effect on the subsequent infection by a protozoan, bacterium or other helminth. In relatively few cases, a prior infection with Schistosoma decreased the severity of the subsequent infection as with Helicobacter pylori, Fasciola hepatica, Echinostoma or Plasmodium, the latter only exhibiting this behaviour when coinfected with Schistosoma haematobium. More often, however, a prior infection with Schistosoma increased the severity of the second infection as with Leishmania, Toxoplasma gondii, Entamoeba histolytica, Staphylococcus aureus or Salmonella. In some of these coinfection studies, the increased severity of the subsequent infection was associated with a specific, prolonged form of the disease in humans, which has implications for patient treatment and recovery. Additional research is needed, particularly on Schistosoma coinfections which currently have a small body of research and are current problems in human populations. Examples of such Schistosoma interactions include the genera of Mycobacteria, Leishmania, Staphylococcus, Necator and Strongyloides. Hopefully, future studies will elucidate valuable new information on the interesting subject of coinfection of Schistosoma with other organisms. Copyright © 2011 Elsevier Ltd. All rights reserved. |
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9. | Trans R Soc Trop Med Hyg. 2012 Jan;106(1):54-9.Evaluation of a novel chromatographic immunoassay based on Dual-Path Platform techn ology (DPP(®) CVL rapid test) for the serodiagnosis of canine visceral leishmaniasis.Grimaldi G Jr, Teva A, Ferreira AL, Dos Santos CB, Pinto IS, de-Azevedo CT, Falqueto A.SourceLaboratório de Pesquisa em Leishmaniose, Instituto Oswaldo Cruz/Fiocruz, Av. Brasil 4365, Rio de Janeiro, RJ 21040-360, Brazil. AbstractCanine 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-positive dogs without signs of CVL. However, the test sensitivity was significantly higher (98%) in diseased cases, indicating that this convenient test may be useful to identify the most infectious dogs. Efforts should be pursued to obtain a more sensitive DPP-multiplexed test parameter (i.e. based on simultaneous yet separate antibody detection of carefully selected multiple antigens of diagnostic utility) for effective serodiagnosis of early-infected dogs, as this will likely allow more efficient canine removal regimens than those used in practice by public health services. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
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10. | Trans R Soc Trop Med Hyg. 2012 Jan;106(1):20-5.In vitro growth kinetics, differentiation and morphological characterisation of Tunisian Leishmania infantum parasites.Kbaier-Hachemi H, Guerbouj S, Turki-Mannoubi L, Kaabi B, Guizani I.SourceLaboratoire d'Epidémiologie et d'Ecologie Parasitaire, LR00SP04 - Research Programme on Applied Genomics and Biotechnologies to Parasitic Diseases, Institut Pasteur de Tunis, 13 place Pasteur, BP 74, 1002 Tunis, Tunisia. AbstractIn 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 state in the Leishmania development process, with a fraction of them sharing common constituents of the surface coat with procyclics and the other with leptomonads. Obtaining a high density of promastigotes undergoing developmental differentiation may be useful for further molecular and biochemical identification of developmental stage-specific markers. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
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