What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2012 June 16
Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"

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PubMed Results

Items 1 - 10 of 11

1.	PLoS Negl Trop Dis. 2012 Jun;6(6):e1662. Epub 2012 Jun 5. Early prediction of treatment efficacy in second-stage gambiense human african trypanosomiasis. Priotto G, Chappuis F, Bastard M, Flevaud L, Etard JF. Source Epicentre, Paris, France. Abstract BACKGROUND: Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Médecins Sans Frontières in Uganda, Sudan, Angola, Central African Republic, Republic of Congo and Democratic Republic of Congo searching for early efficacy indicators. METHODOLOGY/PRINCIPAL FINDINGS: Patients analyzed had confirmed second-stage disease with complete follow-up and confirmed outcome (cure or relapse), and had CSF leucocytes counts (CSFLC) performed at 6 months post-treatment. We excluded patients with uncertain efficacy outcome: incomplete follow-up, death, relapse diagnosed with CSFLC below 50/µL and no trypanosomes. We analyzed the 6-month CSFLC via receiver-operator-characteristic curves. For each cut-off value we calculated sensitivity, specificity and likelihood ratios (LR+ and LR-). We assessed the association of the optimal cut-off with the probability of relapsing via random-intercept logistic regression. We also explored two-step (6 and 12 months) composite algorithms using the CSFLC. The most accurate cut-off to predict outcome was 10 leucocytes/µL (n = 1822, 76.2% sensitivity, 80.4% specificity, 3.89 LR+, 0.29 LR-). Multivariate analysis confirmed its association with outcome (odds ratio = 17.2). The best algorithm established cure at 6 months with < = 5 leucocytes/µL and relapse with > = 50 leucocytes/µL; patients between these values were discriminated at 12 months by a 20 leucocytes/µL cut-off (n = 2190, 87.4% sensitivity, 97.7% specificity, 37.84 LR+, 0.13 LR-). CONCLUSIONS/SIGNIFICANCE: The 6-month CSFLC can predict outcome with some limitations. Two-step algorithms enhance the accuracy but impose 12-month follow-up for some patients. For early estimation of efficacy in clinical trials and for individual patients in the field, several options exist that can be used according to priorities.
	PMID: 22701752 [PubMed - in process]

2.	PLoS One. 2012;7(6):e38489. Epub 2012 Jun 12. Intracellular Pathogen Leishmania donovani Activates Hypoxia Inducible Factor-1 by Dual Mechanism for Survival Advantage within Macrophage. Singh AK, Mukhopadhyay C, Biswas S, Singh VK, Mukhopadhyay CK. Source Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India. Abstract Recent evidence established a crucial role for mammalian oxygen sensing transcription factor hypoxia inducible factor-1 (HIF-1) in innate immunity against intracellular pathogens. In response to most of these pathogens host phagocytes increase transcription of HIF-1α, the regulatory component of HIF-1 to express various effector molecules against invaders. Leishmania donovani (LD), a protozoan parasite and the causative agent of fatal visceral leishmaniasis resides in macrophages within mammalian host. The mechanism of HIF-1 activation or its role in determining the fate of LD in infected macrophages is still not known. To determine that J774 macrophages were infected with LD and about four-fold increase in HIF-1 activity and HIF-1α expression were detected. A strong increase in HIF-1α expression and nuclear localization was also detected in LD-infected J774 cells, peritoneal macrophages and spleen derived macrophages of LD-infected BALB/c mice. A two-fold increase in HIF-1α mRNA was detected in LD-infected macrophages suggesting involvement of a transcriptional mechanism that was confirmed by promoter activity. We further revealed that LD also induced HIF-1α expression by depleting host cellular iron pool to affect prolyl hydroxylase activity resulting in to stabilization of HIF-1α. To determine the role of HIF-1 on intracellular LD, cells were transfected with HIF-1α siRNA to attenuate its expression and then infected with LD. Although, initial infection rate of LD in HIF-1α attenuated cells was not affected but intracellular growth of LD was significantly inhibited; while, over-expression of stabilized form of HIF-1α promoted intracellular growth of LD in host macrophage. Our results strongly suggest that LD activates HIF-1 by dual mechanism for its survival advantage within macrophage.
	PMID: 22701652 [PubMed - in process]

3.	Front Immunol. 2012;3:144. Epub 2012 Jun 11. Adjuvants for Leishmania vaccines: from models to clinical application. Raman VS, Duthie MS, Fox CB, Matlashewski G, Reed SG. Source Pre-clinical Biology, Infectious Disease Research Institute, Seattle, WA, USA. Abstract Two million new cases of leishmaniasis occur every year, with the cutaneous leishmaniasis (CL) presentation accounting for approximately two-thirds of all cases. Despite the high incidence rates and geographic expansion of the disease, CL remains a neglected tropical disease without effective intervention strategies. Efforts to address this deficit have given rise to the experimental murine model of CL. By virtue of its simplicity and pliability, the CL model has been used to provide substantial information regarding cellular immunity, as well as in the discovery and evaluation of various vaccine adjuvants. The CL model has facilitated in vivo studies of the mechanism of action of many adjuvants, including the TLR4 agonist monophosphoryl lipid A, the TLR7/8 agonist imiquimod, the TLR9 agonist CpG, adenoviral vectors, and the immunostimulatory complexes. Together, these studies have helped to unveil the requirement for certain types of immune responses at specific stages of CL disease and provide a basis to aid the design of effective second-generation vaccines for human CL. This review focuses on adjuvants that have been tested in experimental CL, outlining how they have helped advance our understanding of the disease and ultimately, how they have performed when applied within clinical trials against human CL.
	PMID: 22701453 [PubMed - in process]

4.	J Parasitol Res. 2012;2012:467821. Epub 2012 May 31. Application of RFLP-PCR-Based Identification for Sand Fly Surveillance in an Area Endemic for Kala-Azar in Mymensingh, Bangladesh. Alam MS, Kato H, Fukushige M, Wagatsuma Y, Itoh M. Source Parasitology Laboratory, International Center for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka 1212, Bangladesh. Abstract Mymensingh is the most endemic district for kala-azar in Bangladesh. Phlebotomus argentipes remains the only known vector although a number of sand fly species are prevalent in this area. Genotyping of sand flies distributed in a VL endemic area was developed by a PCR and restriction-fragment-length polymorphism (RFLP) of 18S rRNA gene of sand fly species. Using the RFLP-PCR analysis with AfaI and HinfI restriction enzymes, P. argentipes, P. papatasi, and Sergentomyia species could be identified. Among 1,055 female sand flies successfully analyzed for the species identification individually, 64.4% flies was classified as Sergentomyia species, whereas 35.6% was identified as P. argentipes and no P. papatasi was found. Although infection of Leishmania within the sand flies was individually examined targeting leishmanial minicircle DNA, none of the 1,055 sand flies examined were positive for Leishmania infection. The RFLP-PCR could be useful tools for taxonomic identification and Leishmania infection monitoring in endemic areas of Bangladesh.
	PMID: 22701164 [PubMed - in process]

5.	Front Immunol. 2012;3:145. Epub 2012 Jun 8. The immunobiology of Leishmania braziliensis infection. de Oliveira CI, Brodskyn CI. Source Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, Bahia, Brazil. Abstract Leishmaniases are a group of diseases caused by protozoa of the genus Leishmania that affect millions of people worldwide. These diseases are caused by distinct Leishmania species, of which L. braziliensis, a New World representative of the Leishmania genus, has been the least studied. Although leishmaniasis caused by L. braziliensis induces a range of clinical manifestations ranging from mild localized lesions to severe mucosal involvement, few studies have focused on elucidating the immune mechanisms behind this pathology. In this review, we focus on the immunobiology of L. braziliensis infection, emphasizing the innate and adaptive immune responses and taking into consideration both studies performed in endemic areas and experimental models of infection. Additionally, we address recent findings regarding the role of sand fly saliva in disease immunopathogenesis and vaccine development.
	PMID: 22701117 [PubMed - in process]

6.	Science. 2012 Jun 14. [Epub ahead of print] Adenylate Cyclases of Trypanosoma brucei Inhibit the Innate Immune Response of the Host. Salmon D, Vanwalleghem G, Morias Y, Denoeud J, Krumbholz C, Lhommé F, Bachmaier S, Kador M, Gossmann J, Dias FB, De Muylder G, Uzureau P, Magez S, Moser M, De Baetselier P, Van Den Abbeele J, Beschin A, Boshart M, Pays E. Source Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des Prof. Jeener et Brachet, B6041 Gosselies, Belgium. Abstract The parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases. Activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. Using a dominant-negative strategy, we found that reducing adenylate cyclase activity by ~50% allowed trypanosome growth but reduced the parasite's ability to control the early innate immune defense of the host. Specifically, activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these cells. Thus, adenylate cyclase activity of lyzed trypanosomes favors early host colonization by live parasites. The role of adenylate cyclases at the host-parasite interface could explain the expansion and polymorphism of this gene family.
	PMID: 22700656 [PubMed - as supplied by publisher]

7.	Proc Natl Acad Sci U S A. 2012 Jun 13. [Epub ahead of print] Evolution of Fe/S cluster biogenesis in the anaerobic parasite Blastocystis. Tsaousis AD, Ollagnier de Choudens S, Gentekaki E, Long S, Gaston D, Stechmann A, Vinella D, Py B, Fontecave M, Barras F, Lukes J, Roger AJ. Source Centre for Comparative Genomics and Evolutionary Bioinformatics, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4R2. Abstract Iron/sulfur cluster (ISC)-containing proteins are essential components of cells. In most eukaryotes, Fe/S clusters are synthesized by the mitochondrial ISC machinery, the cytosolic iron/sulfur assembly system, and, in photosynthetic species, a plastid sulfur-mobilization (SUF) system. Here we show that the anaerobic human protozoan parasite Blastocystis, in addition to possessing ISC and iron/sulfur assembly systems, expresses a fused version of the SufC and SufB proteins of prokaryotes that it has acquired by lateral transfer from an archaeon related to the Methanomicrobiales, an important lineage represented in the human gastrointestinal tract microbiome. Although components of the Blastocystis ISC system function within its anaerobic mitochondrion-related organelles and can functionally replace homologues in Trypanosoma brucei, its SufCB protein has similar biochemical properties to its prokaryotic homologues, functions within the parasite's cytosol, and is up-regulated under oxygen stress. Blastocystis is unique among eukaryotic pathogens in having adapted to its parasitic lifestyle by acquiring a SUF system from nonpathogenic Archaea to synthesize Fe/S clusters under oxygen stress.
	PMID: 22699510 [PubMed - as supplied by publisher]

8.	Vet Parasitol. 2012 May 15. [Epub ahead of print] Canine leishmaniosis. Modulation of macrophage/lymphocyte interactions by L. infantum. Diaz S, Fonseca IP, Rodrigues A, Martins C, Cartaxeiro C, Silva MJ, Brito TV, Alexandre-Pires G, Santos-Gomes GM. Source Unidade de Ensino e Investigação de Parasitologia Médica, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal. Abstract Canine leishmaniosis, caused by Leishmania infantum, is a systemic disease with variable clinical signs and a progressive evolution. This disease is characterized by impaired T cell-mediated immune response, which has been associated with disease chronicity and high mortality. Protective immunity against leishmaniosis is thought to be mediated by T cell and cytokine production. The T cell activation requires a primary signal delivered by the major histocompatibility complex (MHC) molecules present on the surface of antigen presenting cells, and a non-specific signal generated by co-stimulatory molecules. To characterize canine immune responses in the presence of L. infantum parasites or their antigens, in vitro cell cultures of canine macrophages and lymphocytes were established, and the macrophages presenting MHC class II molecules were evaluated as well as the expression of IL-12 and CD80-86 co-stimulatory molecules and nitric oxide production. The results showed for the first time the up-regulation of MHC class II molecules on the surface in canine peripheral blood monocyte-derived macrophages during L. infantum infection in the presence of lymphocytes. In addition, a lack of co-stimulatory expression and a reduced release of nitric oxide were observed, suggesting a loss of T cell function and consequently an inactivation of the macrophage oxidative burst which, in turn, favors the survival of Leishmania. These results constitute a new contribution for the understanding of the interactions between L. infantum and the canine immune system. Copyright © 2012 Elsevier B.V. All rights reserved.
	PMID: 22698797 [PubMed - as supplied by publisher]

9.	Curr Opin Microbiol. 2012 Jun 12. [Epub ahead of print] Making an anti-amastigote vaccine for visceral leishmaniasis: rational, update and perspectives. Fernandes AP, Coelho EA, Machado-Coelho GL, Grimaldi G Junior, Gazzinelli RT. Source Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Abstract Visceral leishmaniasis is a major health problem in Latina America, as well as the Mediterranean region of Europe and Asia. We aimed to develop a vaccine against visceral leishmaniasis targeting the intracellular amastigotes, which is the parasite stage that persists throughout infections with Leishmania parasites. With this in mind, we identified an amastigote specific antigen (A2) that contains an immunogenic epitope for CD4+ T helper (Th) cells and multiple repetitive units encoding CD8+ cytotoxic T lymphocyte (CTL) epitopes. Vaccine formulations containing the recombinant A2 associated with saponin, alum and IL-12 or expressed by attenuated adenovirus were shown to be protective in mice, dogs and nonhuman-primates. We are currently identifying novel amastigote specific immunogenic proteins that could be aggregated to A2 to further improve the level of vaccine-induced cell-mediated immunity and protection against visceral leishmaniasis. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22698479 [PubMed - as supplied by publisher]

10.	Trends Parasitol. 2012 Apr;28(4):136-41. Epub 2012 Feb 25. The evolution of Trypanosoma cruzi: the 'bat seeding' hypothesis. Hamilton PB, Teixeira MM, Stevens JR. Source Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, United Kingdom. Abstract Recent discussions on the evolution of Trypanosoma cruzi have been dominated by the southern super-continent hypothesis, whereby T. cruzi and related parasites evolved in isolation in the mammals of South America, Antarctica and Australia. Here, we consider recent molecular evidence suggesting that T. cruzi evolved from within a broader clade of bat trypanosomes, and that bat trypanosomes have successfully made the switch into other mammalian hosts in both the New and Old Worlds. Accordingly, we propose an alternative hypothesis--the bat seeding hypothesis--whereby lineages of bat trypanosomes have switched into terrestrial mammals, thereby seeding the terrestrial lineages within the clade. One key implication of this finding is that T. cruzi may have evolved considerably more recently than previously envisaged. Copyright © 2012 Elsevier Ltd. All rights reserved.
	PMID: 22365905 [PubMed - indexed for MEDLINE]
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