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Sent on Sunday, 2011 Feb 13Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | PLoS One. 2011 Feb 2;6(2):e14644.Potency, Efficacy and Durability of DNA/DNA, DNA/Protein and Protein/Protein Based Vaccination Using gp63 Against Leishmania donovani in BALB/c Mice.Mazumder S, Maji M, Das A, Ali N.Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India. AbstractBACKGROUND: Visceral leishmaniasis (VL) caused by an intracellular protozoan parasite Leishmania, is fatal in the absence of treatment. At present there are no effective vaccines against any form of leishmaniasis. Here, we evaluate the potency, efficacy and durability of DNA/DNA, DNA-prime/Protein-boost, and Protein/Protein based vaccination against VL in a susceptible murine model. METHODS AND FINDINGS: To compare the potency, efficacy, and durability of DNA, protein and heterologous prime-boost (HPB) vaccination against Leishmania donovani, major surface glycoprotein gp63 was cloned into mammalian expression vector pcDNA3.1 for DNA based vaccines. We demonstrated that gp63 DNA based vaccination induced immune responses and conferred protection against challenge infection. However, vaccination with HPB approach showed comparatively enhanced cellular and humoral responses than other regimens and elicited early mixed Th1/Th2 responses before infection. Moreover, challenge with parasites induced polarized Th1 responses with enhanced IFN-γ, IL-12, nitric oxide, IgG2a/IgG1 ratio and reduced IL-4 and IL-10 responses compared to other vaccination strategies. Although, vaccination with gp63 DNA either alone or mixed with CpG- ODN or heterologously prime-boosting with CpG- ODN showed comparable levels of protection at short-term protection study, DNA-prime/Protein-boost in presence of CpG significantly reduced hepatic and splenic parasite load by 10(7) fold and 10(10) fold respectively, in long-term study. The extent of protection, obtained in this study has till now not been achieved in long-term protection through HPB approach in susceptible BALB/c model against VL. Interestingly, the HPB regimen also showed marked reduction in the footpad swelling of BALB/c mice against Leishmania major infection. CONCLUSION/SIGNIFICANCE: HPB approach based on gp63 in association with CpG, resulted in robust cellular and humoral responses correlating with durable protection against L. donovani challenge till twelve weeks post-vaccination. These results emphasize the potential of DNA-prime/Protein-boost vaccination over DNA/DNA and Protein/Protein based vaccination in maintaining long-term immunity against intracellular pathogen like Leishmania. |
| PMID: 21311597 [PubMed - in process] | |
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| 2. | PLoS Negl Trop Dis. 2011 Jan 18;5(1):e941.Factors associated with acquisition of human infective and animal infective trypanosome infections in domestic l ivestock in Western kenya.von Wissmann B, Machila N, Picozzi K, Fèvre EM, Dec Bronsvoort BM, Handel IG, Welburn SC.Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom. AbstractBACKGROUND: Trypanosomiasis is regarded as a constraint on livestock production in Western Kenya where the responsibility for tsetse and trypanosomiasis control has increasingly shifted from the state to the individual livestock owner. To assess the sustainability of these localised control efforts, this study investigates biological and management risk factors associated with trypanosome infections detected by polymerase chain reaction (PCR), in a range of domestic livestock at the local scale in Busia, Kenya. Busia District also remains endemic for human sleeping sickness with sporadic cases of sleeping sickness reported. RESULTS: In total, trypanosome infections were detected in 11.9% (329) out of the 2773 livestock sampled in Busia District. Multivariable logistic regression revealed that host species and cattle age affected overall trypanosome infection, with significantly increased odds of infection for cattle older than 18 months, and significantly lower odds of infection in pigs and small ruminants. Different grazing and watering management practices did not affect the odds of trypanosome infection, adjusted by host species. Neither anaemia nor condition score significantly affected the odds of trypanosome infection in cattle. Human infective Trypanosoma brucei rhodesiense were detected in 21.5% of animals infected with T. brucei s.l. (29/135) amounting to 1% (29/2773) of all sampled livestock, with significantly higher odds of T. brucei rhodesiense infections in T. brucei s.l. infected pigs (OR = 4.3, 95%CI 1.5-12.0) than in T. brucei s.l. infected cattle or small ruminants. CONCLUSIONS: Although cattle are the dominant reservoir of trypanosome infection it is unlikely that targeted treatment of only visibly diseased cattle will achieve sustainable interruption of transmission for either animal infective or zoonotic human infective trypanosomiasis, since most infections were detected in cattle that did not exhibit classical clinical signs of trypanosomiasis. Pigs were also found to be reservoirs of infection for T. b. rhodesiense and present a risk to local communities. |
| PMID: 21311575 [PubMed - in process] | |
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| 3. | Science. 2011 Feb 11;331(6018):775-8.Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis.Ives A, Ronet C, Prevel F, Ruzzante G, Fuertes-Marraco S, Schutz F, Zangger H, Revaz-Breton M, Lye LF, Hickerson SM, Beverley SM, Acha-Orbea H, Launois P, Fasel N, Masina S.Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland. AbstractMucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus-1 (LRV1) burden that is recognized by the host Toll-like receptor 3 (TLR3) to induce proinflammatory cytokines and chemokines. Paradoxically, these TLR3-mediated immune responses rendered mice more susceptible to infection, and the animals developed an increased footpad swelling and parasitemia. Thus, LRV1 in the metastasizing parasites subverted the host immune response to Leishmania and promoted parasite persistence. |
| PMID: 21311023 [PubMed - in process] | |
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| 4. | Res Vet Sci. 2011 Feb 8. [Epub ahead of print]Development of a minor groove binding probe based real-time PCR fo r the diagnosis and quantification of Leishmania infantum in dog specimens.Galletti E, Bonilauri P, Bardasi L, Fontana MC, Ramini M, Renzi M, Dosa G, Merialdi G.Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Sezione di Bologna, 40127 Bologna, Italy. AbstractA new quantitative real-time PCR (qPCR) assay based on Taqman® technology and minor groove binding (MGB) probe was developed for the diagnosis of leishmaniosis and quantification of Leishmania infantum DNA in infected dogs. This method was based on the amplification of a 122bp fragment of the highly conserved kDNA minicircles of L. infantum. The reaction was performed using the StepOnePlus™ system with StepOne software™. This assay was able to detect the presence of protozoan parasite DNA in amounts as low as 0.03 parasites per reaction. The standard curve designed for the quantification of parasites showed linearity over seven log DNA concentration range with a correlation coefficient >0.999 and both intra- and inter-assay variability demonstrated the high efficiency and reproducibility of the assay. The qPCR also proved to be successfully applicable to different clinical samples including blood, bone marrow, lymph node aspirates and conjunctival swabs. Copyright © 2011 Elsevier Ltd. All rights reserved. |
| PMID: 21310448 [PubMed - as supplied by publisher] | |
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| 5. | Semin Cell Dev Biol. 2011 Feb 7. [Epub ahead of print]Methylglyoxal metabolism in trypanosomes and leishmania.Wyllie S, Fairlamb AH.Division of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK. AbstractMethylglyoxal is a toxic by-product of glycolysis and other metabolic pathways. In mammalian cells, the principal route for detoxification of this reactive metabolite is via the glutathione-dependent glyoxalase pathway forming D-Lactate, involving lactoylglutathione lyase (GLO1; EC 4.4.1.5) and hydroxyacylglutathione hydrolase (GLO2; EC 3.2.1.6). In contrast, the equivalent enzymes in the trypanosomatid parasites Trypanosoma cruzi and Leishmania spp. show >200-fold selectivity for glutathionylspermidine and trypanothione over glutathione and are therefore sensu stricto lactoylglutathionylspermidine lyases (EC 4.4.1.-) and hydroxyacylglutathionylspermidine hydrolases (EC 3.2.1.-). The unique substrate specificity of the parasite glyoxalase enzymes can be directly attributed to their unusual active site architecture. The African trypanosome differs from these parasites in that it lacks GLO1 and converts methylglyoxal to L-lactate rather than D-lactate. Since T. brucei is the most sensitive of the trypanosomatids to methylglyoxal toxicity, the absence of a complete and functional glyoxalase pathway in these parasites is perplexing. Alternative routes of methylglyoxal detoxification in T. brucei are discussed along with the potential of exploiting trypanosomatid glyoxalase enzymes as targets for anti-parasitic chemotherapy. Copyright © 2011. Published by Elsevier Ltd. |
| PMID: 21310261 [PubMed - as supplied by publisher] | |
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| 6. | Int J Parasitol. 2011 Feb 7. [Epub ahead of print]The protective effect against Leishmania infection conferred by sand fly bites is lim ited to short-term exposure.Rohoušová I, Hostomská J, Vlková M, Kobets T, Lipoldová M, Volf P.Department of Parasitology, Faculty of Science, Charles University in Prague, Vinicna 7, 128 44 Prague 2, Czech Republic. AbstractUnder laboratory conditions, hosts exposed twice to sand fly saliva are protected against severe leishmaniasis. However, people in endemic areas are exposed to the vector over a long term and may experience sand fly-free periods. Therefore, we exposed mice long- or short-term to Phlebotomus duboscqi bites, followed by Leishmania major infection either immediately or after a sand fly-free period. We showed that protection against leishmaniasis is limited to short-term exposure to sand flies immediately before infection. Our results may explain the persistence of leishmaniasis in endemic areas and should be taken into account when designing anti-Leishmania vaccines based on sand fly saliva. Copyright © 2011. Published by Elsevier Ltd. |
| PMID: 21310158 [PubMed - as supplied by publisher] | |
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| 7. | Parasit Vectors. 2011 Feb 10;4(1):18. [Epub ahead of print]Progress towards the eradication of Tsetse from the Loos islands, Guinea.Kagbadouno MS, Camara M, Bouyer J, Courtin F, Onikoyamou MF, Schofield CJ, Solano P.AbstractABSTRACT: BACKGROUND: The tsetse fly Glossina palpalis gambiensis is the main vector of sleeping sickness (Human African Trypanosomiasis - HAT) in West Africa, in particular in littoral Guinea where this disease is currently very active. The Loos islands constitute a small archipelago some 5km from mainland Guinea, where G. p. gambiensis is well known as a nuisance and potential disease vector by inhabitants of the three main islands, Fotoba, Room, and Kassa. The National Control Program against HAT of Guinea has decided to eradicate tsetse in Loos islands in order to sustainably protect humans and economic activities. After baseline data collection, tsetse control began on the islands in 2006. On each of the three islands a specific combination of control methods was implemented according to the entomological situation found. RESULTS: Starting densities before control operations were 10, 3 and 1 tsetse/trap/day in Kassa, Room and Fotoba respectively, but by July 2010, tsetse were no longer caught in any of the sentinel traps used for monitoring. The reduction rate was faster where several control methods were implemented as a combination (impregnated traps and targets ITT, selective groundspraying, epicutaneous insecticide treatment of pigs, and impregnated fences around pig pens), whereas it was slower when ITT were used as the only control method. CONCLUSIONS: This 100% suppression is a promising step in the eradication process, but G. p. gambiensis may still occur at very low, undetectable, densities on the archipelago. Next step will consist in assessing a 0.05 probability of tsetse absence to ascertain a provisional eradication status. Throughout these operations, a key factor has been the involvement of local teams and local communities without whom such results would be impossible to obtain. Work will continue thanks to the partners involved until total eradication of the tsetse on Loos islands can be declared. |
| PMID: 21310074 [PubMed - as supplied by publisher] | |
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| 8. | Anal Biochem. 2011 Jan 1;408(1):86-94. Epub 2010 Sep 7.Favorably orienting recombinant proteins to develop amperometric biosensors to diagnose Chagas' di sease.Belluzo MS, Ribone MÉ, Camussone C, Marcipar IS, Lagier CM.Departamento de Química Analítica, Universidad Nacional de Rosario, Argentina. AbstractClinical immunoassays often display suitable sensitivity but some lack of specificity or vice versa. As a trade-off between specificity improvement and sensitivity loss, biosensors were designed to perform indirect immunoassays with amperometric detection using tailor-made chimeric receptors to react with the analyte, specific anti-Trypanosoma cruzi immunoglobulin G (IgG). Recombinant chimeras were designed to favor their oriented covalent attachment. This allows the chimeras to properly expose their epitopes, to efficiently capture the analyte, and to withstand severe chemical treatment to reuse the biosensors. By further binding the secondary antibody, horseradish peroxidase-labeled anti-human IgG, in the presence of the soluble mediator and the enzyme substrate, a current that increased with the analyte concentration was measured. Biosensors using the chimeric constructions showed 100% specificity with samples that had revealed false-positive results when using other bioreceptors. A protein bearing a poly-Lys chain and thioredoxin as directing elements displayed the highest signal-to-noise ratio (P<0.05). The limit of detection was 62 ng ml⁻¹, which is eight times lower than that obtained with a currently used commercial Chagas enzyme-linked immunosorbent assay (ELISA) kit. Reusability of the biosensor was assessed. The signal was approximately 80% of the original one after performing 10 consecutive determinations. Copyright © 2010 Elsevier Inc. All rights reserved. |
| PMID: 20828530 [PubMed - indexed for MEDLINE] | |
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