Friday, September 4, 2009

What's new for 'Trypanosomatids' in PubMed

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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 -4 of 4

1: Clin Vaccine Immunol. 2009 Sep 2. [Epub ahead of print]

Comparative evaluation in four mouse inbred strains of two vaccine candidates against experimental leishmaniasis due to Leishmania major infection.

Benhnini F, Chenik M, Laouini D, Louzir H, Cazenave PA, Dellagi K.

Laboratoire d'Immuno-Pathologie, Vaccinologie et Génétique Moléculaire (LIVGM), WHO Collaborative Center for Research and Training in Leishmaniasis, and Laboratoire International Associé (LIA) "Ingénierie Biomoléculaire", Centre National de Recherche Scientifique (CNRS), France; Institut Pasteur de Tunis, 13 place Pasteur, BP 74, 1002 Tunis-Belvédère, Tunisia; Unité d'Immunophysiopathologie Infectieuse, CNRS URA 1961 and Université Pierre et Marie Curie, Institut Pasteur, 75724 Paris Cedex 15, France.

Experimental leishmaniasis in BALB/c and C57BL/6 mice are the most investigated murine models that were used for the preclinical evaluation of Leishmania vaccine candidates. We have previously described two new inbred mouse strains named PWK and MAI issued from feral founders, that also support the development of experimental leishmaniasis due to L. major. In this study, we asked whether different mouse inbred strains generate concordant or discordant results when used to evaluate the potential of Leishmania proteins to protect against experimental leishmaniasis. To this end, two Leishmania proteins namely LACK (Leishmania Homolog of Receptor for Activated C Kinase) and LmPDI (L. major protein disulfide isomerase) were compared for their capacity to protect against experimental leishmaniasis in PWK, MAI, BALB/c and C57BL/6 inbred mouse strains. Our data show that the capacity of Leishmania proteins to confer protection depends on the mouse strain used, stressing the important role played by the genetic background in shaping the immune response against the pathogen. These results may have important implications for the preclinical evaluation of candidate Leishmania vaccines: rather than using a single mouse strain, a panel of different inbred strains of various genetic backgrounds should be tested in parallel. The antigen that confers protection in the larger range of inbred strains may have better chances to be also protective in the out bred human populations and should be selected for clinical trials.

PMID: 19726616 [PubMed - as supplied by publisher]

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2: Int J Infect Dis. 2009 Aug 31. [Epub ahead of print]

Treatment of visceral leishmaniasis with intravenous pentamidine and oral fluconazole in an HIV-positive patient with chronic renal failure - a case report and brief review of the literature.

Rybniker J, Goede V, Mertens J, Ortmann M, Kulas W, Kochanek M, Benzing T, Arribas JR, Fätkenheuer G.

1st Department of Internal Medicine, University of Cologne, 50924 Cologne, Germany.

We report the case of an HIV-positive patient with visceral leishmaniasis and several relapses after treatment with the two first-line anti-leishmanial drugs, liposomal amphotericin B and miltefosine. End-stage renal failure occurred in 2007 when the patient was on long-term treatment with miltefosine. A relapse of leishmaniasis in 2008 was successfully treated with a novel combination regimen of intravenous pentamidine and oral fluconazole. Secondary prophylaxis with fluconazole monotherapy did not prevent parasitological relapse of leishmaniasis.

PMID: 19726213 [PubMed - as supplied by publisher]

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3: Vet Immunol Immunopathol. 2009 Aug 7. [Epub ahead of print]

Comparison of monoclonal and polyclonal antibodies for the detection of canine IgG1 and IgG2, and associations with infection outcome in Leishmania infantum naturally infected dogs.

Carson C, Quinnell RJ, Day MJ, Courtenay O.

Populations and Disease Research Group, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.

In murine models of leishmaniasis, IgG subclass expression is a proxy measure for Th1/Th2 cellular immune response bias. However, in dogs, the reservoir of zoonotic visceral leishmaniasis, no consistent association has been described between IgG subclass ratios and disease resistance. Inconsistent results may reflect lack of specificity of commonly used commercial antibodies. Our aim was to measure IgG1 and IgG2 responses to crude Leishmania antigen using commercial polyclonal antibodies for comparison with a panel of commercially unavailable monoclonal antibodies, in a cohort of 60 naturally infected dogs, and to compare associations between subclass responses and clinical or parasitological outcomes. IgG1 and IgG2, measured by both antibodies, were higher in clinically symptomatic than in asymptomatic dogs (P</=0.03), reflecting general upregulation of IgG in infected dogs. Unlike the murine model, canine IgG2:IgG1 ratios were not predictive of clinical or parasitological outcomes of infection. Associations between subclass levels and positivity by bone marrow culture and PCR were not consistent when measured with different antibodies. Further research is needed to re-evaluate the specificity of commercially available IgG subclass antibodies.

PMID: 19726090 [PubMed - as supplied by publisher]

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4: Infect Immun. 2009 Sep;77(9):3948-57. Epub 2009 Jul 13.Click here to read LinkOut

Clinical chemistry of congenic mice with quantitative trait loci for predicted responses to Trypanosoma congolense infection.

Rathkolb B, Noyes HA, Brass A, Dark P, Fuchs H, Gailus-Durner V, Gibson J, de Angelis MH, Ogugo M, Iraqi F, Kemp SJ, Naessens J, Pope ME, Wolf E, Agaba M.

International Livestock Research Institute, Nairobi 00100, Kenya.

Trypanosoma congolense is a protozoan parasite that causes severe diseases in livestock. Three major quantative trait loci (QTL), Tir1, Tir2, and Tir3, control the survival time of mice after infection with T. congolense. Congenic mice carrying the C57BL/6 resistance alleles on the A/J background were developed for each of these loci. The congenic mice were used to physically map the regions containing the QTL gene(s) and to investigate the physiological effect of each locus. Clinical chemistry data for infected A/J, C57BL/6, and BALB/c mice were obtained for 15 analytes at five time points. Congenic mice were assessed for survival, parasitemia, and anemia as well as seven clinical-chemical analytes. The survival times were significantly increased in the Tir1 and Tir2 mice but not Tir3 congenic mice. The survival time of the parental inbred mice correlated negatively with parasitemia but positively with alanine aminotransferase activities in serum, suggesting that inflammatory reactions in the liver had a beneficial effect possibly associated with reduced parasitemia. However, there was no difference in parasitemia or liver enzyme activities of Tir1 and Tir2 congenic mice relative to their controls, showing that survival, parasitemia, and degree of liver damage are not associated with each other, despite the correlation in the parental lines. These data suggest that the congenic loci affect survival but do not affect control of parasite number. They may therefore act by limiting the pathological consequences of T. congolense infection.

PMID: 19596769 [PubMed - indexed for MEDLINE]

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