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Sent on Friday, 2009 Jun 26Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
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A Combined CXCL10, CXCL8 and H-FABP Panel for the Staging of Human African Trypanosomiasis Patients.
Biomedical Proteomics Research Group, Medical University Centre, Geneva, Switzerland.
BACKGROUND: Human African trypanosomiasis (HAT), also known as sleeping sickness, is a parasitic tropical disease. It progresses from the first, haemolymphatic stage to a neurological second stage due to invasion of parasites into the central nervous system (CNS). As treatment depends on the stage of disease, there is a critical need for tools that efficiently discriminate the two stages of HAT. We hypothesized that markers of brain damage discovered by proteomic strategies and inflammation-related proteins could individually or in combination indicate the CNS invasion by the parasite. METHODS: Cerebrospinal fluid (CSF) originated from parasitologically confirmed Trypanosoma brucei gambiense patients. Patients were staged on the basis of CSF white blood cell (WBC) count and presence of parasites in CSF. One hundred samples were analysed: 21 from stage 1 (no trypanosomes in CSF and </=5 WBC/microL) and 79 from stage 2 (trypanosomes in CSF and/or >5 WBC/microL) patients. The concentration of H-FABP, GSTP-1 and S100beta in CSF was measured by ELISA. The levels of thirteen inflammation-related proteins (IL-1ra, IL-1beta, IL-6, IL-9, IL-10, G-CSF, VEGF, IFN-gamma, TNF-alpha, CCL2, CCL4, CXCL8 and CXCL10) were determined by bead suspension arrays. RESULTS: CXCL10 most accurately distinguished stage 1 and stage 2 patients, with a sensitivity of 84% and specificity of 100%. Rule Induction Like (RIL) analysis defined a panel characterized by CXCL10, CXCL8 and H-FABP that improved the detection of stage 2 patients to 97% sensitivity and 100% specificity. CONCLUSION: This study highlights the value of CXCL10 as a single biomarker for staging T. b. gambiense-infected HAT patients. Further combination of CXCL10 with H-FABP and CXCL8 results in a panel that efficiently rules in stage 2 HAT patients. As these molecules could potentially be markers of other CNS infections and disorders, these results should be validated in a larger multi-centric cohort including other inflammatory diseases such as cerebral malaria and active tuberculosis.
PMID: 19554086 [PubMed - in process]
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The Leishmania OligoC-TesT as a simple, rapid and standardized tool for the molecular diagnosis of cutaneous leishmaniasis in Peru.
Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia, Lima, Peru; Tropical Diseases Unit, Division of Infectious Diseases, University Health Network-Toronto General Hospital, Toronto, Canada; Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium; Coris BioConcept, Gembloux, Belgium; Universidad Nacional San Antonio Abad del Cusco, Cusco, Peru; Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia.
Molecular methods such as PCR have become attractive tools for the diagnosis of cutaneous leishmaniasis (CL), both for their high sensitivity and specificity. However, the practical use in routine diagnosis is limited due to the infrastructural requirements and the lack of any standardization. Recently, a simplified and standardized PCR format for molecular detection of Leishmania was developed. The Leishmania OligoC-TesT is based on simple and rapid detection on dipstick of PCR amplified Leishmania DNA. In this study, we estimated the diagnostic accuracy of the Leishmania OligoC-TesT on 61 specimen from 44 CL suspected cases presenting at the leishmaniasis clinic of the Instituto de Medicina Tropical "Alexander von Humboldt", Peru. On the basis of parasitological detection and leishmanin skin test (LST), patients were classified as (i) confirmed CL, (ii) LST positive cases and (iii) LST negative cases. The sensitivity of the Leishmania OligoC-TesT was 74% (95% CI: 60.5%-84.1%) on lesion aspirates and 92% (95% CI: 81.2%-96.9%) on scrapings. A significant higher sensitivity was observed with a conventional PCR targeting the kinetoplast DNA (kDNA) on the aspirates (94%) (p = 0.001), while there was no significant difference in sensitivity on the lesion scrapings (88%) (p = 0.317). In addition, the Leishmania OligoC-TesT was evaluated on 13 CL suspected cases in 2 different peripheral health centers in the central jungle of Peru. Our findings clearly indicate the high accuracy of the Leishmania OligoC-TesT on lesion scrapings for simple and rapid molecular diagnosis of CL in Peru.
PMID: 19553579 [PubMed - as supplied by publisher]
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Pentamidine as secondary prophylaxis for visceral leishmaniasis in the immunocompromised host: report of four cases.
Hospital for Tropical Diseases, London, UK.
We report a retrospective and descriptive study of four immunocompromised patients (three with HIV-1 and one with idiopathic CD4+-lymphopenia) with relapsing visceral leishmaniasis seen at the Hospital for Tropical Diseases, London, in whom pentamidine was used as secondary prophylaxis to prevent relapse. Patients experienced between one and four relapses before commencing prophylaxis with subsequent relapse-free periods ranging from 5 to 98 months. Based on these observational data, we recommend large trials to investigate the efficacy of pentamidine over other agents in preventing relapse of VL in the immunocompromised patient.
PMID: 19552658 [PubMed - as supplied by publisher]
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Risk factors for in-hospital mortality of visceral leishmaniasis patients in eastern Uganda.
Médecins Sans Frontières, Geneva, Switzerland.
Objective To identify risk factors for in-hospital mortality in patients treated for visceral leishmaniasis (VL) in Uganda. Methods Retrospective analysis of VL patients' clinical data collected for project monitoring by Médecins Sans Frontières in Amudat, eastern Uganda. Results Between 2000 and 2005, of 3483 clinically suspect patients, 53% were confirmed with primary VL. Sixty-two per cent were children <16 years of age with a male/female ratio of 2.2. The overall case-fatality rate during pentavalent antimonial (n = 1641) or conventional amphotericin B treatment (n = 217) was 3.7%. There was no difference in the case-fatality rate between treatment groups (P > 0.20). The main risk factors for in-hospital death identified by a multivariate analysis were age <6 years and >15 years, concomitant tuberculosis or hepatopathy, and drug-related adverse events. The case-fatality rate among patients >45 years of age was strikingly high (29.0%). Conclusion Subgroups of VL patients at higher risk of death during treatment with drugs currently available in Uganda were identified. Less toxic drugs should be evaluated and used in these patients.
PMID: 19552645 [PubMed - as supplied by publisher]
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Wild ecotopes and food habits of Triatoma longipennis infected by Trypanosoma cruzi lineages I and II in Mexico.
Département Société et Santé, Unité de Recherche 016 and Unité de Recherche 165, Institut de Recherche pour le Développement, Montpellier, France.
The control of wild triatomine populations that can invade dwellings is a major challenge for Chagas disease control in Mexico, but a better knowledge of the biology of these populations is required to develop appropriate control methods. We describe a new terrestrial ecotope of Triatoma longipennis, a principal vector in the occidental part of Mexico, in addition to its previously identified niche in rock pile boundary walls. Analysis of feeding hosts in the two ecotopes showed that this species is able to diversify its food sources outside of the principal hosts, Dasypus novemcinctus and Procyon lotor, and to disperse in search of new meals. Moreover, T. longipennis are strongly infected not only by the Trypanosoma cruzi I lineage found in the domestic cycle, but also by T. cruzi lineage II. The impact of T. cruzi II on human infection remains to be determined.
PMID: 19478263 [PubMed - indexed for MEDLINE]
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European rabbits (Oryctolagus cuniculus) are naturally infected with different Trypanosoma cruzi genotypes.
Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Santiago, Chile. cbotto@uchile.cl
Trypanosoma cruzi, the etiologic agent of Chagas disease, presents a complex life cycle, cycling between reduviid vectors and wild and domestic mammals. The European rabbit is an introduced species in America, but its role as reservoir in the wild transmission cycle of Chagas disease remains unknown. We used polymerase chain reaction, Southern blot, and hybridization tests to detect infection and characterize genotypes in rabbits from a hyperendemic area of Chagas disease in Chile. Results show 38% of infection with different genotypes. We provide evidence that rabbits are naturally infected with T. cruzi, which may have important epidemiologic consequences for the wild transmission cycle.
PMID: 19478255 [PubMed - indexed for MEDLINE]
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Department of Pathology and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Cyclic AMP-protein kinase A (PKA) signaling is important for the growth and differentiation of Trypanosoma cruzi. Immunofluorescence suggests that PKA can associate with the plasma membrane of trypomastigotes. We found that the PKA regulatory subunit interacts with several P-type ATPases. These P-type ATPases may play a role in anchoring PKA to the plasma membrane in T. cruzi.
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Quantitative computerized western blotting.
School of Veterinary Medicine, Hebrew University of Jerusalem, P. O. Box 12, Rehovot, 76100, Israel.
Western blotting allows analysis of antibody reactivity against multiple antigens separated according to their molecular weights. The distinction between immune dominant and recessive antigens is often difficult and carried out by qualitative or empirical means. Quantitative computerized western blotting (QCWB) addresses this difficulty by analyzing reactivity to specific antigens and providing a statistically measurable value for each band. This allows differentiation between immunodominant and immunorecessive determinants. QCWB is appropriate for either single time point analysis or longitudinal studies where multiple time points are evaluated and the reactivities against individual bands compared. This technique can be used to study humoral responses to complex antigenic mixtures such as allergens and infectious agents, or to identify serologic markers for early diagnosis of cancer, autoimmune, or infectious diseases, or to monitor patient's clinical status.
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[Article in English, Portuguese]Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ Brazil. emedei70@hotmail.com
Chagas' disease is a serious health problem in Latin America. Between 25 to 30% of the infected patients develop the chronic form of the disease, with progressive myocardial damage and often, sudden death. Adrenergic or cholinergic antibodies with G-protein coupled membrane receptor activity may be present in the sera of these patients. The present study discusses the etiology and the contribution of antibodies to the physiopathology of Chagas' disease.
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