Thursday, August 5, 2010

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 - 7 of 7

1. Eur J Immunol. 2010 Jul 9. [Epub ahead of print]

A live Leishmania major vaccine containing CpG motifs induces the de novo generation of Th17 cells in C57BL/6 mice.

Wu W, Huang L, Mendez S.

Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

Abstract

Cutaneous leishmaniasis produces open sores that lead to scarring and disfiguration. We have reported that vaccination of C57BL/6 mice with live Leishmania major plus CpG DNA (Lm/CpG) prevents lesion development and provides long-term immunity. Our current study aims to characterize the components of the adaptive immune response that are unique to Lm/CpG. We find that this vaccine enhances the proliferation of CD4(+) Th17 cells, which contrasts with the highly polarized Th1 response caused by L. major alone; the Th17 response is dependent upon release of vaccine-induced IL-6. Neutralization of IFN-gamma and, in particular, IL-17 caused increased parasite burdens in Lm/CpG-vaccinated mice. IL-17R-deficient Lm/CpG-vaccinated mice develop lesions, and display decreased IL-17 and IFN-gamma, despite normal IL-12, production. Neutrophil accumulation is also decreased in the IL-17R-deficient Lm/CpG-vaccinated mice but Treg numbers are augmented. Our data demonstrate that activation of immune cells through CpG DNA, in the presence of live L. major, causes the specific induction of Th17 cells, which enhances the development of a protective cellular immunity against the parasite. Our study also demonstrates that vaccines combining live pathogens with immunomodulatory molecules may strikingly modify the natural immune response to infection in an alternative manner to that induced by killed or subunit vaccines.

PMID: 20683901 [PubMed - as supplied by publisher]
2. Am J Trop Med Hyg. 2010 Aug;83(2):374-9.

Diagnostic Accuracy and Feasibility of Serological Tests on Filter Paper Samples for Outbreak Detection of T.b. gambiense Human African Trypanosomiasis.

Hasker E, Lutumba P, Mumba D, Lejon V, Büscher P, Kande V, Muyembe JJ, Menten J, Robays J, Boelaert M.

Institute of Tropical Medicine Antwerp, Belgium; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Programme National de Lutte Contre la Trypanosomiase Humaine Africaine, Kinshasa, Democratic Republic of the Congo.

Abstract

Control of human African trypanosomiasis (HAT) in the Democratic Republic of Congo is based on mass population screening by mobile teams; a costly and labor-intensive approach. We hypothesized that blood samples collected on filter paper by village health workers and processed in a central laboratory might be a cost-effective alternative. We estimated sensitivity and specificity of micro-card agglutination test for trypanosomiasis (micro-CATT) and enzyme-linked immunosorbent assay (ELISA)/T.b. gambiense on filter paper samples compared with parasitology-based case classification and used the results in a Monte Carlo simulation of a lot quality assurance sampling (LQAS) approach. Micro-CATT and ELISA/T.b. gambiense showed acceptable sensitivity (92.7% [95% CI 87.4-98.0%] and 82.2% [95% CI 75.3-90.4%]) and very high specificity (99.4% [95% CI 99.0-99.9%] and 99.8% [95% CI 99.5-100%]), respectively. Conditional on high sample size per lot (>/= 60%), both tests could reliably distinguish a 2% from a zero prevalence at village level. Alternatively, these tests could be used to identify individual HAT suspects for subsequent confirmation.

PMID: 20682885 [PubMed - in process]
3. Am J Trop Med Hyg. 2010 Aug;83(2):357-64.

Effectiveness and Safety of Liposomal Amphotericin B for Visceral Leishmaniasis under Routine Program Conditions in Bihar, India.

Sinha PK, Roddy P, Palma PP, Kociejowski A, Lima MA, Rabi Das VN, Gupta J, Kumar N, Mitra G, Saint-Sauveur JF, Seena S, Balasegaram M, Parreño F, Pandey K.

Rajendra Memorial Research Institute of Medical Science, Patna, Bihar, India; Médecins Sans Frontières, Medical Department, Operational Centre Barcelona-Athens, Barcelona, Spain; Médecins Sans Frontières, London, United Kingdom; Médecins Sans Frontières-India, Operational Centre Barcelona-Athens, New Delhi, India.

Abstract

We evaluated, through the prospective monitoring of 251 patients at Sadar Hospital in Bihar, India, the effectiveness and safety of 20 mg/kg body weight of liposomal amphotericin B for the treatment of visceral leishmaniasis. The treatment success rates for the intention-to-treat, per protocol, and intention-to-treat worse-case scenario analyses were 98.8%, 99.6%, and 81.3%, respectively. Nearly one-half of patients experienced mild adverse events, but only 1% developed serious but non-life-threatening lips swelling. The lost to follow-up rate was 17.5%. Our findings indicate that the 20 mg/kg body weight treatment dosage is effective and safe under routine program conditions. Given that the exorbitant cost of liposomal amphotericin B is a barrier to its widespread use, we recommend further study to monitor and evaluate a lowered dosage and a shorter treatment course.

PMID: 20682882 [PubMed - in process]
4. Am J Trop Med Hyg. 2010 Aug;83(2):351-6.

Efficacy of miltefosine for the treatment of american cutaneous leishmaniasis.

Vélez I, López L, Sánchez X, Mestra L, Rojas C, Rodríguez E.

Programa de Estudio y Control de Enfermedades Tropicales, PECET, Universidad de Antioquia, Medellín, Colombia; Dirección de Sanidad, DISAN, Ejército de Colombia; Grupo de epidemiología, Universidad de Antioquia, Medellín, Colombia.

Abstract

Miltefosine is an oral agent used for cutaneous leishmaniasis treatment. An open-label, randomized, phase III clinical trial was carried out in the Colombian army population. Miltefosine, 50 mg capsule was taken orally three times per day for 28 days (N = 145) or meglumine antimoniate, 20 mg/kg body weight per day for 20 days by intramuscular injection (N = 143). The efficacy of miltefosine by protocol was 69.8% (85/122 patients) and 58.6% (85/145 patients) by intention to treat. For meglumine antimoniate, the efficacy by protocol was 85.1% (103/121 patients) and 72% (103/143 patients) by intention to treat. No association was found between drug efficacy and L. (V.) braziliensis or L. (V.) panamensis species of Leishmania responsible for infection. Adverse gastrointestinal events were associated with the use of miltefosine, the meglumine antimoniate treatment was associated with adverse effects on the skeletal musculature, fever, cephalea, and higher toxicity in kidney, liver, pancreas, and hematological system.

PMID: 20682881 [PubMed - in process]
5. Am J Trop Med Hyg. 2010 Aug;83(2):345-350.

Clinical and Demographic Stratification of Test Performance: A Pooled Analysis of Five Laboratory Diagnostic Methods for American Cutaneous Leishmaniasis.

Boggild AK, Ramos AP, Espinosa D, Valencia BM, Veland N, Miranda-Verastegui C, Arevalo J, Low DE, Llanos-Cuentas A.

Tropical Disease Unit, Division of Infectious Diseases, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada; Instituto de Medicina Tropical Alexander von Humboldt, y Departamento de Bioquimica, Biologia Molecular y Farmacologia, Facultad de Ciencias, Universidad Peruana Cayetano Heredia, Lima, Peru; Laboratories Branch, Ontario Agency for Health Protection and Promotion, Etobicoke, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Hospital Nacional Cayetano Heredia, Lima, Peru.

Abstract

We evaluated performance characteristics of five diagnostic methods for cutaneous leishmaniasis. Patients who came to the Leishmania Clinic of Hospital Nacional Cayetano Heredia in Lima, Peru, were enrolled in the study. Lesion smears, culture, microculture, polymerase chain reaction (PCR), and leishmanin skin test (LST) were performed. A total of 145 patients with 202 lesions were enrolled: 114 patients with 161 lesions fulfilled criteria for cutaneous leishmaniasis. Sensitivity and specificity were 57.8% (95% confidence interval [CI] = 50.2-65.4%) and 100.0% for culture, 78.3% (95% CI = 71.9-84.7%) and 100.0% for microculture, 71.4% (95% CI = 64.4-78.4%) and 100.0% for smears, 78.2% (95% CI = 70.6-85.8%) and 77.4% (95% CI = 62.7-92.1%) for LST, and 96.9% (95% CI = 94.2-99.6%) and 65.9% (95% CI = 51.4-80.4%) for PCR. PCR was more sensitive than the other assays (P < 0.001). Sensitivities of culture, smears, and LST varied by lesion duration and appearance. PCR offers performance advantages over other assays, irrespective of patient age, sex, lesion duration, or appearance. That clinical factors influence performance of non-molecular assays offers clinicians a patient-focused approach to diagnostic test selection.

PMID: 20682880 [PubMed - as supplied by publisher]
6. Am J Trop Med Hyg. 2010 Aug;83(2):209.

Colonic leishmaniasis followed by liver transplantation.

Araujo SA, Nascentes Queiroz TC, Demas Alvares Cabral MM.

Program of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Federal University of Minas Gerais, Brazil; Pediatric Gastroenterology, Alfa Institute of Gastroenterology, Hospital of the Clinics, Federal University of Minas Gerais, Brazil; Department of Pathology, Alfa Institute of Gastroenterology, Hospital of the Clinics, Federal University of Minas Gerais, Brazil.

PMID: 20682856 [PubMed - in process]
7. J Cell Sci. 2010 Aug 3. [Epub ahead of print]

Basal body movements orchestrate membrane organelle division and cell morphogenesis in Trypanosoma brucei.

Lacomble S, Vaughan S, Gadelha C, Morphew MK, Shaw MK, McIntosh JR, Gull K.

Abstract

The defined shape and single-copy organelles of Trypanosoma brucei mean that it provides an excellent model in which to study how duplication and segregation of organelles is interfaced with morphogenesis of overall cell shape and form. The centriole or basal body of eukaryotic cells is often seen to be at the centre of such processes. We have used a combination of electron microscopy and electron tomography techniques to provide a detailed three-dimensional view of duplication of the basal body in trypanosomes. We show that the basal body duplication and maturation cycle exerts an influence on the intimately associated flagellar pocket membrane system that is the portal for secretion and uptake from this cell. At the start of the cell cycle, a probasal body is positioned anterior to the basal body of the existing flagellum. At the G1-S transition, the probasal body matures, elongates and invades the pre-existing flagellar pocket to form the new flagellar axoneme. The new basal body undergoes a spectacular anti-clockwise rotation around the old flagellum, while its short new axoneme is associated with the pre-existing flagellar pocket. This rotation and subsequent posterior movements results in division of the flagellar pocket and ultimately sets parameters for subsequent daughter cell morphogenesis.

PMID: 20682637 [PubMed - as supplied by publisher]

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