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Sent on Saturday, 2012 February 04Search: 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 Negl Trop Dis. 2012 Jan;6(1):e1501. Epub 2012 Jan 31.Using Molecular Data for Epidemiological Inference: Assessing the Prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania.Auty HK, Picozzi K, Malele I, Torr SJ, Cleaveland S, Welburn S.SourceDivision of Pathway Medicine and Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, United Kingdom. AbstractBACKGROUND:Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. METHODOLOGY/PRINCIPAL FINDINGS:Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0-0.085) for G. swynnertoni and 0% (0-0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0-0.054) and 0.0089% (0-0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. CONCLUSIONS/SIGNIFICANCE:The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data. |
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| 2. | PLoS Negl Trop Dis. 2012 Jan;6(1):e1484. Epub 2012 Jan 31.Comparative Study of rK39 Leis hmania Antigen for Serodiagnosis of Visceral Leishmaniasis: Systematic Review with Meta-Analysis.Maia Z, Lírio M, Mistro S, Mendes CM, Mehta SR, Badaro R.SourceDepartment of Medicine, Federal University of Bahia Salvador, Bahia, Brazil. AbstractBACKGROUND:The rK39 recombinant protein is derived from a specific antigen produced by the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. We present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. METHODOLOGY/PRINCIPAL FINDINGS:A systematic review with meta-analysis of the literature was performed to compare the rK39 strip-test and ELISA formats against serological tests using promastigote antigens derived from whole or soluble parasites for Direct Aglutination Test (DAT), Indirect Immunofluorescence test (IFAT) and ELISA with a promastigote antigen preparation (p-ELISA). Gold standard diagnosis was defined by the demonstration of amastigotes on hematological specimens. A database search was performed on Medline, Lilacs, Scopus, Isi Web of Science, and Cochrane Library. Quality of data was assessed using the QUADAS questionnaire. A search of the electronic databases found 352 papers of which only 14 fulfilled the selection criteria. Three evaluated the rK39 ELISA, while 13 evaluated the rK39 immunochromatographic strip test. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity of 94%, although the DAT had a slightly higher specificity. The rK39 strip test was more sensitive and specific than the IFAT and p-ELISA. We did not detect any difference in the sensitivity and specificity between strips produced by different manufacturers. CONCLUSIONS:The rK39 protein used either in a strip test or in an ELISA, and the DAT are the best choices for implementation of rapid, easy and efficient test for serodiagnosis of VL. |
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| 3. | Parasitol Res. 2012 Feb 3. [Epub ahead of print]Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani.Kumar D, Singh R, Bhandari V, Kulshrestha A, Negi NS, Salotra P.SourceNational Institute of Pathology, Indian Council of Medical Research, Safdarjung Hospital Campus, New Delhi, India. AbstractResistance to antimony is a major cause of failure to therapy in a large proportion of visceral leishmaniasis cases. Methods to distinguish resistant and sensitive parasite are urgently needed as the standard in vitro intracellular drug susceptibility assays are cumbersome and time consuming. Differential expression profiling studies have led to the identification of several antimony resistance-associated genes; however, their efficacy as a potential biomarker for monitoring antimony resistance remains imprecise. We analysed the expression of eight genes [antimony metabolism-associated genes-multidrug resistance protein A (MRPA), γ-glutamylcysteine synthetase (γ-GCS) and aquaporin-1 (AQP1)-and genes identified by proteome/transcriptome profiling-heat shock protein 83, mitogen-activated protein kinase 1 and histones H1, H2A and H4) in antimony-resistant (n = 10) and antimony-sensitive (n = 4) clinical isolates of Leishmania donovani by quantitative real-time PCR, in comparison with a lab-generated resistant and a standard sensitive isolate. We observed a significant differential expression of MRPA, histone H1 (p < 0.01), γ-GCS, HSP83 (p < 0.005) and histone H2A and H4 (p < 0.0001) in a group of sodium antimony gluconate-resistant isolates compared to sensitive isolates. Preferential AQP1 expression was observed in all the sensitive isolates (p < 0.0001). Overall, expression profile in field isolates for all the genes studied showed altered expression in majority of isolates, while in some, the expression was static. All the isolates showed a mosaic of expression pattern of the genes analysed indicating constellation of genes contributes towards the drug susceptibility of parasite. As none of the genes exhibit an absolute correlation with phenotype, targeted expression analysis of a set of genes should be considered as biomarker for distinguishing the antimony-resistant and antimony-sensitive parasite. |
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| 4. | J Infect Dis. 2012 Feb 1. [Epub ahead of print]Therapeutic Vaccination With Recombinant Adenovirus Reduces Splenic Parasite Burden in Experimental Visceral Leishmaniasis .Maroof A, Brown N, Smith B, Hodgkinson MR, Maxwell A, Losch FO, Fritz U, Walden P, Lacey CN, Smith DF, Aebischer T, Kaye PM.SourceCentre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, Heslington, United Kingdom. AbstractTherapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus-based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNγ(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ∼66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection. |
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| 5. | Sci Transl Med. 2012 Feb 1;4(119):119re1.The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis.Wyllie S, Patterson S, Stojanovski L, Simeons FR, Norval S, Kime R, Read KD, Fairlamb AH.SourceDivision of Biological Chemistry and Drug Discovery, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. AbstractSafer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50,000 to 60,000 people each year in parts of Asia, Africa, and Latin America. Here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs, and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg/kg) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC(99) (effective concentration inhibiting growth by 99%) value for at least 24 hours after a single oral dose. A once-daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of visceral leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat this tropical disease. In African trypanosomes, the mode of action of nitro drugs involves reductive activation via a NADH (reduced form of nicotinamide adenine dinucleotide)-dependent bacterial-like nitroreductase. Overexpression of the leishmanial homolog of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold, indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating visceral leishmaniasis. |
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| 6. | Trans R Soc Trop Med Hyg. 2012 Jan 31. [Epub ahead of print]Clinical features and epidemiology of cutaneous leishmaniasis and Leishmania major/HIV co-infec tion in Cameroon: results of a large cross-sectional study.Ngouateu OB, Kollo P, Ravel C, Dereure J, Kamtchouing P, Same-Ekobo A, von Stebut E, Maurer M, Dondji B.SourceDepartment of Animal Biology and Physiology, University of Yaoundé I, Yaoundé, Cameroon; Mokolo District Hospital, Mokolo, Cameroon; Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany; Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Berlin, Germany. AbstractCutaneous leishmaniasis (CL) is endemic in Central Africa, including Cameroon. However, data on its prevalence and co-infection with HIV are scarce. Here we present the results of a large cross-sectional study reporting the prevalence, clinical features and species identification of CL and HIV co-infection in northern Cameroon. A total of 32 466 subjects were clinically screened for CL during a door-to-door survey, followed by parasitological diagnosis in the field laboratory. Amongst the subjects surveyed, 146 (0.4%) were diagnosed with active CL. Seven (4.8%) of these 146 CL patients tested positive for HIV-1 and/or HIV-2. The number of lesions per CL patient ranged from 1 to 20. Three of the five subjects with >10 active lesions were co-infected with HIV. In both CL and HIV co-infected subjects, three successful parasite isolates were identified as Leishmania major by PCR. This first report of L. major/HIV co-infection in Cameroon and Central Africa confirms the endemicity of CL in the region and highlights a worsened CL pathology in HIV co-infected individuals. These findings provide important data necessary for the development and implementation of successful control programmes against CL and HIV in this geographical area. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. |
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| 7. | Trends Parasitol. 2012 Jan 31. [Epub ahead of print]Parasite-specific aptamers as biosynthetic reagents and potential pharmaceuticals.Göringer HU.SourceGenetics, Darmstadt University of Technology, Schnittspahnstrasse 10, 64287 Darmstadt, Germany. AbstractAptamers are short, synthetic nucleic acid molecules. They are generated by a Darwinian-type in vitro evolution method known as 'systematic evolution of ligands by exponential enrichment' (SELEX). SELEX represents an experimental platform to identify rare ligands with predetermined functionality from combinatorial nucleic acid libraries. Since its discovery about 20 years ago the method has been instrumental in identifying a large number of aptamers that recognize targets of very different chemistry and molecular complexity. Although aptamers have been converted into sophisticated biomolecular tools for a diverse set of technologies, only a limited number of aptamers have been selected as binding reagents for parasites or parasite-derived molecules. Here the published examples of aptamers that target Leishmania-, Trypanosoma- and Plasmodia-specific molecules are reviewed. Copyright © 2012 Elsevier Ltd. All rights reserved. |
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| 8. | Southeast Asian J Trop Med Public Health. 2011 Nov;42(6):1405-9.Cavernicolous species of phlebotomine sand flies from Kanchanaburi Province, with an updated species list for Thailand.Apiwathnasorn C, Samung Y, Prummongkol S, Phayakaphon A, Panasopolkul C.SourceDepartment of Medical Entomology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. tmcaw@mahidol.ac.th AbstractDuring 2008-2009 2,401 Phlebotomine sand flies were collected in 14 limestone caves in Kanchanaburi Province, Thailand to determine the prevalence and type of cavernicolous species that have the potential to be leishmaniasis vectors. Twenty species belonging to the genera Chinius, Nemopalpus, Phlebotomus and Sergentomyia were identified. An additional man-biting species, P. major major was recorded for the first time in Thailand. Ecological observations of the habitats were made. It is expected the diversity of cavernicolous sand flies is more than currently known. An updated list of 26 phlebotomine species for Thailand is provided. |
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| 9. | Southeast Asian J Trop Med Public Health. 2011 Nov;42(6):1395-404.Distri bution of cave-dwelling phlebotomine sand flies and their nocturnal and diurnal activity in Phitsanulok Province, Thailand.Polseela R, Vitta A, Nateeworanart S, Apiwathnasorn C.SourceDepartment of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University Phitsanulok, Thailand. raxsinap@nu.ac.th AbstractAn entomological survey of sand flies was conducted in Naresuan Cave in Noen Maprang District, Phitsanulok Province, during November 2009 to December 2010. A total of 10,115 cave-dwelling sand flies were collected with CDC light traps nocturnally (06:00 AM and 06:00 PM) and diurnally (06:00 PM and 06:00 AM). The ratio between male and female sand flies was 1:1.3 (4,363:5,752). The ratio between the number of sand flies caught nocturnally and diurnally was 2.6:1 (7,268:2,847). In this study, 13 species belonging to 4 genera were identified, of which 4 belonged to the genus Phlebotomus, 7 to Sergentomyia, 1 to Nemopalpus and 1 to Chinius. An abundance of species were observed: Nemopalpus vietnamensis (49.15%), P. argentipes (20.15%), C. barbazani (15.79%), P. teshi (9.53%), and S. anodontis (3.21%). Less common species (<1%) were S. barraudi (0.63%), P. stantoni (0.57%), S. dentata (0.49%), S.quatei (0.17%), P. philippinensis gouldi (0.12%), S.silvatica (0.10%), S. gemmea (0.05%), and S. iyengari (0.04%). The predominant species in the Naresuan Cave was Nemopalpus vietnamensis (49.15%). The data demonstrates variability in sand fly prevalence, species composition, and relative abundance in caves. P. argentipes was found throughout the day in the caves, which is important because it is believed to be the Leishmania spp vector. This study highlights the diurnal activity of the sand fly and the day-time risk of leishmaniasis. In conclusion, although leishmaniasis has not been reported in Phitsanulok, there should be heightened awareness of infection in these areas with vectors of the protozoa. |
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| 10. | Biochemistry (Mosc). 2011 Jul;76(7):727-8. doi: 10.1134/S0006297911070017.Microbial Carbohydrates.Knirel YA. |
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