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Sent on Friday, 2011 Jan 21Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Tropical Diseases Lacking Adequate Control Measures: Dengue, Leishmaniasis, and African Trypanosomiasis.Cattand P, Desjeux P, Guzmán MG, Jannin J, Kroeger A, Medici A, Musgrove P, Nathan MB, Shaw A, Schofield CJ. ExcerptDengue, leishmaniasis, and African trypanosomiasis (sleeping sickness) are serious diseases that the World Health Organization (WHO) characterizes as lacking effective control measures. They are transmitted by insect vectors and can result in epidemic outbreaks. Specific treatment is unavailable for dengue, although good supportive treatment can drastically reduce mortality. For the leishmaniases and for sleeping sickness, treatment relies largely on antiquated drugs based on antimony and arsenic, respectively. Sustained control of the insect vectors is difficult for dengue and leishmaniasis because their high reproductive potential allows the vector populations to recover quickly after intervention wherever adequate breeding conditions exist. By contrast, tsetse flies, the vectors for sleeping sickness, have a much lower reproductive potential and could be eliminated over large areas, given adequate organization and surveillance. Through the African Union, African nations are developing a large-scale initiative for areawide elimination of tsetse flies, partly because of sleeping sickness, but also because of their importance as vectors of animal trypanosomiasis, which poses a serious constraint to livestock development and agriculture. Copyright © 2006, The International Bank for Reconstruction and Development/The World Bank Group |
| PMID: 21250331 [PubMed] | |
| 2. | PLoS Pathog. 2011 Jan 13;7(1):e1001252.Induction of a Peptide with Activity against a Broad Spectrum of Pathogens in the Aedes aegypti Salivary Gland, following Infection with Dengue Virus.Luplertlop N, Surasombatpattana P, Patramool S, Dumas E, Wasinpiyamongkol L, Saune L, Hamel R, Bernard E, Sereno D, Thomas F, Piquemal D, Yssel H, Briant L, Missé D.Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. AbstractThe ultimate stage of the transmission of Dengue Virus (DENV) to man is strongly dependent on crosstalk between the virus and the immune system of its vector Aedes aegypti (Ae. aegypti). Infection of the mosquito's salivary glands by DENV is the final step prior to viral transmission. Therefore, in the present study, we have determined the modulatory effects of DENV infection on the immune response in this organ by carrying out a functional genomic analysis of uninfected salivary glands and salivary glands of female Ae. aegypti mosquitoes infected with DENV. We have shown that DENV infection of salivary glands strongly up-regulates the expression of genes that encode proteins involved in the vector's innate immune response, including the immune deficiency (IMD) and Toll signalling pathways, and that it induces the expression of the gene encoding a putative anti-bacterial, cecropin-like, peptide (AAEL000598). Both the chemically synthesized non-cleaved, signal peptide-containing gene product of AAEL000598, and the cleaved, mature form, were found to exert, in addition to antibacterial activity, anti-DENV and anti-Chikungunya viral activity. However, in contrast to the mature form, the immature cecropin peptide was far more effective against Chikungunya virus (CHIKV) and, furthermore, had strong anti-parasite activity as shown by its ability to kill Leishmania spp. Results from circular dichroism analysis showed that the immature form more readily adopts a helical conformation which would help it to cause membrane permeabilization, thus permitting its transfer across hydrophobic cell surfaces, which may explain the difference in the anti-pathogenic activity between the two forms. The present study underscores not only the importance of DENV-induced cecropin in the innate immune response of Ae. aegypti, but also emphasizes the broad-spectrum anti-pathogenic activity of the immature, signal peptide-containing form of this peptide. |
| PMID: 21249175 [PubMed - in process] | |
| 3. | J Egypt Soc Parasitol. 2010 Aug;40(2):465-78.Isoenzyme electrophetic characterization of Leishmania major, the causative agent of zoonotic cutaneous Leishmaniasis in North and West Saudi Arabia.Bin DS, Mostafa OM, Abdoon A, Al-Quraishy SA, Alqahtani AA.Department of Biology, Faculty of Science, King Khalid University, Abha, Saudi Arabia. saaddajem@kku.edu.sa AbstractSeveral expeditions were carried out to four localities (Al-Madinah Almona-warah, Tabouk region, Al-Jouf and Northern Frontiers regions) in Northern and Western Saudi Arabia for sampling zoonotic cutaneous leishmaniasis (ZCL) cases from patients and rodents. Biopsy samples were collected from 51 patients complaining of skin lesions, most of which (40 or 78.4%) proved to be ZCL. Amastigotes were detected in 33 patients (64.7%), but only 30 (58.9%) gave successful growth of promastigotes in the culture media. The positive cases were Saudis 14(35%) and non-Saudis 26 (65%). Five species of rodents were caught, Meriories libycus, Psammomys obesus, Rattus rattus, jaculus and Hystrix indica. The first species was the most dominant (90%) in which Leishmania parasites were detected. The Leishmania isolates from man and rodents were identified by isoenzyme electrophoresis and proved to be Zymodeme LON-4. |
| PMID: 21246954 [PubMed - in process] | |
| 4. | J Parasitol. 2010 Dec;96(6):1197-203. Epub 2010 Jul 14.The sensitivity of microscopy and PCR-based detection methods affecting estimates of prevalence of blood parasites in birds.Garamszegi LZ.Department of Evolutionary Ecology, Estación Biológica de Doñana-CSIC, c/ Americo Vespucio, s/n, 41092, Sevilla, Spain. laszlo.garamszegi@ebd.csic.es AbstractInferences about the evolution of host-parasitic relationships are often made based on the prevalence of avian malaria, which is usually estimated in a large sample of birds using either microscopic or molecular screening of blood samples. However, different techniques often have variable accuracy; thus, screening methodology can raise issues about statistical bias if method sensitivity varies systematically across parasites or hosts. To examine this possibility, published information was collected on the prevalence of species in 4 genera of avian blood parasites ( Plasmodium, Haemoproteus, Leucocytozoon, and Trypanosoma) from various sources that used different tools. The data were tested to determine if the application of different methods provided different estimates for the same hosts. In these comparisons between the main methodologies, the PCR-based molecular methods were generally found to provide higher estimates for Plasmodium spp. prevalence than microscopic tools, while there was no significant tendency for such a trend in species of Haemoproteus and Leucocytozoon. When analyzing intraspecific variance of prevalence within molecular studies, some studies provided consistently higher estimates for Haemoproteus spp. prevalence than others, indicating that differences between studies can affect detected estimates. Within microscopic studies, surveys that examined more microscopic fields were more likely to report higher prevalence for Plasmodium spp. than those relying on fewer microscopic fields. Consequently, studies making comparisons across parasite genera and/or host species from different sources need to consider several types of bias originating from variation in method sensitivity. |
| PMID: 21158636 [PubMed - indexed for MEDLINE] | |
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| 5. | J Parasitol. 2010 Dec;96(6):1119-22. Epub 2010 Aug 12.Prevalence of antibodies to Trypanosoma cruzi, Toxoplasma gondii, Encephalitozoon cuniculi, Sarcocystis neurona, Besnoitia darlingi, and Neospora caninum in North American opossums, Didelphis virginiana, from southern Louisiana.Houk AE, Goodwin DG, Zajac AM, Barr SC, Dubey JP, Lindsay DS.Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia 24061-0342, USA. AbstractWe examined the prevalence of antibodies to zoonotic protozoan parasites ( Trypanosoma cruzi, Toxoplasma gondii, and Encephalitozoon cuniculi) and protozoans of veterinary importance ( Neospora caninum, Sarcocystis neurona, and Besnoitia darlingi) in a population of North American opossums ( Didelphis virginiana) from Louisiana. Samples from 30 opossums were collected as part of a survey for T. cruzi in Louisiana. Frozen sera from these 30 opossums were examined using an indirect immunofluorescent antibody test (IFAT) against in vitro-produced antigenic stages of these protozoans. Additionally, 24 of the 30 samples were examined using hemoculture, and all 30 were examined in the modified direct agglutination test (MAT) for antibodies to To. gondii. The prevalences of reactive IFAT samples were as follows: 60% for T. cruzi, 27% for To. gondii, 23% for E. cuniculi, 17% for S. neurona, 47% for B. darlingi, and 0% for N. caninum. Hemoculture revealed that 16 (67%) of 24 samples were positive for T. cruzi, compared to 18 of 30 (60%) by IFAT. The sensitivity and specificity for the IFAT compared to hemoculture was 100% for each. The modified direct agglutination test revealed that 9 (30%) of the 30 samples from opossums had antibodies to To. gondii , compared to 8 (27%) using the IFAT. The sensitivity and specificity of the IFAT compared to the MAT was 100% and 72%, respectively. |
| PMID: 21158620 [PubMed - indexed for MEDLINE] | |
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| 6. | Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20411-6. Epub 2010 Nov 8.Phylogenetic character mapping of proteomic diversity shows high correlati on with subspecific phylogenetic diversity in Trypanosoma cruzi.Telleria J, Biron DG, Brizard JP, Demettre E, Séveno M, Barnabé C, Ayala FJ, Tibayrenc M.Unité Mixte de Recherche, Institut de Recherche pour le Développement/Centre National de la Recherche Scientifique, Génétique et Evolution des Maladies Infectieuses, n° 2724, Centre Institut de Recherche pour le Développement, 34394 Montpellier Cedex 5, France. AbstractWe performed a phylogenetic character mapping on 26 stocks of Trypanosoma cruzi, the parasite responsible for Chagas disease, and 2 stocks of the sister taxon T. cruzi marinkellei to test for possible associations between T. cruzi-subspecific phylogenetic diversity and levels of protein expression, as examined by proteomic analysis and mass spectrometry. We observed a high level of correlation (P < 10(-4)) between genetic distance, as established by multilocus enzyme electrophoresis, and proteomic dissimilarities estimated by proteomic Euclidian distances. Several proteins were found to be specifically associated to T. cruzi phylogenetic subdivisions (discrete typing units). This study explores the previously uncharacterized links between infraspecific phylogenetic diversity and gene expression in a human pathogen. It opens the way to searching for new vaccine and drug targets and for identification of specific biomarkers at the subspecific level of pathogens. |
| PMID: 21059959 [PubMed - indexed for MEDLINE] | |
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| 7. | Transfusion. 2010 Dec;50(12):2628-37. doi: 10.1111/j.1537-2995.2010.02756.x.Enhanced classification of Chagas serolog ic results and epidemiologic characteristics of seropositive donors at three large blood centers in Brazil.Sabino EC, Salles NA, Sarr M, Barreto AM, Oikawa M, Oliveira CD, Leao SC, Carneiro-Proietti AB, Custer B, Busch MP; NHLBI Retrovirus Epidemiology Donor Study-II (REDS-II), International Component.Pró-Sangue Foundation and the University of São Paulo, São Paulo, Brazil. sabinoec@gmail.com AbstractBACKGROUND: A major problem in Chagas disease donor screening is the high frequency of samples with inconclusive results. The objective of this study was to describe patterns of serologic results among donors to the three Brazilian REDS-II blood centers and correlate with epidemiologic characteristics. STUDY DESIGN AND METHODS: The centers screened donor samples with one Trypanosoma cruzi lysate enzyme immunoassay (EIA). EIA-reactive samples were tested with a second lysate EIA, a recombinant-antigen based EIA, and an immunfluorescence assay. Based on the serologic results, samples were classified as confirmed positive (CP), probable positive (PP), possible other parasitic infection (POPI), and false positive (FP). RESULTS: In 2007 to 2008, a total of 877 of 615,433 donations were discarded due to Chagas assay reactivity. The prevalences (95% confidence intervals [CIs]) among first-time donors for CP, PP, POPI, and FP patterns were 114 (99-129), 26 (19-34), 10 (5-14), and 96 (82-110) per 100,000 donations, respectively. CP and PP had similar patterns of prevalence when analyzed by age, sex, education, and location, suggesting that PP cases represent true T. cruzi infections; in contrast the demographics of donors with POPI were distinct and likely unrelated to Chagas disease. No CP cases were detected among 218,514 repeat donors followed for a total of 718,187 person-years. CONCLUSION: We have proposed a classification algorithm that may have practical importance for donor counseling and epidemiologic analyses of T. cruzi-seroreactive donors. The absence of incident T. cruzi infections is reassuring with respect to risk of window phase infections within Brazil and travel-related infections in nonendemic countries such as the United States. © 2010 American Association of Blood Banks. |
| PMID: 20576017 [PubMed - indexed for MEDLINE] | |
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| 8. | Acc Chem Res. 2010 Sep 21;43(9):1216-26.Targeting isoprenoid biosynthesis for drug discovery: bench to bedside.Oldfield E.D epartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. AbstractThe isoprenoid biosynthesis pathways produce the largest class of small molecules in Nature: isoprenoids (also called terpenoids). Not surprisingly then, isoprenoid biosynthesis is a target for drug discovery, and many drugs--such as Lipitor (used to lower cholesterol), Fosamax (used to treat osteoporosis), and many anti-infectives--target isoprenoid biosynthesis. However, drug resistance in malaria, tuberculosis, and staph infections is rising, cheap and effective drugs for the neglected tropical diseases are lacking, and progress in the development of anticancer drugs is relatively slow. Isoprenoid biosynthesis is thus an attractive target, and in this Account, I describe developments in four areas, using in each case knowledge derived from one area of chemistry to guide the development of inhibitors (or drug leads) in another, seemingly unrelated, area. First, I describe mechanistic studies of the enzyme IspH, which is present in malaria parasites and most pathogenic bacteria, but not in humans. IspH is a 4Fe-4S protein and produces the five-carbon (C5) isoprenoids IPP (isopentenyl diphosphate) and DMAPP (dimethylallyl diphosphate) from HMBPP (E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate) via a 2H(+)/2e(-) reduction (of an allyl alcohol to an alkene). The mechanism is unusual in that it involves organometallic species: "metallacycles" (η(2)-alkenes) and η(1)/η(3)-allyls. These observations lead to novel alkyne inhibitors, which also form metallacycles. Second, I describe structure-function-inhibition studies of FPP synthase, the macromolecule that condenses IPP and DMAPP to the sesquiterpene farnesyl diphosphate (FPP) in a "head-to-tail" manner. This enzyme uses a carbocation mechanism and is potently inhibited by bone resorption drugs (bisphosphonates), which I show are also antiparasitic agents that block sterol biosynthesis in protozoa. Moreover, "lipophilic" bisphosphonates inhibit protein prenylation and invasiveness in tumor cells, in addition to activating γδ T-cells to kill tumor cells, and are important new leads in oncology. Third, I describe structural and inhibition studies of a "head-to-head" triterpene synthase, dehydrosqualene synthase (CrtM), from Staphylococcus aureus. CrtM catalyzes the first committed step in biosynthesis of the carotenoid virulence factor staphyloxanthin: the condensation of two FPP molecules to produce a cyclopropane (presqualene diphosphate). The structure of CrtM is similar to that of human squalene synthase (SQS), and some SQS inhibitors (originally developed as cholesterol-lowering drugs) block staphyloxanthin biosynthesis. Treated bacteria are white and nonvirulent (because they lack the carotenoid shield that protects them from reactive oxygen species produced by neutrophils), rendering them susceptible to innate immune system clearance--a new therapeutic approach. And finally, I show that the heart drug amiodarone, also known to have antifungal activity, blocks ergosterol biosynthesis at the level of oxidosqualene cyclase in Trypanosoma cruzi, work that has led to its use in the clinic as a novel antiparasitic agent. In each of these four examples, I use information from one area (organometallic chemistry, bone resorption drugs, cholesterol-lowering agents, heart disease) to develop drug leads in an unrelated area: a "knowledge-based" approach that represents an important advance in the search for new drugs. |
| PMID: 20560544 [PubMed - indexed for MEDLINE] | |
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| 9. | Tanpakushitsu Kakusan Koso. 2009 Jun;54(8 Suppl):1053-8.[Host immune response to Trypanosoma cruzi and its evasion mechanism ].[Article in Japanese] Yamamoto M, Takeda K. |
| PMID: 21089540 [PubMed - indexed for MEDLINE] | |
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| 10. | Int J Parasitol. 2009 Oct;39(12):1305-17. Epub 2009 Apr 22.Flow cytometric analysis and microsatellite genotyping reveal extensive DNA content variation in Trypanosoma cruzi populations and expose contrasts between natural and experimental hybrids.Lewis MD, Llewellyn MS, Gaunt MW, Yeo M, Carrasco HJ, Miles MA.Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. michael.lewis@lshtm.ac.uk AbstractTrypanosoma cruzi exhibits remarkable genetic heterogeneity. This is evident at the nucleotide level but also structurally, in the form of karyotypic variation and DNA content differences between strains. Although natural populations of T. cruzi are predominantly clonal, hybrid lineages (TcIId and TcIIe) have been identified and hybridisation has been demonstrated in vitro, raising the possibility that genetic exchange may continue to shape the evolution of this pathogen. The mechanism of genetic exchange identified in the laboratory is unusual, apparently involving fusion of diploid parents followed by genome erosion. We investigated DNA content diversity in natural populations of T. cruzi in the context of its genetic subdivisions by using flow cytometric analysis and multilocus microsatellite genotyping to determine the relative DNA content and estimate the ploidy of 54 cloned isolates. The maximum difference observed was 47.5% between strain Tu18 cl2 (TcIIb) and strain C8 cl1 (TcI), which we estimated to be equivalent to approximately 73 Mb of DNA. Large DNA content differences were identified within and between discrete typing units (DTUs). In particular, the mean DNA content of TcI strains was significantly less than that for TcII strains (P<0.001). Comparisons of hybrid DTUs TcIId/IIe with corresponding parental DTUs TcIIb/IIc indicated that natural hybrids are predominantly diploid. We also measured the relative DNA content of six in vitro-generated TcI hybrid clones and their parents. In contrast to TcIId/IIe hybrid strains these experimental hybrids comprised populations of sub-tetraploid organisms with mean DNA contents 1.65-1.72 times higher than the parental organisms. The DNA contents of both parents and hybrids were shown to be relatively stable after passage through a mammalian host, heat shock or nutritional stress. The results are discussed in the context of hybridisation mechanisms in both natural and in vitro settings. |
| PMID: 19393242 [PubMed - indexed for MEDLINE] | |
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