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 - 9 of 9

1.	PLoS Negl Trop Dis. 2010 Sep 7;4(9). pii: e814. Pediatric Visceral Leishmaniasis in Albania: A Retrospective Analysis of 1,210 Consecutive Hospitalized Patients (1995-2009). Petrela R, Kuneshka L, Foto E, Zavalani F, Gradoni L. Pediatric Department, University Hospital Center "Mother Theresa", Tirana, Albania. Abstract BACKGROUND: Little information is available about infantile visceral leishmaniasis (VL) in Albania as regards incidence, diagnosis and management of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Demographic data, clinical and laboratory features and therapeutic findings were considered in children admitted to University Hospital of Tirana from 1995 to 2009, and diagnosed as having VL. The diagnosis was based on bone-marrow microscopy/culture in 77.5% of patients, serology in 16.1%, and ex juvantibus in 6.4%. A total of 1,210 children were considered, of whom 74% came from urbanized areas. All patients were in the age range 0-14 years, with a median of 4 years. Hepatosplenomegaly was recorded in 100%, fever in 95.4% and moderate to severe anemia in 88% of cases. Concomitant conditions were frequent: 84% had bronchopneumonia; diarrhea was present in 27%, with acute manifestations in 5%; 3% had salmonellosis. First-line therapy was meglumine antimoniate for all patients, given at the standard Sb(v) dosage of 20 mg/kg/day for 21 to 28 days. Two children died under treatment, one of sepsis, the other of acute renal impairment. There were no cases of primary unresponsiveness to treatment, and only 8 (0.67%) relapsed within 6-12 months after therapy. These patients have been re-treated with liposomal amphotericin B, with successful cure. CONCLUSIONS: Visceral leishmaniasis in pediatric age is relatively frequent in Albania; therefore an improvement is warranted of a disease-specific surveillance system in this country, especially as regards diagnosis. Despite recent reports on decreased responses to antimonial drugs of patients with Mediterranean VL, meglumine antimoniate treatment appears to be still highly effective in Albania.
	PMID: 20838650 [PubMed - as supplied by publisher]

2.	PLoS Negl Trop Dis. 2010 Sep 7;4(9). pii: e818. Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent. Meheus F, Balasegaram M, Olliaro P, Sundar S, Rijal S, Faiz MA, Boelaert M. Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium. Abstract BACKGROUND: Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies. METHODS AND FINDINGS: We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh) from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method). The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome) were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range. CONCLUSIONS: Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are available.
	PMID: 20838649 [PubMed - as supplied by publisher]

3.	PLoS Negl Trop Dis. 2010 Sep 7;4(9). pii: e816. Stage-Specific Adhesion of Leishmania Promastigotes to Sand Fly Midguts Assessed Using an Improved Comparative Binding Assay. Wilson R, Bates MD, Dostalova A, Jecna L, Dillon RJ, Volf P, Bates PA. Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Abstract BACKGROUND: The binding of Leishmania promastigotes to the midgut epithelium is regarded as an essential part of the life-cycle in the sand fly vector, enabling the parasites to persist beyond the initial blood meal phase and establish the infection. However, the precise nature of the promastigote stage(s) that mediate binding is not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue we have developed an in vitro gut binding assay in which two promastigote populations are labelled with different fluorescent dyes and compete for binding to dissected sand fly midguts. Binding of procyclic, nectomonad, leptomonad and metacyclic promastigotes of Leishmania infantum and L. mexicana to the midguts of blood-fed, female Lutzomyia longipalpis was investigated. The results show that procyclic and metacyclic promastigotes do not bind to the midgut epithelium in significant numbers, whereas nectomonad and leptomonad promastigotes both bind strongly and in similar numbers. The assay was then used to compare the binding of a range of different parasite species (L. infantum, L. mexicana, L. braziliensis, L. major, L. tropica) to guts dissected from various sand flies (Lu. longipalpis, Phlebotomus papatasi, P. sergenti). The results of these comparisons were in many cases in line with expectations, the natural parasite binding most effectively to its natural vector, and no examples were found where a parasite was unable to bind to its natural vector. However, there were interesting exceptions: L. major and L. tropica being able to bind to Lu. longipalpis better than L. infantum; L. braziliensis was able to bind to P. papatasi as well as L. major; and significant binding of L. major to P. sergenti and L. tropica to P. papatasi was observed. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that Leishmania gut binding is strictly stage-dependent, is a property of those forms found in the middle phase of development (nectomonad and leptomonad forms), but is absent in the early blood meal and final stages (procyclic and metacyclic forms). Further they show that although gut binding may be necessary for parasite establishment, in several vector-parasite pairs the specificity of such in vitro binding alone is insufficient to explain overall vector specificity. Other significant barriers to development must exist in certain refractory Leishmania parasite-sand fly vector combinations. A re-appraisal of the specificity of the Leishmania-sand fly relationship is required.
	PMID: 20838647 [PubMed - as supplied by publisher]

4.	PLoS One. 2010 Sep 8;5(9). pii: e12607. Mitochondrial Redox Metabolism in Trypanosomatids Is Independent of Tryparedoxin Activity. Castro H, Romao S, Carvalho S, Teixeira F, Sousa C, Tomás AM. IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. Abstract Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently.
	PMID: 20838623 [PubMed - as supplied by publisher]

5.	PLoS Pathog. 2010 Sep 9;6(9). pii: e1001090. The Transcriptome of the Human Pathogen Trypanosoma brucei at Single-Nucleotide Resolution. Kolev NG, Franklin JB, Carmi S, Shi H, Michaeli S, Tschudi C. School of Public Health, Yale University, New Haven, Connecticut, United States of America. Abstract The genome of Trypanosoma brucei, the causative agent of African trypanosomiasis, was published five years ago, yet identification of all genes and their transcripts remains to be accomplished. Annotation is challenged by the organization of genes transcribed by RNA polymerase II (Pol II) into long unidirectional gene clusters with no knowledge of how transcription is initiated. Here we report a single-nucleotide resolution genomic map of the T. brucei transcriptome, adding 1,114 new transcripts, including 103 non-coding RNAs, confirming and correcting many of the annotated features and revealing an extensive heterogeneity of 5' and 3' ends. Some of the new transcripts encode polypeptides that are either conserved in T. cruzi and Leishmania major or were previously detected in mass spectrometry analyses. High-throughput RNA sequencing (RNA-Seq) was sensitive enough to detect transcripts at putative Pol II transcription initiation sites. Our results, as well as recent data from the literature, indicate that transcription initiation is not solely restricted to regions at the beginning of gene clusters, but may occur at internal sites. We also provide evidence that transcription at all putative initiation sites in T. brucei is bidirectional, a recently recognized fundamental property of eukaryotic promoters. Our results have implications for gene expression patterns in other important human pathogens with similar genome organization (Trypanosoma cruzi, Leishmania sp.) and revealed heterogeneity in pre-mRNA processing that could potentially contribute to the survival and success of the parasite population in the insect vector and the mammalian host.
	PMID: 20838601 [PubMed - as supplied by publisher]

6.	Antimicrob Agents Chemother. 2010 Sep 13. [Epub ahead of print] Tafenoquine, an anti-plasmodial 8-aminoquinoline, targets Leishmania respiratory Complex III and induces apoptosis. Carvalho L, Luque-Ortega JR, Manzano JI, Castanys S, Rivas L, Gamarro F. Instituto de Parasitología y Biomedicina "López-Neyra". CSIC, Granada, Spain; Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, E-28040 Madrid, Spain. Abstract Tafenoquine (TFQ), an 8-aminoquinoline analogue of primaquine, which is currently under clinical trial (phase IIb/III) for the treatment and prevention of malaria, may represent an alternative treatment for leishmaniasis. In this work, we have studied the mechanism of action of TFQ against Leishmania parasites. TFQ impaired the overall bioenergetic metabolism of Leishmania promastigotes, causing a rapid drop in intracellular ATP levels without affecting plasma membrane permeability. TFQ induced mitochondrial dysfunction through the inhibition of cytochrome c reductase (respiratory complex III) with a decrease in the oxygen consumption rate and depolarization of mitochondrial membrane potential. This was accompanied by ROS production, elevation of intracellular Ca(2+) levels and concomitant nuclear DNA fragmentation. We conclude that TFQ targets Leishmania mitochondria, leading to an apoptosis-like death process.
	PMID: 20837758 [PubMed - as supplied by publisher]

7.	Antimicrob Agents Chemother. 2010 Sep 13. [Epub ahead of print] Anti-leishmanial and anti-trypanosomal activity of the 8-aminoquinoline tafenoquine. Yardley V, Gamarro F, Croft SL. Abstract The 8-aminoquinoline, tafenoquine, showed significant in vitro activity against Leishmania species, including L. donovani amastigotes in macrophages with IC50 values between 0.1 - 4.0 μM for both Sb(V)-sensitive and Sb(V)-resistant strains, and by oral administration in BALB/c mice with ED50 values of 1.2 - 3.5 mg/kg x 5. Tafenoquine was less active against intracellular Trypanosoma cruzi amastigotes with an IC50 value of 21.9 μM.
	PMID: 20837750 [PubMed - as supplied by publisher]

8.	Biomedica. 2009 Dec;29(4):513-22. [The first case of congenital Chagas' disease analyzed by AP-PCR in Colombia] [Article in Spanish] Pavia PX, Montilla M, Flórez C, Herrera G, Ospina JM, Manrique F, Nicholls RS, Puerta C. Laboratorio de Parasitología Molecular, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C, Colombia. Abstract INTRODUCTION: The main route of Chagas disease transmission is through vectors of the insect family Reduviidae. However, the parasite can also be transmitted from infected mothers to their fetus in utero. Until now, no cases of congenital Chagas disease have been reported in Colombia. OBJECTIVE: A congenital Chagas disease case occurred in Moniquirá County, Boyacá, Colombia. It was confirmed by comparing strains isolated from the mother and her baby using polymerase chain reaction (PCR) with arbitrary primers. MATERIALS AND METHODS: The parasite DNA was extracted from positive blood cultures of the afflicted mother and her son. The species confirmation and group detection were performed by PCR. The strain genotypes were determined by AP-PCR with two oligonucleotides based on the genes for the b-globin (5'-CCTCACCTTCTTTCATGGAG-3') and 16S RrNA (5'-ACGGGCAGTGTGTACAAGACC-3'), in different reactions. RESULTS: The T. cruzi strains isolated from the blood cultures of the mother and her son showed the same amplification profile by the two AP-PCR tests; this corresponded with profiles of the T. cruzi I strains used as controls. However, T. cruzi II was also found in the blood culture from the newborn. CONCLUSIONS: This is the first case of Chagas disease transmission reported in Moniquirá, demonstrating that this form of transmission occurs in Colombia. The presence of both groups of T. cruzi in the newborn sample suggests mixed infection in the mother as well, with a higher prevalence of T. cruzi I, at least in the mother's blood culture. Free Article
	PMID: 20440449 [PubMed - indexed for MEDLINE]
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9.	FEMS Microbiol Lett. 2010 May;306(2):97-102. Epub 2010 Feb 24. Trypanosoma cruzi amino acid transporter TcAAAP411 med iates arginine uptake in yeasts. Carrillo C, Canepa GE, Giacometti A, Bouvier LA, Miranda MR, de los Milagros Camara M, Pereira CA. Fundación Instituto Leloir, Universidad de Buenos Aires and CONICET, Argentina. Abstract Trypanosoma cruzi, the aetiological agent of Chagas' disease, is exposed to extremely different environment conditions during its life cycle, and transporters are key molecules for its adaptive regulation. Amino acids, and particularly arginine, are essential components in T. cruzi metabolism. In this work, a novel T. cruzi arginine permease was identified by screening different members of the AAAP family (amino acid/auxin permeases) in yeast complementation assays using a toxic arginine analogue. One gene candidate, TcAAAP411, was characterized as a very specific, high-affinity, l-arginine permease. This work is the first identification of the molecular components involved specifically in amino acid transport in T. cruzi and provides new insights for further validation of the TcAAAP family as functional permeases.
	PMID: 20337715 [PubMed - indexed for MEDLINE]
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