Saturday, June 6, 2009

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 -10 of 24

1: Dtsch Med Wochenschr. 2009 Jun;134(24):1274-1277. Epub 2009 Jun 4.Click here to read

Pancytopenia, fever, and splenomegaly in a 2-year-old boy.

Schmid MB, Leichsenring M, Keller C, Hegasy G.

Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Ulm.

HISTORY: Suspected of having a systemic malignancy a 22-month-old boy was admitted to hospital with fever, pancytopenia and hepatosplenomegaly. The boy was of ethnically German origin and no travel abroad was reported. DIAGNOSIS: Intensive search for a focus of infection, laboratory tests and bone marrow microscopy failed to be diagnostic. Serological findings and detection of Leishmania DNA in bone marrow by polymerase chain reaction (PCR) led to the diagnosis of visceral leishmaniasis. On explicit questioning the child's parents reported a stay in Greece 18 months before onset of symptoms. TREATMENT AND COURSE: On the fourth day of i.v. therapy with liposomal amphotericin B, 3mg/kg/d for 10 days, the fever subsided. Platelets and leukocytes regained normal levels. The child was discharged after 10 days of treatment and received two more doses on days 14 and 21. CONCLUSION: Negative results on microscopic bone marrow inspection do not rule out visceral leishmaniasis. Detection of anti-Leishmania antibodies may support the suspected diagnosis and provide the indication for PCR technique.

PMID: 19499498 [PubMed - as supplied by publisher]

2: Dtsch Med Wochenschr. 2009 Jun;134(24):1269-1273. Epub 2009 Jun 4.Click here to read

Pancytopenia, hepatosplenomegaly and dry cough after breast cancer.

Seilmaier M, Hecht A, Guggemos W, Adorf D, Gehbauer G.

1. Medizinische Klinik, Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin Klinikum Schwabing, Städtisches Klinikum München GmbH, Akademisches Lehrkrankenhaus der Ludwig-Maximilians-Universität München.

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman had suffered for 6 weeks from fatigue, dry cough and fever. Five years previously breast cancer had been diagnosed and had been successfully treated with subtotal mastectomy and postoperative radiotherapy, as well as aromatase inhibitor until shortly before the present admission. There was no history of travel to tropical countries, but during the last summer she had spent two weeks in Northern Italy. On admission her body temperature was 38,5 C with a mild tachycardia (108/min). INVESTIGATIONS: On admission the body temperature was 38,5 C with a mild tachycardia (108/min). TREATMENT, COURSE AND DIAGNOSIS: Treatment with liposomal amphotericin B brought about rapid improvement, the dry cough subsided and the laboratory results became normal. CONCLUSION: Pancytopenia, fever, dry cough and hepatosplenomegaly after travelling to Mediterranean countries should raise suspicion of visceral leishmaniasis. This diagnosis is confirmed by direct detection of the parasite in the bone marrow. Administration of liposomal amphotericin B is efficacious and safe, bringing about full recovery in up to 90% of cases.

PMID: 19499497 [PubMed - as supplied by publisher]

3: Glycoconj J. 2009 Jun 5. [Epub ahead of print]Click here to read

Disease-associated glycosylated molecular variants of human C-reactive protein activate complement-mediated hemolysis of erythrocytes in tuberculosis and Indian visceral leishmaniasis.

Ansar W, Mukhopadhyay S, Habib SH, Basu S, Saha B, Sen AK, Mandal C, Mandal C.

Infectious disease and Immunology Division, Indian Institute of Chemical Biology, 4, Raja S.C Mullick Road, Jadavpur, Kolkata, 700 032, India.

Human C-reactive protein (CRP), as a mediator of innate immunity, removed damaged cells by activating the classical complement pathway. Previous studies have successfully demonstrated that CRPs are differentially induced as glycosylated molecular variants in certain pathological conditions. Affinity-purified CRPs from two most prevalent diseases in India viz. tuberculosis (TB) and visceral leishmaniasis (VL) have differential glycosylation in their sugar composition and linkages. As anemia is a common manifestation in TB and VL, we assessed the contributory role of glycosylated CRPs to influence hemolysis via CRP-complement-pathway as compared to healthy control subjects. Accordingly, the specific binding of glycosylated CRPs with erythrocytes was established by flow-cytometry and ELISA. Significantly, deglycosylated CRPs showed a 7-8-fold reduced binding with erythrocytes confirming the role of glycosylated moieties. Scatchard analysis revealed striking differences in the apparent binding constants (10(4)-10(5) M(-1)) and number of binding sites (10(6)-10(7)sites/erythrocyte) for CRP on patients' erythrocytes as compared to normal. Western blotting along with immunoprecipitation analysis revealed the presence of distinct molecular determinants on TB and VL erythrocytes specific to disease-associated CRP. Increased fragility, hydrophobicity and decreased rigidity of diseased-erythrocytes upon binding with glycosylated CRP suggested membrane damage. Finally, the erythrocyte-CRP binding was shown to activate the CRP-complement-cascade causing hemolysis, even at physiological concentration of CRP (10 mug/ml). Thus, it may be postulated that CRP have a protective role towards the clearance of damaged-erythrocytes in these two diseases.

PMID: 19499327 [PubMed - as supplied by publisher]

4: Proc Natl Acad Sci U S A. 2009 Jun 4. [Epub ahead of print]Click here to read

Extreme inbreeding in Leishmania braziliensis.

Rougeron V, De Meeûs T, Hide M, Waleckx E, Bermudez H, Arevalo J, Llanos-Cuentas A, Dujardin JC, De Doncker S, Le Ray D, Ayala FJ, Bañuls AL.

Génétique et Evolution des Maladies Infectieuses, IRD/CNRS/UMI (UMR 2724), Montpellier F-34394, France;

Leishmania species of the subgenus Viannia and especially Leishmania braziliensis are responsible for a large proportion of New World leishmaniasis cases. The reproductive mode of Leishmania species has often been assumed to be predominantly clonal, but remains unsettled. We have investigated the genetic polymorphism at 12 microsatellite loci on 124 human strains of Leishmania braziliensis from 2 countries, Peru and Bolivia. There is substantial genetic diversity, with an average of 12.4 +/- 4.4 alleles per locus. There is linkage disequilibrium at a genome-wide scale, as well as a substantial heterozygote deficit (more than 50% the expected value from Hardy-Weinberg equilibrium), which indicates high levels of inbreeding. These observations are inconsistent with a strictly clonal model of reproduction, which implies excess heterozygosity. Moreover, there is large genetic heterogeneity between populations within countries (Wahlund effect), which evinces a strong population structure at a microgeographic scale. Our findings are compatible with the existence of population foci at a microgeographic scale, where clonality alternates with sexuality of an endogamic nature, with possible occasional recombination events between individuals of different genotypes. These findings provide key clues on the ecology and transmission patterns of Leishmania parasites.

PMID: 19497885 [PubMed - as supplied by publisher]

5: Proc Natl Acad Sci U S A. 2009 Jun 3. [Epub ahead of print]Click here to read

Structure of a mitochondrial ribosome with minimal RNA.

Sharma MR, Booth TM, Simpson L, Maslov DA, Agrawal RK.

Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201-0509;

The Leishmania tarentolae mitochondrial ribosome (Lmr) is a minimal ribosomal RNA (rRNA)-containing ribosome. We have obtained a cryo-EM map of the Lmr. The map reveals several features that have not been seen in previously-determined structures of eubacterial or eukaryotic (cytoplasmic or organellar) ribosomes to our knowledge. Comparisons of the Lmr map with X-ray crystallographic and cryo-EM maps of the eubacterial ribosomes and a cryo-EM map of the mammalian mitochondrial ribosome show that (i) the overall structure of the Lmr is considerably more porous, (ii) the topology of the intersubunit space is significantly different, with fewer intersubunit bridges, but more tunnels, and (iii) several of the functionally-important rRNA regions, including the alpha-sarcin-ricin loop, have different relative positions within the structure. Furthermore, the major portions of the mRNA channel, the tRNA passage, and the nascent polypeptide exit tunnel contain Lmr-specific proteins, suggesting that the mechanisms for mRNA recruitment, tRNA interaction, and exiting of the nascent polypeptide in Lmr must differ markedly from the mechanisms deduced for ribosomes in other organisms. Our study identifies certain structural features that are characteristic solely of mitochondrial ribosomes and other features that are characteristic of both mitochondrial and chloroplast ribosomes (i.e., organellar ribosomes).

PMID: 19497863 [PubMed - as supplied by publisher]

6: Trans R Soc Trop Med Hyg. 2009 Jun 2. [Epub ahead of print]Click here to read

Emergence of cutaneous leishmaniasis due to Leishmania major in a new focus of central Iran.

Emami MM, Yazdi M, Nilforoushzadeh M.

Kerman University of Medical Sciences, Sepahan Green-Thou Plantpathology and Medical Entomology Centre, Department of Vector Control, No. 147, Masror Street, Pars Ave, Esfahan, Iran.

Reports from a health center in Esfahan province show an increase in cutaneous leishmaniasis (CL) cases in the southern areas during 2000-2002, leading us to carry out an epidemiological study using standard techniques in Mobarakeh county, central Iran in 2003. Data were collected on the prevalence of scars and active lesions among 1237 households in Dehsorkh district (3086 residents) and 191 children attending primary schools in Mobarakeh city. Smears were prepared by scraping the edges of the active lesions. To determine the reservoir host of the disease, rodents and dogs were caught and examined. Sand flies were collected biweekly from indoor and outdoor locations in the study areas. Parasites isolated from humans and rodents were characterized by RAPD-PCR technique. The prevalence of scars and active lesions was 2.5% and 1.6% respectively in the 3086 residents of Dehsorkh district and 6% and 4% respectively in the schoolchildren. Among rodents, 7 of 18 Nesokia indica (39%) and 1 of 9 Meriones persicus (11%) were found to be infected with Leishmania major. Phlebotomus papatasi was the commonest sand fly species indoors and outdoors. Although CL has been present in some northern counties of Esfahan province, our investigation revealed that the disease has spread to southern parts of the province. Rapid treatment of patients, destroying gerbils, and promotion of general and health education for the local population is recommended.

PMID: 19497606 [PubMed - as supplied by publisher]

7: BMC Syst Biol. 2009 Jun 5;3(1):57. [Epub ahead of print]Click here to read

LeishCyc: a biochemical pathways database for Leishmania major.

Doyle MA, Macrae JI, De Souza DP, Saunders EC, McConville MJ, Likic VA.

ABSTRACT: BACKGROUND: Leishmania spp. are sandfly-transmitted protozoan parasites that cause a spectrum of diseases in more than 12 million people worldwide. Much research is now focussing on how these parasites adapt to the distinct nutrient environments they encounter in the digestive tract of the sandfly vector and the phagolysosome compartment of mammalian macrophages, with the view of identifying new drug targets. While data mining and annotation of the genomes of three Leishmania species has provided an initial inventory of predicted metabolic components and associated pathways, resources for integrating this information into metabolic networks and incorporating data from transcript, protein and metabolite profiling are currently lacking. The development of a reliable, expertly curated, and widely available model of Leishmania metabolic networks is required to facilitate systems analysis, discovery and prioritization of new drug targets for this important human pathogen. Description The LeishCyc database was initially built from the genome sequence of Leishmania major (v5.2), based on the annotation published by the Wellcome Trust Sanger Institute. LeishCyc was manually curated to remove errors, correct automated predictions, and add information from the literature. The ongoing curation is based on public sources, literature searches, and our own experimental and bioinformatics studies. In a number of instances we have improved on the original genome annotation, and, in some ambiguous cases, collected relevant information from the literature in order to help clarify gene or protein annotation in the future. All genes in LeishCyc are linked to the corresponding entry in GeneDB (Wellcome Trust Sanger Institute). CONCLUSIONS: The LeishCyc database describes Leishmania major genes, gene products, metabolites, their relationships and biochemical organization into metabolic pathways. LeishCyc provides a systematic approach to organizing the evolving information about Leishmania biochemical networks and is a tool for analysis, interpretation, and visualization of Leishmania 'omics (transcriptomics, proteomics, metabolomics) data in the context of metabolic pathways. LeishCyc is the first such database for the Trypanosomatidae family, which includes a number of other important human parasites. Flexible query/visualization capabilities are provided by the Pathway Tools software and its Web interface. The LeishCyc database is made freely available on the Internet (www.leishcyc.org).

PMID: 19497128 [PubMed - as supplied by publisher]

8: J Med Entomol. 2009 May;46(3):693-702.

A probabilistic risk assessment for deployed military personnel after the implementation of the "Leishmaniasis Control Program" at Tallil Air Base, Iraq.

Schleier JJ 3rd, Davis RS, Barber LM, Macedo PA, Peterson RK.

Department of Land Resources and Environmental Sciences, Montana State University, 334 Leon Johnson Hall, Bozeman, MT 59717, USA. jeromes@montana.edu

Leishmaniasis has been of concern to the U.S. military and has re-emerged in importance because of recent deployments to the Middle East. We conducted a retrospective probabilistic risk assessment for military personnel potentially exposed to insecticides during the "Leishmaniasis Control Plan" (LCP) undertaken in 2003 at Tallil Air Base, Iraq. We estimated acute and subchronic risks from resmethrin, malathion, piperonyl butoxide (PBO), and pyrethrins applied using a truck-mounted ultra-low-volume (ULV) sprayer and lambda-cyhalothrin, cyfluthrin, bifenthrin, chlorpyrifos, and cypermethrin used for residual sprays. We used the risk quotient (RQ) method for our risk assessment (estimated environmental exposure/toxic endpoint) and set the RQ level of concern (LOC) at 1.0. Acute RQs for truck-mounted ULV and residual sprays ranged from 0.00007 to 33.3 at the 95th percentile. Acute exposure to lambda-cyhalothrin, bifenthrin, and chlorpyrifos exceeded the RQ LOC. Subchronic RQs for truck-mounted ULV and residual sprays ranged from 0.00008 to 32.8 at the 95th percentile. Subchronic exposures to lambda-cyhalothrin and chlorpyrifos exceeded the LOC. However, estimated exposures to lambda-cyhalothrin, bifenthrin, and chlorpyrifos did not exceed their respective no observed adverse effect levels.

PMID: 19496443 [PubMed - in process]

Patient Drug Information

9: J Med Entomol. 2009 May;46(3):649-63.

Impact of phlebotomine sand flies on U.S. military operations at Tallil Air Base, Iraq: 4. Detection and identification of leishmania parasites in sand flies.

Coleman RE, Hochberg LP, Swanson KI, Lee JS, McAvin JC, Moulton JK, Eddington DO, Groebner JL, O'Guinn ML, Putnam JL.

520th Theater Army Medical Laboratory, Tallil Air Base, Iraq. russell.coleman@us.army.mil

Sand flies collected between April 2003 and November 2004 at Tallil Air Base, Iraq, were evaluated for the presence of Leishmania parasites using a combination of a real-time Leishmania-generic polymerase chain reaction (PCR) assay and sequencing of a 360-bp fragment of the glucose-6-phosphate-isomerase (GPI) gene. A total of 2,505 pools containing 26,574 sand flies were tested using the real-time PCR assay. Leishmania DNA was initially detected in 536 pools; however, after extensive retesting with the real-time PCR assay, a total of 456 pools were considered positive and 80 were considered indeterminate. A total of 532 samples were evaluated for Leishmania GPI by sequencing, to include 439 PCR-positive samples, 80 PCR-indeterminate samples, and 13 PCR-negative samples. Leishmania GPI was detected in 284 samples that were sequenced, to include 281 (64%) of the PCR-positive samples and 3 (4%) of the PCR-indeterminate samples. Of the 284 sequences identified as Leishmania, 261 (91.9%) were L. tarentolae, 18 (6.3%) were L. donovani-complex parasites, 3 (1.1%) were L. tropica, and 2 were similar to both L. major and L. tropica. Minimum field infection rates were 0.09% for L. donovani-complex parasites, 0.02% for L. tropica, and 0.01% for the L. major/tropica-like parasite. Subsequent sequencing of a 600-bp region of the "Hyper" gene of 12 of the L. donovani-complex parasites showed that all 12 parasites were L. infantum. These data suggest that L. infantum was the primary leishmanial threat to U.S. military personnel deployed to Tallil Air Base. The implications of these findings are discussed.

PMID: 19496439 [PubMed - in process]

10: J Med Entomol. 2009 May;46(3):605-9.

Inhibitor of cysteine peptidase does not influence the development of Leishmania mexicana in Lutzomyia longipalpis.

Jecna L, Svarovska A, Besteiro S, Mottram JC, Coombs GH, Volf P.

Department of Parasitology, Faculty of Science, Charles University, Vinicna 7, 128 44 Prague 2, Czech Republic.

It has been proposed that the natural cysteine peptidase inhibitor ICP of Leishmania mexicana protects the protozoan parasite from insect host proteolytic enzymes, thereby promoting survival. To test this hypothesis, L. mexicana mutants deficient in ICP were evaluated for their ability to develop in the sand fly Lutzomyia longipalpis. No significant differences were found between the wild-type parasites, two independently derived ICP-deficient mutants, or mutants overexpressing ICP; all lines developed similarly in the sand fly midgut and produced heavy late-stage infections. In addition, recombinant L. mexicana ICP did not inhibit peptidase activity of the midgut extracts in vitro. We conclude that ICP has no major role in promoting survival of L. mexicana in the vectorial part of its life cycle in L. longipalpis.

PMID: 19496433 [PubMed - in process]

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