Thursday, August 11, 2011

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 - 8 of 8

1. PLoS Negl Trop Dis. 2011 Aug;5(8):e1257. Epub 2011 Aug 2.

Improving the cost-effectiveness of visual devices for the control of riverine tsetse flies, the major vectors of human african trypanosomiasis.

Esterhuizen J, Rayaisse JB, Tirados I, Mpiana S, Solano P, Vale GA, Lehane MJ, Torr SJ.

Source

Vector Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Abstract

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 1×1 m black targets and small 25×25 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m(2) of cloth) for small targets plus flanking nets is 5.5-15X greater than for 1 m(2) targets and 8.6-37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness.

PMID:
21829743
[PubMed - in process]
2. PLoS Negl Trop Dis. 2011 Aug;5(8):e1249. Epub 2011 Aug 2.

Using Detergent to Enhance Detection Sensitivity of African Trypanosomes in Human CSF and Blood by Loop-Mediated Isothermal Amplification (LAMP).

Grab DJ, Nikolskaia OV, Inoue N, Thekisoe OM, Morrison LJ, Gibson W, Dumler JS.

Source

Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

Abstract

BACKGROUND:

The loop-mediated isothermal amplification (LAMP) assay, with its advantages of simplicity, rapidity and cost effectiveness, has evolved as one of the most sensitive and specific methods for the detection of a broad range of pathogenic microorganisms including African trypanosomes. While many LAMP-based assays are sufficiently sensitive to detect DNA well below the amount present in a single parasite, the detection limit of the assay is restricted by the number of parasites present in the volume of sample assayed; i.e. 1 per µL or 10(3) per mL. We hypothesized that clinical sensitivities that mimic analytical limits based on parasite DNA could be approached or even obtained by simply adding detergent to the samples prior to LAMP assay.

METHODOLOGY/PRINCIPAL FINDINGS:

For proof of principle we used two different LAMP assays capable of detecting 0.1 fg genomic DNA (0.001 parasite). The assay was tested on dilution series of intact bloodstream form Trypanosoma brucei rhodesiense in human cerebrospinal fluid (CSF) or blood with or without the addition of the detergent Triton X-100 and 60 min incubation at ambient temperature. With human CSF and in the absence of detergent, the LAMP detection limit for live intact parasites using 1 µL of CSF as the source of template was at best 10(3) parasites/mL. Remarkably, detergent enhanced LAMP assay reaches sensitivity about 100 to 1000-fold lower; i.e. 10 to 1 parasite/mL. Similar detergent-mediated increases in LAMP assay analytical sensitivity were also found using DNA extracted from filter paper cards containing blood pretreated with detergent before card spotting or blood samples spotted on detergent pretreated cards.

CONCLUSIONS/SIGNIFICANCE:

This simple procedure for the enhanced detection of live African trypanosomes in biological fluids by LAMP paves the way for the adaptation of LAMP for the economical and sensitive diagnosis of other protozoan parasites and microorganisms that cause diseases that plague the developing world.

PMID:
21829738
[PubMed - in process]
3. PLoS Negl Trop Dis. 2011 Aug;5(8):e1246. Epub 2011 Aug 2.

Prevalence of human african trypanosomiasis in the democratic republic of the congo.

Mumba D, Bohorquez E, Messina J, Kande V, Taylor SM, Tshefu AK, Muwonga J, Kashamuka MM, Emch M, Tidwell R, Büscher P, Meshnick SR.

Source

Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

Abstract

Human African Trypanosomiasis (HAT) is a major public health problem in the Democratic Republic of the Congo (DRC). Active and passive surveillance for HAT is conducted but may underestimate the true prevalence of the disease. We used ELISA to screen 7,769 leftover dried blood spots from a nationally representative population-based survey, the 2007 Demographic and Health Survey. 26 samples were positive by ELISA. Three of these were also positive by trypanolysis and/or PCR. From these data, we estimate that there were 18,592 people with HAT (95% confidence interval, 4,883-32,302) in the DRC in 2007, slightly more than twice as many as were reported.

PMID:
21829736
[PubMed - in process]
4. PLoS One. 2011;6(8):e23120. Epub 2011 Aug 1.

Antimonial Resistance in Leishmania donovani Is Associated with Increased In Vivo Parasite Burden.

Vanaerschot M, De Doncker S, Rijal S, Maes L, Dujardin JC, Decuypere S.

Source

Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.

Abstract

Leishmania donovani is an intracellular protozoan parasite that causes visceral leishmaniasis (VL). Antimonials (SSG) have long been the first-line treatment against VL, but have now been replaced by miltefosine (MIL) in the Indian subcontinent due to the emergence of SSG-resistance. Our previous study hypothesised that SSG-resistant L. donovani might have increased in vivo survival skills which could affect the efficacy of other treatments such as MIL. The present study attempts to validate these hypotheses. Fourteen strains derived from Nepalese clinical isolates with documented SSG-susceptibility were infected in BALB/c mice to study their survival capacity in drug free conditions (non-treated mice) and in MIL-treated mice. SSG-resistant parasites caused a significant higher in vivo parasite load compared to SSG-sensitive parasites. However, this did not seem to affect the strains' response to MIL-treatment since parasites from both phenotypes responded equally well to in vivo MIL exposure. We conclude that there is a positive association between SSG-resistance and in vivo survival skills in our sample of L. donovani strains which could suggest a higher virulence of SSG-R strains compared to SSG-S strains. These greater in vivo survival skills of SSG-R parasites do not seem to directly affect their susceptibility to MIL. However, it cannot be excluded that repeated MIL exposure will elicit different adaptations in these SSG-R parasites with superior survival skills compared to the SSG-S parasites. Our results therefore highlight the need to closely monitor drug efficacy in the field, especially in the context of the Kala-azar elimination programme ongoing in the Indian subcontinent.

PMID:
21829701
[PubMed - in process]
5. PLoS One. 2011;6(7):e23107. Epub 2011 Jul 29.

Characterization of Leishmania donovani MCM4: Expression Patterns and Interaction with PCNA.

Minocha N, Kumar D, Rajanala K, Saha S.

Source

Department of Microbiology, University of Delhi South Campus, New Delhi, India.

Abstract

Events leading to origin firing and fork elongation in eukaryotes involve several proteins which are mostly conserved across the various eukaryotic species. Nuclear DNA replication in trypanosomatids has thus far remained a largely uninvestigated area. While several eukaryotic replication protein orthologs have been annotated, many are missing, suggesting that novel replication mechanisms may apply in this group of organisms. Here, we characterize the expression of Leishmania donovani MCM4, and find that while it broadly resembles other eukaryotes, noteworthy differences exist. MCM4 is constitutively nuclear, signifying that, unlike what is seen in S.cerevisiae, varying subcellular localization of MCM4 is not a mode of replication regulation in Leishmania. Overexpression of MCM4 in Leishmania promastigotes causes progress through S phase faster than usual, implicating a role for MCM4 in the modulation of cell cycle progression. We find for the first time in eukaryotes, an interaction between any of the proteins of the MCM2-7 (MCM4) and PCNA. MCM4 colocalizes with PCNA in S phase cells, in keeping with the MCM2-7 complex being involved not only in replication initiation, but fork elongation as well. Analysis of a LdMCM4 mutant indicates that MCM4 interacts with PCNA via the PIP box motif of MCM4 - perhaps as an integral component of the MCM2-7 complex, although we have no direct evidence that MCM4 harboring a PIP box mutation can still functionally associate with the other members of the MCM2-7 complex- and the PIP box motif is important for cell survival and viability. In Leishmania, MCM4 may possibly help in recruiting PCNA to chromatin, a role assigned to MCM10 in other eukaryotes.

PMID:
21829589
[PubMed - in process]
6. Pediatr Infect Dis J. 2011 Aug 8. [Epub ahead of print]

Old World Leishmania infantum Cutaneous Leishmaniasis Unresponsive to Liposomal Amphotericin B Treated With Topical Imiquimod.

Hervás JA, Martín-Santiago A, Hervás D, Rojo E, Mena A, Rocamora V, Dueñas J.

Source

From the *Section of Pediatric Infectious Diseases, †IUNICS, ‡Department of Dermatology, and §Department of Clinical Microbiology, Son Espases University Hospital and University of the Balearic Islands, Palma de Mallorca, The Balearic Islands, Spain.

Abstract

We present a case of a child with Leishmania infantum cutaneous leishmaniasis unresponsive to 2 courses of intravenous liposomal amphotericin B, a treatment failure that has not been reported in this Leishmania species. The patient responded to topical imiquimod and had no relapse. We review the literature on the treatment failure of liposomal amphotericin B for cutaneous leishmaniasis.

PMID:
21829140
[PubMed - as supplied by publisher]
7. Exp Parasitol. 2011 Jul 30. [Epub ahead of print]

Leishmania amazonensis: Characterization of an ecto-3'-nucleotidase activity and its possible role in virulence.

Paletta-Silva R, Vieira DP, Vieira-Bernardo R, Majerowicz D, Gondim KC, Vannier-Santos MA, Lopes AH, Meyer-Fernandes JR.

Source

Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil.

Abstract

Ecto-3'-nucleotidase/nuclease (3'NT/NU) is a membrane-bound enzyme that plays a key role in the nutrition of Leishmania sp. protozoan parasites. This enzyme generates nucleosides via hydrolyzes of 3'mononucleotides and nucleic acids, which enter the cell by specific transporters. In this work, we identify and characterize Leishmania amazonensis ecto-3'-nucleotidase activity (La3'-nucleotidase), report ammonium tetrathiomolybdate (TTM) as a novel La3'-nucleotidase inhibitor and approach the possible involvement of ecto-3'-nucleotidase in cellular adhesion. La3'-nucleotidase presented characteristics similar to those reported for the class I single-strand nuclease family; a molecular weight of approximately 40kDa and optimum activity in an alkaline pH range were observed. Although it is conserved among the genus, La3'-nucleotidase displays different kinetic properties; it can be inhibited by vanadate, molybdate and Cu(2+) ions. Interestingly, ecto-3'-nucleotidase activity is 60-fold higher than that of ecto-5'-nucleotidase in L. amazonensis. Additionally, ecto-3'-nucleotidase activity is two-fold higher in virulent L. amazonensis cells than in avirulent ones. Notably, macrophage-parasite attachment/invasion was increased by 400% in the presence of adenosine 3'-monophosphate (3'AMP); however, this effect was reverted by TTM treatment. We believe that La3'-nucleotidase may play a significant role in the generation of adenosine, which may contribute to mammalian host immune response impairment and establishment of infection.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21827749
[PubMed - as supplied by publisher]
8. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2011 Apr 30;29(2):122-5.

[Immunogenicity of the recombinant plasmid of Leishmania donovani amastin gene].

[Article in Chinese]
Li JF, Chen JP, Tian Y, Yang ZW, Ma Y, Hu XS.

Source

Departmnent of Parasitology, Guiyang Medical College, Guiyang 550004, China.

Abstract

OBJECTIVE:

To investigate the immunogenicity of recombinant plasmid pcDNA3.1-amastin with Leishmania donovani amastin gene.

METHODS:

Eighteen female BALB/c mice were randomly divided into experimental group and control group. Mice in experimental group and control group were intramuscularly injected with 50 microg recombinant plasmid pcDNA3.1-amastin and blank plasmid vector pcDNA3.1(+), respectively, and then received equivalent dose of plamid after 2 weeks. On days 7, 14, and 21 after the second immunization, serum samples were collected from 3 mice each group. The mice were then sacrificed, spleens were removed and splenocytes were collected. Serum antibody level was determined by indirect ELISA. Splenocyte proliferation responses and cytotoxicity of spleen-derived lymphocytes were analyzed by MTT colorimetry after stimulation with ConA. Level of IFN-gamma, IL-2 and IL-4 in the splenocyte culture supernatants was determined by double antibody sandwich ELISA.

RESULTS:

On days 7, 14, and 21 after the second immunization, specific IgG antibody (more than 1:640) was found in experimental group, but not in the control (P < 0.01); stimulation index (SI) of spleen cells in experimental group (428 +/- 0.51, 5.01-0.60, and 4.39 +/- 0.50) was higher than that of control group (P < 0.01); the level of IFN-gamma [(42.06 +/- 4.26), (66.02 +/- 6.02), and (58.29 +/- 3.75) pg/ml] and IL-2 [(38.21 +/- 5.11), (64.79 +/- 8.67), and (52.69 +/- 7.15) pg/ml] in splenocyte culture supernatants of experimental group was higher than that of control group (P < 0.01); IL-4 was not found in the two groups; cytotoxicity of spleen-derived lymphocytes in experimental group [(42.20 +/- 5.96)%, (63.66 +/- 5.44)%, and (52.24 +/- 4.56)%] was stronger than that of control (P < 0.01).

CONCLUSION:

The recombinant plasmid pcDNA3.1-amnastin can induce specific humoral and Th1 type cellular immune responses in mice.

PMID:
21826897
[PubMed - in process]

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