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Sent on Tuesday, 2011 Nov 29Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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1. | Pan Afr Med J. 2011;8:36. Epub 2011 Apr 1.Transmission of human African trypanosomiasis in the Komo-Mondah focus, Gabon.Kohagne TL, M'eyi MP, Kamkuimo RG, Kaba D, Louis JF, Mimpfoundi R.SourceOrganisation de Coordination pour la lutte contre les endémies en Afrique centrale (OCEAC), BP 15665, Yaoundé, Cameroun. AbstractBACKGROUND:Knowledge about transmission of sleeping sickness in a given focus is of a great importance since it governs the efficacy and the cost-effectiveness of control strategy. The Komo-Mondah focus is the most endemic sleeping sickness focus of Gabon. This focus has hardly been investigated and available publications are more than thirty years old. In order to update transmission features of sleeping sickness in that focus, we have conducted epidemiological and entomological surveys in March-April 2008. METHODS:Epidemiological investigation relied on a case-control study using a quantitative and qualitative methodology (a structured questionnaire). Cases were affected people (parasitological positive) diagnosed by the national control program from 2004 to 2007, controls were those found disease-free after clinical examination and biological tests in the same period. They were asked to respond to a standard questionnaire concerning their activities after having signed a written consent. An unvaried analysis was first performed and then a multivariate analysis using the conditional logistic regression for matching method. Traps were then set out for four days in areas where people were working. Tsetse flies captured were identified and dissected; their density and human-fly contact points were determined. RESULTS:A risk of infection was associated with fishing activities (Odds-ratio: 5.69; CI95%: 3.38-9.57). Three species of Glossina were captured: Glossina palpalis palpalis, Glossina fuscipes fuscipes and G. Caliginea. Human-fly contact points were mainly landing stages. CONCLUSION:A combined strategy of case-detection and vector control targeted at landing stages should be efficient against the disease. |
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2. | Indian J Dermatol. 2011 Sep-Oct;56(5):587-90.Successful treatment of mult ifocal cutaneous leishmaniasis with miltefosine.Madke B, Kharkar V, Chikhalkar S, Mahajan S, Khopkar U.SourceDepartment of Dermatology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India. AbstractWe report a 48-year-old immunocompetent male, resident of Central India, who presented with slowly progressive asymptomatic multiple red lesions on different parts of body. On enquiry, the patient gave history of travel to Middle East 6 months back. Examination showed 10 crusted erythematous indurated plaques and nodules over forearms, left leg, right index finger, left wrist and dorsa of both feet. Histopathological examination of tissue biopsy showed multiple intracellular as well as extracellular leishmania donovan bodies. Keeping in mind the higher rate of side effects to pentavalent antimony, we treated this patient with oral miltefosine 50 mg bid and the lesions showed complete resolution over 4 months of therapy. |
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3. | J Antimicrob Chemother. 2011 Nov 25. [Epub ahead of print]Treatment of Leishmania donovani-infected hamsters with miltefosine: analysis of cytokine mRNA expression by real-time PCR, lymphoproliferation, nitrite production and antibody responses.Gupta R, Kushawaha PK, Samant M, Jaiswal AK, Baharia RK, Dube A.SourceDivision of Parasitology, Central Drug Research Institute, Post Box No. 173, Lucknow-226 001, India. AbstractObjectivesMiltefosine, an orally effective antileishmanial drug, works directly on the parasite by impairing membrane synthesis and subsequent apoptosis of the parasite and has also been reported to have macrophage-activating functions that aid parasite killing. We investigated the type of immunological responses generated in miltefosine-treated Leishmania donovani-infected hamsters, which simulate the clinical situation of human kala-azar.MethodsTwenty-five-day-old infected hamsters, treated with miltefosine at 40 mg/kg for 5 consecutive days, were euthanized on days 30 and 45 post treatment (p.t.) and checked for parasite clearance and for real-time analysis of mRNAs of the Th1/Th2 cytokines interferon-γ (IFN-γ), interleukin-12 (IL-12), tumour necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), IL-4, IL-10 and transforming growth factor-β (TGF-β), nitric oxide (NO) production, the lymphocyte transformation test (LTT) and antibody responses. Responses were compared with the normal and Leishmania-infected groups at the same time points.ResultsBy day 45 p.t. there was a significant increase in the mRNA expression of iNOS, IFN-γ, IL-12 and TNF-α, whereas there were significant decreases in IL-4, IL-10 and TGF-β in cured hamsters as compared with their infected counterparts. In vitro stimulation of lymphocytes with concanavalin A and soluble Leishmania donovani antigen showed a maximum LTT response and there was a gradual increase in the NO level (∼7-fold compared with infected counterparts). Anti-Leishmania IgG and IgG1 levels, found to be elevated in the infected group, decreased significantly after treatment but there was a significant increase in IgG2 isotype.ConclusionsTreatment of Leishmania-infected hamsters with miltefosine reverses the Th2-type response into a strong Th1-type immune response. |
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4. | Nat Genet. 2011 Nov 28;43(12):1178. doi: 10.1038/ng.1025.Leishmaniasis geno mes.Bahcall O. |
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5. | J Clin Immunol. 2011 Nov 26. [Epub ahead of print]Intravenous Immunoglobulin Treatment for Macrophage Activation Syndrome Complicating Chronic Granulomatous Disease.Alvarez-Cardona A, Rodríguez-Lozano AL, Blancas-Galicia L, Rivas-Larrauri FE, Yamazaki-Nakashimada MA.SourceClinical Immunology Department, Instituto Nacional de Pediatría, Insurgentes sur 3700-C, Insurgentes Cuicuilco Coyoacan CP, Mexico City, Mexico. AbstractOBJECTIVES:Chronic granulomatous disease is a rare phagocyte disorder characterized by an increased susceptibility to infections and inflammatory complications. We describe two patients with chronic granulomatous disease (CGD) complicated by macrophage activation syndrome (MAS) (secondary hemophagocytic lymphohistiocytosis) treated with intravenous immunoglobulin (IVIG). METHODS:A report of two cases of CGD complicated by MAS who were successfully treated with IVIG was made, and a comparison was made with ten other cases reported in the literature. RESULTS:MAS is a severe potentially fatal complication of CGD. Most cases are associated with Burkholderia cepacia and leishmaniasis infection. The treatment of these patients varies between centers, and one example is the use of the HLH-2004 protocol. IVIG could be an effective first line option for this complication in CGD patients. CONCLUSIONS:The exaggerated inflammatory response characteristic of CGD patients could play a role in the development of this complication. IVIG appears to be a safe and effective first line treatment in these patients. |
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6. | Infect Genet Evol. 2011 Nov 20. [Epub ahead of print]Genome-wide SNP and microsatellite variation illuminate population-level epidemiology in the Leishmania donovani species complex.Downing T, Stark O, Vanaerschot M, Imamura H, Sanders M, Decuypere S, de Doncker S, Maes I, Rijal S, Sundar S, Dujardin JC, Berriman M, Schönian G.SourceWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. AbstractThe species of the Leishmania donovani species complex cause visceral leishmaniasis, a debilitating infectious disease transmitted by sandflies. Understanding molecular changes associated with population structure in these parasites can help unravel their epidemiology and spread in humans. In this study, we used a panel of standard microsatellite loci and genome-wide SNPs to investigate population-level diversity in L. donovani strains recently isolated from a small geographic area spanning India, Bihar and Nepal, and compared their variation to that found in diverse strains of the L. donovani complex isolates from Europe, Africa and Asia. Microsatellites and SNPs could clearly resolve the phylogenetic relationships of the strains between continents, and microsatellite phylogenies indicated that certain older Indian strains were closely related to African strains. In the context of the anti-malaria spraying campaigns in the 1960s, this was consistent with a pattern of episodic population size contractions and clonal expansions in these parasites that was supported by population history simulations. In sharp contrast to the low resolution provided by microsatellites, SNPs retained a much more fine-scale resolution of population-level variability to the extent that they identified four different lineages from the same region one of which was more closely related to African and European strains than to Indian or Nepalese ones. Joining results of in vitro testing the antimonial drug sensitivity with the phylogenetic signals from the SNP data highlighted protein-level mutations revealing a distinct drug-resistant group of Nepalese and Indian L. donovani. This study demonstrates the power of genomic data for exploring parasite population structure. Furthermore, markers defining different genetic groups have been discovered that could potentially be applied to investigate drug resistance in clinical Leishmania strains. Copyright © 2011. Published by Elsevier B.V. |
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7. | Bioorg Med Chem Lett. 2011 Nov 6. [Epub ahead of print]Diamine and aminoalcohol derivatives activ e against Trypanosoma brucei.Olmo ED, Diaz-González R, Escarcena R, Carvalho L, Bustos LA, Navarro M, Feliciano AS.SourceDepartamento de Química Farmacéutica, Facultad de Farmacia - CIETUS, Universidad de Salamanca, Campus Unamuno, E-37007 Salamanca, Spain. AbstractTwenty compounds selected as representative members of three series of long-chain 1,2-diamines, 2-amino-1-alkanols and 1-amino-2-alkanols structurally related to dihydrosphingosin, were synthesized and tested in vitro for their ability to inhibit the sleeping sickness parasites Trypanosoma bruceirhodesiense and Trypanosoma brucei gambiense. Eight compounds showed EC(50) values in the submicromolar range, with selectivity indexes up to 39 related to the respective cytotoxicity values for Vero cells. The parasite phenotype detected after treatment with the most potent compounds showed irreversible cell morphology alterations of the flagellar pocket that lead to inhibition of cell growth and parasite death. Copyright © 2011. Published by Elsevier Ltd. |
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8. | Exp Parasitol. 2011 Nov 19. [Epub ahead of print]Trypanosoma brucei: Inhibition of acetyl-CoA carboxylase by haloxyfop.Vigueira PA, Paul KS.SourceDepartment of Biological Sciences, Clemson University, Clemson, SC 29634, USA. AbstractTrypanosoma brucei, a eukaryotic pathogen that causes African sleeping sickness in humans and nagana in cattle, depends on the enzyme acetyl-CoA carboxylase (ACC) for full virulence in mice. ACC produces malonyl-CoA, the two carbon donor for fatty acid synthesis. We assessed the effect of haloxyfop, an aryloxyphenoxypropionate herbicide inhibitor of plastid ACCs in many plants as well as Toxoplasma gondii, on T. brucei ACC activity and growth in culture. Haloxyfop inhibited TbACC in cell lysate (EC(50) 67μM), despite the presence of an amino acid motif typically associated with resistance. Haloxyfop also reduced growth of bloodstream and procyclic form parasites (EC(50) of 0.8 and 1.2mM). However, the effect on growth was likely due to off-target effects because haloxyfop treatment had no effect on fatty acid elongation or incorporation into complex lipids in vivo. Copyright © 2011 Elsevier Inc. All rights reserved. |
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9. | Ann Trop Med Parasitol. 2011 Sep;105(6):431-7.Gerbillus nanus (Rodentia: Murida e): a new reservoir host of Leishmania major.Azizi K, Moemenbellah-Fard MD, Fakoorziba MR, Fekri S.SourceShiraz University of Medical Sciences, PO Box 71645-111, Shiraz, Iran. AbstractGerbillus nanus Blanford, 1875 known as Baluchistan gerbil, is a granivorous solitary naked-footed species. No evidence of its natural infection with the protozoan parasite, Leishmania, has so far been provided. Cutaneous leishmaniasis (CL) is a major public health problem in many parts of the world, including Iran. The annual nationwide incidence of human CL due to Leishmania major (CLM) in endemic rural areas was above 18 000 cases in 2008. The detection of L. major in rodents is of fundamental importance for incriminating them as potential reservoirs of CLM infection. Between April 2007 and April 2008, following detection of 245 clinical cases in Jask region of south-east Iran, wild rodents were captured and checked by the microscopic slide smears for leishmanial infections. Overall, 106 gerbilline rodents were captured from which 17 were identified as Gerbillus nanus. Females of Meriones hurrianae, Tatera indica and G. nanus were found to be naturally infected with L. MAJOR. The presence of these parasites in G. nanus has never been reported before. All the amastigote-infected rodents came from the eastern plain of this region, except one T. indica from the western plain which was found to be smear-positive or kinetoplast DNA-positive by PCR. The highest (11·8%) prevalence of infection among rodents confirmed by PCR to be infected with L. major was attributed to Baluchistan gerbil, G. nanus, which is thus incriminated as a potential reservoir host of L. MAJOR in Iran. |
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