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Sent on Saturday, 2011 Dec 17Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Parasitol Res. 2011;2011:656523. Epub 2011 Nov 24.Efficacy of Topical Liposomal Amphotericin B versus Intralesional Meglumine Antimoniate (Glucantime) in the Treatment of Cutaneous Leishmaniasis.Layegh P, Rajabi O, Jafari MR, Emamgholi Tabar Malekshah P, Moghiman T, Ashraf H, Salari R.SourceResearch Center for Skin Diseases & Cutaneous Leishmaniasis, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AbstractBackground. Topical treatment of cutaneous leishmaniasis is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. Recently liposomal formulations of amphotericin B have been increasingly used in the treatment of several types of leishmaniasis. Aims. The efficacy of a topical liposomal amphotericin B formulation was compared with intralesional glucantime in the treatment of cutaneous leishmaniasis. Methods. From 110 patients, the randomly selected 50 received a topical liposomal formulation of amphotericin B into each lesion, 3-7 drops twice daily, according to the lesion's size and for 8 weeks. The other group of 60 patients received intralesional glucantime injection of 1-2 mL once a week for the same period. The clinical responses and side effects of both groups were evaluated weekly during the treatment course. Results. Per-protocol analysis showed no statistically significant difference between the two groups (P = 0.317, 95% confidence interval (CI) = 1.610 (0.632-4.101)). Moreover, after intention-to-treat analysis, the same results were seen (P = 0.650, 95% CI = 0.1.91 (0.560-2.530)). Serious post treatment side effects were not observed in either group. Conclusions. Topical liposomal amphotericin B has the same efficacy as intralesional glucantime in the treatment of cutaneous leishmaniasis. |
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| 2. | PLoS One. 2011;6(12):e28493. Epub 2011 Dec 12.Development of Derivatives of 3, 3'-Diindolylmethane as Potent Leishmania donovani Bi-Subunit Topoisomerase IB Poisons.Roy A, Chowdhury S, Sengupta S, Mandal M, Jaisankar P, D'Annessa I, Desideri A, Majumder HK.SourceMolecular Parasitology Laboratory, Indian Institute of Chemical Biology, Kolkata, India. AbstractBACKGROUND:The development of 3, 3'-diindolyl methane (DIM) resistant parasite Leishmania donovani (LdDR50) by adaptation with increasing concentrations of the drug generates random mutations in the large and small subunits of heterodimeric DNA topoisomerase I of Leishmania (LdTOP1LS). Mutation of large subunit of LdTOP1LS at F270L is responsible for resistance to DIM up to 50 µM concentration. METHODOLOGY/PRINCIPAL FINDINGS:In search of compounds that inhibit the growth of the DIM resistant parasite and inhibit the catalytic activity of mutated topoisomerase I (F270L), we have prepared three derivatives of DIM namely DPDIM (2,2'-diphenyl 3,3'-diindolyl methane), DMDIM (2,2'-dimethyl 3,3'-diindolyl methane) and DMODIM (5,5'-dimethoxy 3,3'-diindolyl methane) from parent compound DIM. All the compounds inhibit the growth of DIM resistant parasites, induce DNA fragmentation and stabilize topo1-DNA cleavable complex with the wild type and mutant enzyme. CONCLUSION:The results suggest that the three derivatives of DIM can act as promising lead molecules for the generation of new anti-leishmanial agents. |
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| 3. | J Trop Med. 2011;2011:695382. Epub 2011 Nov 17.An timony resistance in leishmania, focusing on experimental research.Jeddi F, Piarroux R, Mary C.SourceLaboratoire de Parasitologie, Hôpital de la Timone, 264 rue Saint-Pierre, 13385 Marseille Cedex 05, France. AbstractLeishmaniases are parasitic diseases that spread in many countries with a prevalence of 12 million cases. There are few available treatments and antimonials are still of major importance in the therapeutic strategies used in most endemic regions. However, resistance toward these compounds has recently emerged in areas where the replacement of these drugs is mainly limited by the cost of alternative molecules. In this paper, we reviewed the studies carried out on antimonial resistance in Leishmania. Several common limitations of these works are presented before prevalent approaches to evidence antimonial resistance are related. Afterwards, phenotypic determination of resistance is described, then confronted to clinical outcome. Finally, we detail molecular mechanisms and targets involved in resistance and already identified in vitro within selected mutant strains or in clinical isolates. |
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| 4. | J Trop Med. 2011;2011:645203. Epub 2011 Nov 17.Phase 4 pharmacovigilance trial of paromomycin injection for the treatment of visceral leishmaniasis in India.Sinha PK, Jha TK, Thakur CP, Nath D, Mukherjee S, Aditya AK, Sundar S.SourceRajendra Memorial Research Institute of Medical Sciences, Agam Kuan, Patna, Bihar 800 007, India. AbstractBackground. A phase 3 study demonstrated the safety and efficacy of paromomycin (paromomycin IM injection) for treatment of VL in an inpatient setting. Methods. This phase 4 study was conducted to assess the safety and efficacy of paromomycin in children and adults in an outpatient setting in Bihar, India. Results. This study enrolled 506 adult and pediatric patients. Of the 494 patients in the intent-to-treat (ITT) population, 98% received a full course of treatment. The overall study completion rate was 94% (462/494) for the ITT population and 96% (461/479) for the efficacy-evaluable (EE) population. Initial clinical cure was 99.6%, and final clinical cure 6 months after treatment was 94.2%. Grade 3 or 4 adverse events occurred in 5% of patients; events with a frequency of ≥1% were increases in alanine aminotransferase and aspartate aminotransferase. Conclusions. This study confirms the safety and efficacy of paromomycin to treat VL in an outpatient setting. |
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| 5. | J Trop Med. 2011;2011:359145. Epub 2011 Nov 22.Clinical manifestations and distribution of cutaneous lei shmaniasis in pakistan.Afghan AK, Kassi M, Kasi PM, Ayub A, Kakar N, Marri SM.SourceDepartment of Pathology, Bolan Medical College, 8-13/36 Kasi Road, Balochistan, Quetta 87300, Pakistan. AbstractCutaneous leishmaniasis (CL) is a rising epidemic in Pakistan. It is a major public health problem in the country especially alongside regions bordering the neighboring Afghanistan and cities that have had the maximum influx of refugees. The purpose of our paper is to highlight the diverse clinical manifestations of the disease seen along with the geographic areas affected, where the hosts are particularly susceptible. This would also be helpful in presenting the broad spectrum of the disease for training of health care workers and help in surveillance of CL in the region. The increased clinical diversity and the spectrum of phenotypic manifestations noted underscore the fact that the diagnosis of CL should be not only considered when dealing with common skin lesions, but also highly suspected by dermatologists and even primary care physicians even when encountering uncommon pathologies. Hence, we would strongly advocate that since most of these patients present to local health care centers and hospitals, primary care practitioners and even lady health workers (LHWs) should be trained in identification of at least the common presentations of CL. |
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| 6. | Emerg Infect Dis. 2011 Dec;17(12):2322-4. doi: 10.3201/eid1712.110921.Risk for human african trypanosomiasis, central Africa, 2000-2009.Simarro PP, Cecchi G, Franco JR, Paone M, Fèvre EM, Diarra A, Postigo JA, Mattioli RC, Jannin JG.AbstractComprehensive georeference records for human African trypanosomiasis in Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, and Gabon were combined with human population layers to estimate a kernel-smoothed relative risk function. Five risk categories were mapped, and ≈3.5 million persons were estimated to be at risk for this disease. |
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| 7. | BMC Med Genet. 2011 Dec 15;12(1):162. [Epub ahead of print]Genetic and functional evaluation of the role of CXCR1 and CXCR2 in susceptibility to visceral leishmaniasis in north-east India.Mehrotra S, Fakiola M, Oommen J, Jamieson SE, Mishra A, Sudarshan M, Tiwary P, Rani DS, Thangaraj K, Rai M, Sundar S, Blackwell JM.AbstractABSTRACT: BACKGROUND:IL8RA and IL8RB, encoded by CXCR1 and CXCR2, are receptors for interleukin (IL)-8 and other CXC chemokines involved in chemotaxis and activation of polymorphonuclear neutrophils (PMN). Variants at CXCR1 and CXCR2 have been associated with susceptibility to cutaneous and mucocutaneous leishmaniasis in Brazil. Here we investigate the role of CXCR1/CXCR2 in visceral leishmaniasis (VL) in India. METHODS:Three single nucleotide polymorphisms (SNPs) (rs4674259, rs2234671, rs3138060) that tag linkage disequilibrium blocks across CXCR1/CXCR2 were genotyped in primary family-based (313 cases; 176 nuclear families; 836 individuals) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between CXCR1/CXCR2 variants and VL. Quantitative RT/PCR was used to compare CXCR1/CXCR2 expression in mRNA from paired splenic aspirates taken before and after treatment from 19 VL patients. RESULTS:Family-based analysis using FBAT showed association between VL and SNPs CXCR1_rs2234671 (Z-score=2.935, P=0.003) and CXCR1_rs3138060 (Z-score=2.22, P=0.026), but not with CXCR2_rs4674259. Logistic regression analysis of the case-control data under an additive model of inheritance showed association between VL and SNPs CXCR2_rs4674259 (OR=1.15, 95%CI=1.01-1.31, P=0.027) and CXCR1_rs3138060 (OR=1.25, 95%CI=1.02-1.53, P=0.028), but not with CXCR1_rs2234671. The 3-locus haplotype T_G_C across these SNPs was shown to be the risk haplotype in both family- (TRANSMIT; P=0.014) and population- (OR=1.16, P=0.028) samples (combined P=0.002). CXCR2, but not CXCR1, expression was down regulated in pre-treatment compared to post-treatment splenic aspirates (P=0.021). CONCLUSIONS:This well-powered primary and replication genetic study, together with functional analysis of gene expression, implicate CXCR2 in determining outcome of VL in India. |
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| 8. | PLoS Negl Trop Dis. 2011 Aug;5(8):e1276. Epub 2011 Aug 9.Restricted application of insecticides: a promising tsetse control technique, but what do the farmers think of it?Bouyer F, Hamadou S, Adakal H, Lancelot R, Stachurski F, Belem AM, Bouyer J.SourceCentre International de Recherche-Développement sur l'Elevage en zone Sub-humide (CIRDES), Bobo-Dioulasso, Burkina Faso. bouyer@cirad.fr AbstractBACKGROUND:Restricted application of insecticides to cattle is a cheap and safe farmer-based method to control tsetse. In Western Africa, it is applied using a footbath, mainly to control nagana and the tick Amblyomma variegatum. In Eastern and Southern Africa, it might help controlling the human disease, i.e., Rhodesian sleeping sickness as well. The efficiency of this new control method against ticks, tsetse and trypanosomoses has been demonstrated earlier. The invention, co-built by researchers and farmers ten years ago, became an innovation in Burkina Faso through its diffusion by two development projects. METHODOLOGY/PRINCIPAL FINDINGS:In this research, we studied the process and level of adoption in 72 farmers inhabiting the peri-urban areas of Ouagadougou and Bobo-Dioulasso. Variables describing the livestock farming system, the implementation and perception of the method and the knowledge of the epidemiological system were used to discriminate three clusters of cattle farmers that were then compared using indicators of adoption. The first cluster corresponded to modern farmers who adopted the technique very well. The more traditional farmers were discriminated into two clusters, one of which showed a good adoption rate, whereas the second failed to adopt the method. The economic benefit and the farmers' knowledge of the epidemiological system appeared to have a low impact on the early adoption process whereas some modern practices, as well as social factors appeared critical. The quality of technical support provided to the farmers had also a great influence. Cattle farmers' innovation-risk appraisal was analyzed using Rogers' adoption criteria which highlighted individual variations in risk perceptions and benefits, as well as the prominent role of the socio-technical network of cattle farmers. CONCLUSIONS/SIGNIFICANCE:Results are discussed to highlight the factors that should be taken into consideration, to move discoveries from bench to field for an improved control of trypanosomoses vectors. |
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| 9. | PLoS Negl Trop Dis. 2011 Aug;5(8):e1268. Epub 2011 Aug 16.Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease.Morrot A, Terra-Granado E, Pérez AR, Silva-Barbosa SD, Milićević NM, Farias-de-Oliveira DA, Berbert LR, De Meis J, Takiya CM, Beloscar J, Wang X, Kont V, Peterson P, Bottasso O, Savino W.SourceDepartment of Immunology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. morrot@micro.ufrj.br AbstractExtrathymic CD4+CD8+ double-positive (DP) T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire) and tissue-restricted antigen (TRA) genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may contribute to the immunopathological events seen in the Chagas disease. |
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