101 research outputs found

    Journalists as watchdogs of good governance: Challenges and some ways forward5

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    Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni

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    Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi

    The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

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    © 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

    Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

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    Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    ‘Give courage to the ladies’: expansive apprenticeship for women in rural Malawi

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    Apprenticeship in developed and industrialised nations is increasingly understood as a theory of learning which connects workplace activity and formal study. The concept of ‘expansive apprenticeship’ defines frameworks for workforce development where participants acquire knowledge and skills which will help them in the future as well as in their current roles, whilst ‘restrictive’ apprenticeships limit opportunities for wider, lifelong learning. In developing nations apprenticeship is a traditional route to learning and employment, but apprenticeships in these contexts tend to reflect a restrictive approach characterized by narrowly defined roles and weak educational outcomes. This paper examines a project in Malawi which uses concepts of expansive apprenticeship to address barriers to female continuing education and chronic teacher shortages. The Malawi Access to Teaching Scholarship recruited one thousand women to follow a year-long combined programme of academic distance study and practical work experience in rural primary schools. The aim is to increase the numbers of women teachers in Malawi, especially in rural areas. The Scholarship materials and support structures are designed to move participants from restrictive to expansive contexts for learning so that Scholars develop hybrid roles as students, community workers and apprentice pedagogues. The programme’s resources and approach offer an innovative model of expansive apprenticeship in Sub Saharan Africa

    Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study

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    This paper describes how the use of three drugs which are used separately in mass drug distribution programmes when given together appear safe for use in large populations which have been previously treated with the same drugs separately (Mectizan [ivermectin], albendazole and praziquantel). The target diseases—lymphatic filariasis, soil-transmitted worms and schistosomiasis—were prevalent in Zanzibar up to 2000 but have been largely controlled by mass drug administration. The Ministry of Health and Social Welfare, with the support of WHO, initiated a small scale trial in a population of triple therapy in over 5,000 people initially in two sites, and having found there were no severe adverse events associated with the combined treatment then upscaled to treat the whole of the eligible population of over 700,000. Similarly, there were no severe adverse events. This is the first time the three drugs have been used together at the same time at scale in Africa and provide a basis for expansion of integrated preventive chemotherapy of helminths (worms). The next steps need to be initiated in populations which have heavier worm loads and such interventions need to be subject to close monitoring and ethical review

    Downregulation of MIP-1α/CCL3 with praziquantel treatment in Schistosoma haematobium and HIV-1 co-infected individuals in a rural community in Zimbabwe

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    The results of our study show that the MIP-1alpha/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1alpha/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1alpha/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1alpha/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1alpha/CCL3

    Geographical information system and predictive risk maps of urinary schistosomiasis in Ogun State, Nigeria

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    <p>Abstract</p> <p>Background</p> <p>The control of urinary schistosomiasis in Ogun State, Nigeria remains inert due to lack of reliable data on the geographical distribution of the disease and the population at risk. To help in developing a control programme, delineating areas of risk, geographical information system and remotely sensed environmental images were used to developed predictive risk maps of the probability of occurrence of the disease and quantify the risk for infection in Ogun State, Nigeria.</p> <p>Methods</p> <p>Infection data used were derived from carefully validated morbidity questionnaires among primary school children in 2001–2002, in which school children were asked among other questions if they have experienced "blood in urine" or urinary schistosomiasis. The infection data from 1,092 schools together with remotely sensed environmental data such as rainfall, vegetation, temperature, soil-types, altitude and land cover were analysis using binary logistic regression models to identify environmental features that influence the spatial distribution of the disease. The final regression equations were then used in Arc View 3.2a GIS software to generate predictive risk maps of the distribution of the disease and population at risk in the state.</p> <p>Results</p> <p>Logistic regression analysis shows that the only significant environmental variable in predicting the presence and absence of urinary schistosomiasis in any area of the State was Land Surface Temperature (LST) (B = 0.308, p = 0.013). While LST (B = -0.478, p = 0.035), rainfall (B = -0.006, p = 0.0005), ferric luvisols (B = 0.539, p = 0.274), dystric nitosols (B = 0.133, p = 0.769) and pellic vertisols (B = 1.386, p = 0.008) soils types were the final variables in the model for predicting the probability of an area having an infection prevalence equivalent to or more than 50%. The two predictive risk maps suggest that urinary schistosomiasis is widely distributed and occurring in all the Local Government Areas (LGAs) in State. The high-risk areas (≥ 50% prevalence) however, are confined to scatter foci in the north western part of the State. The model also estimated that 98.99% of schools aged children (5–14 years) are living in areas suitable for urinary schistosomiasis transmission and are at risk of infection.</p> <p>Conclusion</p> <p>The risk maps developed will hopefully be useful to the state health officials, by providing them with detailed distribution of urinary schistosomiasis, help to delineate areas for intervention, assesses population at risk thereby helping in optimizing scarce resources.</p

    Diversification of Schistosoma japonicum in Mainland China Revealed by Mitochondrial DNA

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    Despite the existing threat of schistosomiasis in some rural areas along the Yangtze River, the genetic diversity of Schistosoma japonicum has not been investigated across its wide geographical distribution in China, and such information may provide insight into the disease epidemiology and the development of its control measures. In this study, the adult parasites, obtained through infecting mice with cercariae from snails of the genus Oncomelania collected from a wide range of localities in currently endemic areas of schistosomiasis in the middle and lower (ML) reaches of the Yangtze River, and in Sichuan and Yunnan provinces in the upper reaches of the river in southwest (SW) China, were sequenced individually for mitochondrial genes. In general, a relatively high degree of genetic variation was observed in populations in the ML reaches in terms of nucleotide and haplotype diversity, but a low level was observed in populations in the SW. The significant difference in genetic diversity as revealed by F-statistics, and the existence of no shared haplotypes, were observed between populations in the ML reaches and those in the SW, indicating the effect of geographical separation/isolation upon the schistosomes and probably the parasite-snail system in China

    Enhanced Pro-Inflammatory Cytokine Responses following Toll-Like-Receptor Ligation in Schistosoma haematobium-Infected Schoolchildren from Rural Gabon

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    BACKGROUND: Schistosoma infection is thought to lead to down-regulation of the host's immune response. This has been shown for adaptive immune responses, but the effect on innate immunity, that initiates and shapes the adaptive response, has not been extensively studied. In a first study to characterize these responses, we investigated the effect of Schistosoma haematobium infection on cytokine responses of Gabonese schoolchildren to a number of Toll-like receptor (TLR) ligands. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) were collected from S. haematobium-infected and uninfected schoolchildren from the rural area of Zile in Gabon. PBMCs were incubated for 24 h and 72 h with various TLR ligands, as well as schistosomal egg antigen (SEA) and adult worm antigen (AWA). Pro-inflammatory TNF-alpha and anti-inflammatory/regulatory IL-10 cytokine concentrations were determined in culture supernatants. PRINCIPAL FINDINGS: Infected children produced higher adaptive IL-10 responses than uninfected children against schistosomal antigens (72 h incubation). On the other hand, infected children had higher TNF-alpha responses than uninfected children and significantly higher TNF-alpha to IL-10 ratios in response to FSL-1 and Pam3, ligands of TLR2/6 and TLR2/1 respectively. A similar trend was observed for the TLR4 ligand LPS while Poly(I:C) (Mda5/TLR3 ligand) did not induce substantial cytokine responses (24 h incubation). CONCLUSIONS: This pilot study shows that Schistosoma-infected children develop a more pro-inflammatory TLR2-mediated response in the face of a more anti-inflammatory adaptive immune response. This suggests that S. haematobium infection does not suppress the host's innate immune system in the context of single TLR ligation
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