31 research outputs found

    Conserved Protective Mechanisms in Radiation and Genetically Attenuated uis3(-) and uis4(-) Plasmodium Sporozoites

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    Immunization with radiation attenuated Plasmodium sporozoites (RAS) elicits sterile protective immunity against sporozoite challenge in murine models and in humans. Similarly to RAS, the genetically attenuated sporozoites (GAPs) named uis3(-), uis4(-) and P36p(-) have arrested growth during the liver stage development, and generate a powerful protective immune response in mice. We compared the protective mechanisms in P. yoelii RAS, uis3(-) and uis4(-) in BALB/c mice. In RAS and GAPs, sterile immunity is only achieved after one or more booster injections. There were no differences in the immune responses to the circumsporozoite protein (CSP) generated by RAS and GAPs. To evaluate the role of non-CSP T-cell antigens we immunized antibody deficient, CSP-transgenic BALB/c mice, that are T cell tolerant to CSP, with P. yoelii RAS or with uis3(-) or uis4(-) GAPs, and challenged them with wild type sporozoites. In every instance the parasite liver stage burden was approximately 3 logs higher in antibody deficient CSP transgenic mice as compared to antibody deficient mice alone. We conclude that CSP is a powerful protective antigen in both RAS and GAPs viz., uis3(-) and uis4(-) and that the protective mechanisms are similar independently of the method of sporozoite attenuation

    Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events

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    <p>Abstract</p> <p>Background</p> <p><it>Plasmodium </it>sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of <it>Plasmodium </it>parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.</p> <p>Results</p> <p>To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of <it>P. berghei</it>-infected hepatoma cells. The data analysis shows differential expression patterns for 1064 host genes starting at 6 h and up to 24 h post infection, with the largest proportion correlating specifically with the early stages of the infection process. A considerable proportion of those genes were also found to be modulated in liver cells collected from <it>P. yoelii-</it>infected mice 24 and 40 h after infection, strengthening the data obtained with the <it>in vitro </it>model and highlighting genes and pathways involved in the host response to rodent <it>Plasmodium </it>parasites.</p> <p>Conclusion</p> <p>Our data reveal that host cell infection by <it>Plasmodium </it>sporozoites leads to a coordinated and sequential set of biological events, ranging from the initial stage of stress response up to the engagement of host metabolic processes and the maintenance of cell viability throughout infection.</p

    Assessment and improvement of the Plasmodium yoelii yoelii genome annotation through comparative analysis

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    Motivation: The sequencing of the Plasmodium yoelii genome, a model rodent malaria parasite, has greatly facilitated research for the development of new drug and vaccine candidates against malaria. Unfortunately, only preliminary gene models were annotated on the partially sequenced genome, mostly by in silico gene prediction, and there has been no major improvement of the annotation since 2002

    Delivery of maternal health care in Indigenous primary care services: baseline data for an ongoing quality improvement initiative

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    Extent: 10p.BACKGROUND: Australia's Aboriginal and Torres Strait Islander (Indigenous) populations have disproportionately high rates of adverse perinatal outcomes relative to other Australians. Poorer access to good quality maternal health care is a key driver of this disparity. The aim of this study was to describe patterns of delivery of maternity care and service gaps in primary care services in Australian Indigenous communities. METHODS: We undertook a cross-sectional baseline audit for a quality improvement intervention. Medical records of 535 women from 34 Indigenous community health centres in five regions (Top End of Northern Territory 13, Central Australia 2, Far West New South Wales 6, Western Australia 9, and North Queensland 4) were audited. The main outcome measures included: adherence to recommended protocols and procedures in the antenatal and postnatal periods including: clinical, laboratory and ultrasound investigations; screening for gestational diabetes and Group B Streptococcus; brief intervention/advice on health-related behaviours and risks; and follow up of identified health problems. RESULTS: The proportion of women presenting for their first antenatal visit in the first trimester ranged from 34% to 49% between regions; consequently, documentation of care early in pregnancy was poor. Overall, documentation of routine antenatal investigations and brief interventions/advice regarding health behaviours varied, and generally indicated that these services were underutilised. For example, 46% of known smokers received smoking cessation advice/counselling; 52% of all women received antenatal education and 51% had investigation for gestational diabetes. Overall, there was relatively good documentation of follow up of identified problems related to hypertension or diabetes, with over 70% of identified women being referred to a GP/Obstetrician. CONCLUSION: Participating services had both strengths and weaknesses in the delivery of maternal health care. Increasing access to evidence-based screening and health information (most notably around smoking cessation) were consistently identified as opportunities for improvement across services.Alice R. Rumbold, Ross S. Bailie, Damin Si, Michelle C. Dowden, Catherine M. Kennedy, Rhonda J. Cox, Lynette O’Donoghue, Helen E. Liddle, Ru K. Kwedza, Sandra C. Thompson, Hugh P. Burke, Alex D. H. Brown, Tarun Weeramanthri and Christine M. Connor

    Entrepreneurs, Firms and Global Wealth Since 1850

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    CS is a powerful protective T cell antigen in both <i>P. yoelli</i> RAS and <i>uis3(-)</i>, <i>uis4(-)</i> GAPs.

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    <p>BALB/c CS-Tg JhT (−/−) mice were primed and boosted with 1×10<sup>5 </sup><i>P. yoelli</i> RAS or with <i>uis3(-)</i> or with <i>uis4(-)</i> GAPs. All immunized mice were challenged with 1×10<sup>4</sup> wild type infectious sporozoites and infected livers were isolated 42 hours post infection (A) Liver stage burden in indicated groups of immunized mice were assessed by measuring the parasite specific 18S rRNA copy numbers by q-RT PCR. The results are expressed as mean±s.d of 18S rRNA copy numbers from 5 mice per group. (B) IFN-gamma ELISPOT assay to quantify CS specific T cells from indicated groups of JhT (−/−) immunized mice. Results are expressed as mean±s.d of CS-specific CD8+ T cells obtained from 5 immunized mice per group.</p

    Protective immune responses are conserved in <i>P. yoelli</i> RAS and <i>uis3(-)</i>, <i>uis4(-)</i> GAPs.

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    <p>Comparative analysis of protective immune response in BALB/cAnN mice following priming and boosting with 1×10<sup>5 </sup><i>P. yoelli</i> RAS or with <i>uis3(-)</i> or with <i>uis4(-)</i> GAPs. All mice were challenged with 1×10<sup>4</sup> wild type infectious sporozoites and infected livers were isolated 42 hours post infection. (A) Liver stage burden in indicated groups of immunized mice were assessed by measuring the parasite specific 18S rRNA copy numbers by q-RT PCR. (B) CS-specific antibody response in indicated groups of immunized mice. (C) Liver stage burden in mice that received wild type <i>P. yoelli</i> sporozoites following neutralization with sera obtained from naïve or indicated groups of immunized mice. (D) IFN-gamma ELISPOT assay to quantify CS specific T cells from indicated groups of immunized mice. Results are expressed as mean±s.d of CS-specific CD8+ T cells obtained from 5 immunised mice per group. In (A) and (C) results are expressed as mean±s.d of 18S r RNA copy numbers from 5 mice per group.</p
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