107 research outputs found

    Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with West Nile Virus in Man

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    West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2′–5β€² oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The β€˜A’ allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total nβ€Š=β€Š501; ORβ€Š=β€Š1.6 [95% CI 1.2–2.0], Pβ€Š=β€Š0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the β€˜A’ allele (P<0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans

    Cord Blood Sample Screening for Evidence of Maternal Chagas Disease

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    Cord Blood Sample Screening for Evidence of Maternal Chagas Disease

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    Seroconverting blood donors as a resource for characterising and optimising recent infection testing algorithms for incidence estimation

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    CITATION: Kassanjee, R. et al. 2011. Seroconverting blood donors as a resource for characterising and optimising recent infection testing algorithms for incidence estimation. PLoS ONE, 6(6): e20027, doi:10.1371/journal.pone.0020027.The original publication is available at http://journals.plos.org/plosoneIntroduction: Biomarker-based cross-sectional incidence estimation requires a Recent Infection Testing Algorithm (RITA) with an adequately large mean recency duration, to achieve reasonable survey counts, and a low false-recent rate, to minimise exposure to further bias and imprecision. Estimating these characteristics requires specimens from individuals with well-known seroconversion dates or confirmed long-standing infection. Specimens with well-known seroconversion dates are typically rare and precious, presenting a bottleneck in the development of RITAs. Methods: The mean recency duration and a 'false-recent rate' are estimated from data on seroconverting blood donors. Within an idealised model for the dynamics of false-recent results, blood donor specimens were used to characterise RITAs by a new method that maximises the likelihood of cohort-level recency classifications, rather than modelling individual sojourn times in recency. Results: For a range of assumptions about the false-recent results (0% to 20% of biomarker response curves failing to reach the threshold distinguishing test-recent and test-non-recent infection), the mean recency duration of the Vironostika-LS ranged from 154 (95% CI: 96-231) to 274 (95% CI: 234-313) days in the South African donor population (n = 282), and from 145 (95% CI: 67-226) to 252 (95% CI: 194-308) days in the American donor population (n = 106). The significance of gender and clade on performance was rejected (p-value = 10%), and utility in incidence estimation appeared comparable to that of a BED-like RITA. Assessment of the Vitros-LS (n = 108) suggested potentially high false-recent rates. Discussion: The new method facilitates RITA characterisation using widely available specimens that were previously overlooked, at the cost of possible artefacts. While accuracy and precision are insufficient to provide estimates suitable for incidence surveillance, a low-cost approach for preliminary assessments of new RITAs has been demonstrated. The Vironostika-LS and Vitros-LS warrant further analysis to provide greater precision of estimates. Β© 2011 Kassanjee et al.Publisher's versio

    Patients’ attitudes to the summary care record and HealthSpace: qualitative study

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    Objective To document the views of patients and the public towards the summary care record (SCR, a centrally stored medical record drawn from the general practice record) and HealthSpace (a personal health organiser accessible through the internet from which people can view their SCR), with a particular focus on those with low health literacy, potentially stigmatising conditions, or difficulties accessing health care
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