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住院患者中诺如病毒长期排毒和患病的高流行率:体内分子进化模型

High prevalence of prolonged norovirus shedding and illness among hospitalized patients: a model for in vivo molecular evolution.

作者信息

Siebenga J Joukje, Beersma Mathias F C, Vennema Harry, van Biezen Paula, Hartwig Nico J, Koopmans Marion

机构信息

National Institute for Public Health and the Environment, The Netherlands.

出版信息

J Infect Dis. 2008 Oct 1;198(7):994-1001. doi: 10.1086/591627.

DOI:10.1086/591627
PMID:18774885
Abstract

During a 2-year survey in an academic hospital, 8 (8.4%) of all norovirus (NoV)-positive patients showed prolonged norovirus illness and shedding (duration, 21-182 days). All patients had underlying illnesses, resulting in some level of immunodeficiency in 5. Four patients were admitted to the hospital with gastroenteritis, 2 acquired norovirus while hospitalized, and 2 were outpatients. Genotypes GII.4 and GIIb-GII.3 were found. Reinfection occurred in 3 patients. Full capsid sequences were determined from strains detected in sequentially collected stool specimens to study evolution. The greatest number of amino acid mutations in a given patient was 11; they were detected in NoV isolates recovered over a 119-day period and were mapped to positions at or near putative antigenic sites. In the patient with most severe immune dysfunction, only 5 amino acids mutated over 182 days, suggesting immune-driven selection. The severe impact on patients and hospitals and the potential role of prolonged shedders as a reservoir for viral antigenic variants lead us to stress the importance of confinement of outbreaks of NoV infection that occur in hospitals.

摘要

在一家学术医院进行的为期2年的调查中,所有诺如病毒(NoV)阳性患者中有8例(8.4%)出现诺如病毒感染病程延长和病毒排泄(持续时间为21 - 182天)。所有患者都有基础疾病,其中5例存在一定程度的免疫缺陷。4例患者因胃肠炎入院,2例在住院期间感染诺如病毒,2例为门诊患者。检测到GII.4和GIIb - GII.3基因型。3例患者发生了再次感染。从连续采集的粪便标本中检测到的毒株确定了完整衣壳序列,以研究病毒进化。在某一患者中检测到的氨基酸突变数量最多为11个;这些突变在119天内从诺如病毒分离株中检测到,并定位在假定抗原位点或其附近的位置。在免疫功能障碍最严重的患者中,182天内仅5个氨基酸发生了突变,提示存在免疫驱动的选择。诺如病毒感染对患者和医院造成的严重影响以及长期排毒者作为病毒抗原变异体储存库的潜在作用,促使我们强调限制医院内诺如病毒感染暴发的重要性。

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