有轶事证据表明拉沙病毒在体液中持续存在。我们的目的是调查从急性拉沙热恢复后的各种体液,描述精液中拉沙病毒RNA负荷的动态,并评估精液的传染性。
在这个前景中,纵向,队列研究我们收集了血浆,尿液,唾液,泪液,阴道液,和来自江户州Irrua专科教学医院的拉萨热幸存者的精液,尼日利亚。参与者的纳入标准是RT-PCR证实的拉萨热诊断和年龄18岁或以上。在出院时(0个月)和出院后0·5、1、3、6、9、12、18和24个月采集样品。这项研究的主要目的是定量描述病毒的持久性和清除率,并评估精液的感染性。使用实时RT-PCR检测拉沙病毒RNA。在细胞培养和免疫抑制小鼠中测试感染性。我们使用线性混合效应模型来分析精液中病毒持久性随时间变化的动态。
在2018年1月31日至2019年12月11日之间,有165名参与者参加了这项研究。其中159人符合分析条件(49名女性和110名男性)。在第0个月,血浆中检测到少量的拉沙病毒RNA(110名参与者中有49[45%]),尿液(37[34%]),唾液(5[5%]),泪液(十[9%]),和阴道液(33名女性参与者中有7名[21%])。在第3个月时从这些体液中清除病毒RNA。然而,44名男性参与者中有35名(80%)在0个月时精液中存在病毒RNA,中位周期阈值为26·5。拉沙病毒RNA在精液中保持可检测到直到12个月。生物统计学模型估计每月清除率为1·19log10病毒RNA拷贝,并预测50%的男性幸存者在出院后83天内在精液中保持拉沙病毒RNA阳性,10%在精液中保持阳性出院后193天。精液中病毒RNA持续存在3个月或更长时间与较高的病毒血症相关(p=0·006),更严重的疾病(p=0·0075),拉沙热急性期住院时间更长(p=0·0014)。感染性病毒从0至12个月之间收集的93个病毒RNA阳性精液样品中的48个(52%)分离。
从急性疾病中恢复后,拉沙病毒RNA在各种体液中脱落。精液中传染性病毒的持续存在意味着拉沙热的性传播风险。
德国联邦卫生部,德国研究基金会,莱布尼茨协会。
There is anecdotal evidence for Lassa virus persistence in body fluids. We aimed to investigate various body fluids after recovery from acute Lassa fever, describe the dynamics of Lassa virus RNA load in seminal fluid, and assess the infectivity of seminal fluid.
In this prospective, longitudinal, cohort
study we collected plasma, urine, saliva, lacrimal fluid, vaginal fluid, and seminal fluid from Lassa fever survivors from Irrua Specialist Teaching Hospital in Edo State, Nigeria. Inclusion criteria for participants were RT-PCR-confirmed Lassa fever diagnosis and age 18 years or older. Samples were taken at discharge from hospital (month 0) and at months 0·5, 1, 3, 6, 9, 12, 18, and 24 after discharge. The primary objective of this
study was to quantitatively describe virus persistence and clearance and assess the infectivity of seminal fluid. Lassa virus RNA was detected using real-time RT-PCR. Infectivity was tested in cell culture and immunosuppressed mice. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time.
Between Jan 31, 2018, and Dec 11, 2019, 165 participants were enrolled in the
study, of whom 159 were eligible for analysis (49 women and 110 men). Low amounts of Lassa virus RNA were detected at month 0 in plasma (49 [45%] of 110 participants), urine (37 [34%]), saliva (five [5%]), lacrimal fluid (ten [9%]), and vaginal fluid (seven [21%] of 33 female participants). Virus RNA was cleared from these body fluids by month 3. However, 35 (80%) of 44 male participants had viral RNA in seminal fluid at month 0 with a median cycle threshold of 26·5. Lassa virus RNA remained detectable up to month 12 in seminal fluid. Biostatistical modelling estimated a clearance rate of 1·19 log10 viral RNA copies per month and predicted that 50% of male survivors remain Lassa virus RNA-positive in seminal fluid for 83 days after hospital discharge and 10% remain positive in seminal fluid for 193 days after discharge. Viral RNA persistence in seminal fluid for 3 months or more was associated with higher viraemia (p=0·006), more severe disease (p=0·0075), and longer hospitalisation during the acute phase of Lassa fever (p=0·0014). Infectious virus was isolated from 48 (52%) of 93 virus RNA-positive seminal fluid samples collected between month 0 and 12.
Lassa virus RNA is shed in various body fluids after recovery from acute disease. The persistence of infectious virus in seminal fluid implies a risk of sexual transmission of Lassa fever.
German Federal Ministry of Health, German Research Foundation, Leibniz Association.