Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
Vitalant Research Institute, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
Lancet Infect Dis. 2020 Dec;20(12):1446-1456. doi: 10.1016/S1473-3099(19)30708-X. Epub 2020 Jul 13.
Characterisation of the dynamics of Zika virus persistence following acute infection is needed to inform blood donor and diagnostic testing policies and understand the natural history of Zika virus infection. We aimed to characterise the natural history, persistence, and clinical outcomes of Zika virus infection through a prospective study in initially asymptomatic Zika virus RNA-positive blood donors.
Zika virus-infected blood donors identified through Zika virus nucleic acid amplification test (NAAT) screening at three blood collection organisations in the USA were enrolled into a 1-year follow-up study, with blood and body fluid samples and detailed symptom data collected at up to seven visits. All samples were tested for Zika virus RNA by real-time PCR (rtPCR); follow-up plasma, whole blood, and urine were also tested by replicate NAAT. Plasma was tested for flavivirus-specific IgM and IgG by ELISA. Zika virus RNA persistence for each assay or sample type and plasma antibody persistence from estimated date of plasma NAAT-detectable infection were calculated from follow-up data using survival statistical methods.
Between July 6, 2016 and March 7, 2017, we enrolled 53 participants. From the estimated date of plasma NAAT-detectable infection, Zika virus RNA was detectable in plasma for 9·9 days (95% CI 8·1-12·0), in red blood cells for 95·4 days (62·8-129·1), and in whole blood for 73·5 days (39·8-107·5). Replicate NAATs (one or more of eight replicates positive) extended detection of Zika virus RNA in plasma to 34·8 days (19·9-56·2) and in whole blood (at least one of two tests positive) to 104·8 days (76·7-129·9). Urine was rtPCR reactive up to 14·5 days (10·5-20·3) and saliva up to 26·4 days (19·7-38·7). Zika virus IgM persisted for 237·7 days (128·7-459·5) from estimated time since plasma NAAT-detectable infection. Zika virus RNA fell below detectable limits more rapidly in the saliva of participants with pre-existing dengue virus IgG than in those without. Of 25 donors identified pre-seroconversion with symptom data at the first or second study visit, 16 (64%) developed multiple Zika virus-related symptoms after asymptomatic index donations, compared with nine (36%) of 25 donors detected after seroconversion.
Determination of viral marker persistence is enhanced by follow-up of blood donors who are pre-symptomatic or asymptomatic, Zika virus RNA-positive, and antibody negative. Zika virus RNA persists in red blood cells for several months following clearance from plasma and body fluids, and replicate, highly sensitive NAATs extend RNA detection in all compartments. Whole blood testing can extend detection of acute infection for diagnostics and monitoring of pregnant women, sexual partners, and travellers.
National Heart, Lung, and Blood Institute, Biomedical Advanced Research and Development Authority.
为了制定血液捐献者和诊断检测政策，并了解寨卡病毒感染的自然史，需要对急性感染后寨卡病毒持续存在的情况进行描述。本研究旨在通过对最初无症状的寨卡病毒 RNA 阳性献血者进行前瞻性研究，描述寨卡病毒感染的自然史、持续时间和临床结局。
在美国的三个血液采集机构通过寨卡病毒核酸扩增检测（NAAT）筛查发现的寨卡病毒感染献血者被纳入一项为期 1 年的随访研究，最多进行 7 次随访采集血液和体液样本，并详细记录症状数据。所有样本均采用实时 PCR（rtPCR）检测寨卡病毒 RNA；后续的血浆、全血和尿液样本还通过重复 NAAT 进行检测。采用 ELISA 检测血浆中的黄病毒特异性 IgM 和 IgG。利用生存统计方法，根据随访数据计算每种检测或样本类型的寨卡病毒 RNA 持续时间，以及从估计的血浆 NAAT 检测到感染的时间开始计算血浆抗体的持续时间。
在 2016 年 7 月 6 日至 2017 年 3 月 7 日期间，我们共招募了 53 名参与者。从估计的血浆 NAAT 检测到感染的时间开始，寨卡病毒 RNA 可在血浆中检测到 9.9 天（95%CI 8.1-12.0），在红细胞中检测到 95.4 天（62.8-129.1），在全血中检测到 73.5 天（39.8-107.5）。重复的 NAAT（一个或多个样本为 8 个重复中的阳性）将血浆中寨卡病毒 RNA 的检测时间延长至 34.8 天（19.9-56.2），将全血（至少有两个检测样本阳性）的检测时间延长至 104.8 天（76.7-129.9）。尿液的 rtPCR 反应时间最长可达 14.5 天（10.5-20.3），唾液最长可达 26.4 天（19.7-38.7）。从估计的血浆 NAAT 检测到感染的时间开始，寨卡病毒 IgM 持续存在 237.7 天（128.7-459.5）。在唾液中，与没有登革热病毒 IgG 的参与者相比，有预先存在的登革热病毒 IgG 的参与者寨卡病毒 RNA 更快降至检测下限。在首次或第二次研究访问时有症状数据的 25 名预先血清学转化的献血者中，16 名（64%）在无症状的索引献血后出现了多种寨卡病毒相关症状，而在 25 名在血清学转化后检测到的献血者中，有 9 名（36%）出现了这种情况。
对出现症状或无症状、寨卡病毒 RNA 阳性且抗体阴性的献血者进行随访，有助于提高病毒标志物持续存在的确定。寨卡病毒 RNA 在从血浆和体液中清除后，在红细胞中持续存在数月，而高灵敏度的重复 NAAT 则可以延长所有标本的 RNA 检测时间。全血检测可延长急性感染的检测时间，用于诊断和监测孕妇、性伴侣和旅行者。
美国国立心肺血液研究所，生物医学高级研究与发展局。
