家庭接触者中东呼吸综合征冠状病毒的传播。

Transmission of MERS-coronavirus in household contacts.

机构信息

From the Institute of Virology, University of Bonn Medical Center, Bonn (C.D., B.M., M.A.M., V.M.C., A.S.), and Euroimmun, Lübeck (E.L.) - both in Germany; Global Center for Mass Gatherings Medicine, Ministry of Health (M.A.-M., R.F.A., A.M. Assiri, A.I.Z., Z.A.M.), Prince Sultan Military Medical City (A.M. Albarrak), and Alfaisal University (Z.A.M.), Riyadh, Johns Hopkins Aramco Healthcare, Dhahran (J.A.A.-T.), and Regional Laboratory, Ministry of Health, Jeddah (R.H., H.M.) and Riyadh (W.H.) - all in Saudi Arabia; Indiana University School of Medicine, Indianapolis (J.A.A.-T.); the Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands (B.J.B.); and the Division of Infection and Immunity, University College London (UCL), and National Institute for Health Research Biomedical Research Centre, UCL Hospitals, London (A.I.Z.).

出版信息

N Engl J Med. 2014 Aug 28;371(9):828-35. doi: 10.1056/NEJMoa1405858.

DOI:10.1056/NEJMoa1405858

PMID:25162889

Abstract

BACKGROUND

Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission.

METHODS

We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing.

RESULTS

Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing.

CONCLUSIONS

The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.

摘要

背景

控制中东呼吸综合征冠状病毒（MERS-CoV）的策略取决于对人际传播率的了解，包括亚临床感染。缺乏血清学工具阻碍了对传播的针对性研究。

方法

我们研究了 26 例中东呼吸综合征冠状病毒感染的索引患者及其 280 名家庭接触者。从索引患者出现症状到接触患者最后一次采血的中位数时间为 17.5 天（范围，5 至 216；平均值，34.4）。根据来自喉咙拭子的独立 RNA 提取的两种逆转录酶聚合酶链反应（RT-PCR）检测的反应性，以及对 MERS-CoV S1 抗原的酶联免疫吸附试验反应性，支持对重组 S 蛋白免疫荧光的反应性，并证明中和超过 50%的感染病毒种子剂量的斑块减少中和试验，确定了二级传播的可能病例。

结果

在 26 例索引患者的 280 名家庭接触者中，有 12 例可能发生二级传播（4%；95%置信区间，2 至 7）。这些病例中有 7 例通过 RT-PCR 确定，均在索引患者出现症状后 14 天内获得的样本中确定，5 例通过血清学分析确定，均在索引患者出现症状后 13 天或更长时间获得的样本中确定。在 26 个集群中的 6 个集群（23%）中发生了可能的二次传播。在接触者中进行的样本采集时间在暴露后 13 天或更长时间的血清学结果与综合 RT-PCR 和血清学检测的总体研究结果相似。