Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus

Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus
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DOI:
10.1016/s1473-3099(17)30111-1
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发表时间:
2017-06-01
影响因子:
56.3
通讯作者:
Tedder, Richard S.
Tedder, Richard S.
中科院分区:
医学1区
文献类型:
--
作者:
Glynn, Judith R.;Bower, Hilary;Tedder, Richard S.

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背景 埃博拉病毒无症状感染的频率尚不明确:先前的估计各不相同,且没有标准的检测方法。埃博拉病毒无症状感染可能有助于人群免疫,减少传播。如果无症状感染者具有传染性,这可以解释在没有已知接触的情况下埃博拉病毒病(EVD)的再次出现。 方法 我们在克里镇埃博拉治疗中心的幸存者以及塞拉利昂未受埃VD影响的社区对照组中验证了一种新的口腔液抗糖蛋白IgG捕获检测方法。然后,我们在对幸存者的家庭接触者进行的一项横断面研究中评估了埃博拉病毒抗体的血清阳性率。对所有家庭成员进行了访谈。阳性结果需要两次反应性检测,如有差异则进行第三次检测以解决。 结果 该检测方法的特异性为100%(95%置信区间98.9 - 100;339名对照中有339名检测为阴性),敏感性为95.9%(89.8 - 98.9;97名经聚合酶链反应确诊的幸存者中有93名检测为阳性)。在未被诊断患有埃VD的家庭接触者中,47.6%(481人中的229人)有高水平暴露(直接接触尸体、体液,或接触有腹泻、呕吐或出血症状的病例)。在这些接触者中,在其他家庭成员患埃VD时出现症状的接触者中有12.0%(95%置信区间6.1 - 20.4;92人中的11人),无症状的接触者中有2.6%(1.2 - 4.7;388人中的10人)检测为阳性。在无症状接触者中,血清阳性率与暴露水平呈弱相关。 解释 这种新的高度特异性和敏感性的检测方法表明,尽管暴露水平高,但埃博拉病毒无症状感染并不常见。较低的患病率表明无症状感染对埃博拉的群体免疫贡献很小,即使具有传染性,也只能解释很少的传播情况。
Background The frequency of asymptomatic infection with Ebola virus is unclear: previous estimates vary and there is no standard test. Asymptomatic infection with Ebola virus could contribute to population immunity, reducing spread. If people with asymptomatic infection are infectious it could explain re-emergences of Ebola virus disease (EVD) without known contact.Methods We validated a new oral fluid anti-glycoprotein IgG capture assay among survivors from Kerry Town Ebola Treatment Centre and controls from communities unaffected by EVD in Sierra Leone. We then assessed the seroprevalence of antibodies to Ebola virus in a cross-sectional study of household contacts of the survivors. All household members were interviewed. Two reactive tests were required for a positive result, with a third test to resolve any discrepancies.Findings The assay had a specificity of 100% (95% CI 98.9-100; 339 of 339 controls tested negative) and sensitivity of 95.9% (89.8-98.9; 93 of 97 PCR-confirmed survivors tested positive). Of household contacts not diagnosed with EVD, 47.6% (229 of 481) had high level exposure (direct contact with a corpse, body fluids, or a case with diarrhoea, vomiting, or bleeding). Among the contacts, 12.0% (95% CI 6.1-20.4; 11 of 92) with symptoms at the time other household members had EVD, and 2.6% (1.2-4.7; 10 of 388) with no symptoms tested positive. Among asymptomatic contacts, seropositivity was weakly correlated with exposure level.Interpretation This new highly specific and sensitive assay showed asymptomatic infection with Ebola virus was uncommon despite high exposure. The low prevalence suggests asymptomatic infection contributes little to herd immunity in Ebola, and even if infectious, would account for few transmissions.