Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection

Epidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus Infection
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DOI:
10.1128/jvi.01622-18
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发表时间:
2019-02-01
影响因子:
5.4
通讯作者:
Harris, Eva
Harris, Eva
中科院分区:
医学2区
文献类型:
--
作者:
Carrillo, Fausto Bustos;Collado, Damaris;Harris, Eva

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2013年底,基孔肯雅病毒(CHIKV)传入美洲,导致大范围流行。2015年,尼加拉瓜马那瓜发生了由亚洲基孔肯雅病毒(CHIKV)谱系引起的大规模疫情。文献综述通常指出,隐性CHIKV感染的比例从3%到28%不等。这项研究估计了有症状和无症状CHIKV感染的比率,并确定了感染的危险因素。2015年10月至11月,在一项指数群研究中,60名有症状的CHIKV感染儿童被登记为指示病例,并与236名家庭接触者一起进行前瞻性监测。在登记时、第14天或第35天采集样本,用实时反转录-聚合酶链式反应(RRT-PCR)、IgM捕获酶联免疫吸附试验(IgM-ELISA)和抑制ELISA检测登记前和登记后CHIKV感染情况。在236名家庭接触者中,55人(23%)经历过以前或最近感染,41人(17%)在登记时有活动性感染,21人(9%)经历过偶发感染。拥有车辆(多变量调整的风险比[ARR],1.58)增加了CHIKV感染的风险,而>=每周收集4次城市垃圾(ARR,0.38),并有外部自来水(ARR,0.52)保护免受CHIKV感染。在63例活动性和偶发性感染中,31例(49%[95%可信区间{CI},36%,62%])无症状,症状与无症状感染的比率为1:0.97(95%可信区间1:0.56,1:1.60)。尽管我们的估计超出了先前报道的3%至28%的范围,但贝叶斯和模拟分析表明,隐性CHIKV感染的比例与血统有关,而且与亚洲血统有关的隐性感染比与东部/中部/南非(ECSA)血统有关的更多。总体而言,这些数据大大提高了对基孔肯雅疫情的了解。基孔肯雅病毒(CHIKV)是对人类健康的一种未被充分研究的威胁。在2015年尼加拉瓜马那瓜的基孔肯雅疫情期间,我们估计了有症状和无症状的CHIKV感染的比率,这对于了解CHIKV的传播动力学和对公共卫生的影响很重要。这一指数分组研究确定和监测了感染风险人群,从而能够捕获无症状感染。我们估计,63名高危参与者中有31人(49%)有无症状的CHIKV感染,这明显超出了文献综述中报道的3%至28%的范围。然而,最近的血清阳性率研究,包括在同一环境下的两项大型儿科队列研究,也发现隐性感染的百分比在3%至28%的范围之外。根据系统的文献搜索,贝叶斯和模拟分析显示,在流行环境中,隐性感染的百分比因CHIKV系统发育谱系而异。我们的研究量化并首次提供了基孔肯雅病流行特征受CHIKV血统强烈影响的流行病学证据。
In late 2013, chikungunya virus (CHIKV) was introduced into the Americas, leading to widespread epidemics. A large epidemic caused by the Asian chikungunya virus (CHIKV) lineage occurred in Managua, Nicaragua, in 2015. Literature reviews commonly state that the proportion of inapparent CHIKV infections ranges from 3 to 28%. This study estimates the ratio of symptomatic to asymptomatic CHIKV infections and identifies risk factors of infection. In October to November 2015, 60 symptomatic CHIKV-infected children were enrolled as index cases and prospectively monitored, alongside 236 household contacts, in an index cluster study. Samples were collected upon enrollment and on day 14 or 35 and tested by real-time reverse transcription-PCR (rRT-PCR), IgM capture enzyme-linked immunosorbent assays (IgM-ELISAs), and inhibition ELISAs to detect pre- and postenrollment CHIKV infections. Of 236 household contacts, 55 (23%) had experienced previous or very recent infections, 41 (17%) had active infections at enrollment, and 21 (9%) experienced incident infections. Vehicle ownership (multivariable-adjusted risk ratio [aRR], 1.58) increased the risk of CHIKV infection, whereas >= 4 municipal trash collections/week (aRR, 0.38) and having externally piped water (aRR, 0.52) protected against CHIKV infection. Among 63 active and incident infections, 31 (49% [95% confidence interval {CI}, 36%, 62%]) were asymptomatic, yielding a ratio of symptomatic to asymptomatic infections of 1:0.97 (95% CI, 1:0.56, 1:1.60). Although our estimate is outside the 3% to 28% range reported previously, Bayesian and simulation analyses, informed by a systematic literature search, suggested that the proportion of inapparent CHIKV infections is lineage dependent and that more inapparent infections are associated with the Asian lineage than the East/Central/South African (ECSA) lineage. Overall, these data substantially improve knowledge regarding chikungunya epidemics.IMPORTANCE Chikungunya virus (CHIKV) is an understudied threat to human health. During the 2015 chikungunya epidemic in Managua, Nicaragua, we estimated the ratio of symptomatic to asymptomatic CHIKV infections, which is important for understanding transmission dynamics and the public health impact of CHIKV. This index cluster study identified and monitored persons at risk of infection, enabling capture of asymptomatic infections. We estimated that 31 (49%) of 63 at-risk participants had asymptomatic CHIKV infections, which is significantly outside the 3% to 28% range reported in literature reviews. However, recent seroprevalence studies, including two large pediatric cohort studies in the same setting, had also found percentages of inapparent infections outside the 3% to 28% range. Bayesian and simulation analyses, informed by a systematic literature search, revealed that the percentage of inapparent infections in epidemic settings varies by CHIKV phylogenetic lineage. Our study quantifies and provides the first epidemiological evidence that chikungunya epidemic characteristics are strongly influenced by CHIKV lineage.