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在约旦南部的牲畜养殖户家庭中,MERS-CoV 暴露和 MERS-CoV ELISA 血清阳性的危险因素:一项基于人群的横断面研究。

MERS-CoV exposure and risk factors for MERS-CoV ELISA seropositivity among members of livestock-owning households in southern Jordan: a population based cross-sectional study.

机构信息

Department of Pathobiology and Population Sciences, The Royal Veterinary College, London, UK.

Department of Pathobiology and Population Sciences, The Royal Veterinary College, London, UK.

出版信息

Lancet Microbe. 2024 Sep;5(9):100866. doi: 10.1016/S2666-5247(24)00082-X. Epub 2024 Jul 22.

DOI:10.1016/S2666-5247(24)00082-X
PMID:39053480
Abstract

BACKGROUND

Although dromedary camels (Camelus dromedarius) are known to be the host reservoir for MERS-CoV, the virus causing Middle East respiratory syndrome (MERS), zoonotic transmission pathways and camel subpopulations posing highest transmission risk are poorly understood. Extensively managed herds, ubiquitous across the Arabian Peninsula, present a major potential source of primary infection. In this study we aimed to address key knowledge gaps regarding MERS epidemiology among high-risk communities associated with such herds, which is essential information for effective control strategies.

METHODS

We did a cross-sectional study between Sept 27, 2017, and Oct 11, 2018, among members of livestock-owning households in southern Jordan (Aqaba East, Aqaba West, Ma'an East, and Ma'an West regions), with random selection of households (house and tent dwellings) from Ministry of Agriculture lists via computer-generated randomisation lists. Household visits were done, with questionnaires administered to household members regarding potential risk factors for MERS-CoV exposure in the past 6 months and blood samples and nasal and oral swabs collected, alongside physical examination data including blood pressure and blood glucose. Children younger than 5 years and individuals without capacity to provide informed consent were excluded. Serum was tested for IgG antibodies to MERS-CoV spike protein (S1 subunit) and nucleocapsid (N) protein with in-house indirect ELISAs, and viral RNA was detected in nasal and oral samples by RT-PCR. The primary outcome was evidence of MERS-CoV exposure (ascertained by seropositive status on S1 or N ELISAs, or a positive swab sample on RT-PCR); secondary outcomes were potential associations between possible risk factors and seropositive status. RT-PCR data were to be presented descriptively. Seroprevalence estimates were obtained at the individual and household levels, and associations between hypothetical risk factors and seropositive status were assessed with use of mixed-effects logistic regression.

FINDINGS

We sampled 879 household members (median age 27 years [IQR 16-44]; 471 [54%] males and 408 [46%] females) from 204 households. 72 (8%) household members were seropositive on S1 ELISA (n=25, 3%) or N ELISA (n=52, 6%). No positive nasal or oral swab samples were identified on RT-PCR. Within-household clustering was identified for seropositivity on S1 ELISA (intraclass correlation coefficient 0·88 [0·35-0·96]) but not N ELISA (0·00 [0·00-0·27]). On multivariable analysis, S1 ELISA seropositivity was associated with frequently (≥weekly) interacting with young (age <1 year) camels (adjusted odds ratio [OR] 3·85 [95% CI 1·41-11·61], p=0·011), with frequent kissing and petting (OR 4·56 [1·55-15·42], p=0·0074), and frequent feeding and watering (OR 4·97 [1·80-15·29], p=0·0027) of young camels identified as risk activities. Attending camel races (OR 3·73 [1·11-12·47], p=0·029), frequently feeding and watering camels of any age (OR 3·18 [1·12-10·84], p=0·040), and elevated blood glucose (>150 mg/dL; OR 4·59 [1·23-18·36], p=0·021) were also associated with S1 ELISA seropositivity. Among individuals without history of camel contact, S1 ELISA seropositivity was associated with sharing a household with an S1 ELISA-positive household member (OR 8·92 [1·06-92·99], p=0·044), and with sharing a household with an S1 ELISA-positive household member with history of camel contact (OR 24·74 [2·72-306·14], p=0·0050). N ELISA seropositivity was associated with age (categorical, p=0·0069), a household owning a young camel (age <18 months; OR 1·98 [1·02-4·09], p=0·043), and frequently feeding and watering camels of any age (OR 1·98 [1·09-3·69]; p=0·025).

INTERPRETATION

The study findings highlight the importance of effective MERS-CoV surveillance and control strategies among camel-owning communities in Jordan and the Arabian Peninsula. Juvenile dromedaries pose increased risk for zoonotic MERS-CoV transmission and should be prioritised for vaccination once such vaccines become available. Among high-risk communities, vaccination strategies should prioritise camel-owning households, particularly individuals engaged in camel husbandry or racing, and household members who are older or diabetic, with evidence to suggest secondary within-household transmission.

FUNDING

UK Medical Research Council and US National Institute of Allergy and Infectious Diseases.

摘要

背景

虽然单峰骆驼(Camelus dromedarius)已知是中东呼吸综合征冠状病毒(MERS-CoV)的宿主库,MERS-CoV 是引发中东呼吸综合征(MERS)的病毒,但动物向人类传播的途径以及具有最高传播风险的骆驼亚群仍知之甚少。广泛管理的畜群,遍及阿拉伯半岛,是原发性感染的主要潜在传染源。在这项研究中,我们旨在解决与这些畜群相关的高危社区中与 MERS 流行病学相关的关键知识空白,这是有效控制策略的重要信息。

方法

我们于 2017 年 9 月 27 日至 2018 年 10 月 11 日在约旦南部(Aqaba East、Aqaba West、Ma'an East 和 Ma'an West 地区)的牲畜饲养家庭中进行了一项横断面研究,通过计算机生成的随机列表从农业部名单中随机选择家庭(房屋和帐篷居民)。对家庭进行了家访,向家庭成员询问了过去 6 个月中可能接触 MERS-CoV 的潜在危险因素,并采集了血清样本和鼻拭子和口腔拭子,同时进行了包括血压和血糖在内的体检数据。不包括 5 岁以下的儿童和没有能力提供知情同意的个人。使用内部间接 ELISA 检测血清中 MERS-CoV 刺突蛋白(S1 亚单位)和核衣壳(N)蛋白的 IgG 抗体,通过 RT-PCR 检测鼻拭子和口腔拭子中的病毒 RNA。主要结局是确定 MERS-CoV 暴露的证据(通过 S1 或 N ELISA 血清学阳性或 RT-PCR 阳性拭子样本确定);次要结局是潜在危险因素与血清学阳性状态之间的可能关联。将呈现 RT-PCR 数据的描述性。在个体和家庭层面获得血清学阳性率估计值,并使用混合效应逻辑回归评估假设风险因素与血清学阳性状态之间的关联。

结果

我们从 204 户家庭中抽取了 879 名家庭成员(中位数年龄 27 岁[IQR 16-44];471 名男性[54%]和 408 名女性[46%])。72 名家庭成员在 S1 ELISA(n=25,3%)或 N ELISA(n=52,6%)上呈血清学阳性。RT-PCR 未检测到鼻或口腔拭子阳性样本。在 S1 ELISA 上的血清学阳性存在家庭内聚集(内相关系数 0·88[0·35-0·96]),但 N ELISA 不存在(0·00[0·00-0·27])。在多变量分析中,S1 ELISA 血清学阳性与频繁(每周≥1 次)与幼龄(<1 岁)骆驼互动(调整优势比[OR]3·85[95%CI 1·41-11·61],p=0·011)、频繁亲吻和抚摸(OR 4·56[1·55-15·42],p=0·0074)和频繁喂食和饮水(OR 4·97[1·80-15·29],p=0·0027)有关,这些活动被认为是幼龄骆驼的风险活动。参加骆驼比赛(OR 3·73[1·11-12·47],p=0·029)、频繁喂食和饮水任何年龄的骆驼(OR 3·18[1·12-10·84],p=0·040)和血糖升高(>150mg/dL;OR 4·59[1·23-18·36],p=0·021)也与 S1 ELISA 血清学阳性相关。在没有骆驼接触史的个体中,S1 ELISA 血清学阳性与与 S1 ELISA 阳性家庭成员同住(OR 8·92[1·06-92·99],p=0·044)以及与有骆驼接触史的 S1 ELISA 阳性家庭成员同住(OR 24·74[2·72-306·14],p=0·0050)有关。N ELISA 血清学阳性与年龄(分类,p=0·0069)、家庭拥有幼龄骆驼(<18 个月;OR 1·98[1·02-4·09],p=0·043)和频繁喂食和饮水任何年龄的骆驼(OR 1·98[1·09-3·69];p=0·025)有关。

解释

研究结果强调了在约旦和阿拉伯半岛的骆驼饲养社区中实施有效的 MERS-CoV 监测和控制策略的重要性。幼年单峰骆驼具有更高的人畜共患 MERS-CoV 传播风险,一旦此类疫苗问世,应优先为其接种疫苗。在高危社区中,疫苗接种策略应优先考虑骆驼饲养家庭,特别是从事骆驼养殖或比赛的家庭,以及年龄较大或患有糖尿病的家庭成员,有证据表明存在二级家庭内传播。

资金

英国医学研究理事会和美国国立过敏和传染病研究所。

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