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State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus. 基于微生物组的生物标记物的现状与未来:多学科德尔菲共识。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-04 DOI: 10.1016/j.lanmic.2024.07.011
Julie Rodriguez, Zahra Hassani, Carolina Alves Costa Silva, Fay Betsou, Federica Carraturo, Alessio Fasano, Mads Israelsen, Anandhi Iyappan, Aleksander Krag, Amira Metwaly, Robert Schierwagen, Jonel Trebicka, Hub Zwart, Joel Doré, Magali Cordaillat-Simmons, Celine Druart

Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.

虽然微生物组特征已在各种情况下(即非传染性疾病的发病机理和治疗反应)得到确定,但目前临床实践中还没有使用合格的基于微生物组的生物标志物。人类微生物组行动联盟发起了一项德尔菲调查,以就开发合格的基于微生物组的生物标记物的需求、挑战和限制达成共识。调查问卷由科学委员会通过文献查阅和专家访谈制定。为确保调查结果的广泛适用性,邀请了 307 位专家参与;其中 114 位专家对第一轮调查做出了回应,93 位专家完成了第二轮和最后一轮调查。调查显示,专家们对基于微生物的生物标记物在若干适应症或病理方面的潜力充满信心。缺乏经过验证的分析方法似乎是阻碍这些生物标志物鉴定的主要因素。调查还显示,只有开发出配套的、经过验证的、解释简单的分子检测方法,才有可能在临床上应用这些生物标记物。该倡议为设计和实施公私合作项目奠定了基础,以克服挑战并促进基于微生物组的生物标记物的临床应用。
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引用次数: 0
First self-test for hepatitis C virus. 首次丙型肝炎病毒自我检测。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-03 DOI: 10.1016/j.lanmic.2024.100979
Priya Venkatesan
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引用次数: 0
Human cases of avian influenza A(H5) in the USA. 美国人感染甲型 H5 禽流感的病例。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-03 DOI: 10.1016/j.lanmic.2024.100978
Priya Venkatesan
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引用次数: 0
Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in the Democratic Republic of the Congo: a case report study. 刚果民主共和国两名埃博拉病毒病幸存者的致命脑膜脑炎与埃博拉病毒持续存在有关:病例报告研究。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-02 DOI: 10.1016/S2666-5247(24)00137-X
Daniel Mukadi-Bamuleka, François Edidi-Atani, Maria E Morales-Betoulle, Anaïs Legand, Antoine Nkuba-Ndaye, Junior Bulabula-Penge, Placide Mbala-Kingebeni, Ian Crozier, Fabrice Mambu-Mbika, Shannon Whitmer, Olivier Tshiani Mbaya, Lisa E Hensley, Richard Kitenge-Omasumbu, Richard Davey, Sabue Mulangu, Peter N Fonjungo, Michael R Wiley, John D Klena, Martine Peeters, Eric Delaporte, Johan van Griensven, Kevin K Ariën, Catherine Pratt, Joel M Montgomery, Pierre Formenty, Jean-Jacques Muyembe-Tamfum, Steve Ahuka-Mundeke

Background: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence.

Methods: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques.

Findings: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2.

Interpretation: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence.

Funding: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, French National Research Institute for Development, and WHO.

背景:在 2018-20 年刚果民主共和国爆发埃博拉病毒病期间,数以千计的患者接受了前所未有的疫苗接种、单克隆抗体(mAb)治疗或两者兼用,从而产生了大量幸存者。我们旨在报告两名曾接种疫苗并接受过 mAb 治疗的刚果民主共和国埃博拉病毒病幸存者的临床、病毒学、病毒基因组学和免疫学特征:在本病例报告研究中,我们描述了两名埃博拉病毒复发患者的表现、管理和后续调查情况,这两名患者随后患上了致命的脑膜脑炎。我们从流行病学数据库、埃博拉治疗单位、幸存者计划数据库、实验室数据集和医院记录中获取数据。根据 2018-20 年刚果民主共和国疫情爆发期间制定的国家协议,在埃博拉病毒病第一次和第二次发作期间收集了两人的血液、血浆和脑脊液样本,并通过分子(定量 RT-PCR 和下一代测序)和血清学(IgG 和 IgM ELISA 和 Luminex 检测)技术进行了分析:从第一次埃博拉病毒发作结束到第二次发作开始的总时间,1 号患者为 342 天,2 号患者为 137 天。在第二次发病期间,两名患者的血液和脑脊液样本中都检测到了埃博拉病毒 RNA。从这次复发的脑脊液样本中提取的完整基因组与从初次感染时采集的血液样本中测序的基因组显示出系统发育相关性,证实了埃博拉病毒在宿主体内的持续存在。血清学分析显示,患者1出现了抗原特异性体液反应,具有典型的IgM和IgG动力学,但患者2缺乏内源性适应性免疫反应:我们报告了首两例与埃博拉病毒持续存在相关的致命脑膜脑炎病例,这两例病例是在刚果民主共和国接受过疫苗接种和基于 mAb 治疗的埃博拉病毒病幸存者。我们的研究结果突显了对幸存者进行长期监测的重要性,包括持续的临床、病毒学和免疫学分析,以及迫切需要新型治疗策略来预防和减轻埃博拉病毒持续存在对个人和公共卫生造成的后果:资金来源:刚果民主共和国卫生部、国家生物医学研究所、传染病快速反应储备基金、美国疾病控制和预防中心、法国国家发展研究院和世界卫生组织。
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引用次数: 0
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study 新加坡第六个念珠菌支系的检测和特征:基因组和表型研究。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/S2666-5247(24)00101-0
<div><h3>Background</h3><p>The emerging fungal pathogen <em>Candida auris</em> poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual <em>C auris</em> isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known <em>C auris</em> clades (I–V).</p></div><div><h3>Methods</h3><p>In this genotypic and phenotypic study, we characterised three <em>C auris</em> clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these <em>C auris</em> isolates. The complete genomes were compared with representative genomes of all known <em>C auris</em> clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available.</p></div><div><h3>Findings</h3><p>The three investigated isolates were separated by at least 37 000 SNPs (range 37 000–236 900) from all existing <em>C auris</em> clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of <em>C auris,</em> clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade.</p></div><div><h3>Interpretation</h3><p>The discovery of a new <em>C auris</em> clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of <em>C auris</em>, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of <em>C auris</em> infections.</p></div><div><h3>Funding</h3><p>Duke-NUS Academic Medical Center Nurturing Cl
背景:新出现的真菌病原体念珠菌对全球公共卫生构成严重威胁,因为它分布于世界各地,具有耐多药、高传播性、易导致疾病爆发和高死亡率等特点。我们的目的是描述在新加坡检测到的三种不同寻常的念珠菌分离株的特征,并确定它们是否构成了一个新的支系,有别于之前已知的所有念珠菌支系(I-V):在这项基因型和表型研究中,我们对从新加坡一家大型三甲医院的无流行病学关联的住院病人身上培养出的三株银环蛇临床分离株进行了鉴定。指数分离株于 2023 年 4 月发现。我们对这些 C auris 分离物进行了全基因组测序(WGS)并获得了杂交组合。我们将完整的基因组与所有已知 C auris 支系的代表性基因组进行了比较。为了提供全球背景,美国国家生物技术信息中心(NCBI)数据库中的 3651 个国际 WGS 数据被纳入了高分辨率单核苷酸多态性(SNP)分析。我们进行了抗真菌药敏试验,并从三个被调查分离物的 WGS 数据中确定了抗真菌药敏基因、交配型基因座和染色体重排的特征。我们进一步采用贝叶斯逻辑回归模型将分离物归入已知支系,并模拟自动检测属于新支系的分离物,因为它们的 WGS 数据已经可用:所调查的三个分离株与所有现有的肛管癣菌支系之间至少有 37 000 个 SNPs(范围为 37 000-236 900)的差异。这些分离株与其最接近的支系 IV 亲属相比,具有相反的交配型等位基因和不同的染色体重排。这些分离物对所有测试过的抗真菌药物都敏感。因此,我们认为这些分离物代表了 C auris 的一个新支系,即支系 VI。此外,通过 NCBI Sequence Read Archive 获取的来自孟加拉国的独立 WGS 数据集也被发现属于这个新支系。作为概念验证,我们的贝叶斯逻辑回归模型能够将这些离群基因组标记为一个潜在的新支系:在新加坡和孟加拉国的印多马克拉亚区发现了一个新的C auris支系,该支系与最常见于南美洲的支系IV成员关系密切,这突显了C auris未知的遗传多样性和起源,尤其是在资源匮乏的地区。在临床环境中积极开展监测,同时采用有效的测序策略和下游分析,对于鉴定新型菌株、追踪传播情况和遏制 C auris 感染的不良临床影响至关重要:杜克大学-新加坡国立大学学术医学中心临床研究人员培养计划(Nurturing Clinician Researcher Scheme)和Genedant-GIS创新计划(Genedant-GIS Innovation Program)。
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引用次数: 0
To vaccinate or not against highly pathogenic avian influenza? 接种还是不接种高致病性禽流感疫苗?
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/S2666-5247(24)00107-1
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引用次数: 0
Candida auris: new clade, same challenges 白色念珠菌:新的支系,同样的挑战。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/j.lanmic.2024.100977
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引用次数: 0
Harmonising the measurement of neutralising antibodies against chikungunya virus: a path forward for licensing of new vaccines? 统一基孔肯雅病毒中和抗体的测量方法:新疫苗许可的前进之路?
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/S2666-5247(24)00097-1
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引用次数: 0
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 约旦南部畜牧业户成员的 MERS-CoV 暴露和 MERS-CoV ELISA 血清阳性的风险因素:一项基于人口的横断面研究。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/S2666-5247(24)00082-X
<div><h3>Background</h3><p>Although dromedary camels (<em>Camelus dromedarius</em>) 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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Findings</h3><p>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<sub>adj</sub>] 3·85 [95% CI 1·41–11·61], p=0·011), with frequent kissing and petting (OR<sub>adj</sub> 4·56 [1·55–15·42], p=0·0074), and frequent feeding and watering (OR<sub>adj</sub> 4·97 [1·80–15·29], p=0·0027) of young camels identified as
背景:众所周知,单峰骆驼(Camelus dromedarius)是 MERS-CoV 的宿主储库,但人们对导致中东呼吸综合征(MERS)的病毒、人畜共患病传播途径以及传播风险最高的骆驼亚群却知之甚少。阿拉伯半岛到处都有管理严格的骆驼群,它们是主要的潜在原发感染源。在这项研究中,我们旨在填补与此类牧群相关的高危社区中有关 MERS 流行病学的关键知识空白,这些知识是制定有效控制策略的重要信息:2017年9月27日至2018年10月11日期间,我们在约旦南部(亚喀巴东区、亚喀巴西区、马安东区和马安西区)的畜牧业主家庭中进行了一项横断面研究,通过计算机生成的随机名单从农业部的名单中随机选择了家庭(房屋和帐篷住所)。进行了入户访问,向家庭成员发放了有关过去 6 个月中接触 MERS-CoV 潜在风险因素的调查问卷,并采集了血样、鼻腔和口腔拭子以及包括血压和血糖在内的体检数据。小于 5 岁的儿童和没有能力提供知情同意的个人被排除在外。通过内部间接 ELISA 检测血清中的 MERS-CoV 尖峰蛋白(S1 亚基)和核头状蛋白(N)IgG 抗体,并通过 RT-PCR 检测鼻腔和口腔样本中的病毒 RNA。主要结果是MERS-CoV暴露证据(通过S1或N ELISA血清阳性或RT-PCR拭子样本阳性确定);次要结果是可能的风险因素与血清阳性之间的潜在关联。RT-PCR 数据将以描述性方式呈现。在个人和家庭层面获得血清流行率估计值,并利用混合效应逻辑回归评估假设风险因素与血清阳性状态之间的关联:我们从 204 个家庭中抽取了 879 名家庭成员(中位数年龄为 27 岁 [IQR:16-44];男性 471 [54%],女性 408 [46%])。72名(8%)家庭成员在 S1 酶联免疫吸附试验(n=25,3%)或 N 酶联免疫吸附试验(n=52,6%)中血清反应呈阳性。RT-PCR 检测未发现鼻腔或口腔拭子样本阳性。在 S1 ELISA(类内相关系数为 0-88 [0-35-0-96] )而非 N ELISA(0-00 [0-00-0-27])中发现了血清阳性的户内聚集现象。在多变量分析中,S1 ELISA 血清阳性与频繁(≥每周一次)与幼骆驼接触(年龄adj] 3-85 [95% CI 1-41-11-61],p=0-011)、频繁亲吻和抚摸幼骆驼(ORadj 4-56 [1-55-15-42],p=0-0074)以及频繁喂食和喂水(ORadj 4-97 [1-80-15-29],p=0-0027)有关。参加骆驼比赛(ORadj 3-73 [1-11-12-47],p=0-029)、频繁喂养任何年龄的骆驼(ORadj 3-18 [1-12-10-84],p=0-040)和血糖升高(>150 mg/dL;ORadj 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血清阳性与与S1 ELISA阳性家庭成员同住一户有关(ORadj 8-92 [1-06-92-99],p=0-044),与与骆驼接触史的S1 ELISA阳性家庭成员同住一户有关(ORadj 24-74 [2-72-306-14],p=0-0050)。N ELISA血清阳性与年龄(分类,p=0-0069)、拥有小骆驼的家庭(年龄adj 1-98 [1-02-4-09],p=0-043)以及经常喂养任何年龄的骆驼(ORadj 1-98 [1-09-3-69];p=0-025)有关:研究结果凸显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 监控和控制策略的重要性。幼年单峰骆驼传播人畜共患病 MERS-CoV 的风险增加,一旦有疫苗可用,应优先接种。在高风险社区中,疫苗接种策略应优先考虑拥有骆驼的家庭,特别是从事骆驼饲养或赛跑的个人,以及年龄较大或患有糖尿病的家庭成员,因为有证据表明这些人在家庭内部会继发传播:资金来源:英国医学研究委员会和美国国家过敏与传染病研究所。
{"title":"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","authors":"","doi":"10.1016/S2666-5247(24)00082-X","DOIUrl":"10.1016/S2666-5247(24)00082-X","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Although dromedary camels (&lt;em&gt;Camelus dromedarius&lt;/em&gt;) 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.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;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.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;p&gt;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 &lt;1 year) camels (adjusted odds ratio [OR&lt;sub&gt;adj&lt;/sub&gt;] 3·85 [95% CI 1·41–11·61], p=0·011), with frequent kissing and petting (OR&lt;sub&gt;adj&lt;/sub&gt; 4·56 [1·55–15·42], p=0·0074), and frequent feeding and watering (OR&lt;sub&gt;adj&lt;/sub&gt; 4·97 [1·80–15·29], p=0·0027) of young camels identified as ","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266652472400082X/pdfft?md5=4e23a680a4d80620594bd79b719e967b&pid=1-s2.0-S266652472400082X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies 产生丁酸盐的肠道细菌与传染病住院风险之间的关系:两项基于人群的观察性微生物组研究的结果。
IF 20.9 1区 生物学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-01 DOI: 10.1016/S2666-5247(24)00079-X
<div><h3>Background</h3><p>Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.</p></div><div><h3>Methods</h3><p>In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18–70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25–74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5–7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.</p></div><div><h3>Findings</h3><p>We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60–0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77–0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.</p></div><div><h3>Interpretation</h3><p>Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with
背景:微生物群改变在因严重感染而住院的患者中很常见,临床前模型显示,厌氧丁酸肠道细菌可防止全身感染。然而,微生物群紊乱与人类严重感染易感性增加之间的关系仍不清楚。我们在两个大型人群队列中调查了肠道微生物群与未来感染相关住院风险之间的关系:在这项观察性微生物组研究中,我们对荷兰(HELIUS 研究;衍生队列)和芬兰(FINRISK 2002 研究;验证队列)的独立人群队列中的肠道微生物群进行了 16S rRNA 基因测序。HELIUS 研究在荷兰阿姆斯特丹进行,研究对象包括从阿姆斯特丹市政登记册中随机抽样的成年人(纳入时年龄为 18-70 岁)。FINRISK 2002 在芬兰的六个地区进行,是一项人口调查,包括随机抽样的成年人(25-74 岁)。在两个队列中,参与者都填写了调查问卷,接受了体格检查,并在纳入研究时提供了粪便样本(HELIUS参与者为2013年1月3日至2015年11月27日,FINRISK参与者为2002年1月21日至4月19日)。要纳入我们的研究,必须提供粪便样本并成功测序,还必须提供国家登记数据。主要预测变量是微生物群的组成、多样性以及丁酸菌的相对丰度。根据国家登记数据,我们的主要结果是粪便样本采集后 5-7 年随访期间因任何传染病住院或死亡。我们使用微生物生态学和 Cox 比例危险度法研究了微生物群与感染风险之间的关系:我们对 10 699 名参与者(4 248 人[39-7%]来自衍生队列,6451 人[60-3%]来自验证队列)的肠道微生物群进行了分析。602名(5-6%)参与者(152名[3-6%]来自衍生队列;450名[7-0%]来自验证队列)在随访期间因感染住院或死亡。这些参与者的肠道微生物群组成与未因感染住院的参与者有所不同(衍生组群 p=0-041;验证组群 p=0-0002)。具体来说,产生丁酸盐的细菌相对丰度越高,因感染住院的风险越低(丁酸盐产生者每增加 10%,衍生队列特异性病因危险比为 0-75 [95% CI 0-60-0-94],p=0-013;验证队列每增加 10%,危险比为 0-86 [0-77-0-96],p=0-0077)。在对人口统计学、生活方式、抗生素暴露和合并症进行调整后,这些相关性保持不变:在两个独立的欧洲队列中,肠道微生物群的组成,特别是丁酸菌的定植,与普通人群预防感染性疾病住院有关。进一步的研究应探讨调节微生物群是否能降低严重感染的风险:阿姆斯特丹UMC、Porticus、美国国立卫生研究院、荷兰卫生研究与发展组织(ZonMw)和Leducq基金会。
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