Whole-genome sequencing to investigate the prevalence and transmission multidrug-resistant organisms in intensive care units in Hanoi, Vietnam

全基因组测序调查越南河内重症监护病房中多重耐药微生物的流行和传播

• 批准号: MR/N029399/1
• 负责人: Estee Torok
• 金额: $ 49.01万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN029399%2F1
• 关键词: Whole; genome; sequencing; investigate; prevalence

BackgroundIncreasing resistance to antibiotic drugs is one of the greatest threats to human health, and is estimated to cause 700,000 deaths annually. Bacteria that are resistant to many antibiotics are called multidrug-resistant organisms (MDRO). They are more commonly found in hospitals, where they may cause healthcare-associated infections (HCAI). Patients in intensive care units (ICU) are more vulnerable to HCAI. Several outbreaks of infection with MDRO have been reported in intensive care units, and are associated with high death rates. Methods to improve the early detection and prompt management of MDRO are urgently required. Microbial whole-genome sequencing (WGS) is a new technology that is transforming the way that we identify and treat infections. Advances in technology mean that it now possible to work out the genetic code (DNA) of a bacterium in one day at a reasonable cost. This can give us lots of information including the name of the organism, what antibiotics it is resistant to, and what virulence factors are present that may cause harm to humans.Vietnam has a high burden of infectious diseases with rising mortality rates. In 2010, 30% of deaths in state health facilities were estimated to be infectious diseases related. Vietnam also has high levels of resistance to antibiotics. As a result, current antibiotic guidelines are unlikely to be effective and may result in high death rates. There is currently no surveillance system for looking for antibiotic-resistant bacteria, and no national policy or guidelines on the best way to detect and manage these organisms. Aims and objectives of the researchThe aims of this project are four-fold:1. To determine the prevalence and transmission of MDRO in intensive care units (ICU) in two hospitals in Hanoi, Vietnam, using bacterial whole-genome sequencing (WGS)2. To use rapid WGS for the investigation of a putative outbreaks of infection in two intensive care units in Hanoi, Vietnam3. To provide training in sequencing and bioinformatics to Vietnamese scientists and build clinical and laboratory capacity to tackle MDRO in Vietnam4. To use the data from these studies to inform infection control practice and public health policy for the surveillance and management of MDRO in Vietnam.Research studiesWe will conduct two research studies in the ICUs at the National Hospital for Tropical Diseases (NHTD) and Bach Mai Hospital (BMH) in Hanoi, Vietnam:1. Prospective observational cohort studyThis study will include all patients admitted to the ICU during the study period. We will collect clinical and laboratory information and samples on admission to ICU, on discharge from ICU and weekly in patients who are admitted to ICU for 7 days or more. Samples will be processed in the laboratory at NHTD and DNA extracts will be shipped to the Wellcome Trust Sanger Institute (WTSI) in the UK for high throughput WGS. This study will give us information about how common MDRO are in this setting, how often these organisms are transmitted between patients, and provide genomic context for the second study.2. Prospective surveillance and outbreak investigationThis study will perform prospective surveillance for outbreaks of MDRO by performing rapid WGS on samples collected from patients during a suspected outbreaks of infection in the ICUs. Clinical and laboratory information and samples will be collected from all patients in the suspected outbreak and from patients who we do not think are involved in the outbreak (control patients). Samples will be sequenced at NHTD and information will be fed back to clinicians / infection control staff to help them to manage the outbreak. This study will enable sequencing and bioinformatic analysis to be performed locally, thus facilitating translation of rapid microbial WGS into the clinical environment to inform clinical care and infection control practices in real-time.

背景抗生素耐药性的增加是人类健康的最大威胁之一，据估计每年造成70万人死亡。对许多抗生素具有耐药性的细菌被称为多药耐药生物体（MDRO）。它们更常见于医院，在那里它们可能会导致医疗保健相关感染（HCAI）。重症监护室（ICU）的患者更容易受到HCAI的影响。在重症监护病房中已经报告了几次MDRO感染的爆发，并且与高死亡率相关。迫切需要改善MDRO的早期发现和及时管理的方法。微生物全基因组测序（WGS）是一项新技术，正在改变我们识别和治疗感染的方式。技术的进步意味着现在可以在一天内以合理的成本计算出细菌的遗传密码（DNA）。这可以为我们提供大量信息，包括生物体的名称，它对哪些抗生素具有耐药性，以及存在哪些可能对人类造成伤害的毒力因子。越南有很高的传染病负担，死亡率不断上升。2010年，据估计，在国家卫生设施中，30%的死亡与传染病有关。越南对抗生素的耐药性也很高。因此，目前的抗生素指南不太可能有效，并可能导致高死亡率。目前没有寻找耐药细菌的监测系统，也没有关于检测和管理这些生物体的最佳方法的国家政策或指导方针。研究的目的和目标本项目的目的有四个方面：1。使用细菌全基因组测序（WGS）2确定越南河内两家医院重症监护室（ICU）中MDRO的患病率和传播。使用快速WGS调查越南河内两个重症监护病房的疑似感染暴发3。为越南科学家提供测序和生物信息学培训，并建立临床和实验室能力，以应对越南的MDRO 4。为了使用这些研究的数据，以通知感染控制实践和公共卫生政策的监测和管理MDRO在Vietnam.Research studiesWe将进行两项研究，在重症监护室在国家热带病医院（NHTD）和巴赫迈医院（BMH）在河内，越南：1。前瞻性观察性队列研究本研究将纳入研究期间入住ICU的所有患者。我们将在进入ICU时、从ICU出院时以及每周收集进入ICU 7天或以上的患者的临床和实验室信息以及样本。样本将在NHTD的实验室进行处理，DNA提取物将被运送到英国的Wellcome Trust桑格研究所（WTSI）进行高通量WGS。这项研究将为我们提供关于MDRO在这种情况下有多常见，这些生物体在患者之间传播的频率如何的信息，并为第二项研究提供基因组背景。前瞻性监测和暴发调查本研究将通过对ICU疑似感染暴发期间从患者采集的样本进行快速WGS，对MDRO暴发进行前瞻性监测。将从疑似疫情中的所有患者和我们认为与疫情无关的患者（对照患者）中收集临床和实验室信息和样本。样本将在NHTD进行测序，信息将反馈给临床医生/感染控制人员，以帮助他们管理疫情。这项研究将使测序和生物信息学分析能够在当地进行，从而促进将快速微生物WGS转化为临床环境，以实时告知临床护理和感染控制实践。

项目成果

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission.

• DOI: 10.1038/s41467-022-28371-z
• 发表时间: 2022-02-23
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Aggarwal D;Page AJ;Schaefer U;Savva GM;Myers R;Volz E;Ellaby N;Platt S;Groves N;Gallagher E;Tumelty NM;Le Viet T;Hughes GJ;Chen C;Turner C;Logan S;Harrison A;COVID-19 Genomics UK (COG-UK) Consortium;Peacock SJ;Chand M;Harrison EM
• 通讯作者: Harrison EM

Erratum: Antimicrobial resistance in human populations: challenges and opportunities - ERRATUM.

• DOI: 10.1017/gheg.2017.12
• 发表时间: 2017
• 期刊: Global health, epidemiology and genomics
• 作者: Allcock S;Young EH;Holmes M;Gurdasani D;Dougan G;Sandhu MS;Solomon L;Török ME
• 通讯作者: Török ME

Antimicrobial resistance in human populations: challenges and opportunities.

• DOI: 10.1017/gheg.2017.4
• 发表时间: 2017
• 期刊: Global health, epidemiology and genomics
• 作者: Allcock S;Young EH;Holmes M;Gurdasani D;Dougan G;Sandhu MS;Solomon L;Török ME
• 通讯作者: Török ME

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission.

• DOI: 10.1038/s41467-021-27942-w
• 发表时间: 2022-02-08
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Aggarwal D;Warne B;Jahun AS;Hamilton WL;Fieldman T;du Plessis L;Hill V;Blane B;Watkins E;Wright E;Hall G;Ludden C;Myers R;Hosmillo M;Chaudhry Y;Pinckert ML;Georgana I;Izuagbe R;Leek D;Nsonwu O;Hughes GJ;Packer S;Page AJ;Metaxaki M;Fuller S;Weale G;Holgate J;Brown CA;Cambridge Covid-19 testing Centre;University of Cambridge Asymptomatic COVID-19 Screening Programme Consortium;COVID-19 Genomics UK (COG-UK) Consortium;Howes R;McFarlane D;Dougan G;Pybus OG;Angelis D;Maxwell PH;Peacock SJ;Weekes MP;Illingworth C;Harrison EM;Matheson NJ;Goodfellow IG
• 通讯作者: Goodfellow IG

Longitudinal genomic surveillance of multidrug-resistant Escherichia coli carriage in a long-term care facility in the United Kingdom.

英国一家长期护理机构中多重耐药大肠杆菌携带的纵向基因组监测。

• DOI: 10.17863/cam.12000
• 发表时间: 2017
• 作者: Brodrick H