Whole-genome sequencing to investigate the prevalence and transmission multidrug-resistant organisms in intensive care units in Hanoi, Vietnam Background Increasing 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 research The 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, Vietnam 3. To provide training in sequencing and bioinformatics to Vietnamese scientists and build clinical and laboratory capacity to tackle MDRO in Vietnam 4. 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 studies We 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 study This 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 investigation This 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. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.