The MAGIC-WAND Study: Micro-organism and Gram-Negative Infection Control

The MAGIC-WAND Study: Micro-organism and Gram-Negative Infection Control - Wastewater for AMR and Novel Disease Detection

Background

The World Health Organization (WHO) has recognized AMR as one of the top ten global health threats facing humanity (1). Peru is a hotspot of antimicrobial resistance globally and has been identified as a high-risk site for the origin of future pandemics. Children, particularly those undergoing abdominal surgery or chemotherapy for bone marrow transplant, oncological and haematological malignancies are at particularly high risk of sepsis from infection with gram negative resistant organisms. 

Hypothesis

This study aims to: 

  1. Establish the prevalence of carbapenem resistance in intensive care settings Peru .
  2. Determine the major genomic mechanisms of resistance.
  3. Identify novel mechanisms of resistance to last line antimicrobials.
  4. Use wastewater sampling and metagenomic sequencing to identify novel and dangerous pathogens in hospital settings.

Methods

Collaboration with the Hospital de Niños, the Peruvian Ministry of Health and regional microbiology services across the country will enable rapid identification and surveillance of gram-negative organisms circulating in intensive care settings. These isolates together with isolates from wastewater from collaborating institutions will be transported to Universidad Peruana Cayetano Heredia in Lima for phenotyping (using MALDI-TOF, Carba5 and Automated MIC testing) and metagenomic sequencing on the nanopore platform. Novel mechanisms of resistance will be identified from comparative genomic studies and GWAS. Metagenomic sequencing will enable detection of novel and dangerous pathogens which will be fed back to the Peruvian Ministry of Health.

The successful candidate will have the opportunity to learn techniques in micro-organism culture and detection, DNA extraction and metagenomic sequencing at Great Ormond Street Hospital, then will travel to Lima to spend 2-3 years undertaking the project with our field workers and laboratory staff in Peru*.

Timeline

Ethical approval has already been obtained and the project is in the early phases of institutional approval at collaborating centres. In September 2024 the project will be ready to launch in time for the beginning of the PhD program. 

Year 1: Students will learn techniques in DNA extraction, culture and sequencing at Great Ormond Street Hospital Microbiology laboratories. At the end of the first year we expect to have identified and phenotyped 1000 gram negative samples from collaborating institutions. 

Year 2: will be spent extracting DNA from isolates and undertaking metagenomic sequencing analyses of wastewater. 

Year 3: will be spent writing up and analysing data for the thesis. 

*Note this study has the option of being undertaken in the UK if preferred.

References 

World Health Organization. (2019). Ten threats to global health in 2019. https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019

References 

This project is under the supervision of Dr Louis Grandjean. For enquiries please contact l.grandjean@ucl.ac.uk