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Genomic surveillance of Klebsiella for neonatal sepsis vaccine development

LSHTM staff: Kathryn Holt, Ebenezer Foster-Nyarko, Kara Tsang
Funding: Bill & Melinda Gates Foundation
Collaborators: Oxford Big Data Institute, Institut Pasteur
Project duration: 3 years

Klebsiella pneumoniae is a globally prioritised pathogen due to the severity of the disease as well as its broad antimicrobial resistance. It is a major cause of neonatal sepsis, ranking in the top three causative agents in most settings. However, there is a lack of systematic surveillance data and limited understanding of the genomic epidemiology of the pathogen.

This study aims to use technical solutions to develop a comprehensive platform for K. pneumoniae genomic surveillance, enabling researchers to gather and analyse whole genome sequences and epidemiological data from around the world.

The researchers have already developed the tools Kleborate, a genomic surveillance framework and genotyping tool for K. pneumoniae, and Pathogenwatch, a tool led by the Centre for Genomic Pathogen Surveillance, for rapid genomic characterisation and surveillance of Klebsiella. They will integrate these with BIGSdb, a database developed by the Institut Pasteur, that serves as the core repository for genomic data for K. pneumoniae.

In this project, these existing tools will be extended and integrated to provide a one-stop solution for genomic surveillance of Klebsiella, the KlebNET Genomic Surveillance Platform. KlebNET aims to make the power of genomic surveillance accessible to researchers, clinical microbiologists and epidemiologists to use without need for specialist knowledge of Klebsiella or genome analytics.

In doing so, the project will support valuable, real-time data about Klebsiella infections and outbreaks, including the specific genetic makeup of the bacterial strain.This will allow scientists to identify important genetic markers for virulence, drug resistance and surface antigens, which will be used to inform K. pneumoniae vaccine development for neonatal sepsis.

Outputs:

Modelling the cost-effectiveness of AMR interventions in Vietnamese chicken and pig farms

LSHTM staff: David Tresco Emes, Gwen Knight, Nichola Naylor, Jeff Waage, Jo Lines
Funding: CGIAR A4NH
Collaborators: ILRI, OUCRU
Project duration: 2019-2021

Antibiotics are widely used in livestock to prevent and treat infectious diseases, however this can lead to drug-resistant infections that can spread to people, posing a risk to human health.

It’s therefore important that the use of antibiotics in livestock is reduced. Farmers can compensate for this by improving animal husbandry and biosecurity interventions, or alternatively, the antibiotics used in livestock can be replaced with others that are less important to human medicine.

This study is using computer modelling to predict the long-term cost-effectiveness of implementing such interventions in Vietnamese chicken and pig farms.

The researchers are exploring the effect of different variables, including a variety of human infections, methods of estimating workforce productivity loss from disease, the link between animal antimicrobial use and human AMR, and the background growth rate of AMR, over different timeframes.

Their outputs will include estimates of the cost savings to farmers, costs saved to human healthcare and the costs of implementing the changes.

Preliminary results indicate that these interventions can be highly cost-effective, and it’s hoped these findings will encourage policymakers and farmers to reduce our reliance on antibiotics for food production.

Download infographic of the model

AMR historical foresight: comparing AMR to climate change and tobacco control

LSHTM staff: Virginia Berridge
Funding: AHRC
Collaborators: University of Exeter, RAND Europe, University of East Anglia, Tyndall Centre for Climate Change Research, University of Oslo
Project duration: Dec 2017 – Feb 2020

This study aims to understand how AMR has developed as a policy issue by adopting a historical and comparative perspective. By looking at the historical development of climate change and tobacco control as comparator issues, the researchers are examining whether there are lessons that can be learnt  for future AMR scenario planning and decision-making. All three issues share their complexity, enduring nature and significant public health consequences.

The project combines a historical and foresight analysis with engagement with policymakers and key stakeholders in order to achieve three objectives: to understand how AMR has evolved as a policy issue and develop scenarios for policymaking responses informed by historical analysis, to test these scenarios to inform potential policy responses, and to provide evidence for effective and efficient AMR policymaking and methodological development through the use of historical perspectives to inform policy.

Information for this project was collected from review of previous evidence, interviews, methods including horizon scanning and scenario planning and interactive policy events that gather historians and policymakers, the latter being an important part of the project.

MBIRA (Mortality from Bacterial Infections Resistant to Antibiotics)

Whilst AMR is a global issue, it has major implications for African countries where severe bacterial infections are common but access to effective antibiotic treatment remains limited. To date, we lack reliable estimates of the impact of AMR in LMIC settings, which limits our capacity to address the increasing threat.

The MBIRA project is the first multi-national prospective observational study to better understand the mortality burden due to AMR in bloodstream infections in sub-Saharan Africa. The project is focussed on bacteraemia caused by Gram-negative enteric bacteria and includes patients of all age groups, from neonates to adults. The aim is to gather data across 9 hospitals in sub-Saharan Africa to inform larger global burden of disease analyses.

LSHTM staff: Alex Aiken, Andrea Rehman
Funding: Bill & Melinda Gates Foundation, Fleming Fund
Collaborators: Centre for Infectious Disease Research in Zambia (Lusaka, Zambia), Haramaya University (Harar, Ethiopia), Kilimanjaro Clinical Research Institute (Moshi, Tanzania), KEMRI-Wellcome Trust Research Programme (Kilifi, Kenya), Malawi-Liverpool-Wellcome Trust Clinical Research Programme (Blantyre, Malawi), National Hospital Abuja (Abuja, Nigeria), Stellenbosch University (Stellenbosch, South Africa), University of Ghana Medical School (Accra, Ghana), Université des Sciences, des Techniques et des Technologies de Bamako (Bamako, Mali).
Project duration: October 2019 – March 2022

Antibiotic stewardship in agricultural communities in Africa and Asia: A unified One Health strategy to optimise antibiotic use in animals and humans

This is a cluster project that seeks to compare and contrast emerging knowledge from recent and ongoing research across selected countries in Africa, Asia and South America about antibiotic usage and its drivers in humans and animals in agricultural communities and identify key priorities, potential points of nexus and barriers and enablers in order to facilitate the design of novel interventions with a common overarching strategy and contextual adaptations.

LSHTM staff: Sian Clarke, Meenakshi Gautham, Eleanor Hutchinson, Catherine Goodman, Mishal Khan, Johanna Hanefield, Harprakash Kaur
Funding: GCRF Cluster Scheme
Collaborators: University of Glasgow, UK (Tiziana Lembo), RVC, UK (Pablo Alarcon, Ana Mateus, Fiona Tomlin), West Bengal University for Animal and Fishery Sciences, India (Indranil Samanta), Makarere University, Uganda (Freddy Kitutu, Anthony Mbonye), Universidad Antonio Narino, Colombia (Nelson Arenas)
Project duration: June 2020 - May 2021

A multi-stakeholder approach towards operationalising antibiotic stewardship in India’s pluralistic rural health system

The main aims of the study are to engage with multiple stakeholders and co-design and implement (on a small scale) an intervention to operationalise antibiotic stewardship for human and livestock health in rural community settings in India. The intervention design will draw on formative research conducted with rural households, informal and formal primary care providers, veterinarians and paravets, health and regulatory department stakeholders, and stakeholders in pharmaceutical value chains in rural West Bengal, supplemented by an online survey of primary care physicians, informal providers, vets and paravets on their SARS-CoV-2-related practices, including use of antibiotics.

LSHTM staff: Meenakshi Gautham,  Catherine Goodman, Richard Stabler
Funding: MRC (HSRI)
Collaborators: Royal Veterinary College (Pablo Alarcon and Ana Mateus), Institute of Development Studies (Gerald Bloom and Ayako Ebata), Public Health Foundation of India (Prof. Srinath Reddy, Sanghita Bhattacharyya, Sandeep Bhalla), West Bengal University for Animal and Fishery Sciences (Indranil Samanta)
Project duration: Feb 2018 - Jan 2022

WASH and biosecurity interventions for reducing burdens of infection, antibiotic use and antimicrobial resistance

Funding: CGIAR
Collaborators: International Livestock Research Institute 
Project duration: 2019-2021
LSHTM staff: Chris Pinto, Clare Chandler, Sarai Keestra

This mixed methods systematic review investigated how water, sanitation and hygiene (WASH) and biosecurity interventions could reduce infections, antimicrobial use and antimicrobial resistance (AMR) in people working in close contact with animals, such as farmers. The researchers considered different settings, with a focus on low- and middle-income countries. Previous research had suggested that social, cultural, political, economic and environmental factors play an important role in the development of AMR, however, it was not well-understood how these effects could be mitigated. This systematic review, in collaboration with the International Livestock Research Institute (ILRI), aimed to summarise the evidence base for such structural AMR interventions, with the aim of shaping future research, policies and funding in this area.

A total of 104 studies were included in the review, which identified a number of effective interventions to reduce the burden of infections, antimicrobial resistance and antibiotic use in animal agricultural settings. Interventions which undertook biomanagement and bio-containment measures appeared to have positive effects most often. These measures attempted to create and maintain a conducive environment for animal raising in terms of physical infrastructure and protocols. The few studies reporting sanitation measures - which were similar to bio-containment interventions - all reported positive effects. By contrast, efforts to impact water quantity, water quality, and hygiene had more mixed effects on the outcomes assessed. Bio-exclusion interventions had mostly negative effects.

However, risk of bias was high or moderate in many studies, and publication bias should also be considered. These findings demonstrate the need for more, high-quality studies evaluating structural interventions. There are opportunities to learn from biosecurity Interventions for WASH and the authors propose that the 'A' In WASH represents both 'Animals' and 'Air', in recognition of these infection pathways. 

View the final report

OneHealth Poultry Hub

LSHTM staff: Brendan Wren, Richard Stabler
Funding: GCRF
Collaborators: RVC
Project duration: 2019-2024