Research

Anti-Microbials In Society (AMIS): a Global Interdisciplinary Research Hub

Public Health and Policy

Clare Chandler

ESRC, 2017-2021

Our use of antibiotics has escalated. We are often most aware of antibiotic use when we treat infections – for people, and animals. However, their use is more widespread. We use them routinely to reduce risks of infection amongst people with vulnerable immune systems, in farming livestock, to manage infection and to promote growth and even in crop farming. This widespread use is linked to a rise in antibiotic resistance (AMR). The amount of antibiotic chemicals in circulation is held responsible for driving selection pressure amongst bacteria such that some infections become untreatable with previously effective drugs. This can have dramatic consequences for both health and economics. And yet, scientists have emphasised the lack of evidence for using antibiotics in many scenarios. For example, it is estimated that at least 50% of human antibiotic usage has no clinical benefit.

[More]


Infection prevention and control for drug-resistant tuberculosis in South Africa in the era of decentralised care: a whole systems approach

Infectious and Tropical Diseases

Alison Grant

ESRC, 2017-2021

Drug-resistant tuberculosis (DR-TB) is a major threat to global public health, causing one in four estimated worldwide deaths attributable to antimicrobial resistance. In South Africa, DR-TB transmission within clinics, particularly to HIV-positive people, is well-documented. Most TB transmission happens before people start TB treatment, but DR-TB transmission may continue after treatment is started, raising concern as DR-TB services in South Africa are decentralised from hospitals to primary care clinics. The extent to which exposure in clinics, as compared to other community settings, drives ongoing transmission of DR-TB requires better definition, to mobilise necessary resources to address this problem. Guidelines for clinics concerning infection prevention and control (IPC) measures to reduce DR-TB transmission are widely available. There is ample evidence that recommended measures are not put into practice, but limited understanding of the reasons. A comprehensive approach to understanding barriers to implementation is required to design effective IPC interventions for DR-TB.

[More]


Treatment of multi-drug-resistant Acinetobacter baumannii and Klebsiella pneumonia infections using bacteriophage capsule depolymerases
Biological & Pharmacological Sciences
Prof Peter TaylorRichard Stabler, Nick Thomson
MRC, 2016-2019
Acinetobacter baumannii and Klebsiella pneumonia are bacteria with an amazing ability to develop resistance to antibiotics and we are on the verge of having nothing left to treat those infected. We aim to use proteins from viruses that infected the bacteria to disarm it by removing the bacterial protective coat, allowing the human immune system to remove infections.
[More]


Use of herpesvirus genetics to determine pan-antimicrobial mechanism of action
Biological & Pharmacological Sciences
Ursula Gompels
HHV-6 Foundation


Defining reservoirs and transmission of antimicrobial-resistant Escherichia coli using a One Health approach
Biological & Pharmacological Sciences, Clinical & Veterinary Sciences
Catherine Ludden,Sharon Peacock S, Julian Parkhill
Wellcome Trust


Use of transposon-directed insertion site sequencing to identify new essential drug targets
Biological & Pharmacological Sciences
Sam Willcocks
UK Defence Science and Technology Laboratory


The interactions between C. difficile, intestinal microbiota & host response in hospital patients
Biological & Pharmacological Sciences, Clinical & Veterinary Sciences
Brendan Wren
Medical Research Council (MRC, UK)


Sources, seasonality, transmission and control: Campylobacter & human behaviour in a changing environment
Biological & Pharmacological Sciences, Clinical & Veterinary Sciences
Brendan Wren
Medical Research Council (MRC, UK)


Faecal metagenomics on acquisition of AMR in travellers
Biological & Pharmacological Sciences
Michael Brown, Ron Behrens
PHE / UCLH Biomedical Research Centre


Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE)
Clinical & Veterinary Sciences, Economic, Social & Political Sciences
David Mabey (PI), Amit Bhasin, Chrissy Roberts, Clare Chandler, Heidi Hopkins, Coll Hutchison, John Bradley, Rashida Ferrand, Shunmay Yeung
Department for International Development (DFID), 2017-2021
Fever is one of the most common symptoms that leads to health-care seeking and hospital admission across sub-Saharan Africa and Asia. However, little is known about the causes of febrile illness in these regions. Without access to reliable diagnostic facilities, and without evidence on which to base treatment guidelines, in most cases treatment is empiric and too often results in overuse of antimicrobial medicines. The FIEBRE study will help to address these information gaps, using a standard clinical, laboratory and social science protocol, in five representative sites – in Lao PDR, Malawi, Mozambique, Myanmar and Zimbabwe – with a high burden of infectious disease and few or no existing data.
[More]


Personalised Risk assessment in febrile illness to optimise Real-life Management across the European Union (PERFORM)
Clinical & Veterinary Sciences, Economic, Social & Political Sciences
Shunmay Yeung (LSHTM PI and Workpackage 5 lead), Martin Hibberd, Alec Miners
Michael Levin (Imperial College, Consortium Co-ordinator)
European commission (Horizon 2020), 5 years
PERFORM aims at developing new “omics” diagnostic tests to distinguish between bacterial and viral infections in febrile children. Work package 5, led by LSHTM, is responsible for conducting a comparative health services analysis and economic evaluation to evaluate the potential costs and impacts of introducing the tests in different European health system.
[More]


How do policymaker perceptions of antimicrobial resistance drive behaviour and policies for appropriate antimicrobial use? A case study of Pakistan.
Clinical & Veterinary Sciences, Economic, Social & Political Sciences
Johanna HanefeldMishal Khan, Helena Legido-Quigley
Ana Mateus (RVC), Rumina Hasan(Aga Khan University, Pakistan)
The research proposed is for a pump prime award to determine how policymakers’ perceptions of Antimicrobial Resistance (AMR) drive their behaviour and selection of policy options aimed at appropriate use of antimicrobials, focusing on one lower middle income country: Pakistan. Applying qualitative methods and engaging a multidisciplinary team with human and animal health expertise, it will map policy actors and their networks, drawing on the Social Construction Framework, to identify how motivation, social constructions, power relations and contextual factors shape policy maker behaviour.
[More]


Beyond non-inferiority: a practical trial design for optimising antibiotic treatment duration
Clinical & Veterinary Sciences, Epidemiology & Modelling
Matteo Quartagno (LSHTM, MRC-CTU)
Professor James Carpenter (LSHTM and CTU), professor Sarah Walker (CTU), professor Max Parmar (CTU) and Dr Patrick Phillips (CTU).
There is substantial interest in investigating the use of shorter durations of antibiotic treatment for bacterial infections to counter the global threat of AMR. Classic designs compare two arbitrarily chosen durations in a non-inferiority trial. Given their important limitations (including arbitrary non-inferiority margins), our aim was therefore to develop new alternative designs to optimise duration of treatment.Our main idea was to recast the problem of determining an optimal duration as estimating the shape of the `Duration-Response Curve’ (DRC), by means of flexible regression modelling strategies.


Multi-drug resistance in malaria under combination therapy: assessment of specific markers and development of innovative, rapid and simple diagnostics 9 (MALACTRES)
Clinical & Veterinary Sciences, Biological & Pharmacological Sciences
Colin SutherlandRachel HallettBrighid O’NeillTeun Bousama (KCMC)
MALACTRES is a consortium of researchers aiming to tackle multi-drug resistance in malaria under combination therapy. With partners in Europe and Africa, the overall objective is to assess specific genetic markers in Plasmodium falciparum for ACT resistance and to develop innovative, rapid and simple diagnostics for malaria
[More]


Low-cost, non-commercial drug susceptibility testing of MTB
Clinical & Veterinary Sciences
David Moore, Jackie Cliff, Claire Broderick, Kate Gaskell
CRyPTIC Consortium


Multi-disciplinary research of drug resistance in Malaria
Clinical & Veterinary Sciences, Epidemiology & Modelling, Economic, Social & Political Sciences
Colin Sutherland
PHE and UNITAID


Tracking Resistance to Artemisinin Collaboration II
Epidemiology & Modelling, Economic, Social & Political Sciences
Prof Arjen Dondorp (Mahidol Oxford Tropical Medicine Research Unit)
Multi-group, including Shunmay Yeung (LSHTM)
DFID
The second iteration of the TRAC project, known as TRAC II, will not only monitor for the further extension or emergence of drug resistance, but will also investigate the safety, tolerability and efficacy of Triple Artemisinin-based Combination Therapies (TACTs) – the first of its kind. In areas with failing ACTs, the aim of TACTs is restoring antimalarial efficacy, whereas in areas where ACTs still work or artemisinin resistance has not yet arrived, it has the potential to delay the emergence of drug resistance.
[More]


Modeling vaccines and AMR
Epidemiology & Modelling
Mark Jit, Nick DaviesKatherine Atkins
NIHR (2014-2019)
Vaccination is an important weapon in our arsenal in the fight against AMR. Mathematical models are used to understand both AMR transmission and to predict the healthcare impact of vaccination strategies. However there are relatively few studies that quantify the effect of vaccines on AMR dynamics. Our work addresses this gap in our understanding to further our knowledge on how best to quantify the impact of vaccines on AMR and how to integrate these models into public health decision making for vaccines.


Drug-resistant tuberculosis in Hlabisa sub-district: a prospective observational cohort
Epidemiology & Modelling, Clinical & Veterinary Sciences
Richard Lessels
Wellcome Trust


The Fight Against Antimicrobial Resistance: Applying Theory to Practice
Economic, Social & Political Sciences
Clare Chandler, Eleanor Hutchinson, Coll Hutchison
Wellcome Trust
The aim of this seed award is to open up new perspectives on antimicrobial resistance through the application of theories from the social sciences. Substantial bodies of work have the potential for application to the problem of AMR. Through a review of literature and engagement with a range of scientists we intend to stimulate new avenues to approach the problem of AMR.
[More]


Social, behavioural and economic drivers of inappropriate antibiotic use by informal private healthcare providers in rural India
Economic Social & Political Sciences
Meenakshi Gautham, Neil Spicer, Catherine Goodman
MRC/ESRC/DFID/Wellcome Trust


Evaluation of the UK AMR strategy, 2013-2018
Economic, Social & Political Sciences
Nicholas Mays, Elizabeth Eastmore, Rebecca Glover, Mustafa Al-haboubi, Elisabeth Holdsworth
UK Department of Health
The team is using a range of methods including interviews, a series of case studies, systematic reviews, focus groups and a citizens’ jury to explore implementation, and the evidence underpinning the mechanisms of change, in this complex and multi-sector intervention.


Working with plantation owners to control malaria and antimalarial drug resistance
Economic, Social & Political Sciences
Shunmay Yeung
Bill and Melinda Gates Foundation


Economic Evaluation support to a trial that assess strategies to address anti-microbial resistance in malnourished children (FLACSAM)
Economic, Social & Political Sciences
Anna Vassall, Julie Jemutai (KEMRI-Wellcome Trust Research Programme)
Joint Global Health Trials Scheme – DFID, Wellcome Trust
An economic evaluation of first Line Antimicrobials in Children with Complicated Severe Acute Malnutrition.
[More]


Estimating the costs in five countries of the diagnosis and treatment of multi-drug resitance TB (VALUE-TB)
Economic, Social & Political Sciences
Anna Vassall, Sedona Sweeney
Bill and Melinda Gates Foundation
Estimate the economic burden to the health system of multi-drug resistant TB in five countries.


Examining the costs and cost-effectiveness of novel TB regimens
Economic, Social & Political Sciences
Anna Vassall, Gabriela Gomez
Exploring the cost-effectiveness of the introduction of new TB drugs regimens, including the corresponding costs of drug-susceptability testing to prevent resistance.


Estimating the economic burden on the health system and patient of multi-drug resistant TB in South Africa (XTEND sub-study)
Economic, Social & Political Sciences
Anna Vassall, Katherine Fielding, Alison Grant
Bill and Melinda Gates Foundation
Estimate the economic burden to the health system and patients of multi-drug resistant TB in South Africa


A trial of a quality improvement programme in the private sector in Tanzania
Economic, Social & Political Sciences
Tim Powell-Jackson, Catherine Goodman
The Health Systems Research Initiative (MRC/DFID/ESRC/WT)
We are going to collect data on the quality of care, and using these data we will be able to measure the extent to which providers inappropriately prescribe antibiotics and what provider characteristics are associated with such behaviour.


Understanding health system linkages: Formative research to develop strategies to support quality improvement in treatment in the private sector
Economic, Social & Political Sciences
Sian Clarke (co-PI), Eleanor Hutchinson, Catherine Goodman, Heidi Hopkins
DFID/MRC/Wellcome Trust/ESRC. Health Systems Research call, 2017-2019
Through a specific focus on antibiotic treatment and use, this study aims to shed light on the broader processes affecting quality of care in private clinics and drug shops in Uganda. The private sector plays an important role in health care provision in many African countries and cannot be overlooked in strategies to control misuse of antibiotics. Nor can treatment practices and standards be addressed by focusing on one sector in isolation. The private sector interacts with, and is shaped by, the organisation and performance of the public sector, demand from patients and regulatory controls.