Febrile illness etiologies in a broad range of endemicities (FIEBRE)
Funding: Department for International Development (DFID), 2017-2021
LSHTM investigators: David Mabey (PI), Amit Bhasin, Chrissy Roberts, Clare Chandler, Heidi Hopkins, Coll Hutchison, John Bradley, Rashida Ferrand, Shunmay Yeung
Other UK and international collaborators: Quique Bassat, Vilada Chansamouth, John Crump, Ethel Dauya, Nick Feasey, David Lalloo, Hla Hla Win, Yoel Lubell, Mayfong Mayxay, Claudious Muserere, Paul Newton, Antonio Mario Sitoe, Wah Win Htike, Zaw Lynn Aung
Summary: 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. The study will rigorously investigate causes of febrile illness, and antibacterial resistance, in inpatients and outpatients of all ages. Qualitative work will describe how care-seekers, clinicians, and other stakeholders conceptualise fever, and appropriate antimicrobial use. The results of this study will enable us to design new, evidence-based algorithms for the management of febrile illness. Archived patient samples will provide a basis for future evaluation of novel diagnostics, and rational approaches to disease surveillance.
Treatment of multi-drug-resistant Acinetobacter baumannii and Klebsiella pneumonia infections using bacteriophage capsule depolymerases
Biological and Pharmacological Sciences
Staff: Prof Peter Taylor (UCL), Richard Stabler (LSHTM), Nick Thomson (LSHTM/WTSI)
Funding: MRC, 2016-2019
Summary: 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.
Impact of combination therapy on transmission of resistant malaria parasites
Clinical & Veterinary Sciences
Title: Multi-drug resistance in malaria under combination therapy: assessment of specific markers and development of innovative, rapid and simple diagnostics (MALACTRES)
Funding: European Commission Seventh Framework Programme (EU FP7)
Collaborators: Royal Tropical Institute, The Netherlands (Coordinator); The Prince Leopold Institute of Tropical Medicine, Belgium; Centre Muraz, Burkina Faso; Kilimanjaro Christian Medical Centre, Tanzania; Foresite Diagnostics, UK; Biomolecular Sensing and Diagnostics Agrotechnology and Food Innovations, The Netherlands.
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.
A large external network of collaborators has been built, including groups who are running clinical trials from which parasite material can be used for a detailed analysis of known and candidate drug resistance markers. Such markers have previously been investigated at LSHTM. Well-known genetic mutations in the pfcrt and pfmdr1 genes play a role in resistance to most ACT partner drugs and have been sequenced from several geographical locations. The characterisation of new candidate genes, pfATPase6, pfubp-1, pfnhe-1 and pfmrp has begun.
PCR and sequencing protocols are under development and will be applied to field samples, starting with those collected in clinical trials in Kenya and Tanzania in 2009/10. We will look for changes in genotype in our candidates between pre– and post-treatment samples and in successfully infected mosquitoes. This will indicate whether or not any particular genotype survives better and has a transmission advantage in the presence of an ACT, providing evidence of a potential role in ACT resistance.
Gadalla NB, Elzaki SE, Mukhtar E, Warhurst DC, El-Sayed B, Sutherland CJ. 2010. Dynamics of pfcrt alleles CVMNK and CVIET in chloroquine-treatedSudanese patients infected with Plasmodium falciparum. Malar J. Mar 12;9(1):74.
The Fight Against Antimicrobial Resistance: Applying Theory to Practice
Economic, Social and Political Sciences
Staff: Clare Chandler, Eleanor Hutchinson, Coll Hutchison
Funding: Wellcome Trust, 2015
Summary: 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.
Tracking Resistance to Artemisinin Collaboration II
Epidemiology and Modelling
PI: Prof Arjen Dondorp (Mahidol Oxford Tropical Medicine Research Unit)
Co-Is: Multicentered incl Shunmay Yeung at LSHTM
Summary: 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.
Modeling vaccines and AMR
Epidemiology and Modelling
Staff: Mark Jit, Nick Davies and Katherine Atkins
Funding: NIHR (2014-2019)
Summary: 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.
How do policymaker perceptions of antimicrobial resistance drive behaviour and policies for appropriate antimicrobial use? A case study of Pakistan.
Clinical & Veterinary Sciences
Staff: Johanna Hanefeld, Mishal Khan, Helena Legido-Quigley
Co-Is: 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. Research findings will be essential to achieving the ESRC’s underlying objective to identify the specific economic factors, cultural norms, experiences and practices relating to antibiotics that enable the best strategies for action, by providing concrete knowledge and tools for working with policymakers in low- and middle-income countries (LMICs) as they adapt and adopt national policies for appropriate use of antimicrobials.
Key questions this research will address include:
- Who are the key policy actors to engage for effective implementation of interventions and policies concerning appropriate antimicrobial use? How are these actors currently, and potentially, connected?
- How are the selected policy options socially constructed and how do social constructions reinforce or weaken support or opposition for the selected policies?
- What other motivations, power relations and contextual factors drive the selection of specific policies?
- How do these differ among different groups of policymakers identified under objective 1 (e.g. animal health versus human health or political affiliation)?
- Based on analysis of the questions above, how do policies for appropriate use need to be presented and framed to ensure that essential groups of policy actors engage with and respond to these effectively?
Beyond non-inferiority: a practical trial design for optimising antibiotic treatment duration
Clinical & Veterinary Sciences
Staff: Matteo Quartagno (LSHTM, MRC-CTU)
Co-Is: 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.
Current projects at LSHTM
Development of a research proposal on zoonotic transmission of antimicrobial resistant bacteria
London International Development Centre (LIDC)
Use of herpesvirus genetics to determine pan-antimicrobial mechanism of action
Global surveillance and research on artemisinin resistance: the next steps (TRAC 2)
UK Department for International Development (DFID)
Pilot study ahead of cluster-randomised trial of alcohol hand-rub intervention
The Academy of Medical Sciences (UK)
Sources, Seasonality, Transmission and Control: Campylobacter & human behaviour in a Changing Environment
Medical Research Council (MRC, UK)
The interactions between C. difficile, intestinal microbiota & host response in hospital patients
Medical Research Council (MRC, UK)
Defining reservoirs and transmission of antimicrobial-resistant Escherichia coli using a One Health approach
Ludden C, Peacock S, Parkhill J, Wood J.
Drug-resistant tuberculosis in Hlabisa sub-district: a prospective observational cohort
Multi-disciplinary research of drug resistance in Malaria
PHE and UNITAID
Use of transposon-directed insertion site sequencing to identify new essential drug targets
UK Defence Science and Technology Laboratory
Social, behavioural and economic drivers of inappropriate antibiotic use by informal private healthcare providers in rural India.
Gautham M, Spicer N, Goodman C.
MRC / ESRC / DFID / Wellcome Trust
Faecal metagenomics on acquisition of AMR in travellers.
Brown M, Behrens R.
PHE / UCLH Biomedical Research Centre
Low-cost, non-commercial drug susceptibility testing of MTB
Moore D, Cliff J, Broderick C, Gaskell K
Recent AMR MSc research projects
|MSc Course||Year||Supervisor||Title||Disciplinary Pillar||Country|
|Control of Infectious Diseases||2015||Dr. John Stelling and Ms. Holly Prudden||WHONET and SaTScan for Hospital Network and Intra-Hospital Geographic Cluster Analysis of Antimicrobial Resistance||Epidemiology and Modelling|
|Control of Infectious Diseases||2015||Dr Harparkash Kaur and Dr John Stelling||The evaluation of Matrix-Assisted Laser Desorption/Ionisation - Time of Flight Mass Spectrometry (MALDI-TOF MS) for the detection of antimicrobial resistance and microbial sub-typing.||Biological and Pharmacological Sciences|
|Distance Learning Global Health Policy||2015||Dr John Licorish and Dr Sanjay Patel||Antimicrobial stewardship and resistance : how are countries interpreting regional and global policy?||Economic, Social and Political Sciences|
|Medical Microbiology||2014||Victoria Miari and Dr Richard Stabler||Multisite Neisseria gonorrhoeae infection and antimicrobial resistance||Clinical and Veternary Sciences|
|Health Policy, Planning and Financing||2014||-||Is the ban on growth promoting antibiotics an appropriate policy response to rising antimicrobial resistance in humans?||Economic, Social and Political Sciences|
|Control of Infectious Diseases||2010||Dr Elizabeth Sheridan||Antimicrobial resistance in lower respiratory tract isolates from hospital inpatients in England and Wales||Clinical and Veternary Sciences||United Kingdom|
|Control of Infectious Diseases||2010||Dr Catherine Lowndes||Antimicrobial resistance in gonorrhoea: an analysis of patient characteristics associated with gonococcal resistance to past and present therapeutic agents in England and Wales||Clinical and Veternary Sciences||United Kingdom|
|Epidemiology||2009||Dr Natasha Larke||Incidence and Antimicrobial resistance trends of Neisseria gonorrhoea isolates in a Rural Clinical Cohort in Uganda.||Epidemiology and Modelling||Uganda|
|Biology and Control of Disease Vectors||2008||Dr Mary Cameron||Carriage of antimicrobial resistance genes by calyptrate flies in different environments of Central Spain||Biological and Pharmacological Sciences||Spain|
|Control of Infectious Diseases||2008||Dr John Stelling and Dr Peter Vickerman||Nosocomial outbreak detection: Evaluating the use of biochemical profiles and antimicrobial resistance phenotypes with WHONET and a space–time scan statistic||Epidemiology and Modelling|
|Medical Parasitology||2015||Dr Sam Alsford||The molecular dissection of putative Miltefosine/Amphotericin-B cross-resistance determinants in Trypanosoma brucei.||Biological and Pharmacological Sciences|
|Medical Microbiology||2015||Dr Sam Willcocks||Identification and characterisation of antibiotic resistance genes in Yersinia pseudotuberculosis.||Biological and Pharmacological Sciences|
|Medical Parasitology||2015||Dr Colin Sutherland||Surveillance of Artemisinin resistance in Tanzania over a two year period.||Epidemiology and Modelling||Tanzania|
|Immunology of Infectious Diseases||2015||Dr Colin Sutherland||Investigation of drug resistance markers in Kenyan children treated with ACT in Mbita in 2013.||Epidemiology and Modelling||Kenya|
|Medical Parasitology||2015||Dr Khalid Beshir||Parasite clearance in Western Kenya after Artemisinin combination therapy : monitoring the prevalence of Plasmodium falciparum Chloroquine resistance transporter and Kelch-13 mutations.||Epidemiology and Modelling||Kenya|
|Medical Entomology for Disease Control||2015||Dr Raphael N’Guessan||Status of ITNs and IRS for African malaria vector control in the era of insecticide resistance : are there sufficient novel and effective insecticides available for their replacement?||Epidemiology and Modelling|
|Control of Infectious Diseases||2014||Dr Aurelie Jeandron and Dr John Stelling and Professor Xiao Yonghong||Antibiotic resistance and outbreak detection in China||Epidemiology and Modelling||China|
|Medical Statistics||2014||Dr Richard Silverwood and Dr Shunmay Yeung||Investigating predictors of artemisinin resistance is South East Asia||Epidemiology and Modelling||South East Asia|
|Medical Statistics||2014||Dr Taane Clark||Statistical approaches to identify genetic variants associated with tuberculosis drug resistance||Epidemiology and Modelling|
|Control of Infectious Diseases||2014||Dr Paolo D’Ancona||Application of WHONET software to simulated prospective real-time surveillance and analysis of antimicrobial resistance in Italy||Epidemiology and Modelling||Italy|
|Medical Entomology for Disease Control||2014||-||Evaluation of molecular markers of drug resistance in two regions of Nigeria with marked difference in malaria transmission patterns||Humanities and Environmental Sciences||Nigeria|
|Epidemiology||2014||-||Socio-economic status, comorbidities and resistance to cephalosporin antibiotics in Escherichia coli and Klebsiella pneumoniae : a cross-sectional study||Epidemiology and Modelling|
|Control of Infectious Diseases||2014||Dr. Jo Lines||The detection of fine scale heterogeneity in insecticide resistance in Aedes aegypti in two communities in the Yucatan, Mexico||Humanities and Environmental Sciences||Mexico|
|Medical Parasitology||2013||-||Characterisation of the de-ubiquitinating enzyme pfubp-1 and its role as a potential molecular marker for artemisinin resistance in Plasmodium falciparum isolates from Kenya||Biological and Pharmacological Sciences||Kenya|
|Medical Parasitology||2013||Dr Mark Rowland||Real-time PCR design for the quatification of sporozite rates and the evaluation of the effect of insecticide resistance on malaria transmission in Tanzania||Biological and Pharmacological Sciences||Tanzania|
|Molecular Biology of Infectious Disease||2012||Dr David Horn||Investigating melarsoprol and pentamidine action and resistance in African trypanosomes||Biological and Pharmacological Sciences|
|Tropical Medicine and International Health||2012||Professor Diana Lockwood||Leishmania parasite resistance to drugs, mechanisms and strategies for prevention||Biological and Pharmacological Sciences|
|Tropical Medicine and International Health||2012||Dr Richard Lessells||Absence of HIV drug resistance in patients with treatment failure in rural KwaZulu-Natal, South Africa||Clinical and Veternary Sciences||South Africa|
|Distance Learning Public Health||2012||Professor Moses Kamya||Monitoring for 'plasmodium falciparum' drug resistance to artemether - lumefantrine versus dihydroartemesinin - piperaquine in children under 5 years with uncomplicated malaria in Uganda||Epidemiology and Modelling||Uganda|
|Control of Infectious Diseases||2011||Dr. Immo Kleinschmidt||Epidemiology of malaria and surveillance of artemisinin-resistance in seven Containment Provinces in Thailand||Epidemiology and Modelling||Thailand|
|Medical Parasitology||2011||Dr David Horn||Characterisation of putative protein kinases involved in drug resistance against Melarsprol in African Trypanosomes||Biological and Pharmacological Sciences|
|Immunology of Infectious Diseases||2011||Dr Rachel Hallett||Investigation of antimalarial drug resistance-associated genetic polymorphisms in Uganda||Biological and Pharmacological Sciences||Uganda|
|Molecular Biology of Infectious Disease||2010||-||Drug resistance in African trypanosomes.||Biological and Pharmacological Sciences|
|Control of Infectious Diseases||2010||Dr Ruth McNerney||Epidemiology of Mycobacterium tuberculosis, risk factors for drug resistance and implications for its control in North West Province, South Africa||Epidemiology and Modelling||South Africa|
|Medical Parasitology||2009||Dr Rachel Hallet||Prevalence of plasmodium falciparum multidrug resistance 1(pfmdr1) and chloroquine resistance transporter ( pfcrt) sequence mutations and association with Amodiaquine plus treatment failure in Gambian children in 2003.||Biological and Pharmacological Sciences||The Gambia|
|Medical Parasitology||2009||Prof. Simon Croft and Prof. David Warhurst||Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Attapu and Xepon, Laos PDR||Biological and Pharmacological Sciences||Laos|
|Control of Infectious Diseases||2009||Dr John Stelling and Dr Peter Vickerman||Nosocomial outbreak detection : evaluating the use of biochemical profiles and antimicrobial resistance phenotypes with WHONET and a space?time scan statistic.||Epidemiology and Modelling|
|Public Health||2009||Dr Paul Wilkinson||Does cotrimoxazole prophylaxis for opportunistic infections among HIV infected and HIV exposed individuals induce bacterial resistance to other antibiotic classes? A systematic review of the literature.||Clinical and Veternary Sciences|
|Medical Microbiology||2010||Professor David Lewis||Molecular Detection of Emergent Third Generation Cephalosporin resistance among Neisseria gonorrhoeae isolates in South Africa||Epidemiology and Modelling||South Africa|
|Public Health||2015||Dr Jolijn Hendriks||Public-targeted communication interventions to improve antibiotic use.||Economic, Social and Political Sciences|
|Public Health in Developing Countries||2015||Dr Toby Leslie||The effect of rapid diagnostic tests on antibiotic prescribing practices : a secondary analysis of data from a randomised effectiveness trial in Afghanistan.||Clinical and Veternary Sciences||Afghanistan|
|Demography and Health||2015||Dr James Lewis||Socioeconomic determinants of antibiotic consumption in the state of Sao Paulo, Brazil: the effect of restricting over-the-counter sales.||Economic, Social and Political Sciences||Brazil|
|Public Health||2014||Dr Andrew Hutchings||Interventions to improve antibiotic stewardship in residential care settings for older people : a systematic review||Economic, Social and Political Sciences|
|Distance Learning Epidemiology||2014||-||Systematic review and meta-analysis of clinical and demographic risk factors for `Clostridium difficile' : investigating risk factors beyond antibiotic use||Epidemiology and Modelling|
|Medical Microbiology||2013||Dr. Awad-El-Kariem||Evaluation of the antibiotic profiles of vancomycin-resistant enterococci strains endemic in renal dialysis units : recommendation for an antibiotic policy||Biological and Pharmacological Sciences|
|Distance Learning Infectious Disease||2012||-||The role of antibiotic prophylaxis in acute necrotizing pancreatitis : a meta-analysis||Clinical and Veternary Sciences|
|Tropical Medicine and International Health||2010||Dr Tom Doherty||A comparison of antibiotic regimens for treating louse borne relapsing fever: meta-analysis and study design||Clinical and Veternary Sciences|
|Health Policy, Planning and Finance||2009||-||Incentivising antibiotic development: Drawing on the experience of neglected disease drug (and vaccine) development to inform policy intervention.||Economic, Social and Political Sciences|
|Tropical Medicine and International Health||2009||-||A Review of the infection control guidelines for communicable diseases control in complex humanitarian emergencies.||Humanities and Environmental Sciences|
|Control of Infectious Diseases||2010||Dr Greg Reilly||A qualitative evaluation of knowledge and practices related to H1N1 infection control among people who are homeless and service providers in London during the 2009/2010 pandemic period||Humanities and Environmental Sciences||United Kingdom|
|Public Health in Developing Countries||2015||Dr Tanya Marchant||Health care workers' experience of tuberculosis infection control : a review of the literature in sub-Saharan Africa.||Humanities and Environmental Sciences|