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The importance of AMR: A look back at World AMR Awareness Week 2023

We are at a turning point in history: if we fail to change the trajectory of antimicrobial resistance (AMR), by 2050 we face up to 10 million annual global deaths from AMR. Research, solutions, and action in the clinic and at the global political scale are critical to preventing this catastrophe.  

To help raise awareness of AMR and highlight the ways that Imperial College London researchers are contributing to the fight against this challenge, the Institute of Infection created three blogs for Antimicrobial Resistance Week, which took place 18th-24th November. The blogs highlighted research at Imperial to understand, manage, and prevent the development of resistance. First, Dr Frances Davies and Dr Elita Jauneikaite explored how resistance develops, looking at the mechanisms used by bacterial pathogens to combat antibiotics and examining AMR at a patient level with preventive measures and novel technologies for tracking and predicting the spread of infection. Dr Gerald Larrouy-Maumus and Dr Jesus Rodriguez Manzano described new diagnostic tools that can rapidly provide clinicians with critical information about resistance and inform decision-making. Finally, Dr Timothy Rawson explained how his group is using artificial intelligence and biosensor technology for precision antimicrobial prescribing, while Dr Nina Zhu described the ongoing work on improving surveillance for infections and AMR.  

These are just a few examples of the work of hundreds of Imperial researchers across the disciplines, exploring the origins of AMR and potential solutions at different scales, from the molecular to the systems level. To finish this blog series, we look at a few more examples of AMR research being undertaken at Imperial. 

TB and AMR 

In the previous blog, Dr Gerald Larrouy-Maumus described his focus on Mycobacterium tuberculosis (TB), which remains one of the top killers worldwide with over 1.5 million deaths per year. Antimicrobial resistance is a serious component of its threat to health, with around half a million people suffering from drug-resistant tuberculosis in 2021, according to WHO. The COVID-19 pandemic saw a rise in inappropriate prescription of antibiotics, and the number of people with drug-resistant TB increased by 3.4% from 2020-2021.  

Dr Larrouy-Maumus is not the only one who works on TB and AMR, as we found in our review from March 2023, ‘Meet 7 Imperial researchers working to end TB’. In that piece, Dr Leonid Chindelevitch, from the MRC Centre for Global Infectious Disease Analysis, combines genomics and machine learning to understand how Mycobacterium tuberculosis mutates to develop drug resistance. He understands that eradicating tuberculosis may be difficult, but “what is achievable is significantly reducing the burden of disease that it causes,” and hopes we can “go back to focusing more on tuberculosis and put a stop to the overuse of antibiotics in situations where they are not appropriate. This can be achieved using diagnostics.” 

Professor James Seddon (Department of Infectious Disease) explained the impact of resistance on treating tuberculosis in children. “Although we are lucky to be in an age when new antibiotics are being developed, it is disheartening to see resistance develop just as quickly, and the prospect of organisms that are resistant to all known antibiotics is a reality in some rare circumstances, making treatment impossible. However, the only way to completely prevent the development of antibiotic resistance is to not use antibiotics and so there is always a trade-off between responsible use and risk of resistance development.”  

Looking at how new diagnostics can contribute to tackling AMR, Dr Ivana Pennisi pointed out, “The diagnosis of infectious diseases such as TB in children is challenging…Diagnostic methods for tuberculosis rely on the cultivation of the causative bacteria, which takes several weeks and usually requires invasive methods for the acquisition of appropriate samples…The urgency for rapid diagnostics tools is further accelerated by the growing threat of drug-resistant tuberculosis”. 

“Drug-resistant tuberculosis poses an obstacle that is surely challenging the tuberculosis research clock, intensifying the need for timely and verified data in order to make better-informed decisions to tackle the drug-resistant TB crisis.” – Dr Ivana Pennisi.

Read more about TB and AMR: Meet 7 Imperial researchers working to end TB

Resistant fungal diseases 

While most of us think about antimicrobial resistance as a health issue, it also poses major threats to our global food security, environment and ecology, as the Institute of Infection explored in the context of fungi, in our review: ‘How to fight fungal infection: the path of yeast resistance’. 

A special problem in the treatment of fungi is that the same antifungal agents are used in human and animal healthcare and agriculture (as well as in other global industries). This dual use accelerates the spread of resistance across the globe and means that we are losing our first line of defence against opportunistic fungal infections in the clinic as well as against crop-destroying fungi, impacting global food systems. 

Aspergillus fumigatus can cause the disease aspergillosis in at-risk humans and is a very common mould in soils and air. Fungicides, which are used to protect crops from disease, have led to emerging resistance to antifungal drugs by this mould. A recent citizen science project by Professor Mat Fisher et al. showed that more than 5% of A. fumigatus spores in the UK air are now resistant to the azole antifungals in common use in both the clinic and agriculture. We are all exposed to this mould daily, and this is especially serious for people who are immunocompromised, who are at a greater risk of aspergillosis. “However, it’s not all bad: we’ve recently seen the development of two new highly promising antifungal drugs to which resistance is rare or non-existent” – Professor Mat Fisher. 

Imperial researchers, including Professor Darius Armstrong-James and Dr Anand Shah, are also looking at fungal AMR from the clinical perspective. Professor Armstrong-James, who leads the Imperial Fungal Science Network, is looking to immunotherapies as potential treatment options, explaining “[they] are of great potential for infectious diseases such as COVID-19 because of the evolving race that happens between pathogens and their host”. Immunotherapies, therefore, have the potential to avoid antimicrobial resistance. Dr Shah, a Consultant Respiratory Physician and Honorary Clinical Senior Lecturer in the School of Public Health, focuses on ways to combat AMR through improved diagnosis and the use of machine learning and artificial intelligence technologies to understand disease phenotypes, identify patients for stewardship interventions, and integrate complex datasets. He is also working to understand why and how individuals with chronic fungal disease develop antifungal resistance to triazoles (currently the only orally available antifungals) and the source of such resistance  

Finally, Dr Johanna Rhodes (School of Public Health) is using a One Health approach to understand fungal infection outbreaks. She uses omics technologies to understand drug resistance mechanisms, transmission events, and how these pathogens spread. Over the last few years, she has become interested in how drug resistance is evolving in a changing climate, where drug-resistant fungi are coming from in the environment and their effect on humans. She has also developed the first genomic surveillance platform for the fungal pathogen Candida auris that will allow clinicians to identify the drug-resistance profile within a few minutes. 

Read more about Fungal Science and AMR: How to fight fungal infection: the path of yeast resistance’   

Diagnostics to detect antimalarial resistance  

The development of drug-resistant malaria parasites poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality.  

“Malaria parasites are very quick to develop resistance to antimalarial drugs, which has posed a continual challenge for malaria treatment, control and elimination. Right now, we have parasites with resistance to our most effective drugs emerging in high-burden countries in Africa, threatening the progress against malaria made over the last two decades”, said Professor Aubrey Cunnington (Department of Infectious Disease). 

Professor Cunnington co-leads the NIHR Global Health Research Group on Digital Diagnostics for African Health Systems, which is built around an innovative digital molecular diagnostics device called Lacewing that has the potential to revolutionize access to diagnosis and delivery of treatment in Africa. The technology allows for point-of-care detection of parasite DNA from a few microlitres of blood, with a detection time of 15-20 minutes. Through this programme, the interdisciplinary team that spans continents and expertise in medicine, public health, malaria biology, and engineering aims to address several aspects of antimalarial resistance, including through subprojects focussed on detecting antimalarial resistance at the point of malaria diagnosis.  

Read more about the Lacewing platform and how it is being used by the NIHR Global Health Research Group on Digital Diagnostics for African Health Systems. 

Comprehensive AMR research expertise  

The community of Imperial’s AMR researchers truly covers the breadth of research from the molecular to the global scale. To read more about where research is being undertaken, visit some of the centres and networks with major AMR elements listed below; this is certainly not an exhaustive list. Over the coming year, the Institute of Infection will develop a platform to showcase this portfolio of expertise and will continue to draw researchers together across disciplines to combat this global threat.  

AMR: Diagnostics – In conversation with Dr Gerald Larrouy- Maumus and Dr Jesus Rodriguez Manzano

GLM and JRM Imperial Researchers

 

AMR occurs naturally over time, usually through genetic changes. Antimicrobial resistant organisms are found in people, animals, food, plants and the environment (water, soil and air). They can spread from person to person or between people and animals. However, the main drivers of antimicrobial resistance is the misuse and overuse of antimicrobials. This can be caused by poor access to quality, affordable medicines, vaccines and diagnostics, amongst other factors, but is also a consequence of clinicians often not having sufficient information to prescribe the most appropriate course of treatment. For example, it is currently difficult for clinicians to know at the point of diagnosis whether an infection is bacterial or viral: knowing even this level of detail would inform whether antibiotics are appropriate for treatment (for a bacterial infection) or not (for a viral infection) In fact, any technology that can provide information on the pathogen and its level of resistance, information on the host immune system, or the dosing required for individual patients, will be vital in preventing misuse and overuse. This is why diagnostics are such a critical component of our fight against AMR. This requires advances in innovation and increased investment into them.  –   

In our third blog of our AMR series, the Institute of Infection speaks to Dr Gerald Larrouy-Maumus (Department of Life Science) and Dr Jesus Rodriguez Manzano (Department of Infectious Disease) about diagnostics. Dr Larrouy-Maumus’s laboratory is focused on infectious diseases, especially human tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), which is one of mankind’s most successful intracellular pathogens. He aims to determine how Mtb is able to survive within the host cell using the state-of-the-art mass spectrometry instruments available in his laboratory. Dr Jesus Rodriguez Manzano’s group are developing and implementing innovative methods for molecular diagnosis of infectious diseases and AMR. He is working towards transforming the field of medicine by facilitating diagnosis across different environments, to improve clinical outcomes, reduce unnecessary antimicrobial prescribing and help address the challenges of antimicrobial resistance.  

In addition to the work below, we encourage you to check out other diagnostics research programmes at Imperial (including the NIHR Global Health Research Group on Digital Diagnostics for African Health Systems, the DIAMONDS project, and the B2B2B AMRDx network) as well as the centres and networks that have diagnostics for AMR element: the Centre for Antimicrobial Optimisation, the Centre for Bacterial Resistance Biology (CBRB), the NIHR Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance, and the Imperial College Academic Health Science Centre. 

Tell me about yourself and your research  

GLM: I joined Imperial’s Department of Life Science in 2014 as Lecturer, being promoted to Reader in 2023. Since then, I have enjoyed every day of my career there. Being at Imperial surrounded by talented and enthusiastic colleagues, support staff and students is a real privilege and intellectually stimulating. This allow me to be outside my comfort zone daily and be able to contribute to the tackling of  big challenge such as AMR while training the next generation of scientists.  

Over the last years, at the Centre for Bacterial Resistance Biology, my laboratory has developed cutting edge expertise in biochemistry, lipidomics and metabolomics of bacterial pathogens. The major aim of my laboratory is to understand how mycobacterial metabolic flexibility impacts drug resistance and immune persistence. We study mainly the pathogen Mycobacterium tuberculosis, which remains one of the top killers worldwide with over 1.5 million death per year. By being able to understand how the pathogen can adapt and cope to host environmental cues and by interfering with this process, we hope to provide new route to develop new and shorter treatments.  

My lab is also pioneering bacterial antibiotics susceptibility testing on intact bacteria using lipids for identification and read-out of AMR using routine MALDI-ToF, the workhorse of clinical microbiology labs worldwide. That work led, in 2022, to the commercialisation of a kit named MBT Lipid Xtract™ Kit (RUO, Bruker) that allows the rapid detection, within 30 mins of bacteria resistance to last-resort antibiotics, a process that used to take 2 to 3 days. 

JRM: I am a molecular biologist by training. Currently, I hold a Senior Lecturer position at Imperial within the Department of Infectious Disease and am part of the NIHR HPRU in Healthcare Associated Infections and Antimicrobial Resistance. In addition, I serve as the Deputy Director for the Centre for Antimicrobial Optimisation (CAMO) and I am a co-founder and Chief Scientific Officer at ProtonDx. 

I am passionate about merging science and technology to create new diagnostic capabilities and technologies for infectious diseases and AMR.  My aim is to improve patient management and clinical outcomes and to reduce unnecessary antimicrobial prescribing.  

My current research focuses on three key areas: 

  

  1. Development and translation of sample-to-result molecular-based diagnostic devices for point-of-care applications, facilitating the establishment of decentralized healthcare systems. 
  2. Utilization of machine learning approaches in conjunction with PCR-based amplification chemistries to enable accurate high-level multiplexing in both conventional real-time instruments and state-of-the-art digital PCR platforms. This enhances the throughput of diagnostic laboratories without the need for hardware modification. 
  3. Development and validation of a novel framework for biomarker discovery to optimize the translation of host-response signatures from high-throughput platforms (e.g., RNAseq) to PCR-based and point-of-care technologies. 

What are the key challenges in your research area?   

GLM: Undoubtedly, the key challenges are to attract funding and translate the research from the bench to the bed. Investment to tackle TB and more broadly AMR must be drastically inspired by the ones that were allocated to COVID-19 if we want to win the race against the hidden pandemic that is AMR globally.  

JRM: The integration of novel diagnostic approaches into healthcare systems and at the point-of-care is a critical challenge, as it requires overcoming logistical, infrastructural, and regulatory hurdles to ensure widespread adoption. The input from clinical colleagues and other practitioners who will use my diagnostic tools, including healthcare professionals and veterinarians, is essential in overcoming these challenges. I am fortunate to work in an environment that encourages and values the input of a diverse range of professions and disciplines. 

 

Where do you see your research going in 5 years’ time?   

GLM: In the near future, we aim to maximise our impact by providing new diagnostics solutions to the current clinical unmet needs in the field of AMR and providing innovative route to tackle tuberculosis. To this aim, we have recently identified critical metabolic pathways that can definitively be targeted to reduce the burden of persistent TB, which could lead to shorten drug regimen.  

JRM: Overall, my overarching goal is to translate these research developments into tangible improvements in patient management and clinical outcomes in the NHS and in other healthcare settings. I see my work playing a crucial role in revolutionising diagnostic capabilities of infectious diseases and AMR, ultimately contributing to more efficient and personalized healthcare practices. 

 

What do you perceive as the “origins” of antimicrobial resistance?   

GLM: We have to keep in mind that AMR is a natural process and that microorganisms were developing resistance prior to the discovery of penicillin by Sir Alexander Fleming back in 1928 at St Mary’s campus. The misuse and overuse of antimicrobials over the last 80 years have led to an uncontrolled raised of superbugs globally. That is why, alongside new and innovative approaches to target those superbugs, affordable, easy to use and deployed globally diagnostics approached can be a game changer to rapidly provide the appropriate drug regimen and stop “shooting in the dark”.   

JRM: The origin of AMR is intrinsically tied to the use of antimicrobials, rooted in the fundamental principle of natural selection. Nevertheless, the implementation of rigorous antimicrobial stewardship programs, promotion of responsible antibiotic use, and enhancement of diagnostic and surveillance systems to monitor AMR have the potential to mitigate this global issue. 

 

Where do you think Imperial’s strengths lie in this field?   

GLM: Imperial has considerable talent and interdisciplinary research to lead the race against AMR. With world-expert academics focused on molecular mechanisms of AMR at the CBRBto clinicians via cross-disciplinary Institutes, Imperial has the key to being a major player in tackling AMR.    

JRM: Imperial provides an ideal environment for interdisciplinary and translational research, fostering innovation and entrepreneurship. Based on my personal experience, we undoubtedly rank among the top research institutions in this area. The interaction with clinical staff through co-location and joint projects is invaluable. 

What solutions would you like to see in the future?   

GLM: In the future, public engagement along with constant support from funders and policy makers can play a crucial role to generate innovative solutions, train the next generation of scientist and provide a proportionate use of antimicrobials.  

JRM: Within the scope of diagnostics for AMR, I envision affordable and accessible technologies for both genotypic and phenotypic testing methods that can be deployed in resource-limited settings, promoting widespread adoption. Additionally, I would like to see the establishment of global surveillance networks that systematically collect and analyse data to inform diagnostic development, and flexible regulatory pathways capable of accommodating out-of-the-box and disruptive diagnostic solutions. 

How important is an interdisciplinary approach to AMR research?   

GLM: Interdisciplinary research is not only important but the cornerstone of tacking AMR globally. We absolutely need everyone involved to address one of this century’s challenges. 

JRM: It is crucial because AMR is a complex and multifaceted issue that extends beyond the realms of microbiology and medicine. Looking specifically at the diagnostic angle, AMR research involves collaboration between molecular biologists, clinicians, microbiologists, engineers, data scientists, and healthcare policymakers. 

Are you optimistic that we can successfully overcome the challenges posed by AMR? 

GLM: Even though academic research is at the forefront of AMR research, we still have a long way to go before successfully overcoming the challenges posed by AMR. We must pull all in the same direction as we did brilliantly for COVID-19. The silent pandemic posed by AMR can be considered worse that COVID-19 in terms of death and global economy. If nothing is done urgently, even someone with a simple cold due to a bacterial infection can die. We, academics, along with funders, the public, and industry, seriously need to roll up our sleeves and get down to the problem now before it is too late. 

JRM: I believe that by collaborating globally, sustaining research efforts, and implementing public health measures, we can overcome most of the challenges presented by AMR. However, AMR is not an issue that science and technology alone can address. Increased public understanding of AMR is crucial as well. This is to ensure the appropriate use of antimicrobials and the adoption of other important infection prevention behaviours. 

In March 2023, as part of our ‘Meet 7 Researchers working to end TB’ Imperial story we spoke to Ivana Pennisi from Dr Rodriguez-Manzano and Professor Georgiou’s interdisciplinary research groups in the Department of Electrical and Electronic Engineering. She described the new TB diagnostic devices that she’s helping to create.  

Click here to read her extract  

 

 

 

AMR: Precision prescribing and antibiotics decision-making – in conversation with Dr Timothy Rawson and Dr Nina Zhu

Dr Tim Rawson and Dr Nina Zhu

Antimicrobial resistance (AMR) is an increasing worldwide public health problem that can lead to increased morbidity, use of healthcare, mortality, and cost. The UN estimates that AMR could cause 10 million deaths a year by 2050, with costs in the hundreds of billions. A driving force behind AMR is the non-prudent use of antibiotics, so reducing their unnecessary consumption can have an impact on resistance. A variety of actions have been proposed to deal with this, including global awareness campaigns, increasing financial resources for infectious disease in the healthcare sector, the development of new antibiotics, policies aimed at reducing the use of antibiotics, and – as we saw in the last blog of this series – improved diagnostics. The WHO currently considers AMR to be one of the three greatest threats to human health for the next decades.  

According to the CDC, antibiotic stewardship is ‘the effort to measure and improve how antibiotics are prescribed by clinicians and used by patients. Improving antibiotic prescribing and use is critical to effectively treat infections, protect patients from harms caused by unnecessary antibiotic use, and combat antibiotic resistance.’  

Alongside stewardship, we must also focus on precision antimicrobial prescribing, which will move clinical decision-making from its current one-size-fits-all approach towards tailoring the type and dose of antibiotic given to an individual. To improve antibiotic prescribing, effective strategies must be implemented and aligned with evidence-based recommendations for diagnosis and management. Improved prescribing will lead to better individual outcomes and preserve the effectiveness of existing agents whilst reducing the negative consequences of antibiotic therapy on the individual and society. 

In the second blog of our AMR series, we focus on precision prescribing and antibiotics decision-making. We speak to Dr Timothy Rawson, an Honorary Clinical Lecturer in the Department of Infectious Disease, who is also the Research Lead for the Precision Prescribing Theme at the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (HPRU in HCAI and AMR) and a researcher within the Centre for Antimicrobial Optimisation. We also speak to Dr Nina Zhu (Department of Infectious Disease), who is the Research Lead for the Population Health & Policy Theme in the HPRU in HCIA and AMR. 

Tell me about yourself and your research  

TR: I am an Infectious Diseases and Medical Microbiology Specialist Trainee in the NHS and Precision Prescribing Research Theme Lead for the HPRU in HCAI and AMR at Imperial College London. I am an affiliate of the Institute for Molecular Science & Engineering, and this year a Reform Scholar for the Think Tank, Reform. I completed my PhD in 2018 on precision approaches to antimicrobial prescribing in secondary care. I have been fortunate to work across medicine, bioengineering, and electrical engineering. I have an interest in optimising antimicrobial prescribing and antimicrobial resistance and the development of technology. This has included working on new artificial intelligence and biosensor technology for precision antimicrobial prescribing and first-in-human medical device studies, implementation of technology in the NHS, and clinical trials of investigatory medicinal products.  

NZ: I am the research lead of the Population Health and Policy theme of the HPRU HCAI AMR. My background covers bioengineering, epidemiology, and health economics. My research focuses heavily on improving surveillance for infections and AMR and using data intelligently to assess the impact of health interventions.   

What are the key challenges in your research area?   

TR: Despite knowing that drug concentration varies widely between patients receiving one-size-fits-all antibiotic dosing in clinical practice, we have very limited ways of routinely measuring and correcting antibiotic concentration in patients. This means that we don’t truly appreciate drug variation and its impact on clinical outcomes and AMR in the real-world.   

Within the HPRU’s Precision Prescribing Theme and the Centre for Antimicrobial Optimisation (CAMO), we have developed a study, called DATA-TDM, that aims to address this. DATA-TDM will collect drug concentration data from patients with infection across our NHS hospitals and link this data to the patients’ medical records. This will allow us to apply AI-supported algorithms that can begin identifying patient factors (such as vital signs or blood tests) that describe the patient’s response to observed concentrations of antibiotic being achieved. This will provide insight into who may benefit most from individualised therapy and help us develop new AI-based and biosensor tools to address the most urgent needs. We also hope that this model will facilitate direct patient benefit within the NHS through the information that it generates.   

NZ: The key challenges are from the surveillance gaps in resource-limited settings and populations that are socially deprived, with low health literacy or less access to healthcare. These population groups are more vulnerable and have higher risk of contracting infections but there less data is available to help understand what might work for them in terms of interventions and policies. 

Where do you see your research going in 5 years’ time?   

TR: The goal of our research is to develop evidence and interventions to facilitate the precise and individualised use of antibiotics. Hopefully, by improving the precision of antibiotic prescribing, we can improve patient outcomes, limit side effects, and minimise the impact of antibiotic use on the development of antimicrobial resistance.  

Within the precision prescribing theme we aim to: 

  1. Bridge current gaps in our understanding of how variation in drug exposure within individual patients influences treatment outcomes, toxicity, and antimicrobial resistance.  
  1. Develop and implement interventions to support individualised approaches to antimicrobial prescribing (e.g. selection of drug, route, dose, duration).  
  1. Create evidence that can support policy decisions and drive clinical practice.  

Within five years, I hope that we will have a clear understanding of how observed drug concentration affects treatment response. This will provide a clear roadmap of patient populations that will most benefit from individualised treatments and the implementation of technology. I hope that we will have validated – and be using in clinical practice – tools and predictive models to help us make individualised treatment decisions around antibiotic treatment. Through the development of evidence and technology to support precision prescribing, I hope that we will have the ability to design clinical trials to evaluate the impact of these approaches on problems like AMR. This will support the UK government’s national action plan on AMR and the WHO AMR research agenda, which have both placed an important focus on the optimisation of antimicrobial use over the next 5 years.  

NZ: I have a strong interest in developing better metrics to measure health systems’ performance in addressing AMR, this includes quantifying AMR prevalence in different healthcare sectors and populations, and measuring health service capacity and quality. 

What do you perceive as the “origins” of antimicrobial resistance?   

TR: Antimicrobial resistance is just part of natural evolution. All life has evolved due to natural selection with genetic mutations / genes that confirm a survival advantage being more readily passed on through generations.  

Unfortunately for humans, we create selective pressure in bacterial populations when we prescribe antibiotics to treat infections. There is not one antibiotic where we haven’t observed the emergence of resistance to it after has started being used.  

Whilst we can’t stop the inevitable emergence of resistance to an antibiotic, we can develop methods of minimising and slowing down the selection of AMR to maintain the effectiveness of our antibiotic within a population. This is why precision prescribing is vital, as without a better way of treating the individual infection, we continue to overprescribe treatments, increasing the selection pressure for the emergence of drug-resistance.  

NZ: I would say inappropriate use of antimicrobial drugs is one of the major drivers, this includes under-use and over-use. Also, we are exposed to antimicrobials from food and environmental sources so a One Health approach is key. 

Where do you think Imperial’s strengths lie in this field?   

TR: Firstly, Imperial has an incredible pedigree in infectious diseases research. Penicillin was discovered at St Mary’s Hospital by Sir Alexander Fleming and through the last century, Imperial has been at the cutting edge of infectious disease research. Currently, in the field of AMR – led by Professor Alison Holmes – we have had the HPRU in HCAI and AMR that has been running since 2014 and recently the Wellcome Trust funded Centre for Antimicrobial Optimisation Network (CAMO-NET), a multinational collaboration to develop and implement technologies to tackle AMR.  

In terms of technology development and translation, Imperial’s excellence in bioengineering, electrical engineering, chemistry, and maths has allowed for collaborations to be established across disciplines with numerous joint PhD projects and programme grants facilitating a truly collaborative approach.  

The Imperial College Academic Health Science Centre, a collaboration between Imperial College London and Imperial College Healthcare NHS Trust, has provided a platform for identifying clinical need and then rapidly developing and translating solutions back into the clinic. This has been further supported by the Imperial Biomedical Research Centre and its support of projects such as iCARE (Imperial Clinical Analytics, Research and Evaluation) team, which has allowed the improved use of patient data as part of research projects.  

NZ: AMR is far more complex than a medical problem, the strengths of Imperial lie within the multidisciplinary capacity and close connections with policymakers and health practitioners – this means research is guided by the patient and public needs and evidence can be translated to clinical practice rapidly. 

What solutions would you like to see in the future?   

TR: I hope that in the future we can adopt technologies that will allow us to rapidly assess individual patient drug concentrations and response to treatment in real-time, allowing us to make personalised treatment decisions. I hope that we can create wider networks of data generation, like the DATA-TDM study, that will allow us to develop better predictive models and enhance our understanding of the impact of factors, such as drug exposure, on different aspects of treatment outcome, toxicity, and the development of AMR.  

My real hope is that developing technologies and new approaches to the treatment of infections using tools that provide us with better, more real-time data will allow us to be more precise and accurate in the way that we use antibiotics. This will hopefully not only improve outcomes for patients but help us safeguard our current and future antibiotic treatments.  

NZ: I definitely want to see the increased public awareness of AMR, around how each one of us in the society can help combat this serious public health threat. And more interdisciplinary research for instance, AMR and nutrition and food science, AMR and maternal and child health etc. 

How important is an interdisciplinary approach to AMR research?   

TR: Having worked within the HPRU and as part of CAMO over the last 8 years, I have seen the importance of interdisciplinary approaches to AMR first hand. AMR is a complex and multifaceted problem that requires interdisciplinary skills to solve. Creating environments to support truly interdisciplinary collaboration can enhance our ability to approach a problem from different points of view. It can help develop broader skills and understanding of the problem and ensure that interventions are developed grounded in a solid understanding, with expert skill, and then support implementation and adoption in the area with the greatest clinical need. I think that the environment created by Professor Holmes at Imperial and now internationally through CAMO-NET has been an incredible example of how this can be used effectively to address AMR.  

NZ: Extremely, as I mentioned before, AMR is more than a clinical problem, it requires research that spans from molecular biology to understanding the resistant genes all the way to psychology to improve clinicians’ decision-making and patients’ care-seeking behaviour. In my area, good disease surveillance and data requires expertise from statistics, mathematics, computer science and engineering. For instance, mathematical modelling has been commonly used in infectious disease research for decades, but more recently, approaches from other disciplines such as systems engineering, and econometrics have also been used to develop better epidemiological models. Also, addressing AMR requires a One Health approach of which specialists from veterinary, environment, agriculture and aquaculture are just as important as the ones for human health. 

Are you optimistic that we can successfully overcome the challenges posed by AMR? 

TR: I think that the challenge of AMR is something that we are going to be facing in one form or another for as long as we rely on antibiotics for the prevention and treatment of infection. I am optimistic that we are moving in the right direction towards mitigating its impact. By being smarter with how we use data, developing new interventions (whether diagnostics, treatments, or tools to be more precise with how we use agents), being more individualised in our approach to treatment, and focusing on improving patient and prescriber attitudes and behaviours towards antimicrobials, I hope that we will be able to mitigate the impact of AMR on patients and maximise the efficacy of treatments that we have available to us now and in the future.  

NZ: Yes, despite all the challenges, I’m optimistic. AMR has become a public health priority worldwide. The COVID-19 pandemic has slowed global progress in addressing it, but there’s increased public awareness around infection prevention, hand hygiene, genomics. Also, I have seen experts from other disciplines, particularly the younger generations, start to work in AMR. So overall, I feel optimistic. 

 

AMR: Drug Resistance – In conversation with Dr Frances Davies and Dr Elita Jauneikaite

 

Antimicrobial resistance (AMR) is when bacterial, viral, parasitic and fungal infections evolve so that they no longer respond to existing treatments, which has major impact on our ability to combat disease. Resistance to even one antibiotic can mean serious, with the use of second-line and third-line treatments potentially harming patients by causing serious side effects such as organ failure and prolonging care and recovery. When infections are resistant to multiple antimicrobial treatments, diseases can be impossible to treat.  

 

In 2019, WHO described AMR as one of the top ten global threats to public health as it killed at least 1.27 million people worldwide and was associated with nearly 5 million deaths. Now, globally, there are 4.95 million deaths per year that are associated with AMR. The UN estimates that if no action is taken, by 2050, drug-resistant infections could cause up to 10 million deaths each year. The economic impacts are huge, with some estimates projecting that AMR could cost up to $1 trillion annually worldwide. Low- and middle-income countries bear the burden of drug-resistant infections. Antimicrobial resistance has the potential to affect people at any stage of life, as well as healthcare, veterinary, and agriculture industries. This makes it one of the world’s most urgent public health problems.  

 

This World Antimicrobial Resistance Awareness Week, the Institute of Infection is speaking to some of the researchers at Imperial College London working to combat this global treat. Our first blog in the series is about drug resistance and features Dr Frances Davies from the Department of Infectious Disease and Dr Elita Jauneikaite from the School of Public Health  Dr Davies is an Academic Clinical Microbiologist who, in her daily practice, sees patients with infections that are increasingly difficult to treat. Her research focuses on developing new ways to tackle antimicrobial resistance. Dr Jauneikaite is the Research Lead for Priority Pathogens theme in the National Institute of Health Research Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance (NIHR HPRU HCAI AMR). 

 

Tell me about yourself and your research 

 

FD: I am a Consultant Clinical Microbiologist, and my research is driven by the problems I see every day in my clinical practice – and sadly antimicrobial resistance is on the rise. I have two main focusses to my research from this: why do people get AMR infections? and what can we do to prevent them? For the first part, I investigate what has happened at a patient level to cause them to develop a resistant infection: is it something in their medical care or past history that has led to this? is it something to do with the antibiotics that have been tried that has been unsuccessful? or has there been a breakdown in infection prevention and control measures that have led to this? A lot of this information comes from assessing the learning from outbreaks of AMR infections and the ways antibiotic resistance is spread, methods of diagnosis, and rapid testing for diagnosis and accurate testing for AMR; not always as simple as it sounds, particularly on a large scale of a busy diagnostic lab and NHS healthcare setting. The second part – strategies to prevent infection – includes investigating novel technologies for tracking and even predicting the spread of infection, incorporating whole genome sequencing into this for improved accuracy, using antibiotics in the optimum ways, and more novel strategies such as preventing serious infection in vulnerable patients who are colonised by AMR bacteria (carriers), such as restoring healthy gut microbiota to prevent infection.  

 

EJ: I am an Advance Research Fellow in Bacterial Genomics and Epidemiology and I am the Research Lead for the Priority Pathogens theme at the NIHR HPRU HCAI AMR. My research is focused on improving maternal and infant health and reducing global antimicrobial resistance burden. I use DNA sequencing technologies, bioinformatics, and molecular biology techniques to investigate how bacterial pathogens to adapt to combat antibiotics and how these AMR pathogens transmit from person-to-person; findings from my research help to inform patient and public health interventions.    

 

What are the key challenges in your research area?  

 

FD: The adoption of novel technologies into healthcare is difficult as hospitals always have to have a careful eye on the budget, and persuading finance officers that spending money will ultimately save money is very difficult.  

 

EJ: Some of the key challenges in my research area are a lack of longitudinal multi-cohort studies with bacterial sampling at multiple points over time and collection of detailed host information over time as well; also, the lack of data from resource limited areas due to lack of funding that would increase the capacity and functionality of some of the settings.   

 

What do you perceive as the “origins” of antimicrobial resistance?  

 

FD: Bacteria have been around far longer than humans and reproduce very fast (around every 20 minutes for E. coli in the right conditions), and they are surprisingly good at sharing mechanisms of resistance between different species. A lot of the antibiotics we use have been developed over millennia by fungi to fight bacteria, as they have evolved alongside each other. The bacteria have already had time to develop their resistance mechanisms. We use antibiotics not only in human healthcare, but in veterinary practice and in agriculture on a vast scale – if bacteria are meeting the antibiotics derived from those they’ve met before in so many different ways, it was only a matter of time really before they managed to share the existing, and develop new, resistance mechanisms. Sir Alexander Flemming delivered just such a warning when he discovered penicillin.  

 

EJ: Bacteria, like any other live organism, are just trying to survive, so they are adapting to used antibiotics and antimicrobials and will try to adapt to any new ones that we might have in the future. And this is due, not only to the antimicrobials being used to treat humans or animals, but  also about antibiotics leaking into our environment through wastewater or similar. We therefore need to look at the AMR issue as a One Health approach, which includes human, animals, environment. 

  

Where do you think Imperial’s strengths lie in this field?  

 

FD: There are so many talented researchers at Imperial, with different things they bring to the fight against AMR. Without the excellent scientists to discover what is happening at a molecular level or the chemists and engineers who develop new technologies to detect, treat and prevent AMR, and the wealth of clinical staff in all different areas of practice, none of us can solve this problem on our own, and each bring something different to the field. Imperial being an Academic Health Science Centre really benefits that.  

 

EJ: I think Imperial’s strength in the AMR field is multidisciplinary work and very strong connections and collaborations with colleagues at NHS, UKHSA and global partners. Also, Imperial regularly interacts with policymakers, and has a strong record of engaging public and patients in the discussions around AMR, challenges, and potential solution. 

 

What solutions would you like to see in the future?  

 

FD: I’d like to see politicians around the world unite to stop the excessive use of antimicrobials in farming, by improving global farming practices, and introducing policies to restrict antibiotic use to only on the advice of appropriately trained healthcare professionals. Without that, the problem is not going to stop, and we are going to continue to struggle to treat people when they develop AMR infections.  

 

EJ: I am happy to see that the public are more aware about what antibiotics are and when to use them, also the importance of hand-hygiene and other preventative measures for stopping infections spreading person-to-person. This should definitely feature strongly among solutions for managing AMR, as this will help to reduce inappropriate antibiotic usage or overuse of antibiotics.    

 

How important is an interdisciplinary approach to AMR research?  

 

FD: It’s absolutely vital – there is no way this problem can be tackled by just one approach.   

 

EJ: I think that an interdisciplinary approach to AMR research is extremely important as it can really provide us with some proper novel insights by linking the different analyses and synthesising results in a wholesome and coordinated way; some of these insights might be missed by just drawing the information and theoretically applying it to your dataset. I am very pleased to see that more and more interdisciplinary projects are taking place at Imperial as well as globally.   

   

Are you optimistic that we can successfully overcome the challenges posed by AMR?  

 

FD: Yes, but it isn’t going to be easy, and there are significant global problems that need to be addressed to halt the spread of AMR. I don’t think we’ve reached the tipping point for AMR yet, but there needs to be a global response to this – people need to acknowledge and understand the problem and act together to stop it.  

 

EJ: Yes, it will take quite a few years or maybe decades, but I am feeling optimistic as there is more awareness of AMR amongst the public, all specialty healthcare professionals, and policymakers. As AMR is a global problem, it will need global solutions to address AMR challenges from multiple angles. But, I believe we can do it if we all work together.   

 

Where do you see your research going in 5 years’ time?   

 

FD: In 5 years’ time I hope we will have a better understanding of some of these areas, and we can start translating them into patient care.  

 

EJ: I see my research combining more interdisciplinary data or results, and expanding into investigating not only individual bacterial species, but also looking into the dynamics of this species and its environment and that influencing bacterial ability to acquire AMR. I would hope that the findings from my current and future research will inform intervention measures and even maybe provide some targets for point-of-care diagnostics; all that would then help to identify patients, who need targeted interventions to help avoid AMR infections, to manage their AMR infection if they have one, or prevent AMR pathogen transmitting to other persons or environment. 

 

(more…)

Celebrating Black Infection Scientists from the Past and Present

Black History Month allows everyone to share, celebrate, and understand the impact of black heritage and culture. People from African and Caribbean backgrounds have been a fundamental part of British history for centuries. Although it was launched in America in 1926 by Carter G Woodson, the first Black History Month in the UK took place in 1987, the 150th anniversary of the abolition of slavery in the Caribbean. It was arranged by Akyaaba Addai-Sebo, who came to the UK from Ghana as a refugee. Like Woodson before him, he wanted to challenge racism and celebrate the history of black people.  

To mark Black History Month, the Institute of Infection looked back to some of the most influential Black scientists throughout history and collaborated with current Imperial researchers to celebrate their accomplishments and visions for the future.

A look back at history 

Mary Seacole (1805-1881): Carer of victims of cholera and yellow fever epidemics; heroine of the Crimean War 

Mary SeacoleMary was born in Kingston, Jamaica, in 1805. Her mother was black, and her father was a white army officer. From the age of 12, she helped her mother run a boarding house where they treated sick or injured soldiers, and, at 15, she travelled to England and learned about European medicine. Between 1850 and 1851, Mary nursed victims of cholera epidemics in Kingston and Cruces, Panama, using mustard emetics to make the patient vomit, warm clothes to combat chills, mustard plasters on the stomach and back and calomel in varying doses.   

 In 1853, Mary returned to Kingston for the yellow fever epidemic and supervised nursing services at the British Army’s headquarters before transforming her mother’s old lodging house into a hospital. In 1853, after being denied permission by the British War Office in England to serve as a nurse in the Crimean War, she funded her own trip there and set up a hotel to treat soldiers and tend to those on the front lines.  

On her return to London, she continued fundraising efforts, including the Seacole Fund Grand Military Festival, which drew in thousands of attendees. She also published her bestseller book.  

Mary was lost to history for 100 years, but in 2004, she was voted the Greatest Black Briton, and in 2016, her statue was unveiled in the grounds of St Thomas’ Hospital, London.  

Read more about Mary Seacole.

Dr George Rice (1848-1935): Assistant to Sir Joseph Lister and Chief Vaccinator  

Dr George Rice Dr George Rice was born in New York, USA in 1848. After graduating from Dartmouth and training as a surgeon in Edinburgh, he served as a house surgeon at the Royal Edinburgh Infirmary, where he assisted Sir Joseph Lister, the pioneer of antiseptic treatment. Dr Rice then moved to Manchester, worked in the Royal Infirmary as a house physician, and held resident appointments at the Chorlton Union Hospital and Woolwich and Plumstead Infirmary. He also held office under the Metropolitan Asylums Board at the Downs Ringworm Hospital, and was a resident medical officer at the Fulham Workhouse. 

In later years, he worked at local schools for poor and orphaned children, specialised in treating patients with epilepsy, and became District Medical Officer and Chief Vaccinator for Sutton and Cheam areas which now contains a community garden dedicated to him.  

Read more about Dr George Rice 

Dr Harold Moody (1882-1947): Doctor and ambassador for Britain’s Black Community

Dr Harold Moody

Dr Harold Moody was born in 1882 in Jamaica, then moved to London in 1904 to study medicine at King’s College. After qualifying as a doctor in 1910, he applied for a job at the hospital but was denied due to racial discrimination. He would not allow racism to hold him back and, instead, started his own surgery in Peckham in 1913. Dr Moody treated the children of poor families for free, and people would come from near and far to see him. Dr Moody also became an influential community leader and an ambassador for Britain’s Black community. In 1999, Consort Park in Peckham was renamed Dr Harold Moody Park, in 2007, a bronze portrait of him was put on display in Peckham Library, and in 2020, Dr Moody was included in Patrick Vernon and Angelina Osborne’s book “100 Great Black Britons”.  

Read more about Dr Harold Moody

Alice Ball (1892-1916) Inventor of the “Ball Method” treatment for leprosy  

Dr Alice BallAlice Ball became the first African American and woman to graduate with an MSc in Chemistry in 1915 from the University of Hawaii. At 23, she became the University’s first female chemistry instructor. At the time, the only treatment for leprosy was chaulmoogra oil; however, it was almost impossible to use effectively. Ball found a way to create a water-soluble solution of the oil’s active compounds that could be injected safely with minimal side effects. It was called the “Ball Method” and became the first successful treatment.  

For over 30 years, her discovery made a huge impact on thousands of infected individuals until sulfone drugs were introduced. Alice died at the age of 24, and the president of the University of Hawaii continued her research without giving her any credit for the discovery; she remained largely forgotten from scientific history until recently. February 29 is now known as “Alice Ball Day” in Hawaii, and the Alice Augusta Ball scholarship has been established to support students pursuing a degree in chemistry, biology, or microbiology at its University. 

Read more about Alice Ball

Professor Augustus (1883 – 1959) and Dr Jane Hinton (1919 –2003): Prominent bacteriologist and co-inventor of the Mueller-Hinton agar 

Augustus and Jane Dr Jane Hinton was born in May 1919 in Canton, Massachusetts. Her mother was a teacher, and her father, Professor William Augustus Hinton, was a bacteriologist and one of his era’s most prominent African-American medical researchers. In the 1920s, Augustus developed a test for syphilis that was widely used until newer methods were developed after World War II. Augustus was the first African-American professor at Harvard Medical School and the first African-American to write a medical textbook.  His daughter, Jane, joined his lab after graduating in 1939 and became an assistant to John Howard Mueller in Harvard’s Department of Bacteriology and Immunology. She also helped develop the Mueller-Hinton agar, which has become one of the standard methods used to test bacterial resistance to antibiotics. After gaining her doctorate in Veterinary Medicine, she joined the Department of Agriculture as a federal government inspector in Framingham, Massachusetts, and was involved in research and response to outbreaks of disease in livestock.  

Read more about Dr Jane Hinton

Read more about Professor Augusts Hinton

Professor Dame Elizabeth Nneka Anionwu (1947-): UK’s first sickle cell and thalassemia nurse specialist who fought to make the NHS fairer 

Dame Elizabeth AnionwuProfessor Dame Elizabeth Nneka Anionwu was born in Birmingham in 1947 and identifies as Irish/Nigerian heritage. She started working for the NHS as a school nurse assistant in Wolverhampton at 16 and was also a health visitor and tutor for the black community in London. In 1979, she helped to establish the first nurse-led UK Sickle & Thalassaemia Screening and Counselling Centre, and from 1990-1997, she worked at the Institute of Child Health, UCL as a Lecturer then Senior Lecturer in Community Genetic Counselling. She later became a Professor and Dean of the nursing school at the University of West London.

In 1998, she established the Mary Seacole Centre for Nursing Practice, which she led until her retirement in 2007. The Centre, which was set up to address racial inequalities in the nursing profession, offered a framework for student nurses to learn about infections and ran campaigns to increase the number of nurses from minority ethnic backgrounds. Dame Anionwu improved awareness of sickle cell disease within the NHS for forty years. She was granted Damehood (DBE) in 2017 in the Queen’s New Year’s Honours List for her services to nursing, received the Pride of Britain Lifetime Achievement Award in 2019, and was honoured with the Order of Merit in 2022.

Read more about Professor Dame Elizabeth Nneka Anionwu 

Visions of the future: Meet some of the Black researchers at Imperial working to improve infection 

Professor Faith Osier: working to ‘Make Malaria History’  

Professor Faith OsierProfessor Faith Osier studied medicine in Nairobi, Kenya, and while working as a Junior Doctor (1998-2001) in a rural hospital in Kilifi, she would admit up to five children with malaria to the high-dependency unit. Many didn’t survive. This inspired her to think about prevention and how she could stop children from getting malaria in the first place to ‘Make Malaria History’.

Professor Osier won an African Research Leader Award, funded by the UK MRC and the former UK Department for International Development, which kickstarted multicentre research studies that evolved into the SMART South–South Malaria Antigen Research Partnership with Ghana, Senegal, Mali, Tanzania, Uganda, and Burkina Faso. Her work focusses on mechanistic studies to help answer why the burden is disproportionately high in infants and young children and why this vulnerable group becomes increasingly resistant with age. This insight will be critical for developing malaria vaccines.

Professor Osier is currently Chair of Immunology and Vaccinology in the Department of Life Sciences and the Co-Director of Imperial’s Institute of Infection. In 2019, she became the first African (and only the second woman) to become President of the International Union of Immunological Societies (IUIS). Professor Osier is passionate about leadership issues of equity and diversity, particularly elevating the role of women. She is a role model, motivator, and passionate supporter of scientists from low and middle-income countries.

Professor Faith Osier: “Celebrating the achievements of black scientists is vital for changing mindsets about who we are and what we bring to the table – a great step forward towards inclusivity”.

Read more about Professor Faith Osier 

Dr Calvin Tiengwe: Sir Henry Dale Fellow contributing to the understanding of African sleeping sickness    

Dr. Calvin Tiengwe Dr Calvin Tiengwe is a Sir Henry Dale Fellow at the Department of Life Sciences. Originally from Cameroon, he has lived in the UK and USA for 20 years, researching various aspects of trypanosome molecular biology that make them successful pathogens of humans and animals. His fellowship, funded by the Royal Society and Wellcome Trust, allowed him to set up an independent research program at Imperial. He earned his PhD from the University of Glasgow, then undertook postdoctoral fellowships at Johns Hopkins and SUNY Buffalo, USA. More about his work can be found here. 

“Black History Month shines a light on underrepresented minorities within our communities. It promotes an inclusive culture today and inspires the next generation to be equal contributors in a world where equity and inclusivity are inherent. My hope is that, in my career and beyond, we move towards a future where every day reflects the rich diversity of our humanity.” – Dr Calvin Tiengwe  

Read more about Dr Calvin Tiengwe

Dr Julia Makinde: Developing vaccines and strengthening of research capacity  

Dr Julia Makinde Dr Julia Makinde was born in Delta State, Nigeria, where she obtained her Bachelor’s degree in Zoology from the University of Ibadan. The foundations of her career were established at the University College London and Cardiff University Wales, where she obtained a Master’s degree in Molecular Medicine and PhD in Medicine/Immunology, respectively.  

Her interest in translational science fuelled her contributions to our understanding of the fundamental rules that govern immune cell interaction with antigens derived from self, vaccines, and infectious pathogens. Further work in global health research has focused on the development of novel vaccine candidates against infectious pathogens like HIV and the strengthening of research capacity.

Dr Makinde is a Senior Manager of Clinical Immunology and Honorary Lecturer based at the IAVI Human Immunology Laboratory. She currently works on the ADVANCE programme, funded by the International AIDS Vaccine Initiative, a five-year cooperative agreement to further the progress of HIV research, working with a network of researchers from around the world.

“Black History Month is a reminder of our collective history and a universal call for an inclusive and equitable society. Through my career, I hope to be the positive change that I yearn for.” Dr Julia Makinde  

Read more about Dr Julia Makinde

Dr Wayne Mitchell: Championing and leading equality, diversity and inclusion at Imperial 

Dr Wayne Mitchell

Dr Wayne Mitchell is the joint Associate Provost for Equality, Diversity, and Inclusion, Senior Teaching Fellow, and Senior Tutor in the Department of Immunity and Inflammation.

Having graduated from the University of Birmingham with a degree in Biomedical Science, he completed a PhD at University College London in Molecular Genetics before undertaking postdoctoral positions in Cancer Biology and Immunology. He has always been interested in understanding what makes students learn and has taught at all levels of the British Education system. He completed a Master’s in Education at Imperial College, focusing on the experiences of Black British students at elite universities and how their ‘minority status’ impacts on their sense of belonging and identity.  

Dr Mitchell’s passion and flexible working approach has had a positive impact on many students’ academic and personal experience, as well as other staff. In 2018, he was the recipient of the President’s Medal for Excellence in Supporting the Student Experience. He joined Imperial College’s Race Equality Charter-Self Assessment Team in 2019 to help understand the impact that being a member of a minoritized groups at Imperial College has on their sense of belonging and identity as a BME students. He is Co-Chair of Imperial College Race Equity Staff Network -Imperial As One, which promotes greater understanding and inclusivity for the diverse College community. One of his roles includes hosting Imperial As One’s weekly interview series, Belonging, which explores the lived experience of individuals from minoritized groups. In 2021, along with the Co-chairs of Imperial As One, he received the President’s Medal for Excellence for Community and Culture. He was recently appointed joint Associate for Equality, Diversity, and Inclusion at Imperial along with Professor Lesley Cohen. 

“This year we’ve celebrated 75 years of the arrival of British citizens on the Empire Windrush and the birth of the NHS, two momentous events, so it’s important that we take the time to educate and celebrate the contributions that the African Diaspora has made to the everyday life of Britain and across the globe. To quote the late Stuart Hall, ‘We are here because you were there’ meaning that all our histories are connected and we need to recognise and acknowledge that fact. BHM shines a spotlight on the many great achievements and connections and encourages everyone to embrace all aspects of our identities as Black British People who Belong. My hope is that BHM will one day be viewed as British History Months and not be limited to October but celebrated 24/7/365 because Black history is British History recognised for it’s uniqueness and included in the everyday narrative of Britain.” Dr Wayne Mitchell

 

Read more about Dr Wayne Mitchell

 Dr Dauda Ibrahim: Transforming RNA vaccine manufacturing  

Dr Dauda IbrahimDr Dauda Ibrahim is a postdoctoral research associate in the Clean Energy Process (CEP) Laboratory, Department of Chemical Engineering. He received both his MSc and PhD degrees in Chemical Engineering from the School of Chemical Engineering and Analytical Science, University of Manchester. Dr Ibrahim’s research focuses on the development of systematic frameworks for computer-aided working fluid design and optimisation of organic Rankine cycle systems. Dr Ibrahim also worked on pandemic-response adenoviral vector and RNA vaccine manufacturing. This model-based assessment provides key insights to policymakers and vaccine manufacturers for risk analysis, asset utilisation, directions for future technology improvements, and future epidemic/pandemic preparedness, given the disease-agnostic nature of these vaccine production platforms. He was also first author on ‘Model-Based Planning and Delivery of Mass Vaccination Campaigns against Infectious Disease: Application to the COVID-19 Pandemic in the UK’ paper which showed by integrating demand stratification, administration and the supply chain, the synergy amongst these activities can be exploited to allow planning and cost-effective delivery of a vaccination campaign against COVID-19 and demonstrates how to sustain high rates of vaccination in a resource-efficient fashion.

“The importance of Black History Month is to create awareness, honour, celebrate, and promote the contributions and achievements of black people within the UK and across the globe, thus inspiring the young generation” – Dr Dauda Ibrahim  

Read more about Dr Dauda Ibrahim

Dr Fadil Bidmos: Tackling bacterial meningitis, a leading cause of mortality and morbidity in children  

Dr Fadil Bidmos

Dr Fadil Bidmos, an Advanced Research Fellow in the Department of Infectious Disease, focuses on developing novel and cheap-to-produce vaccines that will target the two leading causes of bacterial meningitis, meningococcus and pneumococcus. He uses advanced tools to develop this vaccine in a “next generation” format.  

“Black History Month is essential because it is a time during which the struggles, triumphs, and traditions of the Black community are brought to the forefront of public consciousness. Activities during the month help to break harmful biases and misconceptions, challenge prejudices, inspire future generations, and foster cultural appreciation. The lived experiences of black individuals, past and present, are also on full display during this month; this knowledge is essential in the creation of a more inclusive and equitable society, one in which the invisibility, disregard and undervaluation of blacks is non-existent. By continuing to educate ourselves about black history and acknowledging the systemic barriers that (unfortunately) still exist, we can work towards a future where everyone is treated with the dignity and respect they deserve.” Dr Bidmos  

Read more about Dr Fadil Bidmos

 

 

 

Bacterial meningitis: A leading cause of mortality and morbidity in kids

Earlier this year, the Institute of Infection began the recruitment of several Early Career Researcher Champions. They have wide-ranging research foci and stories, which we will share via this blog.

Fadil Bidmos: Scientist presenting talkTo be introduced first is Dr Fadil Bidmos, an Advanced Research Fellow in the Department of Infectious Disease. Fadil’s research focuses on developing novel and cheap-to-produce vaccines that will target the two leading causes of bacterial meningitis, the meningococcus, and pneumococcus.

Meningitis is an inflammation of the protective membranes covering the brain and spinal cord. It can be caused by bacterial, viral, and in rare cases, fungal or parasitic infections. While viral meningitis is the most common, bacterial meningitis is associated with the most serious mortality and morbidity. According to the National Institute for Health and Care Excellence (NICE), bacterial meningitis affects 1 per 100,000 people in the UK. Despite the availability of vaccines for the most common causes, bacterial meningitis remains a major global health challenge, including being a significant threat to the 450 million people living in the 26 countries in Africa’s Sub-Saharan ‘meningitis belt,’ which has the highest disease burden.

According to the WHO, just four types of bacteria are responsible for more than half of the deaths from meningitis globally, and they cause other severe diseases like sepsis and pneumonia.

“Around 1 in 6 people who get this type of acute bacterial meningitis die, and 1 in 5 have severe complications.” – The WHO.

Research to improve the understanding and treatment of bacterial meningitis is essential and must focus on identifying solutions that will benefit global populations. The development of cheap-to-produce vaccines is a significant component of this challenge, as Dr Bidmos explains.

Please describe your research, especially the parts involving meningitis.

My research focuses on developing novel and cheap-to-produce vaccines that will target the two leading causes of bacterial meningitis, the meningococcus, and the pneumococcus. We are using advanced tools, now available at our disposal, to develop this vaccine in a “next-generation” format.

How is your research helping to find a cure for meningitis, as there is already a vaccine for it?

While there are vaccines already licensed for use against meningitis, continuous efforts are required for further vaccine development as currently, available vaccines do not provide complete protection against the disease. Hence, my research seeks to fill the gap in protection that current vaccines do not offer. Antibiotics help cure meningitis. However, 15 out of every 100 individuals affected by the disease die because of misdiagnosis (early meningitis symptoms – fever, headache, lethargy – are non-specific) or late treatment intervention, even following antibiotic administration. Hence, prevention is better than cure, and vaccines are the preferred prophylaxis option.

What are meningococcal vaccine-candidate antigens, and how did you discover them?

In essence, a vaccine candidate antigen is one that: (1) can induce a functional immune response, (2) is present in abundant amounts on the bacterial surface, and (3) exhibits little to no variation from one type of bacterium to the next. Because of ongoing discussions regarding intellectual property (IP) rights, the exact identity of our identified antigen(s) cannot be revealed at this stage. However, the route to discovery involved an elegant approach known as Reverse Vaccinology 2.0 (RV 2.0).

In RV2.0, antibodies targeting the meningococcus (and, in a separate study, the pneumococcus) were cloned from patients recovering from the disease. These antibodies were tested for their ability to kill the meningococcus/pneumococcus in the lab. Those antibodies that could destroy the meningococcus or pneumococcus were next analysed for what antigen induced their production in the patient. Using RV 2.0, we have successfully identified antigens that have never been considered for vaccine candidacy for either of these pathogens and are, therefore, novel.

What do your meningococcal carriage studies involve?

Because the meningococcus exists in a harmless state in the throat of humans known as carriage, and this carriage state usually precedes disease (“accidental” entry of the bacterium into the systemic circulation), carriage studies inform on what types of the bacterium are circulating. This information helps meningococcal biologists and policymakers to design effective preventive (vaccines) and curative (anti-AMR) measures.

In a carriage study, throat swabs (and, in some cases, small blood samples) are taken from healthy individuals to assess the presence of the meningococcus in the throat, followed by elucidation via molecular genetic analyses of the type of the bacterium it is that an individual is carrying. The blood samples facilitate the assessment of the type, quantity, and quality of the adaptive immune response, if present, to the carried meningococcus or previous carriage events.

How vital is interdisciplinary research, and how have you used it in your research?

The more we understand about the aetiological agents of disease, the more we realise the magnitude of the effort required to diagnose, treat or prevent disease. The magnitude of this effort involves technologies stemming from different disciplines; hence, cross-talk between these disciplines is essential. For example, for developing a cheaper-to-produce glycoconjugate vaccine against bacterial meningitis using protein-glycan coupling technology (PGCT), our research group (composed of mainly microbiologists and immunologists) is collaborating with experts in glycobiology, some of whom are structural chemists. Delivery of such a vaccine may be most effective in a nanoparticle format, in which case the expertise of biophysicists will be required.

What can be done to reduce the number of antimicrobial-resistant meningitis cases?

From the preceding, effective vaccine development is an obvious solution, which robust epidemiological studies will engender. Alternative therapeutics such as novel antibiotic compounds and antibody-based compounds are another, but the latter requires further work as a complete understanding of the exact nature of the contribution of antibodies to pathogen clearance (especially in the case of pneumococcal meningitis) is currently unknown.

What are the critical challenges in meningitis research, and how can they be solved?

Quite a few stemming from different pathogen- and host-borne facets, but I’d like to highlight the diversity embedded in the genomes of and exhibited phenotypically by the pathogens. For example, a key vaccine component in currently available vaccines is the capsule, a water-filled envelope that encases the bacterium and protects it from desiccation during inter-host transmission and from host immune factors. More than 100 structural variants of this capsule exist for pneumococcus. With accruing data showing an inhibitory limit on the number of capsules that can compose an effective vaccine, vaccine research is thus complicated. The situation is much worse with proteins, of which more than 1000 variants can exist, e.g., the immunodominant meningococcal PorA protein.

Rational structure-based approaches in synergy with higher-throughput technologies could solve these challenges. Multicomponent vaccines, already utilised in the 4CMenB meningococcal vaccine, are a viable solution that will increase the breadth of coverage afforded by vaccines, i.e., each component may target a group of strains possessing non-overlapping/non-synonymous antigenic repertoires hence limiting the potential for vaccine escape.

What advances would you like to see in meningitis research in the next ten years?

Technologies/approaches that would facilitate the development of mucosal vaccines.

To help raise awareness on meningitis, do you have a message or call to action for other researchers that you would like to share?

Suppose the clinical endpoint of prevention of asymptomatic infection is too arduous a task to fulfil for vaccines in trials, but prevention of disease is easier to attain. Shall we consider lowering the licensure bar if the latter at least protects that extra life? For example, the 4CMenB vaccine and its usefulness against invasive meningococcal disease incidence in infants.

Fadil Bidmos: Scientist presenting poster of researchWhat opportunities would you like ECR to have to help with your careers?

Funding and individuals in our “Personal boardroom” that fulfil the power roles, i.e., unlocker, sponsor, influencer, and connector.

 

World Hepatitis Day 2022: The Road to Elimination

July 28th marks World Hepatitis Day, and this year’s theme is ‘I can’t wait’, highlighting the need to act fast to tackle viral hepatitis.

Across the globe, more than 350 million people live with viral hepatitis, and somebody dies of a hepatitis-related illness every 30 seconds. Although viral hepatitis is a global phenomenon, it affects low- and middle-income countries the most severely.

Viral hepatitis occurs when a viral infection causes inflammation of the liver. There are five main strains of viral hepatitis, labelled A to E, which all behave differently. Hepatitis can range from mild to severe; some people experience no symptoms at all, whilst others suffer life-threatening infections. In some cases, particularly when patients experience chronic hepatitis B or C, hepatitis can lead to serious complications, like scarring of the liver (cirrhosis) and liver cancer.

In 2016, the World Health Organisation devised a roadmap to eliminate viral hepatitis as a public health threat by 2030. To achieve this, WHO has set targets for the reduction of new infections, the reduction of deaths from cirrhosis and liver cancer, improved access to diagnosis, and improved access to treatment.

Understanding and tackling viral hepatitis requires a broad range of skills and expertise, spanning disciplines from immunology to mathematics. In this post, we’ll highlight just some of the ways in which interdisciplinary research across Imperial is helping to make WHO’s elimination roadmap a reality.

Organ-on-chip technology: using bioengineering to simulate hepatitis B

Imperial scientists were among the first in the world to study how pathogens interact with artificial human organs.

An organ-on-a-chip is a microtechnology than contains live human cells. The chip can control the cells’ characteristics, allowing the system to mimic a human organ.

In a 2018 study, a team of scientists, including specialists in virology and hepatology from what was then Imperial’s Department of Medicine, studied the ways in which a liver-on-chip system responded to the hepatitis B virus. They were the first in the world to study the interaction between a pathogen and an artificial organ.

They found that the artificial liver responded to the hepatitis B virus very similarly to a real human liver. This means that the liver-on-a-chip is a useful tool for studying hepatitis B, understanding how the immune system responds to it, and even testing how drugs can be used to treat the virus.

Getting down to business: increasing access to hepatitis C medication

Changing the way that pharmaceutical companies license medicines can make expensive hepatitis drugs more accessible.

A World Hepatitis Day graphic, showing an image of a man standing with his arms folded, and a caption reading 'I can't wait to get treated'.The medications used to treat hepatitis C are expensive. This means that many patients living in low- and middle-income countries simply cannot afford the treatment they need. But, a 2019 study, conducted in collaboration between the Imperial College Business School and what was then the Department of Medicine, found that changes to pharmaceutical licensing agreements can help bring the price of hepatitis C drugs down.

Normally, patented medicines can only be produced by the manufacturer that owns the patent. This means the manufacturer has the power to set the price. But, pharmaceutical companies can choose to issue ‘voluntary licenses’, which allow other companies to make these medications, too.

In this study, researchers found that when voluntary licenses allowed manufacturers in low- and middle-income companies to produce hepatitis C drugs, the competition in the market brought prices down. This meant that more people were able to access the medication they needed.

Catching cancer early: finding new ways to diagnose liver cancer

Finding new ways to diagnose liver cancer could lead to better outcomes for patients.

Chronic hepatitis B and C infections can lead to a type of liver cancer called hepatocellular carcinoma (HCC). Patients with HCC often don’t notice symptoms until the disease is in a late stage. This means it’s difficult to diagnose HCC early, and as such, prognosis for patients is often poor. Scientists, including researchers from what was then Imperial’s Department of Metabolism, Digestion and Reproduction, are looking for better ways to diagnose HCC.A World Hepatitis Day graphic, showing a smiling women. The caption reads 'I can't wait to get tested'.

Over the years, many studies have suggested potential ‘biomarkers’ which could be used to diagnose HCC. A biomarker is a biological characteristic that can indicate illness. For example, certain molecules in the blood can be used as biomarkers for heart health.

In this study, the team compiled a database of potential biomarkers suggested in previous research, and developed a new statistical tool to assess the potential of each one. This could help future studies focus their efforts in the right places.

Doing the maths: modelling the elimination of hepatitis C

Mathematical modelling predicts that over 15 million hepatitis C infections could be prevented by 2030.

In 2019, research led by Alastair Heffernan from Imperial’s School of Public Health found that over 15 million new hepatitis C infections could be prevented by 2030, if a range of prevention, screening and treatment measures were adopted. This would prevent 1.5 million deaths from cirrhosis and liver cancer.

Hepatitis C is transmitted through blood-to-blood contact, meaning it can spread in unsafe healthcare settings, and amongst people who inject drugs.

A World Hepatitis Day graphic, showing a group of smiling people. The caption reads 'We can't wait for a world without hepatitis'.This study found that four interventions – improving blood safety measures, offering drug users more health and safety support, increasing treatment provision, and expanding access to testing – could drastically reduce the number of people contracting hepatitis C. If we adopt these measures, we could meet the WHO target of reducing new hepatitis C infections 80% by 2030. Deaths could be reduced 65% by 2032.