20 May 2016
The final report of the UK's Review on antimicrobial resistance (AMR) has been published and reinforces the message that the world must act now to tackle an issue that could kill up to 10 million people a year by 2050, up from 700,000 per year today.
This comprehensive report covers a broad spectrum of areas for action and it is clear that nothing short of a determined, collaborative worldwide effort is needed, using approaches that aim to reduce demand for antimicrobials through awareness, surveillance and innovation, while also supporting and incentivising drug development.
The burden of AMR will disproportionately fall on low- and middle-income countries, but high-income countries have a vital role to play in managing the problem, through collaboration, funding research efforts and leading the way in technology development. Given that this is a global crisis with multiple overlapping solutions, what can the UK do to contribute?
Efforts to tackle AMR should start at home – what are the issues affecting the UK health system, and how can we make best use of our world-leading life sciences research base to manage these challenges? Two obvious areas for urgent action are in reducing healthcare associated infections, and developing point of care (POC) diagnostics to improve antibiotic stewardship. A great example of the need for the latter is set out in a supporting document to the main AMR review: a study on the potential impact of rapid diagnostics in the management of gonorrhoea, an infection of concern where drug resistance is increasing.
Current treatment involves two antibiotics, ceftriaxone and azithromycin; there are no reliable alternatives available for resistant infections. The study modelled the use of POC testing in different patient populations to determine antibiotic susceptibility profiles of infections, and the impact of treating infections with other antibiotics such as ciprofloxacin and penicillin. The model showed that using POC tests could lead to an estimated reduction in use of ceftriaxone of 30-80%, which could extend the useful lifespan of this drug significantly.
However, there is a catch: this work is theoretical, and the POC diagnostics necessary to make this happen are not yet available to clinicians. Also, POC tests are likely (initially at least) to be more expensive, so evaluating the cost effectiveness of this approach, and our willingness to pay, will be important. The Longitude Prize aims to tackle the problem of cheap, easy to use POC diagnostics and antibiotic susceptibility profiling. Support for such initiatives is a vital contribution to the management of AMR, and may help consideration of how much we are prepared to pay for the outcomes we want.
Through Public Health England's (PHE) National Infection Service and other initiatives, the UK is already starting (or planning) to use genomics for pathogen genetic epidemiology and infection control, and is developing a whole genome sequencing service for TB. Given that these efforts are progressing and infrastructure is being put in place nationwide, the health system should consider how to make the most of newly acquired sequencing equipment and expertise in reference and diagnostic labs and take the opportunity to tackle issues pertinent to AMR. The data collected by these efforts – genetic sequences, clinical and phenotypic data – will form the backbone of a knowledge base that can be used to develop new drugs and POC tests. Government investment in ensuring that these data are collected, curated and made available is essential.
In addition to this, the impact of the continuous reinforcement of public health messages surrounding hand washing for infection control and public engagement about the appropriate use of antibiotics can't be underestimated. Initiatives such as the Antibiotic Guardian scheme will continue to play a vital role in the public's perception and understanding surrounding the importance of antibiotics as a resource that must be carefully managed.
UK research can lead the way in the development of low cost, rapid POC diagnostics to diagnose infections and drug susceptibility. These technologies will play a vital role in front-line NHS services and improve diagnosis and treatment of infections. We should also consider how to make them available to low- and middle-income countries, which have the greatest burden of infectious diseases. Access programmes such as that for the GeneXpert machine used in TB diagnosis could be used as a model for this.
A recently announced international collaboration to build an open-access database of tuberculosis genetic sequences, led by Prof. Derrick Crook of the University of Oxford and PHE, is a good example of infrastructure to support global efforts to manage disease. The aim of the database will be to collect and analyse around 100,000 drug resistant TB samples from across the world, which will be used to diagnose disease more quickly, and to develop an artificial intelligence that can predict drug resistance, providing a vital resource for lower income countries.
We can also learn from other situations where sequencing technologies have been used to monitor the genetic epidemiology of outbreaks. The use of cutting-edge MinION sequencers in field laboratories during the recent Ebola virus epidemic actively contributed to disease surveillance efforts. While the team faced some technical challenges in the field, including shaky internet access, we should consider how these technologies could be used more widely in similar situations to analyse and monitor diseases and drug resistance in poorer countries and contributing to the 'One Health' agenda that aims to understand the links between animal and human health.
These actions and others outlined in the report will be expensive, but affordable. Investment in technologies to understand, monitor and treat diseases are a few cogs in the complex global machine that will be working towards tackling AMR, which will take an estimated US$ 40 billion globally over 10 years. While this seems like a huge sum, it is a tiny proportion of the overall global health budget – and a reasonable price when set against the cost of inaction, which could lead to one of our greatest medical advances being consigned to history.