5 October 2015
In our recent report Pathogen Genomics Into Practice, we provided 35 recommendations to effectively implement genomics in infectious disease services. Although there are currently many small-scale projects underway where pathogen genomics is being used in a clinical context, implementation is not consistent nor are services available population-wide.
While genomics can have an impact on all aspects of the infectious disease pathway, from diagnosis and identification through to determination of drug susceptibility, infection control is the one area where genomics is now applicable, for all pathogens.
How can whole genome sequencing improve infection control?
Many smaller scale studies have shown how sequencing can overturn conventions about what is causing nosocomial outbreaks and how transmission is occurring. Infection control efforts in hospitals tend to focus on reducing patient to patient transmission, and measures, such as screening and decolonisation of patients, have had a significant effect on the number of bloodstream infections caused by methicillin resistant Staphylococcus aureus (MRSA), for example. One whole genome sequencing (WGS) study carried out in a hospital intensive care unit on S. aureus transmission showed that 7 out of 37 cases were due to transmission from colonised patients, and that WGS was more accurate than current typing methods in confirming or refuting transmission events.
One of the disadvantages of current typing methods, compared to WGS, is that they compare small sections of the genome and therefore tend to overestimate the relationship between isolates. WGS is useful in situations where conventional methods suggest that all cases are related, making it challenging to determine the epidemiology of an outbreak. Being able to determine where infections are coming from – other patients, the environment or an external source – can be vital to prevent infections spreading further, determine whether an outbreak or a series of unrelated cases has occurred, and thus help target infection control efforts appropriately.
Another advantage of using WGS is that it can be used to help determine the direction of transmission, i.e. not just that two cases are related, but who infected who. This is done by comparing the DNA sequences of bacterial samples taken from different patients, and combining this with epidemiological information, if available. The principle behind this method is to measure the relatively constant and random mutation rate within the genome of pathogens, the so-called 'molecular clock'. This figure has been calculated for tuberculosis as being 0.5 changes per genome per year. By comparing the differences between samples collected at different time points, researchers can determine which infections occurred first, and therefore infer which patients transmitted infections. In the case of a disease such as tuberculosis, this technique can help find 'super-spreaders', the minority of patients who are responsible for the majority of onward transmission.
What needs to be considered to optimise pathogen genomics for infection control?
The benefits of using genomics for infection control within hospitals are outlined in the first of two briefing notes, Protecting patients from healthcare associated infections: a role for genomics, describing the advantages of using whole genome sequencing to determine transmission and sources of infection in situations when conventional methods have failed. With benefits that include swifter resolution of outbreaks and better targeting of infection control measures, our policy considerations focus on the assessment of each hospital's needs and the situations where genomics will make an impact.
In the second briefing note, Provision of genomics for infection control: coordinating and meeting local and national needs, we highlight one of the most important issues facing the implementation of pathogen genomics: strategic cooperation and coordination. Genomic information can be used to inform the treatment of the patient, but the genetic sequence of that pathogen is also useful in a public health context. We describe what needs to be considered to ensure that genomics meets the health system's demands at both a local and national level, how we can establish equitable services, collaborate effectively, share information and knowledge, and align priorities.
Our work on infectious disease genomics has shown that whole genome sequencing can have a major impact on the control of infection in hospitals and meet national public health needs, but, for this potential to be realised, a significant coordinated effort and supportive financial investment must be made to establish the infrastructure needed.
If pathogen genomics is implemented effectively into infectious disease services in line with our recommendations, then the English Health System will be world-leading in its use of genomics in medicine.