Added Value Examples

An increase from the currently relatively low prevalence of CPE across much of England would have significant clinical and financial implications.  CPE are resistant to carbapenems which are normally used as last-line antibiotics to treat life-threatening conditions in hospital, so with limited therapeutic options for CPE-infected patients, clinical outcomes are poor, and outbreaks are both difficult and expensive to control for healthcare providers. Early identification of CPE-carriers via admission screening could be an important tool to reduce transmission and inform therapy, but existing evidence was limited for settings with lower CPE prevalence (as is the case in many English NHS Trusts).   

We performed model-based simulations of hospitals, with CPE prevalence covering the range of levels observed in England and used these models to evaluate the existing (2016) national CPE admission screening guidelines and alternatives to them.  Two beneficial protocol changes were identified:  

1) broadening screening selection criteria to include all admissions who had been hospital inpatients anywhere in the last year, rather than just those who had been an inpatient in a ‘problem’ area;  

2) shortening the screening test pathway to a single swab sample, rather than three consecutive swabs, 48 hours apart.   

Our work showed the former could double the CPE-carriers identified for screening in low-prevalence hospitals, and the latter would reduce the burden on test facilities and pre-emptive infection prevention and control (IPC) measures during the screening process, as well as enabling a quicker determination of a screened patient’s CPE status.

Our findings informed revised national guidelines which is the main route to communicate the research outcomes to healthcare staff in hospitals across England.  

Within this document, the screening protocol guidelines (informed by the research outcomes) are communicated in both written form and via a flowchart diagram.  A simple memorable acronym was introduced to help frontline staff assess admissions for screening selection. The final document incorporated feedback from hospital staff to an initial draft.   

The revised guidelines were published October 2020 to coincide with the introduction of mandatory reporting of CPE, when settings would be necessarily addressing their CPE procedures.  This timing was determined by legislative requirements and was unfortunately co-incident with the second wave of the Covid-19 pandemic, hence further communications happened in 2022, when settings would have been less overshadowed by pandemic-related work.     

The findings were presented at the UKHSA AMR programme forum March 2023 whose attendees include regional Health Protection Team AMR leads who are well-placed to offer local support to trusts on the adoption of the new guidelines.   

The SIREN study has provided valuable evidence on immunity following SARS-CoV-2 infection and COVID-19 vaccination and provided surveillance data on infection and emerging variants. This evidence has played a critical role in informing the national COVID-19 response. 

In January 2021 the SIREN study published its first analysis of protection following SARS-CoV-2 infection. Crucially the analysis showed that reinfection was possible and could occur, but that there was an over 80% reduction in infection among people who had previously contracted COVID-19 compared to those who had not.    

In Spring 2021 when the Alpha variant was dominant in the UK the SIREN study published its first analysis on the effectiveness of COVID-19 vaccines, focusing primarily on the Pfizer vaccine. The analysis showed that short-term vaccine effectiveness against infection 21 days after the first dose was 70% in the study population of healthcare workers and rose to 85% seven days after the second dose was received.  

In February 2022 a later publication by the SIREN study looked at protection against SARS-CoV-2 infection following both previous infection and vaccination. It found that in previously uninfected individuals, two doses of the Pfizer vaccine were associated with high short-term protection against SARS-CoV-2 infection but that this protection reduced considerably after six months.  Among those with a previous infection vaccination appeared to boost their immunity, providing strong and longer lasting protection.  This provided important insights for COVID-19 vaccination programmes.  

Additional active workstreams within SIREN include investigating correlates of protection and longitudinal antibody response, which is undertaken in collaboration with academic partners in the SIREN Consortium.

GPAS is the culmination of 20 years’ work, bringing genomic insights into medical microbiology, to improve the tools available for public health and patient care. Before the SARS-CoV-2 pandemic, we demonstrated that outbreaks of hospital bugs like C. difficile could be understood, treated, and stopped by looking at the genetic material of the pathogen. We could tell how individual patients’ bugs were related (which tells us whether they picked up the infection from the same source), and notice whether any dangerous new strains were emerging. We also developed tools to tell which antibiotics would not work on a specific patient’s tuberculosis, allowing physicians to make better prescriptions: this directly helps the patient get the right drugs, saves the health service money on potentially ineffective prescriptions, and helps reduce the spread of “superbugs” which are resistant to antimicrobial treatment.  

When COVID-19 struck, we repurposed these tools to look at SARS-CoV-2. 

From the research supported by the NIHR HPRU, provide a plain English summary of the main findings that you would have reported to the research community. If you include health economic information, please specify the value of the QALY used. Please note that negative, definitive findings that could inform disinvestment are of equal validity (indicative 500 word maximum - insert below). 

This study was the first in the world to directly measure the infectiousness of infected individuals by following their immediate contacts both in and outside the household. 

 The research was in two parts. The first part directly measured the infectiousness of individuals infected with COVID-19. The PCR data from about 1 million individuals who tested positive by attending the Testing Centres from September 2020 to February 2021 (pillar 2) was used to determine their viral load. These infected individuals also routinely name their contacts and, from the Test and Trace database, the infection status of contacts could be determined. Overall about 9% of the 2.5 million contacts were shown to be infected. A large number of patient factors together with the timing and type of contact were also available for analysis.  

 We found that the index patient viral load was a major factor in determining whether or not an infected individual was likely to transmit COVID-19 to their contacts.  

 The second part of the research was to determine the ability of lateral flow devices (LFD) to detect individuals that are infectious rather than simply infected with the virus. Because the study looked at successive individuals attending the test centre the relative distribution of viral loads could be measured. From this, and from the known ability of LFD to detecting virus, the study showed that LFDs were able to detect individuals responsible for 83-90% of transmission events. This means that if LFDs are used to identify and isolate infectious individuals, the risk of passing on COVID-19 could be reduced by 83-90%. These results allowed the UK Government and PHE to make rational recommendations on how best to use LFDs in the wider population  

The study also gave precise details of the chances of individuals at different age groups spreading COVID-19 in separate settings. For example it showed that there was only a low chance of school children spreading COVID-19 to their fellow pupils at school and transmission rates were higher amongst household contacts. This has encouraged schools to re-open. It also showed that the ‘Kent’ strain (B.1.1.7) increased transmission by about 50% confirming the need to maintain social distancing and face mask usage.