Creation of sample collection from "Be on the TEAM" study throat swabs for molecular (PCR) analysis of meningococcal carriage and carriage density.
Bexsero has been offered to all babies in the UK since 2015 and is reducing the numbers of cases of meningitis and sepsis in young children. Although there is strong public support for offering MenB vaccine to older children, it is harder to justify the cost as there are fewer cases in this age group.
However, teenagers carry high numbers of bacteria in the back of their throats, so if MenB vaccines also reduce the chance of those teenagers carrying MenB bacteria, the cost of giving them the vaccine would be worthwhile as this could reduce cases of MenB infection in all age groups. This is called ‘herd immunity’. The government is funding a large study, called “Be on the TEAM” (teenagers against meningitis) in an attempt to find out whether this happens.
What the research team will do
This project will bring together all the swabs collected in the Be on the TEAM study and the bacterial growth from the first analysis – which detects carriers using culture alone – into a single collection. Subject to future funding, these samples can then be investigated further by molecular analysis.
Over the last 5 years, researchers in Bristol have been developing new techniques for studying throat carriage of meningitis-causing bacteria. This has improved ways to take and store throat swabs.
By combining a technique that detects bacterial DNA called polymerase chain reaction (PCR) with conventional methods of growing the bacteria it is possible to detect twice as many carriers. The PCR method alone can also accurately and inexpensively measure the number of bacteria in a swab sample.
How this research will help fight meningitis
Molecular analysis (PCR) of this large collection of samples will provide vital information about the impact of MenB vaccination on bacterial carriage in teenagers, and potentially produce evidence to influence immunisation policy.
By assembling and preserving all these samples into a single collection, the researchers are also creating a resource for future investigation into other aspects of upper respiratory tract microbiology in teenagers.
The aim of the project was to collect, collate and store swabs and products of culture from the UK wide Be on the TEAM study. This would provide a bank of specimens for future research into meningococcal disease, particularly the use of molecular methods to study meningococcal carriage.
The Government-funded Be on the TEAM study aimed to investigate the impact of two meningococcal group B (MenB) vaccines on carriage of meningococci in teenagers. By the autumn of 2019, 24,000 young people from across the UK had been successfully recruited into this study. The COVID-19 pandemic and the first lockdown, with school closures, halted the Be on the TEAM study. It was originally hoped that vaccination and sampling of participants would resume after a few months, but subsequent lockdowns and school closures meant that the study terminated early.
The early termination of the Be on the TEAM study obviously impacted on the Meningitis Now funded project. However, by March 2020 about half of the participants had completed their clinic visits and had given the required samples. This means there are now over 65,000 samples, from around 12,000 participants, stored in the laboratories at the Spencer Dayman Meningitis Laboratories at the University of Bristol.
The reason for wanting to compile this collection of study samples in the first place was to ensure they would be preserved to allow for analysis by molecular methods, which have been shown by the Bristol researchers to be more sensitive than traditional culture. The original plan was that this would effectively constitute an ‘insurance policy’ in case significant effects could not be detected using traditional culture methods.
As the Be on the TEAM study was cut short by the pandemic, fewer paired (pre-/post-vaccine) sample sets are now available for analysis. Using traditional culture methods, the available samples are unlikely to be sufficient to evaluate the study objectives. However, using molecular methods, it may still be possible to do so. With that in mind, the researchers have been working with the study sponsors to obtain the necessary funding for the molecular analysis work. An application to this effect was submitted to the study funders (NIHR) and funding has recently been awarded.
The funding from Meningitis Now, which allowed the preservation and collation of study samples for possible future molecular analysis, means that the Be on the TEAM study now has a second chance to meet its objectives, despite being cut short by the pandemic.
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