Genetic sequencing technique improves detection of viruses in suspected meningitis cases

20 May 2022
Genetic sequencing technique improves detection of viruses in suspected meningitis cases

New research published in the Journal of Infection, and part-funded by the Meningitis Research Foundation, has revealed that metagenomic sequencing (a genetic sequencing approach) was able to detect a virus in 42% of patients with suspected viral meningitis. In 56% of cases, that virus was thought to be the cause of meningitis.

Viruses are the most common cause of meningitis in adults, where a cause is found. But in as many as 40% of cases, a cause is never found, which leads to unnecessary antibiotics and antivirals being administered, and prolonged hospital stays. Many of these cases are assumed to be viral.

Using new approaches to identify the cause of suspected meningitis

To try and enhance the likelihood of identifying the bug in cases of suspected meningitis, a research team used a viral capture sequencing approach called ‘VirCapSeq-VERT’ to test samples in which no cause was previously found using conventional diagnostic methods. This is perhaps because conventional methods are better established for identifying bacteria and fungi, rather than viruses. The ‘VirCapSeq-VERT’ sequencing approach, which involves a probe set that covers the genomes of all viruses known to infect humans, is beneficial as it provides the opportunity to detect bugs, without having to consider in advance what the cause might be.

The research team studied leftover cerebrospinal fluid (CSF) samples from 73 patients with suspected, proven, or disproven infection collected in a previous study funded by Meningitis Research Foundation. Through using this approach, the researchers were able to identify viruses in 42% of patients (31/73) with suspected meningitis. Twelve viruses were detected, three of which are not routinely tested for in meningitis cases in the UK. Two of those three viruses (rotavirus and Saffold virus) had not been described in a case of adult onset meningitis before.

In at least 50% of these cases, the virus identified was thought to be the likely cause of the meningitis. The authors cannot be certain, as the cause is best established when the bug is identified at the site of active disease. Taking a biopsy of the meninges of the brain would however be inappropriate in cases of viral meningitis which are rarely life threatening. Therefore, the team used samples from the CSF fluid – which bathes the brain and spinal cord – as a proxy.

From identifying a cause of meningitis to ensuring appropriate care

Dr Fiona McGill, lead author, and specialist in clinical infection, microbiology and immunology at the University of Liverpool said,

"Our research has found that VirCapSeq-VERT increases the probability of detecting a virus. Using this agnostic approach, we identified Toscana virus which is a well-established cause of viral meningitis in Mediterranean countries, but not routinely tested for in meningitis in the UK. Additionally, our results revealed for the first time in adults, rotavirus and Saffold virus, as potential causative agents in adult meningitis. Further work is needed to determine the prevalence of atypical viral candidates as well as the clinical impact of using sequencing methods in real time."

Liz Rodgers, Head of Research at the Meningitis Research Foundation said,

"Being able to identify the cause of a case of suspected meningitis is really important to ensuring the patient receives the most appropriate treatment and care, and to limit stress and uncertainty. Identifying the cause of meningitis also has benefits for the wider health system through preventing use of unnecessary antibiotics, antivirals, and prolonged hospitalisation. It is encouraging that in this exploratory study, 10% of previously undiagnosed cases had a likely cause found, underlining the potential for more widespread use of genetic sequencing to confirm the diagnosis of meningitis in the 40% of patients in whom the cause is never known."

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