Molecular diagnosis of neonatal bacterial meningitis.
Research type
Research Study
Full title
Prospective feasibility study of PCRctic - a novel assay for detection of bacteria in the cerebro-spinal fluid of newborn babies with suspected meningitis.
IRAS ID
205837
Contact name
Artur Abelian
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
0 years, 6 months, days
Research summary
Bacterial meningitis is a serious illness that can be successfully treated if diagnosed early. Accurate diagnosis of bacterial meningitis rests on the detection of bacteria in the cerebro-spinal fluid (CSF) of a patient with clinically suspected meningitis (high temperature, stiff neck, headache, photophobia (a dislike of bright light)). Accurate diagnosis of neonatal bacterial meningitis (NBM) or lack thereof is significantly more difficult for two reasons: (1) newborn babies do not develop stiff neck, photophobia or any other clinical signs specific of meningitis, (2) the sensitivity of the detection method (bacterial culture) is poor. For example, National Neonatal Audit Programme reported only seven positive CSF cultures from 174 UK neonatal units in 2014. For these reasons, in many babies meningitis could not be promptly confirmed or ruled out with confidence. Consequently, newborn babies are often over-treated with resultant unnecessary prolonged hospitalisation and antibiotic use.
The sensitivity of the detection method can be increased many-fold by using polymerase chain reaction (PCR), which detects even smallest amounts of bacteria present. This is why PCR has already been widely used for diagnosis of infections in children (including meningitis). The reason its use has not been replicated in the diagnosis of infections in newborn babies is that PCR has very narrow specificity - it only detects one type of bacteria per test, whereas neonatal meningitis can be caused by many bacterial types.
To overcome this drawback we have developed PCRctic (IRAS study 129486) - an assay based on 16S rDNA PCR technology, which we modified to enhance its sensitivity and optimised it for CSF. With few exceptions, 16S rDNA PCR detects ANY bacteria as it targets DNA region highly conserved between different types. We therefore expect that PCRctic will detect virtually any bacteria capable of causing NBM. We propose to evaluate this assay in this pre-clinical feasibility study.REC name
Wales REC 5
REC reference
16/WA/0187
Date of REC Opinion
18 Jun 2016
REC opinion
Favourable Opinion