The impact of advances in molecular virology on the clinical epidemiology and management of central nervous system viral infections in infants

Kadambari, Seilesh (2017) The impact of advances in molecular virology on the clinical epidemiology and management of central nervous system viral infections in infants. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Molecular virological techniques have rapidly replaced cell culture as the diagnostic tool of choice across NHS laboratories. This thesis studies two of the commonest causes of CNS viral infections in infants less than 90 days of age to determine whether the introduction of Polymerase Chain Reaction (PCR) based techniques have impacted significantly on their management and epidemiology. Congenital CMV (cCMV) is the commonest congenital infection in the UK and a leading cause of sensorineural hearing loss (SNHL). In the absence of a screening programme the great majority are detected in early childhood outside the time when antiviral therapy has been shown to be effective. This thesis describes a series of coordinated pilot studies that suggest that it is potentially feasible to integrate testing for cCMV using salivary PCR into the Newborn Hearing Screening Programme (NHSP) and start appropriate antiviral management within the first month of life. A programme of work that needs to be conducted before potential national implementation is also outlined. Conventional molecular techniques were used to characterise the variation of five genetic loci of CMV in congenitally infected infants to better understand the current and future medical interventions available. Enterovirus (EV) infections most commonly infect young infants. PCR has been shown to detect viruses with greater accuracy than cell culture. National data over a 10 year surveillance period were analysed to demonstrate a seven fold increase in viral meningo-encephalitis diagnosis rates associated with increased use of PCR. Enteroviruses accounted for 92% of all cases of viral meningo-encephalitis in those aged less than 90 days. The year on year increase in EV infections coincided with increasing PCR-based laboratory diagnosis, which accounted for 36% of reported cases in 2000 and 92% in 2011. These data provided the rationale for the design and implementation of a British Paediatric Surveillance Unit (BPSU) study characterising the burden of EV and human parechovirus meningitis in children aged less than 90 days. This thesis supports the notion that advances in molecular virology can significantly inform the investigation and management of CNS viral infections (as exemplified by cCMV) and alter the apparent epidemiology (as exemplified by EV infections in infants less than 90 days old).