Congenital cytomegalovirus (CMV) infection is responsible for long-term morbidity in the form of sensorineural hearing loss and neurodevelopmental impairment in a high proportion of those with symptomatic infection at birth but only around 14% of those without symptoms. In contrast newborns acquiring infection posnatally, generally from maternal breast milk, do not seem to have any associated long-term sequelae. These differing clinical outcomes remain to be explained. In immunocompromised adults, quantitative CMV DNA PCR has given valuable insight into viral dynamics. Such data have informed treatment, particularly in the transplant setting, where CMV disease has been shown to be directly correlated with various measures of viral load in both blood and urine. Pre-emptive therapy has been adopted in many units as a direct result. Newer immunological techniques have also led to the realisation that a large proportion of the human host's cellular immune response is directed towards maintaining CMV in a latent state lifelong following primary acquisition of this virus. No equivalent data exist for the natural history, viral response to treatment or associated immune responses in neonates. This thesis therefore aimed to apply quantitative, virological and immunological techniques already successfully employed in adult patient groups to help define natural history and immune responses along with other measures of treatment response in this neonatal patient group through multicentre collaboration. The results presented give the first calculations of virus dynamics in response to antiviral treatment in this age group. The possibility is raised of suboptimal drug exposure in the clinical setting and data presented on both viral load and CMV-specific immunological responses have potentially important implications for treatment in these infants and for optimal sampling times which will inform future clinical trials and the continued search for biomarkers of treatment efficacy.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:631944 |
| Date | January 2014 |
| Creators | Luck, S. |
| Contributors | Griffiths, P. D. ; Sharland, M. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1435658/ |
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