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Title: Towards a screening programme for congenital cytomegalovirus
Author: Atkinson, C. E.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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The work in this thesis investigated the detection of cytomegalovirus (CMV) DNA from dried blood spots (DBS) by polymerase chain reaction. The hypothesis was that testing DBS could be formed into a suitable strategy for CMV detection with applications in newborn screening for congenital CMV (CCMV) and in resource limited settings. An iterative approach was taken to assay development in collaboration with clinicians with proven cases and controls. Specificity was greater than 99%, but initial sensitivity for CCMV diagnosis was only 74%. Serial testing of DBS created in the laboratory showed that CMV DNA remained detectable on DBS for 24 months; a clinically relevant timescale for retrospective diagnosis. A significant association between DBS CMV viral load and the degree of sensorineural hearing loss (SNHL) was found. This relationship was non-linear suggesting an explanation for the clinical benefit of short term therapy in neonates with this chronic infection. Sensitivity was increased to 90% for CCMV diagnosis by the development of a one tube nested PCR and this method detected all cases who developed SNHL on follow up. This suggests that DBS testing could be suitable for newborn screening. The role of DBS for studies in resource limited settings was investigated. DBS were compared to plasma for CMV DNA detection. CMV acquisition in infants born to HIV-1 positive mothers was investigated with breast milk CMV viral load and maternal CD4 counts shown to be major determinants of infant CMV acquisition suggesting the possibility that restoring maternal immunity or reducing breast milk CMV levels may reduce transmission. Overall these results support the working hypothesis and provide valuable guidance on the use of DBS in clinical cohorts. Large scale studies of selected and universal screening to allow intervention against CCMV are now warranted.
Supervisor: Griffiths, P. ; Emery, V. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available