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Title: Human herpesvirus virus 6 (HHV-6) infection in immunocompromised children
Author: Lyall, Elizabeth Grace Hermione
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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The current study was designed, to include a retrospective serological assessment of HHV-6 antibody responses in samples taken from children at presentation with malignancy and sequentially during treatment. An indirect fluorescent antibody test (IFA) and an enzyme linked immunosorbent assay (ELISA) were used to detect HHV-6 lgG, and selected samples were tested for HHV-6 lgM by IFA. The paediatric patients, whether solid tumour or leukaemic patients, had a similar response to HHV-6 as age matched controls and almost all (97%) had lgG to the virus at the time of presentation. Acquisition of a response to more than one herpesvirus increased with age in the patients and where there was only a response to one virus it was usually HHV-6. Antibody responses to CMV and VZV were similar in patients and controls. Sequential samples from patients during immunosuppressive treatment showed a gradual decline over time in ELISA index for lgG to HHV-6 and no reactivations of HHV-6 were seen. lgM to HHV-6 was produced by one child with a primary CMV seroconversion but HHV-6 reactivation could not be confirmed as the possibility of cross reactive antibody was not excluded by a cross absorption experiment. A prospective analysis of HHV-6 DNA in saliva and serum was undertaken on new patients presenting between August 1992 - August 1993. HHV-6 is secreted in the saliva of those previously infected, and presence of HHV-6 in the serum implies an active viraemia. Saliva was collected prospectively from new patients, from siblings and from volunteer healthy controls. Serum was collected from patients during treatment. A nested PCR for HHV-6 was developed. The sequence of DNA chosen for amplification contained a cleavage site for the restriction endonuclease Hind 111 which enabled type "A" and "B" HHV-6 to be identified in any PCR positive samples. HHV-6 DNA (type "B") was commonly found in the saliva of healthy controls (74%) and patients (58%), but patients who were febrile, unwell and neutropaenic less frequently secreted HHV-6 in the saliva supernatant (18%). Whether this was a local effect of chemotherapy on the salivary glands was considered. HHV-6 DNA was not detected in any serum samples, suggesting no evidence of active viraemia. The potential role of HHV-6 as a serious pathogen in immunosuppressed patients remains to be fully elucidated, but in this limited study of a small paediatric cohort of oncology patients no evidence of deleterious virus activity was found.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available