Molecular and serological analysis of herpesvirus infections in the immunocompromised host
There are eight described human herpesviruses. All share the ability to achieve latency in their host following primary infection and may subsequently reactivate later in life. In immunocompetent individuals herpesvirus infections, especially those caused by reactivating virus, are usually mild however in patients with impaired cellular immune function they may cause significant morbidity and mortality. In this thesis molecular and serological techniques were used to define the prevalence of the human herpesviruses in a variety of immunocompromised groups as these individuals are at greatest risk of severe herpesviral disease. Human herpesvirus 8 (HHV8) is the most recently discovered of the human herpesviruses. A nested polymerase chain reaction (PCR) for detecting HHV8 genome was designed and used to examine the association between infection with HHV8 and FIIV-associated Kaposi's sarcoma (KS). The prevalence of HHV8 genome carriage in the general UK population was defined, as were potential routes of HHV8 transmission. Novel treatments for HIV-KS were investigated. The value of herpesviral genome detection in predicting associated disease was evaluated, together with the genome load response of cytomegalovirus (CMV), a significant herpesviral pathogen, to a novel chemotherapeutic protocol for immunosuppressed patients receiving allogenic bone marrow transplantation. The prevalence and epidemiology of HHV8 were found to be compatible with that predicted for a causal agent of KS, but not the haematological malignancy multiple myeloma. Apart from 1-IHV8, Epstein-Barr virus and CMV were found to be the most significant herpesvirus pathogens in the immunocompromised host. The use of molecular detection techniques, such as PCR, were shown to be of great value in the diagnostic and epidemiological determination of herpesviral infection in immunocompromised patients.