Diagnosis and prevention of cytomegalovirus infection after organtransplantation

Although the introduction of cyclosporin A (GsA) as the main immunosuppressive agent seems to have influenced the incidence and severity of CMV disease in a positive way, the reported incidence of clinical overt CMV infection is still 2 - 23 % and 1 - 3 % of the transplant recipients die from CMV infection. It is therefore obvious that this virus remains a major pathogen after organ transplantation. DIAGNOSIS OF CMV INFECTION When CMV disease is diagnosed, reduction of immunosuppressive therapy will markedly decrease morbidity and mortality without affecting graft survival. Moreover, antiviral therapy with either ganciclovir or foscarnet can be considered in patients with severe symptomatic disease. This management of symptomatic CMV infections (tapering of immunosuppressive drugs and j or antiviral therapy) makes rapid and early diagnosis necessary. Although the measurement of virus specific antibodies is sensitive, the long physiological response-time of antibody synthesis (one to two weeks ) during active CMV infection makes this method inappropriate for rapid and early diagnosis. Moreover, in patients with immunosuppression antibody synthesis can be impaired. Detection of a morphological cytopathological effect (CPE) of CMV in tissue cultures has the same disadvantage. The method takes long time and is sometimes impossible due to bacterial contaminated specimens or coinfection with the herpes simplex virus. In this thesis two methods for rapid and early diagnosis of CMV infection are described. First, we compared in our patients the results obtained by a low-speed centrifugation assay in combination with immunofluorescence by a monoclonal antibody against early antigen of CMV with the results from the conventional tissue culture method. Second, an indirect method for detection of active CMV infection is described. In the peripheral blood of renal transplant recipients mononuclear subpopulations were monitored with monoclonal antibodies before, during and after CMV infection.