CYTOMEGALOVIRUS-INFECTION AFTER TRANSPLAN TATION - VIROLOGICAL DIAGNOSIS, ANTIVIRAL TREATMENT

Cytomegalovirus (CMV) is an important cause of morbidity in organ tran splant recipients with two major clinical effects : allograft rejectio n and pneumonitis. The issue of effective therapy has increased the ne ed for accurate and rapid laboratory methods for diagnosis of viral in fections. ELISA, as the most serological sensitive tests, are useful f or the identification of active CMV infection, and the serological res ponse can be sometimes detected before viral excretion. There are seve ral commercial reagents for the detection of IgG or IgM CMV antibody, and a great variability in terms of sensibility and specificity. Becau se of the slow process of isolating CMV in cell cultures, immediate-ea rly antigen detection in infected cells within one or two days of cult ure, increases twice the sensitivity of viral isolation for leukocyte or bronchoalveolar (BAL) specimens. Differences in sensitivity of the direct detection of CMV antigen in BAL specimens has been reported. Di rect detection of CMV antigen in leukocytes is particularly important because CMV viremia is considered to be a marker of active infection a nd high antigen levels to be predictive of significant CMV disease. CM V antigen detection within leucocytes, by immunofluorescence with the aid of monoclonal antibodies to CMV phosphoprotein PP-65, appears to b e as specific, more sensitive, and allows a more rapid diagnosis than virus isolation techniques. Some specific CMV probes are now available , but the hybridization techniques involving dot-blot assays of urine or BAL are not enough sensitive to detect small amounts of virus. Clos ely sensitivity to isolation in culture has nevertheless been reported in the polymorphonuclear fraction of the blood cells. Routine applica tion of the DNA amplification techniques using the polymerase chain re action (PCR) is yet limited by some practical problems as for example, the definition of the most suitable primers, the ability to different iate latent genomes from active infection, the quantification of the p ositivity, or the cross contaminations. Several adaptations of these P CR techniques are in evaluation at this time as a rapid diagnostic met hod of active CMV infection : detection of an Herpesviridae DNA and id entification of the CMV genome by enzymatic restriction, research of l ate transcripts in infected cells; detection of CMV DNA in plasma by a nested-PCR. The antiviral treatment of CMV associated disease is base d on the use of ganciclovir GCV and foscarnet. Some data on the preval ence of CMV resistance to ganciclovir and on the testing susceptibilit y of CMV strains are emphasized.