Diagnosis of human cytomegalovirus infections in the immunocompromised host

Background: In the last decade several major advances have been made in the rapid diagnosis of human cytomegalovirus (HCMV) infections and disease in immunocompromised patients both at the immunological and molecular level. Objectives: The objective was to review in some detail the new diagnostic tools allowing determination and quantitation of HCMV infection in blood of transplanted and AIDS patients. Study design: The determination and quantitation as well as the clinical significance of antigenemia, viremia, HCMV-infected circulating endothelial cells (CEC) and DNAemia will be discussed in view of the therapeutic management of HCMV disease. Levels of viremia represent the number of p72-positive cultured fibroblasts inoculated with 2 x 10⁵PBL, while levels of antigenemia represent number of pp65- positive PBL/2 x 10⁵ PBL examined. The number of CEC is determined simultaneously and in parallel with antigenemia. DNAemia, both qualitative and quantitative, can be determined by polymerase chain reaction (PCR) per 1 x 10⁵PBL. The clinical utility of determining either immediate-early or late mRNA is still debated. Results: In solid organ transplant recipients mean levels of viremia of 100 and of antigenemia of 400 correlate with onset of clinical symptoms. The time between first HCMV positivity and the onset of symptoms (≤ 10 days), together with the observation that most patients with reactivated infection clear virus without treatment, allowed the establishment of an antigenemia cut-off of 100 for the initiation of treatment. On the other hand, seronegative recipients of solid organs from seropositive donors must be treated preemptively, i.e. at first appearance of HCMV positivity in blood. Due to the risk of early appearance of HCMV pneumonia, the same preemptive approach must be used in bone-marrow transplant recipients. In acquired immunodeficiency syndrome (AIDS) patients with HCMV infection/disease, general criteria for initiation of treatment are more difficult to establish and treatment must be maintained. CEC are detected only in untreated disseminated HCMV infections with organ involvement. Qualitative DNA determination is useful only in special cases, such as in aqueous or vitreous humor of AIDS patients with HCMV retinitis. Quantitative DNA levels obtained by PCR are much more helpful for diagnosing HCMV disease and establishing initiation of treatment. Conclusions: New diagnostic procedures currently ensure fine monitoring of HCMV infections/diseases and evaluation of the effect of specific antiviral treatment in the immunocompromised host.