Laboratory diagnosis of cytomegalovirus (CMV) infections in immunodepressed patients, mainly in patients with AIDS

Abstract

There is a high prevalence of cytomegalovirus (CMV) infection in the general population. An important proportion of immunodepressed patients are latent carriers of the virus, and under these conditions, the lack of cellular immunity predisposes the patient to an active infection in which the virus is replicating. Consequences for the immunodepressed patients are widely variable, ranging from completely asymptomatic infections to life-threatening situations. An important characteristic of these infections is that they have no specific clinical symptoms and are often indistinguishable from other types of infection. As such, clinical diagnosis should be supported by laboratory tests. There are many diagnostic tests available, the choice of which one to use being made on the basis of clinician-defined objectives. The CMV immunological state of the patient should be ascertained in order to indicate the possibility of reactivation or the risk of primary infection. To this end, serological tests have proven to be the most useful. Laboratory tests also allow the rapid diagnosis of active CMV infections, for which rapid culture techniques (shell-vial) or viral antigen tests (antigenemia pp65) are more appropriate. Given that not all active infections present with symptoms, the most typical problem in clinical practice is to distinguish between symptoms and illnesses caused by CMV (CMV disease: CMVD), and other infectious or non-infectious entities. To clarify this situation, diagnostic histopathology and methods able to quantify the viral load (pp65 antigenemia and quantitative PCR) are of great use. The identification of patients who, during active infection, are at high risk of contracting CMVD in the near future, is a more complex challenge for the laboratory. Once again, tests that are able to quantify the viral load are the most appropriate for identifying those patients who should receive preventive antiviral treatment. In HIV-positive patients, CMVD tends to manifest itself as retinitis and involvement of the gastrointestinal tract. The principal risk factor in the development of CMVD in these patients is the degree of immunodepression, which appears almost exclusively in patients with a CD4+ lymphocyte count lower than 50/mm3 and when other opportunistic infections have occurred. The advent of oral ganciclovir has raised the possibility of long-term prophylactic treatment of CMVD, making the search for virological and immunological markers that identify these high-risk patients a priority. Techniques allowing the quantification of CMV viremia, namely pp65 antigenemia and quantitative PCR, have been most useful to this end