Evaluation of Five Commercial Enzyme Immunoassays for the Detection of Human Cytomegalovirus-Specific IgM Antibodies in the Absence of a Commercially Available Gold Standard

Abstract

In the recent years the number of commercially available immunoassays for the detection of human cytomegalovirus (HCMV)-specific immunoglobulin M (IgM) antibodies has rapidly increased. The aim of the present study was to evaluate five commercial immunoassays for the serological diagnosis of HCMV-infection. These methods, namely the IMx CMV IgM assay, the AxSYM CMV IgM assay (both Abbott), the Gull CMV IgM, the CMV-IgM-ELA test PCS Medac and the Biotest Anti-HCMV recombinant IgM ELISA, were compared for their diagnostic effectiveness and interference with substances eventually producing cross-reactions with HCMV-IgM (Epstein-Barr-virus (EBV)-IgM, rheumatoid factor (RF)). In addition, repeated measurements on samples from kidney and heart transplant recipients with active HCMV infection were examined to compare the temporal development of the HCMV-IgM measured with the five assay systems. Since there is no commercially available gold standard, it was assumed that the true classification, of whether the patient sample is HCMV-IgM positive or negative, was unknown. Hence sensitivity and specificity were assessed based on a maximum likelihood approach using a "latent class" model. The cross-reactions were quantified by a Bayesian statistical model using prior information for the expected prevalences in the EBV-IgM and rheumatoid factor sample groups. The results of the study demonstrated that there are great differences in sensitivity and specificity as well as in cross-reactions with EBV-IgM and RF between the tested ELISAs.

Congenital cytomegalovirus infection: recent advances in the diagnosis of maternal infection

“…However, the search for CMV-specific IgM has always been hampered by the fact that the correlation of results obtained with different commercial kits is poor and results are contradictory if a serum is tested with different kits [14]. Recently available new tests may rapidly change this situation because they seem sensitive and specific enough to detect all pregnant women undergoing active infection (sensitivity 96%; specificity 97%) [15].…”

“…Moreover, recent evidence indicates that although titers are lower, IgM antibody is produced during the acute and late phases of a primary CMV infection and once produced may persist for 6 to 9 months. IgM antibody often is produced during CMV reactivation/reinfection [14,15]. A positive IgM test should therefore be considered only as the starting point for a more thorough diagnostic evaluation to determine whether there is a risk of fetal infection.…”

Laboratory evaluation of the new Access® cytomegalovirus immunoglobulin IgM and IgG assays

“…derived lysates. [18][19][20] Further standardization of CMV serology may be realized using specific combinations of native and recombinant antigens (such as IE1). 21 For both CMV IgG and IgM, similar good agreements were reported between VIDAS and Access.…”

Audiological Outcome of Infants with Congenital Cytomegalovirus Infection in a Prospective Study

“…Counseling pregnant women on ways to prevent CMV infection may be effective in reducing the infection rate. The production of IgM antibody persists for 6-9 months and is induced by CMV reactivation/reinfection [Genser et al, 2001]. The results of screening for CMV IgM antibody in maternal serum samples would indicate whether there is a risk of fetal infection, although congenital CMV infection should be diagnosed based on isolation of CMV from a neonatal urine sample obtained during the 1st week of life [Lazzarotto et al, 2004].…”

“…It is assumed that pregnant women who are positive for CMV IgG seroconversion or who are positive for CMV IgM antibody may transmit the virus to the fetus. Production of IgM antibody persists for 6-9 months [Genser et al, 2001]; therefore, a CMV IgM-positive result alone does not accurately predict the risk of fetal infection. We performed a prospective study on congenital CMV infection which was determined by positive for CMV DNA in the neonatal urine of infants born to women who were positive for IgM antibody or seroconversion of IgG antibody, and focused on the audiological course of infants with asymptomatic CMV infection.…”