The presence of IgM antibody to CMV is consistent with but does not prove primary infection because IgM can also appear during viral reactivation or re-infection. In contrast, the measurement of IgG avidity has been shown to be a reliable indicator of primary CMV infection. The affinity or avidity of IgG is initially low after primary CMV infection and matures slowly over 3 to 4 months. High avidity antibodies that are characteristic of a former infection.
We tested 6000 serum samples from women ages 12-49 years who were part of the National Health and Nutrition Examination Survey (NHANES) III for CMV IgG and IgM. NHANES is a nationally representative sample of over 20,000 participants from the U.S. population collected from 1988 to 1994. Testing was performed using the VIDAS by bioMerieux (Durham, NC). The overall IgG prevalence was 62.8%, and was strongly associated with age. The overall IgM seroprevalence was 2.8% and was less associated with age than IgG; 0-2% in women 12-14 years old, 3-5% in women 15-29 years old, and 1-2% in women 30 and above. Some of these differences were statistically significant. All sera that were IgG and IgM positive were tested for IgG avidity, along with an equal number of sera that were IgG positive and IgM negative. Low avidity antibody occurred in 63% of the IgM+ women 12-19 years old, 27% of the IgM+ women 20-29 years old, and in 12% of the IgM+ 30-49 years old (P value = 0.004), consistent with low avidity reflecting primary CMV infection. Furthermore, low IgG avidity sera were more likely to have higher IgM antibody titers; 6% of IgM negative sera were low avidity, 19% of IgM low titer positive sera were low avidity, 35% of IgM medium titer sera were low avidity, and 64% of high titer sera were low avidity.
The identification of women undergoing primary CMV infection may lead to treatment options for the fetus, identify risk factors for infection, and contribute to the development of strategies for preventing primary CMV infection during pregnancy. CMV IgG avidity testing is not readily available in most clinical virology laboratories, therefore IgM antibody titers may provide additional information to help evaluate whether CMV IgM reactivity represents primary CMV infection.
