Primary Epstein-Barr virus infection in preadolescent children: A prospective study

Epstein-Barr virus (EBV) is not only the principal cause of infectious mononucleosis (IM) but is also a precursor to several cancers and autoimmune disorders. Access to a prophylactic EBV vaccine early in life could be key for the prevention of these conditions. However, the incidence of primary EBV infection (pEBV) in preadolescent children is not currently known. We hypothesized that pEBV is clinically significant, but often undiagnosed.

In this prospective study we screened and followed preadolescent children ages 1.5-11.99 years at a single pediatric primary care clinic to determine incidence of pEBV. Using oral swabs to collect gingival crevicular fluid, we screened participants for the presence of EBV IgG antibody against viral capsid antigen. Participants who lacked EBV antibody (EBV-naïve) were enrolled in the prospective arm of the study with screening for oral EBV antibody every 3 months.

Of 291 children screened, 210 (72.2 %) were EBV-naïve. Of those, 181 (86 %) were enrolled in the prospective study. During 119.8 person-years of participant observation, 11 cases of pEBV were documented. Five cases were symptomatic. The incidence of pEBV was 9.2 cases/100 person-years. Self-identified Asian, Black, and Latino children had greater incidence of pEBV relative to self-identified White children.

We show that the incidence of pEBV in preadolescents is higher than that of other infectious diseases with disease burdens so severe that vaccines have been used for decades to prevent their spread, but diagnosis of pEBV is often missed by parents and clinicians. This study provides a rationale to administer EBV vaccine to preadolescents. EBV is the only infectious agent assessed in the study.