ABSTRACT
We performed an intensive prospective study designed to obtain as much data as possible on the incubation and early illness periods of primary Epstein-Barr virus (EBV) infection. Undergraduate students who lacked EBV antibody and oral EBV DNA (EBV-naive) were seen every 2 weeks during their freshman year. Clinical and behavioral data, oral washes and venous blood were obtained. EBV antibodies were quantified by enzyme immunoassay and viral loads by PCR. During a median 8 months of observation, 14/85 subjects experienced primary EBV infections (24 cases/100 person-years). The only significant risk factor for acquisition of EBV infection was deep kissing (P=0.02). Eleven subjects had infectious mononucleosis with a median duration of 21 days. Two subjects were hospitalized. Infections were initially identified in 12 subjects by finding EBV DNA in oral cells before onset of symptoms and in 2 subjects by symptom reporting. EBV DNA and viral capsid antigen (VCA) IgM and gp350 IgG antibodies were present in the blood before onset of illness. To provide a more robust evaluation of primary EBV infection in undergraduate university students, we combined data on risk factors and antibody responses from this and an earlier study that used the exact same clinical and laboratory methods. The observation that the only significant risk factor for acquisition of EBV infection was deep kissing was confirmed. Most importantly, higher amounts of gp350 antibody correlated significantly with a lower severity of infectious mononucleosis (P<0.0001), which strengthens the rationale for a gp350-based prophylactic EBV vaccine.
ABSTRACT
BACKGROUND: University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity. METHODS: EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. RESULTS: Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (P < .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8(+) T-cells but not in numbers of CD4(+) T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8(+) lymphocytosis (P = .0003). CONCLUSIONS: Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8(+) lymphocytosis correlated with disease severity.
