Abstract & Commentary
Age of Primary Epstein-Barr Virus Infection Affects Immune Control
By Hal B. Jenson, MD, FAAP, Dean, Western Michigan University School of Medicine, Kalamazoo, MI., is Associate Editor for Infectious Disease Alert.
Dr. Jenson reports no financial relationships relevant to this field of study.
Synopsis: Younger age of infection with Epstein-Barr virus occurs in areas of high malaria burden and results in higher viral loads throughout the first 2 years of life that is associated with increased risk for Burkitt lymphoma.
Source: Piriou E, et al: Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from western Kenya: Clues to the etiology of endemic Burkitt lymphoma. J Infect Dis 2012;205:906-13.
Infants in an area with high malaria exposure were infected with EBV at a significantly younger age in infancy, with a much higher incidence of primary EBV infection before 6 months of age. They also had EBV DNA detected more frequently and at higher levels throughout the first two years of life, indicating poor control of EBV infection.
Two cohorts of children in Kenya, one from an area of high malaria transmission and high risk for Burkitt lymphoma and the second from an area of low malaria transmission and low risk for Burkitt lymphoma, were enrolled in 2006. Children were studied prospectively for age of primary Epstein-Barr virus (EBV) infection with blood samples collected at 1 month of age and then every month through 12 months of age, and every 4 months through 24 months of age. EBV DNA was detected by quantitative polymerase chain reaction, and antibody testing was performed using a luminex bead-based assay for VCA-IgM, VCA-IgG, and EBNA1-IgG. Only children born to HIV-uninfected mothers were enrolled.
At the end of 2 years, retention rates were 64% and 78% in the two cohorts, with a total of 150 children completing the study. The age of primary EBV infection was defined as detection of any marker of EBV infection: EBV-DNA, or a 2-fold increase over a previous sample (to account for maternal antibodies) in VCA-IgM, VCA-IgG, EBNA1-IgG, or EBV DNA.
Children born in the region at higher risk of Burkitt lymphoma showed earlier age at time of primary EBV infection (7.28 months +/- 0.33 SEM vs. 8.39 months +/- 0.26 SEM), including higher rate of EBV infection before 6 months of age (35.3% vs. 12.2%; P<0.0001). These children also had significantly higher EBV viral loads based on tie-averaged area under the curve (1.28 log10 copies/ìg vs. 0.78 log10 copies/ìg; P<0.002).
Commentary
Endemic Burkitt lymphoma is the most common childhood malignancy in Saharan Africa, and has been linked to EBV infection. The geographic overlay of Burkitt lymphoma with malaria suggests that malaria is also an important cofactor in the etiology of Burkitt lymphoma. The interplay of EBV causality and the geographic association of malaria for Burkitt lymphoma is unclear.
This study shows that infants in an area with high malaria exposure were infected with EBV at a significantly younger age in infancy, with a much higher incidence of primary EBV infection before 6 months of age, and also had EBV DNA was detected more frequently and at higher levels throughout the first two years of life, indicating poor control of EBV infection. This finding is similar to other viral infections occurring during early infancy, such as hepatitis viruses and cytomegalovirus.
Collectively, these data indicate that early age of primary EBV infection leads to poor control of EBV infection, and is a risk factor for development of endemic Burkitt lymphoma. It is plausible that malaria exposure and infection facilitates early age of EBV infection, which results in poor immunological control of the infection. The association of EBV with several forms of human cancer — Burkitt lymphoma, nasopharyngeal carcinoma, and Hodgkin disease, as well as leiomyosarcoma in immunocompromised persons — underscores the importance and the potential benefits of developing a vaccine strategy against EBV.
Infants in an area with high malaria exposure were infected with EBV at a significantly younger age in infancy, with a much higher incidence of primary EBV infection before 6 months of age.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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