The combination of Epstein-Barr virus (EBV) infection and high malaria exposure are risk factors for endemic Burkitt lymphoma, and evidence suggests that infants in regions of high malaria exposure have earlier EBV infection and increased EBV reactivation. In this study we analyzed the longitudinal antibody response to EBV in Kenyan infants with different levels of malaria exposure. We found that high malaria exposure was associated with a faster decline of maternally derived immunoglobulin G antibody to both the EBV viral capsid antigen and EBV nuclear antigen, followed by a more rapid rise in antibody response to EBV antigens in children from the high-malaria-transmission region. We also observed the long-term persistence of anti-viral capsid antigen immunoglobulin M responses in children from the high-malaria region. More rapid decay of maternal antibodies was a major predictor of EBV infection outcome, because decay predicted time to EBV DNA detection, independent of high or low malaria exposure.Keywords. Epstein-Barr virus; P. falciparum malaria; Burkitt Lymphoma; antibody; immunity.Epstein-Barr virus (EBV) is a gammaherpesvirus causing infectious mononucleosis and also associated with a variety of cancers in humans [1]. In Africa, EBV is associated with endemic Burkitt lymphoma in the presence of Plasmodium falciparum malaria infection [2]. Previous studies in Africa have shown that most children seroconvert to EBV between 6 and 18 months of age [3][4][5] and that living in an area of high malaria transmission is associated with higher EBV load [4] and earlier time of the first EBV infection [5]. Moreover, the presence of P. falciparum infection is correlated with increased EBV load over time and with more frequent detectable EBV in children [5,6] and pregnant women [7]. High levels of antibody against the EBV viral capsid antigen (VCA) are associated with a higher risk of Burkitt lymphoma in both Ugandan [8,9] and Kenyan [10] children. High malaria exposure was also associated with impaired transfer of maternal VCA and EBV nuclear antigen 1 (EBNA1)-specific immunoglobulin (Ig) G from mother to infant [11], and later in life, higher level of EBV-specific IgG antibodies [12]. The measurement of antibodies specific for EBV VCA and EBNA1 have been used in numerous seroepidemiology studies to assess primary and persistent EBV infections (reviewed in [13]). Typically, anti-VCA IgG appears early after infection, with a delay to detection of anti-EBNA1 IgG. Both are then found at relatively stable levels throughout the life of the host. Anti-EBV early antigen diffuse complex (EAd) IgG has been used as a serological marker for evidence of viral reactivation, because its levels are generally much lower than levels of anti-VCA IgG, they decrease after primary infection (in contrast to VCA IgG), and are elevated during viral reactivation. The EBV Z-transactivation antigen (Zta) is an EBV immediate early protein. It has not been used in clinical settings to detect EBV reactivation to our knowledge, but we have found t...