Infants under 24 months with severe malaria have a serological profile of active infection with Epstein Barr Virus
Background: Primary Epstein Barr Virus (EBV) infection occurs during late adolescence and is characterized by the symptomatic manifestation of infectious mononucleosis (IM). Primary EBV infection in malaria-endemic areas often occurs in young children by the age of 2 and is generally asymptomatic. Primary EBV infection in children of this age results in humoral immune suppression to unrelated antigenic challenges for approximately 4 weeks. Whether EBV in infants similarly suppresses the development of antibody responses against Plasmodium falciparum (Pf) predisposing infants to severe malaria is unknown.
Methods: We undertook a cross-sectional study of 195 infants aged 6-24 months in Cameroon. Infants were determined to be parasitaemic by microscopy or RDT, and their disease severity classified based on WHO criteria. The EBV infection status of each child was determined using a standard serological classification system, and the magnitude, breadth, and invasion blocking capacity of the anti-Pf antibody response were quantified.
Results: 24% of children were serologically positive for active EBV infection, and the highest proportion of severe malaria cases was in children with active EBV. An elevated magnitude and breadth of the antibody response with increased in vitro invasion-blocking capacity was observed in children with active EBV but circulating parasitaemia in vivo was similar.
Conclusion: Primary EBV infection may be a risk factor for developing severe malaria in children 6-24 months. Targeting EBV infection in young children may be beneficial in protecting against the development of severe falciparum malaria in children living in malaria-endemic areas.
Wayne T Cheng, Balotin Fogang, Aarti Jain, D Huw Davies, Philip L Felgner, Carole Eboumbou, Paul N Koki, Samuel H Speck, Chester J Joyner, Lawrence S Ayong, Tracey J Lamb. J Infect Dis. 2026 May 15:jiag264. doi: 10.1093/infdis/jiag264.