Abstract
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. Acute EBV infection in children of this age results in humoral immune suppression to unrelated antigenic challenges for approximately 4 weeks. Whether acute 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: 26.7% of children were serologically positive for acute EBV infection, and the highest proportion of severe malaria cases was in children with primary acute EBV. An elevated magnitude and breadth of the antibody response with increased in vitro invasion-blocking capacity was observed in children with acute EBV but circulating parasitaemia in vivo was similar. CONCLUSION: Acute EBV infection is 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. KEY POINTS: Acute EBV infection in infants increases the risk of severe falciparum malaria. This does not appear to be due to an EBV-induced impairment of the anti- Plasmodium humoral immune response which is elevated in magnitude, breadth and function.