Background: Malaria remains a major cause of morbidity and mortality worldwide. Over and above preventing tuberculosis, BCG vaccine has heterologous (‘non-specific’) effects that protect against other infections. In mice, BCG reduces parasitaemia and mortality from malaria. We investigated whether BCG influences the immune response to Plasmodium falciparum in humans.
Methods: Infants were recruited from two on-going studies. In the first, blood was collected ~7 days after neonates were randomised to receive BCG (n=67, male n=41; female n=26 ) or no BCG (n=42, male n=23; female n=19) at birth. In the second, blood was collected before and ~7 days after BCG was given to infants travelling overseas (n=12). Blood was stimulated with P. falciparum (CS2)-infected erythrocytes, uninfected erythrocytes, E. coli or media alone. Supernatants were collected after 24 hours for subsequent cytokine analysis by ELISA (IL-10 and IFN-gamma) and multiplex bead assay (TNF-alpha, IL-1beta, IL-6, IL-8, IP-10, MCP-1, MIP-1alpha, MIG, TNF-beta, GM-CSF).
Results: In the first group, P. falciparum-induced IL-10, IP-10, TNF-alpha, MIG, GM-CSF concentrations were higher and the IL-1beta concentration was lower in BCG-vaccinated infants compared with non-BCG-vaccinated controls. In the second study, P. falciparum-induced IFN-gamma, IL-1beta, IL-6, and MIG concentrations were higher and the IL-10 concentration was lower after BCG-vaccination. Furthermore, cytokine results were influenced by gender.
Conclusions:
Despite inter-individual variation in cytokine levels, BCG and gender influence the immune response to P. falciparum in humans.