Assessing the effect of malaria exposure history on tetanus antibody waning rates among children in Jinja and Tororo Districts, Uganda

Background: Malaria infection causes widespread immune perturbations and has been shown to affect vaccine responses to other pathogens, including tetanus. In endemic settings, repeated malaria infections during childhood could affect the durability of protection against vaccine-preventable diseases. This study assessed variability in tetanus antibody kinetics, including by malaria exposure history. Methods: From 2011 to 2017, 3070 plasma samples were collected from 597 children aged 0-to-10-years enrolled in the PRISM cohort study residing in Tororo (high malaria transmission) and Jinja (low transmission) districts in Uganda. Malaria exposure history was ascertained via both active and passive surveillance. Samples tested for tetanus anti-toxin IgG using a Luminex multiplex bead assay were analyzed to determine decay rates and risk of sero-reversion by district. Correlation structures within individuals with different malaria exposure histories were compared using generalized estimating equations (GEE).Results: Tetanus seroprevalence was 87.5% among 0-year-olds and 90.8% among 1-year-olds. Tetanus antibody titers were estimated to fall below protective levels by age 8.1 years. Antibody decay rate was significantly slower in Jinja (0.05 log(IU) per year [95% CI: 0.2–0.07) than in Tororo (0.25 log(IU) per year [95% CI: 0.23–0.27]), indicating faster waning in high-malaria areas; risk of sero-reversion was also significantly higher in Tororo. GEE models with independent structures were most suitable across all groups of prior malaria exposure history, suggesting that antibodies are not very well correlated within individuals regardless of prior malaria history. Conclusions: Tetanus antibody kinetics waned rapidly regardless of malaria history. However, as children living in areas with malaria transmission may have higher risk of sero-reversion, our results suggest that further research is needed to determine if malaria endemicity should inform the timing of tetanus booster dose delivery.