Assessing the Effect of Malaria Exposure History on Tetanus Antibody Waning Rates Among Children in Jinja and Tororo Districts, Uganda

Abstract Background Malaria causes immune perturbations and affects immunogenicity to vaccines. It is unknown, however, how repeated malaria infections affect the duration of vaccine protection. This study assessed variability in tetanus antitoxin immunoglobulin G (IgG) antibody kinetics including by malaria exposure history at district and individual levels. Methods We analyzed tetanus antitoxin IgG antibody concentrations in 3064 plasma samples from 2011 to 2017 in 597 children aged 6 months to 10 years residing in the Tororo (high malaria transmission) and Jinja (low transmission) districts in Uganda. Mixed-effects models were used to estimate antibody half-lives, and hazard models to estimate the risk of seroreversion. Results Tetanus antitoxin IgG antibody concentrations were estimated to fall below protective levels by age 8.1 years [95% confidence interval (CI), 6.4–10.2 years]. Antibody half-lives were significantly longer in Jinja (15.8 [95% CI, 8.8–28.5] years) than in Tororo (2.8 [2.6–3.1] years). Hazard of seroreversion was significantly higher (2.7-fold [1.7–4.1-fold]) in Tororo than in Jinja. Conclusions Tetanus antibodies waned rapidly. Children living in the district with high malaria transmission had faster waning and a higher risk of seroreversion than those in the district with low transmission, suggesting the need to determine if malaria endemicity should inform timing of tetanus booster delivery.