Abstract
OBJECTIVES: Typhoid remains a persistent contributor to childhood morbidity in communities lacking sanitation infrastructure. Typhoid conjugate vaccine (TCV) is effective in reducing disease risk in vaccinees; however, the duration of protection is unknown. This study measured the longevity of immune response to TCV in children aged under 10 years in Hyderabad, Pakistan, where an outbreak of extensively drug-resistant typhoid has been ongoing. METHODS: A subset of children who received the TCV as part of the outbreak response were enrolled purposively from March 2018 to February 2019. The participants were followed up until January 2023. Blood samples were taken at baseline, 4-6 weeks, 6 months, and annually 1-4 years after vaccination to measure anti-Vi immunoglobulin (Ig) G levels using enzyme-linked immunosorbent assay. Active phone-based surveillance was performed to identify breakthrough infections. Blood culture was offered to any child with a history of fever ≥3 days within the last 7 days. A total of 81 children received a second dose of TCV in November 2019 during a catch-up campaign organized by the Sindh government. RESULTS: Nearly all participants seroconverted (802 of 837; 95.8%) at 4-6 weeks after vaccination. A total of 4 years after vaccination, 438 of 579 (75.6%) participants remained above the seroconversion threshold. The geometric mean titer (U/mL) of anti-Vi IgG at 4-6 weeks was 832.6 (95% confidence interval [CI]: 768.0-902.6); at 4 years after vaccination, the geometric mean titers in children aged 6 months to 2 years (12.6, [95% CI: 9.8-16.3]) and >2-5 years (40.1, [95% CI: 34.4-46.6]) were lower than in children aged >5-10 years (71.1, [95% CI: 59.5-85.0]). During 4 years of follow-up, nine children had culture-confirmed Salmonella Typhi infection; these infections occurred after a median duration of 3.4 years. All enteric fever cases seroconverted at 4-6 weeks after vaccination and seven (70.0%) remained seroconverted 4 years after vaccination. CONCLUSIONS: We observed 95.8% seroconversion after a single dose of TCV. There was a decay in anti-Vi IgG titers, and, at 4 years, approximately 75.6% remained seroconverted. There was a faster decay in children aged ≤2 years. Breakthrough infections were documented after a median 3.4 years after vaccination.