8-year vaccine protection following a single dose of Vi-tetanus toxoid conjugate vaccine in children in Nepal (TyVOID): a prospective cohort follow-up study of the TyVAC Nepal randomised controlled trial.
A single dose of Vi-TT vaccine offers strong protection against typhoid fever in Nepali children for up to 4 years, with effectiveness decreasing by 8 years.
Where it sits
this study against the rest of the semax corpusSummary and findings
The study evaluated the long-term effectiveness of the Vi-tetanus toxoid conjugate vaccine (Vi-TT) in children in Nepal, following a single dose. Vaccine effectiveness was assessed up to 8 years post-vaccination with a focus on blood culture-confirmed typhoid incidence. The study found a vaccine effectiveness of 77% in the 2020-21 cohort and 53% in the 2017-18 cohort.
Abstract
<h4>Background</h4>In low-income and middle-income countries, where typhoid fever remains a major public health problem, WHO recommends the use of typhoid conjugate vaccine (TCV). Here, we report vaccine effectiveness up to 8 years following a single dose of TCV in Nepal.<h4>Methods</h4>TyVOID was a prospective cohort study that extended the follow-up of children enrolled in a phase 3, double-blind, randomised controlled trial in Lalitpur, Nepal (TyVAC; Nov 20, 2017, to Oct 20, 2021). Children aged 9 months to 15 years were randomly assigned (1:1) to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) or a capsular group A meningococcal conjugate (MenA) vaccine. After unmasking and crossover vaccination, our study followed the trial participants until Oct 31, 2025. TyVAC participants who received Vi-TT were eligible for this study and categorised into either the 2017-18 cohort or 2020-21 cohort, depending on when they received the Vi-TT vaccine. The primary outcome, which was assessed in children who received both Vi-TT and MenA vaccines and with known TCV vaccination status during the government catch-up campaign in 2022, was the incidence of blood culture-confirmed typhoid identified through facility-based passive surveillance and medical record review. Adjusted incidence rate ratios (IRRs) were estimated using Poisson regression adjusted for age and sex. Vaccine effectiveness at 1-5 years and 4-8 years post-vaccination was estimated using a test-negative design among febrile children presenting to surveillance clinics, comparing odds of Vi-TT vaccination between culture-confirmed typhoid cases with negative controls.<h4>Findings</h4>16 131 TyVAC participants were enrolled at TyVOID baseline, of whom 14 850 provided information on Vi-CRM<sub>197</sub> vaccination during the government catch-up campaign. After crossover and unmasking, the primary analysis population included 4941 participants vaccinated with Vi-TT in 2017-18 and 4856 participants vaccinated with Vi-TT in 2020-21. In 4856 participants in the 2020-21 Vi-TT cohort, 2402 (49·5%) were female, 2454 (50·5%) were male, and the median age at Vi-TT vaccination was 10·4 years (IQR 7·3-13·7). In 4941 participants in the 2017-18 Vi-TT cohort, 2482 (50·2%) were female, 2459 (49·8%) were male, and the median age at Vi-TT vaccination was 7·7 years (IQR 4·5-11·0). During a median follow-up of 3·7 years (3·7-3·8), the typhoid incidence rate was 111 per 100 000 person-years (95% CI 64-177) in the 2017-18 cohort and 46 per 100 000 person-years (18-94) in the 2020-21 cohort (adjusted IRR 2·41 [95% CI 1·00-5·80]; one-sided p=0·025). Vaccine effectiveness was 77% (95% CI 46-90; p=0·0006) in the 2020-21 Vi-TT cohort (1-5 years after vaccination), and 53% (8-76; p=0·027) in the 2017-18 Vi-TT cohort (4-8 years after vaccination).<h4>Interpretation</h4>A single Vi-TT dose confers strong protection in the first 4 years among Nepali children, with evidence of waning by 8 years. These findings support consideration of a booster dose to sustain protection in school-age children who remain at high risk of typhoid fever.<h4>Funding</h4>Gates Foundation and Wellcome Trust.
Background
Typhoid fever remains a significant public health issue in low- and middle-income countries, prompting the WHO to recommend typhoid conjugate vaccines (TCVs). This study addresses the long-term effectiveness of the Vi-tetanus toxoid conjugate vaccine (Vi-TT) in preventing typhoid fever in children. Understanding the duration of vaccine protection is crucial for informing public health strategies and vaccination schedules.
Methods
The study was a prospective cohort follow-up of a phase 3, double-blind, randomized controlled trial conducted in Lalitpur, Nepal. Children aged 9 months to 15 years were randomized to receive either the Vi-TT vaccine or a capsular group A meningococcal conjugate vaccine. The primary outcome was the incidence of blood culture-confirmed typhoid fever, assessed through passive surveillance and medical record review. Vaccine effectiveness was estimated using a test-negative design among febrile children presenting to surveillance clinics.
Results
The primary analysis included 4941 participants vaccinated with Vi-TT in 2017-18 and 4856 in 2020-21. The typhoid incidence rate was 111 per 100,000 person-years in the 2017-18 cohort and 46 per 100,000 person-years in the 2020-21 cohort. The adjusted incidence rate ratio (IRR) was 2.41 (95% CI 1.00-5.80; p=0.025). Vaccine effectiveness was 77% (95% CI 46-90; p=0.0006) in the 2020-21 cohort and 53% (95% CI 8-76; p=0.027) in the 2017-18 cohort.
Interpretation
The study demonstrates that a single dose of Vi-TT provides substantial protection against typhoid fever in the first few years post-vaccination, with effectiveness waning by the eighth year. While statistically significant, the clinical significance of the waning effectiveness suggests a potential need for booster doses in high-risk populations. The study's findings align with existing literature on the durability of vaccine-induced immunity but are limited by the single geographic location and varying follow-up periods.
Key findings
- 16,131 TyVAC participants were enrolled at TyVOID baseline.
- Vaccine effectiveness was 77% (95% CI 46-90; p=0.0006) in the 2020-21 cohort.
- Vaccine effectiveness was 53% (95% CI 8-76; p=0.027) in the 2017-18 cohort.
- Typhoid incidence rate was 111 per 100,000 person-years in the 2017-18 cohort.
- Typhoid incidence rate was 46 per 100,000 person-years in the 2020-21 cohort.
- Adjusted IRR was 2.41 (95% CI 1.00-5.80; p=0.025) between cohorts.
Limitations
- Single-site study in Nepal.
- Follow-up duration varied between cohorts.
- Potential for unmeasured confounding factors.
- Results may not generalize to other settings.