Long-Term Efficacy of Typhoid Conjugate Vaccines (TCV)

The World Health Organization (WHO) recommends programmatic use of TCVs for typhoid fever control and prioritization of vaccine introduction in countries with the highest typhoid fever incidence or high prevalence of antimicrobial-resistant S Typhi. ¹

A single dose of the Vi polysaccharide vaccine conjugated to tetanus toxoid (Vi-TT) vaccine remains effectively protective for a minimum of 4 years in children from 9 months to 12 years of age and demonstrates efficacy across all age categories, even in those under 2 years old. These findings reinforce the existing WHO guidelines for conducting vaccination campaigns in areas where typhoid is endemic, targeting children aged 9 months to 15 years, and suggest the routine vaccine administration during the first 2 years of life.

Within the intention-to-treat analysis, the Vi-TT showed a 78.3% efficacy rate (with a 95% confidence interval of 66.3% to 86.1%). To prevent a single case of typhoid fever, it was necessary to vaccinate 163 children (ranging from 129 to 222 children depending on the estimate). The vaccine's efficacy varied by age, showing a 70.6% effectiveness (with a range of 6.4% to 93.0%) in children aged 9 months to 2 years, 79.6% (45.8% to 93.9%) in children aged 2 to 4 years, and 79.3% (63.5% to 89.0%) in children aged 5 to 12 years.

“Our data show that the estimated number needed to vaccinate is now 163 children, which is substantially lower than the previous estimate of 278 children reported at the 18–24-month analysis, due to the additional infections prevented with the longer duration of follow-up,” according to investigators. “These results are likely to be reflected in more beneficial cost-effectiveness analyses, representing enhanced value for policymakers.”²

3 Key Takeaways

The study demonstrates that a single dose of the Vi-TT vaccine protects against typhoid fever for at least 4 years in children aged 9 months to 12 years, showcasing broad efficacy across different age groups, including those under 2 years old.
The findings support WHO recommendations for TCV in areas with high incidences of typhoid fever or where antibiotic-resistant strains of S Typhi are prevalent.
Vi-TT vaccine plays a critical role in reducing the disease burden of typhoid fever in high-risk regions.

This phase 3, double-blind, randomized controlled trial conducted in Blantyre, Malawi, enrolled healthy children aged between 9 months and 12 years. Participants were randomly assigned to receive either a single dose of the Vi-TT or a meningococcal capsular group A (MenA) vaccine. Researchers monitored the occurrence of fever from the time of vaccination until the end of the follow-up period. The primary measure of the trial's success was the first instance of blood culture-confirmed typhoid fever.

From February 21, 2018, to September 27, 2018, the trial vaccinated 28,130 children, evenly divided between Vi-TT and MenA vaccines. Over a median follow-up of 4.3 years, the Vi-TT cohort demonstrated a significantly lower incidence of typhoid fever, reinforcing the vaccine's role in reducing disease burden in high-risk areas.

“Although the results of this study are strongly supportive of current WHO recommendations, continued data are needed from real-world post-introduction effectiveness and impact studies,” according to the investigators.” To assess the strength and durability of protection, particularly in those children who receive the vaccine during the routine EPI visit. Although the point estimates of vaccine efficacy in our study did not differ significantly by age group, the lowest point estimate was seen in the youngest children.”²

Despite the encouraging outcomes, the study acknowledges limitations such as diminished participant engagement in passive surveillance activities, potentially underestimating disease incidence. However, this is unlikely to bias the vaccine efficacy analysis, as the decline in participation did not correlate with vaccine allocation, which remained blinded.

This research provides key insights into TCVs' long-term effectiveness, supporting their strategic use in immunization and mass vaccination strategies in high-burden areas. It remains uncertain whether administering a second vaccine dose would offer additional benefits. The question of additional benefits from a second vaccine dose remains. A study assessing the immunogenicity of a booster dose of Vi-TT administered about 5 years after the initial dose is underway in Malawi.