One-dose typhoid conjugate vaccine provides lasting protection

Key takeaways:

• A single dose of a typhoid conjugate vaccine provides at least 4 years of protection, a study showed.
• Vaccine efficacy was 78.3% among children in the study.

A single dose of a typhoid conjugate vaccine provided protection for at least 4 years among children aged 9 months to 12 years enrolled in a phase 3 trial in Malawi, according to results published in The Lancet.

Against a backdrop of rising antibiotic resistance, 2-year findings from the trial reported in 2021 showed the vaccine was effective at protecting children from typhoid fever.

WHO prequalified the vaccine, Typbar-TCV (Bharat Biotech International), in 2018, making it the first typhoid conjugate vaccine (TCV), although it had not been tested in a placebo-controlled trial until the Malawi project.

“This was the first-ever large clinical trial of this vaccine done on the African continent,” Kathleen Neuzil, MD, MPH, director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine, told Healio.

Neuzil and colleagues enrolled 28,130 children aged 9 months to 12 years and assigned half to receive the TCV and half a vaccine against meningitis — a decision that Neuzil said was to ensure that “all children would get some potential benefit.”

“We told the parents that if your child gets sick with fever, bring them back to one of these health centers and we will be there. We will have medical personnel and doctors there,” Neuzil said. “We will get blood cultures and we will diagnose and treat your children, and we will identify how many in the typhoid vaccine group had typhoid in their blood and how many in the meningitis group had typhoid in their blood. And then we would look at the differences there to see how well the vaccine worked.”

During the more than 4 years of follow-up, 24 children in the TCV group and 110 in the meningitis group developed typhoid fever, as confirmed via blood culture, the researchers reported. They calculated the efficacy of the typhoid vaccine to be 78.3%, with one case of typhoid prevented for every 163 children vaccinated.

It was effective in all age groups and over the entire study period, with efficacy decreasing by only 1.3% per year.

“There is durable protection here, which means it's feasible to give these vaccines in a low-resource setting because you don't have to go back and keep giving more doses every year or two,” Neuzil said.

“Based on these results, last May, the government of Malawi rolled out a campaign and gave this single-dose typhoid vaccine to every child up to 15 years of age in the country, or they attempted to give it to every child,” Neuzil said. “It's good science, but it also had a direct and immediate impact on a country’s decision-making.”

The study was accompanied by a commentary authored by Birkneh T. Tadesse, MD, PhD; Rita S. B. Cardona, MD; and Florian Marks, PhD; all from the International Vaccine Institute.

“Extension of the scope of investigation to assess vaccine efficacy and effectiveness beyond the initial 4 years is essential. This expanded investigation will inform the discussion surrounding the need for booster vaccinations,” they wrote. “Future research should include a robust estimation of vaccine effectiveness and its effect in young children and the interplay between [water, sanitation, and hygiene] improvements and TCV vaccination for both adults and children, with focus on identifying their ability to control typhoid in endemic settings.”

References:

Patel PD, et al. Lancet. 2023;doi:10.1016/S0140-6736(23)02031-7.

Tadesse BT, et al. Lancet. 2024;doi:10.1016/S0140-6736(23)02350-4.

Single dose typhoid conjugate vaccine (TCV) provides lasting efficacy in children. https://www.eurekalert.org/news-releases/1032338?. Published Jan. 25, 2024. Accessed Jan. 26, 2024.