Study shows conjugate typhoid vaccine effective in Malawian children

As typhoid fever becomes increasingly resistant to antibiotics, a study published recently in The New England Journal of Medicine showed that a conjugate vaccine for the disease proved effective for Malawi’s younger population.

One of the study’s authors, Kathleen M. Neuzil, MD, MPH, serves as director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine and directs the school’s Typhoid Vaccine Acceleration Consortium.

“Typhoid has been virtually eliminated in places like the United States and other high-income countries, and that's predominantly through improvements in water and sanitation,” Neuzil said in an interview with Healio. “But unfortunately, it still exists in many parts of the world that don't have those benefits.”

Now, Neuzil said, after years of treating the disease with oral antibiotics, the bacteria

Salmonella Typhi has developed resistance.

“It's becoming harder and harder to treat,” Neuzil said. “And so, we're almost going backward to the preantibiotic era where mortality is increasing and serious complications are increasing, because it's harder to treat these infections with simple oral antibiotics.”

Over a period of 2 years, Neuzil and colleagues tested the vaccine Typbar-TCV (Bharat Biotech International) — a WHO-prequalified tetanus-toxoid conjugated Vi polysaccharide typhoid conjugate vaccine (Vi-TCV) containing 25 g of Vi polysaccharide per 0.5 mL dose — among children aged 9 months to 12 years. They used a meningococcal capsular group A conjugate vaccine (MenA; MenAfriVac, Serum Institute of India) as the control vaccine at a dose of 10 g/0.5 mL to children 1 year of age or older and at a dose of 5 g/0.5 mL to children younger than 1 year of age.

The intention-to-treat analysis included 28,130 children randomly assigned to receive either the Vi-TCV vaccine (n = 14,069) or the MenA vaccine (n = 14,061).

Confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 events per 100,000 person-years) and in 62 children in the MenA group (243.2 events per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% CI, 64.2-89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1-91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including six deaths — all in the MenA group.

“It can be given down to 6 months of age, it works well in infants and young children, it's immunogenic, and it should last longer than the 2 years that we've seen with traveler vaccines,” Neuzil said. “With a single dose of vaccine, we can prevent it.”

The next step, she said, would be for the country of Malawi to partner with an organization like Gavi, the Vaccine Alliance to offer the vaccine to children aged 15 years or younger.

“If Malawi wanted to do a one-time campaign and immunize all their children with a single dose typhoid conjugate vaccine up to the age of 15, Gavi would pay for that,” Neuzil said. “They would pay for all the vaccine, and they would pay for the operational costs of doing that. If then Malawi said they would now want to introduce this vaccine at 9 months of age into their routine vaccination program, Gavi would provide them with that vaccine at 20 cents a dose. So this takes away the financial barrier of a poor country introducing this vaccine.”

References:

Patel, P, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2035916

WHO. Typhoid. https://www.who.int/news-room/fact-sheets/detail/typhoid. Accessed Sept. 22, 2021.