One dose of typhoid vaccine still worked after four years in Malawi trial
The final analysis of a 28,130-child trial found roughly 78% efficacy over more than four years, evidence that underpins WHO's push to roll the conjugate vaccine out in endemic countries.
| Group | Value (%) |
|---|---|
| All ages (9 months–12 years) | 78.3 (66.3 to 86.1) |
| 9 months–2 years | 70.6 (6.4 to 93) |
| 2–4 years | 79.6 (45.8 to 93.9) |
| 5–12 years | 79.3 (63.5 to 89) |
A single dose of typhoid conjugate vaccine protected children in Malawi for more than four years, according to the final analysis of a phase 3 randomised controlled trial published in The Lancet [s1]. Efficacy against blood culture-confirmed typhoid fever was 78.3% (95% CI 66.3–86.1) over a median 4.3 years of follow-up, and protection held across every age group, including children under two [s1].
That durability question is the one that matters for policy. Earlier trials had shown high short-term protection, but data beyond two years were sparse [s1] — and a vaccine that fades quickly is far harder to justify rolling into routine childhood schedules than one that lasts.
What the trial did
Between 21 February and 27 September 2018, the TyVAC team in Blantyre, Malawi, vaccinated 28,130 healthy children aged 9 months to 12 years, randomly assigning 14,069 to a single dose of Vi polysaccharide conjugated to tetanus toxoid (Vi-TT) and 14,061 to a meningococcal conjugate vaccine as the control [s1]. Over a median 4.3 years (IQR 4.2–4.5), 24 children in the vaccine group developed a first episode of blood culture-confirmed typhoid — 39.7 cases per 100,000 person-years — against 110 cases in the control group, or 182.7 per 100,000 person-years [s1]. On those figures, 163 children (95% CI 129–222) needed to be vaccinated to prevent one case [s1].
Protection did not drop off in the youngest children, a group in whom some conjugate vaccines underperform. Efficacy was 70.6% (95% CI 6.4–93.0) for children aged 9 months to 2 years, 79.6% (45.8–93.9) for those aged 2–4 years, and 79.3% (63.5–89.0) for those aged 5–12 years [s1]. The wide confidence interval in the youngest band reflects how few cases occurred there, and is worth reading as imprecision rather than weaker protection [s1]. The trial was funded by the Bill & Melinda Gates Foundation [s1].
Why a typhoid vaccine is a priority now
Typhoid remains a large, and increasingly drug-resistant, burden. As of 2019, WHO estimated about 9 million people fall ill with typhoid and 110,000 die from it each year, concentrated in low-income settings with unsafe water and sanitation [s2]. Gavi, which funds the vaccine's introduction in eligible countries, puts the annual infection range higher, at 11–20 million [s3]. The pressing complication is antimicrobial resistance: drug-resistant Salmonella Typhi is spreading across Asia and Africa, narrowing the antibiotics that still work and raising the value of preventing infection in the first place [s2][s3].
WHO recommends the conjugate vaccine for use from 6 months of age, and two typhoid conjugate vaccines have been prequalified by the agency since December 2017 [s2]. The trial's authors frame their result as supporting WHO's current recommendation in endemic areas — mass campaigns among children aged 9 months to 15 years, followed by routine introduction in the first two years of life [s1].
From trial to rollout
The programmatic story is already moving. Gavi funding for the prequalified vaccine became available in 2018; Pakistan became the first country to add it to its routine schedule in 2019, Liberia and Zimbabwe introduced it nationwide in 2021, and Nepal followed in 2022 [s3]. By the end of 2021, more than 3 million children had been reached through routine immunisation and a further 36 million aged up to 15 through catch-up campaigns delivered with Gavi support [s3].
The durability finding strengthens the case for that approach, but it does not settle everything. The trial measures a single site over a single window, and how a one-dose schedule performs across different transmission settings and over still longer horizons will decide how confidently countries can rely on it — a question that sits alongside the broader push on childhood vaccination coverage. For now, the evidence points one way: in a high-burden African setting, one dose was still working four years on.
Sources
- Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children — The Lancet, 25 January 2024
- Typhoid (fact sheet) — World Health Organization, 30 March 2023
- Typhoid conjugate vaccine (TCV) support — Gavi, the Vaccine Alliance
Sources
- Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children — The Lancet , January 25, 2024
- Typhoid (fact sheet) — World Health Organization , March 30, 2023
- Typhoid conjugate vaccine (TCV) support — Gavi, the Vaccine Alliance , January 1, 2023
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