Nepal's typhoid conjugate vaccine cut confirmed disease by 89%, study finds

A typhoid conjugate vaccine introduced across Nepal through a catch-up campaign and routine immunisation was 89% effective at preventing blood-culture-confirmed typhoid fever in children, according to a test-negative study published in The Journal of Infection on 8 March [s1]. The 95% confidence interval ran from 65% to 97% [s1].

The vaccine studied is TYPHIBEV, a Vi-CRM197 conjugate. Typhoid fever is a life-threatening infection caused by the bacterium Salmonella Typhi and is usually spread through contaminated food or water, the World Health Organization says [s2]. As of 2019, an estimated 9 million people get sick from typhoid and 110 000 people die from it every year [s2]. WHO recommends the typhoid conjugate vaccine for use in children from 6 months of age [s2].

How the study was built

The researchers used a test-negative, case-control design, a method that compares vaccination status between people who test positive and negative for the disease at the same health facilities. Cases were vaccine-eligible paediatric patients who tested positive for Salmonella Typhi by blood culture; test-negative controls were vaccine-eligible patients who tested negative [s1]. Controls were matched to cases by age, location, date of blood culture and surveillance site, and the team calculated odds ratios using conditional logistic regression, with vaccine effectiveness defined as one minus the odds ratio [s1].

Between 1 October 2022 and 31 December 2024, the study enrolled 40 typhoid cases and 113 matched, test-negative controls [s1]. Cases and controls were similar in their sociodemographic characteristics and in water, sanitation and hygiene-related living conditions — a point that matters, because it means the effectiveness estimate is less likely to be an artefact of who lives in cleaner conditions [s1].

The numbers

Among the 39 cases and 108 controls whose vaccine status was known, 20 cases (51%) and 91 controls (84%) had received the conjugate vaccine [s1]. That gap between the sick and the well is the raw signal behind the headline figure.

Effectiveness was not uniform across ages. In children aged 5 to 15 years, the vaccine was 98% effective, with a confidence interval of 80% to 100% [s1]. In children under 5, the point estimate fell to 72%, but the confidence interval was very wide — from minus 203% to 97% [s1]. A confidence interval that crosses zero, and stretches deep into negative territory, means the under-five estimate is too imprecise to stand on its own; it reflects how few young cases the study captured rather than evidence that the vaccine fails in that group. The authors reported that effectiveness estimates did not significantly differ when the analysis was restricted to participants with documented vaccination status [s1].

The overall finding held over a 30-month follow-up period after national introduction, and the authors judged the effectiveness comparable to that observed for Typbar-TCV, the other WHO-prequalified typhoid conjugate vaccine [s1].

Why a second option matters

Two typhoid conjugate vaccines have been prequalified by WHO since December 2017 and are being introduced into childhood immunisation programmes in typhoid-endemic countries [s2]. Having more than one prequalified product widens the supply base that endemic countries can draw on, and evidence that the newer option performs in line with the established one removes a reason to prefer one over the other on effectiveness grounds.

That matters most where the disease is hardest to treat. Typhoid fever can be treated with antibiotics, but increasing resistance to different types of antibiotics is making treatment more complicated, WHO says [s2]. Urbanisation and climate change have the potential to increase the global burden of the disease, and rising antibiotic resistance makes it easier for typhoid to spread in communities that lack access to safe drinking water or adequate sanitation [s2]. In that setting a vaccine that heads off infection is worth more than its case count alone suggests, because each case prevented is also a course of increasingly precarious antibiotics not needed.

What the study does not settle

This is a single-country, observational analysis built on a modest number of confirmed cases — 40 in total — and its precision reflects that. The strong overall estimate rests mostly on the 5-to-15 age band; the under-five result is genuinely uncertain, and it is younger children who carry much of the typhoid burden in endemic settings. The 30-month window also cannot speak to how long protection lasts, a question that durability studies of the first-generation conjugate vaccine are still working through.

What the study does establish is narrower and useful: in a real national rollout, not a trial, a second prequalified conjugate vaccine cut confirmed typhoid substantially, at a level consistent with the vaccine that came before it.

Sources

• Effectiveness of the TYPHIBEV® (Vi-CRM197 conjugate) vaccine introduction in Nepal: A test-negative, case-control study — The Journal of Infection, 8 March 2026
• Typhoid (fact sheet) — World Health Organization