Typhoid conjugate vaccine at scale

One dose of typhoid conjugate vaccine (TCV) cut typhoid by 78.3% over more than four years in a trial of 28,130 Malawian children ¹. In that trial, health workers needed to vaccinate 163 children to prevent one case of typhoid ¹. More recent public-sector programmes in India, Zimbabwe, Nepal and Pakistan have shown that this protection holds outside a trial ²³⁴¹⁶. In 2025 alone, more than 80 million children received TCV in introduction campaigns ¹³.

Evidence from Bangladesh shows where the vaccine falls short. Protection fades in the youngest children, and in March 2026 WHO's Strategic Advisory Group of Experts (SAGE) responded by advising a booster dose around age 5 in the settings with the most typhoid ⁶¹¹. This article walks through the burden, the studies, the costs and what comes next.

The burden

Typhoid is caused by the bacterium Salmonella enterica serotype Typhi. It spreads by the faecal-oral route, so it thrives where water and sanitation are poor ¹⁷.

Estimates of its size differ by source and year, but all point the same way: down, and still large.

• The Global Burden of Disease (GBD) 2017 study estimated 14.3 million cases of typhoid and paratyphoid fever in 2017, down 44.6% from 25.9 million in 1990. Typhi caused 76.3% of these cases. Deaths fell 41.0%, from 230.5 thousand in 1990 to 135.9 thousand in 2017 ⁸.
• The same study put global case fatality at 0.95%, with higher case fatality among children and older adults, and in lower-income countries ⁸.
• WHO's fact sheet estimates that, as of 2019, 9 million people fell ill with typhoid and 110,000 died each year ¹⁰.
• The most recent figure, presented to SAGE in March 2026, is about 6 million cases and 72,000 deaths worldwide ¹¹.

Children carry much of it. A GBD 2021 analysis of people aged 0 to 19 found that typhoid deaths in this age group fell from 152,567 in 1990 to 69,364 in 2021. Cases fell from 14.76 million to 4.98 million ⁹. We did not find a verified GBD figure for children under 5 alone, so we report the 0–19 figure.

The review presented to SAGE found that laboratory-confirmed typhoid peaks in children aged 5 to 9 in endemic settings. There is also a significant burden in children aged 2 to 4 where incidence is high or very high ¹¹.

Where. In 2021, South Asia accounted for 3.37 million cases and 44,095 deaths among children and adolescents ⁹. The burden stays concentrated in South Asia, sub-Saharan Africa and Oceania, and in low-income settings ⁹. Bangladesh alone estimates about 478,000 typhoid infections and 8,000 deaths a year, with children accounting for nearly 68% of those deaths ¹⁴.

Resistance makes it worse. Pakistan has faced extensively drug-resistant (XDR) typhoid. In a 2024–2025 cohort of 65 children with culture-confirmed XDR typhoid at POF Hospital in Northern Punjab, every isolate was resistant to ceftriaxone and ciprofloxacin. Only meropenem (100%) and azithromycin (96.9%) still worked well ²⁶. When the cheap oral drugs fail, prevention becomes more valuable.

How it works

What the vaccine is. The outer coat of the typhoid bacterium is made of a sugar called the Vi polysaccharide. Older typhoid vaccines used this sugar alone. A conjugate vaccine joins the sugar to a carrier protein, such as tetanus toxoid (Vi-TT) or CRM197 (Vi-CRM197) ¹⁹²³. This makes the vaccine work in infants and young children, and gives longer protection than the older vaccines ⁸¹⁰.

Who gets it. WHO recommends TCV from 6 months of age, and for adults up to 45 or 65 years depending on the product ¹⁰. It is one injection ¹⁰.

How countries give it. The usual pattern has two parts ¹²¹⁴²¹:

1. A one-time catch-up campaign for all children from 9 months to under 15 years. Gavi pays the full cost of this campaign ¹².
2. Routine immunisation from then on, usually at 9 months of age. Gavi co-finances this part with the country ¹². Malawi, for example, added TCV to the 9-month visit after its 2023 campaign ²¹.

It can share a visit. A phase IV study of 400 infants aged 9 to 12 months in India, run by the manufacturer Biological E, found that TYPHIBEV given with measles-rubella vaccine did not reduce the response to either vaccine. No safety signals were seen ²⁰. Malawi delivered TCV in the same campaign as measles-rubella vaccine, oral polio vaccine and vitamin A ²¹.

Who should get it now. SAGE's March 2026 advice sets clear thresholds ¹¹:

• Introduce TCV where typhoid incidence is high (100 to under 500 cases per 100,000 people a year) or very high (500 or more), or where resistant typhoid is common.
• Consider TCV where incidence is medium (10 to under 100 per 100,000) and case fatality is high.
• Consider a booster around age 5 in very-high-incidence settings for children who got their first dose at 9 to 24 months.
• Consider a booster elsewhere only if vaccinated children show signs of waning protection, especially where case fatality or resistance is high.

SAGE notes that these incidence figures must be adjusted for blood-culture sensitivity and care-seeking. They should not be applied to crude counts from national laboratory registries ¹¹.

What the evidence shows

2019–2021: efficacy before national rollout

The 2019 Nepal phase 3 report randomised 20,019 children aged nine months to 16 years to TCV or a meningococcal control vaccine. Blood-culture-confirmed typhoid occurred in 7 versus 38 children, giving efficacy of 81.6% (95% CI 58.8–91.8) ²⁸. This established protection in an endemic setting; it did not yet establish how long that protection would last.

Pakistan also has direct evidence from an extensively drug-resistant (XDR) outbreak. A 2021 cohort study in Hyderabad analysed 23,407 children and estimated effectiveness of 95% (95% CI 93–96) against culture-confirmed typhoid and 97% (95–98) against XDR typhoid ²⁹. Unlike the Nepal trial, vaccination was not randomised, leaving potential differences in exposure, care-seeking and testing between groups. The result supports outbreak protection but should not be treated as a universal estimate or a measure of long-term durability.

Malawi: the TyVAC trial

The TyVAC trial was run by the Malawi-Liverpool-Wellcome Programme and the University of Maryland in Blantyre. It was a double-blind randomised trial that compared the Vi-TT conjugate vaccine with a meningococcal control vaccine. It enrolled 28,130 children aged 9 months to 12 years and followed them for a median of 4.3 years ¹.

Vaccine efficacy was 78.3% (95% CI 66.3–86.1). Typhoid incidence was 39.7 per 100,000 person-years in vaccinated children against 182.7 in the control group ¹. The number needed to vaccinate to prevent one case was 163 ¹.

The youngest children were also protected. In those aged 9 months to 2 years, efficacy was 70.6%, though the confidence interval was wide (6.4–93.0) ¹.

Caveat. The wide interval means the estimate for this age group is imprecise.

Navi Mumbai, India: a city campaign

In 2018 the Navi Mumbai Municipal Corporation ran a paediatric TCV campaign. A case-control study with the US CDC compared 38 cases with 140 controls. It found an adjusted odds ratio of 0.16 (0.05–0.55), which equals a vaccine effectiveness of 83.7% (45.0–95.3) ².

A routine public programme, run by a city health department, matched the trial results.

Caveat. The estimate rests on only 38 cases ².

Harare, Zimbabwe: an outbreak city

Harare City Health Department analysed 3,401 typhoid cases from 2017 to 2024, before and after vaccination campaigns. In the Western district, the attack rate fell from 1,373 to 341 per 100,000 (RR 0.40). In Mufakose it fell from 1,687 to 33 per 100,000 ³.

After vaccination, antimicrobial resistance was lower and the strain population did not shift ³.

Caveat. This is a before-and-after comparison, not a trial. Other changes in the city over those years could explain part of the fall.

Nepal: the first national programme in South Asia

Dhulikhel Hospital, Kathmandu University, reviewed 62,236 blood cultures from four Kathmandu Valley health facilities from 2018 to 2024. Nepal introduced TCV nationally in 2022, just after the COVID-19 pandemic disrupted care and surveillance ⁴.

After national introduction, the odds of a positive Salmonella Typhi culture in eligible children fell 75% (aOR 0.25, 0.11–0.55) ⁴. This is the first impact signal from a national programme in South Asia.

Caveat. The pandemic changed both typhoid transmission and care-seeking, which makes the vaccine effect harder to isolate. The authors adjusted for this by comparing three periods ⁴.

Pakistan: the first country to introduce

Pakistan was the first country to put TCV into routine immunisation, in 2019 ¹². It has since vaccinated more than 30 million children through campaigns and routine visits ¹³.

A team working with data from the Surveillance for Enteric Fever in Asia Project and a Pakistani impact study (ITRIPP) modelled blood-culture-confirmed cases from 2018 to 2023. Over the first two years after rollout, TCV cut typhoid incidence by 48.9% (95% CI 47.3–50.3) in Sindh and 66.2% (64.7–67.6) in Punjab ¹⁶. The Bill & Melinda Gates Foundation funded the study ¹⁶.

Caveat. The effect declined each year. In Sindh, where typhoid was more common and struck younger children, the model predicted that incidence would return close to pre-vaccine levels in 2024. An extra campaign gave only short-term benefit in the model ¹⁶.

Pooled real-world data

A systematic review and meta-analysis from Indonesia pooled four post-licensure studies of 24,180 children in Pakistan, India and Zimbabwe, all using Typbar TCV. Effectiveness against culture-confirmed typhoid was 87% (95% CI 57–94). Against XDR typhoid it was 97% (95–98) ¹⁷.

Caveat. Only four studies fed the main estimate. A wider sensitivity analysis found that protection was higher in children over 5, and declined significantly 4 to 5 years after vaccination ¹⁷.

Bangladesh: cheaper monitoring works

Countries need to track how well the vaccine works without running new trials. The Oxford Vaccine Group and icddr,b re-analysed a cluster-randomised trial of 62,025 eligible children in Bangladesh ⁵.

Effectiveness was 89% (81–93) in the randomised analysis and 88% (79–93) with a test-negative design, which uses routine fever-clinic data ⁵. A cohort design gave 79% (70–86) ⁵.

The test-negative design compares children with fever who test positive for typhoid against those who test negative. It gives a good estimate at much lower cost than a trial ⁵.

Booster studies: Malawi and Nepal

Malawi. The TyVAC team went back to children vaccinated at 9 to 11 months in the original trial. In 2023, at age 5, 72 got a second Vi-TT dose and 64 got their first ¹⁸.

Four years after the first dose, antibody levels were still higher in previously vaccinated children (18.8 vs 5.7 EU/mL). After the booster, levels rose to 6,867.9 EU/mL, against 2,912.0 in children getting their first dose. All boosted children responded, and side effects were similar in both groups ¹⁸.

Nepal. Nepal's national programme uses a Vi-CRM197 vaccine, and it started four years after a large Vi-TT trial there. This let researchers test a mixed-product booster ¹⁹.

A single dose of Vi-CRM197 gave clearly lower antibody levels than a Vi-TT dose followed by a Vi-CRM197 booster about 4 years later (adjusted ratio 0.24, 95% CI 0.18–0.32). A booster after about 2 years gave an intermediate response ¹⁹. The authors conclude that a booster after a longer interval gives the strongest immunity ¹⁹.

Caveat. Both are antibody studies. They show the immune system responds strongly to a booster, but they do not measure fewer typhoid cases ¹⁸¹⁹.

Results table

LimitsWhat didn't work (or the limits)

Protection wanes in young children. The TyVOID study, led by Firdausi Qadri at icddr,b with the Oxford Vaccine Group in Dhaka, followed the Bangladesh trial to five years ⁶. Children vaccinated earlier had 3.10 times the typhoid rate of those vaccinated recently (IRR 3.10, 1.53–6.29). In the test-negative analysis, effectiveness was 84% for the recently vaccinated group and 55% for the earlier group. The extrapolated effectiveness in years 3 to 5 was 50%, with a wide interval that included zero (−13 to 78).

In children younger than 7 at the time of their fever visit, effectiveness fell to 24% (−29 to 55), which is not statistically significant ⁶. The authors' findings point to a booster dose at school entry. SAGE has now drawn the same conclusion for very-high-incidence settings ¹¹.

Waning shows up at population level too. In Pakistan's Sindh province, the fall in typhoid shrank each year after rollout, and the model predicted a return close to pre-vaccine levels ¹⁶. SAGE's own summary says waning is clearest in very-high-incidence settings and in children vaccinated before age 2 ¹¹.

The campaign did not reduce antibiotic prescribing. Many hoped that TCV would cut antibiotic use and slow drug resistance. The Biomedical Research and Training Institute (BRTI) in Harare and LSHTM studied 27,107 paediatric consultations around Harare's vaccine campaign. The campaign did not change total antimicrobial prescribing (aRR 1.20, 0.70–2.05) or prescribing of antibiotics used for typhoid (aRR 0.93, 0.44–1.96) ⁷. Without better diagnostics and clean water, clinicians still treat fever with antibiotics.

Adults outside the programme. In Nepal, the odds of a positive typhoid culture rose in people aged 16 and over, who were not eligible for the vaccine (aOR 1.59) ⁴. Vaccinating children did not protect unvaccinated adults in this setting.

One dose of a different product may not be the same. In Nepal, children who got a single dose of the Vi-CRM197 vaccine had lower antibody levels than children who had earlier received Vi-TT (adjusted ratio 0.56, 0.47–0.66) ¹⁹. This is an antibody finding, not a disease finding, but it shows that products should not be assumed interchangeable without data.

XDR protection has direct but observational evidence. The 2021 Hyderabad cohort is now inside the review window ²⁹. Its high effectiveness estimate should be read alongside the design limitations; the later pooled estimate ¹⁷ is not independent confirmation of all the same underlying cases.

Small studies. The Navi Mumbai estimate rests on 38 cases, and the Harare outbreak analysis is a pre/post comparison, not a trial ²³. Both agree with the trial data, but each is weaker on its own.

Cost and scale

Price per dose. UNICEF publishes the prices it pays suppliers. For Gavi-supported countries, in 5-dose vials ¹⁵:

Bharat Biotech's price had been $1.50 since 2018 and falls to $0.99 from 2026 ¹⁵. BE Vaccines charged $0.95 from 2021 to 2023 and has since raised its price ¹⁵. Middle-income countries pay $1.50 for the BE Vaccines product ¹⁵.

Manufacturers. Four TCVs were WHO-prequalified by 2025: Typbar TCV, TYPHIBEV, SKYTyphoid and ZyVac TCV ¹⁷.

Cost of delivery. Two government-perspective costing studies, which exclude the price of the vaccine and syringes, give a sense of what countries pay to deliver it:

• Malawi (2023). The integrated campaign aimed to reach more than 9 million children aged 9 months to under 14 years, about half the population. The financial cost per dose for all interventions was $0.49, and the economic cost $0.84. Routine delivery of a TCV dose cost $0.44 financially and $2.37 economically ²¹. The integrated campaign cost less per dose than single-vaccine TCV campaigns reported in India and Zimbabwe ²¹.
• Burkina Faso (2025). The Ministry of Health's national campaign for children aged 9 months to 14 years gave 10.5 million doses. The financial cost per dose was $0.47, and the economic cost $2.16. Costs were higher in rural and conflict-affected areas ²². The financial cost stayed within Gavi's operational support range ²².

Gavi support. Gavi funding for WHO-prequalified TCV became available in 2018 ¹². Gavi pays in full for a one-time catch-up campaign for children up to 15, and co-finances routine introduction ¹².

Countries introduced. Pakistan introduced TCV in 2019. Liberia and Zimbabwe introduced it nationwide in 2021, and Nepal in 2022 ¹². Malawi followed in 2023 ²¹. Burkina Faso, Kenya, Bangladesh and Niger introduced it in 2025 ¹³.

Scale. More than 80 million children received TCV in introduction campaigns in 2025, and more than 130 million in campaigns overall ¹³. Bangladesh's campaign, launched on 12 October 2025, targeted about 50 million children aged 9 months to under 15 years, with 50.4 million doses supplied through UNICEF ¹⁴. Gavi describes Bangladesh as the eighth country in the world to introduce TCV ¹⁴. Routine vaccination of infants there is planned from 2026 ¹⁴.

Coverage. We did not find a verified global coverage figure for routine TCV. Bangladesh set a campaign target of at least 95% coverage ¹⁴.

What to watch

Booster doses. SAGE's March 2026 advice on a booster around age 5 will be published in full in WHO's Weekly Epidemiological Record, and only that wording is final ¹¹. Countries with very high incidence and a 9-month primary dose, such as Pakistan's Sindh province, will need to decide whether and when to add a school-age dose ¹¹¹⁶.

A new product tested in Dhaka. icddr,b has registered a phase III test-negative effectiveness study of Zydus's ZyVac TCV in Dhaka South City Corporation (NCT06757283). It covers children aged 6 months to 15 years in nine city wards, with about 60,000 of 92,000 eligible children expected to be vaccinated ²³.

Combined Salmonella vaccines. GSK's Vaccines Institute for Global Health is testing a vaccine against both invasive non-typhoidal Salmonella and typhoid in infants in the Gambia (NCT07286370, 537 participants, phase 2) ²⁴. It is also testing a four-part pan-Salmonella vaccine in young adults in South Africa (NCT07663032, 196 participants) ²⁵.

Paratyphoid. In Pakistan, S. Paratyphi A remains a prominent cause of bloodstream infection, and TCV does not protect against it ²⁷. Genomic baselines are being built to evaluate future paratyphoid vaccines ²⁷.

Open questions.

• How long does protection last in high- versus very-high-incidence settings ¹¹¹⁶?
• Can products be mixed safely and effectively for a booster ¹⁹?
• Does TCV reduce antibiotic use once diagnostics improve ⁷?
• Can funding keep pace? SAGE notes that further TCV expansion will need close coordination between Gavi, WHO and partners "in a constrained funding context" ¹¹.

What it means

The main result is strong and consistent. One dose of TCV prevents most typhoid in children for several years in Africa and South Asia ¹²⁴¹⁶. It works in city campaigns and in national programmes, run by municipal health departments and ministries of health rather than by trial teams ²³⁴.

For ministries of health:

• Use SAGE's incidence bands. They tell you whether to introduce now, consider it, or wait ¹¹.
• Plan for a booster where typhoid is very common. Protection in the youngest children fades by years 3 to 5 in Bangladesh, and incidence rebounded in Sindh ⁶¹⁶. A booster around age 5 is now WHO-advised in these settings ¹¹. Booster studies in Malawi and Nepal show a strong immune response ¹⁸¹⁹.
• Integrate the campaign. Malawi and Burkina Faso delivered doses for under $0.50 in financial cost per dose, and integration with other vaccines kept Malawi's costs low ²¹²².
• Use test-negative monitoring. It closely matched randomised results and can run on routine hospital data ⁵.

For funders:

• The vaccine itself costs about $1 to $1.34 a dose for Gavi countries ¹⁵. Delivery adds roughly $0.44 to $0.49 in financial cost per dose ²¹²².
• Budget for a second dose in very-high-incidence countries, and for blood-culture surveillance to find them ¹¹.

For clinicians and health workers:

• A vaccinated child with fever can still have typhoid, especially if vaccinated as a toddler several years ago ⁶.
• Do not assume adults in the household are protected ⁴.
• The vaccine does not remove the need for testing and careful antibiotic use. Harare's null result on prescribing shows that diagnostics, water and sanitation are still needed ⁷.

For children who get it, TCV is a highly effective single-dose vaccine. The remaining task is to keep them protected as they grow, and to reach the adults and communities around them.