Typhoid fever vaccination: indications and schedule

Typhoid fever is caused by the bacterium Salmonella Typhi and is transmitted through contaminated water and food. The disease remains endemic in several countries in Africa and Asia and is also found in travelers. In recent years, the problem has been exacerbated by the rise in drug resistance, including extensively resistant strains, increasing the importance of prevention and timely vaccination for travelers. [1]

In the United States and Europe, typhoid vaccination is primarily considered as protection before traveling to risk areas and for laboratory workers and service providers who come into contact with Salmonella Typhi material. Regional recommendations emphasize that even after vaccination, hygiene and safe eating and drinking practices must be observed. [2]

Spain classifies the typhoid vaccine as a travel vaccine. The Ministry of Health publishes separate information on the injectable and oral vaccines and recommends contacting international vaccination centers for an individual assessment of the route, timing, and schedule. [3]

At the global level, the World Health Organization recommends the systematic introduction of typhoid fever conjugate vaccines in countries with high incidence, while for other population groups, individual indications remain a priority, especially before travel. [4]

What vaccines exist and how do they differ?

Three technology lines are currently in use: an inactivated polysaccharide Vi vaccine for intramuscular administration, a live attenuated oral vaccine based on the Ty21a strain, and conjugate typhoid vaccines, where the Vi polysaccharide is linked to a carrier protein to enhance and prolong the immune response. Conjugate technology provides higher efficacy in young children and longer-lasting protection. [5]

Conjugate vaccines have received strong evidence of efficacy in randomized trials in Nepal, Malawi, and Bangladesh, demonstrating consistent protection for at least 4–5 years after a single dose. These data form the basis for recommendations for widespread use in endemic countries. [6]

By early 2025, the World Health Organization prequalified several conjugate vaccines, expanding procurement availability for immunization programs. This increased the sustainability of global supply and reduced the risk of shortages. [7]

The inactivated polysaccharide vaccine Vi and the live oral vaccine Ty21a continue to be widely used to protect travelers. They provide moderate efficacy and require booster shots at regular intervals. The choice between them depends on age, contraindications, and travel logistics. [8]

Table 1. Typhoid fever vaccine technologies and key features

Technology	Impact on immunity	Age limits for use	Duration of protection
Polysaccharide Vi, intramuscular	Humoral response without memory effect in infants	From 2 years old	Usually up to 2 years for travelers
Live attenuated Ty21a, oral	Mucosal and systemic response	From 6 years old	The full course takes about 5 years
Conjugate vaccine against typhoid fever	Stronger and longer lasting response in young children	From 6 months in endemic countries	Confirmed protection for up to 4-5 years and longer according to observational data
[9]

Who is eligible for vaccination and how to assess the need

For travelers over 2 years of age traveling to regions with a confirmed risk of infection, vaccination is recommended as part of their travel preparation. The decision is based on the destination country, length of stay, type of trip, and food and accommodation conditions. [10]

Vaccination is also considered indicated for laboratory workers and epidemiological teams exposed to the pathogen or clinical specimens. In cases of high occupational exposure, regular booster vaccinations are considered according to the selected technology. [11]

In high-incidence countries, typhoid fever conjugate vaccines are recommended for inclusion in childhood immunization programs starting at 6 months of age, with potential campaigns at older ages. This strategy has proven effective in reducing disease severity and the burden on the healthcare system. [12]

For Spain, as a country of departure, the Ministry of Health and regional international vaccination centres recommend seeking advice 4-6 weeks before departure in order to complete the course and, if necessary, combine it with other vaccinations and malaria prophylaxis. [13]

Table 2. Who is most likely to benefit from vaccination?

Category	Reason and commentary
Travelers to risk areas	Recommended for travel to endemic countries in Africa and Asia
Laboratories and epidemiological teams	Working with Salmonella Typhi or clinical specimens
Children in endemic countries	Program from 6 months based on a conjugate vaccine
Family visits and long-term stays	Higher household risk than with a short tour
[14]

Administration schedules, timing and revaccination

The polysaccharide vaccine Vi is administered as a single intramuscular dose at least 2 weeks before potential exposure. Travelers who remain at risk are recommended to repeat the dose every 2 years. This schedule ensures the maintenance of protective titers in adults and children aged 2 years and older. [15]

The live oral Ty21a vaccine is administered as a course of 4 capsules every other day, ending at least 1 week before potential exposure. Each capsule is taken on an empty stomach with cool liquid. If the risk persists, the course is repeated every 5 years. Age of onset: 6 years. [16]

Typhoid fever conjugate vaccine is used as a single dose in endemic countries from 6 months of age, with long-term efficacy confirmed. It is not used for routine travel to countries where such a vaccine is not licensed for this indication. [17]

Spanish travel materials confirm the two forms available in the country—injectable and oral—and emphasize the importance of adhering to the recommended dose intervals and possible reminder doses if the risk persists. The specific booster dose interval is determined based on the form and individual risk. [18]

Table 3. Comparison of schemes for travelers

Vaccine	Age	Scheme	Minimum period before departure	Revaccination
Polysaccharide Vi, intramuscular	From 2 years old	1 dose	≥ 14 days	Every 2 years if risk persists
Live Ty21a, oral	From 6 years old	4 capsules every other day	Complete the course ≥ 7 days before risk	Every 5 years if the risk persists
[19]

Table 4. Trip preparation timing

Situation	What to consider
Departure in 2-3 weeks	Convenient polysaccharide vaccine Vi, 1 injection
Departure in 3-4 weeks	A full course of Ty21a is possible in the absence of contraindications.
Combination with other vaccinations	Acceptable when injection sites are spaced apart and compatibility is taken into account.
Simultaneous planning of malaria prevention	Consider interactions with Ty21a and antimalarial drug schedules
[20]

Contraindications, precautions and compatibility

Both polysaccharide Vi and live Ty21a are not used in acute febrile conditions. Live Ty21a is not used during pregnancy or in immunocompromised individuals, as it is a live vaccine. Polysaccharide Vi is considered preferable in immunocompromised individuals and may be used in pregnant women when the risk of infection is high and the benefit outweighs the potential risk. [21]

Antibacterial drugs suppress the replication of the Ty21a strain, so the oral vaccine course should be started no earlier than 72 hours after completing antibiotics. Antibiotics should not be administered for 72 hours after the last capsule. These intervals are critical for immunity development. [22]

When combined with malaria prophylaxis, there are special rules: the fixed-dose combination of atovaquone plus proguanil is best started no earlier than 10 days after the last Ty21a capsule. Mefloquine and chloroquine are allowed without special intervals, but for a number of other drugs, breaks in the schedule are required. [23]

In cases of gastrointestinal upset, it's best to postpone the Ty21a course until recovery. There are fewer restrictions for the Vi vaccine, but if you have any high fever, it's reasonable to postpone the vaccination until it stabilizes. This reduces the risk of confusion between illness symptoms and reactions to the vaccine. [24]

Table 5. Contraindications and precautions

Vaccine	Absolute contraindications	Important precautions
Polysaccharide Vi	Severe reaction to a previous dose or component	Acute febrile conditions - postpone
Live Ty21a	Pregnancy, immunodeficiency, severe reaction to the component	Acute fever or gastroenteritis - postpone
[25]

Table 6. Interactions and compatibility

Combination	Rule
Ty21a and antibiotics	An interval of at least 72 hours before and after the Ty21a course
Ty21a and atovaquone plus proguanil	Start antimalarial drug 10 days after the last capsule
Ty21a and mefloquine or chloroquine	Acceptable without special intervals
Combination with other vaccinations	It is allowed, with spacing of injection sites and taking into account the instructions.
[26]

Efficiency and duration of protection

Polysaccharide Vi and live Ty21a protect approximately 50-80% of vaccinated individuals and require regular booster vaccinations for travelers. This explains why hygiene measures remain mandatory even after vaccination. [27]

Conjugate vaccines against typhoid fever have demonstrated high efficacy in controlled trials and in real-world practice. In final analyses, efficacy after a single dose in children was maintained for at least 4 years, and according to some cohorts, for up to 5 years. [28]

The combined findings of regulators and experts confirm the good tolerability of conjugate vaccines and their suitability for inclusion in childhood schedules in endemic regions. This is particularly important given the rise in antibiotic resistance. [29]

For travelers from low-incidence countries, the choice is usually made between Vi and Ty21a, taking into account age, individual factors, and travel dates. When time is short, a single-dose injection of Vi is more convenient, while with sufficient time and no contraindications, an oral Ty21a regimen is suitable. [30]

Table 7. Efficacy and timing of revaccination in travelers

Vaccine	Evaluation of effectiveness	Recommended revaccination intervals
Polysaccharide Vi	About 50-80%	Every 2 years if risk continues
Live Ty21a	About 50-80%	Full course every 5 years if risk continues
Conjugate vaccine	Higher and more stable in children	In the programs of countries with high incidence according to national schemes
[31]

Antibiotic resistance and the role of vaccinations

Since 2016, extensively resistant Salmonella Typhi strains associated with the transfer of resistance plasmids have spread in Pakistan. Imported cases have been recorded in a number of countries. In this context, primary prevention, including pre-travel vaccination, takes on added value. [32]

Recent reviews highlight that increasing resistance reduces the reliability of empirical therapy, particularly in late presentations, and increases the importance of preventing infection. Conjugate vaccines are being considered as part of a strategy to reduce overall disease incidence in high-burden countries. [33]

Even if vaccinated, travelers are still required to adhere to strict food and water safety measures, as a large bacterial dose can overcome vaccine immunity. This rule applies equally to both unvaccinated and vaccinated individuals. [34]

Table 8. What stability affects and what a traveler should do

Factor	Practical consequence
Antibiotic resistance	Reduced predictability of treatment, higher risk of complications
Massive use of antibiotics without indications	Increased stability, decreased empirical efficiency
Vaccination	Reducing the risk of disease, especially in high-burden areas
Hygiene and safe water	Required even after vaccination
[35]