Typhoid vaccines: Typhim Vi and Vivotif

The disease and why it matters

Salmonella enterica serotype Typhi causes typhoid fever and serotypes Paratyphi A, B and C cause paratyphoid fever (collectively enteric fever); humans are the only source, and infection is acquired by consuming water or food contaminated by feces of an acutely infected or convalescent person or a chronic carrier. ^[1]

An estimated 9.2 million cases of typhoid fever and 3.8 million cases of paratyphoid fever occur worldwide each year, causing an estimated 133,000 deaths; approximately 85% of typhoid fever and 80% of paratyphoid fever cases in the United States occur among international travelers, and more than 70% of those are in travelers returning from South Asia, primarily Bangladesh, India and Pakistan. ^[1]

The typical incubation period for typhoid fever is 6 to 30 days (1 to 10 days for paratyphoid); fever rises daily to 39 to 40 °C by the third or fourth day, and serious complications (gastrointestinal hemorrhage, intestinal perforation, encephalopathy) occur in 10% to 15% of hospitalized patients, generally after 2 to 3 weeks of illness. Untreated, the case-fatality ratio has been reported at more than 10%, compared with usually less than 1% with prompt medical care. ^[1]

Travelers visiting friends and relatives are at increased risk because they might be less careful with food and water and might not seek pre-travel consultation or typhoid vaccination; travelers have acquired typhoid fever during visits of less than 1 week to highly endemic countries. ^[1]

CDC reports that extensively drug-resistant (XDR) typhoid fever began in an outbreak in Pakistan in 2016 and that cases, including among people in the United States, continue to occur; XDR cases have also been reported in the United States among people without recent international travel. Risk is greatest among people who travel to countries in Africa, Asia or Latin America where the diseases are common, visit rural areas, visit family and friends, or are not vaccinated against typhoid fever. ^[2]

Video and figures

Video

The video loads from YouTube when played.

Typhoid vs. Typhus: What’s the Difference?
Channel: Cleveland Clinic · Uploaded March 14, 2025 · Confirmed available October 12, 2026 · Open on YouTubeRxEvidence has not checked every statement in this video.

Get CE credit

Products available

Two typhoid vaccines are licensed in the United States: a Vi capsular polysaccharide vaccine (ViCPS; Typhim Vi, Sanofi Pasteur) for intramuscular use and a live attenuated Ty21a vaccine (Vivotif) for oral use; both are unconjugated and protect 50% to 80% of recipients, and neither is licensed to prevent paratyphoid fever. ^[1]

The Typhim Vi FDA page is marked content current as of 03/23/2020, and the Vivotif label posted on FDA's page names Crucell as manufacturer and distributor, carries an "Updated September 2013" header, and differs from the FDA page's manufacturer line (Bavarian Nordic) and the Yellow Book's (PaxVax); check the current manufacturer labeling. ^{[3] [6] [5] [1]}

Typhoid conjugate vaccines (TCV) have been licensed in India and some other countries and four TCVs have been prequalified by the WHO as of April 2025, but TCVs are not currently licensed or available in the United States. ^[1]

Who should get it

Typhoid vaccination is not required for international travel but is recommended for travelers to areas such as Africa, Asia, and Central and South America where there is a recognized risk of exposure to S. typhi. ^[4]

Typhoid fever is common in many regions of the world including parts of East and Southeast Asia, Africa, the Caribbean, and Central and South America, and is not common in the United States; routine vaccination in the United States is not recommended. ^[7]

Dosing and schedule, including catch-up

Primary vaccination with ViCPS consists of one 0.5 mL (25 µg) dose given intramuscularly at least 2 weeks before travel, with a dose recommended every 2 years for those who remain at risk; the Typhim Vi label likewise gives a single 0.5 mL injection with reimmunization every two years for U.S. travelers under conditions of repeated or continued exposure. ^{[1] [4]}

Ty21a: four capsules, one taken every other day (days 1, 3, 5 and 7), completed at least 1 week before potential exposure; all four doses must be taken for maximum efficacy; a booster is recommended every 5 years for those who remain at risk, and the Vivotif label says efficacy has been shown to persist for at least 5 years and that the optimum booster schedule has not been determined. ^{[1] [6]}

The approach for addressing a missed oral vaccine dose or taking a dose late is undefined; some suggest minor deviations (for example a dose 1 day late) might not alter efficacy, but no studies have shown the effect of such deviations, and travelers who do not complete four doses might not achieve an optimal immune response. ^[1]

Administration

• Typhim Vi is for intramuscular use only; inspect the syringe or vial and packaging for leakage, premature activation of the plunger or a faulty tip seal and do not administer if any exists; the vaccine must not be mixed with any vaccine in the same syringe, and separate injection sites should be used for concomitant administration. ^[4]
• Vivotif: each capsule should be swallowed whole (not chewed) with cool liquid no warmer than 37 °C (98.6 °F), approximately 1 hour before a meal and at least 2 hours after a previous meal; avoid alcohol 1 hour before and 2 hours after, because alcohol can disintegrate the enteric coating. ^[1]
• Inspect the Vivotif blister to ensure the foil seal and capsules are intact; the capsule should be swallowed as soon after placing in the mouth as possible. ^[6]
• Ty21a can be given simultaneously or at any interval before or after live virus vaccines (for example MMR, oral polio or yellow fever vaccines); no data are available on co-administration with the current oral cholera vaccine (Vaxchora), and simultaneous administration of Ty21a and immune globulin does not appear to pose a problem. ^[1]
• Vaccination with Ty21a should be delayed for more than 72 hours after any antimicrobial agent, and antibiotics should not be given within 72 hours after the last Ty21a dose; atovaquone-proguanil should be given only if 10 days or more have elapsed since the final dose of Vivotif, while mefloquine and chloroquine can be given with Ty21a. ^[1]
• The Vivotif label says several antimalarials with antibacterial activity (mefloquine, chloroquine, proguanil) may interfere with immunogenicity, and that concomitant mefloquine or chloroquine did not significantly reduce the response while simultaneous proguanil did. ^[6]

Storage and handling

• Typhim Vi: store at 2 to 8 °C (35 to 46 °F); do not freeze; discard if the vaccine has been frozen; supplied as a single-dose 0.5-mL syringe without needle or a 20-dose multi-dose vial. ^[4]
• Vivotif: not stable when exposed to ambient temperatures; ship and store at 2 to 8 °C (35.6 to 46.4 °F); the expiration date is valid only if the product has been maintained at 2 to 8 °C; a single foil blister contains the 4 doses; the capsules should be kept refrigerated (not frozen). ^{[6] [1]}

Contraindications and precautions

Safety and adverse events

Adverse reactions most often associated with ViCPS vaccine include headache, injection-site reactions, fever and general discomfort; adverse reactions to Ty21a are rare and mainly consist of abdominal discomfort, diarrhea, fever, headache, nausea, vomiting and rash. Report adverse reactions to VAERS. ^[1]

Typhim Vi clinical trials in more than 4,000 subjects found predominantly minor and transient local reactions (pain, erythema, induration) that almost always resolved within 48 hours; elevated oral temperature above 38 °C (100.4 °F) was observed in approximately 1% of vaccinees and no serious or life-threatening systemic events were reported. ^[4]

Vivotif: in 483 individuals receiving 3 vaccine doses overall symptom rates were abdominal pain (6.4%), nausea (5.8%), headache (4.8%), fever (3.3%), diarrhea (2.9%), vomiting (1.5%) and skin rash (1.0%); only nausea occurred at a statistically higher frequency than with placebo. ^[6]

Neither vaccine protects against paratyphoid fever or other enteric pathogens; the Typhim Vi label says it gives no protection against Salmonella paratyphi A or B, and the Vivotif label says vaccinated individuals should continue personal precautions against exposure to typhoid organisms. ^{[4] [6]}

Special populations

Pregnancy: no information is available on the safety of ViCPS in pregnancy, and ViCPS may be considered for pregnant women when the benefits outweigh potential risks (for example high likelihood of exposure to Typhi); live Ty21a vaccine should not be given to pregnant women. ^[1]

The Typhim Vi label says animal reproduction studies have not been conducted and it should be given to a pregnant woman only if clearly needed, with delay until the second or third trimester a reasonable precaution when possible; the Vivotif label gives pregnancy category C and says it should be given to a pregnant woman only if clearly needed. ^{[4] [6]}

Immunocompromised travelers: the intramuscular ViCPS vaccine presents a theoretically safer alternative than live oral Ty21a for immunocompromised travelers; Ty21a can be given to household contacts of immunocompromised people because secondary transmission of vaccine organisms has not been documented. ^[1]

Children: Typhim Vi safety and immunogenicity in children under 2 years have not been established, and the Vivotif label says safety and efficacy have not been established in children under 6 years of age; newer conjugate Vi vaccines have greater efficacy in children under 2 years but are not available in the United States. ^{[4] [6] [1]}

Counseling pearls for the pharmacy counter

• Typhoid vaccine is not 100% effective and is not a substitute for being careful about what you eat or drink. ^[7]
• Inactivated vaccine is a single injection at least 2 weeks before travel, repeated every 2 years for people who remain at risk; the live oral vaccine is one capsule every other day for 4 capsules, with the last dose at least 1 week before travel. ^[7]
• Keep Vivotif refrigerated, swallow capsules whole with cool liquid, and complete all four doses; tell the provider about antibiotic use and about antimalarial plans before taking the vaccine. ^[1]
• Typhoid fever can be life-threatening: symptoms include persistent high fever, weakness, stomach pain, headache, diarrhea or constipation, cough and loss of appetite, and as many as 30% of people who do not get treatment die from complications. ^[7]

Common patient questions

References

1. Centers for Disease Control and Prevention. Typhoid and paratyphoid fever. In: CDC Yellow Book: Health Information for International Travel, 2026 edition. Page dated April 23, 2025. Accessed October 11, 2026. https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/typhoid-and-paratyphoid-fever.html. Accessed October 11, 2026.
2. Centers for Disease Control and Prevention. Clinical overview of typhoid fever and paratyphoid fever. Page dated May 14, 2024. Accessed October 11, 2026. https://www.cdc.gov/typhoid-fever/hcp/clinical-overview/index.html. Accessed October 11, 2026.
3. U.S. Food and Drug Administration. Typhim Vi product page (content current as of 03/23/2020). Accessed October 11, 2026. https://www.fda.gov/vaccines-blood-biologics/vaccines/typhim-vi. Accessed October 11, 2026.
4. Typhim Vi (typhoid Vi polysaccharide vaccine): package insert as posted on FDA's product page (older-format label; no revision date in the posted document). Sanofi Pasteur SA. U.S. Food and Drug Administration. Accessed October 11, 2026. https://www.fda.gov/media/75993/download?attachment. Accessed October 11, 2026.
5. U.S. Food and Drug Administration. Vivotif product page (content current as of 01/22/2025). Accessed October 11, 2026. https://www.fda.gov/vaccines-blood-biologics/vaccines/vivotif. Accessed October 11, 2026.
6. Vivotif (typhoid vaccine live oral Ty21a): package insert as posted on FDA's product page (older-format label; a page header reads "Updated September 2013"). U.S. Food and Drug Administration. Accessed October 11, 2026. https://www.fda.gov/media/75988/download?attachment. Accessed October 11, 2026.
7. Centers for Disease Control and Prevention. Typhoid vaccine: what you need to know. Vaccine Information Statement, October 30, 2019. Accessed October 11, 2026. https://www.cdc.gov/vaccines/hcp/current-vis/typhoid.html. Accessed October 11, 2026.