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What are the side effects of the oral typhoid (Ty21a) vaccine?

With the increasing ease of international travel, the risk of contracting infectious diseases like typhoid fever remains a concern for many globetrotters. The oral typhoid vaccine, specifically the Ty21a variant, has been a prominent tool in combating this potentially life-threatening illness. Over the years, this vaccine has been widely distributed and has seen extensive use, leading to a wealth of data regarding its side effects. In this blog post, we will explore the side effects of the oral typhoid vaccine, drawing insights from controlled clinical trials and post-marketing surveillance.

Controlled Clinical Trials

The oral typhoid vaccine underwent extensive scrutiny in controlled clinical trials, where its safety and efficacy were rigorously evaluated. More than 1.4 million doses of Ty21a were administered in these trials, and an impressive 150 million doses of Vivotif (Typhoid Vaccine Live Oral Ty21a) have been used worldwide. Two significant studies involving a total of 483 individuals receiving three vaccine doses recorded the side effects experienced after vaccination.

Reported Side Effects

The overall symptom rates from the combined studies revealed the following side effects and their respective frequencies among vaccinated individuals:

  • Abdominal pain: 6.4%

  • Nausea: 5.8% (statistically higher frequency than placebo)

  • Headache: 4.8%

  • Fever: 3.3%

  • Diarrhea: 2.9%

  • Vomiting: 1.5%

  • Skin rash: 1.0%

It's important to note that most of these side effects were relatively mild and infrequent. Also, some of the differences could be explained by random noise in the differences between treatment and control groups. In fact, only one side effect, nausea, occurred at a high enough rate in the treatment condition to obtain statistical significance.

Higher Doses, Mild Reactions

In an open study involving 155 healthy adult males, administration of vaccine doses more than five times higher than the recommended dose resulted in only mild reactions. This finding underscores the vaccine's relatively favorable safety profile even at higher doses.

Post-Marketing Surveillance

Post-marketing surveillance has played a crucial role in monitoring the vaccine's safety in real-world conditions. During the period from 1991 to 1995, over 60 million doses of the oral typhoid vaccine were administered in the form of capsules, and the reported adverse reactions were infrequent and mostly mild.

The recorded side effects included (N is the number of people who reported it):

- Diarrhea (N = 45)

- Abdominal pain (N = 42)

- Nausea (N = 35)

- Fever (N = 34)

- Headache (N = 26)

- Skin rash (N = 26)

- Vomiting (N = 18)

- Urticaria in the trunk and/or extremities (N = 13)

Additionally, there was one isolated case of non-fatal anaphylactic shock, which was considered an allergic reaction to the vaccine. It's worth emphasizing that this allergic reaction was rare, emphasizing the vaccine's overall safety.


The oral typhoid vaccine, specifically the Ty21a variant, has proven to be a valuable tool in preventing typhoid fever. With extensive use and millions of doses administered worldwide, the vaccine's safety profile has been well-documented. The most common side effects, such as abdominal pain, nausea, and headache, were generally mild and self-limiting. Moreover, higher doses of the vaccine were found to cause only mild reactions in healthy adults.

While no vaccine is entirely without risk, the benefits of immunization against typhoid fever far outweigh the potential side effects for most individuals. It's essential to consult with healthcare professionals before receiving any vaccine, considering individual health conditions and travel plans. We offer this service at our travel clinic in Scottsdale, Arizona. As research and surveillance continue, we can remain confident in the efficacy and safety of the oral typhoid vaccine as a vital defense against this serious infectious disease.


Vivotif Package Insert USA – Updated September 2013


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