What are the differences in side effect profiles between the inactivated injectable Vi polysaccharide vaccine and the live attenuated oral Ty21a (Typhoid vaccine) vaccine?

Side Effect Profiles of Typhoid Vaccines: Injectable Vi Polysaccharide vs. Oral Ty21a

The injectable Vi polysaccharide typhoid vaccine has significantly more frequent and severe side effects than the oral live-attenuated Ty21a vaccine, making the oral vaccine preferable from a safety perspective for most eligible patients. 1

Injectable Vi Polysaccharide Vaccine Side Effects

Local Reactions

• Severe local pain and swelling: Occurs in 6-40% of recipients 1
• Injection site reactions: Pain and swelling are common 1

Systemic Reactions

• Fever: Occurs in 14-29% of recipients 1
• Headache: Affects 9-30% of vaccinees 1
• Malaise: Common systemic reaction 1
• Work/school disruption: 13-24% of recipients missed work or school due to adverse reactions 1

Severe Reactions (Rare)

• Serious adverse events: Hypotension, chest pain, and shock have been sporadically reported 1

Oral Ty21a Vaccine Side Effects

Gastrointestinal Reactions

• Abdominal discomfort: Rare occurrence 1
• Nausea and vomiting: Rare occurrence 1
• Abdominal cramps: Reported at a rate of <1/100,000 doses 1

Dermatological Reactions

• Rash or urticaria: Rare occurrence 1

Overall Safety Profile

• Side effects are rare: In safety trials, adverse reactions occurred with equal frequency among vaccine and placebo groups 1
• Well-tolerated: Only 8.9% of recipients experienced minor side effects in one study 2
• Patient preference: Among those who received both vaccines, all preferred the oral vaccine over the injectable form 2

Key Differences and Clinical Implications

1. Frequency of side effects: Injectable vaccine has much higher rates of adverse reactions compared to the oral vaccine 1

2. Severity of reactions: Injectable vaccine can cause severe local reactions and systemic symptoms that interfere with daily activities, while oral vaccine side effects are typically mild 1

3. Patient compliance considerations:

   • Oral vaccine requires adherence to a 4-dose schedule taken every other day 3
   • Approximately 30% of patients show some form of non-compliance with the oral vaccine regimen 2

4. Special populations:

   • Immunocompromised patients: Live-attenuated Ty21a should not be used in immunocompromised persons, including those with HIV infection 1, 3
   • Pregnant women: Safety data is limited for both vaccines in pregnant women 1
   • Antimicrobial therapy: Oral Ty21a should not be administered until 24 hours after any antimicrobial agent 1
   • Mefloquine interaction: Oral Ty21a should be administered at least 24 hours before or after mefloquine 1

Clinical Decision Algorithm

1. For immunocompetent adults and children ≥6 years:

   • Prefer oral Ty21a vaccine due to better side effect profile
   • Ensure patient can comply with the 4-dose regimen and refrigeration requirements

2. Use injectable Vi polysaccharide vaccine when:

   • Patient is immunocompromised
   • Patient is <6 years old
   • Patient is on antimicrobial therapy that cannot be paused
   • Patient is unlikely to comply with the oral vaccine regimen
   • Patient is taking mefloquine and timing cannot be adjusted

3. Contraindications:

   • For injectable vaccine: History of severe reaction to previous dose 1
   • For oral vaccine: Immunocompromised status, children <6 years 1

The choice between these vaccines should primarily be guided by the patient's immune status and ability to comply with the oral regimen, with the understanding that the oral vaccine offers a significantly more favorable side effect profile for eligible patients.