What are typhoid vaccines and how do they work for individuals traveling to high-risk areas or with compromised immune systems?

Typhoid Vaccines: Types and Mechanisms

Typhoid vaccines are immunizations that protect against Salmonella typhi infection by stimulating immune responses to bacterial antigens, available as either an oral live-attenuated vaccine (Ty21a) or injectable polysaccharide vaccines (Vi polysaccharide or Vi-TT conjugate), with both providing 50-80% protection against typhoid fever. 1

Available Vaccine Types and Mechanisms

Oral Live-Attenuated Ty21a Vaccine (Vivotif)

• This vaccine uses a weakened strain of S. typhi that colonizes the gut and stimulates both mucosal and systemic immunity without causing disease. 1
• Administered as four enteric-coated capsules taken on alternate days with cool liquid no warmer than 37°C, approximately 1 hour before meals. 1
• Provides approximately 67% protection for at least 4 years with fewer adverse reactions than parenteral vaccines. 1
• Should NOT be used in immunocompromised persons, including those with HIV infection, as the live organism could potentially cause disease in these patients. 2, 1

Injectable Vi Polysaccharide Vaccine

• This vaccine contains purified capsular polysaccharide from the bacterial surface, which triggers antibody production against the Vi antigen. 1, 3
• Given as a single 0.5 mL intramuscular or subcutaneous dose for adults and children ≥10 years. 1
• Demonstrates 51-76% effectiveness in preventing typhoid fever. 1, 4
• Causes injection site reactions (pain in 76.5%, tenderness in 75.4%) but rarely systemic effects, with fever occurring in only 1.6% of recipients. 3

Vi-TT Conjugate Vaccine (TCV)

• This newer conjugate vaccine links the Vi polysaccharide to a protein carrier, enhancing immunogenicity and providing superior long-term protection. 1
• Demonstrates 78% efficacy over four years, significantly better than older vaccines. 1
• Recommended as the first-choice vaccine when available due to superior efficacy, effectiveness in infants and young children, and less frequent boosting requirements. 1

Who Should Receive Vaccination

Primary Indications

• Travelers to endemic areas in Latin America, Asia, and Africa with prolonged exposure to potentially contaminated food and drink. 1
• Microbiologists and laboratory workers who frequently handle S. typhi cultures. 2, 1
• Persons with intimate household contact with documented typhoid carriers. 1
• Travelers visiting friends and relatives in endemic countries, particularly the Indian subcontinent, face the highest risk and require special attention for prevention. 2, 5

Special Populations

• For immunocompromised patients or those with HIV, only the Vi polysaccharide or TCV vaccines should be used—never the live-attenuated oral vaccine. 2, 1
• Children ≥6 years can receive the oral vaccine, while children ≥10 years can receive the Vi polysaccharide vaccine. 1, 6
• The oral vaccine is not recommended for children <6 years of age. 1

Booster Schedule and Duration of Protection

Oral Ty21a Vaccine

• Requires revaccination with the entire four-dose series every 5 years for continued protection. 1, 6
• Efficacy persists for at least 5 years with the complete four-dose regimen. 1

Vi Polysaccharide Vaccine

• Requires booster doses every 2 years under conditions of continued or repeated exposure. 2, 1
• Three-year cumulative efficacy is approximately 55%. 1

Vi-TT Conjugate Vaccine

• Requires less frequent boosting compared to other vaccines, though specific intervals are still being established. 1

Critical Limitations and Precautions

Efficacy Limitations

• Vaccination is NOT a substitute for careful food and water selection, as vaccines are not 100% effective and protection can be overwhelmed by large bacterial inocula. 1, 6
• Real-world effectiveness in US travelers is approximately 80%, supporting vaccination but emphasizing the need for additional precautions. 7
• No available vaccines protect against Paratyphi A infection, which is increasing in incidence, particularly in Asia. 2, 5

Drug Interactions

• Theoretical concerns exist about reduced immunogenicity of the oral Ty21a vaccine when taken concurrently with antimicrobials (including antimalarial prophylaxis), viral vaccines, or immune globulin. 2
• The oral vaccine should be taken with cool liquid to prevent premature capsule dissolution. 1

Safety Profile

• All typhoid vaccines demonstrate excellent safety profiles with mild, self-limited adverse events. 1
• The oral vaccine has adverse event rates comparable to placebo (<1/100,000 doses). 1
• Serious adverse events requiring hospitalization occur in an estimated 0.47 to 1.3 per 100,000 doses, with no deaths reported. 2

Practical Algorithm for Vaccine Selection

For travelers with normal immune function:

• First choice: Vi-TT conjugate vaccine (TCV) if available, due to superior efficacy and less frequent boosting. 1
• Alternative: Oral Ty21a vaccine for those preferring to avoid injections and willing to complete the four-dose series. 1
• Second alternative: Vi polysaccharide vaccine if TCV unavailable, accepting the need for more frequent boosters. 1

For immunocompromised patients or those with HIV:

• Only use Vi polysaccharide or TCV vaccines—the oral live-attenuated vaccine is absolutely contraindicated. 2, 1

For laboratory workers:

• Either vaccine type is acceptable, with boosters administered on schedule according to manufacturer recommendations. 2