Prevention of typhoid fever in individuals at risk of intimate exposure to a known typhoid carrier (e.g., continued household contact), in those traveling to areas where typhoid fever is endemic because of poor food or water sanitation, and in laboratory workers with frequent contact with Salmonella typhibacilli.
Typhoid fever is an acute, life-threatening febrile illness caused by S. typhibacteria transmitted via food and/or water contaminated with feces, urine, vomitus, or respiratory secretions from typhoid fever carriers. Typhoid fever is uncommon in the US, but is endemic in many less well-developed areas of the world that have poor sanitation and primitive water systems. WHO estimates that about 22 million cases of typhoid fever occur with about 200,000 related deaths annually. Approximately 2–4% of individuals with acute typhoid develop a chronic carrier state. CDC receives reports of about 400 cases of typhoid fever each year in the US, mostly among recent travelers to other countries.
USPHS Advisory Committee on Immunization Practices (ACIP) and AAP do not currently recommend routine immunization against typhoid fever for individuals residing in the US. Although immunization against typhoid fever was recommended in the past for individuals in the US attending summer camps or residing in areas where natural disasters (e.g., flooding) had occurred or for control of common-source outbreaks of typhoid fever, this no longer is considered necessary because of the low probability of exposure in the US. Routine immunization against typhoid fever is warranted for sewage workers only in areas with endemic typhoid.
ACIP and AAP recommend vaccination using oral live typhoid vaccine (Vivotif®) or parenteral inactivated typhoid vaccine (Typhim Vi® ) for adults, adolescents, and children at high risk of exposure to S. typhi bacilli. Efficacy of these vaccines appears to be comparable when administered as recommended; however, the vaccines have different contraindications (see Contraindications under Cautions) and different minimum age limits for use in children (see Pediatric Use under Cautions).
Other factors to consider when selecting a typhoid vaccine include immunization schedule, response time, patient compliance, storage facilities, and immune status of the vaccinee. Because Vivotif® is self-administered over a 1-week period and compliance errors (i.e., dosing errors, improper storage) have been reported, Typhim Vi® may be preferred in patients in whom compliance is likely to be a problem.
Individuals with acute typhoid infection and those who are chronic typhoid carriers should not receive typhoid vaccine.
Vivotif® and Typhim Vi® will not prevent typhoid fever caused by Salmonella species other than S. typhi (e.g., S. paratyphi type A or B) and will not prevent infections caused by other bacteria known to cause enteric disease.
Preexposure Vaccination Against Typhoid Fever in High-risk Groups
Preexposure vaccination in individuals who are or will be at high risk of exposure to S. typhi.
Household contacts of known typhoid carriers should be vaccinated with typhoid vaccine because of increased risk of exposure to typhoid fever.
Travelers to areas where there is a recognized risk of exposure to typhoid fever (e.g., many countries in Africa, Asia, Central and South America) should be vaccinated against typhoid fever. Although vaccination is not currently required for international travel, it is recommended for travelers who may have prolonged exposure to contaminated food and drink in areas with persistent typhoid epidemics or in smaller villages or rural areas outside the usual tourist itinerary. In addition to vaccination, travelers should use caution in selecting food and water in these areas since the vaccines are not 100% effective and vaccine-induced immunity can be overwhelmed by a large inoculum of S. typhi. (See Limitations of Vaccine Effectiveness under Cautions.)
HIV-infected individuals should not receive Vivotif® since the vaccine contains live, attenuated bacteria. If typhoid vaccine is indicated, HIV-infected individuals may receive Typhim Vi®. USPHS/IDSA Prevention of Opportunistic Infections Working Group recommends use of Typhim Vi® in HIV-infected individuals at risk of exposure to typhoid fever. (See Individuals with Altered Immunocompetence under Cautions.)
Dosage and Administration
Administration
Vivotif® is administered orally; Typhim Vi® is administered by IM injection.
Oral Administration
Vivotif®: Administer orally. Do not administer parenterally.
Take on an empty stomach (approximately 1 hour before or 2 hours after a meal).
Do not chew or open the enteric-coated capsules. Swallow whole with cool or lukewarm (≤37°C [body temperature]) liquid (water).
Do not drink alcohol within 2 hours after the dose. (See Specific Drugs under Interactions.)
It is essential that remaining capsules be stored in a refrigerator until the vaccination series is completed. (See Storage under Stability.)
IM Administration
Typhim Vi®: Administer by IM injection. Do not administer IV.
IM injections preferably should be made into the deltoid area in adults and into the deltoid or the vastus lateralis in children. To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass.
Administer undiluted. Do not mix with any other vaccine or solution.
Avoid use of the gluteal area or any area where there may be a nerve trunk. Generally, do not administer vaccines into buttock muscle in children because of potential for injection-associated injury to the sciatic nerve.
Avoid injection of vaccines into or near blood vessels.
Dosage
Dose and dosing schedule vary according to the individual's age and specific vaccine administered (Vivotif®, Typhim Vi®). Follow dosage recommendations for the specific preparation used.
Pediatric Patients
Preexposure Vaccination Against Typhoid Fever in High-risk Groups
Children and Adolescents 6–18 Years of Age (Vivotif®)
Oral
Primary immunization consists of 4 doses. Each dose consists of one enteric-coated capsule.
Give first dose on a selected date; give second, third, and fourth doses every other day after the first dose over a 1-week period.
Primary immunization with the recommended vaccination series before an expected exposure to typhoid fever ensures the highest level of protection. Those who complete the 4-dose series at least 1 week prior to possible typhoid exposure probably will be protected.
Data not available concerning use of Vivotif® as a booster in individuals who received primary immunization with a different typhoid vaccine. ACIP states that the 4-dose Vivotif® vaccination series is a reasonable alternative for booster immunization in individuals previously vaccinated with a parenteral inactivated typhoid vaccine.
Duration of immunity and need for subsequent doses not fully determined. For travelers or individuals at continued or repeated risk of exposure to typhoid fever, additional (booster) doses (i.e., 4-dose vaccination series) are recommended every 5 years. (See Duration of Immunity under Cautions.)
Children and Adolescents 2 –18 Years of Age (Typhim Vi®)
IM
Primary immunization consists of a single 25-mcg dose. Each dose consists of 0.5 mL from the commercially available prefilled single-dose syringe or multidose vial.
Those who receive the recommended dose given at least 2 weeks prior to possible exposure to typhoid fever probably will be protected.
Data not available concerning use of Typhim Vi® for booster immunization in individuals who received primary immunization with a different typhoid vaccine. ACIP states that a single dose of Typhim Vi® is a reasonable alternative as a booster for individuals previously vaccinated with another parenteral inactivated typhoid vaccine.
Duration of immunity and need for subsequent doses not fully determined. For travelers or individuals at continued or repeated risk of exposure to typhoid fever, an additional (booster) dose of 0.5 mL is recommended every 2 years. (See Duration of Immunity under Cautions.)
Adults
Preexposure Vaccination Against Typhoid Fever in High-risk Groups
Adults ≥19 Years of Age (Vivotif®)
Oral
Primary immunization consists of 4 doses. Each dose consists of one enteric-coated capsule.
Give first dose on a selected date; give second, third, and fourth doses every other day after the first dose over a 1-week period.
Primary immunization with the recommended vaccination series before an expected exposure to typhoid fever ensures the highest level of protection. Those who complete the 4-dose series at least 1 week prior to possible typhoid exposure probably will be protected.
Data not available concerning use of Vivotif® as a booster in individuals who received primary immunization with a different typhoid vaccine. ACIP states that the 4-dose Vivotif® vaccination series is a reasonable alternative as a booster for individuals previously vaccinated with a parenteral inactivated typhoid vaccine.
Duration of immunity and need for subsequent doses not fully determined. For travelers or individuals at continued or repeated risk of exposure to typhoid fever, additional (booster) doses (i.e., 4-dose vaccination series) are recommended every 5 years. (See Duration of Immunity under Cautions.)
Adults ≥19 Years of Age (Typhim Vi®)
IM
Primary immunization consists of a single 25-mcg dose. Each dose consists of 0.5 mL from the commercially available prefilled single-dose syringe or multidose vial.
Those who receive the recommended single dose at least 2 weeks prior to possible exposure to typhoid fever probably will be protected.
Data not available concerning use of Typhim Vi® for booster immunization in individuals who received primary immunization with a different typhoid vaccine. ACIP states that a single dose of Typhim Vi® is a reasonable alternative as a booster for individuals previously vaccinated with another parenteral inactivated typhoid vaccine.
Duration of immunity and need for subsequent doses not fully determined. For travelers or individuals at continued or repeated risk of exposure to typhoid fever, an additional (booster) dose of 0.5 mL is recommended every 2 years. (See Duration of Immunity under Cautions.)
Special Populations
Hepatic Impairment
No specific dosage recommendations.
Renal Impairment
No specific dosage recommendations.
Geriatric Patients
No specific dosage recommendations.
Cautions
Contraindications
Oral live typhoid vaccine (Vivotif®): Hypersensitivity to any ingredient in the formulation. Also contraindicated in individuals with altered immunocompetence and in those with acute febrile illness.
Parenteral inactivated typhoid vaccine (Typhim Vi®): Hypersensitivity to any ingredient in the formulation. Also contraindicated in individuals with previous hypersensitivity reactions to any typhoid vaccine.
Warnings/Precautions
Warnings
Individuals with Altered Immunocompetence
Because severe complications have been reported following vaccination with live, attenuated virus or bacterial vaccines in individuals with altered immunocompetence (e.g., patients with leukemia, lymphoma, generalized malignancy, asymptomatic or symptomatic HIV infection, those receiving immunosuppressive therapy) and because safety of oral live typhoid vaccine (Vivotif®) has not been established in immunocompromised individuals, this vaccine should not be used in such individuals. However, ACIP states that Vivotif® can be used, if indicated, in patients who have altered immunocompetence because of asplenia, renal failure, diabetes, alcoholism, or alcoholic cirrhosis.
If typhoid vaccination is considered necessary in individuals with altered immunocompetence, parenteral inactivated typhoid vaccine (Typhim Vi®) theoretically would be a safer alternative than the oral vaccine. However, the vaccine may be less immunogenic in immunocompromised individuals than in immunocompetent individuals. ACIP currently states that recommendations concerning use of parenteral inactivated typhoid vaccine in individuals with altered immunocompetence generally are the same as those for individuals who are not immunocompromised.
Individuals with GI Disorders
Oral live typhoid vaccine (Vivotif®) should not be used in individuals with acute GI illness since the vaccine requires replication in the gut for effectiveness. Postpone initiating the vaccination series in patients with persistent diarrhea or vomiting.
A history of previous sensitivity reactions to typhoid vaccine should be obtained prior to administration.
Epinephrine and other appropriate agents should be readily available in case anaphylaxis or other serious allergic reaction occurs.
General Precautions
Transmission of Vaccine Bacteria
Oral typhoid vaccine (Vivotif®) contains live, attenuated bacteria. Secondary transmission of vaccine bacteria has not been documented following administration of Vivotif®; however, these organisms may be shed transiently in the stools of vaccinees.
Concomitant Illness
A decision to administer or delay vaccination in an individual with a current or recent febrile illness depends on the severity of symptoms and etiology of the illness.
Manufacturer of Vivotif® states that the vaccine should not be administered to individuals during an acute febrile illness. Manufacturer of Typhim Vi® states that the vaccine may be given to individuals with acute infection or febrile illness if withholding the vaccine poses greater risk to the patient.
ACIP states that minor acute illness, such as mild diarrhea or mild upper respiratory tract infection (with or without fever) generally does not preclude vaccination, but vaccination should be deferred in individuals with moderate or severe acute illness (with or without fever) until they have recovered from the acute phase of the illness.
Individuals with Bleeding Disorders
Parenteral inactivated typhoid vaccine (Typhim Vi® ): Because bleeding may occur following IM administration in individuals with thrombocytopenia or a bleeding disorder (e.g., hemophilia) or in those receiving anticoagulant therapy, use caution in such individuals.
ACIP states that vaccines may be given IM to individuals who have bleeding disorders or are receiving anticoagulant therapy if a clinician familiar with the patient's bleeding risk determines that the preparation can be administered with reasonable safety. In these cases, use a fine needle (23 gauge) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes. If patient is receiving antihemophilia therapy, administer the IM vaccine shortly after a scheduled dose of such therapy.
Advise individual and/or their family about the risk of hematoma from IM injections.
Limitations of Vaccine Effectiveness
May not protect all vaccine recipients against typhoid fever infection. Vaccine-induced immunity can be overwhelmed by large inocula of S. typhi. Even travelers who have been immunized against typhoid fever should take precautions to avoid contact with or ingestion of potentially contaminated food or water.
Oral live typhoid vaccine (Vivotif®): Optimum immune response may not be achieved unless the complete 4-dose vaccination series is used. Individuals who complete the 4-dose series at least 1 week prior to possible typhoid exposure probably will be protected.
Parenteral inactivated typhoid vaccine (Typhim Vi®): Individuals who receive a single dose given at least 2 weeks prior to possible typhoid exposure probably will be protected.
May not prevent infection in individuals who do not achieve protective antibody titers; the minimum titer needed to confer immunity has not been established.
Vivotif® and Typhim Vi® provide protection only against S. typhi. These vaccines do not provide protection against other Salmonella species (e.g., S. paratyphi A or B).
Duration of Immunity
Duration of protection and need for subsequent doses after initial and additional (booster) doses of typhoid vaccine not fully determined. Natural infection with S. typhi generally confers lifelong immunity; however, the nature of this immunity is complex and includes both humoral and cell-mediated components.
Oral live typhoid vaccine (Vivotif®): Although additional long-term follow-up studies are needed, limited evidence suggests that protective levels of antibodies following the recommended 4-dose vaccination series may persist for at least 5 years. Additional (booster) doses (i.e., 4-dose oral vaccination series) of Vivotif® recommended every 5 years if continued or renewed exposure to typhoid fever is expected.
Parenteral inactivated typhoid vaccine (Typhim Vi®): Limited data indicate that antibody titers remain elevated for at least 12 months after a single dose in children 5–15 years of age residing in typhoid-endemic areas and for at least 36 months in healthy US adults. Additional (booster) dose of Typhim Vi® recommended every 2 years if continued or renewed exposure to typhoid fever is expected.
Improper Storage and Handling
Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.
Oral live typhoid vaccine (Vivotif®): Unstable when exposed to ambient temperatures. Remaining capsules must be stored in a refrigerator until the vaccination series is completed. Do not administer Vivotif® that has been mishandled or has not been stored at the recommended temperature (2–8°C). (See Storage under Stability.)
Parenteral inactivated typhoid vaccine (Typhim Vi®): Not adversely affected by elevated temperatures (e.g., those that occur in tropical areas). Therefore, the parenteral vaccine may be preferred in situations in which continuous refrigeration cannot be ensured.
Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.
Specific Populations
Pregnancy
Oral live typhoid vaccine (Vivotif®) and parenteral inactivated typhoid vaccine (Typhim Vi®): Category C.
Safety data not available on use of typhoid vaccines in pregnant women. Typhoid vaccine should be given to pregnant women only if clearly needed.
AAP states that Vivotif® is contraindicated in pregnant women.
Because Typhim Vi® is an inactivated vaccine, the theoretical risk to the fetus is expected to be low. AAP states that use of Typhim Vi® may be considered on an individual basis. When giving a vaccine during pregnancy, delaying vaccination until the second or third trimester, if possible, is a reasonable precaution to minimize the possibility of teratogenicity.
Lactation
Not known whether antigens contained in typhoid vaccine are distributed into milk following oral or IM administration. Use with caution in nursing women.
Because inactivated vaccines (e.g., Typhim Vi®) do not multiply within the body, they should not pose any unusual problems for lactating women or their infants.
The manufacturers state that there currently are no data to warrant use of typhoid vaccines in nursing women in an attempt to provide passive transfer of antibodies to protect an infant from typhoid fever.
Pediatric Use
Oral live typhoid vaccine (Vivotif®): Safety and efficacy not established in children <6 years of age. Although efficacy not established, limited evidence indicates adverse effects were uncommon when the vaccine was used in children 1–5 years of age†. Has not been studied in children <1 year of age.
Parenteral inactivated typhoid vaccine (Typhim Vi®): Safety and efficacy not established in children <2 years of age. Has not been studied in children <1 year of age.
Oral live typhoid vaccine (Vivotif®): May be administered simultaneously with or at any interval before or after a parenteral live vaccine (e.g., measles, mumps, and rubella virus vaccine live [MMR], varicella virus vaccine live, yellow fever vaccine). Data not available regarding the immunogenicity of Vivotif® administered concurrently or within 30 days of other live virus vaccines. However, ACIP and AAFP state that if use of Vivotif® is warranted, it should not be delayed because of administration of other live virus vaccines (injectable or intranasal).
Parenteral inactivated typhoid vaccine (Typhim Vi® ): Specific interaction studies involving Typhim Vi® and other vaccines have not been conducted to date. However, since Typhim Vi® is an inactivated vaccine, it generally can be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after live vaccines.
Inactivated Vaccines and Toxoids
Oral live typhoid vaccine (Vivotif®): Can be administered simultaneously with or at any interval before or after inactivated vaccines.
Parenteral inactivated typhoid vaccine (Typhim Vi® ): Specific drug interaction studies involving Typhim Vi® and other vaccines commonly administered prior to international travel (e.g., hepatitis A, meningococcal, poliovirus, tetanus) have not been conducted to date. However, since Typhim Vi® is an inactivated vaccine, it generally can be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after other inactivated vaccines.
Specific Drugs
Drug
Interaction
Comments
Alcohol
Vivotif® : Alcohol may affect dissolution of the vaccine capsules and may inactivate the vaccine
Vivotif® : Avoid alcohol for 2 hours after each vaccine dose
Vivotif®: Potential for anti-infectives with activity against S. typhi to inhibit immune response to the vaccine
Typhim Vi®: Manufacturer states that specific drug interaction studies involving the vaccine and other drugs (e.g., anti-infectives) not conducted to date
Vivotif®: Manufacturer states do not use in individuals receiving anti-infectives; ACIP, CDC, and AAFP state an interval of ≥24 hours should elapse between administration of an anti-infective dose and the vaccine; AAP states that anti-infectives should be avoided for ≥24 hours before the first dose and for 7 days after the fourth vaccine dose
Vivotif®: Potential for antimalarials with antibacterial activity against Salmonella to inhibit the immune response to the vaccine
Vivotif®: Although mefloquine inhibits growth of S. typhi in vitro, including the Ty21a strain contained in the vaccine, no clinical evidence to date that mefloquine or chloroquine interferes with the immune response to the vaccine
Vivotif®: Concurrent use of proguanil (200 mg daily; not commercially available in the US as a single-entity preparation) with the vaccine resulted in decreased immune response
Typhim Vi®: Manufacturer states specific drug interaction studies involving the vaccine and other drugs (e.g., antimalarial agents) not conducted to date
Vivotif®: Manufacturer states the vaccine may be administered in patients receiving mefloquine
To minimize the potential for an inhibitory effect, ACIP states the vaccine should be administered ≥24 hours before or after a mefloquine dose; AAP states mefloquine may be administered simultaneously with the vaccine
Vivotif®: Although an interval of ≥7 days was previously recommended between vaccination and initiation of chloroquine antimalarial prophylaxis, more recent evidence indicates special precautions not necessary
Vivotif®: Manufacturer and AAP state that proguanil therapy should be delayed until ≥10 days after the fourth vaccine dose
Hepatitis A (HepA) vaccine
Vivotif®: Data not available regarding simultaneous administration with HepA vaccine
Typhim Vi®: Concomitant administration of HepA vaccine and parenteral inactivated typhoid vaccine does not appear to affect the immune response or adverse reactions to the vaccines
Immune globulin (IGIM, IGIV) or specific immune globulin (HBIG, RIG, TIG, VZIG)
Vivotif® : No evidence that immune globulin preparations interfere with the immune response to the vaccine
Typhim Vi®: Specific drug interaction studies not available
Vivotif® : May be administered simultaneously with or at any time before or after antibody-containing preparations without a substantial decrease in the immune response to the vaccine
Typhim Vi®: May be administered simultaneously (using different syringes and different injection sites) or at any time before or after immune globulins
Typhim Vi® : Immune response may be reduced in patients receiving immunosuppressive agents
Vivotif®: Contraindicated in patients receiving immunosuppressive therapy
If typhoid vaccination is considered necessary in individuals receiving immunosuppressive agents, Typhim Vi® is recommended
Measles, mumps, and rubella vaccine (MMR)
Vivotif® : Data not available regarding the immunogenicity of oral live typhoid vaccine administered concurrently or within 30 days of MMR
Vivotif®: May be administered simultaneously with or at any interval before or after MMR
Typhim Vi®: May be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after MMR
Meningococcal vaccine
Vivotif® : Data not available regarding simultaneous administration with meningococcal vaccine
Typhim Vi®: Has been administered concomitantly with MCV4 (Menactra®) without reduced antibody response or increased adverse effects
Typhim Vi® : May be administered simultaneously with MCV4 (Menactra®) or at any interval before or after meningococcal vaccine (using different syringes and different injection sites)
Poliovirus vaccine live oral (OPV; no longer commercially available in the US)
Vivotif® : Although there is a theoretical risk that oral typhoid vaccine may interfere with the immune response to OPV, no evidence that OPV suppresses the immune response to typhoid vaccine
Vivotif® : Some experts suggest that ≥2 weeks should elapse between the last dose of Vivotif® and OPV
Data not available regarding simultaneous administration of tetanus vaccine and Vivotif® or Typhim Vi®
Varicella vaccine
Vivotif®: Specific data not available regarding immunogenicity of oral live typhoid vaccine administered concurrently or within 30 days of varicella vaccine
Typhim Vi®: Since this typhoid vaccine is an inactivated vaccine, interactions with live vaccines such as varicella vaccine are unlikely
Vivotif®: May be administered simultaneously with or at any interval before or after varicella vaccine
Typhim Vi®: May be administered simultaneously (using different syringes and different injection sites) or at any interval before or after varicella vaccine
Yellow fever vaccine
Vivotif®: Although specific data not available regarding simultaneous administration, a bivalent vaccine (not commercially available in the US) containing a live oral typhoid vaccine and a cholera vaccine has been administered concomitantly with yellow fever vaccine without a decrease in immune response to the typhoid vaccine or an increase in adverse effects
Typhim Vi®: Yellow fever vaccine has been administered concomitantly at a different site with parenteral inactivated typhoid vaccine with or without concomitant HepA vaccine (Vaqta®) without any apparent decrease in the immune response or increase in adverse effects
Vivotif® : May be administered simultaneously with or at any interval before or after yellow fever vaccine
Typhim Vi® : May be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after yellow fever vaccine
Stability
Storage
Oral
Capsules
Vivotif®: 2–8°C. Potency is adversely affected by exposure to warmer temperatures.
Store remaining capsules in a refrigerator until 4-dose vaccination series is completed.
Vivotif® does not contain thimerosal or any other preservatives.
Parenteral
Injection, for IM Use
Typhim Vi®: 2–8°C. Do not freeze.
Typhim Vi® does not contain thimerosal, but contains phenol 0.25% as a preservative.
Actions
Typhoid vaccine live oral (Vivotif®) is a lyophilized preparation of live S. typhi of the attenuated Ty21a strain. The vaccinebacteria are cultured on a suitable nutrient medium, stabilized, and lyophilized.
Typhoid Vi polysaccharide vaccine Typhim (Vi®) is a sterile solution of 0.9% sodium chloride containing purified cell surface Vi (“virulence”) polysaccharide extracted from S. typhi of the Ty2 strain. The vaccine bacteria are cultured on a suitable nutrient medium; the capsular polysaccharide is then precipitated using cetrimonium bromide and purified.
Oral live typhoid vaccine (Vivotif®) and parenteral inactivated typhoid vaccine ( Typhim Vi®) are commercially available as monovalent vaccines prepared using slightly different strains of S. typhi. Efficacy of these vaccines appears to be comparable when administered as recommended.
Vivotif® and Typhim Vi® are highly immunogenic; 50–80% of vaccinees achieve an adequate immune response against typhoid. Efficacy of Vivotif® appears to be greater in older children and adults than in young children.
Vivotif® stimulates active immunity to typhoid fever by inducing production of both serum and intestinal antibodies and cell-mediated immune responses. Following primary immunization with Vivotif®, serum titers of antibodies to the O antigen of S. typhi appear to correlate with protection against typhoid fever. Administration of Vivotif® may elicit a local immune response in the intestinal tract. Ability of S. typhi to elicit a protective immune response depends on possession by the bacilli of a complete lipopolysaccharide. The S. typhi (Ty21a) strain in Vivotif® is limited in its ability to produce a complete lipopolysaccharide; however, sufficient complete lipopolysaccharide apparently is produced to elicit an adequate immune response.
Typhim Vi® stimulates active immunity to S. typhi by inducing production of antibodies to the Vi antigen. The Vi antigen is considered to be a virulence factor of S. typhi, apparently protecting the organism from the actions of complement; antibodies to the Vi antigen confer protection against typhoid fever.
A reduced immune response to typhoid vaccine and lower antibody titers may occur in immunocompromised individuals (e.g., HIV-infected individuals, those with leukemia, lymphoma, or generalized malignancy, those receiving immunosuppressive therapy).
The principal mode of transmission of typhoid infection is enteric (i.e., through fecal contamination and oral ingestion) most commonly through direct contact with an infected person or with an item contaminated by a typhoid carrier. Onset of illness is usually gradual with signs and symptoms such as high fever, headache, malaise, anorexia, lethargy, abdominal pain and tenderness, splenomegaly, hepatomegaly, and rose spots. Invasive infection and mortality from typhoid infection are typically higher in infants, elderly individuals, and those with immunosuppressive conditions, hemoglobinopathies, malignancies, and HIV infection.
Natural infection with S. typhi generally results in lifelong immunity; however, the nature of this immunity is complex and includes both humoral and cell-mediated components.
The minimum titer of anti-typhoid antibodies conferring protection against typhoid has not been established. Experience using typhoid vaccines in individuals from areas without endemic disease (e.g., US residents) who travel to endemic regions is limited; however, seroconversion rates following primary immunization with Vivotif® or Typhim Vi® in these individuals appear to be comparable to or higher than those attained in residents of endemic areas. Evidence from antibody-titer studies suggests that both the oral and parenteral typhoid vaccines provide protection in vaccinees residing in nonendemic areas.
Advice to Patients
Prior to administration of the vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative (VISs are available at http://www.cdc.gov/vaccines/pubs/vis/default.htm).
Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination with typhoid vaccine.
Advise patient and/or patient's parent or guardian that routine typhoid vaccination is not recommended in the US, but typhoid vaccine is used to prevent typhoid in individuals at high risk of exposure to typhoid (e.g., travelers, household contacts of a typhoid carrier, certain laboratory workers).
Advise patient and/or patient's parent or guardian that oral or parenteral typhoid vaccine may not provide protection in all vaccinees. In addition to vaccination, importance of taking precautions against exposure to typhoid fever by avoiding contact with or ingestion of potentially contaminated food or water.
When oral typhoid vaccine (Vivotif®) is used, importance of completing the 4-dose vaccination series as directed (i.e., a dose on day 1, 3, 5, and 7). Advise vaccinees to swallow capsules whole with cool or lukewarm liquid on an empty stomach (approximately 1 hour before or 2 hours after a meal), avoid drinking alcohol for 2 hours after each dose, and store remaining capsules in the refrigerator until the entire regimen is completed. Importance of completing the vaccination series at least 1 week prior to possible exposure to typhoid fever and importance of receiving additional (booster) doses (i.e., 4-dose vaccination series) every 5 years if at continued or repeated risk of exposure.
When parenteral typhoid vaccine (Typhim Vi®) is used, importance of receiving the initial dose at least 2 weeks prior to possible exposure to typhoid fever and importance of receiving additional (booster) doses every 2 years if at continued or repeated risk of exposure.
Importance of notifying clinicians if patient is immunocompromised since oral typhoid vaccine (Vivotif®) should not be used in individuals with a weakened immune system (e.g., leukemia, lymphoma, HIV/AIDS) or in those receiving treatment that may weaken the immune system (e.g., high-dose corticosteroids) since such patients may have a reduced immune response to vaccination. (See Individuals with Altered Immunocompetence under Cautions.)
Importance of informing clinicians of a history of allergic reactions to typhoid vaccine or any ingredient in the formulation.
Importance of informing clinicians if any adverse reactions (including allergic reactions) occur with typhoid vaccine. Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or http://www.vaers.hhs.gov/.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses. Importance of notifying clinicians if receiving therapy with anti-infective or antimalarial agents. (See Specific Drugs under Interactions.)
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Typhoid Vaccine Live Oral
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Capsules, enteric-coated
2–6.8 × 109 CFU of viable Salmonella typhi Ty21a
Vivotif® (with sucrose 26–130 mg, lactose 100–180 mg, and magnesium 2.6–4.4 mg; preservative-free; available as a 7-day mnemonic pack of 4 capsules)
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.
