Typhoid Vaccine (Monograph)

Brand names: Typhim Vi, Vivotif
Drug class: Vaccines
ATC class: J07AP01
VA class: IM100

Medically reviewed by Drugs.com on Jul 14, 2023. Written by ASHP.

Introduction

Commercially available in US as an oral live, attenuated vaccine (typhoid vaccine live oral Ty21a; Vivotif)^{102 103 115} and as a parenteral inactivated Vi polysaccharide vaccine (typhoid Vi polysaccharide vaccine; Typhim Vi).^{102 115 123} Other typhoid vaccines (e.g., inactivated whole-cell vaccines, inactivated protein-conjugated Vi polysaccharide vaccines) may be available in other countries.^{102 141}

Uses for Typhoid Vaccine

Prevention of Typhoid Fever

Prevention of typhoid fever in US travelers planning to visit areas with a recognized risk of exposure to Salmonella enterica serovar Typhi.^{102 103 115 123}

Prevention of typhoid fever in individuals with intimate exposure (e.g., household contact) to a known typhoid carrier.^{102 103 123}

Prevention of typhoid fever in laboratory personnel with frequent contact with Salmonella Typhi bacilli.^{102 103 123}

Typhoid fever is a potentially severe and occasionally life-threatening, febrile, enteric illness caused by Salmonella Typhi.^{102 103 105 115 138 139 141} Usually acquired by ingestion of food and/or water contaminated with feces from individuals who have typhoid fever or are chronic typhoid carriers.^{102 103 105 115 138 139 141} Overall case-fatality rate in patients who receive early and appropriate antibacterial treatment is typically <1%;¹⁰² if left untreated, case-fatality rate may be ≥10–20%.^{102 141} Approximately 2–4% of individuals with acute typhoid fever develop a chronic carrier state.^{103 123}

Typhoid fever is uncommon in the US, but endemic in many less well-developed areas of the world that have poor sanitation and primitive water systems.^{102 115 138 139} About 22 million cases of typhoid fever and about 200,000 typhoid-related deaths occur annually worldwide.¹¹⁵ In the US, about 300–400 confirmed cases of typhoid fever are reported annually,^{102 115} almost all in recent travelers to other countries (most commonly southern Asia).^{102 115 139}

USPHS Advisory Committee on Immunization Practices (ACIP) and CDC state that routine vaccination against typhoid fever not recommended for individuals residing in the US,^{102 115} but preexposure vaccination is recommended for those at high risk of exposure to Salmonella Typhi.^{102 115}

When vaccination against typhoid fever indicated, either typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine can be used unless contraindicated.^{102 105 115} Consider that the vaccines have different contraindications (see Contraindications under Cautions) and different minimum age limits for use in children (see Pediatric Use under Cautions).^{102 103 123} Other factors to consider when selecting a typhoid vaccine include immunization schedule, response time, patient compliance, storage facilities, and immunocompetence of the vaccinee (see Warnings/Precautions under Cautions).^{102 123 126} Because typhoid vaccine live oral Ty21a is self-administered over a 1-week period and compliance errors (i.e., dosing errors, improper storage) may occur, typhoid Vi polysaccharide vaccine may be preferred if compliance is likely to be a problem.¹³¹

Efficacy of typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine appear to be comparable when administered as recommended;^{102 105 107 109 111 114 115 116 117 118 119 120 121 123 124 125 126} neither vaccine is expected to provide protection against typhoid fever in all vaccine recipients.^{102 103 105 115 123}

Typhoid vaccines will not provide protection against S. enterica serovar Paratyphi or any Salmonella other than Salmonella Typhi and will not provide protection against other bacteria known to cause enteric disease.^{103 123}

Typhoid vaccines are not used for treatment of typhoid fever and should not be used in individuals with acute Salmonella Typhi infection or in chronic typhoid carriers.^{103 123}

There is no evidence to support use of typhoid vaccine to control common source outbreaks or disease following natural disasters or in individuals attending rural summer camps.^{103 123}

Preexposure Vaccination Against Typhoid Fever in High-risk Groups

Travelers to areas with a recognized risk of exposure to Salmonella Typhi should be vaccinated against typhoid fever.^{103 105 115 123} The disease is endemic in many less well-developed areas of the world that have poor sanitation and primitive water systems.^{115 138 141}

CDC recommends typhoid vaccination for travelers to many Asian, African, and Latin American countries, but no longer recommends typhoid vaccination for travelers to certain Eastern European and certain Asian countries.^{102 115 138 141} In recent years, most US cases of typhoid fever reported in individuals who had traveled to southern Asia (especially the Indian subcontinent including India, Bangladesh, or Pakistan) or Africa.^{115 139}

Although risk is greatest for travelers who have prolonged exposure to possibly contaminated food and beverages in areas with persistent typhoid epidemics or in smaller cities and villages or rural areas outside usual tourist itinerary, even short-term travel (<1 week) to high-incidence areas is associated with risk for typhoid fever.^{102 115}

In addition to vaccination, individuals traveling to areas with risk of typhoid fever 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 Salmonella Typhi.^{103 105 115 123} (See Limitations of Vaccine Effectiveness under Cautions.)

Vaccination against typhoid fever and other precautions (safe food and water precautions, frequent handwashing) are especially important for travelers to high-risk areas because fluoroquinolone-resistant and multidrug-resistant Salmonella Typhi have become common or are reported with increasing frequency in many regions of the world (e.g., Indian subcontinent, Africa).^{102 115 139 141}

The most recent information regarding geographic areas with a recognized risk of typhoid fever and additional information on vaccination and other precautions for prevention of typhoid fever are available from CDC at [Web] and [Web].^{115 138}

Close contacts of chronic typhoid carriers with intimate exposure (e.g., household contact) to a documented Salmonella Typhi chronic carrier (defined as excretion of Salmonella Typhi in urine or stool for >1 year) should be vaccinated against typhoid fever.¹⁰²

Laboratory personnel routinely exposed to cultures of Salmonella Typhi or specimens containing the bacilli or who work in laboratory environments where these cultures or specimens are routinely handled should be vaccinated against typhoid fever.¹⁰²

Related/similar drugs

Vivotif, Typhim Vi

Typhoid Vaccine Dosage and Administration

Administration

Typhoid vaccine live oral Ty21a: Administer orally.¹⁰³

Typhoid Vi polysaccharide vaccine: Administer by IM injection.¹²³

Oral Administration

Typhoid Vaccine Live Oral Ty21a

Administer orally as enteric-coated capsules.¹⁰³

Take with cool or lukewarm (≤37°C [body temperature]) liquid (water) approximately 1 hour before a meal.¹⁰³

Swallow whole immediately after placement in mouth;¹⁰³ do not chew.¹⁰³

Do not administer to individuals with acute GI illness^{103 105} or persistent diarrhea or vomiting.¹⁰³ (See Acute Illness under Cautions.)

Capsules must be refrigerated (2–8°C) until just prior to administration.¹⁰³ It is essential that remaining capsules be placed back in the refrigerator after each dose until the 4-dose vaccination series is completed.¹⁰³ (See Storage under Stability.)

IM Administration

Typhoid Vi Polysaccharide Vaccine

Administer IM undiluted.¹²³ Do not mix with any other vaccine.¹²³

Should appear clear and colorless;¹²³ discard if turbid or contains particulates.¹²³

IM injections preferably should be made into the deltoid area in adults and into the deltoid or anterolateral thigh in children.¹²³

Do not inject into gluteal area or any area where there may be a nerve trunk.¹²³

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for individual's age and body mass.¹³⁴

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;^{123 134} such reactions occur most frequently in adolescents and young adults.¹³⁴ Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.¹³⁴ If syncope occurs, observe patient until symptoms resolve.¹³⁴

If multiple vaccines are administered during a single health-care visit, give each parenteral vaccine using different syringe and different injection site.¹³⁴ Separate injection sites by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.¹³⁴

Dosage

Dosing schedules (i.e., number of doses, timing prior to potential exposure) differ between typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine.^{103 123} Follow dosage recommendations for the specific preparation used.^{102 103 123}

Pediatric Patients

Preexposure Vaccination Against Typhoid Fever in High-risk Groups

Children and Adolescents ≥6 Years of Age (Typhoid Vaccine Live Oral Ty21a; Vivotif)

Oral

Primary immunization consists of 4 doses.^{102 103} Each dose consists of one enteric-coated capsule.^{102 103}

Give first dose on a selected date; give second, third, and fourth doses every other day after first dose over a 1-week period (e.g., Sunday, Tuesday, Thursday, and Saturday or day 0, 2, 4, and 6).^{102 103}

Complete the 4-dose regimen ≥1 week prior to potential exposure to Salmonella Typhi.^{102 103}

Duration of response and optimum booster schedule not established.^{102 103} Revaccination with same 4-dose regimen recommended every 5 years in those with continuing or repeated exposure to Salmonella Typhi.^{102 103 115} (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid Vi polysaccharide vaccine or any other typhoid vaccine.¹⁰³

Children and Adolescents ≥2 Years of Age (Typhoid Vi Polysaccharide Vaccine; Typhim Vi)

IM

Primary immunization consists of a single 25-mcg dose.¹²³ The dose consists of 0.5 mL from the commercially available prefilled single-dose syringe or multidose vial.¹²³

Administer the vaccine dose ≥2 weeks prior to potential exposure to Salmonella Typhi.^{102 123}

Duration of response and optimum booster schedule not established.^{102 123} Revaccination with a single 0.5-mL dose recommended every 2 years in those with continuing or repeated exposure to Salmonella Typhi.^{102 115 123} (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid vaccine live oral Ty21a or any other typhoid vaccine.¹²³

Adults

Preexposure Vaccination Against Typhoid Fever in High-risk Groups

Adults ≥18 Years of Age (Typhoid Vaccine Live Oral Ty21a; Vivotif)

Oral

Primary immunization consists of 4 doses.^{102 103} Each dose consists of one enteric-coated capsule.^{102 103}

Give first dose on a selected date; give second, third, and fourth doses every other day after first dose over a 1-week period (e.g., Sunday, Tuesday, Thursday, and Saturday or day 0, 2, 4, and 6).^{102 103}

Complete the 4-dose regimen ≥1 week prior to potential exposure to Salmonella Typhi.^{102 103}

Duration of response and optimum booster schedule not established.^{102 103} Revaccination with same 4-dose regimen recommended every 5 years in those with continuing or repeated exposure to Salmonella Typhi.^{102 103 115} (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid Vi polysaccharide vaccine or any other typhoid vaccine.¹⁰³

Adults ≥18 Years of Age (Typhoid Vi Polysaccharide Vaccine; Typhim Vi)

IM

Primary immunization consists of a single 25-mcg dose.¹²³ The dose consists of 0.5 mL from the commercially available prefilled single-dose syringe or multidose vial.¹²³

Administer the vaccine dose ≥2 weeks prior to potential exposure to Salmonella Typhi.^{102 123}

Duration of response and optimum booster schedule not established.^{102 123} Revaccination with a single 0.5-mL dose recommended every 2 years in those with continuing or repeated exposure to Salmonella Typhi.^{102 115 123} (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid vaccine live oral Ty21a or any other typhoid vaccine.¹²³

Special Populations

Hepatic Impairment

No specific dosage recommendations.^{103 123}

Renal Impairment

No specific dosage recommendations.^{103 123}

Geriatric Patients

No specific dosage recommendations.^{103 123}

Cautions for Typhoid Vaccine

Contraindications

• Typhoid vaccine live oral Ty21a: Hypersensitivity to any component of the vaccine or enteric-coated capsule.¹⁰³

• Typhoid Vi polysaccharide vaccine: Hypersensitivity to any ingredient in the formulation.¹²³

Warnings/Precautions

Warnings

Individuals with Altered Immunocompetence

Typhoid vaccine live oral Ty21a: Contains live, attenuated bacteria and should not be used in individuals with congenital or acquired immunodeficiencies, including HIV-infected individuals and those receiving immunosuppressive therapy.^{103 155 225} Manufacturer states safety not established in individuals deficient in ability to mount a humoral or cell-mediated immune response;¹⁰³ do not use in such individuals, regardless of any possible benefits.¹⁰³ May be used in healthy immunocompetent individuals who reside in a household with immunocompromised patients.²²⁵

Typhoid Vi polysaccharide vaccine: May be used in individuals with altered immunocompetence, including HIV-infected patients; those who are severely immunocompromised because of congenital immunodeficiency, leukemia, lymphoma, aplastic anemia, generalized malignancy, or therapy with alkylating agents, antimetabolites, radiation, or corticosteroids; patients with solid organ transplants or chronic immunosuppressive therapy; or patients with asplenia, renal failure, diabetes mellitus, alcoholism, or alcoholic cirrhosis.^{102 134 155}

ACIP states that recommendations concerning use of typhoid Vi polysaccharide vaccine in individuals with altered immunocompetence are the same as those for individuals who are not immunocompromised.¹³⁴ However, immunization may be less effective in individuals with altered immunocompetence since antibody responses to vaccine antigens may be reduced in such individuals.^{123 134}

Sensitivity Reactions

Hypersensitivity Reactions

Allergic reactions (e.g., anaphylactic shock, pruritus, rash, urticaria, difficulty breathing, hypotension, serum sickness) have been reported rarely with typhoid vaccines.^{103 123}

Prior to administration, take all known precautions to prevent adverse reactions, including a review of patient’s history with respect to health status and possible sensitivity to the vaccine, similar vaccines, or vaccine components.^{103 123}

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or other serious allergic reaction occurs.¹²³

General Precautions

Transmission of Vaccine Bacteria

Typhoid vaccine live oral Ty21a: Contains live, attenuated bacteria and the vaccine strain may be shed transiently in the stool of vaccinees.^{102 103} Secondary transmission of the vaccine bacteria not documented.^{102 103}

Acute Illness

Decision whether to administer or delay vaccination in an individual with a current or recent febrile illness depends largely on the severity of symptoms and etiology of the illness.¹³⁴

Typhoid vaccine live oral Ty21a: Manufacturer states do not administer to individuals with acute febrile illness or acute GI illness (e.g., diarrhea or vomiting).¹⁰³ The oral vaccine requires replication in the gut;¹⁰⁵ may not be effective if given during GI illness or at time of ongoing diarrhea.^{105 141}

Typhoid Vi polysaccharide vaccine: Manufacturer states may be deferred in individuals with acute infection or febrile illness, unless withholding the vaccine poses greater risk.¹²³

ACIP states that minor acute illness, such as mild upper respiratory tract infection (with or without fever) generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever) until they have recovered from the acute phase of the illness.¹³⁴

Limitations of Vaccine Effectiveness

Typhoid vaccines may not protect all vaccine recipients against typhoid fever.^{102 103 115 123} Vaccine-induced immunity can be overwhelmed by large inoculum of Salmonella Typhi.¹⁰²

Regardless of vaccination status, take precautions against exposure to Salmonella Typhi (e.g., safe food and water precautions, frequent handwashing).¹⁰²

Typhoid vaccine live oral Ty21a: It is essential that all 4 doses be administered as recommended.¹⁰³ Complete the 4-dose regimen ≥1 week before potential exposure to Salmonella Typhi.^{102 103} (See Dosage under Dosage and Administration.)

Typhoid Vi polysaccharide vaccine: Administer dose ≥2 weeks before potential exposure to Salmonella Typhi.^{102 123} (See Dosage under Dosage and Administration.)

Will not provide protection against Salmonella Paratyphi or any Salmonella other than Salmonella Typhi and will not provide protection against other bacteria that cause enteric disease.^{103 123}

Not used for treatment of typhoid fever.^{103 123} Do not use in individuals with acute Salmonella Typhi infection^{103 123} or in chronic typhoid carriers.¹²³

No evidence to support use of typhoid vaccine to control common source outbreaks or disease following natural disasters or in individuals attending rural summer camps.^{103 123}

Duration of Immunity

Duration of protection after primary immunization with typhoid vaccines and need for revaccination or subsequent doses not fully determined.^{102 103 123}

Typhoid vaccine live oral Ty21a: Some evidence suggests that protection against typhoid fever persists for at least 5 years (possibly 7 years) after completion of 4-dose vaccination series.^{102 103} Revaccination recommended every 5 years in those with continuing or repeated exposure to Salmonella Typhi.^{102 103 115}

Typhoid Vi polysaccharide vaccine: 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.^{123 128 129} Revaccination recommended every 2 years in individuals with continuing or repeated exposure to Salmonella Typhi.¹²³

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune response in vaccinees.¹³⁴

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.¹³⁴

Typhoid vaccine live oral Ty21a: Unstable when exposed to ambient temperatures and must be shipped and stored at 2–8°C.^{103 126 131} Do not administer if it has been mishandled or has not been stored at recommended temperatures.^{103 126 131} (See Storage under Stability.)

Typhoid Vi polysaccharide vaccine: Not adversely affected by elevated temperatures (e.g., those that occur in tropical areas).^{124 126} (See Storage under Stability.) May be preferred in situations in which continuous refrigeration cannot be ensured.^{124 126}

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.¹³⁴

Specific Populations

Pregnancy

Data not available regarding use of typhoid vaccines in pregnant women.^{102 115}

Typhoid vaccine live oral Ty21a: Use during pregnancy only if clearly needed.¹⁰³ ACIP states that live vaccines generally are contraindicated during pregnancy.¹⁰²

Typhoid Vi polysaccharide vaccine: Use during pregnancy only when clearly needed.^{102 123} Manufacturer suggests that delaying vaccination until second or third trimester is a reasonable precaution to minimize possibility of teratogenicity.¹²³

Lactation

Data not available regarding use of typhoid vaccines in nursing women.^{103 123}

Typhoid vaccine live oral Ty21a: Not known whether distributed into milk.^{103 134} ACIP states that, although live vaccines do multiply in the woman’s body, most have not been shown to distribute into breast milk.¹³⁴

Typhoid Vi polysaccharide vaccine: Not known whether distributed into milk.¹²³ Manufacturer states use with caution.¹²³ Although specific data not available, ACIP states breast-feeding generally not a contraindication for inactivated vaccines since inactivated organisms in the vaccines do not multiply within the body and such vaccines appear to pose no special problems for the woman or her nursing infant.^{115 134}

Pediatric Use

Typhoid vaccine live oral Ty21a: Safety and efficacy not established in children <6 years of age;¹⁰³ not indicated in this age group.¹⁰³

Typhoid Vi polysaccharide vaccine: Safety and efficacy not established in children <2 years of age.¹²³ As with other polysaccharide vaccines, antibody response may be inadequate in children <2 years of age.¹²³ Manufacturer states a decision whether to use the vaccine in children <2 years of age^{† [off-label]} depends on risk incurred by the child on the basis of the epidemiological context.¹²³

Common Adverse Effects

Typhoid vaccine live oral Ty21a: Abdominal pain, nausea, headache, fever, diarrhea, vomiting, rash.^{102 103 115}

Typhoid Vi polysaccharide vaccine: Injection site reactions (pain, tenderness, erythema, induration),^{102 123 125 130 135} malaise/generalized aches,^{123 129 130} headache,^{102 123 125 130 135} myalgia/muscle aches,^{123 130} nausea,^{123 125 130} diarrhea,^{123 130} feverishness,^{123 130} decreased activity/lethargy,^{123 130} vomiting.¹²³

Drug Interactions

Other Vaccines

Typhoid vaccine live oral Ty21a: May be administered concurrently with or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, toxoids, or parenteral live vaccines.¹³⁴ If use of the live, attenuated typhoid vaccine is warranted, do not delay because of administration of other live virus vaccines (injectable or intranasal).^{102 134}

Typhoid Vi polysaccharide vaccine: Specific interaction studies not available.¹²³ Because it is an inactivated vaccine, it generally can be administered concurrently with (using different syringes and different injection sites) or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, toxoids, or live vaccines.¹³⁴

Specific Drugs

Stability

Storage

Oral

Capsules

Typhoid vaccine live oral Ty21a: 2–8°C in a dry place protected from light.¹⁰³

Must be shipped and stored only at 2–8°C.¹⁰³ Potency adversely affected by exposure to temperatures exceeding 2–8°C.¹⁰³

Any remaining capsules must be placed back in a refrigerator after each dose until 4-dose vaccination series completed.¹⁰³

Does not contain thimerosal or any other preservatives.¹⁰³

Parenteral

Injection, for IM Use

Typhoid Vi polysaccharide vaccine: 2–8°C.¹²³ Do not freeze.¹²³

Does not contain thimerosal, but contains phenol 0.25% as a preservative.¹²³

Actions

• Typhoid vaccine live oral Ty21a: Contains live Salmonella Typhi of the attenuated Ty21a strain and is commercially available for oral administration as enteric-coated capsules.^{102 103}

• Typhoid Vi polysaccharide vaccine: Sterile solution of purified cell surface Vi (“virulence”) polysaccharide extracted from Salmonella Typhi of the Ty2 strain in isotonic phosphate-buffered 0.9% sodium chloride for IM injection.^{102 123}

• Principal mode of transmission of typhoid infection is enteric (i.e., through fecal contamination and oral ingestion); most commonly acquired through food and/or water contaminated with feces from an infected person or a chronic typhoid carrier.^{102 103 105 115 138 139 141} Onset of illness usually gradual with signs and symptoms such as high fever, headache, malaise, anorexia, lethargy, abdominal pain and tenderness, splenomegaly, hepatomegaly, and rose spots.^{105 115} Invasive infection and mortality from typhoid infection typically higher in infants, elderly individuals, and those with immunosuppressive conditions, hemoglobinopathies, malignancies, and HIV infection.¹⁰⁵

• Efficacy of typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine for prevention of typhoid fever appear to be comparable when the vaccines are administered as recommended;^{101 102 107 111 114 115 116 117 118 119 120 121 123 124 125 126} neither vaccine is expected to provide protection against typhoid fever in all vaccine recipients.^{102 103 105 115 123}

• Data obtained principally from studies involving populations where typhoid is endemic indicate that both vaccine types provide protection against typhoid fever in approximately 50–80% of vaccinees.^{105 115} Experience 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 typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine in such individuals appear to be comparable to or higher than those attained in residents of endemic areas.^{102 103 123}

• Typhoid vaccine live oral Ty21a: Stimulates active immunity to typhoid fever by inducing production of both intestinal and serum antibodies and cell-mediated immune responses.^{102 103 126} Following primary immunization, serum titers of antibodies to the O antigen of Salmonella Typhi appear to correlate with protection against typhoid fever.¹²⁶ Following oral administration, the vaccine strain replicates in the gut¹⁰⁵ and may elicit a local immune response in the intestinal tract.¹⁰³ Ability of Salmonella Typhi to elicit a protective immune response depends on possession by the bacilli of a complete lipopolysaccharide.¹⁰³ The vaccine strain (Ty21a) in the oral vaccine is limited in its ability to produce a complete lipopolysaccharide;^{103 110 111} however, sufficient complete lipopolysaccharide apparently is produced to elicit an adequate immune response.^{103 110 111 115 119}

• Typhoid Vi polysaccharide vaccine: Stimulates active immunity to Salmonella Typhi by inducing production of antibodies to the Vi antigen.^{123 124 125 126 127 128 129 130} The Vi antigen is considered to be a virulence factor of Salmonella Typhi, apparently protecting the organism from the actions of complement;^{102 111 125 126 129} antibodies to the Vi antigen confer protection against typhoid fever.^{102 111 123 124 125 126 129}

• Reduced immune responses 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).^{123 134}

• Minimum titer of anti-typhoid antibodies conferring protection against typhoid following vaccination with typhoid vaccine not established.¹²³

Advice to Patients

• Prior to administration of typhoid vaccine, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative (VISs are available at [Web]).^{103 112 123}

• Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination with typhoid vaccine.^{103 123}

• Advise patient and/or patient's parent or guardian that routine typhoid vaccination not recommended in the US, but may be used to prevent typhoid in individuals at high risk of exposure to typhoid (e.g., certain travelers, household contacts of a typhoid carrier, certain laboratory personnel).^{103 123}

• Advise patient and/or patient's parent or guardian that oral or parenteral typhoid vaccine may not provide protection in all vaccinees.^{102 103 123} In addition to vaccination, importance of taking other precautions against exposure to typhoid fever (e.g., safe food and water precautions, frequent handwashing).^{102 103 115 123}

• When using typhoid vaccine live oral Ty21a, importance of completing 4-dose vaccination series as directed (i.e., dose every other day for 4 doses).¹⁰³ Advise vaccinees to swallow capsules whole with cool or lukewarm liquid on an empty stomach 1 hour before a meal and store remaining capsules in the refrigerator until entire 4-dose regimen is completed.^{102 103} Importance of completing the vaccination series ≥1 week prior to possible exposure to typhoid fever and importance of revaccination with the 4-dose series every 5 years if at continued or repeated risk of exposure.^{102 103 115}

• When using typhoid Vi polysaccharide vaccine, importance of receiving the dose ≥2 weeks prior to possible exposure to typhoid fever and importance of revaccination every 2 years if at continued or repeated risk of exposure.^{102 123 115}

• Importance of notifying clinicians if patient is immunocompromised since oral typhoid vaccine 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).^{102 103 115} (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.^{103 112 123}

• Importance of informing clinicians if any adverse reactions (including allergic reactions) occur with typhoid vaccine.^{103 112 123} 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 [Web].^{103 112 123} Also can be reported to the manufacturer at 800-533-5899 (PaxVax)¹⁰³ or 800-822-2463 (Sanofi Pasteur).¹²³

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.^{103 123} Importance of notifying clinicians if receiving therapy with anti-infective or antimalarial agents.¹⁰³ (See Specific Drugs under Interactions.)

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{103 123}

• Importance of informing patients of other important precautionary information.^{103 123} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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