VA Class:IM100
ATC Class:J07AP01
Typhoid vaccine is commercially available in the 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
Typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine are used to stimulate active immunity to prevent typhoid fever.103, 123
Typhoid fever is a potentially severe and occasionally life-threatening, febrile, enteric illness caused by Salmonella enterica serovar Typhi and usually is 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 The overall case-fatality rate of typhoid fever in patients who receive early and appropriate antibacterial treatment is typically less than 1%;102 however, if left untreated, the case-fatality rate may be at least 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 (See Travelers under Uses: Prevention of Typhoid Fever.)
The US Public Health Service Advisory Committee on Immunization Practices (ACIP) and US Centers for Disease Control and Prevention (CDC) state that routine vaccination against typhoid fever is not recommended for individuals residing in the US, but is recommended for those traveling to areas with a recognized risk of exposure to Salmonella Typhi.102, 115 In addition, vaccination against typhoid fever is recommended in individuals with intimate exposure (e.g., household contact) to a known typhoid carrier and in laboratory personnel with frequent contact with Salmonella Typhi bacilli.102, 103, 123
There are 2 different typhoid vaccines commercially available in the US for active immunization against typhoid fever.102, 103, 115, 123 Typhoid vaccine live oral Ty21a is an oral vaccine containing live, attenuated Salmonella Typhi of the Ty21a strain.102, 103, 115 Typhoid Vi polysaccharide vaccine is a parenteral inactivated vaccine containing polysaccharide antigens extracted from Salmonella Typhi of the Ty2 strain.102, 115, 123 Although a parenteral whole-cell heat/phenol-inactivated typhoid vaccine was previously used in the US, this vaccine was associated with a high rate of adverse effects and is no longer available in the US.102
When vaccination against typhoid fever is indicated, either typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine can be used unless contraindicated.102, 105, 115 Both vaccines stimulate active immunity to prevent typhoid fever,103, 123 but neither vaccine is expected to provide protection against typhoid fever in all vaccine recipients.102, 103, 105, 115, 123 Efficacy of typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine have not been compared directly in field trials; however, efficacy of the vaccines when administered as recommended appears to be comparable.101, 102, 107, 111, 114, 116, 117, 118, 119, 120, 121, 123, 124, 125, 126
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.102, 115, 141 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 typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine in these individuals appear to be comparable to or higher than seroconversion rates attained in residents of endemic areas.102, 103, 123 Because of the low incidence of typhoid fever in the US, efficacy studies are not possible in this population; however, evidence from antibody-titer studies suggests that both the oral and parenteral vaccine provide protection in vaccinees residing in nonendemic areas.102, 103, 123, 129
In addition to differences in the adverse effects profile of the 2 types of typhoid vaccine (see Cautions: Adverse Effects), other factors to consider when selecting which typhoid vaccine to use include age and immunocompetence of the vaccinee, immunization schedule, patient compliance, and storage facilities.105, 123, 126 The oral live, attenuated vaccine is labeled for use in adults, adolescents, and children 6 years of age or older while the parenteral inactivated typhoid Vi polysaccharide vaccine is labeled for use in adults, adolescents, and children 2 years of age or older.102, 103, 123 Primary immunization with typhoid vaccine live oral Ty21a requires administration of 4 doses on alternate days over a 1-week period, and the 4-dose regimen should be completed at least 1 week before possible exposure to Salmonella Typhi.102, 103 Primary immunization with typhoid Vi polysaccharide vaccine requires a single IM injection, and the dose should be given at least 2 weeks before possible exposure to Salmonella Typhi.102, 123 Because the oral vaccine is self-administered over a 1-week interval and compliance errors (i.e., dosing errors, improper storage) have been reported, the parenteral typhoid Vi polysaccharide vaccine may be preferred in patients in whom compliance is likely to be a problem.131
Typhoid vaccine live oral Ty21a is unstable when exposed to ambient temperatures and must be stored at 2-8°C.103, 126, 131 Because typhoid Vi polysaccharide vaccine reportedly is not adversely affected by elevated temperatures, such as those that occur in tropical areas, the parenteral vaccine may be preferred in situations in which continuous refrigeration cannot be ensured.124, 126
Typhoid vaccine live oral Ty21a is a live, attenuated vaccine and should not be used in individuals with altered immunocompetence;102, 103, 115, 155, 225 therefore, the parenteral inactivated vaccine is recommended in such individuals.102, 115, 155
ACIP and CDC recommend that US travelers planning to visit areas where there is a recognized risk for exposure to Salmonella Typhi should be vaccinated against typhoid fever.102, 115
The local incidence of typhoid fever is determined by the frequency of carriers in the population, adequacy of environmental sanitation, and purity of the water supply.141 Typhoid fever is uncommon in the US, but it is endemic in many less well-developed areas of the world, including many countries in Africa, Asia, Central and South America, and the Caribbean, that have poor sanitation and primitive water systems.115, 138, 141 In recent years, most US cases of typhoid fever have been reported in individuals who had traveled to southern Asia (especially the Indian subcontinent including India, Bangladesh, or Pakistan) or Africa.115, 139
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 Although the 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 the usual tourist itinerary, even short-term travel (less than 1 week) to high-incidence areas is associated with a risk for typhoid fever.102, 115 Most US cases of travel-associated typhoid fever occur in travelers who were visiting friends or relatives and many of these individuals did not seek pre-travel advice regarding vaccination.102
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 being reported with increasing frequency in many regions of the world (e.g., Indian subcontinent, Africa).102, 115, 139, 141 Travelers to areas with a recognized risk of exposure to Salmonella Typhi should be cautioned that vaccination against typhoid fever is not a substitute for careful selection of food and beverages since typhoid vaccines are not 100% effective102, 115, 138 and vaccine-induced protection can be overwhelmed by a large inoculum of Salmonella Typhi.102
Travelers also should be aware that paratyphoid fever caused by S. enterica serovar Paratyphi A, B (tartrate negative), or C is being reported with increasing frequency in many countries (an estimated 6 million cases of paratyphoid fever occur annually worldwide and approximately 100 cases occur annually in the US) and is an illness clinically indistinguishable from typhoid fever.102, 115 Although there is some observational data suggesting that typhoid vaccine live oral Ty21a may offer partial protection against Salmonella Paratyphi B (tartrate negative),102 travelers should be advised that typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine will not provide protection against disease caused Salmonella Paratyphi or any Salmonella other than Salmonella Typhi.103, 123
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
ACIP recommends that individuals 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 longer than 1 year) should be vaccinated against typhoid fever.102
ACIP recommends that microbiologists and other 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
Typhoid vaccine live oral Ty21a is administered orally.103
Typhoid Vi polysaccharide vaccine is administered by IM injection.123
Typhoid Vaccine Live Oral Ty21a
Typhoid vaccine live oral Ty21a is administered orally as enteric-coated capsules.103
The vaccine capsules should be given with cold or lukewarm (not exceeding a temperature of about 37°C [body temperature]) liquid approximately 1 hour before a meal.103
The vaccine capsules should be swallowed whole immediately after placement in the mouth and should not be chewed.103
Typhoid vaccine live oral Ty21a should not be administered to individuals with acute GI illness103, 105 or persistent diarrhea or vomiting.103 (See Typhoid Vaccine Live Oral Typ21a under Cautions: Precautions and Contraindications.)
Vaccinees should be advised that the capsules must be refrigerated (2-8°C) until just prior to administration since potency is adversely affected by exposure to warmer temperatures.103 It is essential that remaining capsules be placed back in the refrigerator after each dose is taken until the 4-dose vaccination series is completed.103 (See Chemistry and Stability: Stability.)
Typhoid Vi Polysaccharide Vaccine
Typhoid Vi polysaccharide vaccine is administered by IM injection.123
The vaccine should appear clear and colorless and should be discarded if it is turbid or contains particulates.123
Typhoid Vi polysaccharide vaccine should be administered undiluted and should not be mixed with any other vaccine.123
In adults, IM injections of typhoid Vi polysaccharide vaccine preferably should be made into the deltoid area.123 In children, IM injections of the vaccine should be made into the deltoid or the anterolateral thigh.123 The vaccine should not be injected into the gluteal area or any area where there may be a nerve trunk.123
To ensure delivery of vaccine 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, thickness of adipose tissue and muscle at the injection site, and injection technique.134 Anatomic variability, especially in the deltoid, should be considered and clinical judgment should be used to avoid inadvertent underpenetration or overpenetration of muscle.134
Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination134 and has been reported following administration of typhoid Vi polysaccharide vaccine.123 Syncope occurs most frequently in adolescents and young adults.134 Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope.123, 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, the patient should be observed until symptoms resolve.134
When multiple vaccines are administered during a single health-care visit, each parenteral vaccine should be given with a different syringe and at different injection sites.134 Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134
Dosing schedules (i.e., number of doses, timing prior to potential exposure to typhoid fever) differ between typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine.103, 123 Dosage recommendations for the specific preparation used should be followed. 102, 103, 123
Typhoid Vaccine Live Oral Ty21a
Primary immunization with typhoid vaccine live oral Ty21a in adults, adolescents, and children 6 years of age or older consists of 4 doses given as 1 capsule every other day (e.g., Sunday, Tuesday, Thursday, and Saturday or day 0, 2, 4, and 6).102, 103
The 4-dose regimen of typhoid vaccine live oral Ty21a should be completed at least 1 week prior to potential exposure to Salmonella enterica serovar Typhi.102, 103
The duration of response and optimum revaccination or booster schedule for typhoid vaccine live oral Ty21a have not been established.102, 103 Revaccination with the same 4-dose regimen of typhoid vaccine live oral Ty21a (i.e., 1 capsule every other day for 4 doses) is recommended every 5 years in individuals with continuing or repeated exposure to Salmonella Typhi.102, 103, 115
Data are not available regarding use of typhoid vaccine live oral Ty21a as a booster in individuals previously vaccinated with typhoid Vi polysaccharide vaccine or any other typhoid vaccine.103
Typhoid Vi Polysaccharide Vaccine
For primary immunization in adults, adolescents, and children 2 years of age or older, typhoid Vi polysaccharide vaccine is administered as a single 25-mcg dose (0.5 mL from the commercially available prefilled single-dose syringe or multidose vial).102, 123
Typhoid Vi polysaccharide vaccine should be administered at least 2 weeks prior to potential exposure to Salmonella Typhi.102, 123
The duration of response and optimum revaccination or booster schedule for typhoid Vi polysaccharide vaccine have not been established.102, 123 Pending further accumulation of data, revaccination with a single 0.5-mL dose of typhoid Vi polysaccharide vaccine is recommended every 2 years in individuals with continuing or repeated exposure to Salmonella Typhi.102, 115, 123
Data are not available regarding use of typhoid Vi polysaccharide vaccine following previous vaccination with typhoid vaccine live oral Ty21a or any other typhoid vaccine.123
Typhoid Vaccine Live Oral Ty21a
Adverse effects have been reported rarely in recipients of typhoid vaccine live oral Ty21a101, 102, 103, 119, 120, 121 and generally were mild and transient.102, 103
In a pilot and field study, adverse effects reported in those who received typhoid vaccine live oral Ty21a were abdominal pain (6.4%), nausea (5.8%), headache (4.8%), fever (3.3%), diarrhea (2.9%), vomiting (1.5%), and rash (1%). Only nausea was reported at a higher rate in vaccine recipients than in individuals who received placebo.103
During postmarketing surveillance over the period of 1991-1995 that involved administration of over 60 million doses of the oral vaccine, adverse effects reported to the manufacturer included diarrhea (45), abdominal pain (42), nausea (35), fever (34), headache (26), rash (26), vomiting (18), urticaria on the trunk and/or extremities (13), and one case of nonfatal anaphylactic shock.103
Typhoid vaccine live oral Ty21a contains live, attenuated Salmonella enterica serovar Typhi of the attenuated Ty21a strain that can be shed transiently in the stool of vaccinees; however, secondary transmission of the vaccine strain has not been documented.102, 103
Typhoid Vi Polysaccharide Vaccine
Adverse effects following administration of typhoid Vi polysaccharide vaccine generally consist of mild and transient local reactions and rarely persist longer than 48 hours.102, 123, 130
In a postmarketing safety study conducted at 11 US travel clinics, the most common adverse effects following administration of typhoid Vi polysaccharide vaccine were injection site pain (77%), tenderness (75%), and muscle aches (39%).102 In other data, tenderness (e.g., pain on direct pressure) was reported in up to 98%,123, 130 injection site pain in 14-69%,123, 125, 129, 130, 135 induration in 1-18%,102, 123, 129, 125, 130, 135 and erythema in 3-43% of vaccinees within 48 hours after administration of typhoid Vi polysaccharide vaccine.102, 123, 125, 129, 130, 135 Pruritus, rash, and paresthesia/tingling also have been reported in recipients of typhoid Vi polysaccharide vaccine.130 Limited data suggest that individuals receiving a booster dose of typhoid Vi polysaccharide vaccine are more likely to experience injection site erythema and/or induration (greater than 1 cm) than those receiving an initial dose.129
Systemic adverse effects reported within 48 hours of administration of typhoid Vi polysaccharide vaccine include malaise/generalized aches in 4-37%,123, 129, 130 headache in 11-27%,102, 123, 125, 130, 135 myalgia/muscle aches in 2-28%,123, 130 nausea in 2-11%,123, 125, 130 diarrhea in 2-4%,123, 130 vomiting in 2%,123 feverishness (subjective assessment) in 3-10%,123, 130 fever greater than 37.8°C in 2%,123 and decreased activity/lethargy in 2%.123, 130 Respiratory tract symptoms also have been reported in a few individuals.130 The frequencies of systemic adverse effects following a booster dose are similar to those reported following an initial dose.123, 129 Serious or life-threatening systemic adverse effects have not been reported following administration of typhoid Vi polysaccharide vaccine in controlled clinical studies.123, 125, 129, 130
In postmarketing experience in Europe, the following additional adverse effects have been reported with typhoid Vi polysaccharide vaccine: lymphadenopathy, asthenia, malaise, flu-like symptoms, abdominal pain, arthralgia, cervical pain, tremor, hypotension, syncope with and without seizures, loss of consciousness, anaphylaxis, allergic-type reactions including urticaria, angioedema, asthma, difficulty breathing, and serum sickness.123 Additional adverse effects reported in European postmarketing experience include diffuse glomerulonephritis, neutropenia, bilateral retinitis, and polyarthritis;123 these individuals had also received other vaccines and a causal relationship to typhoid Vi polysaccharide vaccine has not been established.123
Precautions and Contraindications
Prior to administration of typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine, all known precautions should be taken to prevent adverse reactions, including a review of the 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 and equipment should be available for immediate treatment if an anaphylactic or other serious allergic reaction occurs.123
The patient and/or the patient's parent or guardian should be informed of the benefits and risks of vaccination with typhoid vaccine and should be provided with a copy of the appropriate Vaccine Information Statement (available at CDC website at [Web]).103, 112, 123 Patients and/or the patient's parent or guardian also should be instructed to report any severe or unusual adverse reactions that occur after vaccination to their healthcare provider.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 Adverse reactions to typhoid vaccine also can be reported to the manufacturer at 800-533-5899 (PaxVax)103 or 800-822-2463 (Sanofi Pasteur).123
Individuals who have been vaccinated against typhoid fever should be advised to continue to take other precautions against exposure to Salmonella Typhi (e.g., safe food and water precautions, frequent handwashing).102, 103, 115, 123 (See Limitations of Vaccine Effectiveness under Cautions: Precautions and Contraindications.)
Typhoid Vaccine Live Oral Ty21a
Typhoid vaccine live oral Ty21a is contraindicated in individuals hypersensitive to any component of the vaccine or the enteric-coated capsule.103
Because typhoid vaccine live oral Ty21a contains live, attenuated bacteria, it should not be used in individuals with congenital or acquired immunodeficiencies, including those with human immunodeficiency virus (HIV) infection or those receiving immunosuppressive therapy.103, 155, 225 Safety of the live, attenuated oral vaccine has not been established in individuals deficient in ability to mount a humoral or cell-mediated immune response, and the manufacturer states that the vaccine should not be used in such individuals, regardless of any possible benefits.103
Experts state that typhoid vaccine live oral Ty21a may be used in healthy immunocompetent individuals who reside in a household with immunocompromised patients.225
Typhoid vaccine live oral Ty21a should not be administered to individuals with an acute GI illness;103, 105 vaccination should be deferred in those with persistent diarrhea or vomiting.103 The oral vaccine requires replication in the gut105 and may not be effective if administered during GI illness or at the time of ongoing diarrhea.105, 141
Patients should be advised that it is essential that all 4 doses of typhoid vaccine live oral Ty21a be administered as recommended;103 an optimum immune response may not be achieved if the complete 4-dose regimen is not used.103 (See Typhoid Vaccine Live Oral Ty21a under Dosage and Administration: Dosage.)
Typhoid Vi Polysaccharide Vaccine
Typhoid Vi polysaccharide vaccine is contraindicated in individuals hypersensitive to any component of the vaccine.123
If indicated, typhoid Vi polysaccharide vaccine may be used in patients 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 The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that recommendations concerning use of typhoid Vi polysaccharide vaccine in patients 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
The decision to administer or delay vaccination in an individual with a current or recent acute illness depends on the severity of symptoms and etiology of the illness.134
The manufacturer states that typhoid vaccine live oral Ty21a should not be administered to individuals with acute febrile illness or acute GI illness.103 (See Typhoid Vaccine Live Oral Ty21a under Cautions: Precautions and Contraindications.)
The manufacturer states that administration of typhoid Vi polysaccharide vaccine may be deferred in individuals with acute infection or febrile illness, unless withholding the vaccine poses a greater risk.123
ACIP states that minor acute illness, such as mild upper respiratory infection (with or without fever), generally does not preclude vaccination.134 However, vaccination of individuals with moderate or severe acute febrile illness generally should be deferred until they have recovered from the acute phase of the illness.134 This precaution avoids superimposing adverse effects of the vaccine on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccination.134
Limitations of Vaccine Effectiveness
Typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine may not protect all vaccine recipients against typhoid fever.102, 103, 115, 123
Individuals who have been vaccinated against typhoid fever should be advised to continue to take precautions against exposure to Salmonella Typhi (e.g., safe food and water precautions, frequent handwashing).102
Typhoid vaccines will not provide protection against Salmonella 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 the treatment of typhoid fever and should not be used in individuals with acute Salmonella Typhi infection103, 123 or in chronic typhoid carriers.123
There is no evidence to support the use of typhoid vaccine to control common source outbreaks or disease following natural disasters or in individuals attending rural summer camps.103, 123
The duration of protection after primary immunization with typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine and need for revaccination or subsequent doses have not been fully determined.102, 103, 123
Following completion of the 4-dose vaccination series of typhoid vaccine live oral Ty21a, protection against typhoid fever may persist for at least 5 years (possible 7 years).103, 105 Revaccination with typhoid vaccine live oral Ty21a is recommended every 5 years in individuals with continuing or repeated exposure to Salmonella Typhi.102, 103, 115
Following administration of a single dose of typhoid Vi polysaccharide vaccine, limited data indicate that antibody titers remain elevated for at least 12 months 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 with typhoid Vi polysaccharide vaccine is recommended every 2 years in individuals with continuing or repeated exposure to Salmonella Typhi.123
Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.134
Typhoid vaccine live oral is unstable when exposed to ambient temperatures and must be shipped and stored at 2-8°C.103, 126, 131
Typhoid Vi polysaccharide vaccine is not adversely affected by elevated temperatures (e.g., those that occur in tropical areas).124, 126 Therefore, the parenteral vaccine may be preferred in situations when continuous refrigeration cannot be ensured.124, 126
All vaccines should be inspected upon delivery and monitored during storage to ensure that the appropriate temperature is maintained.134 (See Chemistry and Stability: Stability.)
Vaccine that has been mishandled or has not been stored at the recommended temperature should not be administered.134
If there are concerns about mishandling, the manufacturer or state or local immunization or health departments should be contacted for guidance on whether the vaccine is usable.134
Safety and efficacy of typhoid vaccine live oral Ty21a have not been established in children younger than 6 years of age and the vaccine is not indicated in this age group.103
Safety and efficacy of typhoid Vi polysaccharide vaccine have not been established in children younger than 2 years of age.123 As with other polysaccharide vaccines, the antibody response to typhoid Vi polysaccharide vaccine may be inadequate in children younger that 2 years of age.123 The manufacturer states that a decision whether to use typhoid Vi polysaccharide vaccine in children younger than 2 years of age† depends on the risk incurred by the child on the basis of the epidemiological context.123
Data are not available regarding use of typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine in pregnant women.102, 115 Animal reproduction studies have not been performed with either vaccine, and it is not known whether the vaccines can cause fetal harm or affect reproduction capacity when administered to pregnant women.103, 123
The manufacturer of typhoid vaccine live oral Ty21a states that the vaccine should be used during pregnancy only when clearly needed.103 ACIP states that live vaccines generally are contraindicated during pregnancy.102
Typhoid Vi polysaccharide vaccine should be used during pregnancy only when clearly needed.102, 123 The manufacturer suggests that delaying vaccination until the second or third trimester is a reasonable precaution to minimize the possibility of teratogenicity.123
Data are not available regarding use of typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine in nursing women.103, 123
It is not known whether typhoid vaccine live oral Ty21a is 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 milk.134
It is not known whether typhoid Vi polysaccharide vaccine is distributed into milk.123 The manufacturer recommends that the vaccine be used with caution in nursing women.123 Although specific data are not available, ACIP states that breast-feeding generally is not a contraindication to administration of 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
Anti-infective agents that are active against Salmonella enterica serovar Typhi may also have activity against the bacterial strain contained in typhoid vaccine live oral Ty21a and theoretically may prevent a sufficient degree of multiplication of the vaccine strain that is necessary to induce a protective immune response.102, 103, 115 The manufacturer of typhoid vaccine live oral Ty21a states that the vaccine should not be used in individuals receiving sulfonamides or other anti-infectives.103 The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that typhoid vaccine live oral Ty21a should not be given until at least 3 days (72 hours) after the last dose of anti-infective agent and, if feasible, anti-infective agents should not be initiated or resumed until at least 3 days after the last dose of the oral vaccine.102
The manufacturer of typhoid Vi polysaccharide vaccine states that specific studies evaluating drug interactions between the parenteral vaccine and anti-infective agents have not been conducted to date.123
Several antimalarial agents (e.g., chloroquine, mefloquine, proguanil) have antibacterial activity against Salmonella and it has been suggested that some of these agents may interfere with the immunogenicity of typhoid vaccine live oral Ty21a.103, 132, 133
The manufacturer of typhoid Vi polysaccharide vaccine states that specific studies evaluating drug interactions between the parenteral vaccine and other drugs, including antimalarial agents, have not been conducted to date.123
Concurrent use of proguanil (200 mg daily; not commercially available in the US as a single-entity preparation) and typhoid vaccine live oral Ty21a in healthy adults resulted in decreased immune response to the live, attenuated vaccine.103 Therefore, the manufacturer of typhoid vaccine live oral Ty21a states that proguanil should not be administered until at least 10 days after the final dose of typhoid vaccine live oral Ty21a.103
ACIP states that the fixed combination of atovaquone and proguanil (atovaquone/proguanil) in dosages used for prophylaxis of malaria may be used concurrently with typhoid vaccine live oral Ty21a.102
In a study in healthy adults, concurrent use of chloroquine (500 mg once weekly) and typhoid vaccine live oral Ty21a did not result in a clinically important decrease in the immune response to the live, attenuated vaccine (i.e., no clinically important decrease in humoral IgG or IgA antibody response).103 Therefore, the oral vaccine can be used in patients receiving chloroquine.102, 103
In vitro, mefloquine hydrochloride inhibits the growth of Salmonella Typhi, including the vaccine strain contained in typhoid vaccine live oral Ty21a.132, 133
In a study in healthy adults, concurrent use of mefloquine (250 mg once weekly) and typhoid vaccine live oral Ty21a did not result in a clinically important decrease in the immune response to the live, attenuated vaccine (i.e., no clinically important decrease in humoral IgG or IgA antibody response).103 Therefore, the manufacturer states that the oral vaccine can be used in patients receiving mefloquine.103
Although the manufacturer of typhoid vaccine live oral Ty21a states that data are not available regarding concurrent use with immune globulins,103 ACIP states that the oral vaccine may be administered simultaneously with or at any time before or after antibody-containing preparations (e.g., IGIM, IGIV, immune globulin subcutaneous, hepatitis B immune globulin [HBIG], rabies immune globulin [RIG], tetanus immune globulin [TIG], varicella-zoster immune globulin [VZIG]).102, 134
Because typhoid Vi polysaccharide vaccine is an inactivated vaccine, ACIP states that it can be administered concurrently with or at any time before or after a dose of immune globulin.134 The manufacturer of typhoid Vi polysaccharide vaccine states that specific studies evaluating drug interactions between the parenteral vaccine and immune globulin have not been conducted to date.123
Individuals receiving immunosuppressive therapy (e.g., alkylating agents, antimetabolites, corticosteroids, radiation) may have decreased antibody response to typhoid vaccine live oral Ty21a, and the vaccine should not be used in individuals receiving such therapy.103, 134, 225 Some experts state that live vaccines should be administered at least 4 weeks prior to initiation of immunosuppressive therapy.225 ACIP states that live, attenuated vaccines should not be administered for at least 3 months after immunosuppressive therapy is discontinued.134
Inactivated Vaccines and Toxoids
ACIP states that typhoid vaccine live oral Ty21a can be administered concurrently with or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids.134
The manufacturer of typhoid Vi polysaccharide vaccine states that specific studies evaluating interactions between the parenteral inactivated vaccine and other vaccines (e.g., hepatitis A vaccine, tetanus toxoid adsorbed, poliomyelitis vaccine) have not been conducted to date.123 However, ACIP states that since the parenteral typhoid vaccine is an inactivated vaccine, it generally can be administered concurrently with or at any interval before or after other inactivated vaccines, recombinant vaccines, polysaccharide vaccines, or toxoids.134
MenACWY-D (Menactra®) and typhoid Vi polysaccharide vaccine (Typhim Vi®) have been administered concomitantly at different sites in adults 18 through 55 years of age123, 140 without reduced immune responses to either vaccine123 and without a clinically important increase in adverse effects compared with administration alone.140 Because both vaccines are inactivated vaccines, typhoid Vi polysaccharide vaccine may be administered simultaneously with MenACWY (using different syringes and different injection sites) or at any interval before or after the meningococcal vaccine.134
ACIP states that typhoid vaccine live oral Ty21a may be administered concurrently with or at any interval before or after other live vaccines (e.g., measles, mumps, and rubella virus vaccine live [MMR], varicella virus vaccine live, yellow fever vaccine).102, 134 Although specific data are not available regarding the immunogenicity of typhoid vaccine live oral Ty21a administered concurrently with or within 30 days of live virus vaccines, ACIP states that if use of the oral typhoid vaccine is warranted, it should not be delayed because of administration of a live virus vaccine.134
The manufacturer of typhoid Vi polysaccharide vaccine states that specific interaction studies evaluating drug interactions between the parenteral inactivated vaccine and live vaccines have not been conducted to date.123 ACIP states that since parenteral typhoid vaccine is an inactivated vaccine, it generally can be administered simultaneously with or at any interval before or after live vaccines.134
Although specific data are not available, it has been suggested that the buffer component of cholera vaccine live oral may interfere with typhoid vaccine live oral Ty21a enteric-coated tablets.142 Therefore, if immunization with typhoid vaccine live oral Ty21a and cholera vaccine live oral are both indicated prior to travel, some experts recommend that the first dose of typhoid vaccine live oral Ty21a be administered at least 8 hours after cholera vaccine live oral.142
Concurrent administration of yellow fever vaccine does not interfere with the immune response to typhoid vaccine live oral Ty21a.103, 136 ACIP states that the live, attenuated typhoid vaccine may be administered concurrently with or at any interval before or after yellow fever vaccine.134, 136
Yellow fever vaccine has been administered concurrently at a different site with typhoid vaccine Vi capsular polysaccharide with or without concomitant hepatitis A vaccine (Vaqta®) without any apparent decrease in the immune response or increase in adverse effects.109 The parenteral inactivated typhoid vaccine may be given concurrently with or at any interval before or after yellow fever vaccine.134
Typhoid vaccines are used to stimulate active immunity to typhoid fever in individuals at high risk of exposure to Salmonella enterica serovar Typhi.103, 123 Natural infection with Salmonella Typhi, the causative agent of typhoid fever, generally confers lifelong immunity; however, the nature of this immunity is complex and includes both humoral and cell-mediated components.141
Response to Typhoid Vaccine Live Oral Ty21a
The exact mechanism by which typhoid vaccine live oral Ty21a elicits an immune response is not known; however, the oral vaccine induces production of both intestinal and serum antibodies and cell-mediated immune responses.102, 103, 126 Seroconversion rates in healthy US adults following primary immunization with 3 doses of typhoid vaccine live oral Ty21a are similar to those attained in residents of typhoid-endemic areas.103, 113, 126 Following primary immunization with typhoid vaccine live oral Ty21a, serum titers of antibodies to the O antigen of Salmonella Typhi appear to correlate with protection against typhoid fever.126 Following ingestion, virulent strains of Salmonella Typhi can pass through the stomach acid barrier, colonize the intestinal tract, penetrate the intestinal lumen, and enter the lymphatic system and blood stream, resulting in infection.103 It has been suggested that oral administration of typhoid vaccine containing a live, attenuated strain of the bacilli may elicit a local immune response in the intestinal tract while undergoing an aborted infection, with resultant protection against subsequent infection with a virulent strain.103 However, the ability of Salmonella Typhi to elicit a protective immune response depends on possession by the bacilli of a complete lipopolysaccharide.103 The ability of the live, attenuated strain present in the oral typhoid vaccine to produce a complete lipopolysaccharide is limited since this strain is deficient in enzymes essential for lipopolysaccharide biosynthesis;103, 110, 111 however, sufficient complete lipopolysaccharide apparently is produced to elicit an adequate immune response.103, 110, 111, 119 In addition, despite low levels of lipopolysaccharide biosynthesis by the vaccine strain, sufficient quantities of intermediates of this synthesis accumulate and induce cell lysis before the organism can gain a virulent phenotype.103, 110
In a series of field trials in Chile, efficacy of the live, attenuated vaccine (as enteric-coated capsules) given as a 1- or 2-dose regimen in school-aged children was 21 or 54%, respectively, after 33 months of surveillance.103 When a 3-dose regimen (as enteric-coated capsules) was administered on alternate days (short-schedule immunization) or 21 days apart (long-schedule immunization) in Chilean school-age children, vaccine efficacy was 67 or 49%, respectively, after 36 months of surveillance;101, 103, 111, 120 after 48 months, efficacy of the short-schedule immunization was 68%.103, 111, 116 Efficacy of the live, attenuated vaccine appears to be greater in older children and adults than in young children (e.g., 36 or 60% for those 3-14 or 15-44 years of age, respectively),103, 111, 121 but experience is limited in children younger than 5 years of age.102, 103
Experience in individuals from areas without endemic disease (e.g., US residents) who travel to endemic regions also is limited,102, 103 but seroconversion rates reported following a 3-dose primary immunization series with the live, attenuated vaccine in such individuals are comparable to those in residents of endemic areas.103 Because of the low incidence of typhoid fever in the US, efficacy studies are not possible in this population; however, evidence from antibody-titer studies suggests that the live, attenuated vaccine will provide protection to vaccinees residing in nonendemic areas such as the US.103 The duration of response after primary immunization with typhoid vaccine live oral Ty21a has not been established.102, 103
Response to Typhoid Vi Polysaccharide Vaccine
Administration of typhoid Vi polysaccharide vaccine stimulates 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 and antibodies to the Vi antigen confer protection against typhoid fever.102, 111, 123, 124, 125, 126, 129
IM administration of a single dose of typhoid Vi polysaccharide vaccine in most healthy adults and children 2 years of age or older generally results in a 4-fold or greater increase in serum antibodies specific for the Vi antigen within 2-4 weeks.102, 123, 124, 125, 126, 127, 129, 130 Results of several US studies indicate that a single 25-mcg dose of Vi polysaccharide vaccine results in a 4-fold or greater increase in serum antibodies in 88-96% of healthy adults.102, 123, 129 Because baseline antibody titers from individuals from typhoid-endemic areas (i.e., Nepal, South Africa, Indonesia) indicate prior exposure to Salmonella Typhi, vaccine-induced antibody response in these individuals differs from that produced in “typhoid naive” populations (e.g., most travelers from the US).123 In studies conducted in Nepal, administration of a single 25-mcg dose of typhoid Vi polysaccharide vaccine in children 5-14 years of age, adolescents and adults 15-44 years of age, or adults 45-55 years of age produced a 4-fold or greater increase in antibody titers within 4 weeks in approximately 77, 79, or 63% of individuals, respectively.123, 124 A single 25-mcg dose of the vaccine produced a 4-fold or greater increase in serum antibodies within 4 weeks in about 96% of Indonesian children aged 2-5 years of age.123 The titer of antibody that is protective against typhoid has not been determined to date.123
Limited evidence indicates that antibody titers against the Vi antigen remain elevated for at least 12 months following administration of typhoid Vi polysaccharide vaccine 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 Administration of an additional dose of typhoid Vi polysaccharide vaccine in healthy US adults 27-34 months after the initial dose produces antibody titers comparable to those obtained following the primary dose.123, 129
Efficacy of a single 25-mcg dose of typhoid Vi polysaccharide vaccine in preventing typhoid fever has been demonstrated in a series of field trials in typhoid-endemic areas.102, 123, 124, 125 In a trial in Nepal in individuals 5-44 years of age, those who received the vaccine had 74% fewer cases of culture-confirmed Salmonella Typhi infection over a 20-month period compared with unimmunized individuals.102, 123, 124 Surveillance in immunized South African children indicated that vaccine efficacy was 61, 52, or 50% after 1, 2, or 3 years; overall vaccine efficacy was 55%.102, 123, 125
Typhoid vaccine is commercially available in the US as an oral live, attenuated vaccine (typhoid vaccine live oral Ty21a; Vivotif®)102, 103, 115 and as a parenteral, inactivated capsular polysaccharide vaccine (typhoid Vi polysaccharide vaccine; Typhim Vi®).102, 123, 115
Typhoid Vaccine Live Oral Ty21a
Typhoid vaccine live oral is commercially available as enteric-coated capsules containing lyophilized, live Salmonella enterica serovar Typhi of the attenuated Ty21a strain.102, 103, 111 Commercially available typhoid vaccine live oral Ty21a is prepared by culturing the typhoid bacilli on a suitable nutrient medium (a digest of yeast extract, an acid digest of casein, dextrose, and galactose); collecting the bacteria by centrifugation; stabilization with sucrose, ascorbic acid, and amino acids; and lyophilization.103 The lyophilized bacteria are mixed with lactose and magnesium stearate and filled into gelatin capsules that are then coated with an organic solution to provide resistance against dissolution in the acidic environment of the stomach.103
Each capsule of typhoid vaccine live oral Ty21a contains 2-10 × 109 colony-forming units (CFU) of viable Salmonella Typhi Ty21a and 5-50 × 109 nonviable Salmonella Typhi Ty21a.103 The vaccine does not contain thimerosal or any other preservatives.103
Typhoid Vi Polysaccharide Vaccine
Typhoid Vi polysaccharide vaccine is a sterile solution containing purified cell surface Vi (“virulence”) polysaccharide extracted from Salmonella enterica serovar Typhi of the Ty2 strain.102, 123 The vaccine is prepared by culturing Salmonella Typhi on a suitable semisynthetic medium, precipitating the capsular polysaccharide using hexadecyltrimethylammonium bromide, and purifying the antigen by differential centrifugation and precipitation.123 Potency of typhoid Vi polysaccharide vaccine is expressed in terms of purified Vi polysaccharide (determined by molecular size and O -acetyl content).123
Typhoid Vi polysaccharide vaccine occurs as a clear, colorless liquid.123 Each 0.5-mL dose of the vaccine contains 25 mcg of purified Vi polysaccharide dissolved in isotonic phosphate-buffered 0.9% sodium chloride.102, 123 The vaccine also contains 0.25% phenol as a preservative, residual formaldehyde (not more than 100 mcg) from inactivation of the bacterial culture, and residual polydimethylsiloxane or fatty-acid ester-based antifoam.123
Typhoid Vaccine Live Oral Ty21a
Typhoid vaccine live oral Ty21a enteric-coated capsules should be stored at 2-8°C in a dry place protected from light.103
Potency of typhoid vaccine live oral Ty21a is adversely affected by exposure to temperatures exceeding 2-8°C.103 Therefore, the vaccine capsules should be shipped and stored only at 2-8°C.103 In addition, any remaining capsules must be placed back in the refrigerator after each dose until the 4-dose vaccination series is completed.103
Typhoid Vi Polysaccharide Vaccine
Typhoid Vi polysaccharide vaccine should be stored at 2-8°C and should not be frozen.123
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IM use | 25 mcg Vi capsular polysaccharide per 0.5 mL |
Only references cited for selected revisions after 1984 are available electronically.
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