Mosby’s GenRx®, 10th ed.
Copyright © 2000 Mosby, Inc.
Typhoid Vaccine (002405)
Indications: Immunization, typhoid
Pregnancy Category C
WHO Formulary
FDA Pre 1938 Drugs
FDA DRUG CLASS: Vaccines/Antisera
BRAND NAMES: Typhim Vi (US); Typhoral (India); Typhovax
(Korea); Typh-Vax (New-Zealand); Typh-Vax Oral (Australia); Tyrix Vi (Korea);
Vivotif (Germany); Vivotif Berna (US); Vivotif Berna Capsule (Norway); Vivotif
Oralt Vaccin (Sweden);
Zerotyph (Korea, Philippines);
(International brand names outside U.S. in italics)
Vivotif Berna Vaccine is a live attenuated vaccine for oral
administration
only. The
vaccine contains the attenuated strain Salmonella typhi
Ty21a.1,2
The vaccine strain is grown in fermentors under controlled
conditions in medium containing a digest of yeast extract, an acid digest of
casein, dextrose and galactose.
The bacteria are collected by centrifugation, mixed with a
stabilizer containing sucrose, ascorbic acid and amino acids, and lyophilized.
The lyophilized bacteria are mixed with lactose and magnesium stearate and
filled into gelatin capsules which are coated with an organic solution to
render them resistant to dissolution in stomach acid. The enteric-coated,
salmon/white capsules are then packaged in 4-capsule blisters for distribution.
The contents of each enteric-coated capsule are shown in TABLE 1.
TABLE 1: Contents of One Enteric-coated Capsule of Vivotif
Berna Vaccine
Viable S. typhi Ty21a
2 - 6 × 109 colony-forming units*
Non-viable S. typhi Ty21a
5 - 50 × 109 bacterial cells
Sucrose
26 - 130 mg
Ascorbic acid
1 - 5 mg
Amino acid mixture
1.4 - 7 mg
Lactose
100 - 180 mg
Magnesium stearate
·
Vaccine potency (viable cell counts per capsule) is
determined by inoculation of agar plates with appropriate dilutions of the
vaccine suspended in physiological saline.
Salmonella typhi is the etiological agent of typhoid
fever, an acute, febrile enteric disease. Typhoid fever continues to be an
important disease in many parts of the world.
Travelers entering infected areas are at risk of contracting
typhoid fever
following the
ingestion of contaminated food or water. Typhoid fever is
considered to be
endemic in
most areas of Central and South America, the African
continent, the Near
East and the
Middle East, Southeast Asia and the Indian subcontinent.3
There are
approximately 500
cases of typhoid fever per year diagnosed in the United
States.4 In 62% of
these
patients (data from 1975-1984) the disease was acquired
outside of the
United States
while in 38% of the patients the disease was acquired within
the United
States.5 Of 340
cases acquired in the United States between 1977 and 1979, 23%
of the cases
were
associated with typhoid carriers, 24% were due to food
outbreaks, 23% were
associated with the ingestion of contaminated food or water,
6% due to
household
contact with an infected person and 4% following exposure to
S. typhi in a
laboratory
setting.6
The majority of typhoid cases respond favorably to
antibiotic therapy.
However, the
emergence of multi-drug resistant strains has greatly
complicated therapy
and cases of
typhoid fever that are treated with ineffective drugs can be
fatal.7
Approximately 2-4%
of acute typhoid cases result in the development of a
chronic carrier
state.8 These
non-symptomatic carriers are the natural reservoir for S.
typhi and can
serve to maintain
the disease in its endemic state or to directly infect
individuals.3
Virulent strains of S. typhi upon ingestion are able to
pass through the stomach acid barrier, colonize the intestinal tract, penetrate
the lumen and enter the lymphatic system and blood stream, thereby causing
disease. One possible mechanism by which disease may be prevented is by evoking
a local immune response in the intestinal tract. Such local immunity may be
induced by oral ingestion of a live attenuated strain of S. typhi undergoing an
aborted infection. The ability of S. typhi to cause disease and to induce a protective
immune response is dependent upon the bacteria possessing a complete lipopolysaccharide.1
The S. typhi Ty21a vaccine strain, by virtue of a reduction in enzymes
essential for lipopolysaccharide biosynthesis, is restricted in its ability to produce
complete lipopolysaccharide.1,2 However, a sufficient quantity of complete lipopolysaccharide
is synthesized to evoke a protective immune response.
Despite low
levels of lipopolysaccharide synthesis, the cells lyse before
regaining a
virulent
phenotype due to the intracellular build-up of intermediates
during
lipopolysaccharide
synthesis.1,2
Results from clinical studies indicate that adults and
children greater
than 6 years of age
may be protected against typhoid fever following the oral
ingestion of 4
doses of typhoid
vaccine live oral Ty21a. The efficacy of the S. typhi Ty21a
strain has been
evaluated in
a series of randomized, double-blind, controlled field
trials. Suspected
typhoid cases,
detected by passive surveillance, were confirmed
bacteriologically either
bone marrow culture. The first trial was performed in
Alexandria, Egypt with a study population of 32,388 children aged 6 to 7 years.
Three doses of vaccine, in the form of a freshly reconstituted suspension
administered after ingestion of 1 g of bicarbonate, were given on alternate
days. Immunization resulted in a 95% decrease (95% confidence interval (CI) =
77%-99%) in the incidence of typhoid fever over a 3-year period of surveillance.9
A series of field trials were subsequently performed in Santiago, Chile to
evaluate efficacy when the vaccine strain was administered in the form of an acid-resistant
enteric-coated capsule. The initial trial involved 82,543 school-aged children,
and compared 1 or 2 doses of vaccine given one week apart. After 24 months of
surveillance vaccine efficacy was 29% (95% CI = 4%-47%) for the single dose
schedule and 59% (95% CI = 41%-71%) for the 2-dose schedule.10 A further field
trial was performed in Santiago, Chile involving 109,594 school-aged children.
11Three doses of enteric-coated capsules were administered
either on alternate days (short immunization schedule) or 21 days apart (long
immunization schedule). Following 36 months of surveillance vaccination
resulted in a 67% (95% CI = 47%-79%) decrease in the incidence of typhoid fever
in the short immunization schedule group and a 49% reduction (95% CI = 24%-66%)
in the long immunization schedule group.
48 months of surveillance the short immunization schedule
resulted in a 69% (95% CI = 55%-80%) decrease in typhoid fever.12 An
undiminished level of protection was observed during the fifth year of
surveillance. A field trial was next conducted in Santiago, Chile to determine
the relative efficacy of 2, 3 and 4 doses of enteric-coated vaccine
administered on alternate days to school-aged children. Relative vaccine efficacy
as determined by comparison of disease incidence within the three vaccinated groups
was highest for the four dose regimen.13 The incidence of typhoid fever per 105
study subjects was 160.5 (95% CI = 130-191) for the three dose regimen versus
95.8 (95% CI = 71-121) for the four dose regimen (p<0.004). An additional
field trial to determine vaccine efficacy was conducted in Plaju, Indonesia
involving 20,543 individuals approximately 3 to 44 years of age.14 Due to
logistical considerations three doses of enteric-coated capsules were
administered at weekly intervals, a schedule known to provide suboptimal
protection.11 After 30 months of surveillance vaccine efficacy for all age
groups was 42% (95% CI = 23%-57%).
Vaccine organisms can be shed transiently in the stool of
vaccine recipients.16 However, secondary transmission of vaccine organisms has
not been documented. Ty21a has not been
isolated from blood cultures following immunization. At present, the precise
mechanism(s) by which typhoid vaccine live oral Ty21a confers protection against
typhoid fever is unknown. However, it is known that immunization of adult subjects
can elicit a humoral anti-S. typhi LPS antibody response. Taking advantage of this
fact, the seroconversion rate (defined as a
0.15 increase in optical density units over baseline determined in an
ELISA) was compared in an open study between adults living in an endemic area
(Chile) and non-endemic areas (United States and Switzerland) after the
ingestion of 3 doses of vaccine. Comparable seroconversion rates were seen
between these groups.15 S. typhi Ty21a cultured in medium not containing BHI
induced an anti-S. typhi LPS antibody response comparable to that obtained with
vaccine organisms cultured in medium containing BHI15. Challenge studies in
North American volunteers have shown that the Ty21a strain is capable of providing
significant protection to an experimental challenge of S. typhi .16 Because of the
very low incidence of typhoid fever in United States citizens, efficacy studies
are not currently feasible in this population. However, the above observations support
the expectation that typhoid vaccine live oral Ty21a will provide protection to
recipients from non-typhoid endemic areas such as the United States.
Typhoid vaccine live oral Ty21a is indicated for
immunization of adults and children greater than 6 years of age against disease
caused by Salmonella typhi. Routine typhoid
vaccination is not recommended in the United States of America. Selective immunization against typhoid fever
is recommended for the following groups:
1) travelers to areas in which there is a recognized risk
of exposure to S. typhi, 2) persons with intimate exposure (e.g. household
contact) to a S. typhi carrier, and 3) microbiology laboratorians who work
frequently with S. typhi .7 There is no evidence to support the use of typhoid
vaccine to control common source outbreaks, disease following natural disasters
or in persons attending rural summer camps.
Not all recipients of typhoid vaccine live oral Ty21a will
be fully protected against typhoid fever. Vaccinated individuals should
continue to take personal precautions against exposure to typhoid organisms.
The vaccine will not afford protection against species of Salmonella other than
Salmonella typhi or other bacteria that cause enteric disease. The vaccine is
not suitable for treatment of acute infections with S. typhi.
Hypersensitivity to any component of the vaccine or the
enteric-coated capsule. The vaccine should not be administered to persons
during an acute febrile illness. Safety of the vaccine has not been
demonstrated in persons deficient in their ability to mount a humoral or
cell-mediated immune response, due to either a congenital or acquired immunodeficient
state including treatment with immunosuppressive or antimitotic drugs.
The vaccine should not be administered to these persons
regardless of benefits.
Typhoid vaccine live oral Ty21a is not to be taken during
an acute gastrointestinal illness. The vaccine should not be administered to
individuals receiving sulfonamides and antibiotics since these agents may be
active against the vaccine strain and prevent a sufficient degree of
multiplication to occur in order to induce a protective immune response.
Postpone taking the vaccine if persistent diarrhea or vomiting is occurring.
Unless a complete immunization schedule is followed, an
optimum immune response may not be achieved. Not all recipients of typhoid
vaccine live oral Ty21a will be fully protected against typhoid fever.
Vaccinated individuals should continue to take personal precautions against
exposure to typhoid organisms, i.e., travelers should take all necessary
precautions to avoid contact or ingestion of potentially contaminated food or water.
Drug-Interactions: Several anti-malaria drugs, such as
mefloquine, chloroquine and proguanil (not approved for use in US) possess
anti-bacterial activity which may interfere with the immunogenicity of typhoid
vaccine live oral Ty21a.17, 18To determine the effect of these anti-malaria
drugs on the humoral IgG or IgA anti-S.
typhi immune response, healthy adult subjects were given mefloquine
(250mg at weekly intervals;
N=30) chloroquine (150mg at weekly intervals; N=30) or
proguanil (200mg daily;
N=30) together with the S. typhi Ty21a vaccine strain.19
Concomitant treatment with mefloquine or chloroquine did not result in a
significant reduction in the serum anti-S.
typhi immune response compared to subjects receiving vaccine strain only
(N=45).
The simultaneous administration of proguanil did effect a
significant decrease in the immune response rate. These findings indicate that
mefloquine and chloroquine can be administered together with typhoid vaccine
live oral Ty21a. Proguanil should be administered only if 10 days or more have
elapsed since the final dose of typhoid vaccine live oral Ty21a was ingested.
The concomitant administration of oral polio vaccine or yellow fever vaccine
does not suppress the immune response elicited by the Ty21a vaccine strain.19
There are no data regarding simultaneous administration of other parenteral
vaccines or immunoglobulins with typhoid vaccine live oral Ty21a.
General: The health care provider should take all
necessary precautions to ensure the safe and effective use of the vaccine.
Patients should be questioned about previous reactions to this or similar
products. The previous immunization history of the patient and current
antibiotic usage should be obtained by the health care provider.
Information for the Patient: It is essential that all 4
doses of vaccine be taken at the prescribed alternate day interval to obtain a
maximal protective immune response.
Vaccine potency is dependent upon storage under
refrigeration [between 2°C and 8°C (35.6°F-46.4°F)]. The vaccine should be
stored under refrigeration at all times. It is essential to replace unused
vaccine in the refrigerator between doses. The vaccine capsule should be
swallowed approximately 1 hour before a meal with a cold or luke-warm
[temperature not to exceed body temperature, e.g., 37°C (98.6°F)] drink.
Care should be taken not to chew the vaccine capsule. The
vaccine capsule should be swallowed as soon after placing in the mouth as
possible.
Not all recipients of typhoid vaccine live oral Ty21a will
be fully protected against typhoid fever. Travelers should take all necessary
precautions to avoid contact or ingestion of potentially contaminated food or
water. Several anti-malaria drugs, such as mefloquine, chloroquine and
proguanil (not approved for use in US) possess anti-bacterial activity which
may interfere with the immunogenicity of typhoid vaccine live oral Ty21a.
Clinical results (see WARNINGS, Drug Interactions) indicate that mefloquine and
chloroquine can be administered together with typhoid vaccine live oral Ty21a.
Proguanil should be administered only if 10 days or more have elapsed since the
final dose of typhoid vaccine live oral Ty21a was ingested. Any serious adverse
reactions related to the administration of the vaccine should be reported to
your health care provider. You may also report an adverse reaction directly to
the Vaccine Adverse Event Reporting System (1-800-822-7967).20 Your health care
provider should inform you of the benefits and risks of the vaccine, the
importance of taking all 4 capsules in the correct schedule, and the importance
of proper storage temperature of the capsules.
Carcinogenesis, Mutagenesis, and Impairment of Fertility:
Long-term studies in animals with typhoid vaccine live oral Ty21a have not been
performed to evaluate carcinogenic potential, mutagenic potential or impairment
of fertility.
Pregnancy Category C: Animal reproduction studies have not
been conducted with typhoid vaccine live oral Ty21a. It is not known whether
typhoid vaccine live oral Ty21a can cause fetal harm when administered to
pregnant women or can affect reproduction capacity. Typhoid vaccine live oral
Ty21a should be given to a pregnant woman only if clearly needed.
Nursing Mothers: There is no data to warrant the use of
this product in nursing mothers. It is not known if typhoid vaccine live oral
Ty21a is excreted in human milk.
Pediatric Use: The safety and efficacy of typhoid vaccine
live oral Ty21a has not been established in children under 6 years of age. This
product is not indicated for use in children under 6 years of age.
More than 1.4 million doses of Ty21a have been administered in
controlled
clinical trials
and more than 150 million doses of typhoid vaccine live oral
Ty21a have been
marketed world-wide. Active surveillance for adverse reactions
of
enteric-coated
capsules was performed in a pilot study21 and in a subgroup of
a large
field trial14
involving a total of 483 individuals receiving three vaccine
doses. The
overall symptom
rates from both studies when vaccinated with capsules were
combined and
shown to be:
abdominal pain (6.4%), nausea (5.8%), headache (4.8%), fever
(3.3%), diarrhea
(2.9%), vomiting (1.5%) and skin rash (1.0%). Only the
incidence of nausea
occurred
at a statistically higher frequency in the vaccinated group as
compared to
the placebo
group.14 Administration of vaccine doses more than 5-fold
higher than the
currently
recommended dose caused only mild reactions in an open study
involving 155
healthy
adult males.16
Post-marketing surveillance has revealed that adverse
reactions are infrequent and mild.17 Adverse reactions reported to the
manufacturer during 1991-1995, during which time over 60 million doses
(capsules) were administered, included: diarrhea (N=45), abdominal pain (N=42),
nausea (N=35), fever (N=34), headache (N=26), skin rash (N=26), vomiting
(N=18), or urticaria in the trunk and/or extremities (N=13). One isolated,
non-fatal anaphylactic shock considered to be an allergic reaction to the vaccine
was reported.
One capsule is to be swallowed approximately 1 hour before
a meal with a cold or luke-warm [temperature not to exceed body temperature,
e.g., 37°C (98.6°F)] drink on alternate days, e.g., days 1, 3, 5 and 7.
Immunization (ingestion of all 4 doses of typhoid vaccine live oral Ty21a)
should be completed at least 1 week prior to potential exposure to S. typhi.
The blister containing the vaccine capsules should be
inspected to ensure that the foil seal and capsules are intact. The vaccine
capsule should not be chewed and should be swallowed as soon after placing in
the mouth as possible. A complete immunization schedule is the ingestion of 4
vaccine capsules as described above.
Re-immunization: The optimum booster schedule for
typhoid vaccine live oral
Ty21a has not been determined. Efficacy has been shown to
persist for at least 5 years.
Further, there is no experience with typhoid vaccine live oral
Ty21a as a
booster in
persons previously immunized with parenteral typhoid vaccine.
It is
recommended that
a re-immunization dose consisting of four vaccine capsules
taken on
alternate days be
given every 5 years under conditions of repeated or continued
exposure to
typhoid
fever.7
1. Germanier R., E. Furer. Isolation and characterisation
of Gal E mutant Ty21a of Salmonella typhr. a candidate strain for a live, oral
typhoid vaccine. J. Infect. Dis.
131: 553-558, 1975.
2. Germanier R., E. Furer. Characteristics of the
attenuated oral vaccine strain S. typhi Ty21a. Develop. Biol. Standard 53: 3-7,
1983.
3. Miller S.I., E.L. Hohmann, D.A. Pegues. Salmonella
(including Salmonella typhi ).
In: Principles and practice of infectious diseases. G.L.
Mandell, J.E.
(ed.) fourth edition, Churchill Livingstone Inc.
2013-2033, 1995. 4. Centers for Disease
Control. Summary of notifiable diseases, United States 1995.
MMWR 44 (Supplement), 1996.
5. Ryan C.A., N.T. Hargrett-Bean, P.A. Blake. Salmonella
typhi infections in the United States, 1975-1984: Increasing role of foreign
travel. Rev. Infect.
Dis. 11: 1-8,
1989.
6. Taylor D.N., R.A. Pollard, P.A. Blake. Typhoid in the
United States and the Risk to the International Traveler. J. Infect. Dis. 148:
599-602, 1983. 7. Recommendations of
the Advisory Committee on Immunization Practices (ACIP):
Typhoid Immunization. MMWR 43 (RR-14), 1994. 8. Ames, W.R., M. Robbins. Age and sex as
factors in the development of the typhoid carrier state, and a model for
estimating carrier prevalence. Am. J. Public Health 33:
221-230, 1943.
9. Wahdan M.H., C. Serie, Y. Cerisier, S. Sallam, R.
Germanier. A controlled field trial of live Salmonella typhi strain Ty21a oral
vaccine against typhoid: three-year results.
J. Infect. Dis. 145: 292-296, 1982.
10. Black R.E., M.M. Levine, C. Ferreccio, M.L. Clements, C.
Lanata, J.
Rooney, R.
Germanier, Chilean Typhoid Committee. Efficacy of one or two
doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a
controlled field trial. Vaccine 8: 81-84, 1990.
11. Levine M.M., C. Ferreccio, R.E. Black, R. Germanier,
Chilean Typhoid Committee. Large-Scale Field Trial of Ty21a Live Oral Typhoid
Vaccine in Enteric-Coated Capsule Formulation. Lancet 1: 1049-1052, 1987. 12. Levine M.M., C. Ferreccio, R.E. Black,
C.O. Tacket, R. Germanier, Chilean Typhoid Committee. Progress in vaccines
against typhoid fever. Rev. Infect.
Dis. 11
(Supplement 3): S552-S567, 1989.
13. Ferreccio C., M.M. Levine, H. Rodriguez, R. Contreras,
Chilean Typhoid Committee. Comparative efficacy of two, three, or four doses of
Ty21a live oral typhoid vaccine in enteric-coated capsules: a field trial in
endemic area. J. Infect. Dis.
159: 766-769, 1989.
14. Simanjuntak C.H., F.P. Paleologo, N.H. Punjabi, R.
Darmowigoto, Soeprawoto, H. Totosudirjo, P. Haryanto, E. Suprijanto, N.D.
Witham, S.L. Hoffman. Oral immunisation against typhoid fever in Indonesia with
Ty21a vaccine. Lancet 338:
1055-1059, 1991.
15. Data on File, Swiss Serum and Vaccine Institute Berne,
Switzerland.
16. Gilman R.H., R.B. Homick, W.E. Woodward, H.L. DuPont,
M.J. Snyder, M.M. Levine, J.P.
Libonati. Evaluation of a UDP-glucose-4-epimeraseless mutant of Salmonella
typhi as a live oral vaccine. J. Infect. Dis. 136: 717-723, 1977. 17. Cryz S.J. Jr., Post-marketing experience
with live oral Ty21a Vaccine.
Lancet;
341: 49-50, 1993. Data on File, Swiss Serum and Vaccine
Institute Berne, Switzerland.
18. Horowitz H., CA. Carbonaro, Inhibition of the
Salmonella typhi oral vaccine strain Ty21a, by mefloquine and chloroquine. J.
Infect. Dis. 166:
1462-1464, 1992.
19. Kollaritsch H., J.U. Que, C. Kunz, G. Wiedermann, C.
Herzog, S.J. Cryz Jr. Safety and
immunogenicity of live oral cholera and typhoid vaccines administered alone or
in combination with anti-malarial drugs, oral polio vaccine or yellow fever
vaccine.
J. Infect. Dis. 175: 871-875, 1997.
20. Vaccine Adverse Event Reporting System - United
States. MMWR 39: 730-733, 1990.
21. Levine M.M., R.E. Black, C. Ferreccio, M.L. Clements, C.
Lanata, J.
Rooney, R.
Gemanier. The efficacy of attenuated Salmonella typhi oral
vaccine strain Ty21a evaluated in controlled field trials. In: Development of
Vaccines and Drugs against Diarrhea. 11th Noble Conference,
Stockholm, 1985, p. 90-101. J. Holmgren, A.
Lindberg and R. Molby (eds.). Studentlitteratur, Lund, Sweden, 1986.
Storage: Vivotif Berna Vaccine is not stable when exposed
to ambient temperatures.
Vivotif Berna Vaccine should therefore be shipped and
stored between 2°C and 8°C (35.6°F-46.4°F). Each package of vaccine shows an
expiration date. This expiration date is valid only if the product has been
maintained at 2°C-8°C (35.6°F-46.4°F).
MD Consult L.L.C.
http://www.mdconsult.com
Bookmark URL: /das/drug/view/1/2405/top