Typhim Vi

TYPHIM Vi™

Connaught

Salmonella Typhi Vi

Capsular Polysaccharide Vaccine

Active Immunizing Agent

Action and Clinical Pharmacology:

PharmacologyS. typhi is the etiological agent of typhoid fever, an acute, febrile enteric disease transmitted by contaminated water and food. The fatality rate ranges from 16% in untreated cases to less than 1% in those given appropriate antibiotic therapy.

The incidence of typhoid fever has declined steadily in Canada. Approximately 80 cases are reported annually. Most of these infections are contracted abroad, but a small number occur in Canada. Typhoid vaccination is not required for international travel, but it is recommended for travellers to areas where there is a recognized risk of exposure to S. typhi, the organism which causes typhoid fever. S. typhi is prevalent in many countries of Africa, Asia and Central and South America. Vaccination is particularly recommended for travellers who will have prolonged exposure to potentially contaminated food and water in smaller cities and villages, or rural areas off the usual tourist itineraries. However, even travellers who have been vaccinated should use caution in selecting food and water.

An increase in specific serum antibodies is the predominant immune response elicited by injection of capsular polysaccharides. The Vi vaccine confers significant protection against typhoid fever based on the production of measurable antibodies, predominantly of the IgG class. Both the seroconversion rate (4-fold rise in serum antibodies) and the protective efficacy induced by Vi in the Nepalese were similar (about 75%). The results of the immunogenicity and effectiveness studies in Nepal provide evidence that serum antibodies to the Vi antigen confer immunity to typhoid fever.

The protective efficacy against typhoid fever of a single i.m. injection of 25 g of Typhim Vi was assessed in two randomized double-blind controlled trials.

A clinical trial was done in Nepal in a target population, 5 through 44 years of age, in 5 villages. There were 6 907 vaccinated subjects, of whom 6 438 were members of the target population; 3 457 received Vi and 3 450 received the control vaccine. There were 165 children under 5 years of age and 304 adults over 44. The seroconversion rates (4-fold rise in serum antibodies), 76.9% in the 5 to 14 year age group, 79.1% in the 15 to 44 year age group and 62.5% in the over 45 to 55 year age group, were similar to the protective efficacy. This provides evidence that serum antibodies to the Vi antigen confer immunity to typhoid fever.

In a second double blind, controlled efficacy trial conducted in South Africa 11 384 children ages 5 to 16 were immunized with Typhim Vi or a control vaccine, while a total of 23 075 children were followed. A total of 239 cases of blood-culture proven S. typhi infection occurred during the 21-month follow-up period among the 23 075 children participating, (5.9 cases per annum, per 1 000 children). There were 173 cases in the unvaccinated group (n=11 691) (8.5 cases per annum, per 1 000 children), 47 cases in the children immunized with control vaccine (4.7 cases per annum, per 1 000 children), and 19 cases in children immunized with the Vi vaccine (1.9 cases per annum, per 1 000 children). The incidence of typhoid in the Vi immunized children was significantly lower than in the control vaccinated children (p<0.001). Estimates of vaccine efficacy after 21 months ranged from 60% (comparison to control group, all cases from date of immunization) to 81% (comparison to untreated group, all cases after 6 weeks post-immunization). Serology in a random sample of 0.5% of vaccinees showed an increase in anti-Vi antibodies as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly elevated at 6 and 12 months postvaccination. Follow-up for 3 years following immunization showed a Vi vaccine efficacy of 50% in the third year.

Immunogenicity trials performed in Houston, Texas, in a racially mixed adult American population showed seroconversion rates and antibody levels equal to or greater than those seen in South Africa or Nepal. A single dose of Vi capsular polysaccharide vaccine resulted in a 4-fold increase in antibody titre in between 83 and 96%. A 4-fold rise in antibody level occurred by 1 week in 60%, by 2 weeks in 80%, and by 1 month in 93%. A level of 4-fold rises persisted in 33% of 43 persons tested prior to a booster dose at 27 months following immunization, and 50% of 12 persons tested prior to a booster dose at 34 months following immunization. A second dose of Vi given at 27 to 34 months following initial immunization elicited antibody levels similar to those observed following the first dose.

A double blind, controlled safety and immunogenicity trial of Typhim Vi vaccine was performed in 268 Indonesian children. The overall seroconversion rate was 98.7% one month after vaccination. The seroconversion rates for the different age groups were: 100% for 12 to 24 months, 98% for 24 to 60 months and 99% for 60 to 144 months. Although antibody levels to Vi antigen are generally correlated with the protective levels, there are no specific data available to substantiate the efficacy in children 2 to 5 years old. No data are available on booster doses in children.

Indications and Clinical Uses:

Active immunization against exposure to S. typhi the organism which causes typhoid fever.

For active immunization in persons 2 years of age and older in the following situations: travellers to endemic or epidemic areas or where sanitary conditions may be doubtful and where travellers may be exposed to potentially contaminated food and water (see Pharmacology and Warnings); persons with ongoing household or intimate exposure to an S. typhi carrier; laboratory workers who frequently handle cultures of S. typhi.

The optimum interval for booster doses has not been established, but a booster dose every 3 years under condition of repeated or continuous exposure to the S. typhi organism is recommended.

As with any vaccine, vaccination with Typhim Vi vaccine may not result in protection in all individuals. Travellers should take all necessary precautions to avoid contaminated food and water.

No data are available on the response to Typhim Vi in chronic carriers

Contra-Indications:

Patients with a history of hypersensitivity to any component of this vaccine (Vi antigen, isotonic buffer or phenol).

Immunization should be deferred during the course of any acute illness.

Warnings in Clinical States:

It is advisable that vaccinees be warned that immunization is only one preventive measure and that care in selection of food and water is of primary importance. This is of particular concern when the vaccine is administered less than 2 weeks prior to departure as optimum antibody protection may not yet be reached.

If the vaccine is used in persons receiving immunosuppressive therapy or who are otherwise immunocompromised, the expected immune response may not be obtained.

This vaccine will not afford protection against species of Salmonella other than S. typhi or against other bacteria that cause enteric disease.

As with any vaccine, vaccination with Typhim Vi may not protect 100% of susceptible individuals.

Precautions:

General: Epinephrine HCl solution (1:1 000) should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.

Prior to an injection of any vaccine, all known precautions should be taken to prevent adverse reactions. This includes a review of the patient’s history with respect to possible hypersensitivity to the vaccine or any component including phenol or similar vaccines.

Any febrile illness or acute infection likely to be accompanied by fever is reason to delay the use of Typhim Vi.

Special care should be taken to ensure that Typhim Vi vaccine is not injected into a blood vessel.

A separate sterile needle and syringe should be used for each individual patient to prevent transmission of hepatitis or other infectious agents from one person to another. Do not recap needle.

Drug Interactions:

There are no known interactions of Typhim Vi vaccine with drugs or foods.

Typhim Vi vaccine may be administered simultaneously with vaccines against tetanus and inactivated poliomyelitis vaccine or with meningococcus (groups A and C) vaccine at separate sites with separate syringes. Data on simultaneous administration with other vaccines are not available. If any vaccines are administered at the same visit, they must be given at separate sites and with separate syringes.

Pregnancy: Animal reproduction studies have not been conducted with Typhim Vi vaccine. It is also not known whether Typhim Vi vaccine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Typhim Vi should be given to a pregnant women only if clearly needed.

Children: Safety and immunogenicity of Typhim Vi vaccine have been demonstrated in children 2 years of age and older (see Dosage).

Typhim Vi vaccine is not currently recommended for children under 2 years of age.

Adverse Reactions:

Health care providers should report any occurrences temporally related to the administration of the product in accordance with provincial and federal statutory requirements.

Tolerance has been studied in more than 10 000 subjects both in countries of high and low endemicity. The secondary effects are generally minor and transient.

No serious or life-threatening adverse events attributed to Typhim Vi have been reported.

Adults who received a booster dose of Typhim Vi 27 to 34 months following the initial dose were more likely to develop erythema and/or induration (10/55) than those given a first dose (13/182), but the rate of systemic reactions was not increased.

Dosage And Administration:

The immunizing dose is a single injection of 0.5 mL given i.m.

The vaccine should be inspected visually for extraneous particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.

A separate, sterile syringe and needle or a sterile disposable unit should be used for each individual patient to prevent transmission of hepatitis or other infectious agents from one person to another.

The skin at the site of injection first should be cleansed and disinfected. Shake vial before use. Remove plastic tab of flip-off cap. Cleanse top of rubber stopper of the vial with a suitable antiseptic and wipe away all excess before withdrawing vaccine.

For the single dose presentation, shake the prefilled syringe well before administering dose.

Each person who is immunized should be given a permanent personal immunization record. In addition, it is essential that the health care provider also maintain a permanent record of the immunization history of each individual. This office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.

Availability And Storage:

Each single dose (0.5 mL) of sterile, clear, colorless, isotonic buffered solution contains: purified Vi polysaccharide 25 g. Phenol (0.25% w/v) is added as a preservative. Prefilled syringes of 0.5 mL (1 dose) and vials of 10 mL (20 doses). Store between 2 and 8°C. Do not freeze.

TYPHIM Vi™ Connaught Salmonella typhi Vi Capsular Polysaccharide Vaccine Active Immunizing Agent

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