Canadian Immunization Guide
Seventh Edition - 2006

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Part 4
Active Immunizing Agents

Pertussis Vaccine

Epidemiology Preparations approved for use in Canada Efficacy and immunogenicity Recommended usage Schedule and dosage Route of administration Booster doses and re-immunization

Serologic testing Storage requirements Simultaneous administration with other vaccines Adverse reactions Contraindications and precautions Selected references

Pertussis (whooping cough) is a highly communicable infection of the respiratory tract caused by Bordetella pertussis. The disease can affect individuals of any age; however, severity is greatest among young infants. One to three deaths occur each year in Canada, particularly in infants too young to have begun their immunization and in partially immunized infants (e.g., one or two doses). The number of affected adolescents and adults has steadily increased, and the morbidity in these cases is not insignificant. The goal of pertussis control is to decrease the morbidity and mortality of pertussis across the entire lifespan. Protection of adolescents and adults is a worthy goal for the benefit of these individuals themselves, notwithstanding the added indirect protection that it may provide to infants.

Pertussis has been partially controlled in Canada through immunization, and during the last 50 years its incidence has decreased by > 90% (see Figure 9), although outbreaks continue to occur.

Since the publication of the 2002 Canadian Immunization Guide, a statement about prevention of pertussis in adolescents and adults has been published, as has information about the interval between administration of vaccines against diphtheria, tetanus and pertussis. Information related to these issues is included in the chapter.

Epidemiology

The whole-cell pertussis vaccine was introduced in Canada in the 1940s. It was replaced by the adsorbed whole-cell vaccine in the 1980s and by acellular vaccine in 1997-98. Since the introduction of pertussis vaccination, the number of reported cases has dropped dramatically, from 160 cases per 100,000 just before the introduction of the vaccine to < 20 cases per 100,000 in the 1980s. The incidence of pertussis in Canada was low during the 1980s but has increased since 1990. Between 1990 and 2004, the annual number of reported cases has ranged from 2,165 to 10,151, although this likely under-represents the true burden because of incomplete diagnosis and reporting. The resurgence of pertussis was likely due to a combination of factors, including the low efficacy of the combined adsorbed diphtheria-tetanus-pertussis whole-cell vaccine used in children in Canada between 1980 and 1997, waning immunity among adolescents and adults, as well as increased physician awareness and improved diagnosis and reporting of pertussis disease. A cohort of children immunized solely with the vaccine used between 1980 and 1997 was poorly protected and constitutes the population that has been most affected by pertussis since 1990. The increasing age of cases parallels that of children belonging to the vulnerable cohort.

The proportion of pertussis cases in adolescents ( ≥ 15 years) and adults increased from 9.6% in 1995 to 16.4%, 21.2%, and 31.3% in 1998, 2001 and 2004 respectively. In addition to a greater incidence, part of this increase may be attributable to better recognition, diagnosis and reporting of pertussis in adolescents and adults, as well as waning immunity. The increased incidence among adolescents has also been observed in the United States, France and other countries. Waning of vaccine-induced protection is a universal phenomenon affecting adolescents and adults worldwide. These persons constitute a major reservoir of the disease and are an important source of transmission to infants.

Pertussis is a common cause of prolonged cough illness in adolescents and adults. Active surveillance for pertussis in Canada using a combination of laboratory methods has documented pertussis infection in 10% to 20% of adolescents and adults with a cough illness lasting 7 days or more without improvement. In a placebo-controlled clinical trial of acellular pertussis vaccine conducted in the United States involving 2,781 adults, nine participants from the placebo group developed pertussis in the 2-year follow-up period for an estimated annual rate of 3 per 1,000 person-years. This result was observed during non-epidemic years and would correspond to 60,000 adult cases in Canada annually.

Preparations approved for use in Canada

This chapter will deal only with vaccines that are currently marketed in Canada

• Adacel^® (tetanus and diphtheria toxoids adsorbed combined with component pertussis vaccine, [Tdap]), Sanofi Pasteur Ltd.
• Pentacel^® (Act-HIB^® [Haemophilus influenzae b conjugate vaccine (tetanus protein conjugate)] reconstituted with Quadracel^®), Sanofi Pasteur Ltd.
• Quadracel^® (component pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine, [DTaP-IPV]), Sanofi Pasteur Ltd.
• Tripacel^® (component pertussis vaccine combined with diphtheria and tetanus toxoids adsorbed [classic formulation and hybrid formulation], [DTaP]), Sanofi Pasteur Ltd.

Only acellular vaccines made from purified antigens of B. pertussis are now available in Canada; whole-cell preparations are no longer in use. Acellular vaccines have decreased the frequency and severity of both local and systemic adverse reactions compared with whole-cell pertussis vaccines. In Canada, there is no monovalent acellular pertussis vaccine. Pertussis vaccine is only available in combined form with other agents such as diphtheria (D) and tetanus (T) toxoids with or without inactivated polio vaccine (IPV) and/or Hib conjugate vaccine (Hib).

There are two formulations of acellular pertussis vaccine, the infant/pediatric formulation (aP) and the adolescent/adult formulation (ap). The latter contains a lower concentration of pertussis antigens than the former. For the combination vaccines, the diphtheria toxoid is also present in a lower concentration in the adolescent/adult formulation compared with the infant/pediatric formulation. Therefore, Tdap refers to the adolescent/adult formulation, whereas DTaP refers to the infant/pediatric formulation. The infant/pediatric formulation is approved for use in children from 2 months of age until their seventh birthday. The adolescent/adult formulation is approved for use in persons aged 11 to 54 years.

For a list of all approved products in Canada, please refer to Table 1 in the General Considerations chapter.

Efficacy and immunogenicity

Immunologic correlates of protection against pertussis are still not well-defined. In general, all of the acellular pertussis combination vaccines currently approved for use have demonstrated good immunogenicity of their component antigens and decreased reactogenicity when compared with the whole-cell products. It is likely that antibodies to the different component antigens all play a role in protection against clinical disease, pertussis toxoid being a major contributor. All acellular pertussis vaccines approved for use in Canada have an estimated efficacy of approximately 85%. In adults, one clinical trial has shown an efficacy of 92% over the 2.5 years following immunization.

The duration of protection afforded by acellular pertussis vaccines is not known, but the data seem to indicate that protection does not decline during the first 4 years of follow-up. Long-term follow-up will continue for several of the cohorts that participated in the efficacy studies and will guide future recommendations.

Recommended usage

Acellular pertussis vaccine is recommended for all children ≥ 2 months of age for whom there are no contraindications. All adolescents should receive a single booster dose of the adolescent/adult formulation. All adults who have not previously received a dose of acellular vaccine should receive a single dose of Tdap. The prevention of pertussis in adults, particularly if they are in regular contact with infants (health care workers, parents and grandparents of young children), is desirable. The infant/pediatric formulation of acellular pertussis should be used in children < 7 years and the adolescent/adult formulation should be used thereafter. In children ≥ 7 years of age who have not had a primary immunization series or for whom the immunization status is unknown (e.g., immigrant children), the adolescent/adult pertussis-containing formulation should be used.

Persons who have had natural pertussis infection should continue to receive pertussis-containing vaccines. This practice is preferred because the duration of protection induced by pertussis infection is unknown (waning may begin as early as 7 years after infection) and because the diagnosis of pertussis can be difficult to confirm, particularly with test results other than positive culture for B. pertussis. There are no data to suggest that administering pertussis vaccines to persons with a history of pertussis is unsafe. As well, continuation of immunization with acellular pertussis vaccine may confer additional benefit to infants < 6 months of age, who often have a suboptimal antibody response to natural pertussis infection.

The primary immunization series should, whenever possible, be completed with the same combination product. However, if the original vaccine is not known or not available, it is recommended that an alternative combination DTaP-IPV/Hib product be used to complete the primary immunization series. The National Advisory Committee on Immunization (NACI) recommends that the DTaP-IPV/Hib and DTaP-IPV combination vaccines currently approved for sale in Canada may be used interchangeably for the 18 month and 4-6 year booster, respectively. Since there is no monovalent acellular pertussis vaccine currently available in Canada, a combination product, Tdap, must be used whenever there is a need for a pertussis booster in adolescents and adults who have recently received Td vaccine. NACI has concluded that there is no evidence of increased risk of severe adverse events for Canadian adolescents after receiving diphtheria and tetanus toxoid-containing vaccines at intervals of < 5 years. In the context of catch-up programs, given the vulnerability of this group to pertussis, the pertussis booster (Tdap) should not be delayed for fear of adverse events related to the diphtheria or tetanus toxoid component. Since the evidence is still limited, post-marketing studies remain a priority.

Outbreak control

Acellular pertussis vaccine has been used safely for the control of pertussis outbreaks in defined populations, such as in schools or hospitals, although data supporting its effectiveness are lacking. If Tdap is considered for people ≥ 7 years to achieve outbreak control, this should be undertaken with evaluation of its effectiveness. Ensuring that all children and adolescents are completely immunized remains the most important preventive measure in maximizing control of pertussis. Establishing that the immunizations of daycare, school and community contacts are up to date should be under-taken by public health authorities.

Contacts

Children exposed to a case should have their immunization status reviewed. If immunization is incomplete and in the absence of contraindications, any necessary doses should be given (see Schedule and Dosage).

The role of chemoprophylaxis in the management of contacts is not discussed here. Readers are referred to the proceedings of the 2002 National Consensus Conference on Pertussis for further information.

Schedule and dosage

Primary immunization against pertussis with the infant/pediatric formulation (aP) consists of three doses given at 2, 4 and 6 months of age. Booster doses with the infant/pediatric formulation (aP) should be administered at 18 months of age and 4 to 6 years of age. A booster dose with the adolescent/adult formulation (ap) should be administered at 14-16 years of age. It is very important that immunization against pertussis begin at 2 months and be completed on time to ensure that the greatest possible protection is provided to young infants, in whom the disease can be very serious.

Children < 7 years of age not immunized in early infancy should receive three doses of the infant/pediatric formulation (aP) with an interval of 2 months between doses, followed by a fourth dose administered 6-12 months after the third. A booster dose of infant/pediatric formulation (aP) should be administered between 4 and 6 years. This dose is unnecessary if the fourth dose was administered after the fourth birthday. A booster dose with the adolescent/adult formulation (ap) should be given at 14-16 years of age.

When more rapid protection is preferred, the first three doses may be administered at intervals of 4 weeks and the fourth dose given as soon as 6 months after the third dose. The dose to be administered is that recommended by the manufacturer.

For children 7 to 17 years of age who have not been immunized, including immigrants with unknown status, three doses of adolescent/adult formulation of acellular pertussis vaccine (Tdap) should be administered using a 3-dose schedule: at 0 months, 2 months and 6-12 months later. Adults ≥ 18 years of age who have not been immunized, including immigrants with unknown status, should receive a single dose of the adolescent/adult formulation (Tdap) and receive two more doses of Td using the appropriate schedule. After 17 years of age, it is considered unnecessary to give three doses of pertussis vaccine as the probability of having been in contact with pertussis is quite high, in Canada and elsewhere in the world. This recommendation is based on expert opinion since there is a lack of available evidence; further research may modify this.

For adults who have not previously received a dose of acellular pertussis vaccine, it is recommended that the diphtheria-tetanus (Td) booster dose be replaced by the combined Tdap vaccine. The duration of protection induced by acellular pertussis vaccine is unknown, and therefore at this time there is no recommendation for more booster doses. Further research may modify this recommendation.

Please refer to the Immunization of Immunocompromised Persons chapter for recommendations on hematopoietic stem cell and solid organ transplant recipients.

Route of administration

All combined acellular pertussis vaccines are adsorbed vaccines and must be given intramuscularly.

Booster doses and re-immunization

The recommendations for booster doses vary with age. See Schedule and Dosage section.

Serologic testing

There is no indication for pre- or post-immunization serology.

Storage requirements

Pertussis-containing vaccines should be stored at a temperature between +2° and +8° C and should not be frozen. As with all adsorbed vaccines, pertussis-containing vaccines that have been frozen should not be used.

Simultaneous administration with other vaccines

Vaccines that combine antigens against multiple diseases enhance immunization compliance by decreasing the necessary number of injections and visits, and therefore should be encouraged. Acellular pertussis vaccines are available in combination with diphtheria and tetanus toxoids, as well as with inactivated polio vaccine and Hib conjugate vaccine.

If necessary or convenient, vaccines containing acellular pertussis may be administered simultaneously with other inactivated and live vaccines at separate sites and with separate syringes. Not to do so is a missed opportunity and is likely to result in under-immunization. None of the products should be mixed in the same syringe with any other vaccines, unless specifically approved and described in the package insert.

Adverse reactions

Serious adverse events are rare following immunization and, in most cases, data are insufficient to determine a causal association.

The rate of reactions to acellular pertussis vaccines is less than that reported with whole-cell preparations. In clinical trials, the incidence rates of local adverse reactions, including tenderness, erythema, swelling and general reactions of fever, irritability and drowsiness, were significantly lower after immunization with acellular than with whole-cell pertussis vaccines. Less common adverse reactions, such as persistent crying and hypotonic-hyporesponsive episodes, were also less frequent after administration of acellular pertussis vaccines and were reported with a frequency similar to that among recipients of vaccines not containing pertussis. Convulsions were unusual and were reported less often after immunization with acellular pertussis vaccines in some of the efficacy studies but not in others.

The size and frequency of local reactions increase with the number of doses administered. These local reactions produce large swelling, but pain is generally limited. The presence of a large, local reaction to a previous dose should not be considered a contraindication to continuing the recommended schedule.

Contraindications and precautions

Pertussis vaccine should not be given to individuals who have had an anaphylactic reaction to a previous dose or to any constituent of the vaccine. Because these events are so rare, it is not known which component of the combined DTaP-IPV-Hib, DTaP-IPV, DTaP or Tdap is responsible for allergic reactions. Therefore, no further doses of any of the vaccine components should be given unless an assessment by an allergist can determine the responsible antigen or other vaccine component. In order to maximize the child's benefit, an assessment should be done rapidly.

Inactivated vaccines and toxoids are usually considered safe for the fetus, but the effect of administration of Tdap on the development of the embryo and the fetus has not been assessed. Maternal antibody might provide passive protection to the infant in early life; however, the effect of interference by passive maternal antibody on the ability of the infant to mount an adequate response to pediatric DTaP during infancy is unknown. Immunization of a pregnant woman may be warranted when the risk of disease outweighs the risk of vaccine both for the mother and the fetus. If this condition is not met, vaccination should be deferred until after delivery. Health care providers who choose to administer Tdap should discuss with the pregnant woman the lack of data confirming the safety and immunogenicity of Tdap in pregnant women, and the potential benefits and possible adverse effect on the infant.

Although a causal association has not been established between tetanus and Guillain-Barré syndrome (GBS), at the present time it is prudent to withhold subsequent vaccinations in children and adults who develop GBS within 8 weeks of a previous tetanus vaccine dose. Those who develop GBS outside this interval or have an alternative cause identified (e.g., Campylobacter jejuni infection) may receive subsequent tetanus vaccinations. As pertussis is given in combination with tetanus vaccine, withholding tetanus would necessitate withholding the pertussis component as well.

Conditions not considered contraindications to pertussis vaccine

Certain other events temporally associated with whole-cell pertussis immunization were at one time considered contraindications or precautions to further pertussis immunization. With the use of acellular vaccine, they are no longer considered contraindications.

• High fever within 48 hours of vaccination, attributed to immunization and not to intercurrent illness, indicates the likelihood of recurrence of fever with subsequent doses. Febrile convulsions may be more likely in a susceptible child who develops high fever. However, there are no long-term sequelae from these convulsions, and pertussis immunization can continue.
• Afebrile convulsions have not been shown to be caused by pertussis vaccine and are not a contraindication to immunization.
• Persistent, inconsolable crying and an unusual, high-pitched cry after pertussis vaccination are not associated with any sequelae and are likely to be pain responses at the site of injection in young infants. These reactions do not preclude further pertussis immunization. Acetaminophen prophylaxis may reduce discomfort with subsequent doses.
• Hypotonic-hyporesponsive episodes are not a contraindication to the use of acellular pertussis vaccine. Because these episodes occur after both DTaP and DT, it is difficult to attribute causation to the pertussis components of DTaP; continued immunization with all antigens is recommended.
• Onset of encephalopathy temporally related to pertussis immunization does not indicate that the vaccine was the cause. Encephalopathy itself, from whatever cause, is not a contraindication to pertussis immunization. For further information see the Immunization of Persons with Neurologic Disorders chapter.

Selected references

David ST, Hemsley C, Pasquali PE et al. Enhanced surveillance for vaccine-associated adverse events: dTap catch-up of high school students in Yukon. Canada Communicable Disease Report 2005;31(11):117-26.

Decker MD, Edwards KM, Steinhoff MC et al. Comparison of 13 acellular pertussis vaccines: adverse reactions. Pediatrics 1995;96(3 Pt 2):557-66.

De Serres G, Shadmani R, Boulianne N et al. Effectiveness of a single dose of acellular pertussis vaccine to prevent pertussis in children primed with pertussis whole cell vaccine. Vaccine 2001;19(20-22):3004-8.

Edwards KM, Decker MD. Acellular pertussis vaccines for infants. New England Journal of Medicine 1996;334(6):391-92.

Edwards KM, Meade BD, Decker MD et al. Comparison of 13 acellular pertussis vaccines: overview and serologic response. Pediatrics 1995;96(3 Pt 2):548-57.

Greco D, Salmaso S, Mastrantonio P et al. A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. New England Journal of Medicine 1996;334(6):341-48.

Gustafsson L, Hallander HO, Olin P et al. A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine. New England Journal of Medicine 1996;334(6):349-55.

Halperin SA, Smith B, Russell M et al. An adult formulation of a five component acellular per tussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults. Pediatric Infectious Disease Journal 2000;19(4):276-83.

Health Canada. National Consensus Conference on Pertussis. Canada Communicable Disease Report 2003;29(S3):1-39.

Mikelova LK, Halperin SA, Scheifele D et al. Predictors of death in infants hospitalized with pertussis : a case-control study of 16 pertussis deaths in Canada. Journal of Pediatrics 2003;143:576-81.

National Advisory Committee on Immunization. Prevention of pertussis in adolescents and adults. Canada Communicable Disease Report 2003;29(ACS-5):1-9.

National Advisory Committee on Immunization. Statement on adult/adolescent formulation of combined acellular pertussis, tetanus, and diphtheria vaccine. Canada Communicable Disease Report 2000;26(ACS-1):1-8.

National Advisory Committee on Immunization. Statement on pertussis vaccine. Canada Communicable Disease Report 1997;23(ACS-3):1-16.

Ntezayabo B, De Serres G, Duval B. Pertussis resurgence in Canada largely caused by a cohort effect. Pediatric Infectious Disease Journal 2003;22(1):22-7.

Schmitt HJ, von Konig CH, Neiss A et al. Efficacy of acellular pertussis vaccine in early childhood after household exposure. Journal of the American Medical Association 1996;275(1):37-41.

Stehr K, Cherry JD, Heininger U et al. A comparative efficacy trial in Germany in infants who received either the Lederle-Takeda acellular pertussis component DTP (DTap) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine. Pediatrics 1998;101(1 Pt 1):1-11.

Trollfors B, Taranger J, Lagergard T et al. A placebo-controlled trial of a pertussis-toxoid vaccine. New England Journal of Medicine 1995;333(16):1045-50.

Ward JI, Cherry JD, Chang S et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. New England Journal of Medicine 2005;353(15):1555-63.

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