Canada Communicable Disease Report
Volume 29 ACS-5
1 September 2003

An Advisory Committee Statement (ACS) 
National Advisory Committee on Immunization (NACI)*^†

PREVENTION OF PERTUSSIS IN ADOLESCENTS
AND ADULTS

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Preamble

The National Advisory Committee on Immunization (NACI) provides Health Canada with ongoing and timely medical, scientific, and public health advice relating to immunization. Health Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge, and is disseminating this document for information purposes. People administering or using the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out here may differ from that set out in the product monograph(s) of the Canadian licensed manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs.

This statement updates the previous pertussis control strategy, in particular coverage of adolescents and adults, to reflect results of the National Consensus Conference on Pertussis that took place in May 2002⁽¹⁾. For infant vaccination, please refer to the 2002 edition of the Canadian Immunization Guide⁽²⁾. 

Background

Pertussis, or whooping cough, results from an acute infection of the respiratory tract by Bordetella pertussis. Its main features are a paroxysmal cough ending in an inspiratory whoop and vomiting. The disease is most frequent in children, and the most serious complications and deaths occur in young infants. One to three deaths occur each year in Canada, particularly in unimmunized and partially immunized infants (e.g. one or two doses)⁽³⁾. However, the number of affected adolescents and adults has steadily increased, and the morbidity in these cases is significant^(4,5). 

During the National Consensus Conference on Pertussis in Toronto, May 2002, participants agreed that the goal of pertussis control is to decrease the morbidity and mortality of pertussis across the entire lifespan⁽¹⁾. It was further agreed that protection of adolescents and adults is itself a worthy goal for the benefit of these cohorts. In addition, immunization of adolescents and adults may indirectly protect infants. These goals are endorsed by NACI. 

Until now, the immunization schedule has consisted of a primary series at 2, 4, and 6 months of age, and booster doses at 18 months and 4-6 years. It has long been recognized that protection provided by the whole cell pertussis vaccine waned with time^(6,7). Nevertheless, the use of this vaccine was restricted to children < 7 years of age because the severity of local reactions increased with age. Because of waning immunity, many vaccinated children become susceptible to pertussis in adolescence or adulthood. Pertussis is a frequent cause of cough illness in adolescents and adults^(5,8-14), who are a source of transmission to infants⁽¹⁵⁾. Acellular pertussis vaccine was introduced in Canada in 1997 and has now replaced the previous whole cell vaccine. The adolescent/adult formulation of the acellular vaccine with a lower antigen content is safe, immunogenic and allows a better control of this disease. 

Epidemiology of Pertussis in Canada 

The whole cell fluid pertussis vaccine was introduced in Canada in the late 1940s. It was gradually replaced by the adsorbed whole cell vaccine in the 1980s and by the acellular vaccine in 1997-98 (Table 1). Since the introduction of pertussis vaccination in Canada in the late 1940s, 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 greatly increased since 1990^(16-18). Between 1990 and 2000, the annual number of reported cases has ranged from 2,724 to 10,151, although these figures likely under-represent the true incidence because of incomplete diagnosis and reporting^(16,19,20). The resurgence of pertussis was not due to poor vaccine coverage: coverage has consistently been found to be over 95% for three or more doses^(21-27). The increase was largely attributable to the low efficacy of the combined adsorbed diphtheria-tetanus-pertussis whole cell vaccine used in Canada between 1980 and 1997. Its efficacy has been estimated to be in the range of 20% to 60% in children^(19,21-23). The cohort of children immunized only with this vaccine was poorly protected and constitutes the population that has been most affected since 1990^(17,18).

While children < 10 were the most frequently reported cases, a pattern of steadily increasing age of cases and higher incidence among adolescents and adults have been observed. 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 7.3% in 1988 to 10.3%, 17% and 23% in 1992, 1998 and 2000 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. While the use of a vaccine with a low efficacy may explain the largest part of the increased incidence in younger adolescents in Canada, this is unlikely to explain the increase in older adolescents and adults who did not receive the vaccine (Figure 1). For them, waning of vaccine-induced immunity is the most likely explanation, as evidenced by the increased incidence in adolescents also observed in the United States, France and other countries that used different vaccines^(28-30). 

From active surveillance of pertussis it has been found that 1% to 25% of patients with prolonged cough had B. pertussis infection. In Canada, using a combination of laboratory methods, the Sentinel Health Unit Surveillance System also documented pertussis infection in 9% to 20% of non-improving cough illness of >= 7 days in adolescents and adults⁽⁵⁾. There has been no large-scale assessment of the proportion of susceptible adolescents and adults in Canada, but a reanalysis of the data of three household studies showed that the secondary attack rate ranged between 11% and 18% in household contacts aged 12 to 29 years in households where the reported case was also the primary case. In a placebo-controlled acellular pertussis vaccine clinical trial conducted in the United States and involving 2,781 adults, nine participants from the placebo group developed pertussis in the 2 years of follow-up, for an estimated annual rate of 3 per 1,000 person-years⁽³¹⁾. This result was observed in non-epidemic years and would extrapolate to 60,000 adult cases in Canada annually. 

Despite the large increase in pertussis incidence among adolescents and adults between 1990 and 1998, their hospitalization rates remained low (0.8 and 0.1 per 100,000 population respectively) as compared with rates among children (270, 25 and 5.7 per 100,000 among children < 1 year, 1-4 and 5-9 years respectively)⁽¹⁷⁾. 

Table 1.    Pertussis vaccines used in Canada, by province and territory

*All provinces used Connaught Laboratories (now Aventis Pasteur) fluid vaccine except Quebec, where the fluid vaccine was produced by Institut Armand-Frappier. All adsorbed vaccines were produced by Connaught Laboratories.

Ads:  adsorbed vaccine
Acel: acellular vaccine
FI:    fluid vaccine

Figure 1.  Reported incidence rate of pertussis among adolescents and adults by age: Canada, 1987-2000

Adolescent and Adult Target Population for Protection against Pertussis 

As described earlier, while waning of vaccine-induced protection is a universal phenomenon affecting all adolescents and adults, the Canadian situation is unique because of the presence of a cohort of vulnerable adolescents who were immunized only with the adsorbed whole cell vaccine with a lower protective efficacy⁽¹⁷⁾. 

As the adsorbed whole cell vaccine was introduced between 1980 and 1985, depending on the province/territory, the year of birth of the older children belonging to the affected cohort varies accordingly (Table 1). The youngest were born in 1994-1995, and the acellular vaccine was introduced between 1997 and 1998 throughout Canada. Children born since 1995 should be less vulnerable, as they should have received at least one preschool booster of acellular vaccine. Many children in this cohort have been infected by pertussis during the past decade, and the proportion should be greater in the older ones, given their longer cumulative exposure to pertussis. To best protect this cohort a single dose of acellular pertussis vaccine is recommended. If there is no intervention, Canada should anticipate persistence of high transmission in this cohort. However, mathematical modeling predicts that the overall incidence of pertussis in Canada will be lower in the next decade than it was between 1990 and 2000 because of the better protection in younger children vaccinated with the acellular vaccine⁽¹⁾. 

For children younger than this cohort who were vaccinated with the acellular pertussis vaccine, the risk of becoming vulnerable in adolescence will depend on the duration of the acellular vaccine-induced immunity. This will only be known in a few years with the long-term follow-up of children who received the vaccine. It will then be possible to determine the necessity and optimal timing of subsequent booster dose(s). 

The prevention of pertussis in adults is desirable, and they may be safely and effectively protected by the acellular vaccine. However, the feasibility of a program that would achieve high vaccine coverage has not been demonstrated, and the appropriate interval between booster doses is still unknown. 

Preparations Licensed for Immunization 

Only acellular vaccines made from purified antigens of B. pertussis are available in Canada. Acellular vaccines have been developed to reduce the frequency and severity of both local and systemic adverse reactions associated with whole cell pertussis vaccines. All the currently available acellular vaccines contain pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN). Some also have fimbriae (Fim).

The diphtheria and pertussis antigen content of the combined diphtheria-tetanus-acellular adolescent/adult formulation of this vaccine is lower than the one found in the vaccines used in preschool children. Therefore dTap refers to the adolescent/adult formulation of acellular pertussis vaccine, whereas DTaP refers to the infant formulation. Both are adsorbed on aluminum phosphate. 

Efficacy and Immunogenicity 

In 1995-1996, the results of seven studies of the efficacy of eight DTaP infant vaccines were reported. The studies were not designed to compare the efficacy of the various acellular pertussis vaccines, and they involved different study designs; therefore, few conclusions can be drawn about the relative merits of the various products. All the acellular vaccines were efficacious; most were as effective as or more effective than the whole-cell DTP vaccines included as controls. All acellular pertussis vaccines licensed in Canada have an estimated efficacy of approximately 85%⁽³²⁾. 

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. 

There are limited data about the efficacy of a single dose of adolescent/adult pertussis vaccine given to previously immunized adolescents or adults in the prevention of pertussis infection, disease and transmission. It has been shown that a single dose of vaccine increases pertussis antibody levels far in excess of those observed in Sweden in infants who had received three doses of acellular pertussis vaccine^(33,34). As the efficacy demonstrated in the Swedish trial was 85%, it is reasonable to expect that the protection against severe disease in adolescents and adults would be of the same order. The only study that directly assessed vaccine efficacy in adults found that a single dose of a tri-component acellular pertussis vaccine gave significant protection⁽³¹⁾. The point estimate of vaccine efficacy for the primary case definition was 92%, but as cases were not numerous the confidence interval (32%-99%) was wide. Indirect evidence supporting the protective efficacy of a single dose of DTaP comes from data showing that infants or preschool-aged children previously immunized with the adsorbed whole-cell vaccine had a significantly lower risk of pertussis after acellular than adsorbed whole-cell pertussis vaccine given as a single booster dose⁽³⁵⁾.

Recommended Usage

Adolescents 

All preadolescents and adolescents who have not received a dose of acellular vaccine should receive a single dose of the adolescent/adult formulation of acellular pertussis vaccine. A single campaign to vaccinate the entire cohort is the strategy that would prevent most cases. Ideally, adolescents who have already received their Td booster dose would be given monovalent acellular pertussis vaccine, but this product is not currently marketed in Canada. Alternatively, a dose of the combined dTap can be safely used. Limited data based on adults who received two doses of dTap one month apart showed no increase in adverse reactions⁽³³⁾. At a minimum, dTap should replace Td for the regular adolescent booster dose program. Optimally, the timing of the booster dose should be determined according to local epidemiologic patterns. 

Adults 

For adults who have not previously received a dose of acellular vaccine, it is recommended that a single diphtheria-tetanus (Td) booster dose be replaced by the combined diphtheria-tetanus-acellular pertussis (dTap) vaccine. 

Outbreak Control 

Acellular pertussis vaccine has been used safely for control of pertussis outbreaks in defined populations such as in schools or hospitals, although data supporting its effectiveness for this purpose are lacking. If dTap is considered for people >= 7 years to achieve outbreak control, this should be undertaken with evaluation of its effectiveness.

The role of chemoprophylaxis in the management of contacts is discussed elsewhere⁽¹⁾. 

Schedule and Dosage 

Adolescents and adults should receive a single dose of the combined adolescent/adult formulation of dTap. 

The duration of protection given by that booster dose is not known, and only one dose is currently recommended. NACI will update this recommendation according to the results of long-term follow-up of children immunized with acellular vaccine. 

Route of Administration 

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

Storage Requirements 

Pertussis-containing vaccines should be stored between 2° C 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 containing acellular pertussis may be administered simultaneously with other inactivated or live vaccines but at different sites. Not to do so may result in missed opportunities and lower vaccine coverage. None of the products should be mixed in the same syringe with any other vaccines unless specifically advised in the package insert. 

Adverse Reactions 

In adults, the adverse reaction rate observed with dTap is comparable to that seen with Td (Table 2)⁽³⁴⁾. Local reaction is the most frequent event, with pain occurring in 89%, erythema in 12%, and swelling in 17%. These local reactions are generally mild and transient. By decreasing order of frequency, the systemic adverse events were headache (39%), decreased energy (29%), generalized body ache (20%), nausea (15%), chills (13%), diarrhea (10%), fever (9%), sore and swollen joints (9%), and vomiting (2%). When compared with Td, there is no clinically significant increase in the frequency of adverse events with dTap (Table 2). 

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 (see package insert). 

The presence of a large, local reaction to a previous dose should not be considered a contraindication to continuing the recommended schedule. 

Other Considerations 

The older members of the cohort of children who received the acellular pertussis vaccine for their primary vaccination were born in 1997-1998. To properly determine their need for a booster dose in adolescence, it will be important to actively monitor the duration of their immunity against pertussis over the next several years. Similarly, to formulate a recommendation on the interval between booster doses, research should be conducted to assess the duration of protection afforded by a single booster dose given to adults or to adolescents primed with the whole cell pertussis vaccine. Feasibility research should be done to find effective strategies to obtain high vaccine coverage in adults.

Table 2.    Adverse events reported after immunization with adult formulation tetanus-diphtheria toxoid vaccine alone (Td) or in combination with acellular pertussis vaccine (dTap)⁽³⁴⁾

LEVEL OF EVIDENCE FOR THE RECOMMENDATION 

A single booster dose of dTap should be administered to adolescents and adults in place of the current Td to protect against pertussis (A 1). 

References 

1. Health Canada. National Consensus Conference on Pertussis. CCDR 2003;29S3:1-33. 

2. Health Canada. Canadian immunization guide, 6th ed. Ottawa: Health Canada, 2002. Cat. No. H49-8-2002E. 

3. Halperin SA, Wang EL, Law B et al. Epidemiological features of pertussis in hospitalized patients in Canada, 1991-1997: report of the Immunization Monitoring Program - Active (IMPACT). Clin Infect Dis 1999;28:1238-43. 

4. De Serres G, Shadmani R, Duval B et al. Morbidity of pertussis in adolescents and adults. J Infect Dis 2000;182:174-9. 

5. Senzilet LD, Halperin SA, Spika JS et al. Pertussis is a frequent cause of prolonged cough illness in adults and adolescents. Clin Infect Dis 2001;32:1691-97. 

6. Lambert HP. Epidemiology of a small pertussis outbreak. Public Health Rep 1965;80:365-69. 

7. Jenkinson D. Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study. Brit Med J 1988;296:612-14. 

8. Cromer BA, Goydos J, Hackell J et al. Unrecognized pertussis infection in adolescents. Am J Dis Child 1993;147:575-77. 

9. Mink CM, Sirota NM, Nugent S. Outbreak of pertussis in a fully immunized adolescent an adult population. Arch Pediatr Adolesc Med 1994;148:153-57. 

10. Wirsing von Konig CH, Postels-Multani S, Bock HL, Schmitt HJ. Pertussis in adults: frequency of transmission after household exposure. Lancet 1995;346:1326-29. 

11. Wright SW, Edwards KM, Decker MD, Zeldin MH. Pertussis infection in adults with persistent cough. JAMA 1995;273:1044-46. 

12. Deville JG, Cherry JD, Chirstenson PD et al. Frequency of unrecognized Bordetella pertussis infections in adults. Clin Infect Dis 1995;1:639-42. 

13. Schmitt-Grohé S, Cherry JD, Heininger U et al. Pertussis in German adults. Clin Infect Dis 1995;21:860-66. 

14. Birkebaek NH, Kristiansen M, Seefeldt T et al. Bordetella pertussis and chronic cough in adults. Clin Infect Dis 1999;29:1239-42. 

15. CDC. Transmission of pertussis from adult to infant - Michigan, 1993. MMWR 1995;44:74-76. 

16. Health Canada. Notifiable diseases annual summary 1998. CCDR 2000;26S5:1-151. 

17. Ntezayabo B, De Serres G, Duval B. Pertussis resurgence in Canada largely caused by a cohort effect. Pediatr Infect Dis J 2003;22:22-7. 

18. Skowronski DM, De Serres G, MacDonald D et al. The changing age and seasonal profile of pertussis in Canada. J Infect Dis 2002;185:1448-53. 

19. Halperin SA, Bortolussi R, MacLean D, Chisholm N. Persistence of pertussis in an immunized population: results of the Nova Scotia enhanced pertussis surveillance program. J Pediatr 1989;115:686-93. 

20. Deeks S, De Serres G, Boulianne N et al. Failure of physicians to consider the diagnosis of pertussis in children. Clin Infect Dis 1999;28:840-46. 

21. De Serres G, Boulianne N, Duval B. Field effectiveness of erythromycin prophylaxis to prevent pertussis within families. Ped Infect Dis J 1995;14:969-75. 

22. De Serres G, Boulianne N, Duval B et al. Effectiveness of a whole cell pertussis vaccine in child-care centers and schools. Ped Infect Dis J 1996;15:519-24. 

23. Bentsi-Enchill AD, Halperin SA, Scott J, MacIsaac K, Duclos P. Estimates of the effectiveness of a whole-cell pertussis vaccine from an outbreak in an immunized population. Vaccine 1997;15:301-06. 

24. Health Canada. Childhood vaccination coverage levels in Canada, 1994-1997: progress towards national targets.Update: Vaccine-preventable Diseases 1998;6(1):2-4. 

25. Health Canada. Canadian national report on immunization, 1996. CCDR 1997;23S4:1-50. 

26. Health Canada. Canadian national report on immunization, 1997. Paediatr Child Health 1998;3(suppl B). 

27. Health Canada. Canadian national report on immunization, 1998. Paediatr Child Health 1999;4(suppl C). 

28. Guris D, Strebel PM, Tachdjian R et al. Effectiveness of the pertussis vaccination program as determined by use of the screening method: United States, 1992-1994. J Infect Dis 1997;176:456-63. 

29. Baron S, Njamkepo E, Grimprel E et al. Epidemiology of pertussis in French hospitals in 1993 and 1994: thirty years after a routine use of vaccination. Pediatr Infect Dis J 1998;17:412-18. 

30. Scheil W, Cameron S, Roberts C, Hall R. Pertussis in South Australia 1893 to 1996. Commun Dis Intell 1998;22:76-80. 

31. Ward J, Partridge S, Chang S et al. Acellular pertussis vaccine efficacy and epidemiology of pertussis in adolescents and adults: NIH multicenter adult pertussis trial (APERT). Acellular Pertussis Vaccine Conference, Bethesda, MD, 2000. 

32. National Advisory Committee on Immunization. Statement on pertussis vaccine. CCDR 1997;23(ACS-3):1-16. 

33. Halperin SA, Smith B, Russell M et al. Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults. Pediatr Infect Dis J 2000;19:276-83. 

34. Halperin SA, Smith B, Russell M et al. An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults. Vaccine 2000;18:1312-19. 

35. 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;19:3004-08.

CLARIFICATION

PREVENTION OF PERTUSSIS IN ADOLESCENTS AND ADULTS

Vol 29, ACS-5, 1 September 2003

On page 6, under Recommended Usage, section Adolescents, this statement refers to a published study:

"Alternatively, a dose of the combined dTap can be safely used. Limited data based on adults who received two doses of dTap one month apart showed no increase in adverse reactions⁽³³⁾."

In fact, the referenced study included adults who received one dose of dTap followed one month later by monovalent ap vaccine. Therefore, there are no clinical data describing the safety of two doses of dTap given shortly apart.

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