Adverse reactions after any of the conjugate Hib vaccines are uncommon, are typically mild and usually resolve within 12 to 24 h.12 A randomized, blinded, comparative study found only minor differences among the four vaccines in the frequency and duration of adverse reactions.13
All four conjugate Hib vaccines are highly immunogenic in adults and older children. However, they differ markedly in the immune responses they stimulate among infants.13-16
PRP-OMP is unique among the conjugate Hib vaccines in producing substantial antibody rises after the first dose, given at 2 months of age.13 However, there is only a modest further increase in antibody after the second dose (or after a third dose).13 Consequently PRP-OMP is licensed in the United States as a two-dose primary series, whereas PRP-CRM and PRP-T are licensed as a three-dose primary series.
With the near-elimination of invasive Hib disease after widespread use of conjugate Hib vaccines in infancy, the three vaccines have been considered interchangeable for primary as well as booster vaccination.24 However, after Alaska's change in 1996 from use of PRP-OMP to use of a combination product containing PRP-CRM plus diphtheria and tetanus toxoids and whole cell pertussis vaccine, the Centers for Disease Control and Prevention noted a 2- to 4-fold increase in invasive Hib disease (1995, 2 cases; 1996, 6 cases; 1997, 7 cases).25, 26 Subsequent evaluation of oropharyngeal carriage of Hib among native Alaskan children found carriage rates ranging from 5.6% among children ages 1 to 2 years, to 13.6% among those age 5 to 6 years.21 Although the rates of invasive Hib disease remain low the rates of carriage do not, and concern has been raised that these findings may be a result of the change from PRP-OMP to PRP-CRM. If so, use of PRP-OMP (at least for the first dose) might be more prudent in particularly high risk populations.
The conjugate Hib vaccines are associated with few and mild adverse reactions in all age groups. All are highly immunogenic in older children and adults; they show differing immunogenicities when used for primary immunization of infants: PRP-D is of low immunogenicity and is not suitable for infant use except in highly immunized populations with low Hib prevalence; PRP-OMP is immunogenic after only a single dose, but antibody concentrations after completion of the primary series are lower than those obtained with PRP-T and PRP-CRM. The latter two vaccines produce little antibody after the first two injections and may not be the best choice in populations characterized by high attack rates of Hib disease early in infancy, but they produce substantially higher final antibody concentrations than PRP-OMP after completion of the primary series and might be preferable in populations not marked by early, intense Hib activity. The vaccines are acceptably interchangeable during the primary series, and indeed a sequence in which one injection of PRP-OMP is used followed by two of PRP-T or PRP-CRM appears to provide the optimum antibody response.
1. Funkhouser A, Steinhoff M, Ward J. Haemophilus influenzae
disease and immunization in developing countries. Rev Infect Dis 1991;13:S542-54.
2. Bijlmer HA, Van Alphen L, Greenwood BM, et al. The epidemiology of Haemophilus influenzae
meningitis in children under five years of age in Gambia, West Africa. J Infect Dis 1990;161:1210-15.
3. Wright PF. Approaches to prevent acute bacterial meningitis in developing countries. Bull WHO 1989;67:479-86.
4. Munson RS, Kabeer MH, Lenoir AA, Granoff DM. Epidemiology and prospects for prevention of disease due to Haemophilus influenzae
in developing countries. Rev Infect Dis 1989;11(Suppl):S588-97.
5. Fothergill LD, Wright J. Influenzal meningitis: the relation of age incidence to the bactericidal power of blood against the causal organism. J Immunol 1933;24:273-84.
6. Schneerson R, Rodrigues LP, Parke JC Jr, Robbins JB. Immunity to disease caused by Haemophilus influenzae
type b: II. Specificity and some biologic characteristics of "natural," infection-acquired, and immunization-induced antibodies to the capsular polysaccharide of Haemophilus influenzae
type b. J Immunol 1971;107:1081-9.
7. Anderson P, Smith DH, Ingram DL, Wilkins J, Wehrle PF, Howie VM. Antibody of polyribophate of Haemophilus influenzae
type b in infants and children: effect of immunization with polyribophosphate. J Infect Dis 1977;136(Suppl):S57-62.
8. Peltola H, Käyhty H, Virtanen M, et al. Prevention of Haemophilus influenzae
type b bacteremic infections with the capsular polysaccharide vaccine. N Engl J Med 1984;310:1561-6.
9. Schneerson R, Barrera O, Sutton A, Robbins JB. Preparation, characterization, and immunogenicity of Haemophilus influenzae
type b polysaccharide-protein conjugates. J Exp Med 1980;152:361-76.
10. Heath PT. Hib conjugate vaccines: a review of efficacy data. Pediatr Infect Dis J 1998;17(Suppl):S123-9.
11. Ward J, Lieberman JM, Cochi SL. Haemophilus influenzae
vaccines. In: Plotkin SA, Mortimer EA, eds. Vaccines. 2nd ed. Philadelphia: Saunders, 1994:357.
12. Recommendations for use of Haemophilus
b conjugate vaccines and a combined diphtheria, tetanus, pertussis, and Haemophilus
b vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1993;42(RR-13):1-15.
13. Decker MD, Edwards KM, Bradley R, Palmer P. Comparative trial in infants of four conjugate Haemophilus influenzae
type b vaccines. J Pediatr 1992;120:184-9.
14. Granoff DM, Anderson EL, Osterholm MT, et al. Differences in the immunogenicity of three Haemophilus influenzae
type b conjugate vaccines in infants. J Pediatr 1992;121:187-94.
15. Bulkow LR, Wainwright RB, Letson GW, Chang SJ, Ward JI. Comparative immunogenicity of four Haemophilus influenzae
type b conjugate vaccines in Alaska Native infants. Pediatr Infect Dis J 1993;12:484-92.
16. Capeding MR, Nohynek H, Pascual LG, et al. The immunogenicity of three Haemophilus influenzae
type B conjugate vaccines after a primary vaccination series in Philippine infants. Am J Trop Med Hyg 1996;55:516-20.
17. Takala AK, Peltola H, Eskola J. Disappearance of epiglottitis during large-scale vaccination with Haemophilus influenzae
type B conjugate vaccine among children in Finland. Laryngoscope 1994;104(6 Pt 1):731-5.
18. Peltola H. Haemophilus influenzae
type b disease and vaccination in Europe: lessons learned. Pediatr Infect Dis J 1998;17:S134-40.
19. Ward J, Brenneman G, Letson GW, Heyward WL. Limited efficacy of a Haemophilus influenzae
type b conjugate vaccine in Alaska Native infants. N Engl J Med 1990;323:1393-401.
20. Decker MD, Edwards KM, Bradley R, Palmer P. Responses of children to booster immunization with their primary conjugate Haemophilus influenzae
type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. J Pediatr 1993;122:410-13.
21. Anderson EL, Decker MD, Englund JA, et al. Interchangeability of conjugated Haemophilus influenzae
type b vaccines in infants. JAMA 1995;273:849-53.
22. Greenberg DP, Lieberman JM, Marcy SM, et al. Enhanced antibody responses in infants given different sequences of heterogeneous Haemophilus influenzae
type b conjugate vaccines. J Pediatr 1995;126:206-11.
23. Bewley KM, Schwab JG, Ballanco GA, Daum RS. Interchangeability of Haemophilus influenzae
type b vaccines in the primary series: evaluation of a two-dose mixed regimen. Pediatrics 1996;98:898-904.
24. Recommended childhood immunization schedule: United States, 1998. MMWR 1998;47:8-12.
25. Galil K, Singleton R, Levine O, et al. High prevalence of Haemophilus influenzae
type b (Hib) carriage among Alaska natives despite widespread use of Hib conjugate vaccine [Abstract]. Presented at the 35th Annual Meeting of the Infectious Diseases Society of America, San Francisco, September 13 to 16, 1997.
FIRST INTERNATIONAL CONFERENCE ON HAEMOPHILUS INFLUENZAE TYPE b INFECTION IN ASIA
The Editors thank the Association pur l'Aide à la Médicine Préventive, the Foundation Mérieux, and the World Health Organization for supporting publication of these proceedsings, and Jennifer Wells for her editorial assistance.