Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes

S. Ladhani*, P. T. Heath, M. P.E. Slack, P. B. McIntyre, J. Diez-Domingo, J. Campos, R. Dagan, M. E. Ramsay

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100 000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

Original languageEnglish
Pages (from-to)948-954
Number of pages7
JournalClinical Microbiology and Infection
Issue number7
Publication statusPublished - Jul 2010

Bibliographical note

Funding Information:
The European Union Invasive Bacterial Infections Surveillance (EU-IBIS) Network was funded by EU Biomedicine and Health Research Programme II Reference BMH4960984 (1996–1999) and EU DG SANCO Agreement No. VS/1999/3504 99CVF4-031 (1999–2001). The funding bodies did not have any involvement in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. S. L. was awarded a 2-year Fellowship by the European Society for Paediatric Infectious Diseases (ESPID) to study Hib vaccine failure in children. S.L., P.T.H., J.D. and M.P.S. have received assistance from vaccine manufacturers to attend scientific meetings. P.T.H., J.D. and R.D. are also investigators for clinical trials conducted on behalf of their respective institutions, which were sponsored by vaccine manufacturers, including manufacturers of Hib vaccines. R.D. has provided scientific consultancy for several pharmaceutical companies, including manufacturers of Hib vaccines. All the other authors declare that they have no conflicts of interest.


  • Conjugate vaccine
  • Haemophilus influenzae b (Hib)
  • Underlying diseases
  • Vaccine failure


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