Haemophilus influenzae serotype b vaccine failure: what is the significance of antibody levels?

The introduction of Haemophilus influen-zae serotype b (Hib) conjugate vaccine has been a major step in the prevention of meningitis, epiglottitis, and other manifestations of invasive Hib disease. Because these diseases occur mainly in children, vaccination during infancy prevents the vast majority of cases within a few years. The optimal schedule for Hib vaccination is still a matter of debate. In the United Kingdom, one of the first countries to implement Hib conjugate vaccination in the infant immunization program (in 1992), a vaccine scheme of 3 doses at 2, 3, and 4 months of age was initially applied. Together with a catch-up campaign, this caused a dramatic decrease in the incidence of invasive Hib disease. However, starting in 1999, there was an increase in the number of vaccine failures (i.e., cases of invasive Hib disease after receipt of Hib conjugate vaccine). This prompted a booster campaign in 2003 and, eventually , the introduction of a routine booster dose in the second year of life. A number of other countries had implemented such a vaccination scheme (3 doses in the first year of life and a booster in the second year) from the beginning of their Hib immunization programs [1]. In this issue, Ladhani et al [2] report an extensive and conscientious study of the antibody response to the vaccine substance polyribosylribitol phosphate (PRP), the Hib capsule, in children in the United Kingdom several years after these children experienced Hib vaccine failure. From 1992 through 2005, 388 cases occurred; the authors received a completed questionnaire from 67% and analyzed a blood sample from 167 (43%), which was probably a representative sample. The main conclusions of the study are that a significant proportion (57%) of these children have antibody concentrations below the putative long-term protection level (1.0 mg/mL) and that low antibody concentrations (!0.15 mg/mL) are independently associated with the 3 following factors: young age at Hib disease onset, underlying conditions, and surprisingly, a shorter time from Hib disease to follow-up. This last observation warrants further explanation , because normally, antibody concentrations tend to decrease after infection or immunization and would be expected to be lowest in children with a longer time from Hib disease to follow-up. The authors attribute their finding to the fact that the rate of carriage of Hib in children has decreased since the introduction of routine Hib vaccination. Reduced carriage rates mean less contact of the population …