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A diphtheria/tetanus/acellular pertussis–Haemophilus influenzae type b vaccine (DTaP–Hib), introduced to the UK in 1999, was associated with poor primary Hib responses1 and a resurgence of Hib disease in the population.2 Consequently, in 2003, the UK Department of Health undertook a campaign to immunise children aged 6 months–4 years with an additional dose of Hib. We have previously shown a significant rise in Hib titres following an additional Hib dose, given before one year, in infants with very low primary responses.3 Here we describe how that response persists.
In our previous studies preterm infants with Hib IgG <1.0 µg/ml following primary immunisations with DTaP–Hib1 received a 4th dose of Hib conjugate before 1 year of age.3 In this new study (LREC approved), 33 subjects from the previous studies were enrolled and blood was taken prior to the catch-up campaign. Mean gestational age at birth was 29.6 weeks (range 25–31.7 weeks). Twenty six had received a booster dose at <1 year of age (mean 0.62 years). Mean age at study was 2.89 years (range 2.25–3.41 years). Hib IgG geometric mean concentrations (GMC) after primary immunisations, 4th dose, and at time of study, and proportions achieving concentrations of 0.15 and 1.0 µg/ml are shown in table 1.
Nineteen subjects had previously had concentrations high enough to allow determination of post-4th dose Hib IgG avidity. Of these, seven had an IgG concentration on re-bleeding in this study sufficient to allow determination of avidity. The GM avidity index post-4th dose was 76.94 (95% CI 52.16 to 113.50), increasing to 138.19 (95% CI 71.70 to 266.33) at time of study (p = 0.10).
Within three years of a 4th Hib dose, Hib IgG levels have fallen significantly and the proportion of infants with detectable Hib IgG is very low. There is evidence of avidity maturation over this time, but this should be interpreted cautiously given the small numbers.
If protection from Hib disease depends on a level of circulating Hib IgG and not simply on immunological memory, then our findings suggest that a single additional dose before 1 year may be insufficient in those with poor primary responses. Indeed, even children who had acceptable responses (>1.0 µg/ml) to primary immunisations had low levels of Hib IgG in this study. It remains imperative that Hib surveillance continues and that the potential need for further Hib doses be kept in mind. In some infants one additional dose may be insufficient.
Competing interests: none declared
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