Understanding the impact of Hib conjugate vaccine on transmission, immunity and disease in the United Kingdom

Abstract

A rise in invasive Haemophilus influenzae type b (Hib) infections occurred 8 years after vaccine introduction in the United Kingdom. Aspects of Hib vaccine delivery unique to the United Kingdom have been implicated. The authors developed a fully age-structured deterministic susceptible-infected-resistant-susceptible mathematical model, expressed as a set of partial differential equations, to better understand the causes of declining vaccine effectiveness. We also investigated the consequences of the vaccine's impact on reducing Hib transmission for maintenance of immunity. Our findings emphasized the importance of maintaining high post-immunization antibody titres among age groups at greatest risk of invasive infections. In keeping with UK population-based estimates, low direct efficacy of immunological memory against disease was found, cautioning against over-reliance on evidence of priming alone as a correlate of population protection. The contribution of herd immunity to disease control was reinforced. Possible intervention strategies will be explored in subsequent work.

Haemophilus influenzae serotype B (Hib) seroprevalence in England and Wales in 2009

“…This was subsequently predicted by mathematical modelling of Hib transmission in the UK [25]. In addition, the model did not support a role for natural antibodies derived from other colonising encapsulated bacteria that might cross-react against the Hib capsule and, therefore, serve to boost natural immunity against this organism [17].…”

“…High post-immunisation antibody levels are considered the most important factor in preventing invasive Hib disease both at an individual and at the population level [17]. In England and Wales, Hib disease control is currently excellent [7] and vaccine coverage for both primary Hib immunisation (95-96%) and the 12-month booster (92-94%) remains very high [18].…”

“…This delay is too late to protect against invasive infection following exposure to the pathogen which is thought to occur over a period of a few hours. On the other hand, the mathematical model emphasised the importance of maintaining high post-immunisation antibody titres [17], which would not only protect children against invasive disease but also help reduce carriage acquisition [11,22] and, therefore, transmission to unvaccinated cohorts, particularly adults.…”

“…The validity of these thresholds in unimmunised adults, however, has not been established. It is speculated that natural immunity is acquired following exposure through carriage, for example [17], which is likely to confer much broader protection through development of protective antibodies not only against the polysaccharide capsule (as would occur following vaccination) but also against other Hib surface proteins and antigens. As a consequence, it is possible that individuals may be protected against disease even if they have undetectable anti-PRP antibodies and functional antibody assays to measure bactericidal activity, might be more informative.…”

Avances recientes en inmunización

“…Como exemplo, citamos as recentes epidemias de sarampo e rubéola, que poderiam ter sido evitadas se tivéssemos implantado duas doses da vacina trípli-ce viral há mais tempo no Brasil. Creio que os autores poderiam ter discutido com mais profundidade essa questão, assim como os fatos que motivaram o Reino Unido a adotar a dose de reforço da vacina de Hib em seu calendário em 2006, quando também substituíram as vacinas DPT e OPV por uma vacina combinada contendo IPV e acelular pertussis 4,21 .…”