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Trends in Haemophilus influenzae type b infections in adults in England and Wales: surveillance study
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     1 Immunisation Department, Health Protection Agency Communicable Disease Surveillance Centre, London NW9 5EQ, 2 Statistics, Modelling and Economics Department, Health Protection Agency Communicable Disease Surveillance Centre, 3 Health Protection Agency Specialist and Reference Microbiology Division, Haemophilus Reference Unit, John Radcliffe Hospital, Oxford OX3 9DU

    Correspondence to: M Ramsay mary.ramsay@hpa.org.uk

    Abstract

    Before routine vaccination was introduced, Haemophilus influenzae type b (Hib) was a notable cause of paediatric morbidity in England and Wales, with an annual incidence of invasive infection of about 30 per 100 000 in children under 5 years of age.1 The inclusion of Hib conjugate vaccines in the routine immunisation schedule in October 1992 was associated with a rapid decline in reports of Hib disease. Ten years later, however, infections in children due to this pathogen increased markedly in England and Wales2 despite consistently high coverage in infants.1

    Since 1998 the number of Hib cases in children has almost doubled each year, most of them in children who have been fully immunised according to the United Kingdom's primary vaccination schedule for infants aged 2, 3, and 4 months.2 Contributing factors include lower than anticipated direct protection from infant vaccination,3 wearing off of the initial impact of the "catch up" campaign,4 and the use of less immunogenic, combination vaccines with an acellular pertussis component during 2000-1.5 With the decrease in Hib transmission attributed to use of the conjugate vaccine in the mid-1990s, cases in unimmunised individuals aged 15 years and older also declined,6 presumably as a result of indirect protection or herd immunity. We describe a reduction of this indirect effect of vaccination, as evidenced by a recent increase in invasive Hib infections in adults to prevaccine levels.

    Methods

    After Hib vaccine was introduced in October 1992 the number of cases of invasive Hib disease among adults in England and Wales fell markedly. This phenomenon was attributed to interruption of transmission of the organism from immunised children, or herd immunity.10 A resurgence in adult cases of invasive Hib disease occurred in 2002 and 2003, mirroring trends in paediatric infections over the same period and following a decline in the concentration of serum antibody to Hib in English adults aged 30-39 years. The fall in serum antibody concentrations may have resulted from reduced transmission of the organism, providing fewer opportunities for natural boosting of immunity.

    The data presented here show how difficult it is to ensure consistency of case ascertainment over long periods of time and how important it is to account for this in the analysis. Improved reporting and typing led to an apparent increase in the incidence of invasive ncHi disease,6 11 but more constant numbers in recent years show that ascertainment has been stable since 1995. On the basis of unadjusted data, the number of adult Hib infections in recent years is higher than that observed in 1991. When the enhanced regional surveillance data are used, however, and after adjusting national figures for improved ascertainment, the current incidence in adults is similar to the incidence before the vaccine was introduced.

    We took serum used to measure immunity to Hib in the population from a national serosurvey resource that collects residual sera from participating laboratories.7 These specimens are stored anonymously, with limited linked information. Although it is possible that changes in selection of serum may have produced bias in the results obtained, comparison of a similar collection of sera in Australia showed no major discrepancy in antibody titres to common vaccine antigens with that from a random cluster survey.12

    In contrast to ncHi infection, adults of the ages most likely to mix with children, both as parents and grandparents, seem to be most liable to Hib infections (fig 2). This observation is not surprising, given the high documented rates of parental carriage in families with a child known to be colonised with H influenzae type b or recovering from invasive Hib disease.13-15 It may therefore be predicted that an increase in paediatric Hib infections might be associated with a corresponding rise in adult cases. Of the 11 countries participating in the European Union Invasive Bacterial Infections Surveillance Network (EU-IBIS), only the Netherlands has noted a similar rise in adult Hib cases, from eight reports in 2001 to 15 in 2002,16 the same number observed before the vaccine was introduced in 1993 (source: National Reference Laboratory for Bacterial Meningitis, Netherlands). This increase accompanies an increase in paediatric reports that has been observed despite a vaccine programme that does not use combination vaccines and where a booster is given in the second year of life.17 Although we believe that transmission is most often from child to parent, the reverse may also occur18 and may have contributed to some of the increase in invasive disease observed in children in recent years.

    What is already known on this topic

    Introduction of Hib conjugate vaccines in England and Wales led to a fall in invasive disease in all age groups, including those not eligible for vaccination, through indirect protection or "herd immunity"

    What this study adds

    A recent increase in invasive Hib infections in adults aged 15 years and older in England and Wales is approaching prevaccination levels and is associated with evidence of reduced antibody concentrations in older age groups

    This increase may be due to reduced transmission of the organism and fewer opportunities for natural boosting of immunity by Hib colonisation

    The unanticipated reduction in herd immunity highlights the need for surveillance of vaccine preventable diseases to be conducted across all age groups

    Our data show that the reduction in opportunities for natural boosting of immunity has resulted in a decline in specific Hib antibody titres among adults. Mathematical models of Hib transmission predicted that such a decline may lead to an increase in disease in the older unvaccinated population several years after the vaccine was introduced.19 The clinical presentation of or the case fatality due to Hib disease have not changed, and there is no indication that an increase in the prevalence of underlying conditions that predispose to invasive bacterial infection has contributed to this rise.

    The high quality of surveillance in England and Wales allowed early detection of an increase in paediatric Hib cases, resulting in the withdrawal of poorly immunogenic vaccines and implementation of a national immunisation programme for children younger than 4 years.20 We anticipate that this campaign will rapidly induce herd immunity and prevent any further increase in infections in all age groups. Evaluation of the potential need for change to the routine immunisation schedule is ongoing and needs to include assessments of direct and indirect vaccine effects. Our findings may also be relevant to control of meningococcal and pneumococcal disease, where herd immunity effects in older unvaccinated age groups have also been observed after the conjugate vaccine was given to children.21 22 It will be important to monitor whether such levels of indirect vaccine protection are sustained and this work emphasises the importance of maintaining surveillance of these infections across the entire age spectrum in the longer term.

    We thank all of the microbiologists and clinicians who have reported cases of invasive Hib over the past 10 years. Particular thanks are due to Sue Gurney of the Haemophilus Reference Unit for administrative assistance and Suzanna Stringer for carrying out the laboratory procedures. We also thank LouiseHesketh, Andrew Vyse, and Elizabeth Miller of the HPA seroepidemiology unit for providing the samples for this study. The antibody testing was carried out at HPA Porton Down and we thank Moya Burrage, Lorraine Ransley, Carol Powell, Janet Blake, Jenna Plank, and Annette Crowley-Luke from the immunoassay laboratory. We thank our colleagues at the National Reference Laboratory for Bacterial Meningitis, Netherlands, for allowing us to present their recent Hib incidence figures.

    Contributors: JM, MPES, and MER obtained and analysed disease incidence data. CLT obtained and analysed seroepidemiological data. All authors contributed to study design and preparation of the final manuscript. MER is guarantor.

    Competing interests: MER and MPES have received research grants from vaccine manufacturers. JM was previously employed in an academic research post that was funded by a vaccine manufacturer. MER, MPES, and JM have all received funds from vaccine manufacturers to attend conferences and meetings.

    Funding: The seroepidemiology component of this study was partially funded by the Public Health Laboratory Service Small Scientific Initiatives fund. Surveillance for invasive Hib infections is part of the core work of the Health Protection Agency's Communicable Disease Surveillance Centre and Haemophilus Reference Unit.

    Ethical approval: The Health Protection Agency has approval under Section 60 of the Health and Social Care Act to process confidential information about patients for the purposes of monitoring the efficacy and safety of vaccination programmes.

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