Estimated strain coverage of serogroup B meningococcal vaccines: A retrospective study for disease and carrier strains in Greece (2010-2017).

Invasive meningococcal disease (IMD) is associated with high case fatality rates and long-term sequelae among survivors. Meningococci belonging to six serogroups (A, B, C, W, X, and Y) cause nearly all IMD worldwide, with serogroup B meningococci (MenB) the predominant cause in many European countries, including Greece (~80% of all IMD). In the absence of protein-conjugate polysaccharide MenB vaccines, two protein-based vaccines are available to prevent MenB IMD in Greece: 4CMenB (Bexsero™, GlaxoSmithKline), available since 2014; and MenB-FHbp, (Trumenba™, Pfizer), since 2018. This study investigated the potential coverage of MenB vaccines in Greece using 107 MenB specimens, collected from 2010 to 2017 (66 IMD isolates and 41 clinical samples identified solely by non-culture PCR), alongside 6 MenB isolates from a carriage study conducted during 2017-2018. All isolates were characterized by multilocus sequence typing (MLST), PorA, and FetA antigen typing. Whole Genome Sequencing (WGS) was performed on 66 isolates to define the sequences of vaccine components factor H-binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria adhesin A (NadA). The expression of fHbp was investigated with flow cytometric meningococcal antigen surface expression (MEASURE) assay. The fHbp gene was present in-frame in all isolates tested by WGS and in 41 MenB clinical samples. All three variant families of fHbp peptides were present, with subfamily B peptides (variant 1) occurring in 69.2% and subfamily A in 30.8% of the samples respectively. Sixty three of 66 (95.5%) MenB isolates expressed sufficient fHbp to be susceptible to bactericidal killing by MenB-fHbp induced antibodies, highlighting its potential to protect against most IMD in Greece.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data

Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27­0·37]) and 82% at 8 weeks (0·18 [0·14­0·23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. Funding Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

Kinetics of maternally-derived serogroup A, C, Y and W-specific meningococcal immunoglobulin G in Malian women and infants.

A prospective, randomised, controlled observer-blind trial measuring the efficacy and immunogenicity of trivalent influenza vaccine (TIV) and the immunogenicity of quadrivalent meningococcal conjugate vaccine (MCV) in pregnant women and their infants up to 6 months of age was conducted in Mali. Here we reported the immunogenicity of MCV, which was used as a comparator vaccine to TIV, in this population. Third-trimester pregnant Malian women were randomized to receive TIV or MCV. Blood samples were collected from women prior to vaccination, 28 days post-vaccination, at delivery and 3 and 6 months post-delivery and from infants at birth and 3 and 6 months of age. Meningococcal-specific serogroup (Men) A, C, Y and W-specific antibodies were measured by enzyme linked immunosorbent assay in a randomly selected subset of 50 mother-infant pairs where the mother had received MCV. At birth, 94.0% (47/50) of infants had MenA specific IgG levels ≥ 2 µg/mL decreasing to 72.9% and 30.4% at 3 and 6 months of age. For MenC, 81.3% (39/48) of infants had MenC specific IgG levels ≥ 2 µg/mL at birth decreasing to 29.4% and 17.8% at 3 and 6 months of age. For MenY, 89.6% (43/48) of infants had MenY specific IgG levels ≥ 2 µg/mL at birth decreasing to 64.6% and 62.5% at 3 and 6 months of age. For MenW, 89.6% (43/48) of infants had MenW specific IgG levels ≥ 2 µg/ml at birth decreasing to 62.5% and 41.7% at 3 and 6 months of age. Maternal immunization with MCV conveyed protective levels of IgG at birth through to 3 months of age in the majority of infants.

Lower risk of invasive meningococcal disease during pregnancy: national prospective surveillance in England, 2011-2014.

OBJECTIVE: To describe cases of invasive meningococcal disease (IMD) in women of childbearing age and to estimate the disease incidence and relative risk of IMD in pregnant compared with non-pregnant women. DESIGN: Prospective enhanced national surveillance for IMD. SETTING: England. POPULATION: Women of reproductive age (15-44 years) with laboratory-confirmed IMD. METHODS: Public Health England conducts enhanced national surveillance for IMD in England. Laboratory-confirmed cases are followed up with postal questionnaires to general practitioners. All cases confirmed in women of reproductive age from 1 January 2011 to 31 December 2014 were included. MAIN OUTCOME MEASURES: Annual IMD incidence and relative risk of IMD in pregnant compared with non-pregnant women of reproductive age. RESULTS: During the 4-year surveillance period, there were 1502 cases of IMD in females across England; of these, 310 (20.6%) cases were in women of reproductive age, including four women who were pregnant at the time of IMD confirmation (1.3%). Serogroup distribution of IMD cases in women of childbearing age was similar to the overall distribution. The four cases in otherwise healthy pregnant women were confirmed across all trimesters and all survived; one case in the first trimester had a septic miscarriage. The incidence of IMD was lower in pregnant than in non-pregnant women (0.16 compared with 0.76 per 100 000 pregnant and non-pregnant years, respectively), giving a lower risk of IMD in pregnant women (incidence rate ratio, IRR, 0.21; 95% confidence interval, 0.06-0.54). CONCLUSIONS: Pregnant women are nearly five times less likely to develop IMD compared with non-pregnant women, but the infection can be severe. TWEETABLE ABSTRACT: The risk of meningococcal disease is lower in pregnant women compared with non-pregnant women; the infection can occur across all trimesters and can be severe.

Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before, with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial.

Hajj pilgrims are susceptible to several serious infections and are required to receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate or combination vaccines containing tetanus or diphtheria on concurrent or sequential administration. We examined the immune interaction of separate and concomitant administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with 13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian pilgrims before attending Hajj in 2015. We randomly assigned each participant to one of three vaccination schedules. Group 1 received Tdap 3-4 weeks before receiving MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly. Group 3 received MCV4 and PCV13 3-4 weeks before Tdap. Blood samples were collected at baseline, at each vaccination visit and 3-4 weeks after vaccination and tested for response to meningococcal serogroups C, W and Y using a serum bactericidal antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries after each vaccination. A total of 166 participants aged 18-64 (median 42) years were recruited, of whom 160 completed the study. Compared to the other groups, Group 1 (given Tdap first) had significantly lower proportion of subjects achieving a ≥4-fold rise in rSBA for serogroup W. No difference was detected across the three groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric mean titre (GMT) post vaccination. Group 3, which was given MCV4/PCV13 first, had high levels of antibody against diphtheria and tetanus than the other groups, when tested prior to receipt of Tdap; Only the anti-tetanus responses remained significantly higher after Tdap administration. No serious adverse events were reported. In conclusion, when multiple vaccination is required for Hajj pilgrims, administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses, and avoids meningococcal immune interference, in the convenience of a single consultation. However, giving Tdap 3-4 weeks after MCV4/PCV13 has the advantage of an enhanced tetanus toxoid response. The trial is Trials Registry (ANZCTR): ACTRN12613000536763.

Global Meningococcal Initiative: guidelines for diagnosis and confirmation of invasive meningococcal disease.

The Global Meningococcal Initiative (GMI) is an international group of scientists and clinicians with recognized expertise in meningococcal disease including microbiology, immunology, epidemiology, public health and vaccinology. The GMI was established to promote the global prevention of meningococcal disease through education, research and international cooperation. The GMI held its second summit meeting in 2013 to discuss the different aspects of existing meningococcal immunization programmes and surveillance systems. Laboratory confirmation and characterization were identified as essential for informing evidence-based vaccine implementation decisions. The relative merits of different confirmatory methodologies and their applications in different resource settings were a key component of the discussions. This paper summarizes the salient issues discussed, with special emphasis on the recommendations made and any deficiencies that were identified.

The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.

What Would be the Best Schedule for Prevention of Meningococcal Disease in All Ages? The UK Experience.

Meningococcal disease is a major global public health problem, and vaccination is the optimal means of prevention. Meningococcal vaccination programmes have significantly evolved, for example, in the UK, since their introduction in 1999. The UK, the first country to introduce meningococcal serogroup C conjugate (MCC) vaccination, commenced this in 1999 with a primary infant series at 2, 3 and 4 months of age, together with a catch-up campaign of a single dose for children aged 1-18 years. Subsequent changes to the schedule have occurred in response to increasing knowledge about how MCC vaccines work, together with improved knowledge of meningococcal transmission. Firstly, in 2006, the schedule was refined from a three-dose to a two-dose priming schedule with the addition of a booster in the second year of life. This was followed by a further change in 2013, when the number of priming doses was further reduced to a single priming dose along with a booster maintained at 12 months of age and the introduction of an adolescent MCC booster dose. This in 2015 was changed from monovalent serogroup C to quadrivalent A, C, W and Y in response to an outbreak of serogroup W.

The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults.

Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients.

Interactions of conjugate vaccines and co-administered vaccines.

Conjugate vaccines play an important role in the prevention of infectious diseases such as those caused by the bacteria Haemophilus influenzae (Hi) type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae. Vaccines developed against these 3 pathogens utilize 3 main carrier proteins, non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Current pediatric immunisation schedules include the administration of several vaccines simultaneously, therefore increasing the potential for immune interference (both positively and negatively) to the antigens administered. Knowledge of vaccine interactions is principally derived from clinical trials, these are reviewed here to explore immune interference which may result of from carrier-specific T-cell helper interactions, bystander interference and carrier induced epitopic suppression.

Variations in Neisseria meningitidis carriage by socioeconomic status: a cross-sectional study.

BACKGROUND: Deprivation is associated with an increased risk of invasive Neisseria meningitidis disease, but little is known about the relationship between deprivation and asymptomatic carriage of N. meningitidis. This analysis was conducted to examine the relationship between meningococcal carriage and deprivation. METHODS: As part of a rapid meningococcal carriage prevalence study conducted in West Cumbria to investigate an apparent cluster of invasive meningococcal disease, data were collected on lifestyle and social factors, including area-level indicators of socioeconomic status, to identify factors associated with meningococcal carriage. RESULTS: In a multivariable log binomial regression model adjusted for age, lower socioeconomic status was significantly associated with higher prevalence of meningococcal carriage. A 1-unit increase in Index of Multiple Deprivation (2010) score was associated with a 1.7% increase in meningococcal carriage prevalence (95% confidence interval 0.3-3.0%). Age was the only significant predictor of carriage of Neisseria lactamica. CONCLUSIONS: Living in a deprived area is associated with increased carriage of Group B meningococcus. Deprivation is an important factor to consider in the evaluation of the effectiveness and cost-effectiveness of the introduction of new meningococcal B vaccines and the development and implementation of immunization policies. Further work is required to understand whether deprivation has an effect on meningococcal carriage through other factors such as smoking.

Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015.

Since the epidemiological year 2009/10, the United Kingdom has experienced a year-on-year increase in meningococcal group W (MenW) disease due to rapid expansion of a single endemic hyper-virulent strain belonging to sequence type 11 clonal complex (cc). This strain was identified among cases diagnosed across all regions and was not linked to travel abroad. Consequently, an adolescent MenACWY conjugate vaccination programme for 13-18 year-olds will be introduced in August 2015, with priority given to 17-18 year-olds (school leavers).

Serum bactericidal antibody assays - The role of complement in infection and immunity.

Complement is an essential component of the immune system and human pathogenic organisms have developed various mechanisms for evading complement mediated serum killing. The "gold standard" for measuring the ability of vaccine-induced antibody to kill Neisseria meningitidis is the serum bactericidal antibody (SBA) assay which measures complement mediated killing via antibody. This assay requires active complement, either intrinsic from the serum being tested or the addition of exogenous complement, either from a human or from another species such as rabbit. For serogroup C, an SBA titre of ≥4 was established as the correlate of protection when using human complement and ≥8 as the threshold when using rabbit complement, based on comparative assay results. Licensure of meningococcal vaccines, including polysaccharide protein conjugate vaccines and serogroup B vaccines has been based on the immune responses measured with the SBA assay, thus on a surrogate of vaccine efficacy. This review examines the use of complement and the SBA assay to assess immunity to meningococcal infection, and provides examples of vaccine trials in different age groups where various assays have been used.

Streptococcus pneumoniae serotype 1 burden in the African meningitis belt: exploration of functionality in specific antibodies.

Streptococcus pneumoniae serotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3 S. pneumoniae serotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%, P < 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P < 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

MBL2 deficiency is associated with higher genomic bacterial loads during meningococcemia in young children.

Mannose binding lectin (MBL2) is a soluble pattern recognition receptor that is key to generating innate immune responses to invasive infection, including against the cardinal Gram-negative bacterium Neisseria meningitidis. Individuals homozygous or heterozygous for any of three variant alleles of MBL2 (O/O or A/O genotypes) have deficient concentrations of MBL2 in circulating blood, but previous studies linking MBL deficiency to susceptibility to meningococcal disease have not revealed a consistent association. We genotyped 741 patients with microbiologically-proven meningococcal disease and correlated MBL2 genotype with plasma bacterial load of N. meningitidis with blood samples taken during hospital admission. We show that individuals with genotypes compatible with MBL2 deficiency have higher measurable levels of bacterial plasma genomic load with the greatest effect seen in children <2 years of age. However, the overall impact of this is minor, because there was no evidence that such genotypes are more common in children with meningococcal disease compared with uninfected cohorts. The findings suggest that MBL2 supports innate immune defence against meningococcal disease in the early months of life, before acquired immunity is sufficiently robust for effective natural protection.

Post-acute serum eosinophil and neutrophil-associated cytokine/chemokine profile can distinguish between patients with neuromyelitis optica and multiple sclerosis; and identifies potential pathophysiological mechanisms - a pilot study.

Neuromelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system. It is distinguished from multiple sclerosis (MS) by clinical and radiological features and the presence of aquaporin 4 antibodies in approximately 70%. Despite the discovery of these antibodies and the evidence of neutrophils and eosinophils in the CNS parenchyma, the immunopathogenesis of NMO remains poorly understood. Previous studies attempting to assess the role cytokines and chemokines in NMO have primarily been conducted in acute cerebrospinal fluid from East Asian cohorts, have assessed small numbers of mediators in isolation and have not accounted for important confounding factors including antibody status and disease severity. Therefore we conducted a study of a more extensive range of cytokines and associated mediators in post-acute serum from a UK cohort using unsupervised and multivariate analytical techniques to assess the relative concentration of mediators in concert. Our study of 29 patients (aquaporin 4 antibody positive NMO n=19, MS n=10), matched where possible, including for disease severity, has identified and confirmed some key cytokine/chemokine markers in NMO distinct from MS. Our findings shed further light on the importance of specific inflammatory mediators with predominant function in the differentiation, chemotaxis and activity of neutrophils and eosinophils, particularly CCL4, CCL11, granulocyte-colony stimulating factor and myeloperoxidase, and these may represent potential immunomodulatory targets.

Polysaccharide-protein conjugate vaccination induces antibody production but not sustained B-cell memory in the human nasopharyngeal mucosa.

Colonization of the nasopharyngeal mucosa by meningococcus and other polysaccharide (PS)-encapsulated bacteria precedes invasion. PS-conjugate vaccines induce PS-specific B-cell memory (B(MEM)) and also prevent colonization, thus blocking person-to-person transmission, generating herd protection. However, in isolation the B(MEM) are unable to sustain immunity. Furthermore, the duration of herd protection the vaccines induce appears limited. We demonstrate that, despite the persistence of PS-specific B(MEM), the population is not maintained within the nasopharynx. Although booster immunization results in the transient appearance of PS-specific B(MEM) within the mucosa, this reflects the re-circulation of systemic B(MEM) through the site rather than the generation of resident mucosal B(MEM). The induction of sustained PS-specific B(MEM) in the nasopharynx would allow the population to be activated by colonization, thus inhibiting subsequent invasion. It would also be expected to boost local mucosal immunity, thus extending herd protection. Strategies to generate PS-specific B(MEM) in the mucosa warrant further investigation.

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

A national seroprevalence study was performed to determine the prevalence of Haemophilus influenzae type b (Hib) antibodies in England and Wales in 2009, when Hib disease incidence was the lowest ever recorded. A total of 2,693 anonymised residual sera from routine diagnostic testing submitted by participating National Health Service hospital laboratories were tested for Hib anti-polyribosyl-ribitol phosphate (PRP) IgG antibodies using a fluorescent bead assay. Median anti-PRP IgG concentrations were highest in toddlers aged 1­4 years (2.65 µg/ml), followed by children aged 5­9 years (1.95 µg/ml). Antibody concentrations were significantly lower after this age, but were still significantly higher among 10­19 year-olds (0.54 µg/ml) compared with adults aged >20 years (0.16 µg/ ml; p<0.0001). Half of the adults (51%) did not have Hib antibody concentrations ≥0.15 µg/ml, the level considered to confer short-term protection. Thus, the current excellent Hib control appears to be the result of high anti-PRP antibody concentrations in children aged up to 10 years, achieved through the various childhood vaccination campaigns offering booster immunisation. The lack of seroprotection in adults emphasises the importance of maintaining control of the disease and, most probably carriage, in children, therefore raising the question as to whether long-term routine boosting of either pre-school children or adolescents may be required.