Increase in invasive Streptococcus pyogenes and Streptococcus pneumoniae infections in England, December 2010 to January 2011.

Increases in invasive Streptococcus pyogenes and S. pneumoniae above the seasonally expected levels are currently being seen in England. Preliminary analyses suggest that the high level of influenza activity seen this winter may be contributing to an increased risk of concurrent invasive bacterial and influenza infections in children and young adults.

Hospitalization in two waves of pandemic influenza A(H1N1) in England.

Uncertainties exist regarding the population risks of hospitalization due to pandemic influenza A(H1N1). Understanding these risks is important for patients, clinicians and policy makers. This study aimed to clarify these uncertainties. A national surveillance system was established for patients hospitalized with laboratory-confirmed pandemic influenza A(H1N1) in England. Information was captured on demographics, pre-existing conditions, treatment and outcomes. The relative risks of hospitalization associated with pre-existing conditions were estimated by combining the captured data with population prevalence estimates. A total of 2416 hospitalizations were reported up to 6 January 2010. Within the population, 4·7 people/100,000 were hospitalized with pandemic influenza A(H1N1). The estimated hospitalization rate of cases showed a U-shaped distribution with age. Chronic kidney disease, chronic neurological disease, chronic respiratory disease and immunosuppression were each associated with a 10- to 20-fold increased risk of hospitalization. Patients who received antiviral medication within 48 h of symptom onset were less likely to be admitted to critical care than those who received them after this time (adjusted odds ratio 0·64, 95% confidence interval 0·44-0·94, P=0·024). In England the risk of hospitalization with pandemic influenza A(H1N1) has been concentrated in the young and those with pre-existing conditions. By quantifying these risks, this study will prove useful in planning for the next winter in the northern and southern hemispheres, and for future pandemics.

Open-label, randomised, parallel-group, multicentre study to evaluate the safety, tolerability and immunogenicity of an AS03(B)/oil-in-water emulsion-adjuvanted (AS03(B)) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children 6 months to 12 years of age.

OBJECTIVE: To evaluate the safety, tolerability and immunogenicity of an AS03(B)/oil-in-water emulsion-adjuvanted (AS03(B)) split-virion versus non-adjuvanted whole-virion H1N1 influenza vaccine in UK children aged 6 months to 12 years. DESIGN: Multicentre, randomised, head-to-head, open-label trial. SETTING: Five UK sites (Oxford, Bristol, Southampton, Exeter and London). PARTICIPANTS: Children aged 6 months to < 13 years, for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures, were eligible for inclusion. INTERVENTIONS: A tocopherol/oil-in-water emulsion-adjuvanted (AS03(B)) egg culture-derived split-virion H1N1 vaccine and a non-adjuvanted cell culture-derived whole-virion vaccine, given as a two-dose schedule, 21 days apart, were compared. Participants were grouped into those aged 6 months to < 3 years (younger group) and 3 years to < 13 years of age (older group) and were randomised by study investigators (1 : 1 ratio) to receive one of the two vaccines. Vaccines were administered by intramuscular injection (deltoid or anterior-lateral thigh, depending on age and muscle bulk). Local reactions and systemic symptoms were collected for 1 week post immunisation, and serum was collected at baseline and after the second dose. To assess safety and tolerability, parents or guardians recorded the following information in diary cards from days 0-7 post vaccination: axillary temperature, injection site reactions, solicited and unsolicited systemic symptoms, and medications. MAIN OUTCOME MEASURE: Comparison between vaccines of the percentage of participants demonstrating seroconversion by microneutralisation assay. RESULTS: Among 937 children receiving vaccine, per-protocol seroconversion rates were higher after the AS03(B)-adjuvanted vaccine than after the whole-virion vaccine (98.2% vs 80.1% in children < 3 years, 99.1% vs 95.9% among those aged 3-12 years), as were severe local reactions (3.6% vs 0.0% in those under 5 years, 7.8% vs 1.1% in those aged 5-12 years), irritability in children < 5 years (46.7% vs 32.0%), and muscle pain in older children (28.9% vs 13.2%). The second dose of the adjuvanted vaccine was more reactogenic than the first, especially for fever > 38.0°C in those under 5 years of age (8.9% vs 22.4%). CONCLUSION: The adjuvanted vaccine, although reactogenic, was more immunogenic, especially in younger children, indicating the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION NUMBER: ISRCTN89141709.

Pandemic Influenza A (H1N1) 2009 and mortality in the United Kingdom: risk factors for death, April 2009 to March 2010.

This paper describes the epidemiology of fatal pandemic influenza A(H1N1) cases in the United Kingdom (UK) since April 2009 and in particular risk factors associated with death. A fatal case was defined as a UK resident who died between 27 April 2009 and 12 March 2010, in whom pandemic influenza A(H1N1) infection was confirmed by laboratory or recorded on death certificate. Case fatality ratios (CFR) were calculated using the estimated cumulative number of clinical cases as the denominator. The relative risk of death was estimated by comparing the population mortality rate in each risk group, with those not in a risk group. Across the UK, 440 fatal cases were identified. In England, fatal cases were mainly seen in young adults (median age 43 years, 85% under 65 years), unlike for seasonal influenza. The majority (77%) of cases for whom data were available (n=308) had underlying risk factors for severe disease. The CFR in those aged 65 years or over was nine per 1,000 (range 3 - 26) compared to 0.4 (range 0.2 to 0.9) for those aged six months to 64 years. In the age group between six month and 64 years, the relative risk for fatal illness for those in a risk group was 18. The population attributable fractions in this age group were highest for chronic neurological disease (24%), immunosuppression (16%) and respiratory disease (15%). The results highlight the importance of early targeted effective intervention programmes.

Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study.

OBJECTIVES: To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United Kingdom. DESIGN: Open label, randomised, parallel group, phase II study. SETTING: Five UK centres (Oxford, Southampton, Bristol, Exeter, and London). PARTICIPANTS: Children aged 6 months to less than 13 years for whom a parent or guardian had provided written informed consent and who were able to comply with study procedures were eligible. Those with laboratory confirmed pandemic H1N1 influenza or clinically diagnosed disease meriting antiviral treatment, allergy to egg or any other vaccine components, or coagulation defects, or who were severely immunocompromised or had recently received blood products were excluded. Children were grouped by age: 6 months-<3 years (younger group) and 3-<13 years (older group). Recruitment was by media advertising and direct mailing. Recruitment visits were attended by 949 participants, of whom 943 were enrolled and 937 included in the per protocol analysis. INTERVENTIONS: Participants were randomised 1:1 to receive AS03(B) (tocopherol based oil in water emulsion) adjuvanted split virion vaccine derived from egg culture or non-adjuvanted whole virion vaccine derived from cell culture. Both were given as two doses 21 days apart. Reactogenicity data were collected for one week after immunisation by diary card. Serum samples were collected at baseline and after the second dose. MAIN OUTCOME MEASURES: Primary reactogenicity end points were frequency and severity of fever, tenderness, swelling, and erythema after vaccination. Immunogenicity was measured by microneutralisation and haemagglutination inhibition assays. The primary immunogenicity objective was a comparison between vaccines of the percentage of participants showing seroconversion by the microneutralisation assay (fourfold rise to a titre of >or=1:40 from before vaccination to three weeks after the second dose). RESULTS: Seroconversion rates were higher after the adjuvanted split virion vaccine than after the whole virion vaccine, most notably in the youngest children (163 of 166 participants with paired serum samples (98.2%, 95% confidence interval 94.8% to 99.6%) v 157 of 196 (80.1%, 73.8% to 85.5%), P<0.001) in children under 3 years and 226 of 228 (99.1%, 96.9% to 99.9%) v 95.9%, 92.4% to 98.1%, P=0.03) in those over 3 years). The adjuvanted split virion vaccine was more reactogenic than the whole virion vaccine, with more frequent systemic reactions and severe local reactions in children aged over 5 years after dose one (13 (7.2%, 3.9% to 12%) v 2 (1.1%, 0.1% to 3.9%), P<0.001) and dose two (15 (8.5%, 4.8% to 13.7%) v 2 (1.1%, 0.1% to 4.1%), P<0.002) and after dose two in those under 5 years (15 (5.9%, 3.3% to 9.6%) v 0 (0.0%, 0% to 1.4%), P<0.001). Dose two of the adjuvanted split virion vaccine was more reactogenic than dose one, especially for fever >or=38 masculineC in those aged under 5 (24 (8.9%, 5.8% to 12.9%) v 57 (22.4%, 17.5% to 28.1%), P<0.001). CONCLUSIONS: In this first direct comparison of an AS03(B) adjuvanted split virion versus whole virion non-adjuvanted H1N1 vaccine, the adjuvanted vaccine, while more reactogenic, was more immunogenic and, importantly, achieved high seroconversion rates in children aged less than 3 years. This indicates the potential for improved immunogenicity of influenza vaccines in this age group. TRIAL REGISTRATION: Clinical trials.gov NCT00980850; ISRCTN89141709.

Assessment of baseline age-specific antibody prevalence and incidence of infection to novel influenza A/H1N1 2009.

OBJECTIVES: The objectives of the H1N1 2009 serological surveillance project were twofold: to document (1) the prevalence of cross-reactive antibodies to H1N1 2009 by age group in the population of England prior to arrival of the pandemic strain virus in the UK and (2) the age-specific incidence of infection by month as the pandemic progressed by measuring increases in the proportion of individuals with antibodies to H1N1 2009 by age. METHODS: Residual aliquots of samples submitted to 16 microbiology laboratories in eight regions in England in defined age groups in 2008 and stored by the Health Protection Agency serological surveillance programme were used to document age-stratified prevalence of antibodies to H1N1 2009 prior to the arrival of the pandemic in the UK. Functional antibodies to the H1N1 2009 virus were measured by haemagglutination inhibition (HI) and microneutralisation (MN) assays. For timely measurement of monthly incidence of infection with H1N1 2009 between August 2009 and April 2010, the microbiology serum collections were supplemented by collection of residual sera from chemical pathology laboratories in England. Monthly seroincidence samples were tested by HI only, apart from the final sera collected post pandemic in 2010, which were also tested by MN. Incidence during the pandemic was estimated from changes in prevalence between time points and also by a likelihood-based method. SETTING: Eight regions of England. PARTICIPANTS: Serum samples from patients accessing health care in England from whom blood samples were taken for unrelated microbiological or chemical pathology testing. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Baseline age-specific prevalence of functional antibodies to the H1NI 2009 virus prior to the arrival of the pandemic; changes in antibody prevalence during the period August 2009 to April 2010. RESULTS: Pre-existing cross-reactive antibodies to H1N1 2009 were detected in the baseline sera and increased with age, particularly in those born before 1950. The prediction of immunological protection derived from the baseline serological analysis was consistent with the lower clinical attack rates in older age groups. The high levels of susceptibility in children < 15 years, together with their mixing within school, resulted in the highest attack rates in this age group. Serological analysis by region confirms that there were geographical differences in timing of major pandemic waves. London had a big first wave among the 5- to 14-year age group, with the rest of the country reducing the gap after the second wave. Cumulative incidence in London remained higher throughout the pandemic in each age group. By the end of the second wave it is estimated that as many as 70% of school-aged children in London had been infected. Taken together, these observations are consistent with observations from previous pandemics in 1918, 1957 and 1968 - that the major impact of influenza pandemics is on younger age groups, with a pattern of morbidity and mortality distinct from seasonal influenza epidemics. CONCLUSIONS: Serological analysis of appropriately structured, age-stratified and geographically representative samples can provide an immense amount of information to set in context other measures of pandemic impact in a population, and provide the most accurate measures of population exposure. National scale seroepidemiology studies require cross-agency coordination, multidisciplinary working, and considerable scientific resource. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the Health Protection Agency.

Trends in incidence of pneumococcal disease before introduction of conjugate vaccine: South West England, 1996-2005.

Introduction of pneumococcal conjugate and polysaccharide vaccines into the United Kingdom's routine immunization programmes is expected to change the epidemiology of invasive pneumococcal disease (IPD). We have documented the epidemiology of IPD in an English region (South West) with high-quality surveillance data before these programmes were established. We analysed data on isolates of Streptococcus pneumoniae from blood and CSF between 1996 and 2005 from microbiology laboratories in the South West that were reported and/or referred for serotyping to the Health Protection Agency Centre for Infections. The mean annual incidence of IPD increased from 11.2/100 000 in 1996 to 13.6/100 000 in 2005 (P<0.04). After adjusting for annual blood-culture sampling rates in hospitals serving the same catchment populations, an increase in annual incidence of IPD was no longer observed (P=1.0). Variation in overall incidence between laboratories could also be explained by variation in blood culture rates. The proportion of disease caused by serotypes 6B, 9V and 14 decreased significantly (P=0.001, P=0.007, and P=0.027 respectively) whereas that caused by serotype 4, 7F and 1 increased (P=0.001, P=0.003, and P<0.001 respectively) between 2000 and 2005. The level of penicillin non-susceptibility and resistance to erythromycin remained stable (2% and 12% respectively). This study provides an important baseline to assess the impact of changing vaccination programmes on the epidemiology of IPD, thus informing future use of pneumococcal vaccines.

Risks of convulsion and aseptic meningitis following measles-mumps-rubella vaccination in the United Kingdom.

Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were withdrawn in the United Kingdom in 1992 following demonstration of an increased risk of aseptic meningitis 15-35 days after vaccination. Following introduction of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom) in 1998, active surveillance of aseptic meningitis and convulsion was established to evaluate the risk associated with the new vaccine. No laboratory-confirmed cases of mumps meningitis were detected among children aged 12-23 months after administration of 1.6 million doses of Priorix (upper 95% confidence limit of risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No cases of aseptic meningitis were detected among children aged 12-23 months, who had received over 99,000 doses of Priorix (upper 95% confidence limit of risk: 1:27,000), in a regional database of hospital-admitted cases. This compares with an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence of convulsion was found in the 6- to 11-day period after receipt of Priorix (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with the known effects of the measles component of MMR vaccine-but not in the 15- to 35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as occurred with Urabe-containing vaccines. This study demonstrates the power of active postmarketing surveillance to identify or exclude events too rare to be detected in prelicensure trials.

Similar long-term vaccine efficacy of two versus three doses of HBV vaccine in early life.

WHO currently recommends three vaccinations against hepatitis B to provide optimal protection against infection and carriage. However, immunological theory and mathematical modelling suggest that similar protection could be induced with two doses, and trials among adolescents and adults have shown comparable rates for both primary seroprotection and geometric mean titres following vaccination. We determined vaccine efficacy among 60 children who only received two doses of hepatitis B vaccine as infants and among 463 children who had received three doses after 4-7 years of follow-up. Vaccine efficacy among the two-dose group was 86.3% against anti-HBc positivity (infection) and 92.3% against HBsAg positivity (carriage), which was similar to the vaccine efficacy found among the participants who had received three doses. To confirm this comparable vaccine efficacy a randomised controlled non-inferiority trial with long-term follow-up is needed.

Long-term protection against carriage of hepatitis B virus after infant vaccination.

BACKGROUND: Carriage of hepatitis B virus (HBV) is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Infant vaccination has been effective in preventing horizontal transmission during early childhood. It is unknown whether protection is maintained into early adulthood. METHODS: In 1984, early childhood vaccination was introduced in 2 rural Gambian villages. In 2003, serological assessment of 81.5% of 1,350 eligible participants 1-24 years old was done, to determine vaccine efficacy against infection and carriage. RESULTS: Overall vaccine efficacy against infection and carriage was 83.4% (95% confidence interval [CI], 79.8%-86.6%) and 96.5% (85% CI, 93.9%-98.9%), respectively. Vaccine efficacy against infection was similar when restricted to primary responders (85.3%), but a significant effect of peak antibody concentration was found. Both vaccine efficacy and levels of hepatitis B surface antibody (anti-HBs) decreased with age, resulting in a vaccine efficacy against infection and carriage among 20-24-year-old participants of 70.9% (95% CI, 60.4%-80.5%) and 91.1% (95% CI, 75.8%-100%), respectively. Fifteen years after vaccination, fewer than half of the vaccinees had detectable anti-HBs. The prevalence of carriage in the unvaccinated population was similar to the prevalence 20 years earlier. CONCLUSIONS: HBV vaccination early during life can provide long-lasting protection against carriage, despite decreasing antibody levels. The role played by subclinical boosting and the necessity of a booster need to be evaluated.

Trends in, and determinants of, HIV testing at genitourinary medicine clinics and general practice in England, 1990-2000.

OBJECTIVES: To describe the trends in and determinants of HIV testing and positivity at genitourinary medicine (GUM) clinics and in general practice (GP) in England between 1990 and 2000. METHODS: Data on all first HIV specimens from GUM and GP clinics and tested at seven sentinel laboratories were related to key demographic, clinical, and behavioural variables. RESULTS: During the observation period, 202 892 eligible first HIV tests were reported. 90% (182 746) of specimens were from GUM clinics, of which 55% were from heterosexuals, 12% from men who have sex with men (MSM), and 3% from injecting drug users (IDU). In contrast, only 3% of GP specimens were from MSM and 13% from IDUs. The total number of first HIV tests increased threefold between 1990 and 2000. Overall, 1.6% of GUM and 0.9% of GP first testers were diagnosed HIV positive. In GUM clinics, HIV positivity was highest among heterosexuals who have lived in Africa (11.7%), MSM (6.9%), and IDUs (2.8%) and lowest among heterosexuals with no other specified risk (0.3%). Consistently lower prevalences were observed in GP settings. HIV positivity among GUM first testers declined in MSM, from 13.6% in 1990 to 5.2% in 2000 (p<0.01), and in IDUs, from 7.5% in 1990 to 2.0% in 2000 (p = 0.03). Prevalence remained constant in the groups heterosexually exposed to HIV infection. CONCLUSIONS: HIV testing in GUM settings increased over the decade, with a concomitant reduction in HIV positivity among MSM and IDUs. Increased testing among heterosexual first testers overall was not associated with declining positivity.

Bacterial infections, immune overload, and MMR vaccine. Measles, mumps, and rubella.

Combined measles, mumps, and rubella (MMR) vaccine did not increase the risk of hospitalisation with invasive bacterial infection in the three months after vaccination; rather there was a protective effect. These results provide no support for the concept of "immunological overload" induced by multiple antigen vaccinations, nor calls for single antigen vaccines.

Recall bias, MMR, and autism.

Parents of autistic children with regressive symptoms who were diagnosed after the publicity alleging a link with measles, mumps, and rubella (MMR) vaccine tended to recall the onset as shortly after MMR more often than parents of similar children who were diagnosed prior to the publicity. This is consistent with the recall bias expected under such circumstances.

Immunogenicity and reactogenicity of acellular diphtheria/tetanus/pertussis vaccines given as a pre-school booster: effect of simultaneous administration of MMR.

Four acellular diphtheria/tetanus/pertussis (aDTP) vaccines were compared with two diphtheria/tetanus (DT) vaccines given as a pre-school booster to 1033 children aged 4 to < 6 years who had completed primary immunisation with DTP vaccine according to the UK 2, 3 and 4 month schedule; 71 children had received aDTP vaccine and the remaining 962 a whole cell DTP vaccine for primary immunisation. The effect of simultaneous administration of a second dose of MMR vaccine was evaluated in 374 (37%). Overall, there was little difference in the frequency of post-vaccination symptoms in DT and aDTP vaccinees, although local reactions occurred more quickly in the aDTP group. The concomitant administration of MMR had no effect on local reactions or fever within 10 days, or on the proportions requiring a doctor's visit in the 4--6 week post-vaccination period. Local reactions > or = 3 cm were higher on day 2 in children who had received aDTP for primary immunisation (erythema 32.4% vs. 17.4% for wDTP, P = 0.0012; swelling 28.2% vs. 15.5%, P = 0.0027). Pertussis antibody responses were consistent with the antigen content of the aDTP vaccines. All were more immunogenic with respect to PT -- the only pertussis antigen which by itself has been shown to be protective in clinical trials -- than a wDTP pre-school booster given in an earlier trial. MMR vaccine had no significant effect on antibody responses to either the pertussis or diphtheria and tetanus antigens. Diphtheria antibody responses in children who had received wDTP for primary immunisation were 2.8 times higher than in those who had received aDTP vaccine (P < 0.0001); they were also higher in children who had received a single dose of a Haemophilus influenzae type b vaccine containing CRM(197) conjugate after 12 months of age. For countries currently using DT vaccines as a pre-school booster, replacement with an aDTP vaccine is unlikely to have a perceptible effect on reactogenicity, at least in children given wDTP for primary immunisation, and would boost antibody levels to antigens known to be associated with protection.

Idiopathic thrombocytopenic purpura and MMR vaccine.

A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.

Invasive pneumococcal disease in England and Wales: vaccination implications.

Knowledge of the epidemiology of invasive pneumococcal disease (IPD) will aid in planning the use of pneumococcal vaccines. A United Kingdom (UK)-based surveillance in England and Wales (1995-1997) of 11,528 individuals with IPD and a local enhanced surveillance in the Oxford (UK) area (1995-1999) have been analyzed. IPD has a high attack rate in children, with 37.1-48.1 cases per 100,000 infants <1 year old per year, and in older persons, with 21.2-36.2 cases per 100,000 persons >65 years old per year, for England, Wales, and Oxford. The 7-valent conjugate vaccine includes serotypes causing < or =79% of IPD in children <5 years old, but only 66% in adults >65 years old. The data also indicate that IPD varies by serotype, age, and country, emphasizing that the epidemiology of IPD is heterogeneous and requires continued surveillance.

Does oral polio vaccine cause intussusception in infants? Evidence from a sequence of three self-controlled cases series studies in the United Kingdom.

BACKGROUND: The use of live oral poliomyelitis vaccine (OPV) has led to the elimination of poliomyelitis disease in many countries since licensure in 1960. The discovery of an increased risk of an intestinal obstruction known as intussusception following live rotavirus vaccination raised questions about the possibility of a link between live OPV and intussusception. METHODS: Three self-controlled case-series studies were carried out. The first was exploratory and included 218 intussusception episodes from hospital admissions data linked to vaccination records in the Thames region. The two subsequent studies, which used further hospital admissions data and the General Practice Research Database (GPRD) included 107 and 198 episodes respectively and were used to test hypotheses generated in the first study. RESULTS: In the exploratory study risk periods of up to 6 weeks after each dose were examined. The only period with some evidence of an increased risk was the 14-27-day period after the third dose (relative incidence (RI) = 1.97, p = 0.011). The second hospital admissions study and the GPRD study showed no evidence of an increased relative incidence in any putative risk period and did not confirm the increased risk in the 14-27-day period after dose 3 with a combined RI of 1.03. CONCLUSIONS: The sequence of studies does not support the hypothesis that OPV causes intussusception. The increased RI in the first study may be explained as a chance finding due to the number of risk periods examined and highlights the need for caution when looking at many risk periods without an a priori hypothesis.

Epidemiology of invasive and other pneumococcal disease in children in England and Wales 1996-1998.

UNLABELLED: The results of enhanced national surveillance of pneumococcal disease in children < 15 y of age in England and Wales are reported for the period 1996-1998. Of the 1985 cases of laboratory-confirmed invasive disease (annual incidence 6.6 per 100,000 overall and 39.7 per 100,000 in infants < 1 y of age), 485 (24%) were meningitis (annual incidence of 1.6 per 100,000 overall and 15.7 per 100,000 in infants <1 y of age). Fifty-nine deaths in children with invasive disease were identified-3% of the total reports. Thirty-one different serogroups/types were identified, with organisms in the 7-valent conjugate vaccine responsible for 69% of the infections in children < 5 y of age: this rose to 77% and 82%, respectively, for the 9-and 11-valent vaccines. Resistance to penicillin varied from 2.3% to 6.2% in different years, but erythromycin resistance remained constant at 17%. The vast majority of resistant isolates were in vaccine serotype/groups. Computerized hospital admission records for all children < 15 y of age with a discharge diagnosis code indicating probable pneumococcal disease were also analysed for 1997. The annual incidence for cases with a code specifically mentioning S. pneumoniae was 9.9 per 100,000 compared with 71.2 per 100,000 for lobar pneumonia; the mean duration of stay for both was < 1 wk. The incidence of admission for pneumococcal meningitis (1.9 overall and 19.6 for infants < 1 y of age) was similar to that derived from laboratory reports and resulted in an average duration of stay of 2 wk. CONCLUSION: This surveillance has confirmed the substantial burden of morbidity attributable to pneumococcal disease in British children and the potential public health benefits that could be achieved by the use of pneumococcal conjugate vaccines.