Antibody Persistence After Primary SARS-CoV-2 Infection and Protection Against Future Variants Including Omicron in Adolescents: National, Prospective Cohort Study.

BACKGROUND: Antibodies are a measure of immunity after primary infection, which may help protect against further SARS-CoV-2 infections. They may also provide some cross-protection against SARS-CoV-2 variants. There are limited data on antibody persistence and, especially, cross-reactivity against different SARS-CoV-2 variants after primary infection in children. METHODS: We initiated enhanced surveillance in 18 secondary schools to monitor SARS-CoV-2 infection and transmission in September 2020. Students and Staff provided longitudinal blood samples to test for variant-specific SARS-CoV-2 antibodies using in-house receptor binding domain assays. We recruited 1189 students and 1020 staff; 160 (97 students, 63 staff) were SARS-CoV-2 nucleocapsid-antibody positive at baseline and had sufficient serum for further analysis. RESULTS: Most participants developed sustained antibodies against their infecting [wild-type (WT)] strain as well as cross-reactive antibodies against the Alpha, Beta and Delta variants but at lower titers than WT. Staff had significantly lower antibodies titers against WT as cross-reactive antibodies against the Alpha, Beta and Delta variants than students (all P < 0.01). In participants with sufficient sera, only 2.3% (1/43) students and 17.2% (5/29) staff had cross-reactive antibodies against the Omicron variant; they also had higher antibody titers against WT (3042.5; 95% confidence interval: 769.0-12,036.2) than those who did not have cross-reactive antibodies against the Omicron variant (680.7; 534.2-867.4). CONCLUSIONS: We found very high rates of antibody persistence after primary infection with WT in students and staff. Infection with WT induced cross-reactive antibodies against Alpha, Beta and Delta variants, but not Omicron. Primary infection with WT may not be cross-protective against the Omicron variant.

Emergence of the delta variant and risk of SARS-CoV-2 infection in secondary school students and staff: Prospective surveillance in 18 schools, England.

BACKGROUND: The role of educational settings in SARS-CoV-2 infection and transmission remains controversial. We investigated SARS-CoV-2 infection, seroprevalence, and seroconversion rates in secondary schools during the 2020/21 academic year, which included the emergence of the more transmissible alpha and delta variants, in England. METHODS: The UK Health Security Agency (UKHSA) initiated prospective surveillance in 18 urban English secondary schools. Participants had nasal swabs for SARS-CoV-2 RT-PCR and blood sampling for SARS-CoV-2 nucleoprotein and spike protein antibodies at the start (Round 1: September-October 2020) and end (Round 2: December 2020) of the autumn term, when schools reopened after national lockdown was imposed in January 2021 (Round 3: March-April 2021), and end of the academic year (Round 4: May-July 2021). FINDINGS: We enrolled 2314 participants (1277 students, 1037 staff; one participant had missing data for PCR testing). In-school testing identified 31 PCR-positive participants (20 students, 11 staff). Another 247 confirmed cases (112 students, 135 staff) were identified after linkage with national surveillance data, giving an overall positivity rate of 12.0% (278/2313; staff: 14.1%, 146/1037 vs students: 10.3%, 132/1276; p = 0.006). Trends were similar to national infection data. Nucleoprotein-antibody seroprevalence increased for students and staff between Rounds 1 and 3 but were similar between Rounds 3 and 4, when the delta variant was the dominant circulating strain. Overall, Nucleoprotein-antibody seroconversion was 18.4% (137/744) in staff and 18.8% (146/778) in students, while Spike-antibody seroconversion was higher in staff (72.8%, 525/721) than students (21.3%, 163/764) because of vaccination. INTERPRETATION: SARS-CoV-2 infection rates in secondary schools remained low when community infection rates were low, even as the delta variant was emerging in England. FUNDING: This study was funded by the UK Department of Health and Social Care.

Secondary attack rates in primary and secondary school bubbles following a confirmed case: Active, prospective national surveillance, November to December 2020, England.

BACKGROUND: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. METHODS: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. RESULTS: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. INTERPRETATION: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.

Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection.

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

Antibody persistence and neutralising activity in primary school students and staff: Prospective active surveillance, June to December 2020, England.

BACKGROUND: Prospective, longitudinal SARS-CoV-2 sero-surveillance in schools across England was initiated after the first national lockdown, allowing comparison of child and adult antibody responses over time. METHODS: Prospective active serological surveillance in 46 primary schools in England tested for SARS-CoV-2 antibodies during June, July and December 2020. Samples were tested for nucleocapsid (N) and receptor binding domain (RBD) antibodies, to estimate antibody persistence at least 6 months after infection, and for the correlation of N, RBD and live virus neutralising activity. FINDINGS: In June 2020, 1,344 staff and 835 students were tested. Overall, 11.5% (95%CI: 9.4-13.9) and 11.3% (95%CI: 9.2-13.6; p = 0.88) of students had nucleoprotein and RBD antibodies, compared to 15.6% (95%CI: 13.7-17.6) and 15.3% (95%CI: 13.4-17.3; p = 0.83) of staff. Live virus neutralising activity was detected in 79.8% (n = 71/89) of nucleocapsid and 85.5% (71/83) of RBD antibody positive children. RBD antibodies correlated more strongly with neutralising antibodies (rs=0.7527; p<0.0001) than nucleocapsid antibodies (rs=0.3698; p<0.0001). A median of 24.4 weeks later, 58.2% (107/184) participants had nucleocapsid antibody seroreversion, compared to 20.9% (33/158) for RBD (p<0.001). Similar seroreversion rates were observed between staff and students for nucleocapsid (p = 0.26) and RBD-antibodies (p = 0.43). Nucleocapsid and RBD antibody quantitative results were significantly lower in staff compared to students (p = 0.028 and <0.0001 respectively) at baseline, but not at 24 weeks (p = 0.16 and p = 0.37, respectively). INTERPRETATION: The immune response in children following SARS-CoV-2 infection was robust and sustained (>6 months) but further work is required to understand the extent to which this protects against reinfection.

Emergence of SARS-CoV-2 Alpha (B.1.1.7) variant, infection rates, antibody seroconversion and seroprevalence rates in secondary school students and staff: Active prospective surveillance, December 2020 to March 2021, England.

OBJECTIVES: We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. METHODS: We initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term and at the start of the spring term (March 2021). FINDINGS: In March 2021, 1895 participants (1100 students:795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection from December 2020-March 2021. Nucleoprotein-antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike-antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021, 14.8% (97/656; 95%CI: 12.2-17.7) students and 10.0% (59/590; 95%CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000). INTERPRETATION: By March 2021, a third of secondary school students and staff had evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity.

SARS-CoV-2 infection, antibody positivity and seroconversion rates in staff and students following full reopening of secondary schools in England: A prospective cohort study, September-December 2020.

BACKGROUND: Older children have higher SARS-CoV-2 infection rates than younger children. We investigated SARS-CoV-2 infection, seroprevalence and seroconversion rates in staff and students following the full reopening of all secondary schools in England. METHODS: Public Health England (PHE) invited secondary schools in six regions (East and West London, Hertfordshire, Derbyshire, Manchester and Birmingham) to participate in SARS-CoV-2 surveillance during the 2020/21 academic year. Participants had nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term. Multivariable logistic regression was used to assess independent risk factors for seropositivity and seroconversion. FINDINGS: Eighteen schools in six regions enrolled 2,209 participants, including 1,189 (53.8%) students and 1,020 (46.2%) staff. SARS-CoV-2 infection rates were not significantly different between students and staff in round one (5/948; [0.53%] vs. 2/876 [0.23%]; p = 0.46) or round two (10/948 [1.05%] vs. 7/886 [0.79%]; p = 0.63), and similar to national prevalence. None of four and 7/15 (47%) sequenced strains in rounds 1 and 2 were the highly transmissible SARS-CoV-2 B.1.1.7 variant. In round 1, antibody seropositivity was higher in students than staff (114/893 [12.8%] vs. 79/861 [9.2%]; p = 0.016), but similar in round 2 (117/893 [13.1%] vs.117/872 [13.3%]; p = 0.85), comparable to local community seroprevalence. Between the two rounds, 8.7% (57/652) staff and 6.6% (36/549) students seroconverted (p = 0.16). INTERPRETATION: In secondary schools, SARS-CoV-2 infection, seropositivity and seroconversion rates were similar in staff and students, and comparable to local community rates. Ongoing surveillance will be important for monitoring the impact of new variants in educational settings.

Infection is associated with one in five childhood deaths in England and Wales: analysis of national death registrations data, 2013-15.

OBJECTIVE: To estimate the contribution of infections to childhood deaths in England and Wales over a 3-year period. DESIGN: Retrospective analysis of national electronic death registration data. SETTING: England and Wales. PATIENTS: Children aged 28 days to 15 years who died during 2013-15. MAIN OUTCOME MEASURES: The proportion of children who died of infection compared with total deaths over 3 years; the main pathogens responsible for infection-related deaths in different age groups; comparison with similar data from 2003 to 2005. RESULTS: There were 5088 death registrations recorded in children aged 28 days to <15 years in England and Wales during the three calendar years, 2013-2015 (17.6 deaths/100 000 children annually) compared with 6897 (23.9/100 000) during 2003-05 (incidence rate ratios (IRR) 0.74, 95% CI 0.71 to 0.77). During 2013-15, there were 951 (18.7%, 951/5088) infection-related deaths compared with 1368 (19.8%, 1368/6897) during 2003-05, equivalent to an infection-related mortality rate of 3.3/100 000 compared with 4.8/100 000 during the two periods (IRR 0.69, 95% CI 0.64 to 0.75), respectively. An underlying comorbidity was recorded in 55.0% (523/951) of death registrations during 2013-15 and increased with age. Where recorded, respiratory tract infection was the most commonly reported presentation (374/876, 42.7%) during 2013-15. Central nervous system infections accounted for only 4.8% (42/876). Overall, 63.1% (378/599) of infection-related deaths were associated with a bacterial, 34.2% (205/599) with a viral and 2.5% (15/599) with a fungal infection. CONCLUSIONS: Beyond the neonatal period, all-cause and infection-related childhood mortality rates have declined by 26% and 31%, respectively, over the past decade. However, infection continues to contribute to one in five childhood deaths.

Clinical Characteristics and Risk Factors for Poor Outcome in Infants Less Than 90 Days of Age With Bacterial Meningitis in the United Kingdom and Ireland.

BACKGROUND: To describe the clinical characteristics and risk factors associated with poor outcome in infants <90 days of age with bacterial meningitis. METHODS: Prospective, enhanced, national population-based active surveillance for infants <90 days of age with bacterial meningitis in the United Kingdom and Ireland between July 2010 and July 2011. Infants were identified through the British Paediatric Surveillance Unit, laboratory surveillance and meningitis charities. RESULTS: Clinical details was available for 263 of 298 (88%) infants where a bacterium was identified, 184 (70%) were born at term. Fever was reported in 143 (54%), seizures in 73 (28%), bulging fontanelle in 58 (22%), coma in 15 (6%) and neck stiffness in 7 (3%). Twenty-three (9%) died and 56/240 (23%) of the survivors had serious central nervous system complications at discharge. Temperature instability [odds ratio (OR), 2.99; 95% confidence interval (CI): 1.21-7.41], seizures (OR, 7.06; 95% CI: 2.80-17.81), cerebrospinal fluid protein greater than the median concentration (2275 mg/dL; OR, 2.62; 95% CI: 1.13-6.10) and pneumococcal meningitis (OR, 4.83; 95% CI: 1.33-17.58) were independently associated with serious central nervous system complications while prematurity (OR, 5.84; 95% CI: 2.02-16.85), low birthweight (OR, 8.48; 95% CI: 2.60-27.69), coma at presentation (OR, 31.85; 95% CI: 8.46-119.81) and pneumococcal meningitis (OR, 4.62; 95% CI: 1.19-17.91) were independently associated with death. CONCLUSIONS: The classic features of meningitis were uncommon. The presentation in young infants is often nonspecific, and only half of cases presented with fever. A number of clinical and laboratory factors were associated with poor outcomes; further research is required to determine how knowledge of these risk factors might improve clinical management and outcomes.

Assessment of healthcare delivery in the early management of bacterial meningitis in UK young infants: an observational study.

OBJECTIVE: To define early presenting features of bacterial meningitis in young infants in England and to review the adequacy of individual case management as compared with relevant national guidelines and an expert panel review. DESIGN: Retrospective medical case note review and parental recall using standardised questionnaires. SETTING: England and Wales. PARTICIPANTS: Infants aged <90 days with bacterial meningitis diagnosed between July 2010 and July 2013. RESULTS: Of the 97 cases recruited across England and Wales, 66 (68%) were admitted from home and 31 (32%) were in hospital prior to disease onset. Almost all symptoms reported by parents appeared at the onset of the illness, with very few new symptoms appearing subsequently. Overall, 20/66 (30%) infants were assessed to have received inappropriate prehospital management. The median time from onset of first symptoms to first help was 5 hours (IQR: 2-12) and from triage to receipt of first antibiotic dose was 2.0 hours (IQR: 1.0-3.3), significantly shorter in infants with fever or seizures at presentation compared with those without (1.7 (IQR: 1.0-3.0) vs 4.2 (IQR: 1.8-6.3) hours, p=0.02). Overall, 26 (39%) infants had a poor outcome in terms of death or neurological complication; seizures at presentation was the only significant independent risk factor (OR, 7.9; 95% CI 2.3 to 207.0). For cases in hospital already, the median time from onset to first dose of antibiotics was 2.6 (IQR: 1.3-9.8) hours, and 12/31 (39%) of infants had serious neurological sequelae at hospital discharge. Hearing test was not performed in 23% and when performed delayed by ≥4 weeks in 41%. CONCLUSIONS: In young infants, the non-specific features associated with bacterial meningitis appear to show no progression from onset to admission, whereas there were small but significant differences in the proportion of infants with more specific symptoms at hospital admission compared with at the onset of the illness, highlighting the difficulties in early recognition by parents and healthcare professionals alike. A substantial proportion of infants received inappropriate prehospital and posthospital management. We propose a targeted campaign for education and harmonisation of practice with evidence-based management algorithms.

Meningococcal carriage in adolescents in the United Kingdom to inform timing of an adolescent vaccination strategy.

OBJECTIVES: Recent development of serogroup B meningococcal (MenB) vaccines highlights the importance of pharyngeal carriage data, particularly in adolescents and young adults, to inform implementation strategies. We describe current UK carriage prevalence in this high risk population and compare methods of carriage detection. METHODS: In this multisite study, pharyngeal swabs were collected on 3-4 occasions over 6-12 months, from 1040 school and university students, aged 10-25 years. Meningococcal carriage was detected by standard culture combined with seroagglutination or PCR of cultured isolates, or by direct PCR from swab. The factor H binding protein (fHBP) variants present in meningococcal isolates were determined. RESULTS: Meningococcal serogroups B and Y were most common, with carriage up to 6.5% and 5.5% respectively, increasing throughout adolescence. Identification by seroagglutination was often unreliable, and the sensitivity of direct PCR detection was 66% compared to culture combined with PCR. Of MenB isolates, 89.1% had subfamily A variants of fHBP. The acquisition rate of MenB carriage was estimated at 2.8 per 1000 person-months. CONCLUSIONS: If vaccination is to precede the adolescent rise in MenB carriage, these data suggest it should take place in early adolescence. Studies assessing vaccine impact should use molecular methods to detect carriage.

Incidence of pneumococcal and varicella disease in HIV-infected children and adolescents in the United Kingdom and Ireland, 1996-2011.

BACKGROUND: To define the burden of hospitalization due to 2 vaccine-preventable infections, invasive pneumococcal disease (IPD) and varicella zoster (VZ), among HIV-infected children in the UK and Ireland. METHODS: Analysis of hospitalizations of HIV-infected children <18 years receiving pediatric care and reported to the Collaborative HIV Paediatric Study (CHIPS) between 1996 and 2011. RESULTS: Admissions for IPD and VZ combined accounted for ~5% of all hospital admissions for HIV-infected children each year. When compared with background rates for healthy children, the admission rate ratio for HIV-infected children on combination antiretroviral therapy (cART) was 16.7, 14.8 and 126.7 for IPD, varicella and herpes zoster, respectively, and 156.7, 86.1 and 470, respectively, for HIV-infected children not on cART. Those admitted with IPD or VZ were more likely to have Centers for Disease Control stage B/C at presentation with HIV than those without such admissions (36.8% for IPD, 29.7% for VZ and 22.1% for no IPD or VZ, P = 0.006), and were more likely to subsequently commence cART (94.7%, 91.3% and 80.2% respectively, P = 0.004). CONCLUSIONS: There is a clear increased risk of admission with IPD or VZ in HIV-infected compared with uninfected children, magnified in those who have not yet commenced cART. It is anticipated that the introduction of new guidelines will result in improved vaccine uptake and thereby reduce the burden of IPD and VZ disease. Subsequent evaluation will assess the impact of these guidelines.

Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial.

BACKGROUND: Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds. METHODS: In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850. FINDINGS: Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified. INTERPRETATION: Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented. FUNDING: Novartis Vaccines.

Incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance.

BACKGROUND: Bacterial meningitis remains a major cause of morbidity and mortality in young infants. Understanding the epidemiology and burden of disease is important. METHODS: Prospective, enhanced, national population-based active surveillance was undertaken to determine the incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Ireland. RESULTS: During July 2010-July 2011, 364 cases were identified (annual incidence, 0.38/1000 live births; 95% confidence interval [CI], .35-.42). In England and Wales, the incidence of confirmed neonatal bacterial meningitis was 0.21 (n = 167; 95% CI, .18-.25). A total of 302 bacteria were isolated in 298 (82%) of the cases. The pathogens responsible varied by route of admission, gestation at birth, and age at infection. Group B Streptococcus (GBS) (150/302 [50%]; incidence, 0.16/1000 live births; 95% CI, .13-.18) and Escherichia coli (41/302 [14%]; incidence, 0.04/1000; 95% CI, .03-.06) were responsible for approximately two-thirds of identified bacteria. Pneumococcal (28/302 [9%]) and meningococcal (23/302 [8%]) meningitis were rare in the first month, whereas Listeria meningitis was seen only in the first month of life (11/302 [4%]). In hospitalized preterm infants, the etiology of both early- and late-onset meningitis was more varied. Overall case fatality was 8% (25/329) and was higher for pneumococcal meningitis (5/26 [19%]) than GBS meningitis (7/135 [5%]; P = .04) and for preterm (15/90 [17%]) compared with term (10/235 [4%]; P = .0002) infants. CONCLUSIONS: The incidence of bacterial meningitis in young infants remains unchanged since the 1980s and is associated with significant case fatality. Prevention strategies and guidelines to improve the early management of cases should be prioritized.

The immunogenicity of a novel A (H1N1) vaccine in HIV-infected children.

BACKGROUND: In October 2009, the United Kingdom Department of Health recommended vaccination of high-risk groups, including children with HIV, with a novel, oil-in-water AS03(B) adjuvanted Influenza A (H1N1) vaccine (Pandemrix). There were no published data available regarding the immunogenicity of this vaccine in such children. OBJECTIVES: This study evaluated the immunogenicity of the adjuvanted Influenza A (H1N1) vaccine in HIV-infected children immunised according to national recommendations and assessed the impact of vaccination on individual CD4 counts and HIV viral loads. METHODS: HIV-infected children attending outpatient appointments between 01 November and 31 December 2009 were offered two doses of H1N1 vaccine three weeks apart and a blood test before and 3 weeks after the second dose of vaccine. Serum antibody responses were determined by a haemagglutination inhibition (HAI) assay using standard methods. RESULTS: Of the 39 children recruited for vaccination, 31 (median age 11.2, range 3.0-17.9 years) received both doses of vaccine and provided pre- and post-vaccination blood samples. Eight children (26%) had baseline HAI titres ≥ 1:32. After vaccination, 29 children (94%, 95% CI, 78.6-99.2%) had HAI titres ≥ 1:32 (seroprotection), of whom 27 (87.1%, 95% CI, 70.1-96.4%) had also had a four-fold rise in titres (seroconversion). In the univariate analysis, post-vaccination geometric mean titres (GMTs) were higher among the 21 children receiving highly active anti-retroviral therapy compared with the 10 treatment-naïve children (GMT 406 [95% CI 218-757] vs. 128 [49-336]; P=0.035), but this was no longer statistically significant when adjusted for prevaccine GMTs. There was no significant impact of vaccination on CD4+ T cell count or HIV viral load. CONCLUSION: The AS03(B)-adjuvanted pandemic Influenza A (H1N1) vaccine is highly immunogenic and appears to be safe in HIV-infected children.