RESUMO
BACKGROUND: We investigated whether COVID-19 vaccination reduced SARS-CoV-2 infection risk among adult household contacts of COVID-19 index cases during the Alpha, Delta, and Omicron waves in England. METHODS: Between February 2021 and February 2022, SARS-CoV-2 RT-PCR nasal swabs were collected from COVID-19-confirmed index cases aged ≥20 years and their household contacts at enrolment and three and seven days thereafter. Generalized Estimating Equations models were fitted with SARS-CoV-2 positivity as the outcome and household contacts' vaccination status as the main exposure while adjusting for confounders. RESULTS: SARS-CoV-2 infection was confirmed in 238/472 household contacts (50.4%) aged ≥20 years. The adjusted relative risk (95% confidence interval) of infection in vaccinated versus unvaccinated household contacts was 0.50 (0.35-0.72) and 0.69 (0.53-0.90) for receipt of two doses 8-90 and >90 days ago, respectively, and 0.34 (0.23-0.50) for vaccination with three doses 8-151 days ago. Primary vaccination protected household contacts against infection during the Alpha and Delta waves, but only three doses protected during the Omicron wave. Vaccination with three doses in the index case independently reduced contacts' infection risk: 0.45 (0.23-0.89). CONCLUSIONS: Vaccination of household contacts reduces their risk of infection under conditions of household exposure though, for Omicron, only after a booster dose.
RESUMO
OBJECTIVES: To measure secondary attack rates (SARs) in prospectively followed household contacts of paediatric and adult cases of SARS-CoV-2 infection in England. METHODS: Self-taken nasal swabs from household contacts of PCR confirmed cases of COVID-19 and blood samples on day 35 were tested for evidence of infection with SARS-CoV-2 virus. RESULTS: The secondary attack rate (SAR) among 431 contacts of 172 symptomatic index cases was 33% (95% confidence intervals [CI] 25-40) and was lower from primary cases without respiratory symptoms, 6% (CI 0-14) vs 37% (CI 29-45), p = 0.030. The SAR from index cases <11 years was 25% (CI 12-38). SARs ranged from 16% (4-28) in contacts <11 years old to 36% (CI 28-45) in contacts aged 19-54 years (p = 0.119). The proportion infected who developed symptoms (78%) was similar by age (p = 0.44) though <19 year olds had fewer mean number of symptoms than adults (p = 0.001) and fewer reported loss of sense of taste or smell (p = 0.0001). CONCLUSIONS: There are high risks of transmission of SARS-CoV-2 virus in the home, including those where infection is introduced by a child. The risk of children acquiring infection was lower than that in adults and fewer developed typical symptoms of Covid-19 infection.
Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Criança , Características da Família , Humanos , Incidência , Estudos ProspectivosRESUMO
BACKGROUND: In April 2010, 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunisation schedule in England and Wales. Despite limited serotype replacement in invasive pneumococcal disease (IPD) during the first four post-PCV13 years, non-vaccine type (NVT) IPD increased substantially in 2014/15. We undertook a carriage study in 2015/16 to help understand the reasons for this increase. METHODS AND FINDINGS: Families with a child aged <5 years attending a participating general practice in Gloucestershire or Hertfordshire were invited to provide nasopharyngeal swabs from all consenting members. Swabs from 650 individuals (293 under five, 73 five to twenty and 284 >twenty years) were cultured and serotyped for Streptococcus pneumoniae. Results were compared with those from three previous household studies conducted in the same populations between 2001 to 2013, and with the serotypes causing IPD to estimate case-carrier ratios (CCRs). Overall carriage prevalence did not differ between the four carriage studies with reductions in vaccine-type carriage offset by increases in NVT carriage. While no individual NVT serotype showed an increase in CCR from 2012/13, the composition of the serotypes comprising the NVT group differed such that the overall CCR of the NVT group had significantly increased since 2012/13. Carriage of two PCV13 serotypes, 3 and 19A, was found in 2015/16 (3/650 = 0.5% and 2/650 = 0.3% respectively) with no overall reduction in carriage prevalence of PCV13-7 serotypes since 2012/13, though 6C prevalence, a vaccine-related serotype, had reduced from 1.8% in 2012/13 to 2/648 (0.3%) in 2015/16, p = 0.013. CONCLUSIONS: There was continuing evolution in carried NVTs six years after PCV13 introduction which, in addition to being vaccine-driven, could also reflect natural secular changes in certain NVTs. This poses challenges in predicting future trends in IPD. Elimination of carriage and disease due to serotypes 3 and 19A may not be achieved by PCV13.
Assuntos
Portador Sadio/microbiologia , Nasofaringe/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Inglaterra/epidemiologia , Características da Família , Feminino , Humanos , Imunização , Masculino , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Prevalência , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: While evidence exists to support the effectiveness of neuraminidase inhibitors (NAIs) in reducing mortality when given to hospitalized patients with A(H1N1)pdm09 virus infection, the impact of outpatient treatment on hospitalization has not been clearly established. We investigated the impact of outpatient NAI treatment on subsequent hospitalization in patients with A(H1N1)pdm09 virus infection. METHODS: We assembled general community and outpatient data from 9 clinical centers in different countries collected between January 2009 and December 2010. We standardized data from each study center to create a pooled dataset and then used mixed-effects logistic regression modeling to determine the effect of NAI treatment on hospitalization. We adjusted for NAI treatment propensity and preadmission antibiotic use, including "study center" as a random intercept to account for differences in baseline hospitalization rate between centers. RESULTS: We included 3376 patients with influenza A(H1N1)pdm09, of whom 3085 (91.4%) had laboratory-confirmed infection. Eight hundred seventy-three patients (25.8%) received outpatient or community-based NAI treatment, 928 of 2395 (38.8%) with available data had dyspnea or respiratory distress, and hospitalizations occurred in 1705 (50.5%). After adjustment for preadmission antibiotics and NAI treatment propensity, preadmission NAI treatment was associated with decreased odds of hospital admission compared to no NAI treatment (adjusted odds ratio, 0.24; 95% confidence interval, 0.20-0.30). CONCLUSIONS: In a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalization, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission. These data suggest that community patients with severe influenza should receive NAI treatment.
Assuntos
Antivirais/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Neuraminidase/antagonistas & inibidores , Adolescente , Adulto , Idoso , Assistência Ambulatorial , Antibacterianos/uso terapêutico , Antivirais/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Feminino , Hospitalização , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pacientes Ambulatoriais , Análise de Regressão , Fatores de Risco , Adulto JovemRESUMO
Extensive limb swelling (ESL) after a booster dose of acellular pertussis (aP) containing vaccine can cause concern and has the potential to be confused with cellulitis. In the United Kingdom aP-containing vaccine was introduced for primary immunisation at 2, 3 and 4months of age in 2004, with the first cohorts eligible to receive a fourth dose in 2007 at school entry. We assessed the frequency of ESL (here defined as swelling >100mms diameter) in 973 children receiving a fourth dose of one of four aP vaccines given combined with inactivated polio, tetanus and either low dose diphtheria (TdaP/IPV) or high dose diphtheria (DTaP/IPV) vaccine; 2 of the 3 DTaP/IPV vaccines also contained Haemophilus influenza b conjugate vaccine (Hib). Post-vaccination symptoms and local reactions were recorded in 7-day diaries or by a telephone follow up if no diary was returned. Local swellings >50mm diameter were reported by 2.2% TdaP/IPV recipients compared with 6.6-11.1% of DTaP/IPV recipients; the corresponding proportions for redness >50mms was 7.0% for TdaP/IPV and 13.3-17.7% for DTaP/IPV recipients. Among the latter, the addition of Hib did not affect the frequency or size of local reactions. Pain at the injection site and systemic symptoms did not differ between the four vaccine groups. A history of atopy was not associated with development of local swelling or redness. A total of 13 children (1.3%) experienced an ESL, three after TdaP/IPV. ESLs resolved without systemic upset within a few days and were usually painless; medical advice was only sought for two children. Parents should be informed about the possible occurrence of an ESL with the pre-school aP-containing booster vaccine but can be reassured that it is a benign and transient condition.
Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Edema/epidemiologia , Extremidades/patologia , Imunização Secundária/efeitos adversos , Criança , Pré-Escolar , Diarreia/epidemiologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Edema/patologia , Feminino , Humanos , Letargia/epidemiologia , Masculino , Dor/epidemiologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/efeitos adversos , Reino UnidoRESUMO
BACKGROUND: In England, Public Health England conducts enhanced surveillance of invasive meningococcal disease (IMD). The continuing decline in reported IMD cases has raised concerns that the MRU may be underestimating true IMD incidence. METHODS: We linked five national datasets to estimate disease burden over five years, including PHE Meningococcal Reference Unit (MRU) confirmations, hospital episode statistics (HES), electronic reports of significant infections by National Health Service (NHS) Hospitals, death registrations and private laboratory reports. RESULTS: During 2007-11, MRU confirmed 5115 IMD cases and 4275 (84%) matched to HES, including 3935 (92%) with A39* (meningococcal disease) and 340 (8%) with G00* (bacterial meningo-encephalitis) ICD-10 codes. An additional 2792 hospitalised cases with an A39* code were identified in HES. Of these, 1465 (52%) matched to one of 53,806 samples tested PCR-negative for IMD by MRU and only 73 of the remaining 1327 hospitalised A39* cases were confirmed locally or by a private laboratory. The characteristics of hospitalised cases without laboratory confirmation were similar to PCR-negative than PCR-positive IMD cases. CONCLUSIONS: Interrogation of multiple national data sources identified very few laboratory confirmations in addition to the MRU-confirmed cases. The large number of unconfirmed and PCR-negative cases in HES suggests increased awareness among clinicians with low thresholds for hospitalising patients with suspected IMD.
Assuntos
Bases de Dados Factuais , Infecções Meningocócicas/epidemiologia , Adolescente , Adulto , Inglaterra/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Lactente , Armazenamento e Recuperação da Informação , Masculino , Infecções Meningocócicas/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
INTRODUCTION: In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM. METHODS: Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age. RESULTS: Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold-change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold-differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54-0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM-conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher. CONCLUSIONS: Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM-conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential.
Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Imunidade Materno-Adquirida , Coqueluche/imunologia , Antígenos de Bactérias/imunologia , Estudos de Coortes , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Inglaterra , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Lactente , Masculino , Vacinas Meningocócicas/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Gravidez , Toxoide Tetânico/administração & dosagem , Toxoide Tetânico/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , Coqueluche/prevenção & controleRESUMO
BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) protects against key serotypes that increased after routine immunisation with the seven-valent vaccine (PCV7), but its potential for herd protection and serotype replacement is uncertain. The aim of this study was to analyse the effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction. METHODS: We used a national dataset of electronically reported and serotyped invasive pneumococcal disease cases in England and Wales to estimate incidence rate ratios (IRRs) for vaccine and non-vaccine type invasive pneumococcal disease between July, 2013, and June, 2014, versus the pre-PCV13 and pre-PCV7 baseline. Incidence rates were corrected for missing serotype data and changes in surveillance sensitivity over time. An over-dispersed Poisson model was used to estimate IRRs and confidence intervals. FINDINGS: Incidence of invasive pneumococcal disease in the epidemiological year 2013/14 decreased by 32% compared with the pre-PCV13 baseline (incidence 10·14 per 100,000 in 2008-10 vs 6·85 per 100,000 in 2013/14; IRR 0·68, 95% CI 0·64-0·72). This was due to an 86% reduction of the serotypes covered by PCV7 (1·46 vs 0·20 per 100,000; IRR 0·14, 0·10-0·18) and a 69% reduction of the additional six serotypes covered by PCV13 (4·48 vs 1·40 per 100,000; IRR 0·31, 0·28-0·35). When compared with the pre-PCV7 baseline, there was a 56% overall reduction in invasive pneumococcal disease (15·63 vs 6·85 per 100,000; IRR 0·44, 95% CI 0·43-0·47). Compared with the pre-PCV13 baseline, the incidence of non-PCV13 serotypes increased (incidence all ages 4·19 vs 5·25 per 100,000; IRR 1·25, 95% CI 1·17-1·35) due to increases across a broad range of serotypes in children younger than 5 years and in people aged 45 years or more. In children younger than 5 years, incidence of non-PCV13 serotypes in 2013/14 was higher than in 2012/13 (age <2 years: 12·03 vs 10·83 per 100,000; age 2-4 years: 4·08 vs 3·63 per 100,000). INTERPRETATION: 8 years of PCV use in England and Wales has reduced the overall incidence of invasive pneumococcal disease by more than 50%. The herd protection induced by PCV7 is continuing, and similar indirect protection is occurring from the additional serotypes covered by PCV13. There is, however, evidence of increasing invasive pneumococcal disease due to non-PCV13 serotypes, particularly in children younger than 5 years in 2014. If this increase continues, the maximum benefit of the PCV13 programme in children might already have been achieved. FUNDING: Public Health England funds national surveillance of invasive pneumococcal disease.
Assuntos
Vacinação em Massa/estatística & dados numéricos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Inglaterra/epidemiologia , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Distribuição de Poisson , Sorogrupo , Streptococcus pneumoniae/patogenicidade , Vacinas Conjugadas , País de Gales/epidemiologiaRESUMO
BACKGROUND: Efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) was inferred before licensure from an aggregate correlate of protection established for the seven-valent vaccine (PCV7). We did a postlicensure assessment of serotype-specific vaccine effectiveness and immunogenicity in England, Wales, and Northern Ireland to derive the correlates of protection for individual serotypes. METHODS: We assessed vaccine effectiveness against invasive pneumococcal disease using the indirect cohort method. We measured serotype-specific IgG concentration in infants after they were given two priming doses of PCV7 (n=126) or PCV13 (n=237) and opsonophagocytic antibody titre from a subset of these infants (n=100). We derived correlates of protection by relating percentage protection to a threshold antibody concentration achieved by an equivalent percentage of infants. We used multivariable logistic regression to estimate vaccine effectiveness and reverse cumulative distribution curves to estimate correlates of protection. FINDINGS: For the 706 cases of invasive pneumococcal disease included in the study, PCV13 vaccine effectiveness after two doses before age 12 months or one dose from 12 months was 75% (95% CI 58-84). Vaccine effectiveness was 90% (34-98) for the PCV7 serotypes and 73% (55-84) for the six additional serotypes included in PCV13. Protection was shown for four of the six additional PCV13 serotypes (vaccine effectiveness for serotype 3 was not significant and no cases of serotype 5 infection occurred during the observation period). The vaccine effectiveness for PCV13 and PCV7 was lower than predicted by the aggregate correlate of protection of 0·35 µg/mL used during licensing. Calculated serotype-specific correlates of protection were higher than 0·35 µg/mL for serotypes 1, 3, 7F, 19A, 19F, and lower than 0·35 µg/mL for serotypes 6A, 6B, 18C, and 23F. Opsonophagocytic antibody titres of 1 in 8 or higher did not predict protection. INTERPRETATION: PCV13 provides significant protection for most of the vaccine serotypes. Although use of the aggregate correlate of protection of 0·35 µg/mL has enabled the licensing of effective new PCVs, serotype-specific correlates of protection vary widely. The relation between IgG concentration after priming and long-term protection needs to be better understood. FUNDING: Public Health England and UK Department of Health Research and Development Directorate.
Assuntos
Vacinas Pneumocócicas/imunologia , Anticorpos Antibacterianos/sangue , Pré-Escolar , Estudos de Coortes , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Imunoglobulina G/sangue , Lactente , Licenciamento , Sorotipagem , Vacinas Conjugadas/imunologiaRESUMO
BACKGROUND/AIMS: In April 2010 the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent PCV. We investigated pneumococcal carriage in children eligible for PCV7 or PCV13 and their household contacts. METHODS: Eligible families in Hertfordshire and Gloucester were identified and a nasopharyngeal swab obtained from consenting household members between July 2012 and March 2013. Samples were cultured for Streptococcus pneumoniae and serotyped by standard methods. For each serotype the ratio of its prevalence in invasive pneumococcal disease (IPD) to its carriage prevalence (case:carrier ratio, CCR) was calculated. Results were compared with previous carriage studies in 2001/2002 and 2008/2009, before and after PCV7 introduction. RESULTS: 217 households were included. Among <5-year olds 47.7% (95% confidence interval 41.8-53.5) were carrying a pneumococcus compared with 51.0% (95% CI: 44.0-58.0) in 2008/2009 and 48.4% (95% CI: 44.1-52.7) in 2001/2002. The odds of carrying a PCV7 serotype was significantly reduced in 2008/2009 (0.07, 95% CI: 0.03-0.16) and 2012/2013 (0.01 95% CI: 0.00-0.07) relative to 2001/2002, while the odds of carrying any of the extra six PCV13 serotypes increased after PCV7 introduction (1.38, 95%CI: 0.73-2.59) but declined significantly after PCV13 introduction (0.05, 95%CI: 0.01-0.37). The CCRs for the frequently carried serotypes were relatively low, with the highest CCR observed for serotypes 7F, 19A, 3, 8, and 33F. Across the three carriage studies, CCR estimates were stable for nearly all serotypes. CONCLUSION: Carriage of additional PCV13 serotypes has rapidly reduced post-PCV13 introduction in both vaccinated and unvaccinated individuals with a continued decline in transmission of PCV7 serotypes. Carriage rates in children remain unchanged, but the low CCRs of replacing serotypes would be expected to further reduce overall IPD across all age groups.
Assuntos
Portador Sadio/epidemiologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/classificação , Adolescente , Adulto , Portador Sadio/microbiologia , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Nasofaringe/microbiologia , Infecções Pneumocócicas/prevenção & controle , Prevalência , Sorotipagem , Vacinas Conjugadas/administração & dosagem , Adulto JovemRESUMO
The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis from July 2004 to June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by multilocus sequence typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5-year period. Fifty-two serotypes, 238 sequence types (STs), and 87 clonal complexes were identified, with no significant difference in the yearly Simpson's diversity index values (range, 0.974 to 0.984). STs commonly associated with PCV7 serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual serotypes. Replacement disease following PCV7 introduction was mainly due to serotypes 1, 3, 7F, 19A, 22F, and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a serotype 14 capsule in 2005 and a serotype 28A capsule in 2009. In 2008 to 2009, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145 fatalities/1,030 cases; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 serotypes, including some not covered by the 13-valent vaccine, such as serotypes 22F and 33F, emphasizing the importance of long-term epidemiological and molecular surveillance.
Assuntos
Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Genótipo , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Recém-Nascido , Masculino , Meningite Pneumocócica/mortalidade , Meningite Pneumocócica/prevenção & controle , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Prevalência , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação , Análise de Sobrevida , País de Gales/epidemiologia , Adulto JovemRESUMO
We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3-59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006-March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.
Assuntos
Cardiopatias Congênitas/epidemiologia , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/prevenção & controle , Neoplasias/epidemiologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Streptococcus pneumoniae/imunologia , Doença Aguda , Pré-Escolar , Comorbidade , Inglaterra/epidemiologia , Feminino , Cardiopatias Congênitas/mortalidade , Humanos , Incidência , Lactente , Masculino , Meningite Pneumocócica/imunologia , Meningite Pneumocócica/mortalidade , Neoplasias/mortalidade , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/mortalidade , Fatores de Risco , Estudos Soroepidemiológicos , Sorotipagem , Streptococcus pneumoniae/patogenicidade , Análise de Sobrevida , Vacinação , Vacinas Conjugadas , País de Gales/epidemiologiaRESUMO
In 2003 the existing 23-valent pneumococcal vaccine (PPV23) programme for high risk groups was extended to include all ≥ 65 year olds in England and Wales, starting with ≥ 80 year olds and moving to 75-79 and 65-74 year olds by 2005. We conducted an ecological study to assess the impact of the extended PPV23 programme on serotype-specific incidence of invasive pneumococcal disease (IPD) and a case-control study to assess vaccine effectiveness (VE) using the national IPD surveillance dataset. Between 1998 and 2006 IPD incidence caused by PPV23 serotypes in the targeted age-groups was unchanged. IPD caused by the serotypes covered by the 7-valent conjugate vaccine (PCV7) introduced for children in 2006 declined in ≥ 65 year olds after 2006 but was offset by an increase in non-PCV7 serotypes. This increase was similar for the additional 16 serotypes covered by PPV23 and the non-PPV23 serotypes. For the VE study, vaccine history was obtained for controls (n=1270) with non-PPV23 IPD diagnosed between November 2003 and December 2010 and a subset of cases (n=1272) matched for age and time period. VE declined from 48% (95% confidence interval; 32-60%) within two years of vaccination to 15% (-3% to 30%) after five years. Although differences in VE by age and having risk conditions were not statistically significant the highest estimates were in the youngest age group (65-74 years) and in those without risk conditions with a VE estimate of 65% (23-84%) within 2 years of vaccination for non-risk 65-74 year olds. VE differed by serotype (p=0.005), from -23% (-85% to 19%) for serotype 3 to 63% (29-81%) for 12F. In conclusion PPV23 was effective, particularly in healthy under 75 year olds, but protection waned after 5 years. There was no discernible impact of PPV23 on IPD incidence or PCV7-induced serotype replacement, consistent with the modest overall effectiveness, the 45% increased coverage over the former risk-based programme and lack of herd immunity from the PPV23 programme. Based on the VE estimates PPV23 was still considered a cost-effective intervention for the low risk elderly.
Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/classificação , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/administração & dosagem , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação , País de Gales/epidemiologiaRESUMO
BACKGROUND: Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13). METHOD: Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients' diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5-64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines. RESULTS: The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines' coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals. CONCLUSION: Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss.
Assuntos
Vacinas Bacterianas , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Sorotipagem , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Infecções Pneumocócicas/prevenção & controle , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Especificidade da Espécie , Vacinas Conjugadas , Adulto JovemRESUMO
OBJECTIVE: To inform national policy making on the use of the 13-valent pneumococcal vaccine among risk groups we estimated the increased risk of invasive pneumococcal disease (IPD) outcomes among clinical risk groups. Three years of post 7-valent pneumococcal conjugate vaccine (PCV7) data was included to investigate the herd protection effects. METHODS: Over 22,000 IPD patients in England (March 2002-March 2009 - aged 2 and over) were linked to their hospitalisation records. The prevalence of risk factors in these patients was compared to the prevalence of risk factors in the general population. RESULTS: There was an increased odds ratio (OR) for hospitalisation (OR 11.7 2-15 years; 7.6 16-64; 2.7 65+) and death (OR 2.4 2-15 years, 3.9 16-64, 1.2 65+) from IPD among risk group. The most important risk factors that predict IPD are chronic liver disease, immunosuppression, and chronic respiratory diseases. Herd protection effects due to introduction of the 7-valent vaccine were identical in both patient groups as shown by the similar decline in the proportion of IPD caused by PCV7 serotypes in risk and non-risk groups. CONCLUSIONS: There is a marked increased risk of IPD among those with certain clinical conditions, suggesting potential benefit from a targeted vaccination approach. However, the indirect protection from conjugate vaccination of children suggests PCV vaccination of high-risk groups may not provide substantial additional benefit once herd immunity takes effect.
Assuntos
Bacteriemia/epidemiologia , Meningite Pneumocócica/epidemiologia , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/patogenicidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/prevenção & controle , Criança , Pré-Escolar , Comorbidade , Inglaterra/epidemiologia , Feminino , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Imunidade Coletiva , Masculino , Meningite Pneumocócica/microbiologia , Meningite Pneumocócica/mortalidade , Meningite Pneumocócica/prevenção & controle , Pessoa de Meia-Idade , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Prevalência , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2, 3 and 13 month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD. METHODS AND FINDINGS: We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (nâ=â153) and non vaccine type (nâ=â919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we estimated that effectiveness estimates may be overestimated by about 2 to 5%. CONCLUSIONS: This study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine.
Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Vacinas Conjugadas/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra , Humanos , Programas de Imunização , Lactente , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa , Vacinas/uso terapêutico , País de GalesRESUMO
Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval -18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period.
Assuntos
Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/classificação , Inglaterra/epidemiologia , Humanos , Programas de Imunização , Lactente , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/administração & dosagem , Vigilância da População , Sorotipagem , Vacinação/estatística & dados numéricos , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , País de Gales/epidemiologiaRESUMO
BACKGROUND: The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccination program in September 2006. Previous modelling assumed that the likely impact of PCV7 on invasive pneumococcal disease (IPD) would be similar to the US experience with PCV7. However, recent surveillance data show a more rapid replacement of PCV7 IPD cases by non-PCV7 IPD cases than was seen in the US. METHODS AND FINDINGS: A previous model of pneumococcal vaccination was re-parameterised using data on vaccine coverage and IPD from England and Wales between 2006 and 2009. Disease incidence was adjusted for the increasing trend in reported IPD cases prior to vaccination. Using this data we estimated that individuals carrying PCV7 serotypes have much higher protection (96%;95% CI 72%-100%) against acquisition of NVT carriage than the 15% previously estimated from US data, which leads to greater replacement. However, even with this level of replacement, the annual number of IPD cases may be 560 (95% CI, -100 to 1230) lower ten years after vaccine introduction compared to what it may have been without vaccination. A particularly marked fall of 39% in children under 15 years by 2015/6 is predicted. CONCLUSION: Our model suggests that PCV7 vaccination could result in a decrease in overall invasive pneumococcal disease, particularly in children, even in an environment of rapid replacement with non-PCV7 serotypes within 5 years of vaccine introduction at high coverage.
Assuntos
Vacinas Pneumocócicas/imunologia , Vacinação , Estudos de Coortes , Intervalos de Confiança , Inglaterra/epidemiologia , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Modelos Biológicos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/transmissão , Prevalência , Sorotipagem , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Fatores de Tempo , País de Gales/epidemiologiaRESUMO
In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38 °C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation.