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1.
JAMA ; 324(11): 1068-1077, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930758

RESUMO

Importance: The standard schedule of national immunization programs for infants may not be sufficient to protect extremely and very preterm infants. Objective: To evaluate the immunogenicity of routine vaccinations administered to preterm infants. Design, Setting, and Participants: A multicenter, prospective, observational cohort study of preterm infants stratified according to gestational age recruited from 8 hospitals across the Netherlands between October 2015 and October 2017, with follow-up until 12 months of age (October 2018). In total, 296 premature infants were enrolled and compared with a control group of 66 healthy term infants from a 2011 study, immunized according to the same schedule with the same vaccines. Exposures: Three primary doses of the diphtheria-tetanus toxoids-acellular pertussis-inactivated poliomyelitis-Haemophilus influenza type b-hepatitis B combination vaccine were given at 2, 3, and 4 months after birth followed by a booster at 11 months and a 10-valent pneumococcal conjugate vaccine at 2, 4, and 11 months after birth. Main Outcomes and Measures: Primary end points were (1) proportion of preterm infants who achieved IgG antibody against vaccine antigens at concentrations above the internationally defined threshold for protection after the primary series and booster dose and (2) serum IgG geometric mean concentrations after the primary series and booster vaccination. Proportions and geometric mean concentrations were compared in preterm infants and the control group of term infants. Results: Of 296 preterm infants (56.1% male; mean gestational age, 30 weeks), complete samples before vaccination, 1 month after the primary series, and 1 month after the booster were obtained from 220 preterm infants (74.3%). After the primary series, the proportion of preterm infants across all gestational age groups who achieved protective IgG antibody levels against pertussis toxin, diphtheria, tetanus and 6 of 10 pneumococcal serotypes varied between 83.0% and 100%, Haemophilus influenzae type b between 34.7% and 46.2% (40.6% among all preterm infants overall), and pneumococcal serotypes 4, 6B, 18C, and 23F between 45.8% and 75.1%. After the booster dose, protective antibody levels were achieved in more than 95% of all preterm groups, except for Haemophilus influenzae type b (88.1%). In general, geometric mean concentrations of all vaccine-induced antibodies were significantly lower in all preterm infants vs term infants, except for pertussis toxin and pneumococcal serotypes 4 and 19F after the primary series and booster vaccination. Conclusions and Relevance: Among preterm infants, administration of routine vaccinations during the first year of life was associated with protective antibody levels against most antigens in the majority of infants after the primary series and booster, except for Haemophilus influenzae type b. However, antibody concentrations were generally lower among preterm infants compared with historical controls.


Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Recém-Nascido Prematuro/imunologia , Vacinas/imunologia , Estudos de Coortes , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Vacinas Anti-Haemophilus/imunologia , Estudo Historicamente Controlado , Humanos , Imunização Secundária , Lactente , Masculino , Vacinas Pneumocócicas/imunologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Conjugadas/imunologia
2.
Allergol Immunopathol (Madr) ; 48(5): 500-506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32771236

RESUMO

The reasons for the relative resistance of children to certain infections such as that caused by coronavirus SARS-CoV2 are not yet fully clear. Deciphering these differences can provide important information about the pathogenesis of the disease. Regarding the SARS-CoV2 virus, children are at the same risk of infection as the general population of all ages, with the most serious cases being found in infants. However, it has been reported that the disease is much less frequent than in adults and that most cases are benign or moderate (even with high viral loads), provided there are no other risk factors or underlying diseases. It is not clear why they have lower morbidity and virtually no mortality. A series of findings, relationships and behavioral patterns between the infectious agent and the child host may account for the lower incidence and a greatly attenuated clinical presentation of the disease in children.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Adulto , Fatores Etários , Portador Sadio/transmissão , Portador Sadio/virologia , Criança , Coinfecção/epidemiologia , Coinfecção/imunologia , Coinfecção/patologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Humanos , Sistema Imunitário , Estilo de Vida , Melatonina/imunologia , Melatonina/metabolismo , Pandemias , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Vacinas Pneumocócicas/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/patologia
3.
Neurology ; 95(14): e1999-e2008, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32727835

RESUMO

OBJECTIVE: The phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis. METHODS: Patients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine [23-PPV]), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group). RESULTS: Positive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group. CONCLUSION: Peripherally B-cell-depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta-treated patients, but they can still be expected to be protective. CLINICALTRIALSGOV IDENTIFIER: NCT02545868.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunogenicidade da Vacina/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Adulto , Feminino , Hemocianinas/imunologia , Humanos , Masculino , Vacinas Pneumocócicas/imunologia , Toxoide Tetânico/imunologia
4.
BMC Infect Dis ; 20(1): 423, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552726

RESUMO

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.


Assuntos
Hospitalização , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Vacinação , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Infecções Pneumocócicas/mortalidade , Infecções Pneumocócicas/urina , Estudos Retrospectivos , Fatores de Risco , Singapura/epidemiologia , Centros de Atenção Terciária , Resultado do Tratamento
5.
Int J Infect Dis ; 98: 113-120, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32562849

RESUMO

BACKGROUND: Streptococcus pneumoniae remains a major contributor to childhood infections and deaths globally. In Cameroon, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in July 2011, using a 3-dose Expanded programme on immunization (EPI) schedule administered to infants at 6, 10 and 14 weeks of age. To evaluate PCV13 effects, we assessed pneumococcal nasopharyngeal colonization and serotype distribution among Cameroonian children after PCV13 introduction. METHODS: Nasopharyngeal (NP) swabs were collected from eligible children aged 24-36 months in two cross-sectional surveys conducted from March to July: in 2013 (PCV13-unvaccinated), and in 2015 (PCV13-vaccinated). Using a systematic World Health Organization (WHO) cluster coverage sampling technique in 40 communities, NP swabs collected were processed following WHO recommendations. Standard bacterial culture techniques were used for the isolation of S. pneumoniae from gentamicin-blood agar plates and identification using optochin susceptibility testing. Serotyping was performed using sequential multiplex polymerase chain reaction, supplemented with Quellung test. RESULTS: Among the PCV13-vaccinated children, overall pneumococcal carriage prevalence was 61.8% (426/689) and PCV13 vaccine-type carriage prevalence was 18.0% (123/689). Eleven out of the 13 vaccine serotypes were detected in the vaccinated children. The most common serotypes were 19F (4.5%, 31/689) and 15B/C (7.3%, 50/689). CONCLUSION: In Cameroon, four years after infant vaccination nearly all of the PCV13-serotypes continued to circulate in the population. This suggests that the direct and indirect effects of the vaccination programme have not resulted in expected low levels of vaccine-type transmission. Continuous monitoring is needed to assess the long term effects of the PCV13 on nasopharyngeal carriage and disease.


Assuntos
Nasofaringe/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , Camarões/epidemiologia , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Portador Sadio/microbiologia , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Programas de Imunização , Esquemas de Imunização , Masculino , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/imunologia , Prevalência , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/crescimento & desenvolvimento , Streptococcus pneumoniae/isolamento & purificação , Vacinação
6.
Int J Infect Dis ; 97: 182-189, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32474199

RESUMO

OBJECTIVES: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP). METHODS: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses. RESULTS: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita. CONCLUSIONS: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.


Assuntos
Programas de Imunização/economia , Infecções Pneumocócicas/economia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/economia , Algoritmos , Pré-Escolar , Estudos de Coortes , Análise Custo-Benefício , Cuba , Feminino , Custos de Cuidados de Saúde , Hospitalização/economia , Humanos , Lactente , Masculino , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/imunologia , Anos de Vida Ajustados por Qualidade de Vida , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/economia , Vacinas Conjugadas/imunologia
7.
Int J Infect Dis ; 98: 194-199, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32553718

RESUMO

INTRODUCTION: Community-Acquired Pneumonia (CAP) is one of the most frequent causes of hospital admission in children. Our objective is to measure the impact of the introduction of pneumococcal conjugate vaccines on the hospitalization of previously healthy children due to CAP. METHOD: From 2011 to 2016, a partially retrospective, prospective, and descriptive study was carried out on healthy pediatric patients (3 months-14 years old) with CAP, who required hospital admission. Clinical, epidemiological, and demographic characteristics were collected, and vaccination status was obtained from medical records. RESULTS: A total of 292 cases were included, with a mean age of 33.4 months, 54% males. There was a progressive and significant 42% decrease in the number of admissions each year, without significant changes in the annual percentage of parapneumonic pleural effusion (PPE). Fifty-six percent of patients were immunized with a pneumococcal conjugate vaccine (PCV). The percentage of children who were not vaccinated decreased by 14%, and the coverage with PCV-13 increased by 46%. This revealed a significant increase of PPE in vaccinated patients with PCV-7 (63%) compared with unvaccinated (45%) and with PCV-13 (57%), without association with the presence of severe PPE. Moreover, no significant differences in severity or hospital stay were observed in unvaccinated patients, compared to those who were vaccinated. In >2-year-olds, we observed a significant increase in PPE (59%) compared to 45% in younger children. CONCLUSIONS: The increase in vaccination coverage with PCV-13 resulted in a decrease in hospitalizations due to CAP and PPE. Vaccination with PCV-7 is associated in our sample with an increase in PPE but not with severe PPE nor an increase in the hospital stay. There was an epidemiological shift of severe forms of pneumonia and empyema at later ages (>2 years).


Assuntos
Infecções Comunitárias Adquiridas/terapia , Vacinas Pneumocócicas/administração & dosagem , Pneumonia/terapia , Vacinas Conjugadas/administração & dosagem , Adolescente , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/prevenção & controle , Feminino , Hospitalização , Humanos , Imunização , Lactente , Tempo de Internação , Masculino , Derrame Pleural/microbiologia , Vacinas Pneumocócicas/imunologia , Pneumonia/prevenção & controle , Estudos Prospectivos , Estudos Retrospectivos , Vacinação , Vacinas Conjugadas/imunologia
8.
Nature ; 581(7806): 94-99, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32376956

RESUMO

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.


Assuntos
Antibacterianos , Países em Desenvolvimento/economia , Uso de Medicamentos/estatística & dados numéricos , Vacinas , Antibacterianos/administração & dosagem , Antibacterianos/economia , Pré-Escolar , Diarreia/tratamento farmacológico , Diarreia/prevenção & controle , Diarreia/virologia , Resistência Microbiana a Medicamentos , Uso de Medicamentos/economia , Humanos , Incidência , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Infecções Respiratórias/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/imunologia , Vacinas/administração & dosagem , Vacinas/economia , Vacinas/imunologia , Organização Mundial da Saúde/organização & administração
9.
Epidemiol Infect ; 148: e187, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32418558

RESUMO

Surveillance of new cases of invasive pneumococcal disease (IPD) in Italy was started in 2007 by the Ministry of Health (MoH). In 2012, pneumococcal childhood vaccination was introduced at the national level and, in 2017, for citizens aged 65 years and over. We describe here IPD epidemiology in Italy over the past 10 years investigating the impact of the vaccine programme on disease burden. Reports of IPD cases, data on serotype and vaccination coverage (VC) data were obtained from MoH annual reports, for the period 2007-2017. IPD notification rate and proportion by year, region, age and serotype were calculated. In 2007, 525 cases were reported (rate 0.88/100 000), rising to 1703 cases (rate 2.82/100 000) in 2017. The distribution of IPD cases by age group over time registered the largest share among individuals aged 65 years and over. A decreasing trend in notification rate was observed among those aged 0-4 years. During the same period, the 24-month VC increased, ranging from 80.9% to 96.7% in 2017. Molecular data indicated re-emergence of PPSV23-specific serotypes and non-vaccine serotypes. We observed an increase in IPD notifications during 2007-2017, likely due to an improved surveillance system, at least in some regions, with the relative quota of IPD notifications decreasing among vaccinated children cohorts. Further strengthening of IPD surveillance system, including molecular and vaccine coverage data, would be needed to assess and inform pneumococcal vaccination strategies in Italy.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-32418510

RESUMO

The number of notified cases of invasive pneumococcal disease (IPD) in the second quarter of 2019 was higher than the previous quarter as well as the second quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vigilância da População , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Criança , Pré-Escolar , Notificação de Doenças , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Vacinas Pneumocócicas/administração & dosagem , Streptococcus pneumoniae/imunologia , Fatores de Tempo , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-32418512

RESUMO

The number of notified cases of invasive pneumococcal disease (IPD) in the third quarter of 2019 was higher than in the previous quarter, but lower than in the third quarter of 2018. Following the July 2011 replacement of the 7-valent pneumococcal conjugate vaccine (7vPCV) in the childhood immunisation program with the 13-valent pneumococcal conjugate vaccine (13vPCV), there was an initial relatively rapid decline in disease due to the additional six serotypes covered by the 13vPCV across all age groups, however more recently this decline is no longer evident. Over this period the number of cases due to the eleven serotypes additionally covered by the 23-valent pneumococcal polysaccharide vaccine (23vPPV), and also those serotypes not covered by any available vaccine, has been increasing steadily across all age groups.


Assuntos
Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Vigilância da População , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Criança , Pré-Escolar , Notificação de Doenças , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Vacinas Pneumocócicas/administração & dosagem , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Fatores de Tempo , Adulto Jovem
12.
Epidemiol Infect ; 148: e91, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32299523

RESUMO

Studies on community-acquired pneumonia (CAP) and pneumococcal pneumonia (PP) related to the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in Asia are scarce. This study aimed to investigate the epidemiological and microbiological determinants of hospitalised CAP and PP after PCV13 was introduced in Japan. This observational hospital-based surveillance study included children aged ⩽15 years, admitted to hospitals in and around Chiba City, Japan. Participants had bacterial pneumonia based on a positive blood or sputum culture for bacterial pathogens. Serotype and antibiotic-susceptibility testing of Streptococcus pneumoniae and Haemophilus influenzae isolates from patients with bacterial pneumonia were assessed. The CAP hospitalisation rate per 1000 child-years was 17.7, 14.3 and 9.7 in children aged <5 years and 1.18, 2.64 and 0.69 in children aged 5-15 years in 2008, 2012 and 2018, respectively. There was a 45% and 41% reduction in CAP hospitalisation rates, between the pre-PCV7 and PCV13 periods, respectively. Significant reductions occurred in the proportion of CAP due to PP and PCV13 serotypes. Conversely, no change occurred in the proportion of CAP caused by H. influenzae. The incidence of hospitalised CAP in children aged ⩽15 years was significantly reduced after the introduction of PCV13 in Japan. Continuous surveillance is necessary to detect emerging PP serotypes.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Programas de Imunização , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Adolescente , Antibacterianos/farmacologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Hospitais , Humanos , Lactente , Japão/epidemiologia , Masculino , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Vacinas Conjugadas
13.
PLoS One ; 15(4): e0232151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348330

RESUMO

BACKGROUND: Pneumococcal colonization prevalence and colonization density, which has been associated with invasive disease, can offer insight into local pneumococcal ecology and help inform vaccine policy discussions. METHODS: The Pneumonia Etiology Research for Child Health Project (PERCH), a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children aged 1-59 months. The PERCH Thailand site enrolled children during January 2012-February 2014. We determined pneumococcal colonization prevalence and density, and serotype distribution of colonizing isolates. RESULTS: We enrolled 224 severe/very severe pneumonia cases and 659 community controls in Thailand. Compared to controls, cases had lower colonization prevalence (54.5% vs. 62.5%, p = 0.12) and lower median colonization density (42.1 vs. 210.2 x 103 copies/mL, p <0.0001); 42% of cases had documented antibiotic pretreatment vs. 0.8% of controls. In no sub-group of assessed cases did pneumococcal colonization density exceed the median for controls, including cases with no prior antibiotics (63.9x103 copies/mL), with consolidation on chest x-ray (76.5x103 copies/mL) or with pneumococcus detected in whole blood by PCR (9.3x103 copies/mL). Serotype distribution was similar among cases and controls, and a high percentage of colonizing isolates from cases and controls were serotypes included in PCV10 (70.0% and 61.8%, respectively) and PCV13 (76.7% and 67.9%, respectively). CONCLUSIONS: Pneumococcal colonization is common among children aged <5 years in Thailand. However, colonization density was not higher among children with severe pneumonia compared to controls. These results can inform discussions about PCV introduction and provide baseline data to monitor PCV impact after introduction in Thailand.


Assuntos
Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Antibacterianos/uso terapêutico , Carga Bacteriana , Estudos de Casos e Controles , Pré-Escolar , Humanos , Lactente , Masculino , Nasofaringe/microbiologia , Vacinas Pneumocócicas/imunologia , Pneumonia Pneumocócica/prevenção & controle , Reação em Cadeia da Polimerase , Prevalência , Sorogrupo , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Tailândia/epidemiologia
14.
Sci Rep ; 10(1): 6470, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286332

RESUMO

The conjugation of polysaccharides with an effective carrier protein is critical for the development of effective bacterial polysaccharide vaccines. Therefore, the identification and optimization of carrier proteins to induce an effective immune response is necessary for developing a combined vaccine. In the current study, we utilized hepatitis B virus surface antigen (HBsAg) as a novel carrier protein combined with a capsular polysaccharide molecule to develop a new pneumococcal conjugated vaccine. The specific antibodies and T cell immune response against the capsular polysaccharide and HBsAg in the mice immunized with this conjugated vaccine were evaluated. In addition, the unique gene profiles of immune cells induced by this conjugated vaccine in the immunized mice were analyzed. Our results demonstrated that the vaccine consisting of pneumonia type 33 F capsular polysaccharide (Pn33Fps) conjugated with HBsAg can induce strong specific immune responses against both antigens in vivo in immunized mice. Furthermore, the conjugated vaccine induced higher expression of genes related to the activation of immunity and higher antibody titers against Pn33Fps and HBsAg in mice than those obtained via vaccination with a single antigen. Analyses of the dynamic expression changes in immunity-related genes in mice immunized with Pn33Fps_HBs, Pn33Fps, or HBsAg indicated the potent immunogenicity of the conjugated vaccine. In addition, a pathological evaluation of the organs from immunized mice further suggested that the conjugated vaccine is safe. Together, these results indicate that a conjugated vaccine consisting of Pn33Fps with HBsAg is a novel and effective vaccine.


Assuntos
Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Vacinas Pneumocócicas/imunologia , Animais , Feminino , Regulação da Expressão Gênica , Hepatite B/genética , Hepatite B/imunologia , Hepatite B/patologia , Imunidade , Camundongos Endogâmicos BALB C , Especificidade de Órgãos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linfócitos T/imunologia , Vacinação
15.
BMC Infect Dis ; 20(1): 279, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293324

RESUMO

BACKGROUND: The 13-valent Pneumococcal Conjugate Vaccine (PCV-13) was introduced in the National Immunization Programme (NIP) schedule in Russia in March 2014. Previously, the 7-valent Pneumococcal Conjugate Vaccine (PCV-7) was marketed in Russia in 2009 but has never been offered for mass vaccination. A carriage study was performed among children in Arkhangelsk in 2006. The objective was to determine the prevalence of carriage, serotype distribution, antimicrobial susceptibility and the molecular structure of Streptococcus pneumoniae strains before marketing and introduction of PCV-13. METHODS: A cross-sectional study was conducted on a cluster-randomized sample of children and a self-administrated questionnaire for parents/guardians.  Nasopharyngeal samples were collected from 438 children younger than 7 years attending nurseries and kindergartens in the Arkhangelsk region, Russia. Detailed demographic data, as well as information about the child's health, traveling, exposure to antimicrobials within the last 3 months and anthropometric measurements were collected for all study subjects. Variables extracted from the questionnaire were analysed using statistic regression models to estimate the risk of carriage. All pneumococcal  isolates were examined with susceptibility testing, serotyping and multilocus sequence typing. RESULTS: The overall prevalence of asymptomatic carriage was high and peaking at 36 months with a rate of 57%. PCV-13 covered 67.3% of the detected strains. High rates of non-susceptibility to penicillin, macrolides and multidrug resistance were associated with specific vaccine serotypes, pandemic clones, and local sequence types. Nine percent of isolates represented three globally disseminated disease-associated pandemic clones; penicillin- and macrolide-resistant clones NorwayNT-42 and Poland6B-20, as well as penicillin- and macrolide-susceptible clone Netherlands3-31. A high level of antimicrobial consumption was noted by the study. According to the parent's reports, 89.5% of the children used at least one antimicrobial regime since birth. None of the hypothesised predictors of S. pneumoniae carriage were statistically significant in univariable and multivariable logistic models. CONCLUSIONS: The study identified a high coverage of the PCV-13-vaccine, but serotype replacement and expansion of globally disseminated disease-associated clones with non-vaccine serotypes may be expected. Further surveillance of antimicrobial resistance and serotype distribution is therefore required.


Assuntos
Portador Sadio/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/imunologia , Antibacterianos/uso terapêutico , Portador Sadio/microbiologia , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Lactente , Macrolídeos/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Nasofaringe/microbiologia , Penicilinas/uso terapêutico , Infecções Pneumocócicas/tratamento farmacológico , Prevalência , Federação Russa/epidemiologia , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação
16.
Int J Infect Dis ; 92: 261-268, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32147023

RESUMO

OBJECTIVE: Geographic region can be an important source of variation in the immune response to pneumococcal conjugate vaccines (PCV). The aim of this study was to collate data from available PCV clinical trials in order to characterize the differences in antibody responses in different countries. METHODS: A systematic review and meta-analysis was conducted to examine the difference in antibody responses after primary series of PCVs in infants, associated with geographic regions, compared with each other and with the different PCVs using random-effects models. RESULTS: A total of 69 trials were included. Studies conducted in the Western Pacific Region (WPR) showed higher geometric mean concentrations (GMC) compared to studies conducted in Europe. The pooled GMC for serotype 4 after three doses of PCV7 in the WPR was 5.19 µg/ml (95% confidence interval 4.85-5.53 µg/ml), while for studies conducted in Europe this was 2.01 µg/ml (95% confidence interval 1.88-2.14 µg/ml). The IgG GMC ratios among the WPR versus European regions ranged from 1.51 to 2.87 for PCV7, 1.69 to 3.22 for PCV10, and 1.49 to 3.08 for PCV13. CONCLUSIONS: Studies conducted in the WPR generally showed greater antibody responses than the studies conducted in Europe. Indications of differences among geographic regions highlight the fact that further research is needed to compare the biological factors contributing to immune responses, which may affect vaccination schedules.


Assuntos
Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Formação de Anticorpos , Australásia , Ensaios Clínicos como Assunto , Extremo Oriente , Feminino , Vacina Pneumocócica Conjugada Heptavalente/administração & dosagem , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Humanos , Esquemas de Imunização , Lactente , Masculino , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Sorogrupo , Streptococcus pneumoniae/imunologia
17.
Nat Microbiol ; 5(3): 473-485, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015499

RESUMO

Streptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal that can cause invasive pneumococcal disease (IPD). Each component of current protein-polysaccharide conjugate vaccines (PCVs) generally induces immunity specific to one of the approximately 100 pneumococcal serotypes, and typically eliminates it from carriage and IPD through herd immunity. Overall carriage rates remain stable owing to replacement by non-PCV serotypes. Consequently, the net change in IPD incidence is determined by the relative invasiveness of the pre- and post-PCV-carried pneumococcal populations. In the present study, we identified PCVs expected to minimize the post-vaccine IPD burden by applying Bayesian optimization to an ecological model of serotype replacement that integrated epidemiological and genomic data. We compared optimal formulations for reducing infant-only or population-wide IPD, and identified potential benefits to including non-conserved pneumococcal carrier proteins. Vaccines were also devised to minimize IPD resistant to antibiotic treatment, despite the ecological model assuming that resistance levels in the carried population would be preserved. We found that expanding infant-administered PCV valency is likely to result in diminishing returns, and that complementary pairs of infant- and adult-administered vaccines could be a superior strategy. PCV performance was highly dependent on the circulating pneumococcal population, further highlighting the advantages of a diversity of anti-pneumococcal vaccination strategies.


Assuntos
Metagenômica , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Antibacterianos/farmacologia , Teorema de Bayes , Farmacorresistência Bacteriana Múltipla , Ecologia , Humanos , Incidência , Lactente , Nasofaringe/imunologia , Nasofaringe/microbiologia , Infecções Pneumocócicas/imunologia , Sorogrupo , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologia , Vacinação , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia
18.
Carbohydr Res ; 489: 107951, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32086019

RESUMO

α-Glucosyl diacylglycerols (αGlc-DAGs) play an important role in providing protective immunity against Streptococcus pneumoniae infection through the engagement of the Macrophage inducible C-type lectin (Mincle). Herein, we efficiently synthesised αGlc-DAGs containing C12, C14, C16 and C18 acyl chains in 7 steps and 44-47% overall yields, and demonstrated that Mincle signaling was dependent on lipid length using mMincle and hMincle NFAT-GFP reporter cells. The greatest production of GFP in both cell types was elicited by C14 αGlc-DAG. Accordingly, C14 αGlc-DAG has potential to act as an adjuvant to augment the immune response against S. pneumoniae antigens.


Assuntos
Glicolipídeos/imunologia , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Vacinas Conjugadas/imunologia , Glicolipídeos/síntese química , Glicolipídeos/química , Estrutura Molecular , Infecções Pneumocócicas/terapia , Vacinas Pneumocócicas/síntese química , Vacinas Pneumocócicas/química , Vacinas Conjugadas/química
19.
mSphere ; 5(1)2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024704

RESUMO

Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. A nonfunctional convalescent-phase response was significantly more common among patients with invasive pneumococcal disease (i.e., bacteremia) than in patients without invasive disease (53%; P = 0.019). Remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). No correlation was found between anticapsular Ig concentrations and OPA titers. Our findings indicate that an episode of pneumococcal infection may act as an immunizing event, leading to an improved antipneumococcal adaptive immune status. However, in some cases, when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations are important for opsonic antibody activity in serum.IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response frequently fails to occur after CAP, predominantly among patients with simultaneous bacteremia.


Assuntos
Formação de Anticorpos , Fagocitose , Pneumonia Pneumocócica/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Adulto Jovem
20.
Arthritis Res Ther ; 22(1): 36, 2020 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087733

RESUMO

OBJECTIVE: To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. METHODS: Patients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4-8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 µg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 µg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F. RESULTS: Compared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient - 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients - 1.9 and - 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls. CONCLUSIONS: Prime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered.


Assuntos
Antirreumáticos/uso terapêutico , Hospedeiro Imunocomprometido/imunologia , Imunogenicidade da Vacina/imunologia , Vacinas Pneumocócicas/administração & dosagem , Doenças Reumáticas/tratamento farmacológico , Abatacepte/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunização Secundária/métodos , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/imunologia , Doenças Reumáticas/imunologia , Rituximab/uso terapêutico
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