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OBJECTIVE: To compare dispensed oral antibiotic prescription rates (DAPRs) after implementation of pneumococcal conjugate vaccine (PCV) in high antibiotic-prescribing clinics (HPC) with low antibiotic-prescribing clinics (LPC) in 2 distinct ethnic groups of children (Jewish and Bedouin children) <5 years of age. METHODS: Clinics with ≥50 insured children, active both pre-PCV (2005-2009) and post-PCV (2010-2018) implementation, were included. HPC and LPC were defined by DAPRs above or below the median in each age and ethnic group. Monthly dispensed antibiotic prescription rate (DAPR) trends (adjusted for age and ethnicity) were calculated using interrupted time series. Mean yearly incidence rate-ratios (late PCV13 vs pre-PCV) were calculated. RESULTS: Bedouin HPC had the highest pre-PCV overall-DAPR per 1000 child-years ± SD (2520.4 ± 121.2), followed by Jewish HPC (1885.5 ± 47.6), Bedouin LPC (1314.8 ± 81.6), and Jewish LPC (996.0 ± 19.6). Shortly after PCV implementation, all DAPRs and amoxicillin/amoxicillin-clavulanate DAPRs declined in all groups except Jewish LPC, stabilizing within 4-5 years post-PCV. The rates and magnitudes of declines were directly proportional to the pre-PCV DAPR magnitudes, achieving near-complete closure of the pre-PCV DAPR gaps between the 4 groups (rates during late-PCV13 ranging from 1649.4 ± 23.5 [Bedouin HPC] to 1200.3 ± 72.4 [Jewish LPC]). CONCLUSIONS: PCVs are a powerful tool in reducing outpatient antibiotic consumption among young children, especially in HPC, resulting in partial closure of DAPR gap between HPC and LPC. The higher impact on HPC suggests that PCV-associated declines of respiratory disease may strongly contribute to a judicious antibiotic approach in clinics with high antibiotic consumption.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Criança , Humanos , Lactente , Pré-Escolar , Vacinas Pneumocócicas/uso terapêutico , Antibacterianos/uso terapêutico , Vacinas Conjugadas , Combinação Amoxicilina e Clavulanato de Potássio , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controleRESUMO
Introduction. Streptococcus pneumoniae remains a major cause of mortality and morbidity worldwide in children <5 years of age, even with advances in vaccination programmes.Hypothesis/Gap Statement. Reviewing and reporting trends in the distribution of pneumococcal serotypes and antimicrobial resistance in Paraguay will be useful for decision-making in public health.Aim. This study analysed the serotype distribution and antimicrobial resistance of S. pneumoniae and the characteristics of pneumococcal disease in children <5 years old before and after the introduction of pneumococcal conjugate vaccines (PCVs).Methodology. A total of 885 isolates and 278 S. pneumoniae PCR-positive clinical specimens were referred to the Central Laboratory of Public Health (LCSP) within the meningitis and pneumonia laboratory based-surveillance network in the period 2006-2020. Conventional and molecular microbiological techniques were used for confirmation and characterization.Results. We identified 563 cases of pneumococcal disease in the pre-vaccination period, 325 cases in the post-PCV10 period and 275 cases in the post-PCV13 period. The serotypes covered by PCV10 decreased from 78.6-6.5â%. However, additional serotypes covered by PCV13 increased from 6.6-57.5% and non-PCV13 serotypes increased from 14.8-36.0â% (P<0.001) in the post-PCV13 period. In cases of meningitis, the rate of resistance to penicillin decreased after the introduction of conjugate vaccines. No resistance to ceftriaxone was found in any period. In cases without meningitis, the rate of resistance to penicillin and ceftriaxone decreased slightly. However, the rate of resistance to erythromycin and tetracycline increased and that to trimethoprim-sulfamethoxazole (SXT) decreased in the post-PCV13 period compared to the pre-PCV period. The multidrug resistance rate was 8.5â%.Conclusion. A change in the circulating serotypes and antimicrobial resistance to certain antibiotics was observed. Non-vaccine serotype circulation and multidrug resistance may compromise the success of the conjugate vaccines.
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Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Criança , Lactente , Pré-Escolar , Antibacterianos/farmacologia , Vacinas Conjugadas , Sorogrupo , Ceftriaxona , Paraguai/epidemiologia , Farmacorresistência Bacteriana , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , PenicilinasRESUMO
BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced for childhood vaccination in Brazil's National Immunization Program in 2010. After nine years of PCV10 use, we investigated the carriage prevalence, capsular types, antimicrobial resistance and risk factors among children living in Niterói city, RJ, Brazil. METHODS: Between September and December 2019, we conducted a cross-sectional study and recruited children under 6 years of age. Antimicrobial susceptibility was evaluated by the disk-diffusion method and MICs to beta-lactams and macrolides were determined by E-test®. Capsular types were deduced by multiplex PCR. Logistic regression was used to predict risk factors for pneumococcal carriage. RESULTS: Seventy-five (17.4%) of the 430 children were pneumococcal carriers. The most frequent capsular types were 6C/D (14.7%), 11A/D (13.3%), and 23B (9.3%). PCV10 serotypes represented 5.3%. All isolates were susceptible to levofloxacin, linezolid, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) made up 37.3%, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 µg/ml and 0.064-4.0 µg/ml, respectively. Of the 19 (25.3%) erythromycin-resistant (ERY-R) isolates (macrolide MICs of 6 to >256 µg/ml), most had the cMLSB phenotype (84.2%) and carried the erm(B) gene (73.7%). We detected 17 (22.6%) multidrug-resistant (MDR) isolates, strongly associated with serotype 6C/D. Presence of any symptoms, chronic diseases, childcare center attendance, living with young siblings, slum residence, and unstable income were predictors of pneumococcal carriage. CONCLUSIONS: Long-term universal childhood use of PCV10 has nearly eliminated carriage with PCV10 serotypes, but the high frequency of MDR isolates, especially associated with serotype 6C/D, remains a concern. Replacing PCV10 with PCV13 should reduce the proportion of ERY-R isolates and PNSP by at least 14% and 18%, respectively.
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Infecções Pneumocócicas , Humanos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Brasil/epidemiologia , Prevalência , Estudos Transversais , Farmacorresistência Bacteriana , Streptococcus pneumoniae , Vacinas Pneumocócicas , Sorogrupo , Penicilinas , Eritromicina , Portador Sadio/epidemiologia , Nasofaringe , Fatores de RiscoRESUMO
BACKGROUND: A serogroup W (MenW) outbreak in Chile prompted a meningococcal vaccination campaign using tetravalent meningococcal-conjugate vaccines (MCV-ACWY) in children since 2012, followed by its introduction into the National Immunization Program (NIP) in toddlers from 2014. Direct protection was observed, but no indirect effects in other age-groups were evidenced. The aim of this study was to describe invasive meningococcal disease (IMD) cases in Chile between 2009 and 2019, and its trend after the introduction of MCV-ACWYs. METHODS: IMD cases, cumulative incidence per 100,000 inhabitants, CFR, and vaccination uptake were described. Data were obtained from the Public Health Institute and NIP. RESULTS: Overall-IMD cases increased in 2009-2014 period, followed by a decline in 2015-2019, focused in infants, children <5 years and people ≥60 years. Serogroup B (MenB) and MenW alternate its predominance. Median overall incidence was 0.6/100,000, increasing from 0.6/100,000 in 2009 to 0.8/100,000 in 2014, later decreasing to 0.4/100,000 in 2019. Median incidences for MenB, serogroup C (MenC) and Y (MenY) were 0.25/100,000, <0.01/100,000 and <0.01/100,000, respectively. Median MenW incidence was 0.53/100,000, increasing from 0.01/100,000 in 2009 to 0.56/100,000 in 2014, followed by a constant decline to 0.12 in 2019. Infants, children <5 years and adults ≥60 years were affected the most, with median incidences of 9.7, 0.9 and 0.93, decreasing to 1.3, 0.1 and 0.1/100,000 in 2019, respectively. Median overall-CFR was 19%, 7.5% for MenB and 24.5% for MenW. Median MCV-ACWY uptake was 93% CONCLUSION: Overall-IMD, MenW cases and incidence declined since 2015 after the MCV-ACWY introduction, while MenB, MenC and MenY have been stable. MenW incidence declined in all age groups, including non-immunized infants and people >60 years. Further analysis and a longer period of observation are needed to have a more robust conclusion about this epidemiological trend. By 2019, CFR remains high.
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Infecções Meningocócicas , Vacinas Meningocócicas , Neisseria meningitidis , Adulto , Chile/epidemiologia , Humanos , Lactente , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Pessoa de Meia-Idade , Sorogrupo , Vacinas ConjugadasRESUMO
Disease surveillance data are needed to monitor trends in disease activity, inform decision-making in public health and evaluate disease prevention/control measures. The Sistema Regional de Vacunas (SIREVA) supports laboratory-based surveillance of invasive pneumococcal disease (IPD) in Latin American countries, providing information on identification, distribution, and anti-microbial susceptibility of pneumococcal strains. We estimated the proportion of pneumococcal meningitis and sepsis/bacteremia cases captured by SIREVA, by comparing the number of SIREVA-reported isolates in Argentina, Brazil, Chile, Colombia, Ecuador and Mexico with the estimated expected number of cases based on regional estimates of disease incidence. In all six countries, the number of isolates reported by SIREVA was consistently lower than the number of cases expected, across all years with data available. The proportion of SIREVA-reported isolates was highest in Chile (43-83%) and lowest in Mexico (1.4-3.5%). Passive surveillance systems such as SIREVA are important tools for monitoring circulating strains that could be related to pneumococcal disease, but our results show that SIREVA is likely to underestimate pneumococcal disease incidence. This under-reporting will limit the precision of surveillance data in monitoring changes in the incidence of IPD after vaccine introduction, and this should be considered when assessing the impact of vaccination programs.
PLAIN LANGUAGE SUMMARYWhat is the context?Infectious disease surveillance is an important epidemiological tool to monitor the health of a population.Surveillence can be used to detect trends in disease activity and to trigger disease control measures.In Latin America, the SIREVA surveillance system monitors occurrence of bacterial pneumonia, sepsis/bacteremia and meningitis.However, passive surveillence systems may understimate disease occurrence.What is new?We compared the number of isolates of invasive pneumococcal disease (IPD), specifically meningitis and sepsis/bacteremia, in children aged <5 years reported in SIREVA data in six countries in Latin America with the expected number of cases based on regional estimates of IPD incidence.Our results show that the number of isolates reported by SIREVA was consistently lower than the estimated number of cases, across all six countries and all the years available.The percent difference between SIREVA-reported isolates and estimated number of cases was variable between countries, ranging from 43-83% in chile to 1.4-3.5% in Mexico.What is the impact?Passive surveillance systems such as SIREVA are important tools for monitoring disease incidence, but they are likely to underestimate pneumococcal disease occrruence.This under-reporting will limit the precision of surveillance data in monitoring changes in disease incidence after vaccine introduction, and this needs to be considered when assessing vaccine impact.
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Meningite Pneumocócica , Infecções Pneumocócicas , Humanos , Incidência , Lactente , Laboratórios , América Latina/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , SorotipagemRESUMO
There is a well-known inverse association between mortality rate from infectious diseases and improvements in socioeconomic status, even though longer time-series are required to demonstrate this relationship. This general rule seems to apply to mortality from pneumonia in children in the pneumococcal conjugate vaccine (PCV) era. Two recent published secular trend studies spanning from about 30 years among Brazilians under the age of five show either no effect of PCV - not even death rate decline from pneumococcal meningitis - or a modest one (8% reduction). Time-series mortality studies from pneumonia are needed for both, developed and developing countries, those who have implemented PCV or not. Results from these studies would provide critical input and feedback to public health policy makers.
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Infecções Pneumocócicas , Pneumonia Pneumocócica , Pneumonia , Infecções Respiratórias , Brasil/epidemiologia , Criança , Humanos , Lactente , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/prevenção & controle , Vacinas ConjugadasRESUMO
After 7-valent pneumococcal conjugate vaccine introduction in the United States in 2000, invasive pneumococcal disease (IPD) due to serotype 4 greatly decreased in children and adults. Starting in 2013, serotype 4 IPD incidence increased among adults within 3 of 10 Active Bacterial Core surveillance sites. Of 325 serotype 4 cases among adults in 2010-2018, 36% were persons experiencing homelessness (PEH); incidence of serotype 4 IPD among PEH was 100-300 times higher than in the general population within these 3 areas. Genome sequencing for isolates recovered 2015-2018 (nâ =â 246), revealed that increases in serotype 4 IPD were driven by lineages ST10172, ST244, and ST695. Within each lineage, clusters of near-identical isolates indicated close temporal relatedness. Increases in serotype 4 IPD were limited to Colorado, California, and New Mexico, with highest increases among PEH, who were at increased risk for exposure to and infections caused by these strains.
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Pessoas Mal Alojadas , Infecções Pneumocócicas , Streptococcus pneumoniae , Adulto , California/epidemiologia , Colorado/epidemiologia , Humanos , Incidência , New Mexico/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae/classificação , Vacinas ConjugadasRESUMO
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children < 5 years of age. METHODS: We obtained national-level mortality data between 2000 and 2016 from 10 Latin American and Caribbean countries, using the standardized protocol. Time series models were used to evaluate the decline in all-cause pneumonia deaths during the postvaccination period while controlling for unrelated temporal trends using control causes of death. RESULTS: The estimated declines in pneumonia mortality following the introduction of PCVs ranged from 11% to 35% among children aged 2-59 months in 5 countries: Colombia (24% [95% credible interval {CrI}, 3%-35%]), Ecuador (25% [95% CrI, 4%-41%]), Mexico (11% [95% CrI, 3%-18%]), Nicaragua (19% [95% CrI, 0-34%]), and Peru (35% [95% CrI, 20%-47%]). In Argentina, Brazil, and the Dominican Republic, the declines were not detected in the aggregated age group but were detected in certain age strata. In Guyana and Honduras, the estimates had large uncertainty, and no declines were detected. Across the 10 countries, most of which have low to moderate incidence of pneumonia mortality, PCVs have prevented nearly 4500 all-cause pneumonia deaths in children 2-59 months since introduction. CONCLUSIONS: Although the data quality was variable between countries, and the patterns varied across countries and age groups, the balance of evidence suggests that mortality due to all-cause pneumonia in children declined after PCV introduction. The impact could be greater in populations with a higher prevaccine burden of pneumonia.
Assuntos
Infecções Pneumocócicas , Pneumonia Pneumocócica , Pneumonia , Argentina , Brasil , Criança , Colômbia , República Dominicana , Honduras , Humanos , Lactente , América Latina/epidemiologia , México , Nicarágua , Peru , Vacinas Pneumocócicas , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas ConjugadasRESUMO
The use of conjugate vaccines remains an effective intervention to prevent pneumococcal diseases. In order to expand vaccine coverage, the inclusion of pneumococcal proteins as carriers is a propitious alternative that has been explored over the past few years. In this study, pneumococcal surface protein A (PspA) clade 1, family 1 (PspA1) and clade 3, family 2 (PspA3) were used as carrier proteins for pneumococcal capsular polysaccharide serotype 6B (Ps6B). Employing an improved reductive amination chemistry, 50% of Ps6B was incorporated to each protein, PspA1 and PspA3. The effect of chemical modifications in Ps6B and PspA was assessed by an antigenicity assay and circular dichroism, respectively. Fragmentation and oxidation decreased the antigenicity of Ps6B while conjugation improved antigenicity. In the same manner, introduction of adipic acid dihydrazide (ADH) reduced PspA secondary structure content, which was partially restored after conjugation. Immunization of Ps6B-PspA1 and Ps6B-PspA3 conjugates in mice induced specific IgG antibodies against the Ps6B and the protein; and anti-PspA antibodies had functional activity against two pneumococcal strains with different serotypes. These results suggest that chemical coupling between Ps6B and PspA did not affect antigenic epitopes and support the further development of PspA as a carrier protein in pneumococcal conjugate vaccines to provide broader protection.
RESUMO
BACKGROUND: Pneumococcal conjugate vaccines (PCV) reduce the burden of invasive pneumococcal disease and pneumonia hospitalizations. However, there is limited evidence of the effect of PCVs on pneumonia mortality in children. It is anticipated that indirect effects resulting from PCV use among children might further reduce the remaining burden of adult pneumococcal disease caused by pneumococcal serotypes contained in PCV. Whether this will result in reduced pneumonia mortality in children and adults is still not known. METHODS: We investigated the impact of PCV on pneumonia hospitalization and mortality in in Ecuador, where PCV was introduced in 2010, considering national data from secondary data sources from 2005 to 2015. Time series analysis using regression models were used to evaluate the decline in the number of all-cause pneumonia hospitalizations and deaths in the period post-PCV introduction. The target populations were children under 5 years and adults aged 50 years and over. Outcomes of interest were hospitalizations and mortality in which the main cause of hospital admission and death, respectively, were coded as ICD10 codes J12-18 (pneumonia). Three different models were fitted. RESULTS: We demonstrate a sizeable impact of PCV in pneumonia hospitalization in children < 1 year (27% reduction, 95%CI 12-42%), and < 5 years of age (33% reduction, 95%CI 11-43%). The estimated impact of PCV in pneumonia mortality was a reduction of 14% in < 1 year (95%CI 0-33%), 10% in < 5 years (95%CI 0-25%), and 22% (95%CI 7-34%) in adults aged 50-64 years. Little evidence of a change was detected in elderly ≥ 65 years. CONCLUSION: This study is the first to report on the impact of PCV in pneumonia morbidity and mortality in children and older adults, being relevant to policy makers and global donors. Findings were consistent when using different models. Additional studies on the indirect effect of PCV in older adults are needed.
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Infecções Pneumocócicas , Pneumonia Pneumocócica , Pneumonia , Idoso , Criança , Pré-Escolar , Equador/epidemiologia , Hospitalização , Humanos , Lactente , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Vacinas ConjugadasRESUMO
La tecnología para el desarrollo de vacunas conjugadas preventivas consiste en la unión de polisacáridos bacterianos y una proteína portadora. Este procedimiento constituye uno de los principales desafíos en el mundo de la vacunología y por tanto del Comité Nacional de Expertos en Vacunas. Este órgano, guía y discute las estrategias para el desarrollo e introducción de nuevas vacunas en Cuba. El objetivo de este trabajo fue realizar un análisis de la investigación mundial sobre vacunas conjugadas con la plataforma BD-BiPat (Instituto Finlay de Vacunas, Cuba). La plataforma BD-BiPat permite acceder con formularios de búsqueda directamente a los MeSH a través de PubMed y extraer los datos para su normalización, análisis y visualización. El término usado fue Vaccines, Conjugate. El corpus de datos constó de 3852 registros a los que se aplicaron indicadores métricos de co-ocurrencia y visualizaciones en forma de redes. Los resultados del estudio permitieron evidenciar que es una tecnología muy efectiva, que se ha incrementado rápidamente a nivel mundial. Entre los agentes infecciosos asociados a vacunas conjugadas más estudiados están: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae y Salmonella Typhi. Estados Unidos de América y Reino Unido fueron los países más productivos. Los resultados obtenidos podrían tributar a los decisores en política científica de instituciones dedicadas al desarrollo de vacunas, así como su introducción en programas de vacunación. Igualmente, las funcionalidades de la aplicación web BD-BiPat pueden extenderse a los grupos de vigilancia e inteligencia del sector(AU)
The technology for the development of conjugate vaccines consist of the union of bacterial polysaccharides and a protein carrier. This procedure constitutes one of the main challenges in the world of vaccinology and therefore of the Cuban Expert Committee on Vaccines. This committee guides and discusses strategies for the development and introduction of new vaccines in Cuba. The aim of this work was to perform an analysis of the global research on conjugated vaccines with the BD-BiPat platform (Finlay Institute of Vaccines, Cuba). This platform allows access with search forms directly to the PubMed MeSH and extract data for normalization, analysis and visualization. The term used was Vaccines, Conjugate. The data corpus consisted of 3852 records to which metric indicators of co-occurrence and visualizations in the form of networks were applied. The study showed that it is a novel technology, which has increased rapidly worldwide. Among the most studied infectious agents associated with conjugate vaccines are Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae and Salmonella Typhi. The United States of America and the United Kingdom were the most productive countries. Results could be useful for decision-makers in scientific policy for the vaccine development, as well as introduction of vaccines in programs of immunization. Likewise, the functionalities of the BD-BiPat platform can be extended to surveillance and intelligence groups in this sector(AU)
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Humanos , Masculino , Feminino , Revisão por Pares/métodos , Software , Vacinas Conjugadas/uso terapêutico , Vacinas , CubaRESUMO
Resumen Introducción: En México, cuando se inició la aplicación de la vacuna PCV13 (neumocócica conjugada), se cubría el 70.6% de los serotipos causantes de enfermedad invasiva por neumococo en menores de 5 años. Después de varios años, los casos de enfermedad causada por los serotipos incluidos en la vacuna han disminuido; sin embargo, se ha producido un reemplazo por los serotipos no incluidos en la vacuna. Caso clínico: Se presentan tres casos de pacientes pediátricos que desarrollaron enfermedad invasiva por serotipos no incluidos en la PCV13: uno con meningitis y bacteriemia (serotipo 15C) y dos con neumonía, uno de ellos complicado con derrame (serotipo 35B). Los pacientes fueron atendidos en un hospital pediátrico en Saltillo, Coahuila, durante el periodo de 2015 a 2018. Conclusiones: Resulta alarmante que se presenten tres casos graves por serotipos de Streptococcus pneumoniae no incluidos en la PCV13 en un solo hospital pediátrico en el norte del país. Este es un fenómeno que esta sucediendo a escala nacional e internacional: un incremento de casos de enfermedad invasiva por serotipos de neumococo no incluidos en la vacuna utilizada actualmente.
Abstract Background: In Mexico, 70.6% of serotypes causing invasive pneumococcal disease were covered since the application of the PCV13 vaccine in children under 5 years of age. After several years of immunization, cases of disease caused by the serotypes included in the vaccine have decreased. However, a replacement due to serotypes not included in the vaccine has been observed. Case report: Three cases of pediatric patients who developed invasive disease due to serotypes not included in PCV13 are described: one with meningitis and bacteremia (serotype 15C), and two with pneumonia, of which one complicated with effusion (serotype 35B). Patients were treated in a pediatric hospital in Saltillo, Coahuila, from 2015 to 2018. Conclusions: Three serious cases due to serotypes of Streptococcus pneumoniae not included in PCV13 were reported in a single pediatric hospital in a northern state of Mexico. This phenomenon is taking place nationwide and worldwide: an increase of cases of invasive disease due to pneumococcal serotypes not included in the vaccine currently used.
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Pré-Escolar , Feminino , Humanos , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/classificação , Vacinas Pneumocócicas , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/isolamento & purificação , Sorotipagem , Vacinas Conjugadas , MéxicoRESUMO
Background: In Mexico, 70.6% of serotypes causing invasive pneumococcal disease were covered since the application of the PCV13 vaccine in children under 5 years of age. After several years of immunization, cases of disease caused by the serotypes included in the vaccine have decreased. However, a replacement due to serotypes not included in the vaccine has been observed. Case report: Three cases of pediatric patients who developed invasive disease due to serotypes not included in PCV13 are described: one with meningitis and bacteremia (serotype 15C), and two with pneumonia, of which one complicated with effusion (serotype 35B). Patients were treated in a pediatric hospital in Saltillo, Coahuila, from 2015 to 2018. Conclusions: Three serious cases due to serotypes of Streptococcus pneumoniae not included in PCV13 were reported in a single pediatric hospital in a northern state of Mexico. This phenomenon is taking place nationwide and worldwide an increase of cases of invasive disease due to pneumococcal serotypes not included in the vaccine currently used.
Introducción: En México, cuando se inició la aplicación de la vacuna PCV13 (neumocócica conjugada), se cubría el 70.6% de los serotipos causantes de enfermedad invasiva por neumococo en menores de 5 años. Después de varios años, los casos de enfermedad causada por los serotipos incluidos en la vacuna han disminuido; sin embargo, se ha producido un reemplazo por los serotipos no incluidos en la vacuna. Caso clínico: Se presentan tres casos de pacientes pediátricos que desarrollaron enfermedad invasiva por serotipos no incluidos en la PCV13: uno con meningitis y bacteriemia (serotipo 15C) y dos con neumonía, uno de ellos complicado con derrame (serotipo 35B). Los pacientes fueron atendidos en un hospital pediátrico en Saltillo, Coahuila, durante el periodo de 2015 a 2018. Conclusiones: Resulta alarmante que se presenten tres casos graves por serotipos de Streptococcus pneumoniae no incluidos en la PCV13 en un solo hospital pediátrico en el norte del país. Este es un fenómeno que esta sucediendo a escala nacional e internacional: un incremento de casos de enfermedad invasiva por serotipos de neumococo no incluidos en la vacuna utilizada actualmente.
Assuntos
Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas , Streptococcus pneumoniae/classificação , Pré-Escolar , Feminino , Humanos , México , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/tratamento farmacológico , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação , Vacinas ConjugadasRESUMO
BACKGROUND: Serogroup causing invasive meningococcal disease (IMD) can change abruptly, as it occurred in Chile when serogroup predominance switched from MenB to MenW in 2012. As a response, a national vaccination strategy was implemented since 2012 using tetravalent meningococcal-conjugate vaccines (MCV-ACWY) in children 9â¯months through 4â¯years of age. The aim of this study was to describe IMD cases by MenW in Chile 2009-2016, and to analyse its trend after the introduction of MCV-ACWY. METHODS: Descriptive study of IMD cases in Chile, period 2009-2016. Cumulative incidence and mortality rate per 100,000 inhabitants, and case fatality rate (CRF) were used for descriptive analysis. Linear regression was used for post-intervention trend analysis. RESULTS: In 2012, MenW, mainly ST-11â¯cc, became predominant. MenW incidence rose from 0.01/100,000 inhabitants in 2009 to a maximum of 0.6/100,000 in 2015. Infants and adults 80â¯years of age and older were mostly affected, with an incidence peak of 9.7/100,000 and 1.6/100,000, respectively, in 2015. In the group of children from 1 to 4â¯years of age MenW incidence declined from 1.3/100,000 in 2012 to 0.1/100,000 in 2016, a 92.3% reduction after vaccination implementation. In the same period and age-cohort, CFR decreased from 23% to 0%. High mortality rates concentrated in infants and adults 80â¯years of age and over. CONCLUSION: MenW became predominant in Chile since 2012. IMD cases increased steadily from 2009 to 2016, with higher incidence, CFR and mortality concentrating in infants and people 80â¯years of age and older. MCV-ACWY provided direct protection against MenW, reducing its incidence after mass meningococcal vaccine implementation. Indirect effects of vaccination are not yet observed.
Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Conjugadas/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningite Meningocócica/epidemiologia , Meningite Meningocócica/prevenção & controle , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/uso terapêutico , Pessoa de Meia-Idade , Neisseria meningitidis/imunologia , Neisseria meningitidis/patogenicidade , Sorogrupo , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: This systematic review aims to describe the prevalence, trends, and antibiotic resistance of Streptococcus pneumoniae serotype 19A (Spn19A) that causes invasive and non-invasive diseases in children <5â¯years in Latin-American and Caribbean countries. METHODS: We searched for published (between January 2010 and February 2016) observational and clinical studies within the region including effectiveness and impact on Spn19A after pneumococcal conjugate vaccine (PCV) introduction. We calculated prevalence estimates by country and standardized the frequency of isolates to conduct an interrupted time series analysis for selected countries and to assess the potential changes in disease trends, overall and for Spn19A. RESULTS: We identified and reviewed full-text of 89 publications and included 59 in the analysis. Data from the laboratory surveillance network, SIREVA, were included in 43 (74%) of the invasive pneumococcal disease reports. There are differences in the sensitivity, representativeness, and heterogeneity of laboratory surveillance. There has been and overall reduction in the trend and number of invasive S. pneumoniae isolates in children <5â¯years after PCVs introduction. To date, the prevalence of Spn19A has increased, however, there has been no observed change in the trend. CONCLUSIONS: This updated systematic review provides evidence of a reduction in the total number of invasive pneumococcal disease isolates after the introduction of PCVs in the region but cannot yet conclude a change in the trend of Spn19A disease.
Assuntos
Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/patogenicidade , Vacinas Conjugadas/uso terapêutico , Região do Caribe , Humanos , América Latina , Penicilinas/farmacologia , Infecções Pneumocócicas/tratamento farmacológico , Sorogrupo , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/imunologiaRESUMO
The significant increase in the incidence rates and ongoing outbreaks of serogroup C meningococcal (MenC) disease, associated with the sequence type-103 complex, motivated the incorporation of the meningococcal C conjugate (MCC) vaccine in the routine immunization program in the State of Bahia, Brazil in early 2010, targeting children younger than 5 years of age. In its capital, Salvador, the program also included a catch-up campaign for individuals 10-24 years of age. We performed an observational, ecological study, analyzing data collected from 2007 to 2015, to compare the impact of these two immunization strategies on meningococcal disease incidence and mortality rates. In Salvador, following the vaccination program, a dramatic early impact on MenC disease and mortality rates could be observed, with significant reductions in incidence rates of MenC disease in all age groups, including individuals that were too old to have been vaccinated, indicating the presence of herd protection. Compared to the pre-vaccine period, a virtual disappearance of MenC disease was observed in 2015. However, in the state of Bahia (excluding the city of Salvador), no herd protection could be observed, with significant impact only among vaccine-eligible children within 5 years of introduction of the MCC vaccination program. These results highlight the importance of catch-up campaigns, including adolescents and young adults, to induce herd protection compared to immunization strategies restricted to infants and young children. This information is crucial for identifying optimal immunization policies and future strategies, focused on adolescents, to optimize the impact of MCC vaccination programs.
Assuntos
Surtos de Doenças/prevenção & controle , Imunização Secundária/métodos , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/uso terapêutico , Neisseria meningitidis Sorogrupo C/imunologia , Vacinação/métodos , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Programas de Imunização/métodos , Incidência , Lactente , Masculino , Infecções Meningocócicas/epidemiologia , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento , Vacinas Conjugadas/uso terapêutico , Adulto JovemRESUMO
The bacterial expression of glycoproteins has experienced significant progress in recent years, particularly in regard to the production of conjugate vaccines against pathogens. In this case, a protein carrier conjugated with glycosides is used to produce intense stimulation of the immune system. Glycoconjugate vaccines account for 35% of the global vaccine market, and consequently, several biotechnological companies have developed products for the purification of glycosylated proteins to attain homogeneity. In this chapter we present a general process for glycoprotein production in Escherichia coli and a practice method for purification of glycosylated proteins, using affinity chromatography.
Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Glicoconjugados/metabolismo , Glicoproteínas/metabolismo , Vacinas Conjugadas/metabolismo , Cromatografia de Afinidade/métodos , GlicosilaçãoRESUMO
BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries. METHODS: We evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum. RESULTS: We found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level. CONCLUSIONS: These results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations.
Assuntos
Hospitalização/estatística & dados numéricos , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Pneumocócica/prevenção & controle , Pobreza , Fatores Socioeconômicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/prevenção & controle , Pneumonia Pneumocócica/epidemiologia , Análise Espaço-Temporal , Vacinação , Cobertura Vacinal/estatística & dados numéricos , Adulto JovemRESUMO
Abstract Objective: HIV-infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI. Methods: HIVI and HIV uninfected individuals (HIVU), aged 2-18 years, CD4 >15% were recruited. Seroprotection (hSBA ≥1:4) at baseline and at 12-18 months after immunization was evaluated and the association of the different factors with the long-term persistence was calculated using logistic regression. Results: A total of 145 HIVI, 50 HIVU were recruited and immunized, and their median age was 11 years (median age in HIVI group was 12 years, and 10 years in HIVU group, p-value = 0.02). 85 HIVI (44%) had undetectable viral load (UVL). Seroprotection rate was 27.2%: 24.1% in HIVI and 36% in HIVU 12-18 months after immunization (p = 0.14). Baseline immunity (odds ratio [OR] = 70.70, 95% CI: 65.2-766.6); UVL at entry (OR: 2.87, 95% CI: 0.96-8.62) and lower family income (OR: 0.09, 95% CI: 0.01-0.69) were associated with seroprotection among HIVI. Conclusion: Seroprotection at 12-18 months after single dose of MCC was low for both groups, and higher among individuals who presented baseline immunity. Among HIVI, vaccine should be administered after UVL is achieved.
Resumo Objetivo: As pessoas infectadas pelo HIV (HIVI) estão sujeitas a infecção meningocócica e apresentam menor resposta a vacinas. São escassos os dados a respeito da persistência de longo prazo do anticorpo bactericida no soro humano (hSBA) após vacina conjugada meningocócica C (MCC) em HIVI jovens e visamos a descrever essa persistência em HIVI. Métodos: Foram recrutadas pessoas HIVI e pessoas não infectadas por HIV (HIVU), entre 2 e 18 anos, CD4 > 15%. A seroproteção (hSBA ≥ 1:4) basal aos 12-18 meses após a imunização foi avaliada e a associação dos diferentes fatores com a persistência de longo prazo foi calculada com a regressão logística. Resultados: Foram recrutados 145 HIVI e 50 HIVU e imunizados e sua idade média foi determinada em 11 anos (12 no grupo HIVI e 10 no grupo HIVU, valor de p = 0,02); 85 HIVI (44%) apresentaram carga viral indetectável (CVI). A taxa de seroproteção foi 27,2%: 24,1% no grupo HIVI e 36% no grupo HIVU 12-18 meses após imunização (p = 0,14). A imunidade basal [razão de chance (RC) = 7070, IC: 65,2-7666]; CVI no momento da participação (RC: 2,87, IC de 95%: 0,96-8,62) e renda familiar mais baixa (RC: 0,09, IC de 95%: 0,01-0,69) foram associadas a seroproteção entre as pessoas HIVI. Conclusão: A seroproteção aos 12-18 meses após única dose de MCC mostrou-se baixa em ambos os grupos e mais elevada entre as pessoas que apresentaram imunidade basal. Entre as pessoas HIVI, as vacinas devem ser administradas após a CVI ser atingida.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Síndrome da Imunodeficiência Adquirida/imunologia , Vacinas Meningocócicas/imunologia , Infecções Meningocócicas/prevenção & controle , Anticorpos Antibacterianos/imunologia , Fatores de Tempo , Estudos de Casos e Controles , Vacinas Meningocócicas/administração & dosagem , Anticorpos Antibacterianos/sangueRESUMO
El polisacárido Vi (PsVi) de Salmonella Typhi es un antígeno T-independiente y ha demostrado ser protector en adultos jóvenes. Sin embargo, para aumentar la respuesta de anticuerpos y conferir propiedades T-dependientes al polisacárido, se ha conjugado a proteínas. Dentro de los controles exigidos por los organismos regulatorios para estas vacunas está la identidad antigénica de sus componentes y para eso se recomiendan el uso de técnicas de Resonancia Magnética Nuclear o técnicas serológicas. El objetivo del presente trabajo, fue establecer las condiciones óptimas de trabajo de un Dot Blot que permitiera determinar, rápidamente, la identidad de los antígenos en vacunas conjugadas contra S. Typhi. Para ello, se estudiaron los tiempos de incubación, las concentraciones óptimas de anticuerpo monoclonal (AcM) y del ingrediente farmacéutico activo (IFA), así como los volúmenes de aplicación óptimos para las IFAs y formulaciones vacunales, tanto para el PsVi como para el toxoide diftérico (TD). Los resultados mostraron que para la determinación de la identidad antigénica fueron suficientes 5 µL de muestras de los conjugados monovalentes en una dilución de 1/10 (vol/vol) e igual volumen para las formulaciones vacunales. Quedó demostrado que la concentración de 2,5 µg/mL para el AcM contra el PsVi y a 2 µg/mL para el AcM contra TD fueron suficientes para la determinación; mientras que los tiempos de incubación fueron ajustados a 15 min con incubación a 37 ºC. Como conclusión del trabajo se puede decir que quedaron establecidas las condiciones óptimas de trabajo para la determinación rápida de la identidad antigénica del PsVi y del TD presentes en IFA y formulaciones vacunales conjugadas(AU)
Vi polysaccharide from Salmonella Typhi is a T-independent antigen that has proven to be protective in young adults. However, it has been conjugated to proteins in order to confer T-dependent properties to the polysaccharide, and improving the antibody response. The regulatory agencies require knowing the identity of antigens included in vaccines. The Nuclear Magnetic Resonance spectroscopy and serological techniques are recommended. The aim of this work was to establish the optimal working conditions of a Dot Blot that would allow to determine quickly the identity of the antigens in conjugate vaccines against S. Typhi. The incubation times, optimum concentrations of monoclonal antibodies (MAb) and active pharmaceutical ingredient (API), as well as optimum application volumes for APIs and vaccine formulations were studied for both, PsVi and diphtheria toxoid (DT). It was proven that 5 µL of samples of the monovalent conjugates were sufficient at a dilution of 1/10 (vol/vol) and an equal volume for the vaccine formulations. It was demonstrated that the concentration of 2.5 µg/mL for the MAb against PsVi and 2 µg/mL for the MAb against DT were suitable. The incubation times were adjusted to 15 min with incubation at 37 ºC. It was established a simple and rapid method for the specific identification of PsVi and DT present in API and conjugate vaccines(AU)