Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly. Keywords: Antimicrobial resistance; Chronic diseases; Comorbidity; Invasive pneumococcal diseases; Pneumococcal conjugate vaccine; Pneumococcal serotypes; Pneumococcal vaccine.

Caracterización del polirribosilribitol fosfato por cromatografía de exclusión molecular de alta eficacia con detección ultravioleta / Characterization of polyribosylribitol phosphate by high efficiency size exclusion chromatography with ultraviolet detection

Haemophilus influenzae tipo b es un importante patógeno del hombre causante de varias de las enfermedades invasivas en niños menores de cinco años, contra el cual fueron autorizadas las vacunas glicoconjugadas a partir del polirribosilribitol fosfato. Quimi-Hib® es la primera y única vacuna contra este patógeno que utiliza el polisacárido obtenido por síntesis química. El Ingrediente Farmacéutico Activo es producido por el Centro de Ingeniería Genética y Biotecnología y se obtiene a partir de su conjugación al toxoide tetánico. En el presente reporte se hizo una caracterización del polirribosilribitol fosfato mediante la técnica de cromatografía de exclusión molecular de alta eficacia con detección ultravioleta a 215 nm. En el estudio se evaluaron tres lotes y se determinó el perfil de elución en una columna SuperdexTM 75 10/300 GL Increase con un porciento de pureza de 77,42 ± 8,97 y una masa molar promedio de 7.381 Da ± 210,93. La principal impureza presente en el polirribosilribitol fosfato es el dimetilsulfóxido, disolvente utilizado en la reacción de activación con el éster N-hidroxisuccinimidilo del ácido β-maleimidopropiónico. El polirribosilribitol fosfato se purificó por filtración con un Amicon Ultra-15 de 2.000 Da hasta una pureza de 99,1 por ciento y se conjugó al toxoide tetánico. El rendimiento de la reacción de conjugación con el polisacárido purificado fue de 30,0 por ciento 1,77 el cual no muestra diferencias significativas con el control que fue 33,7 por ciento ± 3,57 demostrándose que el dimetilsulfóxido no afecta el desempeño de la reacción de conjugación(AU)

Haemophilus influenzae type b is an important human pathogen causing some invasive diseases in children less than five years of age. Glycoconjugate vaccines based on polyribosylribitol phosphate have been licensed against this bacterium. Quimi-Hib® is the first and only vaccine against this pathogen using the chemically synthesized polysaccharide. The Active Pharmaceutical Ingredient is produced by the Center for Genetic Engineering and Biotechnology and is obtained from its conjugation to tetanus toxoid. In the present report a characterization of polyribosylribitol phosphate was performed by high performance molecular exclusion chromatography with ultraviolet detection at 215 nm. Three batches were evaluated in the study and the elution profile was determined on a SuperdexTM 75 10/300 GL Increase column with a purity percentage of 77.42 ± 8.97 and an average molecular weight of 7,381 Da ± 210.93. The main impurity present in polyribosylribitol phosphate was dimethylsulfoxide, the solvent used in the activation reaction with N-hydroxysuccinimidyl ester of β-maleimidopropionic acid. Polyribosylribitol phosphate was purified by filtration using a 2,000 Da cut-off Amicon Ultra-15 to a purity of 99.1 percent and conjugated to tetanus toxoid. The yield of the conjugation reaction with the purified polysaccharide was 30.0 percent ± 1.77 which shows no significant difference with the control which was 33.7 percent ± 3.57 demonstrating that dimethylsulfoxide does not affect the performance of the conjugation reaction(AU)

Evaluation of the direct and indirect impact on pneumonia hospitalization after almost a decade of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Brazil

Introduction: Pneumococcal pneumonia is a leading cause of severe disease, leading to approximately 2.2 million hospital admissions in 2019 in Brazil. Since 2010, the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine was introduced in Brazil, as part of the National Immunization Program (NIP) with universal access, approximated coverage of 91.4% in 2019. Although studies from many countries are available, there is still a need to understand the effect of the vaccine introduction on the incidence of pneumonia hospitalizations in Brazil.Methods: Data on hospitalization associated with the diagnosis of pneumonia in the population assisted by the Brazilian Public Health System were accessed to fit a time series analysis, which tested the main hypothesis of the influence of vaccination on the trends for the incidence of pneumonia hospitalizations.Results: The post-vaccination period showed a negative trend, reducing 1.75, 0.16, and 0.11 cases per 100,000 inhabitants per month for the groups < 1, 1­4, and 5­9 years old, respectively. In individuals older than 20 years, the post-vaccination period has a positive trend, but not as great as compared trends before the vaccination period. These results indicate a protective herd effect in the older population, nine years after introducing the pneumococcal vaccine in the NIP.Conclusion: Vaccination with pneumococcal conjugated vaccine reduces hospitalizations associated with pneumonia diagnosis in vaccinated and non-vaccinated populations in a sustained and progressive manner.

Sistema de seguimiento y control eProtect infecciones respiratorias / eProtect respiratory infection monitoring and control system

Las infecciones del tracto respiratorio (ITR) son una de las principales causas de morbilidad y mortalidad en todo el mundo, y representan el 4,4 % de las muertes en todas las edades. A nivel mundial, se han observado disminuciones en la mortalidad causada por las ITR después de la introducción de las vacunas conjugadas contra Haemophilus influenzae tipo b, tos ferina y neumocócica. Sin embargo, las ITR siguen siendo una de las principales causas de mortalidad entre los niños pequeños y los ancianos en los países de ingresos bajos y medios. Se planteó un estudio donde se aplicó un sistema de seguimiento que sirvan para monitorear la vigilancia de las infecciones respiratorias agudas (IRA) en servicios de salud, por laboratorio y en unidades centinela en Perú. Participaron 67 médicos generales o cirujanos de 8 servicios de pediatría. 1453 casos de las IRA fueron de etiología viral, identificando al virus sincitial respiratorio (63,94%), Influenza AH1N1 (16,59%); en el caso de las neumonías bacterianas se aislaron Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae y Streptococcus beta hemolyticus. Durante la última década de reforma del sistema de salud, Perú ha hecho de la construcción de su sistema de APS una prioridad. Sin embargo, el sistema se enfrenta actualmente a desafíos para proporcionar atención de alta calidad y valor a la población debido a deficiencias en varias dimensiones. El sistema de APS ayudará a responder a la transición epidemiológica actual y futura epidemia brotes de manera más eficaz(AU)

Respiratory tract infections (RTIs) are one of the leading causes of morbidity and mortality worldwide, accounting for 4.4% of deaths in all ages. Globally, declines in mortality from RTIs have been observed after the introduction of Haemophilus influenzae type b, pertussis, and pneumococcal conjugate vaccines. However, RTIs remain a leading cause of mortality among young children and the elderly in low- and middle-income countries. A study was proposed where a monitoring system was applied to monitor the surveillance of acute respiratory infections (ARI) in health services, by laboratory and in sentinel units in Peru. A total of 67 general practitioners or surgeons from 8 pediatric services participated. 1453 cases of ARI were of viral aetiology, identifying the respiratory syncytial virus (63.94%), Influenza AH1N1 (16.59%); in the case of bacterial pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus beta hemolyticus were isolated. During the last decade of health system reform, Peru has made building its PHC system a priority. However, the system currently faces challenges in providing high quality and value care to the population due to deficiencies in several dimensions. The PHC system will help respond to current epidemiological transition and future epidemic outbreaks more effectively(AU)

Trajectory of serogroups causing Invasive Meningococcal Disease in Santa Catarina state, Brazil (2007-2019)

Abstract The aim of this study was to compare the trajectory of serogroups causing Invasive Meningococcal Disease (IMD) in the Santa Catarina (SC) state with those of whole Brazil. A retrospective analysis of all IMD cases reported from January 2007 to December 2019 was carried out. During the study period, 26,058 IMD cases were registered in Brazil and 644 and in SC state alone. Overall, Brazil showed progressive reduction in cases since 2010, when the meningococcal C conjugate vaccine was introducted on National Immunization Program, while SC showed an increase in total cases since 2013, particularly from serogroups W and C. Serogroups distribution was significantly different between Brazil and SC. The emergence of serogroup W highlights the improved meningococcal surveillance through increased accuracy in identification methods in SC state. This finding is important for discussing recommendations of quadrivalent (ACWY) conjugate vaccines in different geographical areas of Brazil.

Análisis de la investigación mundial sobre vacunas conjugadas con la plataforma BD-BiPat / Analysis of the global research on conjugate vaccines with the BD-BiPat platform

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)

Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version) / 中华流行病学杂志

Pneumococcal disease is a serious global public health problem and a leading cause of morbidity and mortality of children and adults in China. Antibiotics are commonly used to treat pneumococcal disease. However, antibiotic resistance to Streptococcus pneumoniae has become a severe problem around the world due to widespread antibiotic use. Immunoprophylaxis of pneumococcal disease with pneumococcal vaccines is therefore of great importance. In this article, we review the etiology, clinical presentation, epidemiology, and disease burden of pneumococcal disease and the vaccinology of pneumococcal vaccines. Our review is based on the Expert Consensus on Immunoprophylaxis of Pneumococcal Disease (2017 version), the Pneumococcal Vaccines WHO Position Paper (2019), and recent national and international scientific advances. This consensus article aims to provide public health and vaccination staff with appropriate evidence for pneumococcal vaccine use and to improve professional capacity for pneumococcal disease prevention and control.

Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version) / 中华预防医学杂志

Pneumococcal disease is a serious global public health problem and a leading cause of morbidity and mortality of children and adults in China. Antibiotics are commonly used to treat pneumococcal disease. However, antibiotic resistance to

A phase Ⅲ clinical trial study on the safety and immunogenicity of ACYW135 group meningococcal conjugate vaccine inoculated in 3 month old infants / 中华预防医学杂志

The aim of this study was to evaluate the safety and immunogenicity of the first domestic ACYW135 meningococcal conjugate vaccine and a control vaccine named AC group meningococcal conjugate vaccine for 3 months (90-119 days) infants. From February 2017 to June 2018, a randomized, blinded, and similar vaccine-controlled clinical trial design was adopted at the Henan Vaccine Clinical Research Base. The subjects were 3 months old healthy infants, a total of 720, based on a 1∶1 ratio. The random allocation table for entry was randomly assigned to the experimental group and the control group. According to the 3, 4, and 5 month-old vaccination procedures, the subjects were vaccinated with test vaccine (ACYW135 group meningococcal conjugate vaccine) and control vaccine (group A group C meningococcal polysaccharide conjugate vaccine), of which 720 were given the first dose, 696 were given the second dose (test group: 346; control group: 350), and 692 were given the third dose (test group: 344; Control group: 348). The overall adverse reaction rate of the test vaccine was 21.90% (230 cases), which was lower than the 32.04% (339 cases) of the control vaccine (0.05). Group Y and W135 was 88.17% (298 cases), 99.41% (336 cases), respectively. The GMT results showed that the test vaccine group A was 56.24, the control vaccine was 57.43 (>0.05); the group C test vaccine (43.53) was higher than the control group (27.28) (<0.001). The group Y and W135 are 89.22 and 140.66, respectively. Among them, the proportion of the group C GMT antibody ≥ 1∶128 for test vaccine (31.07%, 105 cases) was higher than the control vaccine (16.22%, 55 cases) (<0.001). ACYW135 group meningococcal conjugate vaccine has more safety and immunogenicity after application to 3 month old infants.

Signal Detection of Adverse Events Following Pneumococcal Vaccines from the Korea Adverse Event Reporting System Database, 2005–2016

PURPOSE: We aimed to analyze the surveillance reports of adverse events (AEs) due to different types of pneumococcal vaccines, in addition to detecting and validating signals of pneumococcal vaccines by comparing AEs with labels.MATERIALS AND METHODS: We analyzed the percentages of AEs according to vaccine type [pneumococcal polysaccharide vaccines (PPSVs) and pneumococcal conjugate vaccines (PCVs)] in children and adults using data from the Korea Adverse Event Reporting System (KAERS) database from 2005 to 2016. A signal was defined as an AE that met all three indices of data mining: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). We validated the detected signals by calculating sensitivity, specificity, as well as positive and negative predictive values of the signals against label information.RESULTS: Of the 39933 AE reports on vaccination, 5718 (7.0%) were related to pneumococcal vaccine. The most frequent AE after vaccination with PPSV was fever (23.9%) in children and injection-site reaction in adults. The most frequent AE after vaccination with PCV in children was pharyngitis (26.2%). In total, 13 AEs met all three indices for signal detection. Among these, hypotension, apathy, sepsis, and increased serum glutamic oxaloacetic transaminase level were not listed on vaccine labels. In validation analysis, PRR and ROR performed slightly better than IC for adults who were vaccinated with PPSVs.CONCLUSION: Overall, 13 new signals of PPSVs, including four signals not listed on the labels, were detected. Further research based on additional AE reports is required to confirm the validity of these signals for children.

Infecciones invasivas por serotipos no vacunales de Streptococcus pneumoniae: una amenaza creciente / Invasive infections by non-vaccine serotypes of Streptococcus pneumoniae: a growing threat

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.

Comparison of Immune Responses to Two Quadrivalent Meningococcal Conjugate Vaccines (CRM197 and Diphtheria Toxoid) in Healthy Adults

BACKGROUND: After the introduction of the meningococcal ACWY-CRM197 conjugate vaccine (MenACWY-CRM) in 2012 and the meningococcal ACWY-diphtheria toxoid conjugate vaccine (MenACWY-DT) in 2014, immunization was recommended for certain high-risk groups including new military recruits in Korea. However, comparative immunogenicity studies for these vaccines have not been performed in Korea. Here, we compared the immunogenicity of these two vaccines in healthy adults. METHODS: A total of 64 adults, 20–49 years of age, were randomly divided into two groups (1:1) to receive either of the two vaccines. The sera were obtained before and 1 month after vaccination and tested for serogroup-specific serum bactericidal activity using baby rabbit complement. RESULTS: There were no significant differences post-vaccination in the geometric mean indices and the seropositive rate to all serogroups between the vaccines. The proportion of seropositive subjects after vaccination ranged from 88% to 100%. CONCLUSION: Both meningococcal conjugate vaccines showed good immunogenicity in healthy Korean adults without statistically significant differences. Further investigations for serotype distribution of circulating meningococci and the immune interference between other diphtheria toxin-containing vaccines concomitantly used for military recruits are needed to optimize immunization policies. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002460

Experts' consensus on immunization with meningococcal vaccines in China / 中华预防医学杂志

Meningococcal vaccines in the Chinese market include meningococcal polysaccharide vaccine, meningococcal polysaccharide conjugate vaccine, and a combined vaccine. Meningococcal conjugate vaccines immunization schedules vary by vaccine manufacturer, and often cause confusion in immunization practices. Based on the epidemiological characteristics of meningococcal disease, serogroup distribution of Neisseria meningitidis, and research progress on the immunogenicity and safety of meningococcal vaccines, we developed an experts' consensus on immunization with meningococcal vaccines to provide guidance for immunization providers and for centers for disease control and prevention staff.

Efficacy, safety, and cost-effectiveness of meningococcal vaccines / 中华预防医学杂志

Meningococcal meningitis is an acute, severe respiratory infectious disease caused by Neisseria meningitidis. Immunization with meningococcal vaccine is the most effective measure to control and prevent transmission of meningococcal meningitis. Meningococcal vaccines in the Chinese market include meningococcal polysaccharide vaccine, meningococcal polysaccharide conjugate vaccine, and a combined vaccine containing meningococcal polysaccharide conjugate vaccine. This article reviews research progress on the efficacy, safety, and cost-effectiveness of meningococcal vaccines, particularly in the Chinese market, to support appropriate use of the various meningococcal vaccines for preventing meningococcal meningitis.

Status of group B streptococcal vaccine development

Streptococcus agalactiae (group B streptococcus, GBS) is a leading causal organism of neonatal invasive diseases and severe infections in the elderly. Despite significant advances in the diagnosis and treatment of GBS infections and improvement in personal hygiene standards, this pathogen is still a global health concern. Thus, an effective vaccine against GBS would augment existing strategies to substantially decrease GBS infection. In 2014, World Health Organization convened the first meeting for consultation on GBS vaccine development, focusing on the GBS maternal immunization program, which was aimed at reducing infections in neonates and young infants worldwide. Here, we review the history of GBS infections, the current vaccine candidates, and the current status of immunogenicity assays used to evaluate the clinical efficacy of GBS vaccines.

Expert consensus on immunization for prevention of pneumococcal disease in China (2017) / 中华流行病学杂志

Pneumococcal disease is one of the serious global public health problems, and an important leading cause of the morbidity and mortality of children and adults in China. Currently, antibiotics are the most choices for its clinical treatment. However, antibiotic resistance of has become a severe problem around the world due to the wide use of antibiotics. Hence, the prevention of pneumococcal disease by using pneumococcal vaccines is of great importance. In this article, we reviewed the etiology, clinic, epidemiology, disease burden of pneumococcal disease, and the vaccinology of pneumococcal vaccines, based on the Pneumococcal Vaccines WHO Position Paper (2012) and other latest evidence globally, to introduce comprehensive knowledge of pneumococcal disease, and for the purpose to improve the capacity of the professionals working on pneumococcal disease control and prevention and to provide appropriate evidences of pneumococcal vaccine applications for people who are engaged in public health and immunization vaccination.

Validation of a Multiplexed Opsonophagocytic Assay for 11 Additional Pneumococcal Serotypes and Its Application to Functional Antibody Evaluation Induced by Pneumococcal Polysaccharide Vaccine

BACKGROUND: Various pneumococcal vaccines have been evaluated for immunogenicity by opsonophagocytic assay (OPA). A multiplexed OPA (MOPA) for 13 pneumococcal serotypes was developed by Nahm and Burton, and expanded to 26 serotypes in 2012. The development of new conjugate vaccines with increased valence has necessitated expanded MOPAs to include these additional serotypes. In this study, we validated this expanded MOPA platform and applied to measure antibodies against 11 additional serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F) in human sera. METHODS: All materials, including serum, complement, bacterial master stocks, and HL-60 cells, were evaluated for assay optimization. Following optimization, the assay was validated for accuracy, specificity, and intra- and inter-assay precision with sera from adult donors following standard protocols. The assay was applied to evaluate functional antibodies of 42 sera immunized with 23-valent pneumococcal polysaccharide vaccine (PPV23). RESULTS: The expanded MOPA platform was specific for all serotypes, with the exception of serotype 20. The assay results were highly correlated with those obtained from single-serotype OPA, indicating acceptable accuracy. The coefficients of variation were 7%–24% and 13%–39% in tests of intra- and inter-assay precision, respectively, using three quality-control samples. A MOPA that included 11 additional serotypes in the PPV23 was established and validated with respect to accuracy, specificity, and precision. The opsonic indices of immune sera were obtained using this validated assay. CONCLUSION: The expanded MOPA will be useful for evaluation of the immunogenicity of PPV23 and future conjugate vaccine formulations.

Disease Burden and Etiologic Distribution of Community-Acquired Pneumonia in Adults: Evolving Epidemiology in the Era of Pneumococcal Conjugate Vaccines

Pneumonia is the leading cause of morbidity and mortality, particularly in old adults. The incidence and etiologic distribution of community-acquired pneumonia is variable both geographically and temporally, and epidemiology might evolve with the change of population characteristics and vaccine uptake rates. With the increasing prevalence of chronic medical conditions, a wide spectrum of healthcare-associated pneumonia could also affect the epidemiology of community-acquired pneumonia. Here, we provide an overview of the epidemiological changes associated with community-acquired pneumonia over the decades since pneumococcal conjugate vaccine introduction.