Neumonía bacteriana en niños en Ecuador: una mirada al impacto de las vacunas

Introducción: La neumonía adquirida en la comunidad es una de las enfermedades con mayor prevalencia en la comunidad pediátrica en nuestro país. De las diferentes etiologías que pueden causarlas, la neumonía ocasionada por Streptococcus pneumoniae puede ser prevenida con el uso de inmunización. Actualmente se disponen de tres tipos de vacunas antineumocócicas conjugadas autorizadas de uso pediátrico de forma sistemática. Objetivo: Identificar la prevalencia de neumonía bacteriana en niños bajo 5 años de edad, que requirieron hospitalización comparando la vacuna neumocócica recibida: 10 valente (PCV10) versus 13 valente (PCV13). Pacientes y Métodos: Estudio de descriptivo, retrospectivo. Se incluyeron pacientes hospitalizados bajo 5 años de edad, con diagnóstico de neumonía bacteriana mediante codificación CIE10 en un hospital de tercer nivel de la ciudad de Quito-Ecuador, durante el año 2019. Resultados: Se estudiaron 175 pacientes de los cuales 74 cumplieron con criterios clínicos de neumonía, de estos 46 recibieron PCV10 y 28 recibieron vacuna PCV13. Discusión y Conclusiones: La prevalencia de neumonía bacteriana fue mayor en los pacientes inmunizados con PCV10 lo que sugiere una relación de menor probabilidad de neumonía con el uso de la vacuna PCV13.

Background: Community-acquired pneumonia is one of the most prevalent diseases in the pediatric community in our country, of the different etiologies that can cause them, pneumonia caused by Streptococcus pneumoniae can be prevented with the use of immunization. Currently there are three types of authorized pneumococcal conjugate vaccines for pediatric use in a systematic way. Aim: To identify the prevalence of bacterial pneumonia in children under 5 years of age who required hospitalization by comparing the pneumococcal vaccine received: 10 valent (PCV10) versus 13 valent (PCV13). Methods: Descriptive, retrospective study. Hospitalized patients under 5 years of age with a diagnosis of bacterial pneumonia by ICD10 coding in a third level hospital in the city of Quito - Ecuador during 2019 were included. Results: 175 patients were studied, of which 74 patients met clinical criteria for pneumonia, of these 46 received PCV10 and 28 received PCV13 vaccine. Discussion and Conclusions: The prevalence of bacterial pneumonia was higher in patients immunized with PCV10, suggesting a relationship of lower probability of pneumonia with the use of the PCV13 vaccine.

Impacto de la vacuna antineumocócica en la incidencia y hospitalización de niños con neumonía adquirida en la comunidad

Introducción: A nivel mundial, el 99 % de las muertes por neumonía la sufren los niños menores de 5 años. La Organización Mundial de la Salud recomienda la inclusión de vacunas antineumocócicas en los programas de inmunización infantil con ampliación internacional para reducir muertes anuales en este grupo de edad. Objetivo: Evaluar el impacto de la vacuna antineumocócica en la incidencia y hospitalización de niños menores de 5 años con neumonía adquirida en la comunidad. Métodos: Revisión sistemática de diversas publicaciones científicas relacionadas con el tema. Las fuentes de búsqueda fueron PubMed, SciELO y Google Scholar. Las palabras clave fueron: "niños", "vacuna neumocócica" en combinación con "neumonía adquirida en la comunidad" o "child", "pneumococcalvaccines" y "pneumonia, bacterial". Se seleccionaron los artículos de corte analítico publicados desde 1 de enero de 2017 hasta 6 de octubre de 2021. Se excluyeron los artículos que no consignen autor o Digital Object Identifier System o se refieran a neumonías intrahospitalarias o nosocomiales. Análisis y síntesis de la información: De los 136 artículos encontrados se descartaron 125 por no cumplir con los criterios de inclusión y exclusión, quedaron 4 artículos para la base teórica y 7 artículos para esta revisión. Se observó que la vacuna antineumocócica PCV 13 disminuye la incidencia hasta 22 % y las tasas de hospitalización en 35 %. Conclusión: La vacunación es una estrategia de salud muy eficaz para reducir esta clase de enfermedades, prevenibles por medio de la inmunización.

Introduction: Globally, 99% of pneumonia deaths are children under 5 years old. The World Health Organization recommends the inclusion of pneumococcal vaccines in internationally expanded childhood immunization programs to reduce annual deaths in this age group. Objective: To evaluate the impact of pneumococcal vaccine on the incidence and hospitalization of children under 5 years of age with community-acquired pneumonia. Methods: Systematic review of various scientific publications related to the subject. The search sources were PubMed, SciELO and Google Scholar. The key words were: "children", "pneumococcal vaccine" in combination with "community-acquired pneumonia" or "child", "pneumococcal vaccines" and "pneumonia, bacterial". Analytical articles published from January 1, 2017 to October 6, 2021 were selected. Articles that do not include an author or Digital Object Identifier System or refer to hospital or nosocomial pneumonias were excluded. Analysis and synthesis of information: Of the 136 articles found, 125 were discarded for not meeting the inclusion and exclusion criteria, 4 articles remained for the theoretical basis and 7 articles for this review. Pneumococcal vaccine PCV 13 was found to decrease incidence by up to 22% and hospitalization rates by 35%. Conclusion: Vaccination is a very effective health strategy to reduce this kind of diseases, which are preventable through immunization.

Enfermedad neumocócica invasiva en pacientes de un hospital pediátrico de Perú, 2017-2020 / Invasive pneumococcal disease in patients from a pediatric hospital in Peru, 2017-2020

El propósito del presente estudio fue describir las características clínicas, serotipos y susceptibilidad antibiótica en pacientes con enfermedad neumocócica invasiva (ENI). Se revisaron las historias clínicas de los pacientes con ENI hospitalizados en el Instituto Nacional de Salud del Niño-Breña (Lima, Perú). Se evaluaron a 29 pacientes. La mediana de edad fue 1,9 años (rango intercuartílico 1 a 4 años). El 51,7% eran mujeres y la forma clínica de la ENI más frecuente fue la bacteriemia en 18 (62,1%) pacientes. El 65,5% tenía el esquema de vacunación completo, según el Ministerio de Salud de Perú. El 82,8% del aislamiento del germen fue de sangre. La resistencia antibiótica fue más frecuente a la eritromicina (55,2%), trimetoprim-sulfametoxazol (48,3%) y penicilina (24,1%). Los serotipos registrados fueron 6C, 19A, 23A y 24F. Un paciente falleció por meningitis. En conclusión, la ENI fue más frecuente en niños de uno a cinco años y en la forma clínica de bacteriemia. Se encontraron cinco serotipos reportados en estudios previos con resistencia a penicilina y eritromicina.

This study aimed to describe the clinical characteristics, serotypes, and antibiotic susceptibility in patients with invasive pneumococcal disease (IPD). The medical records of patients with IPD who were hospitalized at the Instituto Nacional de Salud del Niño-Breña (Lima, Peru) were reviewed. We evaluated 29 patients. The median age was 1.9 years (interquartile range: 1 to 4 years). Of the sample, 51.7% were women and the most frequent clinical form of IPD was bacteremia in 18 (62.1%) patients; 65.5% had a complete vaccination schedule, according to the Peruvian Ministry of Health. Germ isolation was performed from blood samples in 82.8% of patients. Antibiotic resistance to erythromycin (55.2%) was the most frequent, followed by resistance to trimethoprim-sulfamethoxazole (48.3%) and penicillin (24.1%). The isolated serotypes were 6C, 19A, 23A and 24F. One patient died of meningitis. In conclusion, IPD was more frequent in children aged one to five years and the most frequent clinical form was bacteremia. Five serotypes reported in previous studies were found to be resistant to penicillin and erythromycin.

The inverse correlation between serum levels of anti-pneumococcal and ferritin after pneumococcal vaccination in splenectomised beta thalassemia major

Splenectomy is necessary in beta thalassemia major patients when the spleen becomes hyperactive, leading to extreme destruction of erythrocytes. This study assessed the ferritin effect on serum pneumococcal antibody response following pneumococcal vaccination, in patients with beta thalassemia major after splenectomy. In this case series study, convenience sampling was used to recruit 347 splenectomised beta thalassemia patients under the auspices of Jahrom University of Medical Sciences. Demographic data such as age, sex, and time after splenectomy were recorded by a questionnaire. All participants had been splenectomised and received a dose of Pneumovax1 23 vaccine 14 days before surgery. The IgG antibody responses to pneumococcal vaccine and levels of serum specific ferritin were determine by commercial enzyme immunoassay kits. For the analysis, SPSS software version 16 was used. A p-value less than 0.05 was considered statistically significant. Most of the participants (63.4 percent) were hypo-responders to pneumococcal vaccine. Also, serum anti-pneumococcal IgG antibody was related to post splenectomy duration and serum ferritin (p 0.05). An important result was a relation of serum anti-pneumococcal IgG antibody to serum ferritin according to post splenectomy duration groups. Therefore, in three groups of post splenectomy duration, the serum ferritin was higher in hypo-responder than in good responder subjects. Our results indicate that serum anti-pneumococcal IgG antibody decreased with increment of serum ferritin and post splenectomy duration. Thus, there is a need to re-address the approach towards revaccination in this immune-compromised group of patients by administering a booster pneumococcal vaccination in an attempt to recover immunity and reduce morbidity(AU)

La esplenectomía es necesaria en pacientes con beta talasemia mayor cuando el bazo se vuelve hiperactivo, lo que lleva a una destrucción extrema de los eritrocitos. Este estudio evaluó el efecto de la ferritina sobre la respuesta de anticuerpos antineumocócicos en suero después de la vacunación antineumocócica, en pacientes con talasemia beta mayor a los que se les realizó esplenectomía. En este estudio de serie de casos, se utilizó un muestreo de conveniencia para reclutar a 347 pacientes con beta talasemia esplenectomizados bajo los auspicios de la Universidad de Ciencias Médicas de Jahrom. Los datos demográficos como la edad, el sexo y el tiempo después de la esplenectomía se registraron mediante un cuestionario. Todos los participantes fueron esplenectomizados y recibieron una dosis de la vacuna Pneumovax® 23, 14 días antes de la cirugía. Las respuestas de anticuerpos IgG a la vacuna neumocócica y los niveles de ferritina sérica específica se determinaron mediante estuches comerciales de inmunoensayo enzimático. Para el análisis se utilizó el programa SPSS versión 16. Un valor de p inferior a 0,05 se consideró estadísticamente significativo. La mayoría de los participantes (63,4 por ciento) resultaron hiporrespondedores a la vacuna antineumocócica. Además, el anticuerpo sérico antineumocócico IgG se relacionó con la duración de la esplenectomía y la ferritina sérica (p0,05). Un resultado importante fue la relación del anticuerpo sérico IgG antineumocócico con la ferritina sérica según los grupos de duración postesplenectomía. Por lo tanto, en tres grupos de duración posterior a la esplenectomía, la ferritina sérica fue mayor en los sujetos con hiporrespuesta que en los sujetos con buena respuesta. Nuestros resultados indican que el anticuerpo sérico IgG antineumocócico disminuyó con el incremento de la ferritina sérica y la duración posterior a la esplenectomía. Por lo tanto, existe la necesidad de volver a abordar el enfoque hacia la revacunación en este grupo de pacientes inmunocomprometidos mediante la administración de una vacunación antineumocócica de refuerzo en un intento por recuperar la inmunidad y reducir la morbilidad(AU)

Mortalidad por neumonía y por todas las causas en niños menores de 5 años en Colombia entre el 2005 y 2016 / Pneumonia and all causes mortality in children under 5 year old in Colombia between 2005 and 2016

RESUMEN Introducción: Las infecciones neumocócicas son una de las causas más importantes de enfermedades en niños menores de 5 años en Colombia. Objetivo: Calcular la mortalidad por neumonía y por todas las causas en niños menores de 5 años en Colombia. Métodos: Estudio ecológico, los principales desenlaces del estudio fue mortalidad por todas las causas y neumonía (CIE-10 J12-18). Resultados: Durante el año 2005 al 2016 se encontraron un total de 122.074 muertes por todas las causas, de las cuales 13359 (10.94%) correspondieron a muerte por neumonía, 750 a meningitis (0.61%) y 17.511 a muerte por otras causas respiratorias (14.34%). Conclusiones: Se ha observado una disminución de la mortalidad en las tasas de mortalidad por todas las causas, y las demás estudiadas en este artículo.

ABSTRACT Introduction: Pneumococcal infections are one of the most important causes of diseases in children under 5 years old in Colombia. Objective: Evaluate mortality from pneumonia and all causes in children under 5 years old in Colombia. Methods: Ecological study, the main outcomes of the study was all-cause mortality and pneumonia (ICD-10 J12-18). Results: During 2005 to 2016, a total of 122,074 deaths were found for all causes, of which 13,359 (10.94%) corresponded to death due to pneumonia, 750 to meningitis (0.61%) and 17,511 to death due to other respiratory causes (14.34% ). Conclusions: A decrease in mortality has been observed in all-cause mortality rates, and the others studied death causes in this article.

Factores de riesgo asociados a colonización nasofaríngea en niños vacunados con vacunas antineumocócicas. Cienfuegos 2015-16 / Risk factors associated with nasopharyngeal colonization in children vaccinated with pneumococcal vaccines. Cienfuegos, 2015-16

Introducción: La colonización nasofaríngea por neumococo se define como el momento inicial en el que la bacteria se aloja en la nasofaringe del individuo. Objetivo: Estimar la proporción de factores de riesgo asociados a la colonización nasofaríngea por neumococo en niños vacunados con vacunas conjugadas antineumocócicas (PCV). Material y Métodos: Un año después de la vacunación antineumócocica mediante un ensayo clínico fase II/III, controlado, aleatorizado y doble ciego en niños de 1 a 5 años, se ejecutó un estudio de seguimiento con un diseño casos y controles, tipo caso-caso. El horizonte temporal fue desde noviembre de 2015 hasta abril de 2016. Se incluyó 50 por ciento del total de vacunados en el estudio experimental. El universo lo constituyó los 1 135 niños vacunados en el ensayo clínico. Se siguió un muestreo aleatorio simple y se incluyeron 555 sujetos. Se realizó una encuesta y una toma de muestra de exudado nasofaríngeo. Se presentaron tablas de frecuencias. Se utilizó la razón de prevalencia como medida de asociación. Se calcularon los intervalos de confianza a 95 por ciento para cada proporción. Resultados: Tener entre 2 y 5 años actúa como factor protector para la colonización nasofaríngea con respecto al niño pequeño. Convivir con personas mayores de 65 años constituye un factor de riesgo significativamente relacionado con la colonización nasofaríngea. Conclusiones: La introducción de vacunas antineumocócicas en niños preescolares puede impactar de manera significativa la carga de colonización y en la trasmisión de la enfermedad neumocócica(AU)

Introduction: Nasopharyngeal colonization by pneumococci is defined as the initial moment when the bacterium lodges in the nasopharynx of the person. Objective: To estimate the proportion of risk factors associated with nasopharyngeal colonization by pneumococci in children vaccinated with conjugate pneumococcal vaccines (CPV). Material and Methods: One year after pneumococcal vaccination, a follow-up case-case-control study was conducted in children aged 1-5 years by means of a phase II/III controlled, randomized, double-blind clinical trial. The time horizon was from November 2015 to April 2016. The study included 50 percent of the total of children vaccinated during the experimental study. The universe consisted of 1135 children who were vaccinated during the clinical trial. A simple random sampling that included 555 persons was applied. A survey was conducted and nasopharyngeal exudate samples were taken. Tables of frequencies were presented. Prevalence ratio was used as a measure of association. Also, 95 percent confidence intervals were calculated for each proportion. Results: Being between the ages of 2-5 years acts as protective factor against nasopharyngeal colonization with respect to the young child. Living with persons older than 65 years is a significantly associated risk factor with nasopharyngeal colonization. Conclusions: The introduction of pneumococcal vaccines in pre-school children can have a significant impact on colonization burden and the transmission of pneumococcal diseases(AU)

Bases inmunológicas de la enfermedad neumocócica y el candidato vacunal PVC7-TT / Immunological bases of pneumococcal disease and vaccine candidate PVC7-TT

Introducción: Las enfermedades infecciosas del tracto respiratorio se encuentran entre las primeras causas de entidades respiratorias en edades extremas de la vida. Objetivo: Describir las bases inmunológicas de la enfermedad y el nuevo candidato vacunal conjugado antineumocócico PCV7-TT desarrollado en Cuba. Métodos: Se realizó una búsqueda en las bases de datos Medline, Pubmed, SciELO, LILACS, Cochrane Library y Web of Science, de documentos publicados entre mayo del 2018 y marzo del 2020. Se seleccionaron los 64 artículos de mayor relevancia y novedad. Resultados: Streptococcus pneumoniae es el agente etiológico de la enfermedad neumocócica; se le atribuye alrededor de un millón de defunciones anuales, principalmente en países en vías de desarrollo. Es un coco Gram-positivo, anaerobio facultativo y encapsulado que se encuentra dividido en 48 serogrupos y 97 serotipos tipificados. Presenta varios factores de virulencia que garantizan su mecanismo de patogenicidad; uno de los más importantes es el polisacárido capsular que constituye la diana de las vacunas antineumocócicas conjugadas y no conjugadas existentes. En el presente artículo se consideró la proteína de superficie C del neumococo como un posible candidato en la investigación y desarrollo de vacunas preventivas. Asimismo, las vesículas extracelulares podría ser un posible candidato para adyuvante vacunal con fines preventivos y terapéuticos. Conclusiones: El neumococo es un problema de salud a nivel global y el uso de vacunas conjugadas antineumocócicas constituye la herramienta más eficaz para su prevención. El candidato vacunal PCV7-TT desarrollado en Cuba es seguro, bien tolerado, inmunogénico y no inferior a las vacunas actualmente registradas(AU)

Introduction: Infectious diseases of the respiratory tract are among the leading causes of respiratory conditions in patients at extreme ages. Objective: Describe the immunological bases of the disease and the new conjugate pneumococcal vaccine candidate PCV7-TT developed in Cuba. Methods: A search was conducted in the databases Medline, Pubmed, SciELO, LILACS, Cochrane Library and Web of Science for documents published from May 2018 to March 2020. The 64 most relevant and novel papers were selected. Results: Streptococcus pneumoniae is the causative agent of pneumococcal disease, a condition causing about one million deaths a year worldwide, mainly in developing countries. It is a Gram-positive facultative anaerobic encapsulated coccus divided into 48 serogroups and 97 typified serotypes. Several virulence factors ensure its pathogenicity mechanism. One of the most important of these is the capsular polysaccharide constituting the target of the existing conjugate and non-conjugate pneumococcal vaccines. The study considered pneumococcal surface protein C as a possible candidate for the research and development of preventive vaccines. On the other hand, extracellular vesicles could be a possible vaccine adjuvant candidate for preventive and therapeutic use. Conclusions: Pneumococcus is a global health problem, and the use of conjugate pneumococcal vaccines is the most effective tool for its prevention. The vaccine candidate PCV7-TT developed in Cuba is safe, well-tolerated, immunogenic and not inferior to the vaccines so far registered(AU)

Invasive pneumococcal disease in children with cancer: Incidence density, risk factors and isolated serotypes

ABSTRACT Background: Pediatric oncology patients (POP) have a high risk of infections due to impaired immunity. Invasive pneumococcal disease (IPD) is an important cause of severe infection in these patients and it is associated with high mortality. This study aimed to evaluate the incidence and risk factors associated with IPD at a Pediatric Oncology Center in Brazil. Methods: This was a retrospective case-control study. All IPD cases in children with cancer from 2005 through 2016 were reviewed. Each case of IPD was matched with two controls from a cohort of patients matched for year of IPD, age and disease in order to assess risk factors. The incidence density was calculated as the number of IPD per 100,000 patients-year. Results: A total of 51 episodes of IPD in 49 patients was identified. All pneumococci were isolated from blood cultures. The median age was five years and 67% were male; mortality rate was 7.8%. The IPD incidence density rate in POP was 311.21 per 100,000 patients-year, significantly higher than the rate in the general pediatric population. Severe neutropenia was the only risk factor associated with IPD, after multivariate conditional logistic regression analysis. Conclusion: Although pneumococcal disease decreased after the introduction of 10-valent pneumococcal vaccine in the Brazilian national immunization schedule in 2010, there was no decrease in the IPD incidence rate in our cohort. A higher coverage rate of pneumococcal vaccination in children in the general population might be necessary to reduce the incidence rate in this high-risk population.

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.

Updates of adult immunization in Korea

An increase in the number of patients with infectious diseases in Korea, can be attributed to various factors, such as the prevalence of new infectious diseases of the 21st century, the re-emergence of past infectious diseases, an increase in the number of elderly individuals, patients with chronic diseases, immune deficiency, and globalization. In this context, vaccination becomes vital for the adult population. Although, the guidelines for adult immunization are currently being updated, the rate of adult vaccination remains lower than that of infant vaccination. At present, the major challenges for increasing the rate of adult immunization include negative views on the need for some immunizations and a lack of understanding of group immunity among the youth. Consequently, a successful immunization program will be required to direct efforts towards educating patients and spreading awareness. Based on the current guidelines and practical applications, varicella zoster; Japanese encephalitis; tetanus, diphtheria, and pertussis; pneumococcus; measles, mumps, and rubella; and hepatitis A vaccines could effectively be considered for adult vaccination.

Deficiência de anticorpos específicos antipolissacarídeos / Specific polysaccharide antibody deficiency

A deficiência de anticorpos específicos antipolissacarídeos é um dos erros inatos da imunidade predominantemente de anticorpos, destacando-se entre os defeitos mais frequentes. É caracterizada por uma permanência de imaturidade da resposta imunológica a antígenos polissacarídeos, estando normais linfócitos B, classes e subclasses de imunoglobulinas. O paciente apresenta maior suscetibilidade a infecções por bactérias encapsuladas, especialmente Streptococcus pneumoniae e Haemophilus influenzae. As principais manifestações clínicas são otites, sinusites, traqueobronquites e pneumonias de repetição; pode haver meningite pneumocócica e septicemia. A investigação é feita por titulação de anticorpos antipolissacarídeos antes e após a aplicação da vacina pneumocócica não conjugada. Até dois anos, há imaturidade fisiológica desse setor da imunidade, por isso, o diagnóstico não pode ser feito antes desta idade. O tratamento, além de antibiótico precoce em vigência de quadros infecciosos, inclui antibióticos profiláticos, aplicação de vacina conjugada com proteínas e/ou reposição de imunoglobulina humana endovenosa ou subcutânea. O diagnóstico e o tratamento precoce melhoram a qualidade de vida do paciente, diminuindo o risco de sequelas e até de óbito por infecção, e quando não são precoces, é possível que haja sequelas como bronquiectasias, hipoacusia ou danos neurológicos.

Specific polysaccharide antibody deficiency is an inborn error of immunity predominantly affecting antibodies, being one of the most frequent primary immunodeficiencies of childhood. It is characterized by persistent immaturity of the immune response to polysaccharide antigens, with normal levels of B lymphocytes, immunoglobulin classes and subclasses. Patients are more susceptible to infections by encapsulated bacteria, especially Streptococcus pneumoniae and Haemophilus influenzae. The main clinical manifestations are recurrent otitis, sinusitis, tracheobronchitis and pneumonia; there may be pneumococcal meningitis and septicemia. The investigation is done by dosages of polysaccharide antibodies before and after unconjugated pneumococcal vaccination. As this area of immunity is physiologically immature until two years of age, diagnosis cannot be made earlier. Treatment, in addition to antibiotics as soon as infections are detected, includes prophylactic antibiotic therapy, use of pneumococcal vaccine conjugated to protein and/or replacement of intravenous or subcutaneous human immunoglobulin. Early diagnosis and treatment improve patients' quality of life, reducing the risk of sequelae and even death from infection, while lack of early measures can lead to sequelae such as bronchiectasis, hearing loss and neurological damage.

Spatial analysis of pneumococcal meningitis in São Paulo in the pre- and post-immunization era

ABSTRACT OBJECTIVE To analyze the pneumococcal meningitis incidence rates in the State of São Paulo, Brazil, by age group, municipalities and micro-regions, as well as the spatial distribution of pneumococcal meningitis incidence rates among children under 5 years old in the pre- (2005-2009) and post-vaccination (2011-2013) periods and its associations with socioeconomic variables and vaccination coverage. METHODS The data source was the Brazilian Notifiable Diseases Information System. For the pre- and post-vaccination periods, thematic maps were built for pneumococcal meningitis incidence in under-5 children, by São Paulo state micro-regions, vaccination coverage and socioeconomic variables, using QGIS 2.6.1 software. Scan statistics performed by the SatScan 9.2 software were used to analyze spatial and spatiotemporal clusters in São Paulo municipalities and micro-regions. A Bayesian inference for latent Gaussian model with zero-inflated Poisson model through the integrated nested Laplace approximation was used in the spatial analysis to evaluate associations between pneumococcal meningitis incidence rates and socioeconomic variables of interest in São Paulo micro-regions. RESULTS From 2005 to 2013, 3,963 pneumococcal meningitis cases were reported in São Paulo. Under-5 children were the most affected in the whole period. In the post-vaccination period, pneumococcal meningitis incidence rates decreased among this population, particularly among infants (from 4.17/100,000 in 2005 to 2.54/100,000 in 2013). Two clusters were found in pre-vaccination - one of low risk for pneumococcal meningitis, in the northwest of the state (OR = 0.45, p = 0.0003); and another of high risk in the southeast (OR = 1.62, p = 0.0000). In the post-vaccination period, only a high-risk cluster remained, in the southeast (RR = 1.97, p = 0.0570). In Bayesian analysis, wealth was the only variable positively associated to pneumococcal meningitis (RR = 1.026, 95%CI 1.002-1.052). CONCLUSIONS Pneumococcal meningitis is probably underdiagnosed and underreported in São Paulo. Differentiated rates of pneumococcal meningitis diagnosis and reporting in each microregion, according to the São Paulo Index of Social Responsibility, might explain our results.

Analysis of knowledge, attitude, behavior, and practice and the influencing factors of pneumococcal vaccination in type 2 diabetes mellitus patients / 中华健康管理学杂志

Objective This study aimed to analyze the knowledge, attitude, behavior, and practice of pneumococcal vaccination in type 2 diabetes mellitus patients. Methods From January to March 2018, 3000 patients with type 2 diabetes mellitus were randomly selected from patients with type 2 diabetes registered and managed in community health service centers to participate in a questionnaire survey, using multi-stage cluster random sampling. The questionnaire included basic information, pneumococcal vaccine awareness, and pneumococcal vaccination status and inoculation intention, 2896 valid questionnaires were collected. The chi-squared test and multivariate logistic regression analysis were used to analyze the knowledge, attitude, behavior, and practice and influencing factors of pneumococcal vaccination. Results Of all the patients, 1267 (43.75％) patients with type 2 diabetes were willing to receive pneumococcal vaccination, and 23 (0.79％) patients with type 2 diabetes were vaccinated against pneumococcal, 1295(44.72％) patients with type 2 diabetes believed that patients with chronic diseases were susceptible to pneumococcal. Eight hundred seventy-seven (30.38％) patients believed that pneumococcal vaccination for chronic disease patients could reduce the risk of outpatient, hospitalization and death. Seven hundred ninety-nine (27.59％) patients believed that diabetic patients were the primary recipients of the pneumococcal vaccine. Multivariate logistic regression analysis showed that retired patients; those who thought that patients with chronic diseases were susceptible to pneumonia; those who thought that pneumococcal vaccination could reduce the risk of needing outpatient care, hospitalization, and death;and those who thought that diabetes was the priority of pneumococcal vaccination were more willing to receive pneumococcal vaccination (OR=1.442, 0.764, 1.494, 1.713, P all<0.05). Conclusion Patients with type 2 diabetes in Shenzhen have lower pneumococcal vaccine awareness, inoculation intention, and vaccination rates. Health education on the prevention of diabetes complications and pneumococcal vaccination should be promoted.

The Status and Effects of Influenza and Pneumococcal Vaccination in Hospitalized Patients Population with Chronic Conditions

BACKGROUND: This study was aimed to analyze the status and effects of influenza vaccine (IV) and pneumococcal vaccine (PV) in hospitalized patients in a University Hospital with chronic conditions.METHODS: The study is based on the medical records of 3,279 inpatients in pulmonary center of Yeungnam University Medical Center (Korea) between October 2015 and September 2016. The subjects were divided into two groups by age (under 65 years old and over 65 years old), and the preventive effects of IV and PV were analyzed by comparing vaccination rate, hospitalized period, pneumonia attach rate, and mortality rate. Vaccination data were obtained from the Korea Centers for Disease Control and Prevention web system. The chi-squared test, linear regression analysis and logistic regression analysis were used to analyze factors associated with the types of vaccinations and underlying medial factors.RESULTS: In the group under 65 years old, those without any vaccination had higher mortality rate. In addition, patients with IV vaccination were more likely to have shorter hospitalized periods. On the contrary, a group of people without any vaccination, hospitalized period increased. However, in the group of over 65 years old with various underlying conditions, the mortality rate was higher when IV or both IV and PV were vaccinated.CONCLUSION: The preventive effects show the opposite results in two age groups. This study indicates that the vaccines are more effective in the group under 65 years old than the group over 65 years old with chronic conditions.

Pneumococcal vaccines

Streptococcus pneumoniae continues to take a heavy toll on childhood mortality and morbidity across the developing world. An estimated 10.6 million invasive pneumococcal diseases (IPDs) occur every year, with nearly 1 million deaths in children under 5 years of age. Introduction of vaccines in the childhood immunisation programme in developed world has brought down the incidence of the disease considerably. However, childhood immunocompromising illnesses including HIV have increased the risk of IPD several folds. There is also a growing concern on the increasing antibiotic resistance among these invasive strains to penicillin, other beta-lactams and macrolides, making treatment difficult and expensive. It is estimated that about 62% of IPD worldwide is caused by the 10 most common serotypes. Although the ranking of individual pneumococcal serotypes causing serious disease varies among nations, the 7� serotypes included in pneumococcal conjugate vaccines (PCVs) may prevent 50%�% of all paediatric pneumococcal diseases globally. The World Health Organization has recommended the use of PCV-10/13 in the national immunisation programmes (NIPs) of developing countries. Four doses of PCV-13 have been recommended by the US Association of Pediatrics and Centers for Disease Control and Prevention, at intervals of each 2 months for the first 6 months and by the 12th to 15th months after birth. This is expected to reduce the morbidity and mortality associated with IPD and simultaneously decrease colonisation with circulating antibiotic-resistant strains in immunized communities. Nevertheless, continued surveillance of antimicrobial resistance in non-vaccine serotypes is necessary to prevent the resurgence of resistance. Other virulence factors which are not serotype specific also need to be studied to overcome the drawbacks of serotype-specific pneumococcal vaccines. PCV-13 was launched during May 2017 under the NIP of five Indian states with the highest pneumococcal diseases in the country and is expected to be rolled out in the other parts of the country in the coming days.

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.

Community acquired pneumonia incidence among children less than 5 years of age in Concordia, Argentina: vaccination impact / Incidencia de la neumonía extrahospitalaria en menores de 5 años en Concordia (Argentina): repercusión de la vacunación / Incidência de pneumonia adquirida na comunidade em crianças menores de 5 anos em Concordia, Argentina: impacto da vacinação

ABSTRACT Objective To measure the effectiveness of pneumococcal conjugated vaccine (PCV13) against Community Acquired Pneumonia (CAP) and invasive pneumococcal disease, 2 years after the vaccine (2+1) was included into the National Immunization Program of Argentina, and to describe variables associated with bacterial pneumonia and hospitalization. Methods This was a prospective, population-based surveillance study of CAP incidence (ambulatory and hospitalized) among children less than 5 years of age in the Department of Concordia (Entre Rios, Argentina) from April 2014 - March 2016. The diagnosis of probable bacterial pneumonia (PBP) was determined following the standardized WHO protocol. Incidence during the post-vaccine introduction period was compared with the results from a previous study that used similar methodology for the pre-PCV13 introduction period from 2002 - 2005. Results During the study period, 330 patients had a clinical diagnosis of CAP, of which 92 were PBP (6 with pleural effusion). S. pneumoniae was not isolated from any sample. No factors associated with PBP were found in multivariable analysis. The decrease in PBP and pleural effusion was significant in relation to the previous study: 63% (P < 0.0001) and 80.9% (P < 0.003), respectively. PCV13 uptake was 97.3% for the 1st dose and 84.8% for the booster dose. Conclusions PCV13 was effective to reduce incidence of consolidated pneumonia and pleural effusion, among children less than 5 years of age in Concordia, Argentina. Vaccination is a very effective public health strategy for reducing vaccine preventable diseases, with impact on burden of disease and hospitalization.

RESUMEN Objetivo Medir la efectividad de la vacuna antineumocócica conjugada (VNC13)contra la neumonía extrahospitalaria y las enfermedades neumocócicas invasoras, dos años después de que se incorporara la vacuna (2+1) en el Programa Nacional de Vacunación de Argentina, y describir las variables asociadas con la neumonía bacteriana y la hospitalización. Métodos Se llevó a cabo un estudio prospectivo de vigilancia poblacional de la incidencia de la neumonía extrahospitalaria (pacientes ambulatorios y hospitalizados) en menores de 5 años en el departamento Concordia (Entre Ríos, Argentina) desde abril del 2014 hasta marzo del 2016. Se determinó el diagnóstico de probable neumonía bacteriana según el protocolo estandarizado de la OMS. Se comparó la incidencia durante el período posterior a la incorporación de la vacuna con los resultados de un estudio anterior en el que se usó una metodología similar para el período previo a la incorporación de la VNC13 entre el 2002 y el 2005. Resultados Durante el estudio, 330 pacientes presentaron un diagnóstico clínico de neumonía extrahospitalaria, de los cuales 92 presentaron probable neumonía bacteriana (6 con derrame pleural). No se aisló ninguna muestra del S. pneumoniae. No se encontraron factores asociados con la neumonía bacteriana probable en el análisis multivariante. La disminución de la neumonía bacteriana probable y el derrame pleural fue significativa en relación con el estudio anterior: 63 % (P < 0,0001) y 80,9 % (P < 0,003), respectivamente. La absorción de la VNC13 fue de 97,3 % para la primera dosis y de 84,8 % para la dosis de refuerzo. Conclusiones La VNC13 fue efectiva para reducir la incidencia consolidada de derrame pleural y neumonía en menores de 5 años en Concordia (Argentina). La vacunación es una estrategia de salud pública muy efectiva para reducir las enfermedades prevenibles por vacunación, con repercusión en la carga de enfermedad y la hospitalización.

RESUMO Objetivo Avaliar a efetividade da vacina pneumocócica conjugada (PCV13) em prevenir pneumonia adquirida na comunidade (PAC) e doença pneumocócica invasiva (DPI) após 2 anos da incorporação da vacina (2 + 1) ao Programa Nacional de Vacinação da Argentina e descrever as variáveis associadas à ocorrência de pneumonia bacteriana e internação hospitalar. Métodos Estudo prospectivo de base populacional de vigilância da incidência de PAC (atendimento ambulatorial e em internação hospitalar) em crianças menores de 5 anos de idade realizado no Departamento de Concordia, Entre Rios, na Argentina, de abril de 2014 a março de 2016. O diagnóstico de provável pneumonia bacteriana foi determinado segundo o protocolo padronizado da OMS. A incidência no período pós-introdução da vacina foi comparada aos resultados de um estudo anterior realizado com metodologia semelhante no período pré-introdução da PCV13 de 2002 a 2005. Resultados No período de estudo, foi feito o diagnóstico clínico de PAC em 330 pacientes, dos quais 92 foram casos de provável pneumonia bacteriana (6 com derrame pleural). A bactéria Streptococcus pneumoniae não foi isolada em nenhuma amostra. Não foi observado nenhum fator associado à provável pneumonia bacteriana na análise multivariada. Houve uma redução significativa da ocorrência de provável pneumonia bacteriana e derrame pleural em relação ao estudo anterior: 63% (P < 0,0001) e 80,9% (P < 0,003), respectivamente. A cobertura vacinal de PCV13 foi de 97,3% para a primeira dose e 84,8% para a dose de reforço. Conclusões A PCV13 foi efetiva em reduzir a incidência de pneumonia com consolidação e derrame pleural em crianças menores de 5 anos em Concordia, na Argentina. A vacinação é uma estratégia de saúde pública muito efetiva para reduzir doenças que podem ser evitadas com vacina, com impacto na morbidade e nas internações hospitalares.

Impacto da vacina pneumocócica na redução das internações hospitalares por pneumonia em crianças menores de 5 anos, em Santa Catarina, 2006 a 2014 / El impacto de la vacuna neumocócica en la reducción de las hospitalizaciones por neumonía en niños menores de 5 años, en Santa Catarina, Brasil, 2006 a 2014 / The impact of pneumococcal vaccine in reducing pneumonia hospitalizations in children under 5 years old, in Santa Catarina, Brazil, 2006 a 2014

Objetivo: analisar o impacto da vacina pneumocócica conjugada (PCV10) nas internações hospitalares por pneumonia em menores de 5 anos de idade, em Santa Catarina, Brasil, no período 2006-2014. Métodos: estudo ecológico com dados do Departamento de Informática do Sistema Único de Saúde (Datasus) em 2006-2009 (período pré-vacinal) e 2010-2014 (período pós-vacinal); tendências temporais foram avaliadas pelo coeficiente de regressão de Poisson. Resultados: comparados os períodos pré e pós-vacinal, a diferença percentual da taxa de internação por pneumonia em menores de 1 ano variou de -44,1% na região Oeste a -1,4% no Planalto Serrano, e nas crianças de 1-4 anos, de -37,1% no Planalto Norte a 16,9% no Planalto Serrano (p<0,05), implicando reduções nas taxas de internação no estado de 23,3% em <1 ano e de 8,4% em crianças de 1-4 anos. Conclusão: observou-se redução significativa da taxa de internação por pneumonia em menores de 1 ano, sugerindo a efetividade da vacina.

Objetivo: analizar el impacto de la vacuna neumocócica conjugada (PCV10) en las internaciones por neumonía, en niños, en Santa Catarina, Brasil, en 2006-2014. Métodos: estudio ecológico con datos del Departamento de Informática del Sistema Único de Salud (Datasus), entre 2006-2009 y 2010-2014; se evaluaron las tendencias temporales por medio del coeficiente de regresión de Poisson. Resultados: comparados ambos períodos, la diferencia porcentual de la tasa de internación por neumonía en menores de 1 año varió de -44,1% en la región Oeste a -1,4% en el Planalto Serrano, y en los niños de 1-4 años, de -37,1% en el Planalto Norte al 16,9% en el Planalto Serrano (p<0,05, siendo la reducción en las tasas de internación en el estado del 23,3% en <1 año y del 8,4% en 1-4 años. Conclusión: se observó una reducción significativa de la tasa de internación por neumonía en menores de un año, sugiriendo la efectividad de la vacuna.

Objective: to analyze the impact of pneumococcal conjugate vaccine (PCV10) on pneumonia hospital admissions among children in Santa Catarina, Brazil, 2006-2014. Methods: this was an ecological study using data obtained from Brazilian National Health System Information Technology Department (Datasus) for 2006-2009 (pre-vaccination period) and 2010-2014 (post-vaccination period); time trends were evaluated using the Poisson regression coefficient. Results: in the comparison between pre- and post-vaccination periods, the percentage difference in the hospitalization rate for children under 1 year old ranged from -44.1% in the Western region to -1.4% in the Serrano Plateau region, and in children between 1-4 years old it ranged from -37.1% in the Northern Plateau region to 16.9% in the Serrano Plateau region (p<0.05); hospitalization rates in the state reduced by 23.3% in children under 1 year old and by 8.4% in those aged 1-4 years. Conclusion: a significant reduction in the rate of pneumonia hospitalization in children under 1 year old age was found, suggesting the effectiveness of the vaccine in reducing hospitalizations.

Meningitis por Streptococcus pneumoniae en paciente pediátrico previamente inmunizado: reporte de un caso / Streptococcus pneumoniae meningitis in a previously immunized pediatric patient: report of a case

La meningitis bacteriana constituye una importante causa de morbimortalidad en el mundo y, a pesar de que la incidencia se ha reducido en los años posteriores a la inclusión de la vacuna antineumocócica en los calendarios de inmunizaciones, no se ha podido evitar el surgimiento de cepas emergentes. Presentamos el caso de una paciente de 5 años con inmunizaciones completas para la edad, con un cuadro clínico sugerente de meningoencefalitis, cuya evolución (con gran compromiso sistémico y pobre respuesta al tratamiento) nos hizo sospechar de la presencia de cepas emergentes y/o resistencia antimicrobiana, en el planteamiento de interrogantes respecto a estados de inmunodeficiencia o respuesta inadecuada a la vacunación, el impacto que realmente tiene la vacuna en nuestro país y la necesidad de realizar una más stricta vigilancia epidemiológica para la identificación de serotipos emergentes

Bacterial meningitis is an important cause of morbidity and mortality all over the world; and, in spite of a reduction in its incidence because of the introduction of an anti-pneumococcal vaccine in the immunization programs in many places, the occurrence of emerging strains has not been stopped. We present the case of a 5-year old girl with complete immunizations for her age, with a clinical condition suggesting meningoencephalitis, whose progress and outcome (significant systemic involvement and poor response to therapy) lead us to think in the possibility of emerging strains and/or resistance to antibacterial agents, and also to ask ourselves about an underlying immune deficiency or inadequate response to vaccination, the real impact of the vaccine in our country, and the need for performing more stringent epidemiological vigilance in order to identify emerging serotypes

Avaliação de custo-efetividade da vacina pneumocócica conjugada 13-valente comparada à vacina pneumocócica polissacarídica e não vacinação no Sistema de Saúde Suplementar Brasileiro / Cost-effectiveness evaluation of pneumococcal conjugate vaccine 13-valent compared to the polysaccharide pneumococcal vaccine and non-vaccination in the Brazilian Supplementary Health System

RESUMO Objetivo: As doenças causadas pela bactéria Streptococcus pneumoniae (pneumococo) são importantes causas de morbimortalidade no mundo, principalmente em indivíduos nos extremos de idade. O objetivo deste estudo foi avaliar os benefícios e custos incrementais associados à vacina pneumocócica conjugada 13-valente PCV13 (Prevenar® 13), comparada à não utilização de vacina e à utilização de vacina pneumocócica polissacarídica PPSV23 no Sistema de Saúde Suplementar, por meio de uma análise de custo-efetividade. Métodos: Foi realizado um estudo de custo-efetividade utilizando um modelo de Markov que englobou os estados de saúde saudável, doença pneumocócica e morte. Neste estudo foram incluídos dados clínicos de pacientes com doença pneumocócica (bacteremia, meningite, internações por pneumonia e pneumonias ambulatoriais), custos médicos diretos e indiretos, considerando um horizonte de tempo de três anos, com ciclos anuais e uma coorte hipotética de pacientes com 50 anos ou mais. Análises de sensibilidade univariada e probabilística também foram realizadas. Resultados: A utilização da vacina PCV13 se mostrou dominante em relação às demais estratégias nos pacientes com risco baixo, moderado e alto. A análise de sensibilidade probabilística indica que a chance de PCV13 ser a estratégia mais custo-efetiva é de 90%, quando um limiar de R$ 12.000 para cada ano de vida ganho é definido. Conclusões: Foi possível observar que a utilização da vacina PCV13 para a prevenção de doenças pneumocócicas em adultos com 50 anos ou mais, considerando o desfecho clínico "anos de vida salvos", pode ser a estratégia mais eficiente quando comparada à não vacinação ou à utilização da vacina PPSV23.

Diseases caused by the bacteria Streptococcus pneumoniae are important sources of morbidity and mortality around the world, specially in regard to elderly people. We sought to assess costs and benefits inherent to 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar® 13) compared to pneumococcal polysaccharide vacine (PPSV23) and the policy of does providing vaccine in the perspective of Brazilian Private Health System. Methods: A cost-effectiveness analysis model was performed by means of a Markov modelling which comprised the health states healthy, pneumococcal disease and death. In this study were included clinical data of patients with pneumococcal disease (bacteremia, meningitis, hospitalization due to pneumonia and community acquired pneumonia) and direct and indirect medical costs. A three year time horizon and an annual cycle were set. The hypothetic cohort corresponds to patients aging 50 years or more. One-way and probabilistic sensitivity analyses were performed. Results: PCV13 is dominant over PPSV23 and non- -vaccination policy in low- moderate- and high-risk patients. Probabilistic analysis shows that PCV13 has a probability of being 90% more cost-effective when a threshold of BRL 12.000 is defined for each incremental life-year gained. Conclusions: Considering the outcome life-years gained PCV13 is the strategy that most promote value for money in patients aging 50 years or more, in the Brazilian Private Health System.