Vacina pneumocócica 23-valente (polissacarídica) para imunização da população de idosos (60 anos ou mais) contra a doença pneumocócica / 23-valent pneumococcal (polysaccharide) vaccine for immunization of the elderly population (60 years and older) against pneumococcal disease

INTRODUÇÃO: A doença pneumocócica (DP), causada pelo Streptococcus pneumoniae, também denominado de pneumococo, é uma condição de elevada incidência na população mundial e brasileira. Ela compreende uma gama de infecções em que se destacam a pneumonia adquirida na comunidade, otite média aguda, sinusite bacteriana e meningite bacteriana aguda. Sua manifestação mais grave ocorre nos quadros de infecção secundária de corrente sanguínea pelo pneumococo, em geral por uma pneumonia primária, e nas meningites, condições definidas como doença pneumocócica invasiva (DPI) e que apresentam elevado risco de óbito. A doença pneumocócica está entre as principais causas de internação no Brasil e também de óbito. Certas condições de base aumentam muito o risco de desenvolvimento de DP e DPI, bem como elevam sua letalidade, das quais se destaca a população idosa. A presença de comorbidades tais como doença pulmonar obstrutiva crônica, insuficiência cardíaca, asma, doença renal ou hepática crônica, diabete mélito e tabagismo, associados a redução do movimento mucociliar na mucosa respiratória e a imunossenescência tornam a população idosa muito vulnerável a DP e DPI. Além disso, é crescente a resistência bacteriana do pneumococo incrementando as taxas de mortalidade por esta condição. A prevenção da DP

Evolução das taxas de hospitalização e mortalidade por doença pneumocócica invasiva em municípios da Região Sudeste do Brasil, no período de 2005 a 2015 / Evolution of hospitalization and mortality rates due to invasive pneumococcal disease in municipalities in the Southeast Region of Brazil, from 2005 to 2015

O presente estudo avaliou a evolução das taxas de hospitalização e mortalidade por doença pneumocócica invasiva (DPI) em crianças menores de 1 ano, nos municípios da região sudeste do país. Foram descritas as evoluções das taxas no período de 2005 a 2015, pré e pós introdução da vacina no programa nacional de imunização, nos municípios com mais de 100 mil habitantes e analisados os efeitos dos fatores socioeconômicos, acesso aos serviços de saúde, cobertura vacinal e esquema vacinal adotado. Trata-se de um estudo ecológico, no qual utilizou-se o modelo de regressão de joinpoint para descrever potenciais modificações nas tendências das taxas ao longo dos anos e o modelo de regressão de Poisson multinível para analisar os efeitos das variáveis independentes sobre as taxas. Tendências decrescentes foram identificadas tanto para as taxas de hospitalização, quanto para mortalidade. A introdução da vacina esteve associada a uma redução de 14% (RT=0,86; intervalo de 95% de confiança: [0,85-0,86]) na taxa de hospitalização e de 6% (RT=0,94 [0,90-0,97]) na mortalidade. No período pós-vacinal, após 2010, os resultados demonstraram que o índice de desenvolvimento humano municipal esteve associado a menores taxas de hospitalização e de mortalidade (RT=0,738 [0,577-0,943] e RT=0,467 [0,386-0,565], respectivamente). Maiores coberturas vacinais estiveram associadas a menores taxas de hospitalização (RT=0,995 [0,992-0,998]) enquanto o acesso a serviços de saúde apresentou relação direta com hospitalização (RT=1,22 [1,118-1,331]). O esquema vacinal com doses aos 3-5-7 meses em comparação ao esquema aos 2-4-6 meses associou-se a maior mortalidade (RT=1,921 [1,62-2,278]), enquanto o acesso aos serviços de saúde implicou em menor mortalidade (RT=0,906 [0,839-0,979]). As taxas de mortalidade não apresentaram padrão de evolução temporal similar às de hospitalização, com queda observada já no período pré-vacinal, o que pode estar relacionado a outros aspectos de ordem socioeconômica. Os resultados destacam a importância e as dificuldades das pesquisas realizadas com dados oriundos dos sistemas de informação de saúde e apontam para a necessidade da continuidade de estudos que busquem a compreensão do fenômeno por meio de diferentes abordagens, contribuindo para o aperfeiçoamento dos serviços de vigilância e para a consolidação das políticas públicas em saúde

The present study evaluated the evolution of hospitalization and mortality rates due to invasive pneumococcal disease (IPD) in children under one year of age in the municipalities of the southeastern region of the country. The evolution of rates between 2005 and 2015, before and after vaccination in the national immunization program, was described in municipalities with more than 100 thousand inhabitants and were analyzed the effects of socioeconomic factors, access to health services, vaccination coverage and vaccination schedule adopted. It is an ecological study in which the joinpoint regression model was used to describe potential changes in rate trends over years and the Poisson multilevel regression model to analyze the effects of the independent variables on rates. The decreasing trends were identified for both hospitalization and mortality rates. The introduction of the vaccine was associated with a reduction of 14% (RR =0.86, 95% confidence interval: [0.85-0.86]) in the hospitalization rate and 6% (RR = 0.94 [0.90-0.97]) in mortality. In the post-vaccination period, after 2010, the results showed that municipal human development index was associated with lower rates of hospitalization and mortality (RR = 0.738 [0.577-0.943] and RR = 0.467 [0.386-0.565], respectively). Higher vaccine coverage was associated with lower hospitalization rates (RR = 0.995 [0.992-0.998]), while access to health services was directly related to hospitalization (RR = 1.22 [1.118-1.331]). The vaccination schedule with doses at 3-5-7 months compared to the schedule at 2-4-6 months was associated with higher mortality (RR = 1.921 [1.62-2.278]), while access to health services was associated with lower mortality (RR = 0.906 [0.839-0.979]). The Mortality rates did not show a time evolution pattern similar to those of hospitalization, with a decrease observed in the pre-vaccination period, which can be related to other socioeconomic aspects. The results highlight the importance and the difficulties to investigate data from the currently available health information systems and point out to the need for continuity of studies that seek to understand the phenomenon through different approaches, contributing to the improvement of surveillance services and for the consolidation of public health policies

Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria

Abstract The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011-2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p < 0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin - 46.5%, trimethoprim-sulfamethoxazole - 45.4%, erythromycin - 43.9%, tetracycline - 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions.

Clinical and bacteriological characteristics of invasive pneumococcal disease after pneumococcal 10-valent conjugate vaccine implementation in Salvador, Brazil

Abstract Invasive pneumococcal disease is a relevant public health problem in Brazil, especially among children and the elderly. In July/2010 a 10-valent pneumococcal conjugate vaccine was introduced to the immunization schedule of Brazilian children under two years of age. Between July/2010 and December/2013 we conducted a case-series study on invasive pneumococcal disease in Salvador, Brazil to describe the clinical and bacteriological profile of invasive pneumococcal disease cases during the post-implementation period. Eighty-two cases were eligible. Mean age was 31 years (interquartile range, 3–42); 17.1% and 30.5% were under 2 years and 5 years, respectively. Pneumococcal meningitis (n = 64, 78.1%), bacteraemic pneumococcal pneumonia (n = 12, 14.6%) and bacteraemia (n = 6, 7.3%) were the clinical syndromes identified. Thirty-three different serotypes were found. Of these, serotype 14 (n = 12, 14.6%) was the most common, followed by 23F (n = 10, 12.2%), 12F (n = 8, 9.8%), 18 C (n = 5, 6.1%) and 6B (n = 5, 6.1%). Investigations conducted in Salvador in the pre-vaccine period did not identify serotype 12F as one of the most prevalent serotypes. Increase of serotype 12F was observed in different regions of Brazil, in the post-vaccine period. Among children under two years of age, the target group for 10-valent pneumococcal conjugate vaccine, 11 (78.6%) of the 14 isolated strains of Streptococcus pneumoniae belonged to vaccine serotypes; at least 50% of these children were not vaccinated. The relatively recent implementation of 10-valent pneumococcal conjugate vaccine in Brazil reinforces the need to maintain an active surveillance of invasive pneumococcal disease cases, considering the possible increase of invasive pneumococcal disease cases related to non-vaccine serotypes and the changes on the clinical presentation of the disease.

Meningitis neumocóccica por serotipo 19 A, de curso fatal: ¿Un caso prevenible? / Fatal pneumococcal meningitis due to serotype 19 A: A preventable case?

Invasive pneumococcal disease (IPD) remains as an important cause of morbidity in the world and in our country, while in Chile the incidence has decreased after the incorporation of the 10 valent pneumococcal conju-gate vaccine, in the routine infant inmunization schedule (EPI). One of the expected effects of the program after vaccination with 10-valent pneumococcal vaccine is the likely replacement serotype phenomenon that means the presence of ENI caused by serotypes not included in the vaccine. In this context, we present the case of a child with pneumococcal meningitis caused by serotype 19 A of fatal course. The occurrence of ENI in a later stage of pneumococcal vaccine incorporation in Chile reinforces the importance of active surveillance, in order to know in detail the impact of vaccination, distribution of circulating serotypes and their correlation with the different clinical disease and their severity.

La enfermedad neumocóccica invasora (ENI) sigue siendo una causa importante de morbilidad en el mundo y en nuestro país, si bien en Chile la incidencia ha disminuido luego de la incorporación de la vacuna neumocóccica conjugada 10-valente al Programa Nacional de Inmunizaciones (PNI). Uno de los efectos esperables luego de la vacunación programática con la vacuna antineumocóccica 10-valente es el probable fenómeno de reemplazo, que corresponde a la presencia de ENI por serotipos no incluidos en la vacuna. En este contexto, se presenta el caso de un pre-escolar con meningitis neumocóccica causada por el serotipo 19 A, de curso fatal. La presencia de casos de ENI en una etapa posterior a la implementación de la vacuna anti-neumocóccica en el PNI de Chile, demuestra la importancia de realizar una vigilancia activa, con el objetivo de conocer en forma detallada el impacto de la vacunación, la distribución de los serotipos circulantes y su correlación con los diferentes cuadros clínicos y su evolución.

Impact of IgM Antibodies on Cross-Protection against Pneumococcal Serogroups 6 and 19 after Immunization with 7-Valent Pneumococcal Conjugate Vaccine in Children

Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes.

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.

Puesta al día en vacunación antineumocócica en adultos / Update on pneumococcal vaccination in adults

La enfermedad invasiva por Streptococcus pneumoniae constituye una importante causa de morbilidad y mortalidad, y es la primera causa de muerte prevenible mediante vacunación en el mundo, no solo en niños sino en todas las edades. Tanto la vacuna polisacárida como la vacuna conjugada antineumocócicas han demostrado reducción de las tasas de enfermedad invasiva en adultos. En los últimos años, a la luz de nueva evidencia disponible, los esquemas de vacunación antineumocócica para esta población han sufrido modificaciones. Este documento ofrece una actualización sobre las recomendaciones de vacunación a través de los fundamentos que han llevado a dicho cambio. (AU)

The Streptococcus pneumoniae invasive disease is a major cause of morbidity and mortality, being the leading cause of vaccine-preventable death in the world, not only in children but in all ages. Both the polysaccharide vaccine and pneumococcal conjugate vaccine have shown reduced rates of invasive disease in adults. In recent years, in light of new evidence available, schedules of pneumococcal vaccination for this population have changed. This document provides an update on vaccine recommendations through the rational that have led to this change. (AU)

Functional low vision in adults from Latin America: findings from population-based surveys in 15 countries / Baja visión funcional en adultos de América Latina: resultados de las encuestas poblacionales realizadas en 15 países

OBJECTIVE: To review data on functional low vision (FLV) (low vision-visual acuity (VA) < 6/18 (<20/60) to > perception of light (PL+) in the better eye-that is untreatable and uncorrectable) in adults aged 50 years or older from published population-based surveys from 15 countries in Latin America and the Caribbean. METHODS: Data from 15 cross-sectional, population-based surveys on blindness and visual impairment (10 national and five subnational) covering 55 643 people > 50 years old in 15 countries from 2003 to 2013 were reanalyzed to extract statistics on FLV. Eleven of the studies used the rapid assessment of avoidable blindness (RAAB) method and four used the rapid assessment of cataract surgical services (RACSS) method. For the 10 national surveys, age-and sex-specific prevalence of FLV was extrapolated against the corresponding population to estimate the total number of people > 50 years old with FLV. RESULTS: Age- and sex-adjusted prevalence of FLV in people > 50 years old ranged from 0.9% (Guatemala, Mexico, and Uruguay) to 2.2% (Brazil and Cuba) and increased by age. The weighted average prevalence for the 10 national surveys was 1.6%: 1.4% in men and 1.8% in women. For all 10 national studies, a total of 509 164 people > 50 years old were estimated to have FLV. Based on the 910 individuals affected, the main causes of FLV were age-related macular degeneration (weighted average prevalence of 26%), glaucoma (23%), diabetic retinopathy (19%), other posterior segment disease (15%), non-trachomatous corneal opacities (7%), and complications after cataract surgery (4%). CONCLUSIONS: FLV is expected to rise because of 1) the exponential increase of this condition by age, 2) increased life expectancy, and 3) the increase in people > 50 years old. These data can be helpful in planning and developing low vision services for the region; large countries such as Brazil and Mexico would need more studies. Prevention is a major strategy to reduce FLV, as more than 50% of it is preventable.

OBJETIVO: Analizar los datos de las encuestas poblacionales publicadas provenientes de 15 países de América Latina y el Caribe sobre baja visión funcional (BVF) (baja visión, desde una agudeza visual [AV] inferior a 6/18 [20/60] hasta > percepción de luz (PL+), en el mejor ojo, no tratable ni corregible) en adultos de 50 años de edad o mayores. MÉTODOS: Con objeto de extraer información estadística en materia de BVF, se volvieron a analizar los datos de 15 encuestas transversales poblacionales sobre ceguera y deficiencia visual realizadas del 2003 al 2013 (10 a escala nacional y cinco subnacio-nales) que abarcaron a 55 643 personas de > 50 años de edad en 15 países. Once de los estudios emplearon el método de Evaluación Rápida de la Ceguera Evitable y cuatro utilizaron el método de Evaluación Rápida de de Catarata y Servicios Quirúrgicos. Al analizar las 10 encuestas nacionales, se extrapoló la prevalencia específica por edad y sexo de la BVF frente a la población correspondiente, con objeto de calcular el número total de personas de > 50 años de edad con BVF. RESULTADOS: La prevalencia de la BVF ajustada por edad y sexo en personas de > 50 años de edad varió desde 0,9% (en Guatemala, México y Uruguay) a 2,2% (en Brasil y Cuba) y aumentó con la edad. La prevalencia promedio ponderada en las 10 encuestas nacionales fue de 1,6%: 1,4% en hombres y 1,8% en mujeres. Al considerar los 10 estudios nacionales en su conjunto, se calcularon un total de 509 164 personas de > 50 años de edad con BVF. Con base en las 910 personas afectadas, las principales causas de BVF fueron la degeneración macular relacionada con la edad (prevalencia promedio ponderada de 26%), el glaucoma (23%), la retinopatía diabética (19%), otras enfermedades del segmento posterior del ojo (15%), las opacidades corneales no tracomatosas (7%) y las complicaciones posteriores a la cirugía de la catarata (4%). CONCLUSIONES: Se prevé que la BVF aumente como consecuencia de 1) el aumento exponencial de esta afección con la edad, 2) la mayor esperanza de vida, y 3) el aumento de personas de > 50 años de edad. Estos datos pueden ser útiles para planificar y extender los servicios de atención a la disminución de la agudeza visual en la Región; países extensos, como Brasil y México, requerirían nuevos estudios. La prevención constituye una estrategia muy importante para reducir la BVF, ya que más de 50% de los casos se pueden prevenir.

Internações sensíveis à atenção primária específicas de mulheres / Sensitive female-specific hospitalization in primary care

Objetivou-se analisar as internações por condições sensíveis à atenção primária (ICSAP) específicas em mulheres e os fatores que determinam ou influenciam a ocorrência dessas internações (fatores socioeconômicos, sociodemográficos e controle de saúde) por meio de um inquérito de morbidade hospitalar realizado com amostra de 429 mulheres internadas em hospitais conveniados ao Sistema Único de Saúde. O percentual de ICSAP foi 49,42% (n = 212), com destaque para as internações específicas do sexo feminino 19,35% (n = 83). Associaram ao risco de internar por CSAP: idade superior a 60 anos, baixa escolaridade, internação prévia, realização de controle regular de saúde, falta de vínculo com a Estratégia Saúde da Família (ESF) e ser gestante. As causas evidentes foram as condições relacionadas à gravidez, ao parto e ao puerpério e às inflamações nos órgãos pélvicos femininos. Os resultados sugerem falhas no atendimento ambulatorial que deveria ser oportuno e resolutivo no contexto da saúde da mulher.

The scope of this paper was to analyze female-specific sensitive hospitalization occurring in primary care conditions and factors that determine or affect the occurrence of such hospitalizations (social, economic and demographic factors; health control). Analysis was performed by surveys on hospital morbidity with a sample of 429 females attended in Unified Health System (SUS) contracted hospitals. The sensitive hospitalizations percentage in primary care reached 49.42% (n = 212), highlighting female-specific hospitalization at 19.35% (n = 83). Hospitalization risks comprised elderly people over sixty, low schooling, previous hospitalizations, normal health control, lack of association with the Family Health Strategy and pregnancy. Evident causes were related to conditions of pregnancy, childbirth, post-partum and inflammations of the female pelvic organs. Results suggested flaws in outpatient attendance that should be adequate and provide solutions in women’s health.

Efeito da vacina pneumocócica 10-valente em eventos de colonização nasofaríngea em crianças na cidade de Salvador-Bahia / Effect of pneumococcal 10-valent in nasopharyngeal colonization events in children in the city of Salvador, Bahia

Streptococcus pneumoniae é uma bactéria patogênica que afeta crianças e idosos em todo o mundo, sendo responsável por elevada morbidade e mortalidade, especialmente nos países em desenvolvimento onde o acesso às vacinas pneumocócicas conjugadas (PCVs) é limitado. A colonização da nasofaringe precede o desenvolvimento de infecções e as crianças são o principal reservatório deste patógeno na comunidade. As vacinas pneumocócicas conjugadas reduzem a taxa de colonização e de doenças causadas por sorotipos vacinais, entretanto, pouco se sabe sobre seu efeito em eventos na substituição de sorotipos. Os objetivos deste estudo foram determinar o efeito da vacina pneumocócica conjugada 10-valente (PCV10) na colonização nasofaríngea por pneumococos em crianças menores que um ano, saudáveis e que apresentaram doença crônica ou desordem imunológica nos períodos pré- e pós esquema vacinal primário entre maio de 2011 a janeiro de 2014 e determinar a influência desta vacina na distribuição de sorotipos, da susceptibilidade antimicrobiana e do perfil genotípico dos pneumococos. Foram investigadas 168 crianças, sendo 63 do grupo de portadores de doenças clínicas (Grupo I) e 105 do grupo de crianças sadias (Grupo II). O isolamento, a identificação e a avaliação da resistência antimicrobiana do pneumococo foram realizados através de técnicas microbiológicas convencionais. A determinação dos sorotipos capsulares foi realizada através das técnicas de reação de polimerase em cadeia multiplex e reação de Quellung. A taxa de colonização pneumocócica total foi de 24%, sendo 17% (11/63) e 28% (29/105) para os grupos I e II, respectivamente...

Streptococcus pneumoniae is a pathogenic bacterium that affects children and elderly throughout the world, accounting for high morbidity and mortality, especially in developing countries where acess to pneumococcal conjugate vaccines (PCVs) is limited. Nasopharyngeal colonization precedes the development of infections and children are the main reservoir of this pathogen in the community. The pneumococcal conjugate vaccine has been effective in reducing colonization and disease by vaccine serotypes, however, little is known about its effect on the overall rate of colonization due to serotypes replacement events. The study aims to evaluate the effect of pneumococcal conjugate vaccine on nasopharyngeal carriage in children younger than one years old, healthy, suffering from crhonic diseases or immune disorders during vaccine primary immunization with PCV-10 between may 2011 and jaanuary 2014 and the influence of this vaccine in the distribution of serotypes, antimicrobial susceptibility and genotypic profile of pneumococcus. A total of 168 children were enrolled, 63 with chronic diseases (Group I) and 105 of the group of healthy children (Group II). The isolation, identification and evaluation of antimicrobial resistance of pneumococci were made using conventional microbiological techniques. The determination of capsular serotypes was performed using the multiplex-PCR and/or Quellung reaction. Overal, the pneumococcal colonization rate was 24%, being 17% (11/63) and 28% (29/105) to group I and II, respectively...

Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

Phenotypic and Functional Analysis of HL-60 Cells Used in Opsonophagocytic-Killing Assay for Streptococcus pneumoniae

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.

The Association between Asthma and Invasive Pneumococcal Disease: A Nationwide Study in Korea

The purpose of this study was to investigate the association between asthma and invasive pneumococcal disease (IPD) in Korea. A retrospective population-based cohort study was conducted using the Korean Health Insurance Review and Assessment database 2010-2011. The subjects included 935,106 (2010) and 952,295 (2011), of whom 398 (2010) and 428 (2011) patients with IPD were identified. There was significant difference in the prevalence of IPD in patients with and without asthma (0.07% vs. 0.02% in 2010 and 0.08% vs. 0.01% in 2011; P<0.001). After adjusting for age and gender, patients with asthma showed over a three-fold increased risk of IPD compared with patients without asthma (adjusted odds ratio [aOR] 3.90, 95% confidence interval [CI] 3.02-5.03 in 2010 / aOR, 5.44; 95% CI, 4.10-7.22 in 2011; P<0.001). These findings were also significant in children (aOR, 2.08; 95% CI, 1.25-3.45 in 2010; P=0.005 / aOR, 3.26; 95% CI, 1.74-6.11 in 2011; P<0.001). Although diabetes mellitus was also significantly associated with IPD, relatively low ORs compared with those of asthma were noted (aOR, 1.85; 95% CI, 1.35-2.54 in 2010 / aOR, 2.40; 95% CI, 1.78-3.24 in 2011; P<0.001). Both children and adults with asthma are at increased risk of developing IPD.

Vacunas anti-neumocóccicas en población pediátrica: actualización / Pneumococcal vaccines in children: an update

Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was mantained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

Las vacunas antineumocóccicas conjugadas han tenido un impacto notable en la prevención de enfermedad neumocóccica invasora (ENI) en grupos vacunados y en contactos no vacunados (efecto rebaño). En Chile se incorpora en el PNI la vacuna conjugada de 10 serotipos (PCV10), el año 2011 a los 2, 4 y 6 meses , con un refuerzo a los 12 meses (esquema 3+1) y el año 2012 se elimina la dosis de los 6 meses (esquema 2+1), manteniendo esquema 3+1 en el prematuro. No se incluyen otros grupos etarios o pacientes con condiciones de riesgo. La vacunación ha reducido las tasas de ENI en 66% en menores de 12 meses, y en 60% en niños de 12 a 24 meses. A tres años de introducida la vacuna no hay evidencia de efecto rebaño. En relación a ST no contenidos en PCV10, se observa un incremento de ST 3, aunque no de ST 19A. La vigilancia realizada muestra que otra vacuna disponible (PCV13), tendría una cobertura de ST entre 5 y 15% superior a PCV10. Este hecho y el nulo efecto rebaño de PCV 10, hacen necesario considerar el reemplazo de PCV10 por PCV13 en el PNI.

Distribution of Serotypes and Antibiotic Susceptibility Patterns Among Invasive Pneumococcal Diseases in Saudi Arabia

BACKGROUND: Streptococcus pneumoniae causes life-threatening infections such as meningitis, pneumonia, and febrile bacteremia, particularly in young children. The increasing number of drug-resistant isolates has highlighted the necessity for intervening and controlling disease. To achieve this, information is needed on serotype distribution and patterns of antibiotic resistance in children. METHODS: All cases of invasive pneumococcal disease (IPD) in children aged less than 15 yr recorded at King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, were reviewed for serotyping and antibiotic susceptibility. Isolates were collected from 78 consecutive patients with IPD between 2009 and 2012. All collected isolates were subjected to serotyping by co-agglutination, sequential multiplex PCR, and single PCR sequetyping as previously described. RESULTS: The most frequently isolated IPD serotypes were 23F, 6B, 19F, 18C, 4, 14, and 19A, which are listed in decreasing order and cover 77% of total isolates. The serotype coverage for the pneumococcal conjugate vaccine (PCV)7, PCV10, and PCV13 was 77%, 81%, and 90%, respectively. Results from sequential multiplex PCR agreed with co-agglutination results. All serotypes could not be correctly identified using single PCR sequetyping. Minimum inhibitory concentration showed that 50 (64%) isolates were susceptible to penicillin, whereas 70 (90%) isolates were susceptible to cefotaxime. CONCLUSIONS: The most common pneumococcal serotypes occur with frequencies similar to those found in countries where the PCV has been introduced. The most common serotypes in this study are included in the PCVs. Addition of 23A and 15 to the vaccine would improve the PCV performance in IPD prevention.

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in Mexico / Inmunogenia y seguridad de la vacuna antineumocócica conjugada 13 valente en México

OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13) after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG) concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe) was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.

OBJETIVO: Evaluar la seguridad y la respuesta inmunitaria inducida por una vacuna antineumocócica conjugada 13 valente (PCV13) tras la vacunación de lactantes en México. MÉTODOS: Se administró la PCV13, junto con otras vacunas habituales de la niñez, a 225 lactantes a los 2, 4, 6 y 12 meses de edad en México. RESULTADOS: Las proporciones de lactantes que alcanzaron concentraciones de inmunoglobulina G (IgG) iguales o superiores a 0,35 µg/ml después de las tres primeras dosis (serie del lactante) y tras la cuarta (dosis del inicio de la deambulación) fueron de ≥ 93,1% y ≥ 96,7%, respectivamente, para los 13 serotipos. Las medias geométricas de las concentraciones de IgG antineumocócica específica de serotipo después de las tres primeras dosis y tras la cuarta variaron de 1,18 a 9,13 µg/ml, y de 1,62 a 15,41 µg/ml, respectivamente. Las reacciones local y sistémica más frecuentes después de cada dosis fueron respectivamente el dolor en el punto de inyección y la irritabilidad. En la mayor parte de los casos, la fiebre fue de carácter leve; no se notificó ningún caso de fiebre de más de 40,0 °C (fiebre grave). Un lactante fue excluido del estudio como consecuencia de la aparición de una enfermedad de Kawasaki cinco días después de la primera dosis de la vacuna, aunque se consideró que este proceso no estaba relacionado con la PCV13. CONCLUSIONES: En términos generales, la PCV13, administrada conjuntamente con las vacunas pediátricas habituales, se mostró inmunógena e inocua en lactantes sanos de México.

Estandarización en Colombia de una prueba ELISA para la evaluación de los niveles séricos de anticuerpos IgG contra diez serotipos de Streptococcus pneumoniae / An immunoenzymatic test for IgG antibody levels against 10 serotypes of Streptococcus pneumoniae

Introducción. Streptococcus pneumoniae es causante de gran morbimortalidad en niños pequeños y ancianos. Sin embargo, en Colombia no está disponible una prueba que evalúe la respuesta humoral a la vacunación específica contra este microorganismo Objetivo. Estandarizar en Colombia un ensayo inmunoenzimático para evaluar los niveles séricos de anticuerpos IgG contra diez serotipos de S. pneumoniae en respuesta a la vacunación específica y caracterizar esta respuesta en individuos sanos de nuestra población. Materiales y métodos. Se hizo un ELISA en fase sólida utilizando como antígenos los polisacáridos capsulares 1, 3, 4, 5, 6B, 9V, 14, 18, 19F y 23F de S. pneumoniae. Resultados. Los sueros de referencia y control reaccionaron fuertemente contra los polisacáridos evaluados, especialmente contra 14 y 19F. En los cinco niños sanos evaluados, los polisacáridos 5 y 19F presentaron los mayores títulos antes de la vacunación. Antes de la vacunación en los niños, y antes y después de la vacunación en los adultos, los polisacáridos 14 y 19F reaccionaron fuertemente. Para todos los polisacáridos, excepto para el 5, existe una relación inversa entre títulos altos de anticuerpos IgG antes de la vacunación y la razón de incremento de los títulos después de la misma. Conclusión. Esta prueba ELISA cuantifica de forma confiable los niveles de IgG sérica contra diez serotipos de S. pneumoniae y, de acuerdo con los resultados obtenidos en individuos sanos de nuestra población, en este trabajo se validan los parámetros internacionales para considerar adecuada la respuesta a la vacuna 23-valente contra este microorganismo.

Introduction. Streptococcus pneumoniae is a major cause of morbi-mortality in early childhood and elderly. However, a test to measure the antibody responses after specific vaccination is not available in Colombia. Objective. An immunoenzymatic test was standardized for the measurement of serum IgG levels against 10 serotypes of S. pneumoniae in response to the specific vaccination. Material and methods. Capsular polysaccharides 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, 23F of S. pneumoniae were used as antigens in a solid-phase ELISA. These responses were characterized in a randomized selected healthy individuals from a Colombian population. Results. The reference and control sera showed great reactivity against all the polysaccharides evaluated, especially against polysaccharide 14 and 19F. The lowest reactivity in these two sera was observed against polysaccharide 3 and 4. Among the children evaluated, polysaccharide 5/19F showed the highes pre-vaccination reactivity, and polysaccharide 14/19F showed the highest post-vaccination reactivity. Among the adults, polysaccharides 14 and 19F showed the greatest reactivity pre- and post-vaccination. For all the polysaccharides (excepting polysaccharide 5), an inverse association among high polysaccharide-specific pre-vaccination- and the increase of post-vaccination-IgG levels was observed. Conclusion. This ELISA test reliably quantifies the serum levels of specific IgG against 10 serotypes of S. pneumoniae. According to the responses by healthy individuals, the current study validates parameters used internationally as an adequate the response to the 23-valent pneumococcal vaccine.