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

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

Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital / Cobertura vacinal pneumocócica teórica: análise de sorotipos isolados de pacientes internados em hospital terciário

ABSTRACT Objective: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). Methods: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. Results: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. Conclusions: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.

RESUMO Objetivo: Avaliar os sorotipos de Streptococcus pneumoniae isolados de uma população internada em um hospital terciário para verificar a cobertura vacinal teórica das vacinas conjugada pneumocócica 13-valente (VCP13) e pneumocócica polissacarídica 23-valente (VPP23). Métodos: Estudo transversal envolvendo 118 pacientes internados no Hospital São Lucas, na cidade de Porto Alegre (RS), cujas amostras de cultura de sangue, líquor ou outro líquido estéril apresentaram isolados de pneumococos entre janeiro de 2005 e dezembro de 2016. A cobertura vacinal teórica foi estudada em relação aos sorotipos observados na amostra e sua relação com os contidos nas vacinas pneumocócicas disponíveis no Brasil. Resultados: A maioria da população era masculina (n = 66; 55,9%), com mediana de idade de 57 anos (intervalo interquartil: 33-72 anos). O agravo mais frequente foi pneumonia, e o pneumococo foi mais frequentemente isolado em hemocultura. Mais de um quarto da população estudada tinha algum grau de imunossupressão (n = 34; 28,8%). Na amostra geral, 39 pacientes (33,1%) foram a óbito. Não houve associações significativas do número de óbitos com o tipo de comorbidades, internação em UTI ou necessidade de ventilação mecânica. A cobertura vacinal teórica da VPP23 e da combinação VCP13 + VPP23 foi de 31,4% e 50,8%, respectivamente. Conclusões: Nesta amostra, se os pacientes tivessem sido previamente vacinados com a combinação VCP13 seguida de VPP23, teoricamente, 50,8% dos casos de doença pneumocócica invasiva que necessitaram de internação hospitalar poderiam ter sido prevenidos potencialmente. Essa doença deve ser prevenida com a vacinação não só de crianças e idosos, mas também de adultos em idade economicamente ativa, para reduzir o custo socioeconômico, a morbidade e a mortalidade ainda associados à doença, especialmente em países subdesenvolvidos.

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.

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.

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.

Enfermedad neumoccócica invasora en recién nacidos, antes y después de la vacunación universal con vacuna conjugada 7 y 13 valente en Uruguay / Pneumococcal invasive disease in newborns before and after 7-valent and 13-valent universal pneumococcal vaccination in Uruguay

Introduction: Streptococcus pneumoniae infections are not frequent in neonates, but presents high morbidity and mortality. In 2008, the 7-valent pneumococcal conjugate vaccine (PCV) was introduced in the childhood vaccination schedule and then replaced by 13-valent PCV in 2010. First dose is given at 2 months of age. Protection of neonates is expected with universal vaccination. Objective: To describe the clinical presentation, microbiology and outcome of neonates with pneumococcal invasive infections (PII) detected in two hospitals in Uruguay in 2001-2007 (pre-vaccination), 2008 (intervention) and 2009-2013 (post-vaccination). Methods: A descriptive, retrospective study was done at Pereira Rossell Hospital and Paysandú Hospital. All isolates of S. pneumoniae obtained from normally sterile fluids were included. Data were obtained from the clinical records and the microbiology laboratory. A statistical analysis with absolute frequencies, relative, rates and relative risk was performed. Results: 25 neonates were enrolled with diagnosis of: sepsis (n = 13), meningitis (n = 9), bacteremia (n = 1), pneumonia with empyema (n = 1) and pneumonia (n = 1). The incidence of PII in the prevaccination period was 19/25, with a rate of 0.30/1,000 births, compared to post-vaccination rate of 0.04/1,000. The relative risk was 5.9. 6/20 (30%) cases of death were reported (meningitis n = 3; sepsis n = 2; empyema n = 1). Most common serotypes were 5 and 1 (14/25) and 24/25 strains were susceptible to penicillin. Discussion: The symptoms were indistinguishable to infections caused by other pathogens. PII cases decreased and no deaths occurred in the post-vaccination period. No increase in non-vaccine serotypes was observed.

Introducción: Streptococcus pneumoniae infrecuentemente produce infecciones en recién nacidos (RN), presentando elevada morbi-mortalidad. En Uruguay, en 2008 se incorporó al calendario de inmunizaciones infantil la vacuna conjugada neumocóccica (VCN) 7 valente, (sustituída por VCN13 en 2010). La vacunación comienza a los dos meses de vida. Se espera que la vacunación universal tenga impacto en la protección de RN. Objetivo: Describir la presentación clínica, microbiología y evolución de RN con enfermedad neumocóccica invasora (ENI), identificados en dos hospitales de Uruguay, años 2001-2007 (pre-vacunación), 2008 (intervención) y 2009-2013 (post-vacunación). Material y Métodos: Estudio descriptivo, retrospectivo. Lugar: Hospital Pereira Rossell y Hospital Paysandú. Se incluyeron todos los aislados de S. pneumoniae a partir de líquidos normalmente estériles. Fuente de datos: laboratorios de bacteriología e historias clínicas. Análisis estadístico: frecuencias absolutas, relativas, tasas y riesgo relativo. Resultados: RN con ENI: 25, sepsis (n: 13), meningitis (n: 9), bacteriemia (n: 1), neumonía con empiema (n: 1), neumonía (n: 1). Incidencia de ENI en el período pre-vacunación 19/25, tasa 0,30/1.000 nacimientos; tasa post-vacunación: 0,04/1.000. Riesgo relativo 5,9. Fallecimientos: 6/20 (30%): meningitis (n: 3), sepsis (n: 2), empiema (n: 1). Los serotipos más frecuentes fueron: 5 y 1 (14/25). Susceptibles a penicilina: 24/25. Discusión: Los síntomas fueron indistinguibles de infecciones causadas por otros patógenos. Disminuyeron los casos de ENI y no ocurrieron fallecimientos en el período post-vacunación. No aumentaron los serotipos no vacunales.

Distrofia muscular facioescapulohumeral en Chile: presentación de serie en hospital de referencia terciario / Facioscapulohumeral muscular dystrophy: Report of seven patients

Background: Facioscapulohumeral muscular dystrophy is the third most common muscular dystrophy with an estimated prevalence of 1 per 20.000 and a normal life expectancy in the majority of patients. However, approximately 15% of patients become wheelchair bound in the course of their life. It is a hereditary autosomal dominant disease with high (95%) penetrance by the age of 20, but with variable degree of phenotypic expression even in the same family group. Symptoms frequently start in the second decade of life, with facial and scapular weakness. Aim: To report the clinical features of seven patients with the disease, seen at a public hospital. Material and Methods: Analysis of seven patients with genetic study seen in a public Hospital in Santiago. Results: The age of patients fluctuated from 18 to 61 years and four were females. The mean age at onset of symptoms was 29 years and four had a family history of the disease. The usual presenting complaint was arm or shoulder asymmetric weakness. Four patients had bone pain. Facial involvement was present in four. A genetic study was done in five patients, the other two patients were relatives, confirming the contraction or lower number of repetitions in D4Z4 region. After 12 years of follow up only 2 patients older than 60 years cannot work and one female patients is in a semi dependent state at the age of 30. Conclusions: The clinical workup in the diagnosis and the timely indication of genetic studies are highlighted, to avoid unnecessary and invasive procedures. The variability in the phenotypic expression in a similar genetic defect is discussed and the genetic or epigenetic mechanisms of this muscular dystrophy are described.

Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil / Impacto de la vacuna neumocócica conjugada 10-valente en la meningitis neumocócica en niños de hasta dos años de edad en Brasil / Impacto da vacina pneumocócica conjugada 10-valente na meningite pneumocócica em crianças com até dois anos de idade no Brasil

The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009) and post-vaccination (2011-2012) periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness.

El objetivo de este estudio fue analizar el impacto de la vacunación contra el Streptococcus pneumoniae en la morbilidad y mortalidad de la meningitis neumocócica en niños ≤ 2 años en Brasil, 2007-2012. Se trata de un estudio descriptivo ecológico que analiza los datos del Sistema de Información Enfermedades de Notificación Obligatoria en Brasil. El período previo (2007-2009) y posterior a la vacunación (2011-2012) fueron examinados para comparar las tasas de incidencia y mortalidad. 1.311 casos de meningitis neumocócica con 430 muertes se registraron durante el período de estudio. Hubo una disminución de la incidencia de 3,70 casos por 100.000 habitantes en 2007, a 1,84/100.000 en 2012, mientras que la tasa de mortalidad cayó 1,30 a 0,40 óbitos/100.000, se produjeron reducciones del 50% y 69%, respectivamente, con mayores impactos identificados entre los niños de 6-11 meses de edad. Los resultados indican una reducción en la morbilidad y mortalidad por meningitis neumocócica dos años después de la introducción de la vacuna conjugada antineumocócica 10-valente, lo que sugiere su eficacia.

O objetivo deste trabalho foi analisar o impacto da vacinação contra o Streptococcus pneumoniae na morbidade e mortalidade por meningite pneumocócica em crianças ≤ 2 anos, no Brasil, entre 2007-2012. Este é um estudo descritivo com análise ecológica, utilizando dados do Sistema de Informação de Agravos de Notificação. Foram definidos os períodos pré-vacinal (2007-2009) e pós-vacinal (2011-2012) para comparar as taxas de incidência e mortalidade. Foram identificados 1.311 casos e 430 óbitos no período do estudo. A taxa de incidência diminuiu de 3,70/100.000 no ano de 2007 para 1,84/100.000 em 2012, e a mortalidade reduziu de 1,30/100.000 para 0,40/100.000, o que significa uma redução de 50% e 69%, respectivamente, com maior impacto identificado na faixa etária de 6 a 11 meses. Os resultados indicam uma diminuição nos indicadores de morbidade e mortalidade de meningite pneumocócica, observados dois anos após a introdução da vacina pneumocócica conjugada 10-valente, sugerindo sua efetividade.

Impacto da vacina pneumocócica conjugada 10-valente na meningite pneumocócica na região metropolitana de Salvador, Bahia / Impact of pneumococcal conjugate vaccine 10-valent pneumococcal meningitis in the metropolitan region of Salvador, Bahia

INTRODUÇÃO: Em 2010, a vacina conjugada 10-valente (PCV10) foi incorporada ao programa nacional de imunizações (PNI) brasileiro. Este imunobiológico confere imunização contra os dez principais tipos capsulares de Streptococcus pneumoniae, patógeno responsável por diversas manifestações clínicas e com elevada contribuição nas taxas de incidência e mortalidade por meningite, que é a condição clínica mais grave. OBJETIVO: O presente estudo teve como objetivo avaliar o impacto da PCV10 na epidemiologia da meningite pneumocócica na região metropolitana de Salvador (RMS) Bahia, comparando o período anterior (2008-2010) e posterior (2011-2013) a sua utilização, bem como realizar uma caracterização molecular minuciosa a partir de uma série histórica (1996-2012) entre os isolados resistentes a enicilina (PNSSP com CIM≥ 0,125 μg/mL) e para os sorotipos não-vacinais (2008-2012). MATERIAL E MÉTODOS: Foram incluídos todos casos de meningite pneumocócica confirmados laboratorialmente no período entre 1996 a 2013. Taxas de incidência para a Salvador e RMS foram calculadas com base nos dados populacionais do IBGE/2010. A determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a nove antimicrobianos foi testada através das técnicas disco-difusão,microdiluição e E-test. Para caracterizar o perfil molecular foram aplicadas as técnicas de genotipagem de PFGE e MLST. RESULTADOS: Um total de 939 casos de meningite pneumocócica foram identificados no período de 1996-2013, sendo que 70 casos ocorrem entre 2011 a 2013 (período pós-vacinal). A incidência de meningite pneumocócica em todas as faixas etárias na RMS reduziu de 0,70 casos/100.000 habitantes para 0,59 casos/100.000 habitantes considerando o período de três anos antes e após a vacinação com PCV10 [p<0,05; RR IC 95%: 1,46 (1,03-2,05)]. Esta redução foi significativa na faixa etária de 0-2 anos e nos casos por sorotipos relacionados à PCV10. Não houve aumento significativo de casos por sorotipos não vacinais nesta casuística,apesar do surgimento de casos por sorotipos não-vacinais não detectados anteriormente na série histórica de MP (10F, 21, 22F, 15A e 24F). Os isolados resistentes à penicilina analisados na série histórica se restringiram a 13 sorotipos, entre os quais: 14 (45,1 %; 78/173), 23F (19,1%; 33/173), 6B (14,4 %; 25/173), 19F (9,2 %; 16/173) e 19A (5,2 %; 9/173). 94% dos casos nãosusceptíveis à penicilina (PNSSP) foram de sorotipos vacinais. Os grupos clonais caracterizados pelo PFGE/MLST predominantes ao longo dos anos foram representados pelo sorotipo 14, denominado grupo A/ST 66 [35,3 %(61/173)] e grupo GK/ST 156 [4.6 % (8/173)], este último associado com níveis elevados de resistência a penicilina e ceftriaxona. Não foram detectados grupos clonais emergentes associados a tipos capsulares não-vacinais.CONCLUSÕES: Estes achados sugerem que a introdução da PCV10 modificou a epidemiologia da meningite pneumocócica na população estudada.

INTRODUCTION: In 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Brazilian national immunization program (NIP). This immunobiological provides immunization against the main ten capsular types of Streptococcus pneumoniae, the pathogen responsible for different clinical manifestations and high contribution in the incidence and mortality from meningitis, which is the most severe clinical condition. OBJECTIVE: This study aimed to evaluate the impact of PCV10 in the epidemiology of pneumococcal meningitis in the metropolitan area of Salvador (RMS) Bahia, comparing the previous (2008-2010) and after (2011-2013) periods its use, as well as conduct a thorough molecular characterization from a historical series (1996-2012) among isolates resistant to penicillin (PNSSP with CIM≥ 0.125 g / ml) and nonvaccine serotypes (2008-2012). MATERIAL AND METHODS: We included all cases of pneumococcal meningitis laboratory confirmed for the period 1996 to 2013. Incidence rates for Salvador and RMS were calculated based on population data from IBGE/2010. The capsular type determination was performed by multiplex PCR and/or Quellung reaction. Isolates Nine antibiotics were tested by disk-diffusion test, broth micro-dilution and E-test. To characterize the molecular profiling techniques were applied genotyping PFGE and MLST...

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.

Colonização Nasofaringeana por streptococcus pneumoniae: estudo lngitudinal em crianças menores de cinco anos de idade / Colonization nasopharyngeal by Streptococcus pneumoniae: longitudinal study in children under Five years old

Streptococcus pneumoniae é um dos agentes etiológicos mais importantes em infecções adquiridas na comunidade. Este patógeno coloniza o trato respiratório de indivíduos saudáveis, apresentando maior prevalência entre 1 e 2 anos de idade (aproximadamente 50%) e depois diminui com a idade adulta (aproximadamente 10%). A alta incidência das doenças pneumocócicas e a crescente resistência aos antimicrobianos, favoreceu a introdução das vacinas conjugadas (ano de 2000). Após a introdução das vacinas conjugadas foi observado à queda na incidência da doença pneumocócica e diminuição da prevalência de colonização por sorotipos vacinais. Em contrapartida vem sendo notado o aumento de casos de doença sorotipos não vacinais. Por isso a importância de verificar a dinâmica da colonização nasofaringeana por pneumococos em crianças < 5 anos de idade antes da introdução da vacina. Foram selecionadas radomicamente 203 crianças residentes da comunidade de Pau da Lima, Salvador, Bahia, das quais foi colhido a amostra nasofaringeana em quatro períodos durante um ano com intervalo de três a quatro meses entre cada coleta. No período de janeiro de 2008 a janeiro de 2009 foram colhidos um total de 721 swabs, sendo 398 positivos para pneumococos (56%)...

Streptococcus pneumoniae is one of the most important etiologic agents in community-acquired infections. This pathogen colonizes the respiratory tract of healthy individuals shortly after birth, with higher prevalence of between 1 and 2 years of age (approximately 50%) and then decreases with age reaching adult rates below 10%. The high incidence and increasing antimicrobial resistance, favored the introduction of conjugate vaccines in 2000. After the introduction of conjugate vaccines a decreasing incidence of pneumococcal disease and carriage rates by vaccine serotypes was observed. In contrast we observe an increase in number of cases of disease and carriage by non-vaccine serotypes. Thus, this study aims to determine the dynamics of nasopharyngeal colonization by pneumococci in children <5 years of age after introduced the conjugate vaccine. A total of 203 children were random selected at the community of Pau da Lima in Salvador, Bahia, of whom the nasopharyngeal swab was collected in four periods with interval of 3 to 4 months between each collection. A total of 721 swabs were collected from January 2008 to January 2009, with 398 positive for pneumococci (56%)...

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.

Epidemiologia molecular de Streptococcus pneumoniae sorotipos 1 e 5 isolados de doenças invasiva em Moçambique / Molecular epidemiology of Streptococcus pneumoniae serotypes 1 and 5 isolated from invasive disease in Mozambique

Streptococcus pneumoniae é a principal causa de morbi-mortalidade no mundo. Em Moçambique, os sorotipos 1 e 5 são os mais prevalentes. Este estudo investigou a relação clonal de isolados de pneumococo obtidos de doença invasiva entre o período de 2002-2007, utilizando três procedimentos laboratoriais: Box-PCR, PFGE e MLST. Um total de 105 isolados (sendo 72 do sorotipo 1 e 33 do sorotipo 5), foram submetidos a técnica de Box-PCR. O sorotipo 5 apresentou cinco padrões, sendo um clonal com 20 isolados e quatro padrões não clonais. O padrão A foi o predominante com 61% dos isolados, enquanto que por PFGE, 100% dos isolados foram agrupados em um único clone (clone A), e pela técnica de MLST foi identificado apenas um único ST (ST 289). Por outro lado, o sorotipo 1 apresentou maior diversidade clonal pelos três métodos; por Box-PCR os isolados foram agrupados em 3 clones, sendo predominante o padrão B com 58 isolados, padrão C e N com dois isolados cada. Um total de 12 isolados foram não clonais. O clone B apresentou 20 subtipos, sendo o mais frequente o sub-tipo B1 com 20 amostras idênticas, seguido por B2, B6, B7 com 5 amostras idênticas cada. Por PFGE, 19 amostras confirmaram ser do mesmo perfil clonal (clone B), enquanto que 12 amostras demonstraram ser não clonais. Quando submetidos ao MLST, foram identificados 6 STs; ST 217 (7 isolados), ST 853 (1 isolado), e quatro novos STs, ST 4125, ST 2909, ST 3779 e ST 4166. O ST 217 pertence ao clone Suécia1-27 (ST217), identificados previamente em surtos de meningite na África, enquanto o ST 289 foi identificado como um representante do clone Colômbia5-19 (ST289) que circulam na América Latina desde 1994. A taxa de não susceptibilidade à penicilina foi de 3%, e à cotrimoxazole foi de 39%. A maior taxa de resistência foi encontrada entre os isolados de sorotipo 1. Este trabalho mostra a persistência de dois sorotipos responsáveis por causar doença pneumocócica invasiva graves, bem como seus respectivos clones em uma região do sul de Moçambique.

Análise das cepas de Streptococcus pneumoniae causadores de pneumonia invasiva: sorotipos e sensibilidade aos antimicrobianos / Analysis of invasive pneumonia-causing strains of Streptococcus pneumoniae: serotypes and antimicrobial susceptibility

OBJETIVOS: Identificar os sorotipos de pneumococo mais frequentemente isolados de crianças internadas com pneumonia invasiva, comparar os sorotipos com os incluídos em vacinas conjugadas e analisar sua sensibilidade aos antimicrobianos mais utilizados na faixa etária pediátrica. MÉTODOS: Estudo descritivo, retrospectivo das pneumonias pneumocócicas identificadas em crianças internadas no hospital universitário da Universidade de São Paulo, no período de janeiro de 2003 a outubro de 2008. Os critérios de inclusão foram: faixa etária de 29 dias até 15 anos incompletos com diagnóstico clínico e radiológico de pneumonia e com cultura de sangue e/ou líquido pleural com crescimento de Streptococcus pneumoniae. RESULTADOS: Foram incluídas no estudo 107 crianças. Os sorotipos mais frequentes foram: 14 (36,5 por cento), 1 (16,7 por cento), 5 (14,6 por cento), 6B (6,3 por cento) e 3 (4,2 por cento). A proporção de sorotipos contidos na vacina conjugada heptavalente seria de 53,1 por cento, na vacina 10-valente de 86,5 por cento e na 13-valente seria de 96,9 por cento. De acordo com os padrões do Clinical and Laboratory Standards Institute 2008, 100 cepas (93,5 por cento) de pneumococos foram sensíveis à penicilina (concentração inibitória mínima, CIM < 2 µg/mL), 7 cepas (6,5 por cento) com resistência intermediária (CIM = 4 µg/mL) e nenhuma com resistência (CIM > 8 µg/mL). Verificamos alta taxa de sensibilidade para as cepas testadas para vancomicina, rifampicina, ceftriaxone, clindamicina, cloranfenicol e eritromicina. CONCLUSÕES: Nossos resultados confirmam um expressivo impacto potencial das vacinas conjugadas, principalmente pela 10-valente e 13-valente, sobre os casos de pneumonias invasivas. Os resultados de sensibilidade à penicilina evidenciam que a opção terapêutica de escolha para o tratamento das pneumonias invasivas continua sendo a penicilina.

OBJECTIVES: To identify the most common pneumococcal serotypes in children hospitalized with invasive pneumonia, correlate isolated serotypes with those included in conjugate vaccines, and ascertain the sensitivity of the isolated pneumococcal strains to penicillin and other antibiotics. METHODS: From January 2003 to October 2008, a retrospective study of hospitalized children with a diagnosis of Streptococcus pneumoniae pneumonia was conducted at the university hospital of Universidade de São Paulo. Criteria for inclusion were: age greater than 29 days and less than 15 years, radiological and clinical diagnosis of pneumonia, and isolation of Streptococcus pneumoniae in blood cultures and/or pleural effusion. RESULTS: The study included 107 children. The most common serotypes were 14 (36.5 percent), 1 (16 percent), 5 (14.6 percent), 6B (6.3 percent) and 3 (4.2 percent). The proportion of identified serotypes contained in the heptavalent, 10-valent and 13-valent conjugate vaccines was 53.1, 86.5, and 96.9 percent, respectively. Pneumococcal strains were sensitive to penicillin (minimum inhibitory concentration, MIC < 2 µg/mL) in 100 cases (93.5 percent) and displayed intermediate resistance (MIC = 4 µg/mL) in 7 cases (6.5 percent). No strains were penicillin-resistant (MIC > 8 µg/mL) according to the Clinical and Laboratory Standards Institute 2008 standards. Tested isolates were highly sensitive to vancomycin, rifampicin, ceftriaxone, clindamycin, erythromycin, and chloramphenicol. CONCLUSIONS: Our results confirm a significant potential impact of conjugate vaccines, mainly 10-valent and 13-valent, on invasive pneumonia. Furthermore, susceptibility testing results show that penicillin is still the treatment of choice for invasive pneumonia in our setting.

Desenvolvimento e avaliação da resposta imune humoral de uma vacina anti-pneumocócica conjugada polissacarídeo capsular sorotipo 14 - proteína de superfície pneumocócica A / Development and evaluation of the humoral immune response of na antipneumococcal conjugate vaccine: capsular polysaccharide serotype 14-pneumococcal surface protein A

Streptococcus pneumoniae é uma bactéria encapsulada que coloniza a nasofaringe, sendo uma das principais causas de morte por pneumonia e meningite em crianças e idosos. As vacinas contra S. pneumoniae são compostas por polissacarídeos capsulares (PS) livres ou conjugados à uma proteína. A vantagem do polissacarídeo conjugado em relação ao livre é a resposta timo-dependente. Pelo fato de existirem pelo menos 92 diferentes sorotipos capsulares, a utilização de uma proteína pneumocócica em uma vacina conjugada com apenas alguns sorotipos poderia aumentar a sua cobertura vacinal. Para tal, a utilização da proteína de superfície pneumocócica A (PspA) foi utilizada como carreador protéico covalentemente ligado ao polissacarídeo capsular sorotipo 14. Este trabalho também apresenta uma nova metodologia para a síntese de vacinas conjugadas, que vem demonstrando melhores resultados em nosso laboratório em comparação aos métodos clássicos de conjugação. O conjugado PS14-PspA foi administrado em camundongos BALB/c e o título de IgG anti-PS14 e anti-PspA, o índice de avidez, a deposição de complemento e a distribuição das subclasses de IgG foram avaliados. O título de IgG anti-PS14 conjugado foi significativamente maior do que título de IgG anti-PS14 livre. A avidez e a deposição de complemento do soro anti-PS14 conjugado também foram maiores. A principal subclasse de IgG induzida pelo PS14 livre foi IgG3 enquanto o PS14 conjugado induziu preferencialmente IgG1. No entanto, o índice de avidez, o perfil de distribuição das subclasses de IgG e a medida funcional da atividade opsonofagocítica dos soros anti-PspA livre e conjugada foram os mesmos.

Streptococcus pneumoniae is an encapsulated bacterium that colonizes the nasopharynx, being one of the leading causes of death from pneumonia and meningitis in infants and elderly. Vaccines against S. pneumoniae are constituted by plain capsular polysaccharide (PS) or conjugated to a protein. The advantage of conjugated PS on plain PS vaccine is the thymus dependent immune response. Since there are at least 92 different capsular serotypes, the use of a pneumococcal protein in a conjugate vaccine using only few serotypes might broader its coverage. For this purpose the pneumococcal surface protein A (PspA) was used as protein carrier to bind covalently to the capsular polysaccharide serotype 14. This work also presents a new methodology for the synthesis of conjugate vaccines, which showed better results in our laboratory in comparison to the classic ones. The conjugate PS14-PspA was injected in BALB/c mice and sera were measured for IgG titer against PS14 and PspA. IgG avidity index, complement deposition, and anti-PS14 and anti-PspA IgG subclasses were also evaluated. IgG titer against conjugated PS14 was significantly higher than IgG titer against control PS14. The avidity and the complement deposition of conjugated anti-PS14 serum were also higher. The main IgG subclass induced by free PS14 was IgG3 while conjugated PS14 induced preferably IgG1. Nevertheless, the avidity index, the IgG subclasses distribution profile, and the functional opsonophagocytic measure from free and conjugated anti-PspA sera were the same.