Streptococcus pneumoniae: distribution of serotypes and antimicrobial susceptibility in patients with cáncer / Streptococcus pneumoniae: distribución de serotipos y susceptibilidad antimicrobiana en pacientes con cancer

Abstract: Objective: To describe the distribution of pneumococcal serotypes causing infectious diseases in patients with hematological malignancies and solid tumors and their antimicrobial susceptibility before and after introduction of pneumococcal conjugate vaccine (PCV7) in Mexico. Materials and methods: Consecutive pneumococcal isolates from hospitalized patients from the SIREVA-network were serotyped using the Quellung reaction and antimicrobial susceptibility was performed using the broth microdilution method. Results: A total of 175 pneumococcal isolates were recovered, 105 from patients with hematological malignancies and 70 with solid tumors. Serotypes 19A (22.7%), 19F (20.4%), and 35B (17.7%) were the most frequent isolates in the first group and serotypes 3 (27.2%) and 19A (28.6%) in the second group. No decreased susceptibility to beta-lactams or TMP/SMX was observed after introduction of PCV7. Conclusions: An increase in non-vaccine types is observed without significate changes in antimicrobial susceptibility after introduction of PCV7.

Resumen: Objetivo: Describir la distribución de serotipos neumocócicos en pacientes con neoplasias hematológicas y tumores sólidos, así como la susceptibilidad antimicrobiana antes y después de la introducción de la vacuna conjugada contra neumococo (PCV7) en México. Material y métodos: Se tipificaron, mediante la reacción de Quellung, los aislamientos consecutivos en hospitales de la Red SIREVA-México. Se determinó la susceptibilidad antimicrobiana mediante microdilución en placa. Resultados: Se recuperaron 175 aislamientos, de los cuales 105 provenían de pacientes con neoplasias hematológicas y 70 con tumores sólidos. Los serotipos 19A (22.7%), 19F (20.4%) y 35B (17.7%) fueron los más frecuentes en el primer grupo y los serotipos 3 (27.2%) y 19A (28.6%) en el segundo. No se observó disminución de la resistencia a betalactámicos o TMP/SMX después de la introducción de PCV7. Conclusiones: Se observa un incremento de serotipos no vacunales, sin cambios significativos en la susceptibilidad antimicrobiana antes y después de la introducción de PCV7.

Efectos de la vacuna neumocócica conjugada (VCN7 y VCN13) en los niños turcos con enfermedad neumocócica invasiva: experiencia en un solo centro / The effects of pneumococcal conjugate vaccine (PCV7 and PCV13) on Turkish children with invasive pneumococcal disease: a single center experience

Introducción: Nuestro objetivo fue determinar los cambios en la incidencia de enfermedad neumocócica invasiva (ENI), la distribución de serotipos y patrones de resistencia antibiótica del Streptococcus pneumoniae en niños con ENI tras el período de vacunación (de 1 a 7 años) con vacuna neumocócica de 7 serotipos (VCN7) (2008) y de 13 serotipos (VCN13) (2011). Población y métodos: El estudio se realizó en 39 niños con ENI de 1 mes a 18 años de edad en Angora, Turquía. Se identificó Streptococcus pneumoniae en sangre, líquido cefalorraquídeo, líquido pleural, y otros tejidos y líquidos corporales estériles mediante procedimientos estándar. Se analizó la resistencia de cepas aisladas de S. pneumoniae a penicilina y ceftriaxona con la prueba de epsilometría (E-test). Los serotipos de las cepas se determinaron con la reacción de Quellung. Resultados: La incidencia anual de ENI disminuyó significativamente de 7,71 (intervalo de confianza --#91;IC--#93; del 95%: de 1,99 a 13,4) a 1,58 (IC del 95%: de 0,6 a 3,77; reducción del riesgo relativo= -79,5; p= 0,006) cada 100 000 habitantes de < 5 años de edad sin enfermedad preexistente. Durante todo el período del estudio, los serotipos en la VCN7 y en la VCN13 representaron el 27,8% y el 63,8% de las cepas aisladas, respectivamente. Los serotipos en la VCN13 correspondían al 81,8% de los casos de ENI en la era previa a la introducción de esta vacuna, y disminuyeron al 56% en los cuatro años posteriores. Las tasas de resistencia a penicilina y ceftriaxona (en el caso de la meningitis) fueron del 48,5% y el 9,1%, respectivamente. Conclusiones: Este estudio observó una disminución significativa en la incidencia de ENI después de la introducción de la VCN13.

Introduction. The aim of this prospective singlecenter study was to determine the changings in incidence of invasive pneumococcal disease (IPD), serotype distribution and the antimicrobial resistance patterns of S. pneumoniae in children with IPD after the period (1 to 7 years) of vaccination with PCV7 (2008) and PCV13 (2011). Population and methods. The study was conducted on 39 Turkish children with IPD between ages 1 month and 18 years in Ankara, Turkey. Streptococcus pneumoniae was identified using standard laboratory procedures from blood, cerebrospinal fluid (CSF), pleural fluid, and other sterile body fluids and tissues. S. pneumoniae isolates were tested for resistance to penicilin and ceftriaxone using the E-test methodology. Serotypes of the isolates were determined by Quellung reaction. Results. The overall annual incidence rate of IPD decreased significantly from 7.71 (95% CI, 1.99-13.4) to 1.58 (95% CI, 0.6-3.77; RRR= -79.5; p= 0.006) per 100 000 population among <5 years of age without underlying disease. During the overall study period, the PCV7-serotypes and PCV13-serotypes represented 27.8% and 63.8% of isolates, respectively. PCV13-serotypes made up 81.8% of cases of IPD in the pre-PCV13 era and decreased to 56% in the 4 years after PCV13. The penicillin and ceftriaxone (for meningitis) resistance rates were 48.5% and 9.1%, respectively. Conclusions. This is the first study about the changing pattern of the incidence of IPD in Turkish children after the implementation of the PCV7 and PCV13 in Turkish national vaccine schedule and a prominent decrease in incidence of IPD has seen after the implementation of PCV13.

Bacteriemia oculta en niños atendidos en el Complejo Asistencial Dr. Sótero del Río: experiencia post vacuna neumocóccica conjugada / Occult bacteremia in Sótero del Río Hospital: experience after pneumococcal conjugated vaccine

Background: Occult bacteremia (OB) is one of the possible diagnoses of children younger than 3 years with fever without source in the emergency room. Objective: describe OB in the era after introduction of pneumococcal vaccine in Chile. Patients and Methods: Prospective descriptive review of data of children with possible OB diagnosis, referred from the emergency department between 2010-2013. Results: Possible OB was diagnosed on 391 patients. 233 had focus, mainly respiratory virus and urinary tract infection. On 158 patients, probable BO was diagnosed, 20 had proven OB from which 15 had positive blood culture for Streptococcus pneumoniae. From these, 7 were fully or partially vaccinated. The serotype was identified on 14 cases: 6 were PCV10 vaccine serotypes (none of them vaccinated), 2 were serotype related (both partially vaccinated) and 6 were non vaccine serotypes (partially or totally vaccinated). Discussion: It is necessary to improve diagnostic methods for respiratory viruses and urinary tract infections and try to expand coverage of pneumococcal conjugated vaccines in the pediatric population in order to reduce the risk of invasive pneumococcal disease in Chile.

Introducción: La bacteriemia oculta (BO) es uno de los diagnósticos que se plantean en los niños bajo 3 años de edad que se presentan con fiebre sin foco en el servicio de urgencia. Objetivo: Describir el diagnóstico de BO luego de la introducción de la vacunación universal para Streptococcus pneumoniae en Chile. Materiales y Métodos: Revisión descriptiva de seguimiento prospectivo de datos de niños con diagnóstico de BO posible derivados del SU entre 2010 y 2013. Resultados: Se diagnosticó BO posible en 391 pacientes. En 233 pacientes se encontró foco, siendo infecciones respiratorias virales e infección urinaria las más frecuentes. En 158 pacientes se diagnosticó BO probable, en 20 BO probada y 15 tuvieron hemocultivos positivos para S. pneumoniae. De estos últimos 7 estaban total o parcialmente vacunados. Se identificó serotipo en 14 casos: 6 serotipos vaccinales incluidos en PCV10 (ninguno vacunado), 2 serotipos relacionados (ambos parcialmente protegido) y 6 serotipos no vaccinales (parcial o totalmente vacunados). Discusión: Es necesario mejorar las técnicas diagnósticas de infecciones respiratorias virales e infección urinaria e intentar ampliar la cobertura de las vacunas neumocóccicas conjugadas en la población pediátrica, para reducir el riesgo de enfermedades neumocóccicas invasoras en Chile.

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.

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.

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.

Prevalencia de Streptococcus pneumoniae serotipo 19A antes y después de la introducción de la vacuna conjugada heptavalente en México / Prevalence of Streptococcus pneumoniae serotype 19A before and after the introduction of the heptavalent conjugate vaccine in Mexico

Objetivo. Conocer la prevalencia de S. pneumoniae serotipo 19A (Spn19A) antes y después de la introducción de la vacuna conjugada heptavalente (PCV7) en México. Material y métodos. Estudio descriptivo realizado con la información sobre vigilancia de enfermedades causadas por neumococos, generada por la red Sireva. Se realizó un análisis de regresión lineal con la proporción de cepas de Spn19A por año, en dos periodos. Los datos se analizaron con el paquete estadístico SPSS v.18. Resultados. Durante el periodo 2000-2012 se recuperaron 1 825 cepas de S. pneumoniae causantes de infección en población pediátrica, de las cuales 225/12.3% fueron Spn19A, y de éstos, 75/6.3% se aislaron en el periodo 2000-2008 y 150/23.6% en el periodo 2009-2012. La resistencia antimicrobiana post-vacunal aumentó para todos los fármacos, excepto a vancomicina. Conclusión. Se observó que la frecuencia de este serotipo y la resistencia a antimicrobianos aumentó posterior a la introducción de la PCV7.

Objective. To determine the prevalence of S. pneumoniae serotype 19A (Spn19A), before and after the introduction of heptavalent pneumococcal conjugate vaccine (PCV7) in Mexico. Materials and methods. Descriptive study carried out in Mexico with surveillance information of pneumococcal disease, generated from the Sireva network. We performed lineal regression analysis with the proportion of Spn19A by year in two study periods. Data were analyzed using SPSS v.18 software. Results. A total of 1825 S. pneumoniae strains causing infection in pediatric population were recovered in the period 2000-2012, 225/12.3% were Spn19A, and of these, 75/6.3% were isolated in 2000-2008 and 150/23.6% in 2009-2012. There was an increase in antimicrobial resistance post-vaccination for all drugs except vancomycin. Conclusion. It was observed that the frequency of this serotype and antimicrobial resistance increased after the introduction of PCV7.

Cross-reaction of 6B and 19F Specific Antibodies to Serotypes 6A, 6C, and 19A after Immunization with 7-valent Pneumococcal Conjugate Vaccine in Korean Children Aged 12-23 Months / 소아감염

PURPOSE: The cross-protection of 7-valent pneumococcal conjugate vaccine (PCV7) against vaccine-related serotypes has been controversial. We investigated the serological properties of cross-protective antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in young children aged 12-23 months after booster immunization of PCV7. METHODS: IgG and IgM antibody concentrations and opsonic index (OI) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were measured by ELISA and opsonophagocytic killing assay (OPA) in 4 selected immunesera. The serological properties and antigenic specificity of protective antibodies were determined by IgM depletion of immunesera, OPA, and competitive OPA against serogroup 6 and 19 pneumococci. RESULTS: Compared to pre-IgM depleted immunesera, OI of IgM-depleted immunesera against 6B and 19F decreased and OI against 6A, 6C, and 19A decreased, too. In competition OPA, free 6B and 19F polysaccharide completely inhibited the immune protection against vaccine-related serotypes 6A, 6C, and 19A as well as vaccine types 6B and 19F. CONCLUSIONS: The booster immunization of PCV7 certainly induced cross-protective antibodies against vaccine-related serotypes 6A, 6C, and 19A with both IgG and IgM isotypes. Furthermore, IgM antibodies are more highly contributed to opsonophagocytic activity against vaccine-related serotypes as well as most of vaccine types than do IgG antibodies. Further studies are needed for the more immunized sera in the children as well as adults.

Haemophilus influenzae type B conjugate vaccine (HiBCV) and heptavalent pneumococcal conjugate vaccine (PCV7) immunization status of patients 5 years and below hospitalized for pneumonia

@#Introduction: Community-acquired pneumonia remains to be an important cause of morbidity and mortality among the pediatric age group with Streptococcus pneumoniae and Haemophilus influenzae typ B being the predominant bacteria identified. Conjugate vaccines against these organisms are available however, the prevalence of pneumonia in our country continues to be high. Objectives: The aim of this research is to determine the HiBCV and PCV 7 immunization status of children 5 years and below who were hospitalized due to pneumonia compared to controls. This study also aims to describe the clinical outcome of pneumonia among children who were vaccinated with HiBCV and/or PCV7 compared to those without vaccination. Methods: This retrospective case-control study was conducted in Makati Medical Center from January 1, 2009 to August 31, 2010. Cases were children five years old and below discharged with the final diagnosis of pneumonia. Controls were patients five years and below discharged without pneumonia during the same study period. Medical records were reviewed for information on age, gender, clinical findings upon admission, laboratory results, vaccination status, interventions and outcomes. Conclusion: The findings indicated that clinical and radiologically-confirmed pneumonia still occurred among children with complete vaccination with HiBCV and PCV7. Although not statistically significant, those without vaccination had higher odds of having pneumonia.

Immune response to 19A serotype after immunization of 19F containing pneumococcal conjugate vaccine in Korean children aged 12-23 months / 소아과

PURPOSE: The purpose of this study was to evaluate the immune response to serotype 19A in children aged 12-23 months after immunization of the 19F containing 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Blood samples from a total of 45 subjects (age 12-23 months) were included in the study. Subjects were categorized according to immunization status into three groups as follows: 18 subjects with 3 primary doses and 1 booster dose of PCV7 (booster group), 21 subjects with 3 primary doses before 12 months of age (primary group), and 6 subjects with no vaccination history of PCV7 (control group). An ELISA and opsonophagocytic killing assay (OPKA) was done to evaluate the immune responses against serotypes 19F and 19A. RESULTS: According to the ELISA, all subjects had antibody titers > or =0.35 microg/mL for serotypes 19F and 19A in the booster and primary group and 83.0% and 66.7% in the control group, respectively. According to the OPKA, subjects with opsonic activity (> or =20) against serotypes 19F and 19A were 100% and 61.1% of the subjects in the booster group and 66.7% and 19.0% in the primary group, respectively. No subjects in the control group had opsonic antibodies against both serotypes. CONCLUSION: In conclusion, in children 12-23 months age who were previously vaccinated with PCV7, a cross-reactive immune response is elicited against serotype 19A after a primary series of 3 doses in a small proportion of subjects, and this response is amplified after booster vaccination.

Direct and Indirect Effects of Pneumococcal Protein Conjugate Vaccine

Streptococcus pneumoniae is a major etiology of serious bacterial infection among children worldwide. Among the 91 serotypes, the majority of invasive infections are caused by 10 common serotypes, 14, 16, 18, 19, 23, 4, 9, 7, 1, and 3. However, the ranking and serotype prevalence differ by age group and country. The heptavalent pneumococcal conjugate vaccine (PCV7) was licensed for use among infants and young children in many countries including Korea. The routine use of PCV7 has resulted in a decreased incidence of invasive pneumococcal disease by the vaccine serotypes among the vaccines (direct effect). However, it is notable that substantial declines in invasive diseases among older children and adults ensued through indirect effects on transmission (i.e., herd immunity). In addition, there are increasing evidences to suggest that routine immunization with PCV7 is changing the epidemiology of pneumococcal diseases such as serotype distribution of invasive disease, nasopharyngeal colonization, and antibiotic resistance patterns. In contrast, there is a small increase in the number of invasive diseases caused by nonvaccine serotypes, so called 'replacement phenomenon', though it is still minor compared with overall declines of vaccine-serotype diseases. Of those, the increase in the 19A-related disease has become most prominent. In Korea, a remarkable increase of 19A was noted before the introduction of PCV7. The emergence of resistance and replacement of disease by nonvaccine strains should be closely monitored.