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.

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.

Korean Clinical Practice Guidelines: Otitis Media in Children

Acute otitis media (AOM) and otitis media with effusion (OME) are common infections in children, and their diagnosis and treatment have significant impacts on the health of children and the costs of providing national medical care. In 2009, the Korean Otologic Society organized a committee composed of experts in the field of otolaryngology, pediatrics, and family medicine to develop Korean clinical practice guidelines (CPG) for otitis media in children with the goal of meeting regional medical and social needs in Korea. For this purpose, the committee adapted existing guidelines. A comprehensive literature review was carried out primarily from 2004 to 2009 using medical search engines including data from Korea. A draft was written after a national questionnaire survey and several public audits, and it was editorially supervised by senior advisors before publication of the final report. These evidence-based guidelines for the management of otitis media in children provide recommendations to primary practitioners for the diagnosis and treatment of children younger than 15 yr old with uncomplicated AOM and OME. The guidelines include recommendations regarding diagnosis, treatment options, prevention and parent education, medical records, referral, and complementary/alternative medicine for treating pediatric otitis media.

Changes in Serotype Distribution and Antibiotic Resistance of Nasopharyngeal Isolates of Streptococcus pneumoniae from Children in Korea, after Optional Use of the 7-Valent Conjugate Vaccine

We investigated serotype distribution and antimicrobial resistance of pneumococcal carriage isolates from children after optional immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in Korea. From June 2009 to June 2010, 205 (16.5%) pneumococcal isolates were obtained from 1,243 nasopharyngeal aspirates of infants and children at Seoul National University Children's Hospital, Korea. Serotype was determined by Quellung reaction and antibiotic susceptibility was tested by E-test. The results were compared to previous studies done in the pre-PCV7 period. In this study, the most common serotypes were 6A (15.3%), 19A (14.7%), 19F (10.2%), 35B (7.3%), and 6D (5.6%). The proportion of PCV7 serotypes decreased from 61.9% to 23.8% (P < 0.001). The overall penicillin nonsusceptibility rate increased from 83.5% to 95.4% (P = 0.001). This study demonstrates the impact of optional PCV7 vaccination in Korea; the proportion of all PCV7 serotypes except 19F decreased while antimicrobial resistant serotypes 6A and 19A further increased.

Streptococcus pneumoniae serotypes isolated from the middle ear of Mexican children diagnosed with acute otitis media / Serotipificación de Streptococcus pneumoniae aislados de líquido de oído medio en niños mexicanos con diagnóstico de otitis media aguda

OBJECTIVE: The aim of this study was to identify the etiology and the serotypes of S. pneumoniae (Sp) in Mexican children with acute otitis media (AOM). MATERIALS AND METHODS: The study includessamples frompatientsdiagnosed with AOM at the Federico Gomez Children's Hospital of Mexico (2002-2003),with positive culture for Sp bacteriologically confirmed in middle ear fluid obtained by tympanocentesis. All Sp were serotyped. A total of 138 samples from 135 children with AOM were included. RESULTS: Sp was isolated in 72 samples from 70 children. Sixty (85.7 percent) were previously healthy and 10 (14.3 percent) were immunocompromised. The most common serotypes were 6B and 19F (16.67 percent), and 6 A, 14 and 23F (15.27 percent). CONCLUSION: The distribution of serotypes among the children with AOM in the study is similar to that reported in developing cities, and 63.9 percent of the isolated serotypes are found to be included in the 7-Valent Pneumococcal Conjugate Vaccine (PCV), 68.1 percent in the 10-Valent PCV and 83.3 percent in 13-Valent PCV.

OBJETIVO: Conocer la etiología y serotipos de S. pneumoniae (Sp) en niños mexicanos, con otitis media aguda (OMA). MATERIAL Y MÉTODOS: Se incluyeron las muestras de pacientes con OMA del Hospital Infantil de México Federico Gómez (2002-2003), con cultivo positivo para Sp, (bacteriológicamente confirmados en el líquido del oído medio obtenido por timpanocentesis). Todos los Sp. fueron serotipificados. Se incluyeron 138 muestras de 135 niños con OMA. RESULTADOS: Sp. se aisló en 72 muestras de 70 niños: 60 (85.7 por ciento) eran previamente sanos y 10 (14.3 por ciento) eran inmunocomprometidos. Los serotipos más frecuentes fueron 6B y 19F (16.67 por ciento), y 6 A, 14 y 23F (15.27 por ciento). CONCLUSIONES: La distribución de los serotipos en niños con otitis media aguda fue similar a la reportada en ciudades en desarrollo y se observó que 63.9 por ciento de los serotipos aislados están incluidos en la vacuna conjugada 7-valente, 68.1 por ciento en la 10-valente y 83.3 por ciento en la 13-valente.

Immunogenicity of Haemophilus influenzae Type b Conjugate Vaccines in Korean Infants: A Meta-analysis

A meta-analysis was performed on the immunogenicity of Haemophilus influenzae type b (Hib) conjugate vaccines after 2 (2 and 4 months) and 3 doses (2, 4, and 6 months) in Korean infants. A database search of MEDLINE, KoreaMed, and Korean Medical Database was done. The primary outcome measure was the proportion of infants with anti-polyribosylribitol phosphate (PRP) concentrations > or =1.0 microgram/mL. Eight studies including eleven trials were retrieved. One trial reported on the diphtheria toxoid conjugate vaccine (PRP-D) and 2 trials each on the mutant diphtheria toxin (PRP-CRM) and Neisseria meningitidis outer-membrane protein (PRP-OMP) conjugate vaccine. Heterogeneity in study designs between trials on PRP-CRM was noted and one trial reported on a monovalent and another on a combination PRP-OMP vaccine. Thus, a meta-analysis was conducted only on the tetanus toxoid conjugate vaccine (PRP-T). After a primary series of 2 doses and 3 doses, 80.6% (95% confidence interval [CI]; 76.0-85.1%) and 95.7% (95% CI; 94.0-98.0%) of infants achieved an antibody level > or =1.0 microgram/mL, respectively. The immunogenic response to the PRP-T vaccine was acceptable after a primary series of 3 doses and also 2 doses. A reduced number of doses as a primary series could be carefully considered in Korean infants.

Pattern of functional antibody activity against Haemophilus influenzae type b (Hib) in infants immunized with diphtheria-tetanus-pertussis/Hib Brazilian combination vaccine

We evaluated the functional activity of Haemophilus influenzae B (Hib) antibodies elicited in a group of infants immunized with the diphtheria-tetanus-pertussis vaccine combined with an Hib vaccine produced totally in Brazil after technological transfer of Hib vaccine production from Glaxo SmithKline, Belgium. Blood samples from immunized infants (N = 985) were collected for the determination of Hib antibodies. Total Ig and IgM and IgG subclasses of antibodies against polyribosyl ribitol phosphate (PRP) were analyzed by ELISA. Almost all vaccinees (97.56 percent, 961/985) developed a strong anti-PRP IgG antibody response (¡Ý1.0 ¦Ìg/mL), while an anti-PRP IgM response was observed in 64.24 percent (634/985) of them (¡Ý0.15 ¦Ìg/mL). Only 18.88 percent (186/985) of the infants in the group with high PRP antibody IgG concentrations (¡Ý1.0 ¦Ìg/mL) developed a high IgM antibody response. Anti-PRP IgG antibody levels were significantly higher than anti-PRP IgM. These results demonstrate the predominance of IgG antibodies over IgM antibodies in response to PRP, with a ratio of 17:1. IgG antibodies were predominantly of the IgG1 subclass. An increase in IgG avidity was also observed during the course of immunization.

Immunogenicity and safety of a pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus, haemophilus influenzae type b conjugate combination vaccine (pentaxim™) with hepatitis B vaccine.

Objective: To obtain immunogenicity and safety data for a pentavalent combination vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate). Design: Multicenter, open, Phase III clinical study. A DTaP-IPV//PRP~T vaccine (PentaximTM) was given at 6,10,14 weeks of age; and Hepatitis B vaccine at 0,6,14 or at 6,10,14 weeks of age. Immunogenicity assessed 1 month post-3rd dose; safety assessed for 30 minutes by the investigator, then by parents and investigators to 8 days and 30 days post-vaccination. Setting: Tertiary-care hospitals. Participants/patients: 226 healthy Indian infants (6 weeks of age). Main outcome measures: Immunogenicity and safety. Results: Immunogenicity was high for each vaccine antigen, and similar to a historical control study (France) following a 2,3,4 month of age administration schedule. Post-3rd dose, 98.6% of subjects had anti-PRP ³0.15 mg/mL and 90.0% had titers ³1.0 mg/mL; the anti-PRP GMT was 4.1 µg/mL. Seroprotection rates for diphtheria and tetanus (³0.01 IU/mL) were 99.1% and 100%; and 100%,99.1% and 100%, for polio types 1,2 and 3 (³8 [1/dil]) respectively. Anti-polio GMTs were 440.5,458.9, and 1510.7 (1/dil) for types 1,2 and 3 respectively. The vaccine response rates to pertussis antigens (4-fold increase in antibody concentration) were 93.7% for PT and 85.7% for FHA; the 2-fold increase was 97.1% and 92.4%. Vaccine reactogenicity was low with adverse reaction incidence not increasing with subsequent doses. Conclusion: The DTaP-IPV//PRP~T vaccine, given concomitantly with monovalent hepatitis B vaccine, was highly immunogenic at 6, 10 and 14 weeks of age in infants in India. The vaccine was well tolerated.

Vacinas meningocócicas conjugadas: eficácia e novas combinações / Meningococcal conjugate vaccines: efficacy and new combinations

OBJETIVO: A doença meningocócica é, ainda hoje, um sério problema de saúde pública, estando associada a elevadas taxas de morbidade e letalidade no mundo e, em especial, no Brasil. Além de discutir as recentes mudanças na epidemiologia da doença meningocócica no mundo, analisamos o desenvolvimento e o impacto das novas vacinas conjugadas na prevenção da doença meningocócica, com ênfase nas diferentes estratégias de imunização utilizadas com essas vacinas. FONTE DOS DADOS: Foram pesquisadas as bases de dados MEDLINE no período de 1996 a 2006, com destaque para artigos de revisão, ensaios clínicos e epidemiológicos. Também foi realizada busca de informações nos portais do Centro de Controle de Doenças, Ministério da Saúde do Brasil e Centro de Vigilância Epidemiológica do Estado de São Paulo. SíNTESE DOS DADOS: Cinco sorogrupos (A, B, C, W135 e Y) respondem por virtualmente todos os casos da doença no mundo, com marcantes diferenças regionais e temporais. As novas vacinas conjugadas contra o meningococo C apresentam inequívocas vantagens em relação às vacinas polissacarídicas. Induzem uma resposta de anticorpos mais eficiente e duradoura, propiciando memória imunológica e redução da incidência de portadores. Os resultados imediatos da introdução dessas vacinas nos programas de imunização foram animadores, com dramática redução da incidência de doença, inclusive em não-vacinados (imunidade de rebanho). Entretanto, recentemente constatou-se perda da eficácia após alguns anos da aplicação da vacina, especialmente entre os lactentes vacinados. CONCLUSÕES:A perda de efetividade das vacinas conjugadas contra o meningococo C, observada após alguns anos da imunização de lactentes jovens, justifica a mudança dos esquemas de vacinação, com a incorporação de uma dose de reforço entre 12 e 18 meses de idade para garantir uma proteção mais duradoura. O recente licenciamento da vacina quadrivalente meningocócica conjugada representa, enfim, a real possibilidade de uma proteção mais abrangente contra a doença meningocócica, restando ainda a necessidade de se desenvolver uma vacina eficaz contra o meningococo B.

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

Vacinas glicoconjugadas, cujo carboidrato da superfície de um microrganismo está covalentemente ligado a uma proteína carreadora, vêm sendo consideradas como efetivas para gerar respostas imunes que previnem um grande número de doenças. A tecnologia é genérica e aplicável a vários patógenos, se os anticorpos contra os carboidratos de superfície forem capazes de proteger contra a infecção. Três vacinas contra Haemophilus influenzae tipo b, Neissseria meningitidis Grupo C e sete sorotipos de Streptococcus pneumoniae já foram licenciadas e muitas outras estão em desenvolvimento. Este artigo discute o racional para o desenvolvimento e uso de vacinas glicoconjugadas; os mecanismos pelos quais elas induzem respostas imune dependentes de célula T e suas implicações para o seu desenvolvimento; o papel dos métodos físico-químicos na caracterização e no controle de qualidade dessas vacinas; e os produtos novos que estão em desenvolvimento.

Evaluation of serogroup A meningococcal vaccines in Africa: a demonstration project.

Endemic and epidemic meningococcal disease constitutes a major public-health problem in African countries of the 'meningitis belt' where incidence rates of the disease are many-fold higher (up to 25 cases per 100,000 population) than those in industrialized countries, and epidemics of meningococcal disease occur with rates as high as 1,000 cases per 100,000 people. Using the precedent established during the licensing of conjugate vaccines against Haemophilus influenzae type b and serogroup C meningococci and components of currently-licensed meningococcal polysaccharide vaccines, new meningococcal conjugate vaccines will likely be licensed using immunological endpoints as surrogates for clinical protection. Post-licensure evaluation of vaccine effectiveness will, therefore, be of increased importance. One vaccine being developed is the serogroup A meningococcal (Men A) conjugate vaccine produced by the Meningitis Vaccine Project (MVP), a partnership between the World Health Organization and the Program for Applied Technology in Health. This vaccine will likely be the first meningococcal conjugate vaccine introduced on a large scale in Africa. This paper summarizes the general steps required for vaccine development, reviews the use of immunogenicity criteria as a licensing strategy for new meningococcal vaccines, and discusses plans for evaluating the impact of a meningococcal A conjugate vaccine in Africa. Impact of this vaccine will be measured during a vaccine-demonstration project that will primarily measure the effectiveness of vaccine. Other studies will include evaluations of safety, vaccine coverage, impact on carriage and herd immunity, and prevention-effectiveness studies.

Conjugate vaccines--a breakthrough in vaccine development.

The encapsulated bacteria Streptococcus pneumoniae (the pneumococcus), Neisseria meningitidis (the meningococcus) and Haemophilus influenzae type b (Hib) are the main causes of purulent meningitis, the peak incidence of which is seen in the first two years of life. The polysaccharide capsule of these bacteria is an essential virulence determinant, and antibodies to it are protective, suggesting that a polysaccharide vaccine could prevent these diseases. The young child is, however, unable to respond with antibody production to these polysaccharides, making such vaccines useless in infancy. Conjugation of the polysaccharide to a protein carrier has proven a way to solve the problem. Immunization of infants with such a Hib conjugate vaccine was shown in 1987 to result in the desired antibody production and protection from Hib meningitis and bacteremia. The Hib vaccine is now a part of national infant immunization programs in large parts of Europe, the Americas and Australia, and has resulted in the virtual disappearance of Hib disease from these areas. A group C meningococcal and 7-valent pneumococcal vaccine, available since 2000, are likewise proving highly effective in preventing bacteremic disease. Further advantages of the conjugate vaccines are their ability to elicit immunologic memory and to reduce asymptomatic carriage of the bacteria, resulting in marked herd immunity. This paper was delivered as a lecture in January 2003 in Bangkok on the occasion of the Prince Mahidol Award for a life's work in the field of vaccinology.

Transplacental transfer and age-related levels of serum IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae types 14 and 19 in Korea

Little is known about the prevalence of naturally acquired IgG antibodies to the capsular polysaccharides of Streptococcus pneumoniae (pneumococcal IgG) in Korea. In the present study, we investigated transplacental transfer and age-related levels of pneumococcal IgG to provide background seroepidemiologic data for S. pneumoniae in Korea. One hundred thirty eight sera were assayed by ELISA for IgG to pneumococcal polysaccharide capsular serotypes 14 and 19, the predominant serotypes for under 15 yr of age in Korea. The subjects were divided into 7 subgroups according to age. The cord/maternal geometric mean titer of pneumococcal were 4.47+/-5.88/5.21 +/- 5.88 for serotype 14, and 4.68 +/- 5.55/6.55 +/- 6.92 for serotype 1 9 (mean +/- standard deviation, microg/mL). After birth, the geometric mean titers of pneumococcal IgG for serotypes 14 and 19 expressed in microg/mL were 1.18+/-2.12 and 1.41+/-2.17 in the 0-6 months group, 0.27+/-0.19 and 0.69+/-0.93 in 7-12 months, 0.21+/-0.22 and 0.64+/-1.32 in 1-2 yr, 0.69+/-0.78 and 2.65+/-2.46 in 3-6 yr, 2.52+/-2.72 and 8.29+/-4.24 in 7-10 yr, respectively. In conclusion, reduced transplacental transfer and very low serum concentrations of pneumococcal IgG may contribute to the susceptibility of neonates, infants, and young children to S. pneumoniae infection.

Analise critica sobre o uso das vacinas conjugadas contra o Haemophilus influenzae do tipo b em diferentes paises / Critical analysis about the use of Haemophylus influenzae type b conjugate vaccines in different countries

O Haemophylus influenzae do tipo b (Hib) e um dos principais agentes causadores de doencas invasivas em criancas, tais como meningite, epiglotite, pneumonia e bacteremia. Desde 1987, as vacinas conjugadas contra o Hib vem sendo amplamente utilizadas em diversos paises desenvolvidos, e o sucesso da imunizacao pode ser comprovado pelo rapido desaparecimento das infeccoes graves causadas pelo Hib, apos a introducao da vacinacao de rotina contra o Hib para todas as criancas com idade entre 2 meses e 5 anos. Neste artigo, a autora apresenta uma revisao sobre o impacto epidemiologico da vacinacao contra o Hib, em 4 paises desenvolvidos - Finlandia, Estados Unidos, Inglaterra e Suecia - e analisa as dificuldades relacionadas a introducao desta vacina nos paises em desenvolvimento

Antibody response of Mexican infants to Haemophilus influenzae type b capsular polyribosylribitol phosphate. Differences between natural and vaccine induced (Oligosaccharide-CRM197 conjugated vaccine) immunization

In this study we compared natural vs induced Haemophilus influenzae type b (hib) anti-capsular polyribosylribitol phosphate (PRP) antibody response in a low socioeconomic population. One hundred twenty five 2-month-old children received the complete HbOC vaccine immunization scheme and a boster dose at 15 month of age. One hundred twenty five non-immunized children served as the control group. Serum Hib anti-PRP antibody titers were determuined by ELISA in all children. We found at the end of the primary immunization scheme an antibody concentration of 27.28 µg/ml in the immunized group vs. 7.48 µg/ml in the control group. The antibody response was mainly of the IgG1 class in both groups. After the booster dose the antibody concentration was 30.14 g/ml in the vaccinated group vs. 6.06 µg/ml in the control group (p<0.01). Ninety nine percent of immunized and non-immunized infants had titers greater than 1 µg/ml. These results confirm that immunization with the HbOC vaccine induces an important increase in anti-PRP specific antibody titer, but they also demonstrate that natural exposure induces responses higher than those referred as protective (1 µg/ml)