Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children / 中国当代儿科杂志

OBJECTIVES@#To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines.@*METHODS@#The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage.@*RESULTS@#The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates.@*CONCLUSIONS@#There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

ABSTRACT Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others Results: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

Parental knowledge of pneumococcal diseases and pneumococcal conjugate vaccines: A cross-sectional study in Immunization Clinic, Medical College, and Hospital, Kolkata

Background: Pneumococcal conjugate vaccine (PCV) had been introduced in National Immunization Schedule recently in West Bengal in view to prevent pneumococcal diseases mainly pneumonia and meningitis, which was a leading cause mortality and morbidity particularly in under 5 age group. Like all other health program, success of this initiative would be dependent on awareness level of beneficiaries. Aim and Objective: The present study aimed at estimating parenteral awareness level related to pneumococcal diseases and PCV. Materials and Methods: The observational and analytic study was conducted among parents of 404 children (who were eligible for PCV-1) attended in Immunization Clinic, Medical College, Kolkata. Sociodemographic parameters of families of study participants were elicited. Parenteral knowledge regarding pneumococcal diseases and PCV was assessed. Results: About 58.4% of parents neither had any awareness regarding pneumococcal diseases, nor had any idea related to PCV. Only 30.7% of parents had any knowledge regarding pneumococcal diseases and 31.7% had any awareness related to PCV. Maternal education, social class, and residence were found to significant predictor of parenteral knowledge both in unadjusted model as well as when adjusted with sociodemographic variables. Conclusion: As parenteral knowledge level in the present study was not satisfactory, more stress to be given in conducting awareness generation campaign for newly introduced PCV vaccine throughout the state in general, and in vulnerable urban areas particularly, where awareness among beneficiaries was significantly poorer.

Cross Sectional Study of Knowledge about Pneumococcal Conjugate Vaccine Among Medical and Nursing Students studying at Civil Hospital campus, Ahmedabad

Introduction: India is committed to to prevent pneumonia related deaths in children which is leading cause of vaccine preventable deaths among children under five globally and in India. Objective : To know awareness about pneumococcal (PC) vaccine among medical and nursing students of civil hospital, Ahmedabad. Method: This cross sectional study was conducted on medical and nursing students of civil hospital, Ahmedabad, Gujarat. Baseline knowledge of PC Vaccine, side effects of PC vaccine, was assessed by a self-administered structured questionnaire. Statistical analysis - Data analysis was done in Microsoft excel and chi square test was applied. Results: There were 444 respondents and among them 240 (54%) were medical students and 204 (46%) were nursing students, with male female ratio was 95:127. Awareness regarding PC vaccine integration to national immunization schedule found significantly more in nursing students as compare to medical students, (Chi-square = 63.4 at p < 0.05). Medical students had more knowledge about PC vaccine as compared to nursing students. Conclusion: There is still gap in awareness of PC vaccine integration to national immunization schedule among medical students. Field visits among nursing students have positive effects on awareness of nursing students. Medical students should visit to this type of field activities to improve their knowledge about ongoing activities like this

Vacunas antineumocócicas conjugadas: una revisión de las consideraciones éticas e impacto socio-económico / Pneumococcal conjugate vaccines: a review of ethical considerations and socio-economic impact

Introducción: Desde hace más de 15 años, las vacunas antineumocócicas conjugadas (PCVs) están disponibles en muchas partes del mundo, y son efectivas en la prevención de las enfermedades neumocócicas en niños. La OMS recomienda la inclusión de las PCVs en los programas de inmunización infantil en todo el mundo. Objetivo: Valorar el abordaje ético y el impacto socioeconómico de las vacunas antineumocócicas conjugadas para la decisión de uso en diferentes contextos. Material y Métodos: Se realizó una búsqueda bibliográfica en las bases de datos PubMed y SciELO, considerando informes de la web de la OMS. Desarrollo: Está globalmente considerado que para la reglamentación, el desarrollo y el uso de las PCVs，se deben tener en cuenta aspectos regulatorios, resultados de investigaciones y el consentimiento informado (CI) de los sujetos. En el contexto de países como China，la PCV13 de la empresa Pfizer es de la Clase II debido a su alto precio de importación, en otros contextos como Cuba no se ha introducido la vacunación contra neumococo por limitaciones financieras. Los equipos de investigación trabajan en el desarrollo de las PCVs para reducir el coste de la importación de estas vacunas, haciendo realidad la inclusión de las PCVs en el programa nacional de inmunización. A pesar de complejidad cada vez mayor de la investigación vacunológica, los investigadores seguirán obligados a adherirse a los principios éticos. Conclusiones: Es necesario una vacuna antineumocócica conjugada más económica para tener un impacto socio-económico más alto. Los profesionales sanitarios tienen la obligación de ser éticos y rigurosos en las investigaciones vacunológicas. Además, estas investigaciones requieren de la revisión por parte de un consejo de revisión ética a escala nacional y su seguimiento debe ser sistemático. Cabe señalar que los estudios en población infantil deben ser fuertemente regulados y controlados(AU)

Introduction: Pneumococcal conjugate vaccines (PCVs) have been available in many parts of the world for more than 15 years and are effective in preventing pneumococcal diseases in children. The WHO recommends the inclusion of PCVs in childhood immunization programmes worldwide. Objective: To value the approach to ethics and the socioeconomic impact of the conjugate pneumococcal vaccines. Material and Methods: A bibliographic review was carried out in databases such as PubMed and SciELO, considering reports from the WHO website. Development: It is globally considered that regulatory aspects, research results and informed consent (IC) of the subjects should be taken into account for the regulation, development and use of PCVs. In the context of countries such as China，the PCV13 of the Pfizer company is Class II due to its high import price. In other contexts, such as Cuba, pneumococcal vaccination has not been introduced due to financial limitations. Research teams are working on the development of PCVs to reduce the cost of importing these vaccines, making the inclusion of PCVs in the national immunization program a reality. Despite the increasing complexity of vaccinology research, researchers will continue to be obliged to adhere to ethical principles. Conclusions: A cheaper pneumococcal conjugate vaccine would be needed to have a higher socioeconomic impact. Healthcare professionals have the obligation to be ethical and rigorous in vaccinology research. In addition, such research requires review by a national ethical review board and should be systematically monitored. It should be noted that studies in the pediatric population should be strongly regulated and controlled(AU)

Female Patient with Invasive Pneumococcal Disease Due to Non-vaccine Serotype 24B Streptococcus pneumoniae / 日本プライマリ・ケア連合学会誌

We report the case of a 1-year-old female with invasive pneumococcal disease (IPD) after three administrations of the 13-valent pneumococcal conjugate vaccine (PCV13) according to the immunization schedule for children in Japan. Blood culture detected Streptococcus pneumoniae 24B, which is a non-vaccine serotype. In Japan, PCV7 introduced in 2010 reduced the number of IPD patients under 5 years of age. However, the number of children under 5 years of age with IPD due to non-vaccine serotypes gradually increased after 2014 even though PCV13 was introduced in 2013. Pneumococcal vaccination cannot completely prevent IPD. Therefore, medical practitioners should pay attention to IPD due to non-vaccine serotypes.

A review of Pneumonia in the Philippines

@#This review article gives an overview of pneumonia in the Philippines, with focus on childhood pneumonia. Its primary objective is to provide information on epidemiology, etiology, economic burden, risk factors and prevention of pneumonia. A review of literature was done to gather information about the disease, with emphasis on local data. In the Philippines, pneumonia is the third leading cause of death across all ages and is the most common cause of death among children<5 years of age. A prospective study on Invasive Pneumococcal Disease conducted in the Philippines looked at the incidence of chest x-ray–confirmed pneumonia (N=5,940) in three hospitals over a 2-year period. The highest incidence was seen in those 28 days to <6 months of age at two sites and those 6–12 months of age in another site. Risk factors include not exclusively breastfeeding infants <6 months, undernutrition, zinc deficiency, crowding and exposure to indoor air pollution, low birth weight, poverty and socio-economic factors, presence of underlying comorbidities and immunodeficiency states. CAP ranks number one in processed Philippine Health Insurance (PhilHealth) claims, showing the huge economic burden. Therefore, rationalizing its management with simple standardized guidelines, exclusive breastfeeding for 6 months and continued breastfeeding with appropriate complementary feeding, improving indoor air pollution, and promoting vaccination are effective interventions.

A health benefit and cost-effectiveness analysis of pneumococcal conjugate vaccination program in Nigeria

Background: Nigeria ranks third just behind India and China in the global disease burden of pneumococcal disease. The current sustainability approach for an affordable pneumococcal conjugate vaccine (PCV) for the national immunization program from 2014 till 2025 involves a cost sharing plan funded with a 75% financial support from GAVI and a subsidy from Pfizer pharmaceuticals. There is a strong need to generate evidence on the cost-effectiveness of the national PCV program in Nigeria from 2014-2025 and beyond 2025.Methods: The following parameters (demography, disease burden, health services utilization and costs, vaccination coverage, vaccine efficacy, and vaccination costs) were used in a static cohort model to estimate the total cost, health and economic benefit, and cost-effectiveness of the implementation of PCV vaccination program, compared with no PCV vaccination among under-five children in Nigeria from 2014-2025 and from 2026-2033. A sensitivity analysis was conducted to evaluate the robustness of the data used.Results: The national PCV vaccination program would have an approximated 31.4% and 30% reduction of the total burden of pneumococcal diseases over the period of 2014-2025 and 2026-2033 respectively. One-way sensitivity analysis reveals vaccine efficacy as most sensitive parameter followed by disease incidence rate and treatment cost. Removal and addition of DTP3 and 3+1 (measles vaccine) dose respectively resulted to a similar ICER from both.Conclusions: The estimated ICER suggests that the national PCV program in Nigeria will be cost-effective post 2025 era. In addition, it is recommended for policy-makers adoption considering the budget and equity impact of the intervention in Nigeria.

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.

Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version) / 中华预防医学杂志

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

Pneumococcal conjugate vaccine rollout in India: Expectations and challenges

India is one among the four Asian countries with the greatest number of deaths due to pneumococcal infection among children under 5 years. pneumococcal conjugate vaccine (PCV) has been introduced in a phased manner in five major Indian states. Ambiguity remains in choosing the appropriate type of PCV and optimum schedule with maximum effectiveness specific for each country. Here, we discuss the evidences with respect to serotype coverage, immunogenicity, reactogenicity and dosage schedule for introduction of PCV13 in India. In addition, the expected PCV impact and the challenges are detailed. PCV13 is expected to provide >75% serotype coverage for invasive pneumococcal disease (IPD) serotypes in Indian children combined with the replacement by nonvaccine serotypes which is unpredictable due to lack of complete data. Nasopharyngeal (NP) surveillance is easy, feasible and can replace IPD surveillance in resource-poor settings. Continuous IPD as well as NP surveillance in all the regions are necessary to assess the impact of PCV in India.

La vacunación antineumocócica en Cuba. Retos y desafíos

El desarrollo de la Medicina ha reflejado la necesidad de prevenir enfermedades trasmisibles a través de vacunas. Después de la descripción del papel que juega el neumococo en la génesis de enfermedades, se inició una carrera destinada a prevenirlas. En el presente siglo se licenció la primera vacuna conjugada contra el Streptococcus pneumoniae para ser utilizada en niños. En Cuba, a pesar de los esfuerzos realizados, no se ha introducido la vacuna antineumocócica y desde hace más de una década se trabaja en un candidato vacunal conjugado heptavalente, actualmente en evaluación clínica avanzada. En este trabajo se hacen consideraciones al respecto.

Medicine development has shown the need of preventing transmissible diseases by means of Vaccines. After a description of the role of pneumococcus in the origin of diseases, a career towards preventing them was started. In the current century, the first conjugated vaccine was certified against Streptococcus pneumonia to be used in children. In Cuba, in spite of the efforts, the anti-pneumococcal vaccine has not been introduced and for more of a decade time scientists have been working in a heptavalent conjugated vaccine, currently in an advanced clinical evaluation. In this work, considerations in this regard are made.

Disease Burden and Etiologic Distribution of Community-Acquired Pneumonia in Adults: Evolving Epidemiology in the Era of Pneumococcal Conjugate Vaccines / 감염과화학요법

Pneumonia is the leading cause of morbidity and mortality, particularly in old adults. The incidence and etiologic distribution of community-acquired pneumonia is variable both geographically and temporally, and epidemiology might evolve with the change of population characteristics and vaccine uptake rates. With the increasing prevalence of chronic medical conditions, a wide spectrum of healthcare-associated pneumonia could also affect the epidemiology of community-acquired pneumonia. Here, we provide an overview of the epidemiological changes associated with community-acquired pneumonia over the decades since pneumococcal conjugate vaccine introduction.

The Evolving Epidemiology of Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Strains Isolated from Adults in Crete, Greece, 2009–2016 / 감염과화학요법

BACKGROUND: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009–2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). MATERIALS AND METHODS: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ≥2 non-β-lactam antimicrobials. RESULTS: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. CONCLUSION: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

Disease Burden and Etiologic Distribution of Community-Acquired Pneumonia in Adults: Evolving Epidemiology in the Era of Pneumococcal Conjugate Vaccines / 감염과화학요법

Pneumonia is the leading cause of morbidity and mortality, particularly in old adults. The incidence and etiologic distribution of community-acquired pneumonia is variable both geographically and temporally, and epidemiology might evolve with the change of population characteristics and vaccine uptake rates. With the increasing prevalence of chronic medical conditions, a wide spectrum of healthcare-associated pneumonia could also affect the epidemiology of community-acquired pneumonia. Here, we provide an overview of the epidemiological changes associated with community-acquired pneumonia over the decades since pneumococcal conjugate vaccine introduction.

The Evolving Epidemiology of Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Strains Isolated from Adults in Crete, Greece, 2009–2016 / 감염과화학요법

BACKGROUND: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009–2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). MATERIALS AND METHODS: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ≥2 non-β-lactam antimicrobials. RESULTS: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. CONCLUSION: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

Expert consensus on immunization for prevention of pneumococcal disease in China (2017) / 中华流行病学杂志

Pneumococcal disease is one of the serious global public health problems, and an important leading cause of the morbidity and mortality of children and adults in China. Currently, antibiotics are the most choices for its clinical treatment. However, antibiotic resistance of has become a severe problem around the world due to the wide use of antibiotics. Hence, the prevention of pneumococcal disease by using pneumococcal vaccines is of great importance. In this article, we reviewed the etiology, clinic, epidemiology, disease burden of pneumococcal disease, and the vaccinology of pneumococcal vaccines, based on the Pneumococcal Vaccines WHO Position Paper (2012) and other latest evidence globally, to introduce comprehensive knowledge of pneumococcal disease, and for the purpose to improve the capacity of the professionals working on pneumococcal disease control and prevention and to provide appropriate evidences of pneumococcal vaccine applications for people who are engaged in public health and immunization vaccination.

PCV13 (13-valent pneumococcal conjugate vaccine) containing capsular polysaccharides of Streptococ-cus pneumoniae serotypes 6A and 6B confers cross-protection against newly discovered serotypes 6C and 6D / 中华微生物学和免疫学杂志

Objective To investigate whether capsular polysaccharides of Streptococcus pneumoniae serotypes 6A and 6B contained in 13-valent pneumococcal conjugate vaccine ( PCV13 ) could induce cross- protective antibodies against newly discovered serotypes 6C and 6D and the differences between them. Methods New Zealand rabbits were radomly divided into three groups and respectively muscularly administrated with three doses of PCV13, PCV6A and PCV6B on days 0, 14 and 28. PCV6A and PCV6B were conjugates of capsular polysaccharides of serotypes 6A and 6B chemically coupled with diphtheria toxin mutant CRM197. Serum samples were collected on days 0 and 35. Enzyme-linked immunosorbent assay (ELISA) recommended by World Health Organization (WHO) was used to quantitatively measure serotype-specific antibodies to capsular polysaccharides of serotypes 6A, 6B, 6C and 6D. Opsonophagocytosis assay ( OPA) of WHO pneumococcal serology reference laboratory was used to determine antibody functional activities targeting serotypes 6A, 6B, 6C and 6D. Results Immunization rabbits with PCV13 induced the secretion of antibodies to capsular polysaccharides of serotypes 6A and 6B. These antibodies were able to not only cross-react with capsular polysaccharides of serotypes 6C and 6D but also recognize and bind to target Streptococcus pneumoniae serotypes 6A, 6B, 6C and 6D, resulting in the activation of complements and further phagocytosis of target bacteria by differentiated HL60 cells. Bactericid-al titers were largely even among these serotypes except for serotype 6D which was slightly lower. PCV6A could induce antibody against capsular polysaccharide of serotype 6A, which was able to cross-react with capsular pol-ysaccharides of serotypes 6B, 6C and 6D and showed higher bactericidal titers to serotypes 6A, 6B and 6C over serotype 6D. PCV6B could induce antibody against capsular polysaccharide of serotype 6B, which was able to cross-react with capsular polysaccharides of serotypes 6A, 6C and 6D and showed higher bactericidal titers to se-rotypes 6A, 6B and 6C over serotype 6D. Antibody concentrations and bactericidal titers specific to serotypes 6A, 6B, 6C and 6D were significantly increased following immunization with PCV13, PCV6A or PCV6B (P<0. 01). Conclusion PCV13 containing pneumococcal serotypes 6A and 6B induced antibodies against capsular polysaccharides of serotypes 6A and 6B in New Zealand rabbits, which were able to cross-react with capsular polysaccharides of serotypes 6C and 6D and provide cross-protection to bacteria of serotypes 6C and 6D. Both serotypes of 6A and 6B contained in PCV13 contributed to the induction of cross-protective antibodies, especially to serotype 6C.

Establishment of rabbit model for immunogenicity evaluation of pneumococcal conjugate vaccine / 中华微生物学和免疫学杂志

Objective To establish an animal model for evaluating immunogenicity of pneumococcal conjugate vaccine.Methods New Zealand rabbits were intramuscularly administrated with three doses of 13-valent pneumococcal conjugate vaccine (PCV13) with two weeks interval between each injection.Serum samples were collected at different time points before and after vaccination.Quantitative enzyme-linked immunosorbent assay (ELISA) and opsonophagocytosis assay (OPA) that were in conformity with the World Health Organization (WHO) standards were used to detect the concentrations of serotype-specific antibodies and their bactericidal activities.Results The concentrations (Geometric mean concentration, GMC) of serotype-specific antibodies in rabbit serum samples were well correlated with their bactericidal activities (Geometric mean titer, GMT) following vaccination.Moreover, the dynamic changes of GMC and GMT of the same serotype-specific antibody remained consistent as time went by.Conclusion Rabbit model can be used to analyze the immunogenicity of PCV13 vaccine with quantitative ELISA and OPA, which indicates that it is a suitable animal model for evaluating immunogenicity of pneumococcal conjugate vaccine.

Estimates on state-specific Pneumococcal Conjugate Vaccines (PCV) coverage in the private sector in the year 2012: Evidence from PCV utilization data.

The pneumococcal conjugate vaccine (PCV) is not available through universal immunization programs but is available through private healthcare providers. Because the PCV coverage rates are unknown, we developed a Microsoft Excel-based coverage assessment model to estimate state-specific PCV coverage for the year 2012. Our findings suggest that in the private sector, the "overall PCV coverage" was around 0.33% that ranged between a minimum of 0.07% for Assam, India and a maximum of 2.38% for Delhi, India. Further, in major metropolitan areas, overall PCV coverage rates were: 2.28% for Delhi, India, 13.31% for Mumbai (Maharashtra), India 0.76% for Lucknow (Uttar Pradesh), India, 1.93% for Kolkata (West Bengal), India, and 4.92% for Chennai (Tamil Nadu), India highlighting that urban centers are major drivers for PCV utilization driver in the states with high PCV consumption. Hence, to improve PCV coverage, both demand side (increasing consumer awareness about pneumonia prevention) and supply side (controlling vaccine prices and indigenous vaccine production) interventions are required.