Impact of pneumococcal conjugate vaccine on infections caused by antibiotic-resistant Streptococcus pneumoniae

Studies have shown that vaccination with seven-valent pneumococcal conjugate vaccine (PCV7) results in a decline in nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae , in carriage of vaccine-type pneumococci, and in replacement by non-vaccine serotypes. Vaccines can reduce pneumococcal resistance in vaccinated and unvaccinated populations by reducing the carriage of antibiotic-resistant serotypes, which protects the vaccinated population and prevents spread of disease to others, and by decreasing antibiotic resistance through overall reduction in antibiotic use. However, while reducing the level of vaccine serotypes and drug-resistant serotypes in the nasopharynx, PCV7 also causes non-vaccine pneumococci replacement. The impact of serotype replacement on disease is not clearly understood. Pelton et al. surveyed two communities shortly after the introduction of the PCV7 immunization programme and found that while colonization with vaccine serotypes declined from 22% to 2% from 2000 to 2003, prevalence of non-vaccine serotypes increased from 7% to 16%. Although penicillin-resistant colonizing S. pneumoniae isolates initially declined, penicillin-intermediate isolates increased 2 years following PCV7 introduction. The change was primarily accounted for by an increase in penicillin-intermediate serotype 19A. Serotype 19A is the only serotype not affected by PCV7 that is prevalent worldwide, clinically important, and highly multidrug-resistant. A study by Hicks et al. established serotype 19A as the predominant post-PCV7 cause of invasive pneumococcal disease (IPD) in children and the elderly. An increase in IPD rates caused by antibiotic-resistant serotype 19A isolates can also occur without vaccination; reports indicate increases in regions characterized by extensive antibiotic use, underscoring the importance of strategies to contain antibiotic resistance.     

Impact of the conjugation method on the immunogenicity of Streptococcus pneumoniae serotype 19F polysaccharide in conjugate vaccines

7vCRM (Pfizer, Inc.) and PHiD-CV (GlaxoSmithKline Biologicals) are two pneumococcal conjugate vaccines licensed for the prevention of invasive pneumococcal disease and acute otitis media caused by the vaccine serotypes of Streptococcus pneumoniae. Neither vaccine contains serotype 19A, but both contain the closely related serotype 19F. No decrease in the incidence of serotype 19A disease has been observed following the introduction of 7vCRM, suggesting that this serotype 19F-containing vaccine provides limited cross-protection against serotype 19A. To investigate the impact that conjugation methods may have on antipolysaccharide immune responses and to determine whether this limited cross-protection is characteristic of the serotype 19F polysaccharide or rather of the 19F-CRM (cross-reacting material) conjugate, we compared naturally induced antibodies against serotypes 19F and 19A with antibodies induced after vaccination with different pneumococcal conjugate vaccines. We found that conjugation of the serotype 19F polysaccharide using reductive amination (as in 7vCRM) resulted in the formation of at least one additional epitope that is not present in the native form of the 19F polysaccharide or following 19F conjugation using a bifunctional spacer (as in the prototype vaccine 7vOMPC) or cyanylation (as in PHiD-CV). We also found that pneumococcal vaccines conjugated using cyanylation induce more opsonophagocytic antibodies against serotype 19F and a considerably higher level of cross-opsonophagocytic antibodies against serotype 19A than vaccines conjugated using reductive amination. In conclusion, these results suggest that the conjugation method can influence the functionality of the antibodies induced against the homologous serotype 19F and the cross-reactive serotype 19A of S. pneumoniae.     

Resurgence of pneumococcal meningitis in Europe and Northern America

BackgroundStreptococcus pneumoniae is the most common pathogen causing bacterial meningitis. The routine use of multivalent conjugate pneumococcal vaccines has led to a decline of invasive pneumococcal disease caused by serotypes included in the vaccine serotypes. Recently, several reports have described a concomitant rise in the incidence of non-vaccine serotypes, suggesting serotype replacement.ObjectiveWe aim to review the effect of pneumococcal vaccination on the incidence of pneumococcal meningitis in Europe and northern America with a particular interest in serotype replacement.SourcesArticles that include data on invasive pneumococcal disease incidence before and after the introduction of vaccination, or on invasive pneumococcal serotype, are discussed, with a focus on pneumococcal meningitis.ContentThe introduction of pneumococcal conjugate vaccines has universally resulted in a decline in vaccine-serotype pneumococcal meningitis incidence throughout Europe and northern America. Serotype replacement by non-vaccine serotypes has however been reported following the introduction of the 7-, 10- and 13-valent pneumococcal conjugate vaccines, which in several regions abolished the overall effect of vaccination on pneumococcal meningitis incidence.ImplicationsThe promising decline in the incidence of pneumococcal meningitis following the introduction of vaccination seems to have been temporary. Replacement by non-vaccine serotypes illustrates that pneumococcal meningitis continues to pose a major challenge. We need new approaches to prevention, new vaccines and continued efforts to improve treatment for patients with pneumococcal meningitis.     

Detection of Streptococcus pneumoniae and identification of pneumococcal serotypes by real-time polymerase chain reaction using blood samples from Italian children ≤ 5 years of age with community-acquired pneumonia

Streptococcus pneumoniae is a leading cause of severe life-threatening infections. Laboratory identification and serotyping of this pathogens is desirable to monitor vaccine impact and coverage; however, especially in pediatric patients, the yield of traditional microbiological diagnostic procedures can be very low. The aim of this study was to develop real-time polymerase chain reaction (PCR)-based assays to be performed directly on blood samples to identify the most common capsular serotypes causing pneumonia in Italian children (≤ 5 years of ages) after the introduction of the 7-valent conjugate vaccine. Our real-time PCR-based assays showed high sensitivity (at least 35 fg of pneumococcal DNA), and they were validated with 49 well-characterized pneumococcal isolates, 8 nonpneumococcal isolates, 13 simulated blood clinical samples loaded with S. pneumoniae of known serotypes, and 46 blood clinical samples. All the strains tested and the simulated blood clinical samples were correctly typed by the technique. Real-time PCR allowed serotyping in 37/46 children ≤ 5 years of age (80.4%) in whom pneumonia was diagnosed in four Italian hospitals. Non-PCV7 serotypes accounted for at least 47.8% (22/46) of cases, serotype 19A being the most common (34.7%, 16/46). Although, it is not known at present whether the incidence of 19A serotype is attributable to the use of PCV7 only, expanding pneumococcal serotype coverage has clearly the potential to prevent a larger number of pneumonias in Italian children less than ≤ 5 years of age. Molecular methods are of increasing importance in the diagnosis of pneumococcal pneumonia and in monitoring serotype distribution and replacement.     

The antimicrobial resistance profile of Streptococcus pneumoniae

Antibacterial resistance in pneumococci is increasing worldwide, primarily against β -lactams and macrolides. Understanding the role played by molecular determinants of resistance, transformation and competence in the evolution of Streptococcus pneumoniae is important in addressing this trend. Data from the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) study indicate that about 40% of pneumococci display multidrug-resistant phenotypes (resistance to three or more antibiotics), with highly variable prevalence rates observed in different countries. Alterations in the structure of six penicillin-binding proteins (PBPs) have been described in S. pneumoniae (1a, 1b, 2x, 2a, 2b and 3), enabling resistance to β -lactam antibiotics. Mechanisms conferring macrolide resistance include resistance mediated through the erm (B) gene, which results in macrolide–lincosamide–streptogramin B resistance, or through the mef (A) gene, which encodes an antibiotic efflux pump. Another variant, mef (E), is also expressed in S. pneumoniae ; both mef (A) and mef (E) variants are associated with strains belonging to serotype 14. In addition to the selection pressure resulting from misuse of antibiotics, widespread vaccination programmes may contribute to changing pneumococcal epidemiology. Since the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7), the rate of invasive pneumococcal disease due to PCV7 serotypes has declined significantly in many countries, but some countries have reported an increase in non-PCV7 serotypes. This phenomenon, termed 'replacement', is associated with certain pneumococcal serotypes or clones (e.g. serotype 19A). Whether novel 'vaccine escape recombinant' pneumococcal strains are emerging or changes in distribution are part of a secular cycle remains to be determined.     

Pediatric invasive pneumococcal disease in the United States in the era of pneumococcal conjugate vaccines

Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development.     

Pneumococcal empyema and complicated pneumonias: global trends in incidence,prevalence, and serotype epidemiology

This review evaluates the serotype epidemiology of complicated pneumococcal pneumonia (CPP) during the period 1990–2012. PubMed and EMBASE were searched using the terms “empyema”, “complicated pneumonia”, “pleural infection”, “necrotizing pneumonia”, “pleural effusion”, “parapneumonic effusion”, “pneumatocele”, or “lung abscess”; “pneumococcal” or “Streptococcus pneumoniae”; and “serotype” for studies on the epidemiology of complicated pneumonias published from January 1, 1990 to October 1, 2013. Studies with data on incidence and serotypes were included; reviews, case reports, and conference abstracts were excluded. Of 152 papers, 84 fitted the inclusion criteria. A few pneumococcal serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14, and 7F. CPP was a more common manifestation of pneumococcal disease among older (>2 years old) than younger children. The data support increases in both reported incidence rates and proportions of CPP in children and adults during the period 1990–2012; specific increases varied by geographic region. The proportions of serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas most studies show declines in serotype 14. Serotype 1 has been a predominant cause of CPP since 1990, while antibiotic resistance was infrequent among serotype 1 isolates. The reported incidence and proportions of CPP among pneumonia cases steadily increased from 1990 to 2012. Several factors might account for these increases, including enhanced disease detection due to a higher index of suspicion, more sophisticated diagnostic assays, and changes in the prevalence of serotypes with capacity to invade the pleural space that were not targeted by the 7-valent pneumococcal conjugate vaccine (PCV7).     

Clonal evolution leading to maintenance of antibiotic resistance rates among colonizing Pneumococci in the PCV7 era in Portugal

The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in Portugal led to extensive serotype replacement among carriers of pneumococci, with a marked decrease of PCV7 types. Although antimicrobial resistance was traditionally associated with PCV7 types, no significant changes in the rates of nonsusceptibility to penicillin, resistance to macrolides, or multidrug resistance were observed. This study aimed to investigate the mechanisms leading to maintenance of antimicrobial resistance, despite marked serotype replacement. We compared, through molecular typing, 252 antibiotic-resistant pneumococci recovered from young carriers in 2006 and 2007 (era of high PCV7 uptake) with collections of isolates from 2002 and 2003 (n=374; low-PCV7-uptake era) and 1996 to 2001 (n=805; pre-PCV7 era). We observed that the group of clones that has accounted for antimicrobial resistance since 1996 is essentially the same as the one identified in the PCV7 era. The relative proportions of such clones have, however, evolved substantially overtime. Notably, widespread use of PCV7 led to an expansion of two Pneumococcal Molecular Epidemiology Network (PMEN) clones expressing non-PCV7 capsular variants of the original strains: Sweden(15A)ST63 (serotypes 15A and 19A) and Denmark(14)ST230 (serotypes 19A and 24F). These variants were already in circulation in the pre-PCV7 era, although they have now become increasingly abundant. Emergence of novel clones and de novo acquisition of resistance contributed little to the observed scenario. No evidence of capsular switch events occurring after PCV7 introduction was found. In the era of PCVs, antimicrobial resistance remains a problem among the carried pneumococci. Continuous surveillance is warranted to evaluate serotype and clonal shifts leading to maintenance of antimicrobial resistance.     

Pediatric osteoarticular infections caused by Streptococcus pneumoniae before and after the introduction of the heptavalent pneumococcal conjugate vaccine

Streptococcus pneumoniae is an uncommon cause of osteoarticular infections (OAI) in children. The objective of this study was to investigate the clinical and laboratory characteristics of pneumococcal OAI before and after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). Data were retrospectively collected from children aged?<16?years who were hospitalized for pneumococcal OAI between 1997 and 2007 in four Parisian teaching hospitals. Forty-three children were included (32 with arthritis and 11 with osteomyelitis) and the median age of these children was 12.5?months (range 3?months to 14?years). Serotypes were available for 19/43 strains (44?%) from 1997 onwards and for 12/13 strains (92?%) from 2005 onwards. Seven unvaccinated children were infected with vaccine serotypes and we observed only one vaccine failure. After the introduction of PCV7, we noted an increase in short-term complications and the emergence of serotype 19A, which was penicillin-intermediate in 86?% of cases. After PCV7 introduction, serotype 19A was the most frequent serotype implicated in pediatric pneumococcal OAI. The 13-valent pneumococcal conjugate vaccine introduced in France in June 2010 should cover the emerging serotype.     

Management of antibiotic-resistant Streptococcus pneumoniae infections and the use of pneumococcal conjugate vaccines

The epidemiology of Streptococcus pneumoniae , a major cause of meningitis, pneumonia, bacteraemia and acute otitis media in both children and adults, has been altered by the availability of the seven-valent pneumococcal conjugate vaccine (PCV7) and selection pressure from broad-spectrum antibiotics. In Spain, the rates of antimicrobial consumption and resistance are high; of all S. pneumoniae isolates collected between 2001 and 2003, 9.2% were penicillin-resistant and 26.4% were penicillin-intermediate. These rates were even higher in children aged ≤4 years; 52.3% of isolates were penicillin-resistant or penicillin-intermediate. Serogroup 14 comprises nearly 9% of pneumococcal strains and exhibits the highest resistance to penicillin (69%). Since the introduction of PCV7 in Madrid, the isolates collected from hospitalized children aged <15 years from 21 hospitals revealed that only 8% of cases involving S. pneumoniae isolates were due to PCV7 serotypes, and no PCV7 vaccination failures were identified. These isolates demonstrated low rates of penicillin–non-susceptible and erythromycin–non-susceptible strains. Among multiresistant strains, serotype 19A was identified as most important. Although the recent WHO position paper on childhood immunizations speaks to the growing resistance of pneumococci, antibiotic resistance in Spain is noted to be decreasing and must be evaluated in conjunction with global studies.     

Changes in Molecular Epidemiology of Streptococcus pneumoniae Causing Meningitis following Introduction of Pneumococcal Conjugate Vaccination in England and Wales

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis from July 2004 to June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by multilocus sequence typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5-year period. Fifty-two serotypes, 238 sequence types (STs), and 87 clonal complexes were identified, with no significant difference in the yearly Simpson''s diversity index values (range, 0.974 to 0.984). STs commonly associated with PCV7 serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual serotypes. Replacement disease following PCV7 introduction was mainly due to serotypes 1, 3, 7F, 19A, 22F, and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a serotype 14 capsule in 2005 and a serotype 28A capsule in 2009. In 2008 to 2009, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145 fatalities/1,030 cases; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 serotypes, including some not covered by the 13-valent vaccine, such as serotypes 22F and 33F, emphasizing the importance of long-term epidemiological and molecular surveillance.     

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.     

Review on the immunogenicity and safety of PCV-13 in infants and toddlers

Pneumococcal polysaccharide-protein conjugate vaccines (PCVs) generally protect against vaccine-serotype-specific pneumococcal disease. Additional serotypes included in the new 13-valent PCV (PCV-13) formulation and not in the first-generation 7-valent PCV (PCV-7) formulations are 1, 3, 5, 6A, 7F and 19A. Importantly, serotype 1 is associated with a high proportion and burden of pneumococcal disease in low-income countries, whilst serotype 19A emerged as the dominant disease-causing serotype following widespread PCV-7 immunization in the USA. In this article we present the available data on the immunogenicity and safety of PCV-13 in infants and children. Noninferiority studies indicate a similar immunogenicity profile between PCV-13 and PCV-7 recipients against most of the common serotypes. A favorable immunogenicity profile was also observed for at least five of the additional serotypes in PCV-13. An attenuated anamnestic response to serotype 3 was reported in five out of 14 studies. PCV-13 was demonstrated to have a similar acceptable safety profile to PCV-7 and no interference in immunogenicity of other concomitantly administered childhood vaccines was observed among PCV-13 recipients.     

Changes in antimicrobial resistance,serotypes and genotypes in Streptococcus pneumoniae over a 30-year period

Over the past three decades, antimicrobial resistance in Streptococcus pneumoniae has dramatically increased worldwide. Non-susceptibility to penicillin in S. pneumoniae was first described in Australia in 1967, and later in New Guinea (1974), South Africa (1977), and Spain (1979). Most of these strains showed resistance to multiple antibiotics and belonged to serotypes 6A, 6B, 19A, 19F, and 23F. By the late 1980s and 1990s, the emergence and rapid dissemination of antibiotic-resistant pneumococci was observed in southern and eastern Europe, North America, South America, Africa, and Asia. Great geographical variability, both in serotype distribution and in the prevalence of resistant pneumococci, has been reported. However, the highest rates of resistance to penicillin and erythromycin worldwide were found in serotypes 6B, 6A, 9V, 14, 15A, 19F, 19A, and 23F. The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in the 2000s and a reduction in antimicrobial use were associated with a significant decline in the incidence of invasive pneumococcal infections and in rates of antibiotic resistance in the USA. However, an increase in the incidence of infections caused by non-PCV7 serotypes, especially multiresistant serotype 19A pneumococci, has been observed in many countries over the last 5 years. The dynamic character of serotypes and antibiotic resistance in S. pneumoniae should be controlled by a policy of prudent antibiotic use and by implementation of the new generation of conjugate vaccines.     

PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.     

Pneumococcal serotypes causing pneumonia with pleural effusion in pediatric patients

To determine the prevalence of serotypes of Streptococcus pneumoniae responsible for pneumonia with pleural effusion, we determined the capsular polysaccharide (PS) type directly on 49 pleural fluid specimens collected from pediatric patients during 2007 to 2009 with laboratory-confirmed pneumococcal pneumonia by using monoclonal antibodies and a multiplex, bead array immunoassay. Because the fluids had to be heated to remove nonspecific reactivity before being tested in the immunoassay and type 19A PS is heat labile, the pleural fluid samples were also tested for serotype 19A capsule gene locus by PCR. Use of the multiplex immunoassay combined with type-specific 19A PCR allowed for serotype determination on 40 of 49 pleural fluids. Pneumococcal pneumonia with pleural effusion was associated with a limited number of serotypes, with types 1, 3, 7F/A, and 19A accounting for 75% of the typeable cases. The concentration of capsular PS in the pleural fluids was often greater than 1 μg/ml and sufficient to inhibit the opsonic capacity of sera from individuals who had received the 23-valent pneumococcal PS vaccine. Based on the serotypes observed before and after introduction of the 7-valent pneumococcal conjugate vaccine, the recently licensed 13-valent pneumococcal conjugate vaccine may reduce the incidence of pneumonia with pleural effusions.     

Pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine; immunogenicity in patients with ataxia-telangiectasia

The immunodeficiency in Ataxia-telangiectasia (A-T) is characterised by low T and B cell counts, low levels of IgE, IgA and/or IgG2, and especially low levels of pneumococcal antibodies. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has previously been shown not to be effective in A-T, but these patients are capable of making protective antibodies to other vaccines such as diphtheria and tetanus toxin, promising effect of the seven-valent pneumococcal conjugated vaccine (PCV7). Nine A-T patients and 25 age and sex matched controls were vaccinated with both PCV7 and PPV23, and three A-T patients were vaccinated with PCV7 only. In the A-T patients, no significant increase in pneumococcal antibody levels were observed after the single PCV7, while the subsequent PPV23 vaccination resulted in a significant increase in antibody levels to the PPV23 mix, as well as to serotype 4, 14, 19F and to the geometric mean of serotype 4, 6B, 14, 18C, 19F, 23F which increased from median 0.2 (range 0.1-0.5) microg/mL to 0.6 (0.2-1.5) microg/mL (P= 0.014). Compared to the patients' baseline levels, the vaccinations induced a 1.5- to 7-fold increase in antibodies to the six different serotypes tested. The increases in pneumococcal antibody titres were lower than those observed in the controls (9- to 34-fold increase). The results are valuable in planning the care of A-T patients, using PCV7 to trigger and PPV23 to booster the immune response and possibly prevent severe pneumococcal disease.     

Immunogenicity and tolerance of a 7-valent pneumococcal conjugate vaccine in nonresponders to the 23-valent pneumococcal vaccine

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 microgram/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 microgram/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.     

Changes in serotypes causing invasive pneumococcal disease (2005–2007 vs. 1997–1999) in children under 2 years of age in a population with intermediate coverage of the 7-valent pneumococcal conjugated vaccine

Serotypes causing invasive pneumococcal disease (IPD) in children aged <2 years in Catalonia (Spain) before and after licensing of the 7-valent pneumococcal conjugated vaccine (7vPCV) were assessed, using samples taken during 1997–1999 and 2005–2007 respectively. The distribution of serotypes causing IPD within these groups was obtained by serotyping strains sent by 22 Catalan hospitals to the Carlos III Health Institute, Madrid. Between 1997–99 and 2005–2007, the proportion of vaccine serotypes causing IPD in Catalonia fell from 70.54% to 31.67% (p <0.0001). The proportion of vaccine-related serotypes, mainly serotype 19A, increased from 9.82% to 32.50% (p <0.0001). The proportion of non-vaccine, non-related serotypes (serotypes not related to vaccine serotypes) rose from 19.64% to 35.83% (p <0.05). Within this group, the proportions of serotype 24F increased significantly. There has been a change in the distribution of serotypes isolated from cases of IPD in children <2 years old in Catalonia, comprising a reduction in the proportion of 7-valent vaccine serotypes, a rise in vaccine-related serotypes, especially 19A, and a smaller rise in non-vaccine, non-related serotypes, especially serotype 24F. A new 13-valent vaccine will cover 77.91% of the serotypes causing IPD in children <2 years old in Catalonia from 2005 to 2007.     

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.