Serotype 19F Research Articles

Investigation of Appropriate Cultivation Approach for Capsular Polysaccharide Production by Streptococcus pneumoniae Serotype 19F

With the aim of determining an appropriate cultivation approach for the capsular polysaccharide production by Streptococcus pneumoniae serotype 19F, the influence of environmental and culture medium conditions on the pneumococcal culture was investigated. Using 5% CO2 atmosphere instead of using an aeration limited environment enhanced the capsule production 3.5 fold. Buffering the cultivation medium prevented the culture pH drop to the acidic condition and increased the capsule production almost 5 fold. Utilizing casamino acid as the nitrogen source of the culture medium instead of soytone provided 1.3 fold increase in the capsule production. Glucose, sorbitol, lactose and sucrose were investigated as carbon sources of the culture medium. Regarding costs of these sugars and their effects on the capsule production, lactose was the best carbon source. Our results demonstrated that buffering the cultivation medium had the most profound effect on the serotype 19F capsule production. The capsule was produced at 1.706 mg/ml in the buffered medium. Applying this culture method allows the cost effective production of the serotype 19F pneumococcal capsule for inclusion in pneumococcal vaccines.

In silico Analysis of Surface Proteins of Streptococcus pneumoniae Serotype 19F for Identification of Immunoprotective Epitopes

Pneumococcal conjugate vaccines (PCVs) were developed through chemical coupling of polysaccharide capsules of pneumococci to immunogenic carrier proteins and World Health Organization recommends inclusion of these vaccines in national immunization programs for children. However, the PCVs implementation in developing countries can be prevented by the high manufacturing costs. This issue can be overcome by construction of protein based vaccines against pneumococci. We already identified three pneumococcal surface proteins including D-alanyl-D-alanine-carboxy peptidase (DDCP), choline binding protein D (CBPD), and cell wall surface anchor family protein (CWSAP) as appropriate protein candidates for eliciting protection against S. pneumoniae serotype 19F. The protein protective antigenicity, the absence of autoimmunity induction, and the amino acid sequence conservancy in serotype 19F pneumococcal strains were used as selection criteria. However, regarding the requirement of both antibody and cellular immune responses for protection against pneumococci, analysis of protective B and T-cell epitopes of these proteins is necessary to examine their usefulness in new vaccine formulations. In the present study, therefore, we aim to identify protective epitopes of these proteins via widely used bioinformatic tools. The Bepipred program was used for identification of linear B-cell epitopes. The conformational B-cell epitopes were predicted using the CBTope program. T-cell epitopes were identified using the Immune Epitope Database tool. The immunoprotective abilities of epitopes were evaluated using VaxiJen. Our results showed that all of the three studied proteins included protective epitopes. However, the greatest number of epitopes was identified in a truncated form of CWSAP. Moreover, the most probable immunoprotective epitopes reside in this protein and these epitopes were highly conserved in CWSAPs of the most common pneumococcal serotypes in the world. Therefore, the truncated CWSAP was an appropriate candidate for development of protein based vaccines against the most common pneumococcal serotypes.

Serotypes, antimicrobial susceptibility, and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012–2014

Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6–71.4%, p=0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p=0.029 and p=0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden15A-25 clone).

Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine

This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6–17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14–0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35–0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13–0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90–2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07–0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.

Effect on nasopharyngeal pneumococcal carriage of replacing PCV7 with PCV13 in the Expanded Programme of Immunization in The Gambia

IntroductionIn 2011, two years after the introduction of 7-valent Pneumococcal conjugate vaccine (PCV7), the Gambian immunization programme replaced PVC7 with PCV13 (13-valent). Our objective was to assess the additional impact of PCV13 on prevalence of pneumococcal nasopharyngeal carriage. MethodsWe recruited healthy Gambian infants who had received three PCV doses. Nasopharyngeal swabs were collected from infants and their mothers during two cross-sectional surveys (CSS) conducted in infants vaccinated with PCV7 (CSS1) and vaccinated with PCV13 (CSS2). Pneumococci were isolated and serotyped following standardized methods. Whole genome sequencing was performed on non-typable pneumococcus isolated in CSS1 and CSS2. Results339 and 350 infants and their mothers were recruited in CSS1 and CSS2, respectively. Overall prevalence of pneumococcal carriage was 85.4% in infants. Among infants, prevalence of vaccine type (VT) carriage was lower in CSS2 [9.4% versus 4.9% (p=0.025) for PCV7-VT; 33.3% versus 18.3% (p<0.001) for PCV13-VT and 23.9% versus 13.7% (p=0.001) for the 6 additional serotypes included in PCV13]. At CSS2, there was a decrease of serotypes 6A (from 15.3% to 5.7%, p<0.001) and 19F (from 5.6% to 1.7%, p=0.007), and an increase of non-typable pneumococci (0.3–6.0%, p<0.001), most of which (82.4%) were from typable serotype backgrounds that had lost the ability to express a capsule. Prevalence of overall and VT carriage in mothers was similar in CSS1 and CSS2. ConclusionsReplacing PCV7 for PCV13 rapidly decreased prevalence of VT carriage among vaccinated Gambian infants. An indirect effect in mothers was not observed yet. Vaccine-driven selection pressure may have been responsible for the increase of non-typable isolates.

Serotype Distribution, Antimicrobial Susceptibility, and Molecular Epidemiology of Streptococcus pneumoniae Isolated from Children in Shanghai, China.

Objective Streptococcus pneumoniae is a common pathogenic cause of pediatric infections. This study investigated the serotype distribution, antimicrobial susceptibility, and molecular epidemiology of pneumococci before the introduction of conjugate vaccines in Shanghai, China.MethodsA total of 284 clinical pneumococcal isolates (270, 5, 4,3, and 2 of which were isolated from sputum, bronchoalveolar lavage fluid, blood, cerebral spinal fluid, and ear secretions, respectively) from children less than 14 years of age who had not been vaccinated with a conjugate vaccine, were collected between January and December in 2013. All isolates were serotyped by multiplex polymerase chain reaction or quellung reactions and antimicrobial susceptibility testing was performed using the broth microdilution method. The molecular epidemiology of S.pneumoniae was analyzed by multilocus sequence typing (MLST).ResultsAmong the 284 pneumococcal isolates, 19F (33.5%), 19A (14.1%), 23F (12.0%), and 6A (8.8%) were the most common serotypes and the coverage rates of the 7-, 10-, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) were 58.6%, 59.4% and 85.1%, respectively. Antimicrobial susceptibility showed that the prevalence rates of S.pneumoniae resistance to penicillin were 11.3% (32/284). Approximately 88.0% (250/284) of the isolates exhibited multi-drug resistance. MLST analysis revealed a high level of diversity, with 65 sequence types (STs) among 267 isolates. Specifically, the four predominant STs were ST271 (24.3%, 65/267), ST320 (11.2%, 30/267), ST81 (9.7%, 26/267), and ST3173 (5.2%, 14/267), which were mainly associated with serotypes 19F, 19A, 23F, and 6A, respectively.ConclusionsThe prevalent serotypes among clinical isolates from children were 19F, 19A, 23F, and 6A and these isolates showed high resistance rates to β-lactams and macrolides. The Taiwan19F-14 clone played a predominant role in the dissemination of pneumococcal isolates in Shanghai, China. Therefore, continued and regional surveillance on pneumococcal isolates may be necessary.

Invasive disease potential of pneumococci before and after the 13-valent pneumococcal conjugate vaccine implementation in children

BackgroundChanges in serotype distribution have been induced after pneumococcal conjugate vaccines (PCV) implementation, and non-vaccine serotypes are now circulating. Among these latter serotypes, we aimed to distinguish those with high invasive disease potential before (2008–2009) and after PCV13 implementation (2012–2013). MethodsInvasive pneumococcal disease (IPD) serotypes isolated from children 6 to 24 months were compared with nasopharyngeal-colonizing serotypes in healthy children. To assess the invasive potential of a given serotype, odds ratios (ORs) were calculated. For each serotype, OR >1 indicated increased probability of association with IPD and OR <1 decreased probability. ResultsIn 2008/2009 and 2012/2013, 355 pneumococci were isolated from 1212 healthy children and from 569 IPD, including 166 meningitis, 114 pneumonia, and 289 other IPDs. In period 1, serotypes 7F, 3, 1, 24F, and 19A showed highly significant invasive disease potential whereas in period 2, only serotype 24F was associated with a significant high OR (6.6 [95% CI 2.6; 16.2]). Of note, for serotype 12F, OR could not be calculated because of no carrier recorded, however, if there had been a single 12F carrier, the OR would be among the highest, in period 2, 15.7 [95% 3.4; 73.0]). Only two serotypes appeared negatively associated with IPD, 11A and 23B in the period 2 as compared with nine in period 1. In the second period, pneumococcal penicillin non-susceptible isolates were mostly represented by serotypes 19A, 15A, 19F, 35B and 24F both in carriers and IPD. Only one strain was resistant to penicillin with MIC=4μg/ml (serotype 19A) during the first period. ConclusionIn children <2 years old, compared to the previous period, the number of serotypes having a high disease potential decreased after PCV13 implementation, only two non-vaccine serotypes, 24F and 12F, had high invasive disease potential.

Multilocus sequence types of invasive pneumococcal isolates from Danish infants (0-90 days) 2003-2013.

BackgroundA pneumococcal conjugate vaccine (PCV) has been part of the Danish childhood immunization programme since October 2007. It is administered at the ages of 3, 5 and 12 months and healthy infants younger than 90 days are consequently not vaccinated. Initially the PCV-7 vaccine was used but this was replaced by the PCV-13 in April 2010. Vaccination coverage in Denmark is approximately 90 %.The aim of this study was to present multilocus sequence typing (MLST) profiles of Streptococcus pneumoniae isolates from Danish infants (0–90 days) with invasive pneumococcal disease (IPD) in the period 2003–2013.Findings32 IPD isolates were investigated for their MLST profiles. The identified sequence types (STs) had previously been observed in other European countries. Among the clones were ST 306 (serotype 1), ST 180 (serotype 3) and ST 191 (serotype 7F).ConclusionsThe ST profile distribution in this study is similar to that observed in other European studies and show a variety of STs. Our data show that the majority of STs found in Denmark is also observed in other European countries, indicating that the IPD isolates were from clones generally circulating in Europe.

Streptococcus pneumoniae Serotypes and Mortality in Adults and Adolescents in South Africa: Analysis of National Surveillance Data, 2003 - 2008.

BackgroundAn association between pneumococcal serotypes and mortality has been suggested. We aimed to investigate this among individuals aged ≥15 years with invasive pneumococcal disease (IPD) in South Africa.MethodsIPD cases were identified through national laboratory-based surveillance at 25 sites, pre-pneumococcal conjugate vaccine (PCV) introduction, from 2003–2008. We assessed the association between the 20 commonest serotypes and in-hospital mortality using logistic regression with serotype 4 (the third commonest serotype with intermediate case-fatality ratio (CFR)) as referent.ResultsAmong 3953 IPD cases, CFR was 55% (641/1166) for meningitis and 23% (576/2484) for bacteremia (p<0.001). Serotype 19F had the highest CFR (48%, 100/207), followed by serotype 23F (39%, 99/252) and serotype 1 (38%, 246/651). On multivariable analysis, factors independently associated with mortality included serotype 1 (OR 1.9, 95%CI 1.1–3.5) and 19F (OR 2.9, 95%CI 1.4–6.1) vs. serotype 4; increasing age (25–44 years, OR 1.8, 95%CI 1.0–3.0; 45–64 years, OR 3.6, 95%CI 2.0–6.4; ≥65 years, OR 5.2, 95%CI 1.9–14.1; vs. 15–24 years); meningitis (OR 4.1, 95%CI 3.0–5.6) vs. bacteremic pneumonia; and HIV infection (OR1.7, 95%CI 1.0–2.8). On stratified multivariate analysis, serotype 19F was associated with increased mortality amongst bacteremic pneumococcal pneumonia cases, while no serotype was associated with increased mortality in meningitis cases.ConclusionMortality was increased in HIV-infected individuals, which may be reduced by increased antiretroviral therapy availability. Serotypes associated with increased mortality are included in the 10-and-13-valent PCV and may become less common in adults due to indirect effects following routine infant immunization.

Pneumococcal Meningitis Vaccine Breakthroughs and Failures After Routine 7-Valent and 13-Valent Pneumococcal Conjugate Vaccination in Children in France.

We collected cases of pneumococcal meningitis vaccine breakthrough (VBT) and vaccine failure (VF) from 2003 to 2013 after the implementation of pneumococcal conjugate vaccines (PCVs) in France. VBT accounted for 3.2% of the cases (PCV7 era: 24 of 943, PCV13 era: 15 of 290) and VF 0.6% (PCV7 era: 6 of 943, PCV13 era: 2 of 290). VBT and VF are rare and occur in most cases in children younger than 2 years. The serotype 19F was the most frequent cause even after the introduction of PCV13.

An Invasive Pneumococcal Infection Due to Streptococcus pneumoniae Serotype 24.

To the Editors: Levy et al1 report a 67% decrease of pediatric pneumococcal meningitis due to serotypes contained in the 13-valent pneumococcal conjugate vaccine (PCV13). Non-PCV13 serotypes that dominate in their setting are 12F, 24F, 22F and 15B/C. We report the recent case of a previously healthy 9-month-old child who presented with septic shock, purpura fulminans, multiorgan failure and meningitis. He received 2 doses of PCV13 at 2 and 4 months of age. Streptococcus pneumoniae serotype 24 was isolated from blood and cerebrospinal fluid. His clinical course was marked by acute renal failure, rhabdomyolysis and intravascular disseminated coagulation. His skin condition worsened with large areas of necrosis. Amputation of 3 necrotic extremities and prolonged course of antibiotics resulted in a slow recovery. It is yet unclear whether PCV13 will lead to the emergence of new dominant serotypes similarly to what has been observed previously with 19A in the PCV7 era.2 Yet, the present case and the study by Levy et al raise the question of the potential invasiveness and replacement capacity of serotype 24. Levy et al reported that 15% of pneumococcal meningitis was attributed to serotype 24F, in 2012, in France. However, evidence of an increased proportion of serotype 24 IPD has not been documented in the actual post-PCV13 era in other settings. Besides, low prevalence of invasive pneumococcal diseases due to serotype 24 has been reported after PCV7 and before PCV13 implementation.3 In addition, increased incidence of invasive pneumococcal diseases due to non-PCV13 serotypes as observed in many settings is not related to the emergence of clearly dominant serotypes.4 If this trend is confirmed by ongoing microbiologic surveillance, the development of new conjugated vaccines will no longer be the appropriate strategy. Tarahomjoo5 in a recent review article details new potential options for vaccine development, including the use of surface protein vaccines that could be coadministered with conjugated vaccines to reach a wider coverage of invasive strains. We hope that these potential new vaccines will contribute to the disappearance of such devastative infections in properly vaccinated children, in the future. Eugénie Gradoux Department of Paediatrics Sandra Asner, MD, MSc, MER1 Unit of Paediatric Infectious Diseases Department of Paediatrics Marie-Hélène Perez, MD Paediatric Intensive Care Unit Department of Paediatrics Pierre A. Crisinel, MD Unit of Paediatric Infectious Diseases Department of Paediatrics University Hospital Centre Lausanne, Switzerland

Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model

ABSTRACTCompetitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself.

Secular trends (1990–2013) in serotypes and associated non-susceptibility of S. pneumoniae isolates causing invasive disease in the pre-/post-era of pneumococcal conjugate vaccines in Spanish regions without universal paediatric pneumococcal vaccination

This study analyzed temporal trends of non-susceptibility/serotypes in invasive pneumococci from Spanish regions where pneumococcal conjugate vaccines (PCVs) were not included in paediatric immunization programmes. All invasive pneumococcal isolates voluntarily sent to the Spanish Reference Laboratory for Pneumococci (January 1990–December 2013) from hospitals located in target study regions were analyzed by age group. The PCV estimated coverage in children <24 months was correlated with 13-valent PCV (PCV13) serotypes trends. A total of 28,124 invasive isolates were analyzed: 3138 (11.2%) from children <24 months, 2161 (7.7%) from children 24–59 months, 781 (2.8%) from children 5–14 years, and 22,044 (78.4%) from adults. The estimated coverage increased from 17.6% (2002) to around 40% (2010–2013). The percentage of PCV13 serotypes among all isolates over time followed a cubic significant trend (R2=0.884), with an increasing trend up to 2001 followed by a decrease (more prominent from 2010 onwards). The estimated PCVs coverage was significantly correlated with the decrease in the percentage of PCV13 isolates in children <24 months (r2=0.824) and in adults (r2=0.786), mainly due to decreases in serotypes 1 and 7F in adults, and in serogroup 6 and serotypes 7F and 19A in children <24 months. None of the non-PCV13 serotypes stood out with substantial increases in the last period. This study showed that the different serotypes (and its associated non-susceptibility trends) were not equally affected by low PCVs disposition. Lack of impact in certain serotypes as serotype 1 (in children 24–59 months), 6C (in all age groups), and 19A (in adults) suggests the need for increasing vaccine coverage in the target vaccine population to increase direct and indirect protection.

Distribution and annual changes in Streptococcus pneumoniae serotypes in adult Japanese patients with pneumonia.

Streptococcus pneumoniae is one of the main causative bacteria in patients with pneumonia; however, there are no data regarding serotype changes in adult patients with pneumonia after the introduction of the pneumococcal vaccine (PCV7) for childhood immunization in Japan. We herein evaluated the serotype distribution in adult patients with pneumonia. This retrospective epidemiological study was performed at the University of Occupational and Environmental Health, Japan from January 2011 to December 2013. The serotypes of pneumococcal isolates obtained from patients with pneumonia were evaluated along with the patients' clinical information. A total of 81 patients with pneumococcal pneumonia (89 episodes) from whom S. pneumoniae was isolated were included. The numbers (percentages) of sample types were as follows: sputum 55 (61.8%), intratracheal tube suction 15 (16.9%), intrabronchial sampling 5 (5.6%) and bronchoalveolar lavage fluid 14 (15.7%). The PCV7 serotypes decreased significantly among the patients with pneumococcal pneumonia from 46.4% in 2011 to 20.0% in 2013 (p < 0.05). Conversely, PCV13 and 23-valent pneumococcal polysaccharide vaccination (PPSV23) serotypes other than PCV7 serotypes mildly increased during this period. In addition, the frequency of serotypes 19F, 23F and 4 (which are covered by PCV7) decreased annually; however, the changes in the frequencies of the other serotypes were not significant. This study demonstrated the yearly decrease of PCV7 serotypes in adult pneumococcal pneumonia patients after introducing PCV7 into the childhood immunization schedule in Japan. Continued surveillance of pneumococcal serotype changes is important for the proper use of different pneumococcal vaccines.

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

BackgroundPatients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients with and without immunosuppressive treatment four weeks post vaccination. MethodsIn a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. ResultsPCV13 induced a significantly higher antibody response for one serotype (23F) in IS treated patients and for two serotypes (9V and 23F) in untreated patients compared to CD patients vaccinated with PPV23. Untreated PPV23 recipients had higher responses for serotypes 9V and 18C compared to IS+TNF-α treated PPV23 recipients. Comparison between treatment groups showed that immunosuppressive treatment impaired the antibody response to both vaccines and that TNF-a treatment further conveyed additional impairment of the response. ConclusionPCV13 induces higher antibody response for some serotypes compared to PPV23. In addition, CD patients treated with immunosuppressive drugs alone or in combination with TNF-α antagonists had an impaired antibody response to both PPV23 and PCV13 compared to patients not receiving any of these treatments.The study has been registered in the European Clinical Trials Database (EudraCT, record no 2012-002867-86) and ClinicalTrials.gov (record no. NCT01947010).

High-Level Genetic Diversity among Invasive Streptococcus pneumoniae Isolates in Turkey.

This study obtained information on the serotypes and molecular typing characteristics of Streptococcus pneumoniae strains causing invasive diseases in Turkey. Sixty-eight S. pneumoniae isolates causing invasive pneumococcal diseases were collected from different regions of Turkey from 2009 to 2011. The isolates were characterized by performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and capsular serotyping, and 25 different serotypes were identified. Serotypes 19F, 23F, 1, 14, and 7F were common and accounted for 52.9% of all the serotypes. In addition, 54 different PFGE profiles (pulsotypes) were observed. Twenty-three of the 68 (33.8%) isolates were clustered into 9 pulsotypes. MLST analysis yielded 36 sequence types, of which 12 (33.3%) were novel. A comparison of results with the global pneumococcal MLST database by performing eBURST analysis showed that our strains belonged to 20 different clonal complexes and 5 singletons. In addition, we identified 4 new alleles: 2 gdh, 1 xpt, and 1 ddl. Thus, the results of this study highlighted a high level of diversity among pneumococcal isolates. In addition, the study identified a case of possible capsular switching.

The Efficacy and Duration of Protection of Pneumococcal Conjugate Vaccines Against Nasopharyngeal Carriage: A Meta-regression Model.

Pneumococcal conjugate vaccines (PCVs) reduce disease largely through their impact on nasopharyngeal (NP) carriage acquisition of Streptococcus pneumoniae, a precondition for developing any form of pneumococcal disease. We aimed to estimate the vaccine efficacy (VEC) and duration of protection of PCVs against S. pneumoniae carriage acquisition through meta-regression models. We identified intervention studies providing NP carriage estimates among vaccinated and unvaccinated children at any time after completion of a full vaccination schedule. We calculated VEC for PCV7 serotypes, grouped as well as individually, and explored cross-protective efficacy against 6A. Efficacy estimates over time were obtained using a Bayesian meta-logistic regression approach, with time since completion of vaccination as a covariate. We used data from 22 carriage surveys (15 independent studies) from 5 to 64 months after the last PCV dose, including 14,298 children. The aggregate VEC for all PCV7 serotypes 6 months after completion of the vaccination schedule was 57% (95% credible interval: 50-65%), varying by serotype from 38% (19F) to 80%. Our model provides evidence of sustained protection of PCVs for several years, with an aggregate VEC of 42% (95% credible interval: 19-54%) at 5 years, although the waning differed between serotypes. We also found evidence of cross-protection against 6A, with a VEC of 39% 6 months after a complete schedule, decreasing to 0 within 5 years postvaccination. Our results suggest that PCVs confer reasonable protection against acquisition of pneumococcal carriage of the 7 studied serotypes, for several years after vaccination, albeit with differences across serotypes.

Investigation of the protective effects of beta-D-glucan against invasive encapsulated Streptococcus pneumoniae sepsis in splenectomized rats

In asplenic individuals depending on the weakness of the immune response, sepsis are known to be developed with a high mortality rate. The most common species which are responsible for sepsis are encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis. Sepsis caused by immune deficiencies linked to splenectomy leads to infections particularly in the lungs and liver and causes multiple organ failure. On the other hand, -D-glucan (BDG), a branched glucose polymer, shows immunomodulatory activity, by enhancing the resistance of the host against microbial agents, and promotes phagocytic and proliferative activities of reticuloendothelial system. The aim of this experimental study was to investigate the effects of BDG alone and in combination with ceftriaxone on sepsis caused by encapsulated invasive S.pneumoniae serotype 19F. A total of 36 Sprague-Dawley rats were used in the study, and the animals (6 in each group) were equally divided into six groups as control, splenectomy, sepsis, BDG, ceftriaxone and BDG+ceftriaxone groups. Treatment groups were intravenously infected with S.pneumoniae 19F strain, and after sacrification, microbiological [bacterial counts (cfu/mL)], biochemical (myeloperoxidase activity, DNA oxidation, specific IgM and IgG levels) and histopathological analysis were performed in the tissue samples. In the study, BDG, ceftriaxone and BDG+ceftriaxone groups had statistically significant decrease in the amount of bacteria in all tissues when compared to the sepsis group (p<0.05). We demonstrated that, BDG alone or combined treatment partially recovered the low serum IgM levels in splenectomized rats (p<0.001 ve p<0.02, respectively) and completely inhibited oxidative DNA damage in lung and liver after S.pneumoniae infection (p<0.00001). In addition, BDG alone or combined treatment fairly minimized the presence of bacteria in all tissues, when compared with sepsis group (p<0.00001). The data of our study suggests that, BDG, an immunomodulatory agent, alone and in combination with ceftriaxone can reverse the systemic inflammatory reaction in S.pneumoniae sepsis and thereby can reduce multiple organ failure.

Characterization of 19A-like 19F pneumococcal isolates from Papua New Guinea and Fiji.

Molecular identification of Streptococcus pneumoniae serotype 19F is routinely performed by PCR targeting the wzy gene of the capsular biosynthetic locus. However, 19F isolates with genetic similarity to 19A have been reported in the United States and Brazil. We screened 78 pneumococcal carriage isolates and found six 19F wzy variants that originated from children in Papua New Guinea and Fiji. Isolates were characterized using multilocus sequence typing and opsonophagocytic assays. The 19F wzy variants displayed similar susceptibility to anti-19F IgG antibodies compared to standard 19F isolates. Our findings indicate that these 19F variants may be more common than previously believed.

Noninvasive Streptococcus pneumoniae serotypes recovered from hospitalized adult patients in the United States in 2009 to 2012.

This study was conducted to determine the serotype distribution and trends over time of Streptococcus pneumoniae strains associated with noninvasive infections among adult patients ≥18 years of age in the United States (2009 to 2012). A total of 2,927 S. pneumoniae isolates recovered from patients presenting with respiratory infections and obtained mainly (87.0%) from lower respiratory tract specimens (sputum) were included. The levels of the 7-valent pneumococcal conjugate vaccine (PCV7) serotypes remained stable over the 4-year study period (4.6% to 5.5%; P = 0.953). Overall, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were identified in 32.7% of samples, declining from 33.7% to 35.5% in 2009 to 2011 to 28.2% in 2012 (P = 0.007), with a significant decrease in the levels of serotypes 7F (P = 0.013) and 6A (P = 0.010). The levels of 19A remained constant (15.8% to 17.1%) during 2009 to 2011, dropping to 12.2% in 2012 (P = 0.089). The prevalence of serotypes associated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23), but not PCV13, remained generally stable; however, the prevalence of serotypes 15B and 15C (15B/15C) increased from 2.7% to 6.3% (P = 0.010). The proportion of nonvaccine serotypes increased gradually during the study period (P = 0.044), particularly for serotype 35B (from 3.6% in 2009 to 8.2% in 2012; P = 0.001). Nonsusceptibility rates for penicillin (susceptible breakpoint, ≤2 μg/ml) and clindamycin against PCV7 serotypes decreased over the period. These results suggest the emergence of indirect effects following introduction of PCV13 for infants and young children; continued surveillance is needed to assess the burden of PCV13 serotypes in the adult population after the implementation of age-based recommendations in the United States.