Serotype 19F Research Articles

Residual colonization by vaccine serotypes in rural South Africa four years following initiation of pneumococcal conjugate vaccine immunization

ABSTRACT Background We evaluated pneumococcal colonization in children and adults between the time of 7-valent pneumococcal conjugate vaccine (PCV) introduction in the immunization program in 2009 to two years after transitioning to PCV13 in 2011. Methods Community-based carriage surveillance was undertaken between May-November 2013 (Period-3), with similar surveys in 2009 (Period-1) and 2011 (Period-2). Households with children below two years had a similar probability of being sampled in all surveys. Nasopharyngeal swabs were processed using standard methods and serotyped by Quellung. Results In children>9-59 months old, overall pneumococcal colonization prevalence declined from 81.8% in Period-1 to 65.0% in Period-3 (p<0.001). Reductions of 70% (41.2% vs. 13.6%) in PCV7-serotypes colonization and 66% (15.3% vs. 4.4%) for the six additional PCV13-serotypes (PCV13-add6VT) were observed. There was, however, high residual colonization by PCV7-serotypes 19F (14.9% vs. 6.3%) and 23F (8.5% vs. 4.1%), despite reduction of 57% and 52%, respectively. Among individuals>12 years of age, there was 61% reduction in PCV7-serotype colonization (3.1% vs. 1.3%) and 75% decrease for PCV13-add6VT (2.1% vs. 0.6%) between Period-1 and Period-3. Conclusions The residual prevalence of serotypes 19F and 23F, four years after introducing PCV in the South Africa, suggests ongoing community transmission and transient vaccine effects.

Reduction of antimicrobial resistant pneumococci seven years after introduction of pneumococcal vaccine in Iceland

Penicillin non-susceptible (PNSP) and multi-resistant pneumococci have been prevalent in Iceland since early nineties, mainly causing problems in treatment of acute otitis media. The 10-valent protein conjugated pneumococcal vaccine (PHiD-CV) was introduced into the childhood vaccination program in 2011. The aim of the study was to investigate the changes in antimicrobial susceptibility and serotype distribution of penicillin non-susceptible pneumococci (PNSP) in Iceland 2011-2017. All pneumococcal isolates identified at the Landspítali University Hospital in 2011-2017, excluding isolates from the nasopharynx and throat were studied. Susceptibility testing was done according to the EUCAST guidelines using disk diffusion with chloramphenicol, erythromycin, clindamycin, tetracycline, trimethoprim/sulfamethoxazole and oxacillin for PNSP screening. Penicillin and ceftriaxone minimum inhibitory concentrations (MIC) were measured for oxacillin resistant isolates using the E-test. Serotyping was done using latex agglutination and/or multiplex PCR. The total number of pneumococcal isolates that met the study criteria was 1,706, of which 516 (30.2%) were PNSP, and declining with time. PNSP isolates of PHiD-CV vaccine serotypes (VT) were 362/516 (70.2%) declining with time, 132/143 (92.3%) in 2011 and 17/54 (31.5%) in 2017. PNSP were most commonly of serotype 19F, 317/516 isolates declining with time, 124/143 in 2011 and 15/54 in 2017. Their number decreased in all age groups, but mainly in the youngest children. PNSP isolates of non PHiD-CV vaccine serotypes (NVT) were 154/516, increasing with time, 11/14, in 2011 and 37/54 in 2017. The most common emerging NVTs in 2011 and 2017 were 6C, 1/143 and 10/54 respectively. PNSP of VTs have virtually disappeared from children with pneumococcal diseases after the initiation of pneumococcal vaccination in Iceland and a clear herd effect was observed. This was mainly driven by a decrease of PNSP isolates belonging to a serotype 19F multi-resistant lineage. However, emerging multi-resistant NVT isolates are of concern.

Pneumococcal colonisation is an asymptomatic event in healthy adults using an experimental human colonisation model.

Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported pneumococcal colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses the experimental human pneumococcal challenge (EHPC) model to explore whether pneumococcal colonisation is a symptomatic event in healthy adults. Healthy participants aged 18-50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between the two groups was compared and a correlation analysis performed. Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with serotype 6B, 17 with serotype 23F) and 8 received saline (control). In total, 14 became experimentally colonised (30.4%), all of which were inoculated with serotype 6B. There was no statistically significant difference in nasal (p = 0.45) or non-nasal symptoms (p = 0.28) between the inoculation group and the control group. In those who were colonised there was no direct correlation between colonisation density and symptom severity. In the 22% (12/52) who were co-colonised, with pneumococcus and respiratory viruses, there was no statistical difference in either nasal or non-nasal symptoms (virus positive p = 0.74 and virus negative p = 1.0). Pneumococcal colonisation using the EHPC model is asymptomatic in healthy adults, regardless of pneumococcal density or viral co-colonisation.

Molecular Detection and Serotyping of Streptococcus pneumoniae in Children with Suspected Meningitis in Northeast Iran.

Background: To date, more than 90 Streptococcus pneumoniae (S. pneumoniae) capsular serotypes are known. The prevalence of these serotypes varies according to the geographical area and the regional vaccination program. Due to the lack of regular vaccination programs for S. pneumoniae in developing countries, serotyping of the prevalent isolates is useful in selecting the correct vaccine. The present study aimed to evaluate common serotypes of pneumococcal meningitis in Bojnurd, Iran.Methods: All cerebrospinal fluid (CFS) samples suspected for bacterial meningitis were analyzed. The samples were collected during 2014-2018 in the Laboratory of Imam Reza Hospital (Bojnurd, Iran). Due to the high rate of false-negative cultures, polymerase chain reaction (PCR) was used for the detection of lytA and psaA genes of S. pneumoniae. In addition, the modified Marimon’s PCR method was used for serotyping the bacteria. The data were analyzed using Pearson’s Chi-square test.Results: Out of the 901 CSF samples, 106 cases tested positive for S. pneumoniae using the PCR method, while only 92 cases tested positive using the conventional methods. Based on the Marimon’s PCR method, serotypes 23F, 19F, 19A, 1, 14, and serogroup 6A/B were the most common types. Serogroups 18C, 15A/F, 15B/C, 9A/V, 7A/F, 11A/D/F, and 22A/F were also detected in isolates. Note that 2.8% of the samples were non-typable (NT).Conclusion: The results showed that only 13 serotypes were responsible for all meningitis cases. Pneumococcal capsular vaccine-13 (PCV-13) is the preferred choice against common serotypes of S. pneumoniae in northeast Iran.The abstract was presented in Iran’s 19th International Congress of Microbiology, as a poster and published in the congress abstracts book.

Clinical Relevance and Molecular Pathogenesis of the Emerging Serotypes 22F and 33F of Streptococcus pneumoniae in Spain

Streptococcus pneumoniae is the main bacterial cause of respiratory infections in children and the elderly worldwide. Serotype replacement is a frequent phenomenon after the introduction of conjugated vaccines, with emerging serotypes 22F and 33F as frequent non-PCV13 serotypes in children and adults in North America and other countries. Characterization of mechanisms involved in evasion of the host immune response by these serotypes is of great importance in public health because they are included in the future conjugated vaccines PCV15 and PCV20. One of the main strategies of S. pneumoniae to persistently colonize and causes infection is biofilm formation. In this study, we have evaluated the influence of capsule polysaccharide in biofilm formation and immune evasion by using clinical isolates from different sources and isogenic strains with capsules from prevalent serotypes. Since the introduction of PCV13 in Spain in the year 2010, isolates of serotypes 22F and 33F are rising among risk populations. The predominant circulating genotypes are ST43322F and ST71733F, being CC433 in 22F and CC717 in 33F the main clonal complexes in Spain. The use of clinical isolates of different origin, demonstrated that pediatric isolates of serotypes 22F and 33F formed better biofilms than adult isolates and this was statistically significant. This phenotype was greater in clinical isolates from blood origin compared to those from cerebrospinal fluid, pleural fluid and otitis. Opsonophagocytosis assays showed that serotype 22F and 33F were recognized by the PSGL-1 receptor on leukocytes, although serotype 22F, was more resistant than serotype 33F to phagocytosis killing and more lethal in a mouse sepsis model. Overall, the emergence of additional PCV15 serotypes, especially 22F, could be associated to an enhanced ability to divert the host immune response that markedly increased in a biofilm state. Our findings demonstrate that pediatric isolates of 22F and 33F, that form better biofilm than isolates from adults, could have an advantage to colonize the nasopharynx of children and therefore, be important in carriage and subsequent dissemination to the elderly. The increased ability of serotype 22F to avoid the host immune response, might explain the emergence of this serotype in the last years.

Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients

ObjectiveTo explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls.MethodsPatients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 μg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F.ResultsCompared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls.ConclusionsPrime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab.Trial registrationClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered

Effect of HIV-exposure and timing of antiretroviral treatment initiation in children living with HIV on antibody persistence and memory responses to Haemophilus influenzae type b and pneumococcal polysaccharide-protein conjugate vaccines

BackgroundWe investigated the effect of in utero HIV-exposure, timing of antiretroviral treatment (ART) initiation, and ART interruption on memory responses and persistence of immunity induced by pneumococcal (PCV) and Haemophilus influenzae type b (HibCV) polysaccharide-protein conjugate vaccines. MethodsChildren were enrolled (6–12 weeks of age), and vaccinated with a three-dose primary series of 7-valent PCV (PCV7) and HibCV at 6, 10 and 14 weeks of age. Study groups included infants infected with HIV perinatally with CD4+ ≥ 25% initiating ART following immunological or clinical deterioration (ART-Def), or immediately upon enrolment followed by interruption at 40 (ART-Immed/40w) or 96 weeks (ART-Immed/96w); and HIV-uninfected infants with (HEU), and without HIV (HIV-unexpsoed) exposure in utero. Within each group, children were randomized to receive either a booster dose of PCV7 or HibCV at 15 months of age. PCV serotype-specific and polyribosyl ribitol phosphate (PRP) IgG were measured pre-boost, two-weeks post-boost and at two-years of age. Opsonophagocytic activity (OPA) to serotypes 9V, 19F and 23F was measured post-booster dose. ResultsPersistence of IgG to PCV vaccine–serotypes and anti-PRP was similar in all groups of children living with HIV (CLWH) compared to HIV-unexposed children. Anamnestic responses to PCV and HibCV were also similar in all three groups of CLWH compared to HIV-unexposed children. CLWH, however, tended to have lower functional antibody (OPA) titers than HIV-unexposed children after the PCV booster dose for some serotypes. Immunity to PCV and HibCV was similar between the ART-Immed/40w and ART-Immed-96w groups. There were no differences in IgG kinetics between HEU and HIV-unexposed children. ConclusionsA three dose primary series, with or without PCV or HibCV booster doses in CLWH initiated on ART during infancy, would likely be similarly effective in preventing invasive bacterial disease as in HIV-unexposed children.

The antimicrobial susceptibility in adult invasive pneumococcal disease in the era of pneumococcus vaccination: A hospital-based observational study in Taiwan.

A regional antibiotic susceptibility data of common pathogens is crucial to first-line physician for clinical judgment and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiology data of drug resistance of pneumococcus causing invasive pneumococcal disease (IPD) in adults. From the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients in three hospitals in Taiwan from July 2011 to June 2015. Antibiotic resistance and serotypes of the isolates and clinical manifestations were further analyzed. A total of 150 non-duplicated isolates were collected. According to CLSI meningitis breakpoint, the proportion of ceftriaxone non-susceptible pneumococcus (CNSP) showed an increasing trend from 4.5% in 2011 to>40% in 2013-2015 (p=0.007). Serotypes 19A and 23F were significantly associated with CNSP. Imipenem and meropenem had a relative low susceptible rate of 36.7% and 50.7%, respectively. Serotypes 6A, 14, 19A and 19F were significantly associated with the non-susceptibility to these carbepanems. The increase in the prevalence of CNSP using meningitis breakpoint was observed. For treating pneumococcal meningitis, empirical monotherapy with ceftriaxone might not be adequate. Imipenem and meropenem might not be a good choice for empirical treatment of adult IPDs. Antibiotic resistance of pneumococcus to ceftriaxone, cefepime, imipenem and meropenem were associated with 13-velent pneumococcal conjugate vaccine serotypes.

Immunogenicity and safety after the third vaccination with the 23-valent pneumococcal polysaccharide vaccine in elderly patients with chronic lung disease

ABSTRACT An observational study to assess immunogenicity before and after the first, second, and third vaccinations with the 23-valent pneumococcal polysaccharide vaccine in a cohort of 16 elderly patients with chronic lung diseases was conducted. The safety of this vaccine was also compared between the first, second, and third vaccinations. Serotype-specific immunoglobulin G (IgG) and the opsonization index (OI) for serotypes 6B, 14, 19F, and 23F were analyzed, and adverse local and systemic reactions were compared. The levels of serotype-specific IgG and OI increased significantly 1 month after the first, second, and third vaccinations. Peak IgG levels were higher after the third vaccination than after the second vaccination, but the levels of serotypes 6B, 14, and 19F were not higher than after the first vaccination. Serotype-specific OIs did not differ after the third vaccination compared with the first and second vaccinations. The level of serotype-specific IgG required for killing 50% of bacteria decreased significantly 1 month after the second vaccination. This level was slightly elevated immediately before the third vaccination but decreased after the third vaccination. Although self-limited local and systemic reactions were more frequent after the second and third vaccinations than after the first vaccination, no serious systemic reactions were seen after any vaccination. These data suggest that sustained functional serotype-specific IgG is produced after the first, second, and third vaccinations and they confirm the safety of the second and third vaccinations in elderly people with chronic lung disease.

Carrier-Induced Hyporesponsiveness to Pneumococcal Conjugate Vaccines: Unraveling the Influence of Serotypes, Timing, and Previous Vaccine Dose.

BackgroundPneumococcal conjugate vaccines (PCVs) elicit lower immune response against serotypes carried before or at the time of vaccination (hyporesponsiveness) in infants. The limited studies conducted to date did not permit comprehensive insights regarding this phenomenon. This study, the largest ever conducted with both carriage and serologic endpoints, attempted to add insight on serotype-specific hyporesponsiveness in relation to the number of PCV doses administered before carriage acquisition.MethodsIn a double-blind randomized clinical trial (n = 1754 infants), 7-valent or 13-valent PCV was administered at ages 2, 4, 6, and 12 months. New acquisition was defined based on nasopharyngeal swabs at ages 2, 4, 6, 7, and 12 months. Serotype-specific immunoglobulin G levels were obtained 1 month after the infant series and 1 month after the toddler dose.ResultsA lower immune response after the infant series and the toddler dose was consistently observed for carriers of serotypes 6A, 6B, 18C, and 19F at predefined time points, with a similar trend observed in carriers of serotype 23F. In contrast, carriage of serotypes 9V, 14, and 19A did not generally affect immune responses. For some but not all serotypes, hyporesponsiveness was decreased with an increased number of vaccine doses received before acquisition. A complex interrelationship between carriage and immune response was observed between cross-reacting serotypes.ConclusionsCarrier-induced hyporesponsiveness to PCVs is common, differs among serotypes, and depends on timing of carriage acquisition and prior number of administered PCV doses.Clinical Trials RegistrationNCT00508742.

Re-validation and update of an extended-specificity multiplex assay for detection of Streptococcus pneumoniae capsular serotype/serogroup-specific antigen and cell-wall polysaccharide in urine specimens.

National surveillance of pneumococcal disease at the serotype level is essential to assess the effectiveness of vaccination programmes. We previously developed a highly sensitive extended-specificity multiplex immunoassay for detection of Streptococcus pneumoniae serotype-specific antigen in urine in the absence of isolates. The assay uses human mAbs that detect the 24 pneumococcal serotype/groups targeted by the pneumococcal conjugate vaccines (PCVs) and pneumococcal polysaccharide vaccine (PPV-23) plus some cross-reactive types and the pneumococcal cell-wall polysaccharide. However, the previous assay had some limitations, namely the reduced specificity of the serotype 7F, 20 and 22F assays, for which non-specific binding in urine samples was observed. Here we report on the further development and re-validation of a new version of the assay (version 2.1), which offers improved sensitivity towards serotypes 7F, 18C and 19F and increased specificity for serotypes 7F, 20 and 22F by replacement of some of the antibody clones with new clones. Using a panel of urine specimens from patients diagnosed with community-acquired pneumonia or pneumococcal disease, the overall clinical sensitivity of this version of the assay based on isolation of S. pneumoniae from a normally sterile site is 94.3 % and the clinical specificity is 93.6 %, in comparison with clinical sensitivity and specificity values of 96.2 % and 89.9 % in the previous assay.

Pneumococcal serotype determines growth and capsule size in human cerebrospinal fluid

BackgroundThe polysaccharide capsule is a major virulence factor of S. pneumoniae in diseases such as meningitis. While some capsular serotypes are more often found in invasive disease, high case fatality rates are associated with those serotypes more commonly found in asymptomatic colonization. We tested whether growth patterns and capsule size in human cerebrospinal fluid depends on serotype using a clinical isolate of S. pneumoniae and its capsule switch mutants.ResultsWe found that the growth pattern differed markedly from that in culture medium by lacking the exponential and lysis phases. Growth in human cerebrospinal fluid was reduced when strains lost their capsules. When a capsule was present, growth was serotype-specific: high carriage serotypes (6B, 9 V, 19F and 23F) grew better than low carriage serotypes (7F, 14, 15B/C and 18C). Growth correlated with the case-fatality rates of serotypes reported in the literature. Capsule size in human cerebrospinal fluid also depended on serotype.ConclusionsWe propose that serotype-specific differences in disease severity observed in meningitis patients may, at least in part, be explained by differences in growth and capsule size in human cerebrospinal fluid. This information could be useful to guide future vaccine design.

Distribution of PCV13 and PPSV23 Streptococcus pneumoniae serotypes in Argentinean adults with invasive disease, 2013–2017

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. To identify the serotypes most commonly associated with infection in adults in Argentina, 791 pneumococcal isolates from 56 hospitals belonging to 16 provinces and Buenos Aires city were serotyped. The isolates were submitted as part of a National Surveillance Program for invasive pneumococcal disease in adults, which started in 2013. Serotypes 3, 8, 12F, 7F and 1 were the most prevalent among adult patients. During the study period there was no significant difference in serotype distribution between the age groups studied (18–64 and ≥65 years old), except for serotype 1, 3 and 23A. Most prevalent serotypes in pneumonia were serotype 7F, 1, 12F, 8, and 3. When the clinical diagnosis was meningitis, serotype 3 and 12F were the most prevalent, whereas when the diagnosis was sepsis/bacteremia the most prevalent was serotype 8. In this work, for the 18–64-year-old group, PPSV23 and PCV13 serotypes accounted for 74.56% and 44.54% respectively of the cases in the studied period. On the other hand, for the ≥65-year-old group, these serotypes represented 72.30% and 41.42% respectively. The aim of this work was to establish the knowledge bases of the serotypes that cause invasive pneumococcal diseases in the adult population in Argentina and to be able to detect changes in their distribution over time in order to explore the potential serotype coverage of the vaccines in current use.

Exploring the broad nucleotide triphosphate and sugar-1-phosphate specificity of thymidylyltransferase Cps23FL from Streptococcus pneumonia serotype 23F.

Glucose-1-phosphate thymidylyltransferase (Cps23FL) from Streptococcus pneumonia serotype 23F is the initial enzyme that catalyses the thymidylyl transfer reaction in prokaryotic deoxythymidine diphosphate-l-rhamnose (dTDP-Rha) biosynthetic pathway. In this study, the broad substrate specificity of Cps23FL towards six glucose-1-phosphates and nine nucleoside triphosphates as substrates was systematically explored, eventually providing access to nineteen sugar nucleotide analogs.

Changing Epidemiology and Predisposing Factors for Invasive Pneumococcal Disease at Two Australian Tertiary Hospitals.

Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality in children. Universal pneumococcal conjugate vaccination has changed the epidemiology of IPD. In vaccinated children, IPD can be a marker of an underlying immunodeficiency. This is a retrospective audit of children younger than 18 years with IPD admitted to 2 tertiary pediatric hospitals in Australia between 2011 and 2017. Data on predisposing conditions, immunologic evaluation, pneumococcal serotype, antibiotic susceptibility and treatment were collected. During the 7-year period, there were 131 presentations with IPD in 127 children; 3 children had recurrent IPD. Patients presented with sepsis (41%), empyema (29%), meningitis (18%), mastoiditis (12%), pneumonia (10%) and septic arthritis (4%). In 19 (15%) presentations, risk factors for IPD were present, including malignancy, hematologic disorder, chronic liver disease, chronic kidney disease and cochlear implant. Pneumococcal serotypes were determined in 78/131 (60%) of presentations: the most frequent serotypes were 19A (19%), 3 (13%), 7F (10%) and 19F (8%) and non-vaccine serotypes 22F (8%), 35B (6%), 15A (4%) and 38 (4%). Overall, 11% of isolates were non-susceptible to ceftriaxone. Only 36 patients (32%) had an immunologic evaluation, and 4 patients had proven or probable immunodeficiency. Although pneumococcal conjugate vaccine serotypes 19A, 3, 19F and 7F remain frequent causes of IPD, non-vaccine serotypes are emerging. Our data support vancomycin treatment for children with pneumococcal meningitis given 11% of our isolates were not susceptible to ceftriaxone. It is important to consider underlying conditions predisposing to IPD in a population with high rates of pneumococcal vaccination.

Chimeric oligosaccharide conjugate induces opsonic antibodies against Streptococcus pneumoniae serotypes 19A and 19F.

Streptococcus pneumoniae 19A (ST19A) and 19F (ST19F) are among the prevalent serotypes causing pneumococcal disease worldwide even after introduction of a 13-valent pneumococcal conjugate vaccine (PCV13). Synthetic glycoconjugate vaccines have defined chemical structures rather than isolated polysaccharide mixtures utilized in marketed vaccines. Ideally, a minimal number of synthetic antigens would cover as many bacterial serotypes to lower cost of goods and minimize the response to carrier proteins. To demonstrate that a chimeric oligosaccharide antigen can induce a protective immune response against multiple serotypes, we synthesized a chimeric antigen (ST19AF) that is comprised of a repeating unit of ST19A and ST19F capsular polysaccharide each. Synthetic glycan epitopes representing only ST19A, and ST19F were prepared for comparison. Semisynthetic glycoconjugates containing chimeric antigen ST19AF induced high antibody titers able to recognize native CPS from ST19A and ST19F in rabbits. The antibodies were able to kill both strains of pneumococci. Chimeric antigens are an attractive means to induce an immune response against multiple bacterial serotypes.

Epidemiology of pneumococcal serotypes in children with outpatient pneumonia and carriers in Krasnoyarsk

Objective: The objective is to analyze the seroepidemiology and resistance of Streptococcus pneumoniae in children over 5 y.o.Methods: 57 patients with pneumonia and 186 healthy children were examined. The induced sputum and nasopharyngeal swabs were analyzed with culture and molecular assays.Results: S. pneumoniae incidence among healthy children was 15.1 %. Serotype flora was represented by 4 serotypes and 6 serogroups with prevalence of 19F, 37 (for 17.8 % each), 6АВС, 3 (for 10.7 % each). 17.8 % of strains were antibiotic resistant, four of them was 19F serotype, and one was of the 6th serogroup. All of them were multiresistant: to macrolides, lincosamides, tetracyclines, cephalosporins of II generation along with moderate resistance to penicillin. In children with pneumonia, pneumococcocus was detected in 24.6 % of cases: serotypes 19F (64.3 %), 19А (21.4 %), 23F (14.3 %). 57.1 % of strains were multiresistant and was of 19F and 19А serotypes. Phenotype of the resistance was identic to the described above except the resistance to amoxicillin: all strains were resistant to it. All given isolates were moderately resistant to ceftriaxone.Conclusions: Serotype flora of pneumococci in healthy children of school age was distinct in significant variety with high incidence of ‘mucoid’ serotypes 3 and 37 (28.6 %). In pneumonia, pneumococci of 19F and 19A types occurred significantly frequently. The main resistant serotype of S. pneumoniae in both groups was 19F with lowered sensitivity to beta-lactam antibiotics.

Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015–2017

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages.

Epidemiological and molecular characterization of invasive Streptococcus pneumoniae isolated following introduction of 7-valent conjugate vaccine in Kinki region, Japan, 2008–2013

Streptococcus pneumoniae is one of the most common bacteria causing community-acquired pneumonia and meningitis. The use of 7-valent pneumococcal conjugate vaccine (PCV7) has reduced the incidence of pneumococcal disease while changing pneumococcal population through herd immunity and non-vaccine pneumococci replacement. This study investigated molecular epidemiologic characteristics of pneumococcal strains in the Kinki region of Japan from 2008 to 2013. A total of 159 invasive pneumococcal isolates were characterized by serotyping, antibiotic susceptibility testing, PCR analysis of penicillin-binding protein genes, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). In adult populations, pediatric PCV7 introduction decreased isolates expressing PCV7 serotypes via herd immunity and increased isolates expressing non-PCV7 serotypes. The rate of penicillin resistance and isolates with alterations in all three pbp genes was higher in PCV7 type isolates than in non-PCV7 type isolates. In MLST analysis, all of serotype 19F isolates were of the same sequence type, ST236, which is the antimicrobial-resistant clone Taiwan19F-14, and the majority of serotypes 23F and 19A isolates were of ST1437 and ST3111 respectively, which are the predominant clones of antimicrobial-resistant pneumococci in Japan. In PFGE profiles, serotype 6B-ST2224, serotype 19F-ST236, serotype 19A-ST3111, and serotype 23F-ST1437 formed six separate clusters composed of genetically identical strains, and genetically identical serotype 22F-ST433 formed two different clusters between the pre- and post-PCV7 period. The results of molecular analysis suggest the spread and persistence of these identical antimicrobial resistant clones in the Kinki region and genetic changes of epidemic clone serotype 22F-ST433 before and after pediatric PCV7 introduction.

The shifting epidemiology and serotype distribution of invasive pneumococcal disease in Ontario, Canada, 2007-2017.

BackgroundOntario, Canada introduced a publicly-funded 13-valent pneumococcal conjugate vaccine (PCV13) for infants in 2010, replacing the 10-valent (PCV10, 2009–2010) and the 7-valent (PCV7, 2005–2009) conjugate vaccine programs; a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been available for older adults since 1996. We examined the epidemiology and serotype distribution of invasive pneumococcal disease (IPD) in Ontario in the context of provincial immunization programs.MethodsWe included confirmed IPD cases reported in Ontario between 2007 and 2017. We grouped serotypes according to Ontario’s current immunization program (PCV13, PPV23, and non-vaccine-preventable) and calculated incidence rates (per 100,000 population) using population data.ResultsBetween 2007 and 2017, annual incidence of IPD in Ontario ranged between 7.3 and 9.7/100,000 per year. Measures of illness severity were high throughout the period of surveillance. After PCV13 program implementation in 2010, incidence due to PCV13 serotypes decreased significantly across all age groups, with the greatest reductions in children <5 years and adults ≥65 years. Conversely, incidence due to PPV23 unique serotypes increased significantly between 2007 and 2017, with the greatest increases observed in adults 50–64 years (1.4 to 3.5/100,000) and ≥65 years (2.3 to 7.2/100,000). Similar increases were observed in incidence due to non-vaccine-preventable serotypes among all age groups, except infants <1 year. Within specific serotypes, incidence due to serotypes 3 (0.42 to 0.98/100,000) and 22F (0.31 to 0.72/100,000) increased significantly between 2007 and 2017, while incidence due to serotypes 19A and 7F decreased significantly during the PCV13 period (2010–2017).ConclusionsEight years after PCV13 implementation in Ontario, our data suggest both direct and indirect effects on serotype-specific incidence in young children and older adults. However, overall provincial rates have remained unchanged, and IPD continues to be a severe burden on the population. The rising incidence of IPD due to PPV23 unique and non-vaccine-preventable serotypes, and the growing burden of serotypes 3 and 22F, require further study.