13-valent Conjugate Research Articles

Serotypes and Antimicrobial Susceptibility of Nasopharyngeal Isolates of Streptococcus pneumoniae from Children Less Than 5 Years Old in Egypt.

PurposeStreptococcus pneumoniae (S. pneumoniae) is the etiology of severe and life-threatening infections in children less than 5 years old. Though pneumococcal conjugate vaccines (PCVs) are effective in the prevention of pneumococcal infections, yet they are not included in the National Immunization Program in Egypt pending the identification of pathogenic serotypes. As S. pneumoniae colonization of the pharynx predisposes to pneumonia and invasive pneumococcal disease (IPD) caused by the colonizing serotypes, identification of the nasopharyngeal (NP) serotypes can be a surrogate to the invasive serotypes. In this study, we aimed to 1. Identify the serotypes and antimicrobial susceptibility testing (AST) of Streptococcus pneumoniae colonizing the nasopharynx of Egyptian children younger than 5 years in two successive winter seasons. 2. Correlate the identified serotypes with vaccine coverage of the 13-valent conjugate pneumococcal vaccines (PCV13). 3. Compare the serotypes and AST of S. pneumoniae from NP to those of IPD that were routinely identified in our clinical laboratory during the study period.Materials and MethodsThe study was conducted in two successive winter seasons (December 2015–March 2016; December 2016–March 2017). We enrolled 334 children, aged 6 months to 5 years, attending the outpatient general clinics of Cairo University Children Hospital, excluding those with fever, signs of infection, history of antibiotic intake or hospitalization in the preceding month. We tested NP swabs for S. pneumoniae by culture and real-time PCR. Serotyping was performed by sequential multiplex PCR for all positive samples. AST was done to S. pneumoniae isolates by Vitek-2™ (BioMérieux, Marcy-L’Etoile, France). We included routinely detected S. pneumoniae from sterile body sites during the study period, and identified their serotypes and AST.ResultsPCR was positive for pneumococci in 217 out of 334 pharyngeal swabs (65%), including 186 typable samples. The most common serotypes were serotypes 1, 6ABC, 19 F, 5 and 18ABC. By culture, we isolated only 110 out of 334 pharyngeal swabs (32.9%). The theoretical coverage of the PCV13 vaccine for the detected serotypes was 77.4%. The AST of NP isolates revealed low susceptibility rates to all antimicrobials except for vancomycin, linezolid, levofloxacin and clindamycin. During the study period, we identified 40 IPD; 21 identified by PCR and 19 by culture. The commonest pneumococcal serotypes were 1, 18ABC, 6ABC and 5. The PCV13 coverage was 75%. By Vitek-2, the isolates showed 100%, 100%, 94.7%, 89.5%, 84.2%, 84.2% and 78.9% susceptibility to vancomycin, linezolid, clindamycin, levofloxacin, penicillin, cefotaxim and erythromycin, respectively.ConclusionBased on the serotype vaccine coverage and the emerging antimicrobial resistance of S. pneumoniae, PCVs will be valuable to Egyptian children.

Incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate pneumococcal vaccine in British Columbia: A retrospective cohort study.

A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.

An Increase in Invasive Pneumococcal Disease

Following the introduction in 2000 of the pneumococcal 7-valent conjugate vaccine (PCV7), the incidence of invasive pneumococcal disease (IPD)

Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis

The phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis. Patients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine [23-PPV]), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group). Positive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group. Peripherally B-cell-depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected. This study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta-treated patients, but they can still be expected to be protective. NCT02545868.

Serotype distribution of Streptococcus pneumoniae isolated from children in Moscow before
 and after introduction of 13-valent pneumococcal conjugate vaccination

Introduction. In 2014, a 13-valent conjugated pneumococcal vaccine (PCV13) was introduced into the children’s immunization program in Russia. In this regard, to describe and analyze the epidemiology of pneumococcal infections, it is important to study and evaluate the distribution of serotypes and the effect of PCV13 vaccination on the serotype distribution of the nasopharyngeal Streptococcus pneumoniae isolates isolated in children from 2010 to 2018. Materials and methods. The study included 708 nasopharyngeal pediatric pneumococcal isolates recovered from 2010 to 2018, in patients under 5 years of age, who received inpatient and outpatient care at the National Medical Research Center for Children’s Health (Moscow). Serotyping was performed using antisera and / or molecular typing by PCR Results. In total, 33 different serotypes were identified in the S. pneumoniae collection. Six predominant serotypes were accounted for 68.6% of the total distribution and included serotypes: 19F, 6B, 23F, 14, 15B/C, 6A. The average prevalence of vaccine serotypes was of 77.7% in 2010-2015, with a significant decrease to 52% in 2018, which was accompanied by an increase in the prevalence of serotype 15B/C (16% in 2018) and serotypes 11A and 23A, from 1.1% in 2010 to 9.3% and 8% respectively in 2018. Conclusion. The use of PCV13 vaccination in Russia has led to a significant decrease in the carriage of pneumococcal vaccine serotypes. These results emphasize the need for careful monitoring of an ever-changing pneumococcal population.

Serotypic distribution and antimicrobial resistance of Streptococcus pneumoniae in Chinese children under 5 years after the introduction of the 13-valent conjugate pneumococcal vaccine: protocol for a scoping review

The World Health Organization (WHO) recommends that pneumococcal conjugate vaccines (PCVs) be included in immunization programs worldwide. In China, the 7-valent pneumococcal conjugate vaccine (PREVNAR 7®) was authorized in 2008 but was not included in the national immunization programs. In 2016, PREVNAR 13®, a 13-valent pneumococcal conjugate vaccine (PCV13), was licensed for optional use in China. We will conduct a scoping review of the distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in children aged under 5 years in China since the introduction of PCV13. We will obtain data from PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Med Online. We will also review epidemiological data from WHO and the China Antimicrobial Surveillance Network (CHINET). Our analysis will include the condition of interest, the intervention, and the geographical region. All types of studies will be eligible for inclusion in the study database if they meet the inclusion criteria. This scoping review is intended to outline how S. pneumoniae serotypes are distributed, and it will map their antimicrobial resistance in children aged under 5 years in China. The results of this study will provide useful information on the impact of PCV13 in China.

Efficacy and Effectiveness of the PCV-10 and PCV-13 Vaccines Against Invasive Pneumococcal Disease.

Pneumococcal conjugate vaccines (PCVs) (pneumococcal 13-valent conjugate vaccine [PCV-13] and pneumococcal 10-valent conjugate vaccine [PCV-10]) are available for prevention of pneumococcal infections in children. To determine the vaccine effectiveness (VE) of PCV-13 and PCV-10 in preventing invasive pneumococcal disease (IPD) and acute otitis media (AOM) in children <5 years. Systematic searches of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Cochrane. Eligible studies examined the direct effectiveness and/or efficacy of PCV-10 and PCV-13 in reducing the incidence of disease in healthy children <5 years. Two reviewers independently conducted data extraction and methodologic quality assessment. Significant effectiveness against vaccine-type IPD in children ≤5 years was reported for ≥1 dose of PCV-13 in the 3 + 1 (86%-96%) and 2 + 1 schedule (67.2%-86%) and for PCV-10 for the 3 + 1 (72.8%-100%) and 2 + 1 schedules (92%-97%). In children <12 months of age, PCV-13 VE against serotype 19A post-primary series was significant for the 3 + 1 but not the 2 + 1 schedule. PCV-10 crossprotection against 19A was significant in children ≤5 years with ≥1 dose (82.2% and 71%). Neither PCVs were found effective against serotype 3. PCV-13 was effective against AOM (86%; 95% confidence interval [CI]: 61 to 94). PCV-10 was effective against clinically defined (26.9%; 95% CI: 5.9 to 43.3) and bacteriologically confirmed AOM (43.3%; 95% CI: 1.7 to 67.3). Because of the large heterogeneity in studies, a meta-analysis for pooled estimates was not done. Both PCVs afford protection against pneumococcal infections, with PCV-10 protecting against 19A IPD, but this VE has not been verified in the youngest age groups.

Serotypic distribution and antimicrobial resistance of Streptococcus pneumoniae in Chinese children under 5 years after the introduction of the 13-valent conjugate pneumococcal vaccine: protocol for a scoping review.

The World Health Organization (WHO) recommends that pneumococcal conjugate vaccines (PCVs) be included in immunization programs worldwide. In China, the 7-valent pneumococcal conjugate vaccine (PREVNAR 7®) was authorized in 2008 but was not included in the national immunization programs. In 2016, PREVNAR 13®, a 13-valent pneumococcal conjugate vaccine (PCV13), was licensed for optional use in China. We will conduct a scoping review of the distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in children aged under 5 years in China since the introduction of PCV13. We will obtain data from PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Med Online. We will also review epidemiological data from WHO and the China Antimicrobial Surveillance Network (CHINET). Our analysis will include the condition of interest, the intervention, and the geographical region. All types of studies will be eligible for inclusion in the study database if they meet the inclusion criteria. This scoping review is intended to outline how S. pneumoniae serotypes are distributed, and it will map their antimicrobial resistance in children aged under 5 years in China. The results of this study will provide useful information on the impact of PCV13 in China.

Neumonía adquirida en la comunidad. Normativa de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Actualización 2020

The guidelines for community-acquired pneumonia, last published in 2010, have been updated to provide recommendations based on a critical summary of the latest literature to help health professionals make the best decisions in the care of immunocompetent adult patients. The methodology was based on 6 PICO questions (on etiological studies, assessment of severity and decision to hospitalize, antibiotic treatment and duration, and pneumococcal conjugate vaccination), agreed by consensus among a working group of pulmonologists and an expert in documentation science and methodology. A comprehensive review of the literature was performed for each PICO question, and these were evaluated in in-person meetings. The American Thoracic Society guidelines were published during the preparation of this paper, so the recommendations of this association were also evaluated. We concluded that the etiological source of the infection should be investigated in hospitalized patients who have suspected resistance or who fail to respond to treatment. Prognostic scales, such as PSI, CURB 65, and CRB65, are useful for assessing severity and the decision to hospitalize. Different antibiotic regimens are indicated, depending on the treatment setting - outpatient, hospital, or intensive care unit - and the resistance of PES microorganisms should be calculated. The minimum duration of antibiotic treatment should be 5 days, based on criteria of clinical stability. Finally, we reviewed the indication of the 13-valent conjugate vaccine in immunocompetent patients with risk factors and comorbidity.

Estimating the Impact of Switching from a Lower to Higher Valent Pneumococcal Conjugate Vaccine in Colombia, Finland, and The Netherlands: A Cost-Effectiveness Analysis.

IntroductionWidespread use of ten-valent (Synflorix™, GSK) or 13-valent (Prevenar 13™; Pfizer) conjugate vaccination programs has effectively reduced invasive pneumococcal disease (IPD) globally. However, IPD caused by serotypes not contained within the respective vaccines continues to increase, notably serotypes 3, 6A, and 19A in countries using lower-valent vaccines. Our objective was to estimate the clinical and economic benefit of replacing PCV10 with PCV13 in Colombia, Finland, and The Netherlands.MethodsCountry-specific databases, supplemented with published and unpublished data, informed the historical incidence of pneumococcal disease as well as direct and indirect medical costs. A decision-analytic forecasting model was applied, and both costs and outcomes were discounted. The observed invasive pneumococcal disease (IPD) trends from each country were used to forecast the future number of IPD cases given a PCV13 or PCV10 program.ResultsOver a 5-year time horizon, a switch to a PCV13 program was estimated to reduce overall IPD among 0–2 year olds by an incremental − 37.6% in Colombia, − 32.9% in Finland, and − 26% in The Netherlands, respectively, over PCV10. Adults > 65 years experienced a comparable incremental decrease in overall IPD in Colombia (− 32.2%), Finland (− 15%), and The Netherlands (− 3.7%). Serotypes 3, 6A, and 19A drove the incremental decrease in disease for PCV13 over PCV10 in both age groups. A PCV13 program was dominant in Colombia and Finland and cost-effective in The Netherlands at 1 × GDP per capita (€34,054/QALY).ConclusionIn Colombia, Finland, and The Netherlands, countries with diverse epidemiologic and population distributions, switching from a PCV10 to PCV13 program would significantly reduce the burden of IPD in all three countries in as few as 5 years.Electronic supplementary materialThe online version of this article (10.1007/s40121-020-00287-5) contains supplementary material, which is available to authorized users.

Practical experience of using pneumococcal thirteen-valent conjugate vaccine among premature infants

Aim. To ground the necessity of premature infants vaccination against pneumococcal infection and estimate the reactogenicity and immune activity of pneumococcal 13-valent conjugate vaccine when vaccinating infants with different degree of prematurity.&#x0D; Materials and methods. The clinical study enclosed 88 children including 16 (18.2 0.25 %) infants with extremely low birth body mass (ELBM) and 28 infants (31.8 0.32 %) with very low body mass (VLBM). The mean gestation age was 31 0.41 weeks. The mean birth weight was 1530 66.58 grams. Bronchopulmonary dysplasia was diagnosed in 27 0.25 % of infants. Thirty one infants underwent assessment of the concentration of the total level of specific blood serum IgG antibodies to S. Pneumonia antigens contained in vaccine. The mean age of these infants was 9.71 0.74 months, the mean gestation age at birth 30 0.41 weeks (25 to 41 weeks). The mean birth weight 1441 66.58 grams, ELBM 14 infants, VLBM 18 infants.&#x0D; Results. The mild general postvaccinal reactions were noted in 11.3 1.24% of infants, which were arrested for 2 days with no drugs used. The moderate and severe reactions were observed in 2.27 0.62 % of infants. No local postvaccinal reactions were registered. When studying the concentration of the total level of specific IgG antibodies to S. Pneumonia antigens, there was revealed a more than 4- fold increase in geometric mean of pneumococcal antibody titer that proves a high immunogenicity of this vaccine in premature infants. A high level of pneumococcal antibodies after vaccination was reached in 24 infants (75 1.24 % of infants).&#x0D; Conclusion. The necessity of immunization of premature infants against pneumococcal infection was scientifically grounded. The application of conjugate 13-valent pneumococcal vaccine among premature infants confirmed a high profile of its safety and high immunogenicity. Improvement of communicative habits between parents and medical personnel regarding the necessity of vaccination of premature infants against pneumococcal infection, as an advanced technology, will permit to provide a timely coverage of infants with immunization (98 %).

Vaccination against Pneumococcal Infections of High-Risk People: Pharmacoeconomic Aspects

Relevance. Vaccination of people at high risk against pneumococcal infection with a 13-valent conjugate vaccine (PCV13) can significantly reduce the corresponding incidence and mortality.The aim of the work was to assess the pharmacoeconomic aspects of vaccination of 65 year olds with a high risk of pneumococcal infection.Material and methods. The analysis was carried out by the method of Markov modeling from the position of the health care system. The time horizon is 5 and 15 years. It was assumed that vaccination is carried out with 1 dose of PCV13 and 1 dose of polysaccharide pneumococcal vaccine (PPV23) after 8 weeks with revaccination with 1 dose of PPV23 after 5 years. The costs of treatment of pneumococcal infections were calculated on the basis of the Compulsory medical insurance rates for St. Petersburg in 2019. The costs of vaccination were calculated on the basis of the price of auctions for the purchase of PCV13 and PPV23 for 2019.Results. For 15 years, vaccination of 100 ths people from the high risk group will prevent 1.7 ths cases of community-acquired pneumonia, 1.4 ths cases of invasive pneumococcal infections, and 397 cases of pneumococcal infections deaths. The cost-effectiveness ratio with a 15-year horizon is 161.4 ths rubles/quality-adjusted life year gained (QALY). Even if the time horizon is reduced to 5 years, vaccination can be considered as an economically highly effective intervention (cost-effectiveness ratio –571.9 ths rubles/QALY). At the same time, in 5 years, 37.6% of the money spent on vaccination will be returned to the budget of the health care system, and in 15 years – 49.3%.Conclusion. Vaccination of citizens of the Russian Federation from a high-risk group against pneumococcal infection can be considered as a socially and economically highly effective intervention that provides a significant reduction in the incidence and mortality caused by it.

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

BackgroundHemophagocytic lymphohistiocytosis (HLH) is an infrequent but life-threatening disease due to excessive immune activation. Secondary HLH can be triggered by infections, autoimmune diseases, and malignant diseases. Streptococcus pneumoniae is a pathogenic bacterium responsible for invasive pneumococcal disease (IPD) such as meningitis and bacteremia. Although the pneumococcal conjugate vaccine (PCV) has led to reductions in IPD incidence, cases of IPD caused by serotypes not included in PCV are increasing. There are few reports of secondary HLH caused by IPD in previously healthy children. We herein report a rare case of a previously healthy boy with secondary HLH complicating IPD of serotype 23A, which is not included in the pneumococcal 13-valent conjugate vaccine (PCV-13).Case presentationAn 11-month-old boy who had received three doses of PCV-13 was hospitalized with prolonged fever, bilateral otitis media, neutropenia and elevated C-reactive protein (CRP) levels. Blood culture on admission revealed S. pneumoniae, leading to a diagnosis of IPD. HLH was diagnosed based on a prolonged fever, neutropenia, anemia, hepatosplenomegaly, hemophagocytosis in the bone marrow, and elevated serum levels of triglycerides, ferritin, and soluble interleukin-2 receptor. He received broad-spectrum antibiotics and intravenous immunoglobulins for IPD and high-dose steroid pulse therapy and cyclosporine A for HLH; thereafter, his fever resolved, and laboratory findings improved. The serotype of the isolated S. pneumoniae was 23A, which is not included in PCV-13.ConclusionsIt is important to consider secondary HLH as a complication of IPD cases with febrile cytopenia or hepatosplenomegaly, and appropriate treatment for HLH should be started without delay.

Epidemiologic Benefits of Pneumococcal Vaccine Introduction into Preventive Vaccination Programs.

Vaccination against pneumococci is one of the most effective methods of preventing pneumococcal diseases. Currently, 10- and 13-valent conjugate vaccines (PCV10 and PCV13) and 23-valent polysaccharide vaccine (PPSV23) are used. Only the conjugate vaccines are used in children. The PCV can be used both in children and adults, but children can receive only PCV. A side effect of vaccination was that bacterial serotypes not included in a vaccine started increasingly emerging in pneumococcal infections, replacing the serotypes eliminated by the vaccine. The basic vaccination schedule consists of three or four doses, according to the country's recommendation. In Poland, it consists of two primary doses followed by a supplementary dose of the PCV-10, with some modifications in case of specific risk factors. The use of preventive vaccinations has helped reduce antibiotic resistance, as serotypes characterized by a rapid acquisition of drug resistance are included in the vaccine serologic spectrum, making their environment prevalence decrease. The research is currently underway on conjugate vaccines that contain a greater number of bacterial serotypes and on more universal vaccines that would eliminate the emergence of new serotypes.

Активность системного ювенильного идиопатического артрита у детей, иммунизированных 13-валентной конъюгированной пневмококковой вакциной: проспективное когортное исследование

Evaluation of the safety profile of vaccines in patients with rheumatic diseases requires an assessment of their impact on disease activity. The effect of antipneumococcal vaccination on the activity of systemic juvenile idiopathic arthritis (sJIA) has not been studied so far. Objective. To evaluate the dynamics of sJIA activity after immunization with pneumococcal 13-valent conjugate vaccine (PCV13) of patients receiving biologicals. Patients and methods. This study included patients with sJIA in remission or active disease receiving biologicals during inpatient treatment and vaccinated with PCV13. To evaluate the effect of immunization on sJIA activity, we measured serum levels of high-sensitivity C-reactive protein (hs-CRP) and calprotectin. In addition to that, we assessed the number of new cases, when concentration of these markers was above the upper limit (UL) 4 weeks after PCV13 administration. Results. In 18 out of 53 patients in remission (34%) and 3 out of 25 patients with active sJIA (12%), hs-CRP levels were undetectable (0.1 mg/L) at both time-points (baseline and after 4 weeks). Among those with detectable hs-CRP levels in at least one time-point 4 weeks after vaccination, patients in remission (n = 35) had no significant changes in hs-CRP (median -0.17 mg/mL; 95% CI -0.84…0.41), whereas patients with active sJIA (n = 22) demonstrated a 3-fold decrease in hs-CRP level (median -0.94 mg/mL (95% CI -3.93…0.05). We observed no significant difference in calprotectin levels in the groups. Concentration of hs-CRP above the UL 4 weeks after vaccination was detected in 2 out of 53 sJIA patients in remission (4%) and none of the patients with active sJIA. Сoncentration of calprotectin above the UL 4 weeks after vaccination was detected in 8 out 53 (15%) and 5 out 25 (20%) sJIA patients in remission and with active disease, respectively. Conclusion. Vaccination against pneumococcal infection in patients with sJIA led to an increase in the level of highly sensitive laboratory markers of sJIA activity in 4–20% of patients. Key words: disease activity, safety, high-sensitivity C-reactive protein, biological drugs, calprotectin, juvenile idiopathic arthritis, pneumococcal 13-valent conjugate vaccine

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.

Prevalence of Bacteremia in Febrile Patients With Sickle Cell Disease: Meta-Analysis of Observational Studies.

Pneumococcal vaccination has decreased the bacteremia rate in both the general pediatric and sickle cell disease (SCD) populations. Despite this decrease, and an increasing concern for antibiotic resistance, it remains standard practice to obtain blood cultures and administer antibiotics in all febrile (>38.5°C) patients with SCD. We conducted a systematic review and meta-analysis of the available studies of the prevalence of bacteremia in febrile patients with SCD. We searched the medical literature up to November 2018 in PUBMED, EMBASE, and Web of Science with terms epidemiology, prevalence, bacteremia, and sickle cell anemia. We only included studies with patients after 2000, when the pneumococcal 7-valent conjugate (PCV7) vaccine became widely available. The prevalence of bacteremia [95% confidence interval (CI)] was calculated by dividing the number of positive blood cultures by the number of febrile episodes. The I2 statistic measured heterogeneity between prevalence estimates. Bias in our studies was quantified by the Newcastle-Ottawa Quality Assessment Scale. Our search identified 228 citations with 10 studies meeting our inclusion/exclusion criteria. The weighted prevalence of bacteremia across all studies was 1.9% (95% CI, 1.22%-2.73%), and for Streptococcus pneumoniae bacteremia, it was 0.31% (95% CI, 0.16%-0.50%). Risks for bacteremia except central lines could not be determined because of the low prevalence of the outcome. There appears to be a need to develop a risk stratification strategy to guide physicians to manage febrile patients with SCD based on factors including, but not limited to, history and clinical examination, vaccination status, use of prophylactic antibiotics, laboratory values, likely source of infection, and accessibility to health care.

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.

The impact of clinical pharmacy services on pneumococcal vaccine frequency and appropriateness in a family medicine clinic

ObjectiveTo evaluate the impact of an ambulatory clinical pharmacy service (inclusive of immunization needs assessments) on the frequency and appropriateness of pneumococcal vaccine administration in a family medicine clinic. MethodsThis cohort study had an observational and retrospective design and included patients who received pneumococcal vaccines at a family medicine clinic in a medically underserved area in Southwestern Pennsylvania across a 42-month period from January 1, 2015, to June 30, 2018. The outcome measures included the administration and appropriateness of pneumococcal 13-valent conjugate (PCV13) and pneumococcal 23-valent polysaccharide (PPSV23) vaccines across 3 time cohorts including before, during, and after the establishment of a clinical pharmacy service. ResultsA total of 457 pneumococcal vaccines were administered, including 198 (43.3%) PCV13 and 259 (56.7%) PPSV23, across all time cohorts. Overall vaccine administration per month increased by 143% with the introduction of a dedicated clinical pharmacy service, including a 270% increase for PCV13 and an 87% increase for PPSV23. A strong correlation was found between recommendations made and doses administered for both pneumococcal vaccines (r = 0.89; P < 0.003). Across the entire time frame, PPSV23 administrations were appropriate in more than 96% of instances, whereas the appropriateness of PCV13 administrations were statistically significantly improved after the introduction of a fully dedicated clinical pharmacy service (58.5% vs. 90.8%; P < 0.05). The appropriateness of vaccine administration remained high even after the reduction of clinical pharmacy services. ConclusionClinical pharmacy service implementation in a family medicine clinic was associated with increased pneumococcal vaccine administration and increased appropriateness of PCV13 administrations.

Kawasaki Disease Associated with Pneumococcal Infection

We report a case of a 15-month-old Japanese girl with Kawasaki disease (KD) associated with bacteremia caused by Streptococcus pneumoniae (S. pneumoniae) 12F (a nonvaccine serotype). The patient had completed the pneumococcal 13-valent conjugate vaccination according to the immunization schedule for children in Japan. She presented at the emergency department of our hospital with fever for 3 days and all other KD symptoms and was admitted. Despite the detection of S. pneumoniae 12F in the blood culture on admission, initial treatment for KD with 2 g/kg of intravenous immunoglobulin and 30 mg/kg/day of oral aspirin without antibiotic administration improved both KD symptoms and bacteremia. The patient did not develop coronary aneurysm. Even though there were no reports of KD with bacteremia caused by S. pneumoniae (except in our case), the presence of bacteremia may not affect the treatment response or coronary artery outcome if KD is appropriately treated.