Nasopharyngeal carriage of Streptococcus pneumoniae among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction.

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged <5 years before 13-valent PCV (PCV13) introduction. Nasopharyngeal swabs were collected during visits to community integrated health service posts at one peri-urban and one rural study site. Specimens were analyzed by culture, and isolates were serotyped using sequential multiplex polymerase chain and Quellung reaction. Antibiotic susceptibility was performed by broth microdilution method. We enrolled 1,007 children in Gunungkidul District, Yogyakarta (peri-urban) and 815 in Southwest Sumba, East Nusa Tenggara (rural). Pneumococcal carriage prevalence was 30.9% in Gunungkidul and 87.6% in Southwest Sumba (combined: 56.3%). PCV13 serotypes (VT) carriage was 15.0% in Gunungkidul and 52.6% in Southwest Sumba (combined: 31.8%). Among pneumococcal isolates identified, the most common VT were 6B (16.4%), 19F (15.8%), and 3 (4.6%) in Gunungkidul (N = 323) and 6B (17.6%), 19F (11.0%), and 23F (9.3%) in Southwest Sumba (N = 784). Factors associated with pneumococcal carriage were age (1-2 years adjusted odds ratio (aOR) 1.9, 95% CI 1.4-2.5; 3-4 years aOR 1.5, 95% CI 1.1-2.1; reference <1 year), other children <5 years old in the household (aOR 1.5, 95% CI 1.1-2.0), and presence of ≥1 respiratory illness symptom (aOR 1.8, 95% CI 1.4-2.2). Overall, 61.5% of the pneumococcal isolates were non-susceptible to ≥1 antibiotic class and 13.2% were multi-drug non-susceptible (MDNS) (non-susceptible to ≥3 classes of antibiotics). Among 602 VT isolates, 73.9% were non-susceptible and 19.9% were MDNS. These findings are critical to establish a pre-PCV13 carriage prevalence and demonstrate the complexity in evaluating the impact of PCV13 introduction in Indonesia given the wide variability in the carriage prevalence as shown by the two study sites.

Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

BACKGROUND: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. METHODS: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. RESULTS: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). CONCLUSION: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

Facilitating pneumococcal vaccination among high-risk adults: Impact of an assertive communication training program for community pharmacists.

BACKGROUND: Community pharmacies are vital access points to provide a range of vaccines to adults, including pneumococcal vaccines; however, despite a growth in the number of vaccines given at these sites, the most recent rates of adults being immunized against pneumococcal disease remain below the goals set by Health People 2020. Low patient awareness is a leading reason for suboptimal vaccination rates, suggesting that a need exists to improve provider communication in recommending pneumococcal vaccination in high-risk adults. OBJECTIVES: To evaluate the impact of a communication training program to improve pharmacist promotion of the pneumococcal vaccine among high-risk adults in Tennessee. METHODS: A multiphase training program was initiated in partnership with 2 regions of a nationwide community pharmacy chain (n = 100) focusing on improving evidence-based, presumptive recommendations related to pneumococcal vaccination. All locations were randomized to one of 3 arms on the basis of training intensity: (1) no training; (2) online training only; and (3) online and in-person simulation training. The program focused on improving evidence-based, pharmacist vaccine recommendations using health behavior theories, sales techniques, and improvisation provided through online and in-person simulation training. Changes in vaccinations (compared with the same 6-month period in the previous year) and provider self-efficacy were evaluated by Mann-Whitney U tests, chi-square tests, and general linear models. RESULTS: Completing the full training program led to nominal changes in pharmacist self-efficacy across the 6 items measured (P > 0.05). Overall counts of all pneumococcal vaccines were lower (-11.3%) across all stores in the period after training; however, a small increase (2.1%) was observed in the stores that underwent the full training, versus changes of -22.0% (P = 0.084) and -9.4% (P = 0.199) in control and online-only training comparisons, respectively. CONCLUSIONS: Pharmacists' vaccine-related self-efficacy may be improved through an evidence-based communication training program, but a more holistic focus on all recommended adult vaccines may be necessary to realize meaningful improvements.

Clonal lineages and antimicrobial resistance of nonencapsulated Streptococcus pneumoniae in the post-pneumococcal conjugate vaccine era in Japan.

OBJECTIVES: The emergence and spread of nonencapsulated Streptococcus pneumoniae (NESp) is a public health concern in the post-pneumococcal conjugate vaccine era. We analyzed the prevalence, molecular characteristics, and antimicrobial resistance of NESp responsible for noninvasive infections in northern Japan. METHODS: NESp isolates were identified using molecular and phenotypical methods among 4463 S. pneumoniae isolates from noninvasive infection cases during 4 study periods between January 2011 and January 2019. NESp isolates were analyzed for antimicrobial susceptibility, genotype, and virulence-associated genes. RESULTS: Seventy-one NESp isolates were identified (1.6% of total clinical isolates) and assigned to the null capsule clade (NCC)1 (pspK+) (94.4%) or NCC2 (aliC+/aliD+) (5.6%). The dominant sequence types (STs) were ST7502 (23.9%), ST4845 (19.7%), ST16214 (11.3%), ST11379 (9.9%), and ST7786 (7.0%). These 5 dominant STs and all 7 novel STs were related to the sporadic NESp lineage ST1106 or PMEN clone Denmark14-ST230. High non-susceptibility rates of NESp were observed for trimethoprim-sulfamethoxazole, erythromycin, and tetracycline (>92.9%), and multidrug resistance was observed in 88.7% of the NESp isolates, including all ST7502, ST4845, and ST11379 isolates. CONCLUSIONS: The study revealed that the dominant clonal groups of NESp were associated with a high prevalence of non-susceptibility to antimicrobials in northern Japan.

Risk of infection associated with Janus Kinase (JAK) inhibitors and biological therapies in inflammatory intestinal disease and rheumatoid arthritis. Prevention strategies. / Riesgo de infección asociado a los inhibidores de las quinasas Janus (JAK) y las terapias biológicas en enfermedad inflamatoria intestinal y artritis reumatoide. Estrategias de prevención.

Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive. These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.

Paradoxical health care utilization patterns among children in Korea who did not receive mandatory pneumococcal vaccination.

BACKGROUND: Unvaccinated children in the National Immunization Program (NIP) are a public health concern. We used Korean national population data to analyze health care utilization patterns of NIP-eligible children and identify the unvaccinated group. METHODS: Pneumococcal vaccination (PCV) records were reviewed to determine the vaccination status of children born between 2013 and 2015. Children who received three doses or more from a 3 + 1 schedule were defined as vaccinated, while those who had not received any pneumococcal vaccinations were defined as unvaccinated. Corresponding health care utilization records were retrieved from the National Health Insurance Review and Assessment Service. The incidence of combined pneumococcal infections and health care utilization rates were estimated and the proportion of complementary and alternative medicine (CAM) utilization among the total health care utilization records was measured. RESULTS: In total, 26,893 (2.1%) of 1,272,685 children remained unvaccinated. The incidence of pneumococcal infection was lower in unvaccinated children, at 10.1 cases (9.8-10.3) per 1000 person-months. However, their health care utilization was significantly lower than that noted for vaccinated children (hospital visit rate: 26.6 (95% confidence interval [CI] 26.5-26.7) vs. 3.2 (3.2-3.3) visits annually), indicating underdetection. CAM treatment was sought at least three times often more in unvaccinated children than in vaccinated children (3.5% vs. 1.1%). CONCLUSION: Unvaccinated children showed significantly lower utilization of overall health care than the vaccinated children; however, a higher preference for CAM was noted among unvaccinated children than among vaccinated children. These differences in care-seeking patterns should be considered when identifying unvaccinated children and providing protection through vaccination programs.

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

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Phosphorylcholine intranasal immunization with a 13-valent pneumococcal conjugate vaccine can boost immune response against Streptococcus pneumoniae.

OBJECTIVE: This study aimed to investigate whether systemic immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) followed by intranasal (IN) immunization with phosphorylcholine (PC) can boost immune response against Streptococcus pneumoniae. MATERIALS AND METHODS: Two weeks after the intraperitoneal (IP) injection of PCV13, mice were divided into two groups (mice requiring another IP injection of PCV13 and mice requiring PC-keyhole limpet hemocyanin IN immunization in combination with cholera toxin as a mucosal adjuvant) to compare the magnitude of systemic and mucosal immune responses against S. pneumoniae and PC. RESULTS: Serum immunoglobulin (Ig) G antibody titer against the vaccine strains of S. pneumoniae was similar between the PCV13 systemic immunization group and PC IN immunization group, while the serum IgG antibody titer against PC was significantly higher in the PC IN immunization group. PC-specific IgA antibody titer in the nasal lavage and PC-specific IgA-producing cell number in the nasal mucosa were also significantly higher in the PC IN immunization group. Induction of PC-specific IgA in the PC IN immunization group enhanced the clearance of bacteria from the middle ear. CONCLUSION: Additional IN immunization with PC after PCV13 immunization, which is currently conducted under a periodic vaccination program, can produce a booster effect comparable to that achieved by additional systemic immunization as well as PC-specific mucosal immune response, thereby providing protection against S. pneumoniae serotypes not contained in PCV13.

Evaluation of pneumococcal and influenza vaccination coverage in rheumatology patients receiving biological therapy in a regional referral hospital. / Evaluación de las coberturas de vacunación antineumocócica y antigripal en pacientes reumatológicos con terapia biológica de un hospital autonómico de referencia.

OBJECTIVE: Vaccination coverage for seasonal influenza and pneumococcus in rheumatology patients receiving biological treatment. To identify variables that predict vaccination adherence. MATERIAL AND METHOD: Descriptive cross-sectional study. The study involved rheumatology patients who initiated biological therapy between 01/01/2016 and 12/31/2016 in a regional referral hospital. Variables included sociodemographic information, diagnostic data, treating physician, referral to the vaccine unit and vaccination against pneumococcus with 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), as well as seasonal influenza (2016/17). Univariate, bivariate (Chi-square) and multivariate analysis (logistic regression) were performed. The differences were considered significant (P<.05) and the PASW v.18 software package was used. RESULTS: In all, 222 patients were included. Vaccination coverage was: PCV13, 80.2%; PPSV23, 77.9%; influenza 2016/17, 78.8%; PCV13+PPSV23, 75.2%; PCV13+PPSV23+influenza 2016/17, 68.9%. Axial spondylitis had the highest coverage (>80%) for pneumococcal vaccination and combination of pneumococcal with influenza. Overall, 27% of the patients were not referred to the unit. The treating physician was associated with statistical significance in each vaccine alone or combined, but referral to the vaccine unit was independently associated with the highest vaccination coverage (P<.001) in all cases. CONCLUSIONS: Compared to the scientific literature, we consider that the coverage of our patients against pneumococcus and influenza is high. Referral of these patients to the vaccine unit is the key to guarantee a correct immunization and to minimize some of the possible infectious adverse effects of biological therapies.

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.

Vaccination against influenza and pneumococcal infections in patients with autoimmune disorders under biological therapy: Coverage and attitudes in patients and physicians.

BACKGROUND: Patients under biological therapy for auto-immune disease are considered immunosuppressed and several recent recommendations highlight the need for vaccination against influenza and pneumococcal infections. The aims of this study were to evaluate influenza and pneumococcal vaccine coverage among patients receiving biological therapy and identify factors associated with vaccine uptake within this population. METHODS: A retrospective cross-sectional study was performed in adult patients attending hospitals for an auto-immune/inflammatory disease and treated with biological therapy. Vaccine uptake was evidenced from patient's medical records or from their pharmacist's records. Questionnaires about attitudes and knowledge regarding vaccinations were administered to patients and their physicians. Multivariable logistic regression was used to determine factors significantly associated with influenza and pneumococcal vaccine receipt. RESULTS: A total of 208 patients were included: 52% female and mean age 50.6 (± 14.7) years. Among them 173 completed the questionnaire while 72 physicians replied. Underlying inflammatory diseases were rheumatisms (46%), bowel diseases (31%) and skin diseases (23%). Vaccine uptake was 28% for influenza, 48% for pneumococcus and 22% received both vaccines. Main factors associated to positive uptake were receiving a prescription from a physician, as well as having a good knowledge of vaccines. Factors limiting vaccination were a negative attitude toward vaccines in general, and belonging to the group of inflammatory bowel diseases. CONCLUSIONS: Vaccine coverage for influenza and pneumococcal infections are low in the patients under biologics for auto-immune/inflammatory disease. Health policies should reinforce information and promotion of these vaccines among these patients but also the prescribers.

Direct effect of the 13-valent pneumococcal conjugate vaccine use on pneumococcal colonization among children in Brazil.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has been commercially available in Brazil since 2010. We investigated the carriage prevalence, capsular types, and antimicrobial resistance among pneumococci isolated from children immunized with PCV13 in Brazil. METHODS: We analyzed 500 children < 6 years old attending public (n = 270) and private (n = 230) clinics in Niterói/RJ, Brazil, in 2014. We determined the antimicrobial susceptibility and capsular types for all isolates. RESULTS: Thirty-eight (7.6%) of 500 children had received at least one PCV13 dose. Since only two (0.7%) of 270 children at the public clinic were vaccinated with PCV13, major analyses focused on 36 (15.7%) of 230 children attending private clinics. Nine (25%) of 36 children were pneumococcal carriers. Characteristics associated with carriage were age ≥ 2 years, cough/expectoration, and childcare center attendance (p ≤ 0.01). The capsular types found were 15B/C (n = 2), 6C, 11A/D, 16F, 23A, and 23F. Two isolates were non-typeable (NT). Three (33.3%) isolates were multidrug resistant. We found four (44.4%) penicillin non-susceptible pneumococci, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 µg/ml and 0.023-0.5 µg/ml, respectively. We also detected two (22.2%) erythromycin-resistant isolates (MICs of 3.0 and 256 µg/ml). CONCLUSIONS: Colonization with PCV13 serotype was rare among the vaccinated children. Increasing PCV13 coverage might help reduce the frequency of major serotypes currently associated with invasive pneumococcal diseases in Brazil, such as 3 and 19A. The isolation of multidrug-resistant serotype 6C and NT isolates in carriage, however, requires close monitoring.

Spread of ceftriaxone non-susceptible pneumococci in South Korea: Long-term care facilities as a potential reservoir.

Despite the availability of a pneumococcal National Immunization Program, which provides free PPSV23 vaccination for older adults aged ≥65 years in South Korea, pneumococcal pneumonia remains one of the most common respiratory infections, with increasing antimicrobial resistance. From January to December in 2015, all pneumococcal isolates were collected from a 1,050-bed teaching hospital in South Korea. All isolates were analyzed for serotype, genotype, and antimicrobial susceptibility. Demographic, clinical and microbiological data were compared between ceftriaxone susceptible and non-susceptible cases. Among 92 microbiologically identified pneumococcal isolates, ceftriaxone non-susceptible pneumococci (CNSP) accounted for 32 cases (34.8%). Some of these cases also showed levofloxacin resistance (25%, 8/32 isolates) and all CNSP cases were multidrug resistant. Compared to patients with ceftriaxone susceptible pneumococci (CSP), long-term care facility residents (odds ratio [OR] 7.0, 95% confidence interval [CI] 0.8-62.1) and patients with chronic lung (OR 4.1, 95% CI 1.1-15.0) and renal diseases (OR 9.1, 95% CI 1.2-70.5) were more common among those with CNSP on multivariate analysis. PPSV23-unique serotypes not included in PCV13 were more common in CNSP than in CSP (34.4% versus 13.3%, p = 0.02). Regarding genotypes, ST320 (10 cases), ST166 (7 cases) and ST8279 (3 cases) were dominant in CNSP, and ST8279 was only detected in previous long-term care facility residents. Clonal expansion and spread of CNSP strains should be monitored among patients with chronic lung/renal diseases and residents of long-term care facilities.

Long-term impact of 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease among children in Finland.

BACKGROUND: The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types). METHODS: We used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction. RESULTS: Among vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74-83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant. In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8-52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD. CONCLUSION: Overall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained.

Late onset of injection site reactions after vaccination with the 13-valent pneumococcal conjugate vaccine in adult study populations.

Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1-2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM197), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts. Subjects received PCV13 with aluminum phosphate (AlPO4, n = 5667) or without AlPO4 (n = 304); 1097 subjects received 23-valent pneumococcal polysaccharide vaccine (PPSV23). Late ISRs with onset between days 6-14 were observed in 8/8 cohorts aged ≥65 years after PCV13 with AlPO4 (incidence across cohorts for redness, 2.3%-19.6%; swelling, 0.9%-10.8%; pain, 1.6%-10.0%) and in 1/1 cohort after PCV13 without AlPO4 (redness 10.5%; swelling 7.5%; pain 12.3%); and in 2/4 cohorts aged 50 to 64 years after PCV13 (redness 3.1%-4.8%; swelling 1.0%-3.2%; pain 3.7%-5%). Late ISRs were not generally observed in 1/1 cohort aged 18 to 49 years after PCV13; in 2/2 cohorts aged ≥53 years after PCV13 revaccination; and in 3/3 cohorts aged ≥60 years who received PPSV23, which does not contain CRM197. Post hoc analysis demonstrated numerically higher pneumococcal immune responses in subgroups with late ISRs versus those without. In conclusion, causality of late ISRs is likely multifactorial, with age and the PCV13 carrier protein CRM197 potentially associated. AlPO4, a vaccine adjuvant, did not appear causally related. Observations do not affect the favorable risk-benefit profile of PCV13.

Etiology of Acute Otitis Media and Characterization of Pneumococcal Isolates After Introduction of 13-Valent Pneumococcal Conjugate Vaccine in Japanese Children.

BACKGROUND: Acute otitis media is a leading cause of childhood morbidity and antibiotic prescriptions. We examined etiologic changes in acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine as routine immunization for Japanese children in 2014. Serotypes, resistance genotypes, antibiotic susceptibilities and multilocus sequence typing of pneumococcal isolates were also characterized. METHODS: Otolaryngologists prospectively collected middle ear fluid from 582 children by tympanocentesis or sampling through a spontaneously ruptured tympanic membrane between June 2016 and January 2017. Causative pathogens were identified by bacterial culture and real-time polymerase chain reaction for bacteria. Serotypes, resistance genotypes, sequence types and susceptibilities to 14 antimicrobial agents were determined for pneumococcal isolates. RESULTS: At least 1 bacterial pathogen was identified in 473 of the samples (81.3%). Nontypeable Haemophilus influenzae (54.8%) was detected most frequently, followed by Streptococcus pneumoniae (25.4%), Streptococcus pyogenes (2.9%) and others. Pneumococci of current vaccine serotypes have decreased dramatically from 82.1% in 2006 to 18.5% (P < 0.001). Commonest serotypes were 15A (14.8%), 3 (13.9%) and 35B (11.1%). Serotype 3 was significantly less frequent among children receiving 13-valent pneumococcal conjugate vaccine compared with 7-valent pneumococcal conjugate vaccine (P = 0.002). Genotypic penicillin-resistant S. pneumoniae accounted for 28.7%, slightly less than in 2006 (34.2%; P = 0.393); the penicillin-resistant serotypes 15A and 35B had increased. Serotypes 15A, 3 and 35B most often belonged to sequence types 63, 180 and 558. CONCLUSIONS: Our findings are expected to assist in development of future vaccines, and they underscore the need for appropriate clinical choice of oral agents based on testing of causative pathogens.

Change in Pneumococcus Serotypes but not Mortality or Morbidity in Pre- and Post-13-Valent Polysaccharide Conjugate Vaccine Era: Epidemiology in a Pediatric Intensive Care Unit over 10 Years.

Aim: Pneumococcus is a common commensal and an important pathogen among children for which immunization is available. Some serotypes occasionally cause severe pneumococcal disease with high mortality and morbidity. We reviewed all pneumococcal serotypes and mortality/morbidity in a pediatric intensive care unit (PICU) following universal pneumococcal conjugate vaccine (PCV) immunization. Methods: A 13-valent PCV was introduced in the universal immunization program in late 2011 in Hong Kong. We retrospectively reviewed all pneumococcal serotypes in the pre-(2007-11) and post-(2012-16) 13-valent PCV era. Results: There were 29 (1.9%) PICU patients with pneumococcal isolation, of which 6 died (20% motality). Serogroups 6 and 19 predominated before and Serogroup 3 after 2012. In the post-13-valent PCV era, the prevalence of pneumococcus isolation in PICU was increased from 1 to 2% (p = 0.04); Serogroup 3 was the major serotype of morbidity, despite supposedly under vaccine coverage. The majority of pneumococcus were penicillin-sensitive (94%) in the post 13-valent PCV era. All pneumococcus specimens were sensitive to cefotaxime and vancomycin. Binary logistic regression showed that there were reductions in Serogroup 6 (odds ratio [OR], 0.050; 95% confidence interval [CI], 0.004-0.574; p = 0.016) and Serogroup 19 (odds ratio [OR], 0.105; 95% confidence interval [CI], 0.014-0.786; p = 0.028) but not mortality or morbidity for patients admitted after 2012. Conclusions: SPD is associated with significant morbidity and mortality, despite treatment with systemic antibiotics and ICU support. The expanded coverage of 13-valent PCV results in the reduction of Serotypes 6 and 19 but not mortality/morbidity associated with SPD in the setting of a PICU.

Predominance of Serogroup 19 CC320/271 among Penicillin-Nonsusceptible Streptococcus pneumoniae Isolates after Introduction of the PCV7 Vaccine in Several Regions of Japan.

Multidrug-resistant Streptococcus pneumoniae serogroup 19, including serotypes 19A and 19F, associated with clonal complex 320/271 (CC320/271), has been previously shown to be predominant in many countries after introduction of a 7-valent pneumococcal conjugate vaccine (PCV7). However, in Japan there has been no epidemiological research focused on penicillin-nonsusceptible isolates after this event. Therefore, we aimed to characterize penicillin-nonsusceptible S. pneumoniae (PNSSP; penicillin minimum inhibitory concentration [MIC] ≥ 4.0 µg/ml) after the introduction of PCV7 in Japan. Throughout Japan, we collected 1,057 pneumococcal isolates from 2010 to 2014. We then evaluated MICs and performed serotyping, multilocus sequence typing, and sequencing of penicillin-binding protein genes in 51 isolates (penicillin MIC ≥ 2.0 µg/ml). Twenty-three isolates (2.2%) showed penicillin nonsusceptibility (penicillin MIC ≥ 4.0 µg/ml). Serotypes 19F (14 isolates, 60.9%) and 23F (4 isolates, 17.4%), which are covered by the vaccine, were predominant among PNSSP strains. Only 3 isolates belonged to nonvaccine serotype 19A. Among the PNSSP isolates, CC320/271 (16/23 strains, 69.6%) was the most prevalent clone. Moreover, CC320/271 clones showed high MIC values of a third-generation cephalosporin. Thus, we demonstrated clonal predominance of serogroup 19 CC320/271 with strong resistance to ß-lactams including a third-generation cephalosporin among PNSSP isolates.

Evaluation of Protective Efficacy of Selected Immunodominant B-Cell Epitopes within Virulent Surface Proteins of Streptococcus pneumoniae.

Four previously identified immunodominant B-cell epitopes, located within known virulent pneumococcal proteins CbpD, PhtD, PhtE, and ZmpB, had shown promising in vivo immunological characteristics, indicating their potential to be used as vaccine antigens. In this study, we further evaluated the opsonophagocytic activity of antibodies against these epitopes and their capacity to protect mice from pneumococcal sepsis. An opsonophagocytic killing assay (OPKA) revealed that OPKA titers of human anti-peptide antibodies against pneumococcal serotypes 1, 3, and 19A were significantly higher (P < 0.001) than those of the control sera, suggesting their functional potential against virulent clinical isolates. Data obtained from mice actively immunized with any of the selected epitope analogues or with a mixture of these (G_Mix group) showed, compared to controls, enhanced survival against the highly virulent pneumococcal serotype 3 (P < 0.001). Moreover, passive transfer of hyperimmune serum from G_Mix to naive mice also conferred protection to a lethal challenge with serotype 3, which demonstrates that the observed protection was antibody mediated. All immunized murine groups elicited gradually higher antibody titers and avidity, suggesting a maturation of immune response over time. Among the tested peptides, PhD_pep19 and PhtE_pep40 peptides, which reside within the zinc-binding domains of PhtD and PhtE proteins, exhibited superior immunological characteristics. Recently it has been shown that zinc uptake is of high importance for the virulence of Streptococcus pneumoniae; thus, our findings suggest that these epitopes deserve further evaluation as novel immunoreactive components for the development of a polysaccharide-independent pneumococcal vaccine.

Associations between complementary medicine utilization and influenza/pneumococcal vaccination: Results of a national cross-sectional survey of 9151 Australian women.

Influenza and pneumococcal vaccination is recommended for all adults, with older adults considered a high-risk group for targeted intervention. As such it is important for factors affecting vaccine uptake in this group to be examined. Complementary medicine (CM) use has been suggested as a possible factor associated with lower vaccination uptake. To determine if associations exist between influenza and pneumococcal vaccine uptake in older Australian women and the use of CM, data from women aged 62-67years surveyed as part of the Australian Longitudinal Study on Women's Health (ALSWH) were analyzed in 2013 regarding their health and health care utilization. Associations between the uptake of influenza and pneumococcal vaccinations and the use of CM were analyzed in 2016 using chi-squared tests and multiple logistic regression modelling. Of the 9151 women, 65.6% and 17.7% reported that they had influenza and pneumococcal vaccination within the past 3years respectively. Regression analyses show that women who consulted naturopaths/herbalists (OR=0.64) and other CM practitioners (OR=0.64) were less likely to have vaccination (influenza only), as were women who used yoga (OR=0.77-0.80) and herbal medicines (OR=0.78-0.83) (influenza and pneumococcal). Conversely, women using vitamin supplements were more likely to receive either vaccination (OR=1.17-1.24) than those not using vitamin supplements. The interface between CM use and influenza and pneumococcal vaccination uptake in older women appears complex, multi-factorial and often highly individualized and there is a need for further research to provide a rich examination of the decision-making and motivations of stakeholders around this important public health topic.