13-valent Pneumococcal Conjugate Vaccine Research Articles

Dose-response relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children

To investigate the potential relationship between age and Streptococcus pneumoniae vaccination coverage in kindergarten children, and to provide a basis for guiding vaccination and developing new protein vaccines. The stratified cluster random sampling method was used to select 1 830 healthy children from six kindergartens in Shunde District, Foshan City, China, and nasopharyngeal swabs were collected for the isolation and identification of Streptococcus pneumoniae. The logistic regression model based on restricted cubic spline was used to analyze the dose-response relationship between age and Streptococcus pneumoniae vaccination coverage. The rate of nasal Streptococcus pneumoniae carriage was 22.46% (411/1 830) among the kindergarten children, with the predominant serotypes of 6B, 19F, 15A, 23A, 34, and 23F. The coverage rates of 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) were 53.0% and 57.9%, respectively, and there was a significant non-linear dose-response relationship between age and the coverage rates of PCV10 and PCV13 (P<0.05), with a higher coverage rate of PCV10 (88.0%) and PCV13 (91.1%) in the children aged 2 years. There was a significant non-linear dose-response relationship between age and the coverage rates of pilus islet 1 (PI-1) and pilus islet 2 (PI-2) (P<0.05), with a lower vaccination coverage rate for PI-1 (37.7%) and PI-2 (16.1%). The coverage rates of PI-1 (13.0%-58.5%) and PI-2 (6.0%-29.4%) were lower in all age groups. The virulence genes lytA (99.5%) and ply (99.0%) associated with candidate protein vaccines showed higher vaccination coverage rates. There is a significant non-linear dose-response relationship between the age of kindergarten children and the coverage rates of PCV10 and PCV13 serotypes, and kindergarten children aged 2 years have a relatively high coverage rate of PCV. The high prevalence of the virulence genes lytA and ply shows that they are expected to become candidate virulence factors for the development of a new generation of recombinant protein vaccines.

Bacteriological and molecular characterization of temperature- and CO2-dependent Streptococcus pneumoniae serotype 24F ST162 isolated from Japanese children.

Streptococcus pneumoniae serotype 24F is one of the most prevalent non-vaccine serotypes that causes invasive pneumococcal disease (IPD) in many countries, including Japan. This study aimed to analyze the bacteriological and molecular characteristics of serotype 24F sequence type (ST) 162, which has been increasingly isolated from pediatric patients with IPD in Japan recently. The examination of growth conditions, sequencing of genes associated with the CO2 dependence, and antimicrobial susceptibility testing at 35°C under 5% CO2 were performed for 10 isolates obtained from Japanese children with IPD caused by serotype 24F ST162. All isolates failed to grow at 35°C in ambient air; however, they showed growth at 30°C in ambient air and at 35°C under 5% CO2. Sequencing of murF involved in cell wall synthesis indicated that all isolates had a single amino acid substitution, MurFA179V. Additionally, all isolates were sensitive to penicillin G and resistant to trimethoprim-sulfamethoxazole. Furthermore, 25 non-capnophilic strains were obtained from all CO2-dependent isolates, and their murF sequences were compared. Thirteen of the 25 non-capnophilic strains displayed a different amino acid substitution, MurFV179A, whereas the other 12 presented the previously described MurFA179V. This suggests that a proportion of the CO2-dependent phenotype of serotype 24F ST162 may have been conferred by MurFA179V; however, the mechanism for the CO2 dependence of these isolates warrants further investigation. The CO2-dependent serotype 24F ST162 pneumococcal isolates shared common characteristics in terms of growth patterns, molecular basis, and antimicrobial susceptibility; therefore, future epidemiological trends of this clone must be closely monitored. IMPORTANCE We characterized Streptococcus pneumoniae serotype 24F sequence type (ST) 162 isolated from Japanese children with invasive pneumococcal disease (IPD). Owing to its highly invasive nature, serotype 24F is expected to be isolated from clinically significant cases. Serotype 24F ST162 isolates tested in the present study did not grow at 35°C in ambient air. Therefore, antimicrobial susceptibility testing using the broth microdilution method, which is usually conducted in ambient air, cannot be performed, posing a clinical challenge. Clinical practitioners and laboratory personnel should be aware of the epidemiological, bacteriological, and molecular characteristics of serotype 24F ST162. We believe that our findings can help diagnose and treat IPD caused by serotype 24F ST162, a serotype expected to become problematic in the post-13 valent pneumococcal conjugate vaccine era.

Analysis on the vaccination coverage of 13-valent pneumococcal conjugate vaccine in China from 2017 to 2021

Objective: To explore the vaccination coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China from 2017 to 2021. Methods: Using the reported number of PCV13 administrated doses from 2017 to 2021 and the population data from 31 provinces in China, which were collected by the Immunization Program Information System and summarized data at different levels (prefecture, provincial, and national). Collecting batch release data of PCV13 during the same period through the official website of the National Institutes for Food and Drug Control. The average coverage level of PCV13 was calculated by comparing the number of PCV13 vaccinations reported annually to the number of births in that year, and the spatial auto-correlation analysis was conducted in 2021 at the prefecture level. The coverage of PCV13 vaccination was estimated by the total vaccine doses administered each year divided by the number of newborn in the year, as of the administrated dose number per 100 people. Results: From March 2017 to December 2020, the total batch release of PCV13 was 20.06 million, with a total of 71.54, 384.75, 475.45, and 10.8886 million doses each year. During the same period, PCV13 reported doses were 20.2369 million and the vaccination doses from 2017 to 2021 were 4.08, 170.46, 407.52, 599.77, and 8.4185 million doses, respectively. From 2017 to 2021, the ratio of PCV13 doses administrated per 100 infants in each year was 0.25, 10.26, 23.81, 38.16, and 69.90 doses per 100 people, respectively. The range of the ratio in each province increased from 3.85 doses in 2017 to 264.41 doses per 100 people in 2021. The spatial auto-correlation analysis results showed that based on prefecture-level cities, there was spatial clustering in a certain area of PCV13 coverage from 2017 to 2021, and the spatial correlation in 2021 was the highest. The hotspot analysis showed that the hotspot areas with high coverage levels of PCV13 were concentrated in Jiangsu, Zhejiang, Shanghai, Fujian and their surrounding areas. The cold spots with low vaccine coverage were concentrated in Yunnan, Qinghai, Tibet, and their surrounding areas. Conclusion: The average coverage level of PCV13 is low in China with significant regional differences.

Assessing prescription of antibiotics after vaccination against pneumococcal pneumonia; using prescription sequence symmetry analysis

ObjectivesPrescription sequence symmetry analysis (PSSA) is used to detect adverse event signals using administrative claims databases. In this study, we investigated whether PSSA can be applied to gauge the effects of PCV13 vaccination on antibiotic prescription rates in elderly patients. MethodsWe studied prescription records of patients aged 65 or older between 1 January 2014 and 31 December 2020, from the Helsana Swiss claims database. PSSA was performed to explore the relationship between 13-valent pneumococcal conjugate vaccine (PCV13) and six antibiotics recommended by the Swiss Society of Infectious Diseases for community-acquired pneumonia treatment (amoxicillin-clavulanate, azithromycin, clarithromycin, doxycycline, levofloxacin, and moxifloxacin), three additional antibiotics (amoxicillin, ciprofloxacin, and fosfomycin), and ten control drugs. ResultsAmoxicillin-clavulanate, clarithromycin, and levofloxacin were more likely to be prescribed before than after vaccination, for all time windows between 25 and 104 weeks. Adjusted sequence ratio (ASR) values ranged from 0.599 to 0.614, 0.508 to 0.568, and 0.514 to 0.752, respectively. Lower prescription rates after vaccination were also observed for azithromycin (all time windows between 38 and 104 weeks, ASR 0.705–0.739) and moxifloxacin (all time windows between 52 and 104 weeks, ASR 0.658–0.772). PCV13 did not have statistically significant associations with doxycycline, amoxicillin, ciprofloxacin, fosfomycin, or any of the ten controls. DiscussionThe lower prescription rate of antibiotics for community-acquired pneumonia after vaccination could be attributed to a protective effect of PCV13. This novel application of PSSA can be used to compare the real-world impact of other vaccines on drug consumption.

Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experiencing Homelessness-Alaska, 2011-2020.

Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in US adults. We describe the epidemiology of IPD among Alaska adults and estimate the proportion of IPD cases potentially preventable by new vaccines. We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CIs) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. During 2011-2020, 1164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100 000 adults per year (95% CI, 20.1-22.5). Incidence increased significantly during the study period (P < .01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI, 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than in the general adult population (95% CI, 59-89). Overall, 1032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

A multicenter study on the epidemiology of complicated parapneumonic effusion in the era of currently available pneumococcal conjugate vaccines

BackgroundParapneumonic effusion (PPE) is a common complication of pneumonia. Streptococcus pneumoniae is the most common cause of bacterial pneumonia. A reduction in pneumonia hospitalizations has been observed since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Despite this apparent benefit, an increase in the incidence of PPE was recorded in some countries following PCV7 implementation. As the 13-valent pneumococcal conjugate vaccine (PCV13) was expected to provide a wider protection against PPE, the aim of the present study was to evaluate the impact of PCV13 introduction on the epidemiology of complicated parapneumonic effusion (c-PPE) among children in the Athens greater area. MethodsAll cases of community-acquired pneumonia (CAP) with PPE requiring chest tube insertion (complicated PPE, c-PPE) hospitalized in the 3 public Children’s hospitals in Athens between 01/01/2004 and 31/12/2019 were included in the study. ResultsA total of 426 cases of c-PPE associated with pneumonia were recorded of which 198 were admitted during 2004–2010 (period A, prePCV13/PCV −7 introduction period) and 228 during 2011–2018 (period B, post - PCV13 period). A definite bacterial etiology was established in 44.4 % of all cases and of those 25.4 % were caused by S. pneumoniae. An increasing trend in c-PPE incidence was observed during period A; although, a significant decrease on c-PPE annual rates was observed during the period B (p = 0.011), a remarkable increase in serotype 3 cases was recorded. ConclusionA decreasing time trend in c-PPE cases among children was shown after the introduction of PCV13 in our area. However, serotype 3 is nowadays a common cause of PPE. Hence, continuous surveillance is imperative in order to follow c-PPE epidemiology over time.

Health and economic outcomes of 20-valent pneumococcal conjugate vaccine compared to 15-valent pneumococcal conjugate vaccine strategies for adults in Greece.

Higher valency pneumococcal conjugate vaccines (PCVs) are expected to improve protection against pneumococcal disease through coverage of additional serotypes. The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 15-valent pneumococcal conjugate vaccine (PCV15) alone or followed by 23-valent polysaccharide vaccine (PPV23) for adults in Greece. A published Markov model was adapted to simulate lifetime risk of clinical and economic outcomes from the public payer's perspective. The model population was stratified based on age and risk profile (i.e., low, moderate, or high-risk of developing pneumococcal disease). Epidemiologic parameters, serotype coverage and vaccines' effectiveness were based on published literature, while direct medical costs (prices €, 2022) were obtained from official sources. Main model outcomes were projected number of invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP) cases and attributable deaths, costs and quality-adjusted life-years (QALY) for each vaccination strategy. Sensitivity analyses were performed to ascertain the robustness of model results. Over the modeled time horizon, vaccination with PCV20 compared to PCV15 alone or PCV15 followed by PPV23 prevents an additional 747 and 646 cases of IPD, 10,334 and 10,342 cases of NBP and 468 and 455 deaths respectively, resulting in incremental gain of 1,594 and 1,536 QALYs and cost savings of €11,183 and €48,858, respectively. PSA revealed that the probability of PCV20 being cost-effective at the predetermined threshold of €34,000 per QALY gained was 100% compared to either PCV15 alone or the combination of PCV15 followed by PPV23. PCV20 is estimated to improve public health by averting additional pneumococcal disease cases and deaths relative to PCV15 alone or followed by PPV23, and therefore translates to cost-savings for the public payer. Overall results showed that vaccination with PCV20 was estimated to be a dominant vaccination strategy (improved health outcomes with reduced costs) over PCV15 alone or followed by PPV23 for prevention of pneumococcal disease in adults in Greece.

Vaccination in Kidney Transplant Candidates.

Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective single-center study of contemporary KT candidates was conducted to assess vaccination rates and vaccine uptake. All KT candidates ≥18 y evaluated between January 1, 2020, and December 31, 2020, were retrospectively reviewed for history of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine. Positive hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG were assessed as surrogate markers of immunity. Vaccine uptake among vaccine-eligible candidates was also assessed. Among 150 KT candidates, the rate of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine (latter among patients ≥50 y) was found to be as low as 11%. Hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG seropositivity rates were 30%, 66%, 88%, 78%, 90%, and 96%, respectively. Only 7 (5%) of 150 patients had complete immunization or seropositivity. Five (3%) of 143 vaccine-eligible patients declined vaccination. Hepatitis A vaccine declination was relatively common with 15 (16%) of 94 vaccine-eligible patients declining it. KT candidates have low baseline rates of prior immunization/seropositivity against most recommended vaccines. Overall vaccine uptake among eligible candidates was high.

Pneumococcal infections in children with sickle cell disease before and after pneumococcal conjugate vaccines

AbstractChildren with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.

Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study

Background and purposePneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. MethodsThis retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. ResultsThe cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = −0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = −0.006, p = 0.787 and rs = −0.156, p = 0.398). ConclusionAfter the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months–3 years with a discharge diagnosis of bronchopneumonia and pneumonia.

Health Care Provider Knowledge and Attitudes Regarding Adult Pneumococcal Conjugate Vaccine Recommendations - United States, September 28-October 10, 2022.

Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence.

Factors and Reasons for Non-vaccination among Patients with Systemic Lupus Erythematosus: A Single-centre, Cross-sectional Study.

Objective This study aimed to clarify the vaccination coverage of vaccine-preventable diseases and the factors and reasons for non-vaccination among patients with systemic lupus erythematosus (SLE). Methods This single-centre, cross-sectional study was conducted from 1 September to 30 November 2020 in a 715-bed regional tertiary-care teaching hospital in Japan. A questionnaire survey was undertaken to investigate the vaccination status of patients with SLE, and the factors and reasons for not receiving the influenza vaccine, 23-valent-pneumococcal-polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), varicella vaccine live (VVL), and recombinant zoster vaccine (RZV). Results The vaccination coverage for the influenza vaccine, PPSV23, PCV13, VVL, and RZV was 61%, 22%, 19%, 3.4%, and 0%, respectively, among 261 patients. The most common reason for vaccine hesitancy was 'efficacy concerns about vaccines' for the influenza vaccine and 'cost' for PPSV23 and PCV13. The factors significantly associated with non-vaccination were prescription of high-dose glucocorticoids and no history of visits to other internal medicine clinics for the influenza vaccine; a younger age and prescription of high-dose glucocorticoids for PPSV23; and a younger age, no medication with hydroxychloroquine, no history of hospitalisation in internal medicine, and extensive clinical experience of the doctor for PCV13. Conclusion These findings, which demonstrated that the factors and reasons for non-vaccination varied by vaccine type, suggest that individualised strategies should be used to promote vaccination in this population.

Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study

The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage. We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed. Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci. This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination. Wellcome Trust.

Molecular Identification and Detection of Streptococcus pneumoniae Serotypes Isolated from the Cerebrospinal Fluid of Children with Suspected Meningitis: First Report From Alborz, Iran

Background: Pneumococcus causes various infections, some of which are life-threatening, including pneumonia, meningitis, otitis media, bacteremia, and sinusitis. Currently, more than 95 serotypes have been identified. Objectives: The purpose of this study was to isolate and determine Streptococcus pneumoniae serotypes from the cerebrospinal fluid (CSF) of children with suspected meningitis using the multiplex polymerase chain reaction (PCR) method. Materials and Methods: A total of 864 CSF samples were taken from children with suspected meningitis who were admitted to Imam Ali Hospital of Karaj for one year (January 2019 to January 2020). To collect positive S. pneumonia samples, the lytA gene was traced using specific primers and PCR techniques. Results: The results of this study indicated that only 16 patients have a pneumococcal infection (1.85%), of whom 50% have encapsulated pneumococci. Furthermore, serotypes 38 (12.5%), 7F (12.5%), 23F (25%), and 6A/B (50%) were the most common serotypes causing invasive pneumococcal infections in the included samples. Conclusion: Among the techniques for serotyping S. pneumoniae, the multiplex PCR technique is known as a fast, easy, and low-cost method that can serotype a large number of samples. The results also showed that the 13-valent pneumococcal conjugate vaccine can cover at least 50% of the strains that cause invasive pneumococcal diseases (IPDs), which are life-threatening, especially in children. Therefore, it is suggested that the healthcare administrators of Iran design and implement a public vaccination program.

Effectiveness of 13-valent pneumococcal conjugate vaccine on all-cause pneumonia in children under 5 years in Shanghai, China: An observational study

BackgroundStreptococcus pneumoniae (Spn) is a common respiratory pathogen and the main cause of bacterial pneumonia, meningitis, and bacteremia, acute otitis media. Imported 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in China and introduced in Shanghai in 2017. We aim to describe PCV13 vaccination trends and pneumonia incidence of children under 5 from 2017 to 2020, then estimate the effectiveness of PCV13 against community-acquired pneumonia (CAP) in children under 5 in Shanghai, China. MethodsBy calculating propensity scores with logistic regression, a comparison group was formed by frequency matching one unvaccinated child to one vaccinated child. For matching, we used the nearest-neighbor matching algorithm and exact matching, and then created distinct matched analysis sets for two cohorts. A Kaplan-Meier analysis was conducted to measure the cumulative incidence of all-cause pneumonia in both groups and used the log-rank test to assess the differences between the two cumulative incidence curves. Cox proportional hazards regression was used to compare the adjusted hazard ratios (HR) of differences in all-cause pneumonia between the two groups. ResultsChildren received three or more doses PCV13 accounted for 85.7% of all vaccinated children. The incidence of pneumonia in Shanghai’s Songjiang district decreased rapidly from 2017, when PCV13 vaccination presented an overall increasing trend. The estimated vaccine effectiveness against visits for all-cause pneumonia was 19% (95% CI: 3 to 32) after the first dose in children vaccinated with at least one dose of PCV13. The protective effectiveness of PCV13 was found to be higher for hospitalized pneumonia (30%, 95% CI: 5% to 49%) than for outpatient pneumonia (19%, 95% CI: 4% to 32%). ConclusionsPCV13 vaccination among children aged 0–5 years substantially reduced the incidence of all-cause pneumonia. Direct immunization of children under 5 years is an effective strategy to combat outpatient pneumonia, and hospitalized pneumonia.

Prognoses of patients undergoing hemodialysis administered 23-valent pneumococcal polysaccharide versus 13-valent pneumococcal protein conjugate vaccines

IntroductionSequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23. MethodsPatients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed. ResultsThe study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period. ConclusionsPatients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group.

Cost-effectiveness analysis of pediatric immunization program with 15-valent pneumococcal conjugate vaccine in Japan

BackgroundThe 15-valent pneumococcal conjugate vaccine (PCV15 or V114) has recently been approved for pediatric vaccination against pneumococcal diseases (PDs) in Japan. The study aims to evaluate the cost-effectiveness of pediatric vaccination with V114 versus 13-valent PCV (PCV13) in Japan.MethodsThe study used a decision analytical Markov model to estimate the cost and effectiveness outcomes for a birth cohort in Japan over a 10-year time horizon. The model tracked the occurrences of acute PD events, including invasive PD (IPD), non-bacteremic pneumococcal pneumonia (NBPP) and pneumococcal acute otitis media (AOM) and the long-term impact of post-meningitis sequalae. Vaccine effectiveness was estimated based on literature and assumptions, and accounted for indirect effects and vaccine waning. The base case took the societal perspective, including both direct and indirect costs, while a healthcare payer perspective was modeled in a scenario analysis. Additional scenario analyses and sensitivity analyses were conducted.ResultsIn the base case, V114 was associated with an incremental gain of 24 quality-adjusted life years and a reduction of ¥365,610,955 in total costs compared to PCV13. It was expected to reduce the number of pneumococcal AOM, NBPP, and IPD cases by 1,832, 1,333 and 25, respectively. All scenario analyses and most sensitivity analyses showed that V114 was a dominant strategy compared to PCV13.ConclusionsPediatric vaccination with V114 is expected to lead to cost savings and more health benefits compared to PCV13 in Japan from both societal and healthcare payer perspectives. The findings are robust under plausible assumptions and inputs.

Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to Higher-Valent Options in Greek Infants.

In June 2010, Greece introduced the 13-valent pneumococcal conjugate vaccine (PCV13) for pediatric vaccination and has since observed a large decrease in pneumococcal disease caused by these vaccine serotypes, yet the disease prevalence of non-vaccine serotypes has increased. Two higher-valent conjugate vaccines, a 15-valent (PCV15) and a 20-valent (PCV20), were developed to improve serotype coverage and combat serotype replacement. A decision-analytic model was adapted to the Greek setting using historical pneumococcal disease trends from PCV13 to forecast future clinical and economic outcomes of higher-valent PCVs over a 10-year period (2023-2033). The model estimated outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and otitis media (OM) resulting from a switch in vaccination programs to PCV15 in 2023 or switching to PCV20 in 2024. Cost-effectiveness was evaluated from the third-party payer's perspective in the Greek healthcare system. Compared to implementing PCV15 one year earlier, switching from PCV13 to PCV20 in 2024 was estimated to be a cost-saving strategy by saving the Greek health system over EUR 50 million in direct medical costs and averting over 250 IPD cases, 54,800 OM cases, 8450 pneumonia cases, and 255 deaths across all ages over a 10-year period.

Coadministered pneumococcal conjugate vaccine decreases immune response to hepatitis A vaccine: a randomized controlled trial

ObjectivesWe explored the influence of coadministration on safety and immunogenicity of the most common travellers' vaccine hepatitis A (HepA) and the pneumococcal conjugate vaccine (PCV) increasingly used both at home and before travel. MethodsVolunteers aged ≥18 years (n = 305) were randomly assigned 1:1:1 into three groups receiving: 13-valent PCV (PCV13) + HepA, PCV13, or HepA. Anti-pneumococcal IgG concentrations, opsonophagocytic activity (OPA) titres, and total hepatitis A antibody (anti-HAV) concentrations were measured before and 28 ± 3 days after vaccination. Adverse events (AEs) were recorded over 4 weeks. ResultsAfter vaccination, the anti-HAV geometric mean concentration was significantly lower in the PCV13+HepA than the HepA group: 34.47 mIU/mL (95% CI: 26.42–44.97 mIU/mL) versus 72.94 mIU/mL (95% CI: 55.01–96.72 mIU/mL), p < 0.001. Anti-HAV ≥10 mIU/mL considered protective was reached by 71 of 85 (83.5%) in the PCV13+HepA group versus 76 of 79 (96.2%) in the HepA group, p 0.008. The increases in anti-pneumococcal IgG and OPA levels were comparable in the PCV13+HepA and PCV13 groups, apart from a bigger rise in the PCV13+HepA group for serotype 3 (one-way ANOVA: serotype 3 IgG p 0.010, OPA p 0.002). AEs proved more frequent among those receiving PCV13 than HepA, but simultaneous administration did not increase the rates: ≥one AE was reported by 45 of 56 (80.4%) PCV13, 43 of 54 (79.6%) PCV13+HepA, and 25 of 53 (47.2%) HepA recipients providing structured AE data. DiscussionCoadministration of HepA and PCV13 did not cause safety concerns, nor did it impact the patients' response to PCV13, apart from serotype 3. However, coadministered PCV13 significantly impaired antibody responses to HepA.

Safety and Immunogenicity of V114 in Preterm Infants: A Pooled Analysis of Four Phase Three Studies.

Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in PCV13 plus 2 unique serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (<37 weeks gestational age) enrolled in 4 pediatric phase 3 studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. Healthy preterm infants were randomized 1:1 to receive V114/PCV13 in the 4 studies. Safety was evaluated as the proportion of participants with adverse events (AEs) following receipt of PCV. Serotype-specific antipneumococcal immunoglobulin G (IgG) geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were measured at 30 days postdose 3, pretoddler dose and 30 days postdose 4. V114 and PCV13 were administered to 174 and 180 participants, respectively. Mean gestational age was 35.4 weeks (range: 27 - <37 weeks). Proportions of participants with AEs were comparable between vaccination groups; most AEs experienced were of short duration (≤3 days) and mild-to-moderate intensity. V114-elicited IgG geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days postdose 3 and postdose 4. In preterm infants, V114 was well tolerated and induced comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to serotypes 22F and 33F. Results support the use of V114 in preterm infants.