Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

BACKGROUND: Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). METHODS: Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. RESULTS: Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. CONCLUSIONS: PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

Pneumococcal carriage and serotype distribution in children with nephrotic syndrome.

BACKGROUND: Patients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS. METHODS: Pneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR. RESULTS: The pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all). CONCLUSIONS: The pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS.

Impacts of the COVID-19 pandemic on immunization with pneumococcal vaccines in children and older adults in Brazil.

The COVID-19 pandemic has profoundly impacted individuals, resulting in long-lasting consequences. One of the effects has been a decline in vaccine adherence attributed to physical distancing measures, potentially contributing to the resurgence of preventable diseases, and posing diagnostic challenges. Consequently, monitoring immunization rates becomes crucial as an indicator for health promotion campaigns and to mitigate the strain on healthcare systems. This study aims to assess the effects of the COVID-19 pandemic on immunization with pneumococcal vaccines in children and older adults in Brazil from 2018 to 2021. Data was collected from the Department of Informatics of the Unified Health System, focusing on the number of doses administered and vaccination coverage with pneumococcal vaccines across the country. A total of 21,780,450 doses were administered, with a decline of 19.97% in vaccine coverage throughout the evaluation period. An overall negative trend was observed in the time series analysis for all states in Brazil. However, not all showed a statistically significant change associated with the pandemic. Therefore, it is essential for states that experienced a decline in vaccination rates during the COVID-19 pandemic to closely monitor changes in pneumococcal vaccination. Failure in the process may lead to an increase in pneumococcal infections and place an additional burden on the healthcare system.

Increased Incidence of Invasive Pneumococcal Disease among Children after COVID-19 Pandemic, England.

During July-December 2021, after COVID-19 restrictions were removed in England, invasive pneumococcal disease incidence in children <15 years of age was higher (1.96/100,000 children) than during the same period in 2020 (0.7/100,000 children) and in prepandemic years 2017-2019 (1.43/100,000 children). Childhood vaccine coverage should be maintained to protect the population.

Development of a novel flow cytometry method for detecting pneumococcal-specific B cells.

Antigen-specific B cell identification by flow cytometry is crucial for investigating their immunophenotype, subset distribution, and kinetics post-infection or immunization. Methods using biotinylated polysaccharide antigens have been described, but there is still room for improvement regarding sensitivity and applicability. The aim of this study was the development and validation of a multimer bead-based method for detecting pneumococcal polysaccharide serotypes (PS)-specific B cells following pneumococcal immunization. PS was chemically biotinylated and mounted on anti-biotin beads, and labeled with phycoerythrin (PE)-conjugated anti-biotin antibody to form a PS-multimer used for cell staining. Labeled beads were washed to remove excess fluorochrome and diminish non-specific labeling and background noise. Optimal ratios of PS-bead conjugate to PE and PS-multimer to cells were determined with titration assays. Comparison between the PS-multimer and a PS-PE monomer revealed enhanced detection of PS-specific cells and considerable signal amplification, attributed to the multimeric form of the detection probe and increased availability of antigen epitopes. To validate the specificity of the method, a competition assay using unbound PS was performed. Following pre-incubation with increasing PS concentrations, detection of PS-specific B cells with the PS-multimer was inhibited in a stepwise manner. Pre-incubation with excess PS completely blocked the fluorescent signal. This novel bead-based flow cytometry approach is a sensitive method demonstrating high specificity. It generated enhanced signals, provided clear-cut results, and was easily applicable, not requiring B cell pre-enrichment. It could be modified to adapt other antigens of interest, especially polysaccharides and proteins that could be used to probe antigen-specific B cell responses. The study of such responses may elucidate the underlying mechanisms involved in the establishment of long-term protection, provide evidence-based rationale for improving currently available vaccines and vaccination strategies, and pave the way for future vaccine development.

Unmet needs in pneumonia research: a comprehensive approach by the CAPNETZ study group.

INTRODUCTION: Despite improvements in medical science and public health, mortality of community-acquired pneumonia (CAP) has barely changed throughout the last 15 years. The current SARS-CoV-2 pandemic has once again highlighted the central importance of acute respiratory infections to human health. The "network of excellence on Community Acquired Pneumonia" (CAPNETZ) hosts the most comprehensive CAP database worldwide including more than 12,000 patients. CAPNETZ connects physicians, microbiologists, virologists, epidemiologists, and computer scientists throughout Europe. Our aim was to summarize the current situation in CAP research and identify the most pressing unmet needs in CAP research. METHODS: To identify areas of future CAP research, CAPNETZ followed a multiple-step procedure. First, research members of CAPNETZ were individually asked to identify unmet needs. Second, the top 100 experts in the field of CAP research were asked for their insights about the unmet needs in CAP (Delphi approach). Third, internal and external experts discussed unmet needs in CAP at a scientific retreat. RESULTS: Eleven topics for future CAP research were identified: detection of causative pathogens, next generation sequencing for antimicrobial treatment guidance, imaging diagnostics, biomarkers, risk stratification, antiviral and antibiotic treatment, adjunctive therapy, vaccines and prevention, systemic and local immune response, comorbidities, and long-term cardio-vascular complications. CONCLUSION: Pneumonia is a complex disease where the interplay between pathogens, immune system and comorbidities not only impose an immediate risk of mortality but also affect the patients' risk of developing comorbidities as well as mortality for up to a decade after pneumonia has resolved. Our review of unmet needs in CAP research has shown that there are still major shortcomings in our knowledge of CAP.

Effectiveness of Pneumococcal Vaccines on Otitis Media in Children: A Systematic Review.

OBJECTIVES: We aimed to determine the effectiveness of pneumococcal vaccines on otitis media (OM) and acute otitis media (AOM) in children. METHODS: We conducted a systematic search in databases PubMed (MEDLINE), Embase, Lilacs, and Web of Science. We included observational studies that evaluated any pneumococcal vaccine - including 7, 10, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) and 23-valent polysaccharide vaccines (PPSV23) as the intervention, in children aged less than five years. RESULTS: Out of the 2112 screened studies, 48 observational studies complied with the eligibility criteria and therefore were included in this review. Of the included studies, 30 (63%) were before-after, eleven (23%) cohort, six (13%) time series, and one (2%) case-control study designs. Vaccine effectiveness (VE) in preventing OM or AOM varied by vaccine type. In children under 24 months VE ranged from 8% and 42.7% (PCV7), 5.6% to 84% (PCV10) and 2.2% to 68% (PCV13). In children aged less than 60 months, VE ranged between 13.2% and 39% for PCV7, 11% to 39% for PCV10 (only children under 48 months), and 39% to 41% (PCV13). CONCLUSIONS: Our results demonstrate significant effect of pneumococcal vaccination in decreasing OM or AOM in children under five years old in several countries supporting the public health value of introducing PCVs in national immunization programs.

Identification and molecular characterization of penicillin-nonsusceptible Streptococcus pneumoniae isolates recovered from invasive infections in a pre-pneumococcal vaccine era.

BACKGROUND: Given the significant role of penicillin-nonsusceptible Streptococcus pneumoniae in inducing severe infectious diseases, identifying serotypes and genotypes that can mediate antimicrobial resistance has become a pillar of treatment strategies. This study aims to determine the correlation between the minimum inhibitory concentration of antimicrobial agents and amino acid mutations in penicillin-binding proteins. Moreover, molecular serotyping and multiple-locus variable number tandem repeat analysis typing were first-ever performed to characterize the invasive penicillin-nonsusceptible S. pneumoniae isolates in Iran. METHODS: Of 149 isolates, antimicrobial susceptibility tests were performed against penicillin, ceftriaxone, and cefotaxime by the MIC Test Strip, and sequence analysis of the pbp genes was performed through PCR-sequencing method. All penicillin-nonsusceptible S. pneumoniae isolates were serotyped and genotyped by sequential multiplex PCR and multiple-locus variable-number tandem repeat analysis, respectively. RESULTS: Among pneumococcal isolates, 53 isolates were classified as penicillin-nonsusceptible S. pneumoniae, of which 38 (71.7%) and 15 (28.3%) were resistant and intermediate to penicillin, respectively. Furthermore, ceftriaxone- and cefotaxime-nonsusceptible pneumococci constituted 33 (62.2%) and 29 cases (54.7%), respectively. Of note, there were 8 and 41 different serotypes and multiple-locus variable-number tandem repeat analysis types, respectively. CONCLUSIONS: Due to the increasing resistance to antimicrobial agents, the most efficient approach to preventing pneumococcal infection mortality as vaccine-preventable diseases is focusing on wide-spectrum vaccination. Based on our findings, the 13-valent pneumococcal conjugate vaccine could considerably reduce the incidence of invasive pneumococcal diseases due to the high rate of serotype coverage.

Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan.

INTRODUCTION: Streptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era). METHODS: A total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. RESULTS: The prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166). CONCLUSIONS: Our findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents.

Clinical Effectiveness of Conjugate Pneumococcal Vaccination in Hematopoietic Stem Cell Transplantation Recipients.

Hematopoietic stem cell transplantation (HSCT) recipients are vulnerable to invasive pneumococcal disease (IPD), with reported IPD rates ranging from 3.81 to 22.5/1000 HSCT. This IPD risk could relate to immunodeficiency, low vaccination uptake, and poor immunogenicity of pneumococcal polysaccharide vaccine (PPV). Literature comparing the clinical effectiveness of pneumococcal conjugate vaccination (PCV) and PPV after HSCT is limited. In this retrospective analysis of HSCT recipients at our center from 2004 to 2015, we evaluated vaccination uptake and compared IPD rates in patients receiving PPV (pre-2010 group) and PCV (post-2010 group). IPD was determined from microbiological results for all HSCT recipients from January 2004 to June 30, 2019. Eight hundred patients had a total of 842 HSCT events, including autologous HSCT (auto-HSCT; n = 562) and allogeneic HSCT (allo-HSCT; n = 280). More than 90% of the HSCT recipients were enrolled, and >93% of surviving HSCT recipients completed the vaccination protocol. Fifteen IPD episodes occurred in 13 patients between 2004 and June 30, 2019. Thirteen episodes occurred in the pre-2010 group, even though 9 of 13 (69%) serotyped isolates were covered by PPV. Two episodes occurred in the post-2010 group; neither serotype was covered by PCV. Thus, with PCV introduction, IPD rate was significantly reduced from 38.5/1000 unique HSCTs pre-2010 to 4.0/1000 unique HSCTs post-2010 (P < .001). A significant reduction was seen in both auto-HSCTs (from 29.4 to 3.1 /1000 unique auto-HSCTs; P = .011) and allo-HSCTs (from 58.3 to 5.6/1000 unique allo-HSCTs; P = .011). PCV demonstrated superior clinical effectiveness over PPV, highlighting its importance in preventing infectious complications after HSCT. Robust vaccination programs at transplantation centers are needed to optimize vaccination uptake and completion.

Serotype distribution of Streptococcus pneumoniae among healthy carriers and clinical patients: a systematic review from Iran.

Streptococcus pneumoniae is associated with high morbidity and mortality in the world. Commercially licensed and available pneumococcal conjugate vaccines (PCVs) contain 10 (PCV10) and 13 (PCV13) pneumococcal serotypes. The most common serotypes of S. pneumoniae causing clinical diseases and carriers of S. pneumoniae in Iran are not yet known. Reviewing and reporting trends in the distribution of pneumococcal serotypes in Iran will be useful for policy-making as PCV is being introduced into Iran's routine immunization program. Here, we report a systematic literature review of studies regarding S. pneumoniae serotype distribution in clinical and carrier patients in Iran. MEDLINE (via PubMed), Scopus, Embase, Ovid, Google Scholar, Web of Science, and the Iranian Database were used to identify relevant papers published from 1 January 2000 to 21 August 2019. The search returned 8 relevant articles. Among serotypes causing invasive pneumococcal diseases (IPD), serotype 23F (16.4%) was the most circulating serotype followed by 19F (15.2%), 19A (11.3%), 6A/B (9.2%), 9 V (5.8%), and 11A (5.14%). In carrier patients, the most common serotypes were, in rank order, 6A/B (10%), 19F (9%), 14(6.2%), 17F (4.8%), and 20(4.5%). Vaccine coverage among IPD patients would be 67.1% for PCV10-TT and 73.8% for PCV13. The present review demonstrates that the serotypes which were most responsible for disease in Iran are included in PCV10-TT and PCV13. However, sentinel surveillance must be continued in representative parts of the country to assess changing trends in the distribution of pneumococcal serotypes and their implications for vaccine selection and rollout in Iran.

Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study.

BACKGROUND: Streptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore. METHODS: Retrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design. RESULTS: We identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson's score 1 (IQR 0-4), vs 3 (1-5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8-17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06-0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson's score > 3. CONCLUSION: Patients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.

Influenza, pneumococcal and herpes zoster vaccination rates among patients over 65 years of age, related factors, and their knowledge and attitudes.

BACKGROUND: In this study, we aimed to determine influenza, pneumococcal, and herpes zoster (HZ) vaccination status, among patients aged 65 or above, and to determine their level of knowledge about these vaccines and the factors affecting the vaccination rates. METHODS: This was a cross-sectional descriptive study conducted through face-to-face interviews with patients who were admitted to Gemerek State Hospital Family Medicine Clinics. The questionnaire prepared by the researchers following the literature review was applied by researchers. RESULTS: The study included a total of 326 participants with a mean age of 71.59 ± 6.96 (min: 65, max: 96). Influenza, pneumococcal, and HZ vaccination rates were 21.8% (n = 71), 4.3% (n = 14), and 1.8% (n = 6), respectively. The odds ratio (OR) in the patients for whom influenza vaccination was recommended was calculated to be 15.25 compared to those for whom influenza vaccination was not recommended (95% CI 8.73-26.64, p < 0.001), OR in the patients for whom pneumococcal vaccination was recommended was calculated to be 257.5 compared to those for whom pneumococcal vaccination was not recommended (95% CI 50.75-1306.44, p < 0.001), and OR in the patients for whom HZ vaccination was recommended was calculated to be 126.0 compared to those for whom HZ vaccination was not recommended (95% CI 18.59-853.92, p < 0.001). CONCLUSIONS: The main findings of the present study are that the vaccination rate for all three vaccines is low, vaccination recommendation by a physician significantly increases vaccination rates, and the vaccination rate of patients, who have been informed by the physician about the vaccine, is higher.

Pediatric parapneumonic effusion before and after national pneumococcal vaccination programs in Taiwan.

BACKGROUND: Reports on the effectiveness of pneumococcal conjugate vaccines (PCVs) on pediatric parapneumonic effusion are limited. We report the changes in cases and etiologies of pediatric parapneumonic effusion in a children's hospital before and after national PCV13 vaccination programs. METHODS: We screened medical records of children 0-18 years admitted to the National Taiwan University Hospital with diagnoses of lobar pneumonia and parapneumonic effusion between 2008 and 2017. Patients with effusion analyses were included. Results of blood, pleural fluid, and respiratory specimens surveyed as standard care were analyzed. RESULTS: Diagnostic testing revealed at least a pathogen in 85% of 202 children with lobar pneumonia and parapneumonic effusion. After national PCV13 immunization, pneumococcal empyema decreased by 72% among 2- to 5-year olds. Mycoplasma pneumoniae was the second most common etiology. There were marked differences in effusion characteristics, metabolic, and respiratory parameters between children infected with pneumococcus and M. pneumoniae. CONCLUSION: The effectiveness of the national PCV13 immunization programs on pneumococcal empyema was evident and remained substantial after 4 years in Taiwan. Continuous surveillance is important to monitor the emergence of other pathogens including non-PCV serotypes and M. pneumoniae.

[Analysis on the project personnel's attitude and its influential factors of 23-valent pneumococcal polysaccharide vaccination program for the elderly in Shanghai].

Objective: To understand the project personnel's attitude towards the 23-valent pneumococcal polysaccharide vaccination program for the elderly in Shanghai and its conversion to routine vaccination and to explore its influential factors, so as to provide reference for the further development of the program. Methods: In 2016, a one-to-one questionnaire survey was conducted among the people involved in the project in the 9 districts of Shanghai and the data of demographic characteristics, cognition of pneumococcal pneumonia and PPV23, evaluation of the project, support rate of the project and its conversion to routine vaccination of the project personnel were collected. Results: Among the 2005 respondents, 28.6% (574 persons) of them were male, 85.5% (1 714 persons) of them supported the free vaccination for the elderly, and 69.5% of them (1 394 persons) supported the routine vaccination. For the 23-valent pneumococcal polysaccharide vaccination program, people under 55 years old, in Qingpu District, with poor cognition of pneumonia and 23-valent pneumococcal polysaccharide vaccine (PPV23) or having lower evaluation of the project's scientificity or enforceability had lower support rate than others, and the OR (95%CI) were 0.38 (0.19-0.75), 0.21 (0.10-0.43), 0.16 (0.06-0.41) and 0.26 (0.10-0.69). People believing that the elderly were susceptible to pneumococcal pneumonia and PPV23 was safe and reliable, and those who were willing to vaccinate the elderly at home had higher support rate, and the OR (95%CI) were 2.30 (1.18-4.47), 2.84 (1.62-4.69) and 5.60 (3.74-8.38). For the program's conversion to routine vaccination, people under 35 years old, in Qingpu District, in the vaccination clinic, and those believing that the project was not scientific and difficult to implement had low support rate, and the OR (95%CI) were 0.56 (0.32-0.98), 0.48 (0.26-0.89), 0.26 (0.12-0.59), 0.58 (0.42-0.79) and 0.50 (0.30-0.81); people with technical secondary school or senior school, in Jiading, Putuo or Minhang District, believing that PPV23 was effective in the prevention of pneumococcal pneumonia in the elderly, and those who were willing to vaccinate the elderly with PPV23 had higher support rate, and the OR (95%CI) were 1.63 (1.11-2.39), 2.28 (1.71-3.03), 1.69 (1.25-2.28) and 4.10 (2.86-5.88). Conclusion: The support rate of pneumococcal vaccination project for the elderly in Shanghai needs to be improved, especially its conversion to the routine vaccination.

Indirect Effects of 10-Valent Pneumococcal Conjugate Vaccine Against Adult Pneumococcal Pneumonia in Rural Western Kenya.

BACKGROUND: Data on pneumococcal conjugate vaccine (PCV) indirect effects in low-income countries with high human immunodeficiency virus (HIV) burden are limited. We examined adult pneumococcal pneumonia incidence before and after PCV introduction in Kenya in 2011. METHODS: From 1 January 2008 to 31 December 2016, we conducted surveillance for acute respiratory infection (ARI) among ~12 000 adults (≥18 years) in western Kenya, where HIV prevalence is ~17%. ARI cases (cough or difficulty breathing or chest pain, plus temperature ≥38.0°C or oxygen saturation <90%) presenting to a clinic underwent blood culture and pneumococcal urine antigen testing (UAT). We calculated ARI incidence and adjusted for healthcare seeking. The proportion of ARI cases with pneumococcus detected among those with complete testing (blood culture and UAT) was multiplied by adjusted ARI incidence to estimate pneumococcal pneumonia incidence. RESULTS: Pre-PCV (2008-2010) crude and adjusted ARI incidences were 3.14 and 5.30/100 person-years-observation (pyo), respectively. Among ARI cases, 39.0% (340/872) had both blood culture and UAT; 21.2% (72/340) had pneumococcus detected, yielding a baseline pneumococcal pneumonia incidence of 1.12/100 pyo (95% confidence interval [CI]: 1.0-1.3). In each post-PCV year (2012-2016), the incidence was significantly lower than baseline; with incidence rate ratios (IRRs) of 0.53 (95% CI: 0.31-0.61) in 2012 and 0.13 (95% CI: 0.09-0.17) in 2016. Similar declines were observed in HIV-infected (IRR: 0.13; 95% CI: 0.08-0.22) and HIV-uninfected (IRR: 0.10; 95% CI: 0.05-0.20) adults. CONCLUSIONS: Adult pneumococcal pneumonia declined in western Kenya following PCV introduction, likely reflecting vaccine indirect effects. Evidence of herd protection is critical for guiding PCV policy decisions in resource-constrained areas.

Pneumococcal Conjugate Vaccine Impact on Meningitis and Pneumonia Among Children Aged <5 Years-Zimbabwe, 2010-2016.

BACKGROUND: Streptococcus pneumoniae is a leading cause of pneumonia and meningitis in children aged <5 years. Zimbabwe introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2012 using a 3-dose infant schedule with no booster dose or catch-up campaign. We evaluated the impact of PCV13 on pediatric pneumonia and meningitis. METHODS: We examined annual changes in the proportion of hospitalizations due to pneumonia and meningitis among children aged <5 years at Harare Central Hospital (HCH) pre-PCV13 (January 2010-June 2012) and post-PCV13 (July 2013-December 2016) using a negative binomial regression model, adjusting for seasonality. We also evaluated post-PCV13 changes in serotype distribution among children with confirmed pneumococcal meningitis at HCH and acute respiratory infection (ARI) trends using Ministry of Health outpatient data. RESULTS: Pneumonia hospitalizations among children aged <5 years steadily declined pre-PCV13; no significant change in annual decline was observed post-PCV13. Post-PCV13 introduction, meningitis hospitalization decreased 30% annually (95% confidence interval [CI], -42, -14) among children aged 12-59 months, and no change was observed among children aged 0-11 months. Pneumococcal meningitis caused by PCV13 serotypes decreased from 100% in 2011 to 50% in 2016. Annual severe and moderate outpatient ARI decreased by 30% (95% CI, -33, -26) and 7% (95% CI, -11, -2), respectively, post-PCV13 introduction. CONCLUSIONS: We observed declines in pediatric meningitis hospitalizations, PCV13-type pneumococcal meningitis, and severe and moderate ARI outpatient visits post-PCV13 introduction. Low specificity of discharge codes, changes in referral patterns, and improvements in human immunodeficiency virus care may have contributed to the lack of additional declines in pneumonia hospitalizations post-PCV13 introduction.

Indirect Effects of Pneumococcal Childhood Vaccination in Individuals Treated With Immunosuppressive Drugs in Ambulatory Care: A Case-cohort Study.

BACKGROUND: The extent to which iatrogenically-immunosuppressed individuals benefit from indirect effects of childhood vaccination with pneumococcal conjugate vaccines (PCVs) is unknown. We determined how the sequential introduction of PCV7 (2006) and PCV13 (2011) in the Norwegian childhood vaccination program has affected the epidemiology of invasive pneumococcal disease (IPD) in individuals treated with immunosuppressants in ambulatory care. METHODS: We conducted a case-cohort study comprising 7926 IPD cases reported to the Norwegian Surveillance System for Communicable Diseases in 2005-2014 and 249998 individuals randomly selected from the National Registry in 2012. We defined immunosuppressive treatment groups based on dispensed prescriptions retrieved from the Norwegian Prescription Database. Incidences and age-adjusted relative risks (RR) were estimated. RESULTS: IPD incidences decreased in all groups. The PCV13 incidence decreased by 5-12% across groups. The non-PCV13 incidence increased by 4-10%, mostly in individuals on chemotherapy (overlapping 95% confidence intervals). In the PCV13 era, the RR for IPD was highest (significant) and the percentage of cases caused by the polysaccharide vaccine PPV23 serotypes lowest (numerical) in individuals on chemotherapy (RR = 20.4, PPV23 = 52%), followed by individuals on corticosteroids (RR = 6.2, PPV23 = 64%), other immunosuppressants (RR = 5.6, PPV23 = 68%), and no immunosuppressants (RR = 1 [reference], PPV23 = 74%). CONCLUSIONS: IPD incidences declined after PCV introduction in both immunocompetent and iatrogenically-immunosuppressed individuals, underscoring the benefit of childhood vaccination for the entire population. Still, individuals treated with immunosuppressants in ambulatory care are at increased risk of IPD caused by a more diverse group of serotypes.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine Among Adults: A Systematic Review and Meta-analysis.

BACKGROUND: A notable reduction of the pneumococcal disease burden among adults was observed after the introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in many jurisdictions; a comparative assessment of PCV13's impact was missing. Our objective was to summarize the available data and assess the change in the incidence of invasive pneumococcal disease (IPD) in adults after the introduction of PCV13 in childhood immunization programs. METHODS: We conducted a systematic literature search from January 1946 to May 2017 of randomized, controlled trials and observational studies OBS reporting the incidence of IPD, non-invasive pneumococcal disease, hospitalizations, and mortality in adults for the periods before and after the introduction of PCV13. Incidence rate ratios (IRRs) were pooled across studies using restricted, maximum-likelihood, random-effects models. RESULTS: From 3306 records,we included 29 OBS studies and 2033961 cases. Significantly lower IPD rates were seen after PCV13 introduction in adults aged <65 years (IRR 0.78, 95% confidence interval [CI] 0.72-0.85) and those aged ≥65 years (IRR 0.86, 95% CI 0.81-0.91). Lower rates of IPD were seen with PCV7 (IRR 0.45, 95% CI 0.38-0.54) and PCV13 serotypes (IRR 0.60, 95% CI 0.54-0.68). A significantly higher IRR of 1.10 (95% CI 1.04-1.17) for non-vaccine serotypes was observed, especially among those aged 65 years and older (IRR 1.20, 95% CI 1.11-1.29). CONCLUSIONS: PCV13 use in children had a moderate impact on reducing the overall and vaccine-type IPDs, but there was a significant increase in non-vaccine type IPDs among adults, especially in those over 65 years.