Pneumococcal Disease In Adults Research Articles

Severe outcomes following invasive pneumococcal disease in adults in France

Abstract Pneumococcal vaccine serotypes and host factors may increase the risk of severe invasive pneumococcal disease (IPD). In France, pneumococcal vaccination in adults is recommended for at-risk groups (immunosuppression or at-risk conditions/diseases). In 2014-2017, we conducted a study of IPD in adults to identify factors/serotypes associated with disease severity. We included IPD cases, excluding meningitis, in adults from 25 acute-care sentinel hospitals in six regions. Severe cases were IPD patients either admitted to an ICU or under mechanical ventilation or with severe sepsis or shock. Infectious disease specialists collected clinical/microbiological data on all cases. We calculated adjusted risk ratios (aRR) using binomial regression. In 2014-2017, 908 cases (median age 71 (range 18-101) years) were diagnosed; 48%(431/908) were severe and 84%(764/908) were at-risk. Compared with non-risk individuals, the risk of severe disease increased from 20% (aRR 1.2; 95%CI 1.0-1.4) in cases with 1-2 chronic diseases to 30% (aHR 1.3; 95%CI 1.0-7.0) in those with >2 chronic diseases. The risk of severe disease was 42% (aRR 1.4; 95%CI 1.2-1.6) higher for PCV13 serotypes compared with non-vaccine serotypes. Among cases infected with PCV13 serotypes, the risk of severe disease did not differ (aRR 0.96; 95%CI 1.2-23) between no-risk or at-risk cases. However, among cases infected with non-vaccine serotypes, the risk increased 49% (aRR 1.5; 95%CI 2.1-22) in at-risk compared with no-risk cases (homogeneity test p = 0.03). We observed a cumulative effect of concurrent comorbidities on severe IPD outcomes. The risk of severe IPD increased for vaccine serotypes regardless of risk status. However, non-vaccine serotypes increased the risk of severe outcomes only in risk groups, suggesting a different interplay between host factors and the pathogen in vulnerable groups. We recommend enhancing vaccination among risk groups and especially in those most at risk for poor IPD-related outcomes. Key messages Cumulative effect of concurrent comorbidities on severe invasive pneumococcal disease outcomes. Non-vaccine serotypes increase the risk of severe invasive pneumococcal disease outcomes only in vulnerable groups.

2706. Indirect Effects of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Adults in British Columbia, Canada

BackgroundMany jurisdictions report a significant reduction in invasive pneumococcal disease (IPD) in adults following implementation of the pneumococcal conjugate vaccines, 7-valent (PCV7) and 13-valent (PCV13) in childhood immunization programs. This study evaluates the indirect effect of conjugate vaccines on IPD in British Columbia, Canada over a 14 year period (2002–2015).MethodsUsing provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in adults 18 years of age and older. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.ResultsA total of 3793 cases were reported over the 14 year period. The overall annual incidence increased from 4.32 cases per 100,000 population in 2002 to 8.61 cases per 100,000 population in 2015. Overall, IPD has increased by 80% (IRR: 1.80; 95% CI: 1.59–2.04) compared with baseline, especially in adults ≥ 85 years of age (PCV13 vs baseline: IRR: 1.90; 95% CI: 1.25–03.05). This increase was the highest after introduction of PCV7 (IRR: 1.87; 95% CI: 1.65–2.11); the incremental change after introduction of PCV13 was non-significant (IRR 0.96; 95% CI: 0.90–1.03). While PCV7 type IPD plummeted by 76% (IRR 0.24; 95% CI: 0.18–0.31) since introduction of PCV7 compared with baseline, a modest decline in PCV13 type IPD of 20% was seen (IRR 0.80; 95% CI: 0.71–0.89) since introduction of PCV13.ConclusionAlthough PCV7-type IPD has decreased substantially, only a modest reduction in IPD from the additional 6 serotypes in the PCV13 vaccine was observed.Disclosures All authors: No reported disclosures.

2716. Persistence of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Serotypes in Invasive Pneumococcal Disease in Adults in Southern Ontario Canada Despite Routine Pediatric Vaccination

BackgroundIn Ontario, Canada, PCV13 is covered for immunocompromised (IC) adults over 50y. PCV13 programs are thought not to be cost-effective in other adults because it is assumed that herd immunity from pediatric vaccination programs (PCV7 since 2005; PCV13 since 2010) will reduce PCV13 disease burden dramatically in adults. We analyzed data from the Toronto Invasive Bacterial Diseases Network (TIBDN) to ask whether PCV13-type invasive pneumococcal disease (IPD) in adults persists in our population.MethodsTIBDN performs population-based surveillance for IPD in Toronto+Peel Region, Ontario (pop4.1M). All microbiology laboratories receiving specimens from residents report cases of IPD and submit isolates to a central study lab for serotyping; annual audits are conducted. Demographic, medical and vaccination information are obtained from patients, families and physicians. Population data are from Statistics Canada.ResultsSince 1995, 10,365 episodes of IPD have been identified; detailed medical information was available for 9,801 (95%) and serotyping for 9411 (91%). Among 8658 adult cases, 4,273 (49%) were in those aged 15–64 years, and 4,285 (51%) in those aged >645 years. The most common diagnoses were pneumonia (5,978/8,025, 74%) and bacteremia without focus (1,030, 13%); 470 (4.6%) cases had meningitis; the case fatality rate (CFR) was 21%. The incidence of disease due to STs in PCV13 in adults declined from 7.0/100,000/year 2001 to 2.9/100,000/year in 2015–2018 and was stable from 2015–2018 (Figure 1). The incidence was > 5/100,000/year in non-IC patients over 65 years, and younger patients with cancer and kidney disease (Figure 2). In IPD from 2015 to 2018, adult patients with PCV13 ST disease were younger (median age 64 years vs. 67 years, P = .03) than other patients; there was no significant difference in the proportion with at least one underlying chronic condition (253, 69% PCV13ST, vs. 541,74% other ST, P = 0.08), or in CFR (59, 16% PCV13 vs. 145, 20% other, P = 0.13). The ST distribution of cases due to PCV13 STs is shown in Figure 3.ConclusionA significant burden of IPD due to PCV13 serotypes persists in adults in our population despite 8 years of routine pediatric PCV13 vaccination. This burden needs to be considered in assessing the value and cost-effectiveness of PCV programs for adults. Disclosures All authors: No reported disclosures.

Evolution of serotypes in bacteremic pneumococcal adult pneumonia in the period 2001–2014, after introduction of the pneumococcal conjugate vaccine in bizkaia (spain)

The introduction of pneumococcal conjugate vaccines (PCV7 and PCV13) in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease in adults. The aim of this study is to analyze the distribution of pneumococcal serotypes in adults with bacteremic pneumococcal community-acquired pneumonia (BPP) after the introduction of PCVs in childhood, and the impact of age and comorbidity on this distribution. We conducted an observational study of all adults hospitalized with BPP between 2001 and 2014, in two tertiary hospitals. Overall, we identified 451 cases of BPP (2001–2005: 194, 2006–2010: 134, 2011–2014: 123). The rate of appearance of new cases decreased over the study period. In 70% of the cases, the serotypes found were among those included in PCV13. The most prevalent serotypes were 3 (23.1%), 7F (14.6%), 19A (8.4%) and 1 (7.5%). There was a significant trend to decrease in the percentage of BPP cases due to PCV7 from period 2001–2005 to 2011–2014 (p = 0.0166) and a significant trend to increase in the six serotypes added to form PCV 13 (p = 0.0003). Serotype 3 was the most frequent in patients who developed complications during hospitalization. We did not detect a significant increase in cases caused by non-PCV13 serotypes. The most frequent non-PCV13 serotype was 22F. In conclusion, a significant proportion of adults continue to develop BPP with vaccine serotypes despite infant pneumococcal vaccination. There is a need for further strategies to reduce the current burden of this disease on adults.

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BackgroundFew studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. MethodsThis observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. ResultsOf 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status. ConclusionsAfter implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.

Cost-effectiveness of the 13-valent pneumococcal conjugate vaccine in adults in Portugal versus “no vaccination” and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine

ABSTRACT The burden of pneumococcal disease in adults is substantial from a social and economic point of view. This study assessed the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults versus “no vaccination” and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A Markov model was used to simulate three strategies: no vaccination, complete vaccination with PPSV23 and complete vaccination with PCV13. The comparison between strategies allowed the estimation of clinical and economic outcomes including incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR). The model took into account the distributions of age, risk profile, vaccination status, type of immunization and time since vaccination in the population. A societal perspective was adopted and a lifetime horizon was considered. Different sources of data and assumptions were used to calibrate PPSV23 and PCV13 effectiveness. Inpatient costs were based on the 2013 diagnosis-related group (DRG) database for National Health Service (NHS) hospitals and expert opinion; NHS official tariffs were the main source for unitary costs. PCV13 shows ICURs of €17,746/QALY and €13,146/QALY versus “no vaccination” and vaccination with PPSV23, respectively. Results proved to be robust in univariate sensitivity analyses, where all ratios were below a €20,000 threshold, with the exception of the scenario with PCV13 effectiveness halved. In a probabilistic sensitivity analysis, 94% of simulations showed cost-effectiveness ratios lower than €20,000/QALY, in both strategies. It was found that PCV13 is a cost-effective strategy to prevent pneumococcal disease in adults in Portugal.

Indirect costs of adult pneumococcal disease and productivity-based rate of return to PCV13 vaccination for older adults and elderly diabetics in Denmark

Indirect costs of adult pneumococcal disease and productivity-based rate of return to PCV13 vaccination for older adults and elderly diabetics in Denmark

Human monoclonal antibodies isolated from a primary pneumococcal conjugate Vaccinee demonstrates the expansion of an antigen-driven Hypermutated memory B cell response

BackgroundCommunity-acquired pneumonia is a leading infectious cause of hospitalization. A few vaccines exist to prevent pneumococcal disease in adults, including a pneumococcal polysaccharide unconjugated vaccine and a protein conjugated polysaccharide vaccine. Previous studies on the human immune response to the unconjugated vaccine showed that the vaccine boosted the existing memory B cells. In the present study, we investigated the human B cell immune response following pneumococcal polysaccharide conjugate vaccination.MethodsPlasmablast B cells from a pneumococcal polysaccharide conjugate vaccinee were isolated and cloned for analysis. In response to primary vaccination, identical sequences from the plasmablast-derived antibodies were identified from multiple B cells, demonstrating evidence of clonal expansion. We evaluated the binding specificity of these human monoclonal antibodies in immunoassays, and tested there in vitro function in a multiplexed opsonophagocytic assay (MOPA). To characterize the plasmablast B cell response to the pneumococcal conjugated vaccine, the germline usage and the variable region somatic hypermutations on these antibodies were analyzed. Furthermore, a serotype 4 polysaccharide-specific antibody was tested in an animal challenge study to explore the in vivo functional activity.ResultsThe data suggests that the pneumococcal polysaccharide conjugate vaccine boosted memory B cell responses, likely derived from previous pneumococcal exposure. The majority of the plasmablast-derived antibodies contained higher numbers of variable region somatic hypermutations and evidence for selection, as demonstrated by replacement to silent ratio’s (R/S) greater than 2.9 in the complementarity-determining regions (CDRs). In addition, we found that VH3/JH4 was the predominant germline sequence used in these polysaccharide-specific B cells. All of the tested antibodies demonstrated narrow polysaccharide specificity in ELISA binding, and demonstrated functional opsonophagocytic killing (OPK) activity in the MOPA assay. The in-vivo animal challenge study showed that the tested serotype 4 polysaccharide-specific antibody demonstrated a potent protective effect when administered prior to bacterial challenge.ConclusionsThe findings on the pneumococcal polysaccharide conjugate vaccine responses from a vaccinated subject reported in this study are similar to previously published data on the pneumococcal polysaccharide unconjugated vaccine responses. In both vaccine regimens, the pre-existing human memory B cells were expanded after vaccination with preferential use of the germline VH3/JH4 genes.

1426. Impact of Routine Pediatric PCV13 on the Incidence and Severity of Invasive Pneumococcal Disease in Adults in Ontario, Canada

BackgroundMonitoring the incidence and severity of disease due to varied pneumococcal (Pn) serotypes (STs) over time is important in assessing the benefit of Pn vaccines. We describe changes in adult IPD after the 2010 introduction of routine infant PCV13 in Ontario, Canada (PCV13 is funded only for immunocompromised adults ≥50 years as of 2015).MethodsTIBDN has conducted population-based surveillance for IPD in Toronto/Peel, Canada (pop 4.3M) since 1995. Cases are reported to a central office; one isolate/case is serotyped. Demographic and clinical data are collected by chart review and patient/family physician interview.ResultsOf 6,275 episodes of adult IPD, 5,674 (90%) have STs and 6,007 (96%) detailed clinical data. Incidence of IPD decreased from 14.2/100,000/year in 1995 to 6.0/100,000/year in 2013–2017). One thousand two hundred and three (19%) adults with IPD were 15–44 years, 1,889 (30%) were 45–64 years, 3,182 (51%) ≥65 years. Figures 1 and 2 show rates over time by ST group and age. In multivariable analyses, there was no difference across vaccine ST groups (nonvaccine type (NVT) vs. PPV23 not PCV vs. PCV13) in patient age, proportion with ICU admission, requirement for mechanical ventilation (MV), death, length of stay (LOS) or diagnosis of meningitis, except that patients with NVT isolates were more likely to require ICU admission (OR 1.5, 95% CI 1.2,2.0), and to have meningitis (OR 1.9, 95% CI 1.1,3.3). Case fatality declined from 25% (480/1,949) 1995–2001 to 19% (148/763) in 2012–2017 (multivariable OR/year 0.98 95% CI 0.97,0.99); requirements for ICU admission (26–31%; OR/year 1.02, 95% CI 1.01,1.03) and MV (OR/year 18–22%; 1.02, 95% CI 1.01–1.03) increased, LOS did not change. From 2013 to 2017, the distribution of vaccine group STs has not changed: 37% PCV13 (383/1,031); 20% PCV20not13 (205); 9% PPV23not 20 (94), 34% NVT (349). NVT strains include over 23 ST, most commonly 23A (72, 21%), 15A (46, 13%), 35B (37,11%), 6C (36, 10%), 23B (20, 8%).ConclusionIn our population, with infant but no routine adult PCV13, the incidence of adult IPD appears to have stabilized, with PCV13 ST strains contributing 37% of IPD. Case fatality has decreased; ICU admission increased. Adult vaccination may be required to further reduce PCV13 ST infections.Figure 1: IPD incidence, adults 15–65 years, by ST group, 2006–2017. Infant PCV7 started 2005 and PCV13 in 2010.Figure 1.IPD incidence, adults ≥65 years, by ST group, 2006–2017. Infant PCV7 started 2005 and PCV13 in 2010. Disclosures A. McGeer, Pfizer: Grant Investigator and Scientific Advisor, Research grant and Research support; Merck: Scientific Advisor, Research support; GlaxoSmithKline: Grant Investigator and Scientific Advisor, Research support.

1443. Serotypes 8 and 3 Are the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2015–2017)

BackgroundIn Portugal, following the use of PCVs in children, there were major changes in the serotype distribution of the pneumococcal population in adult pneumococcal invasive disease (IPD). The inclusion of PCV13 in the National Immunization Plan in 2015 could have an even greater impact on adult IPD. To evaluate this, we monitored the serotypes and antimicrobial resistance of invasive pneumococcal isolates in 2015–2017.MethodsA total of 1,495 adult IPD isolates were recovered, serotyped by Quellung and tested for susceptibility to antimicrobials by disk diffusion or Etest.ResultsThe number of isolates recovered in each year remained approximately constant. Among the 1,495 isolates, 58 different serotypes were found and only a small proportion of these were nontypeable (0.6%, n = 9). The most common were serotypes 8 (18%), 3 (15%), 22F and 14 (7% each), 19A (6%), and 20 (4%). The majority of isolates expressed serotypes exclusively found in the 23-valent polysaccharide vaccine (41%, n = 619). A considerable number of isolates expressed PCV serotypes (n = 563), of which 207 isolates (14%) expressed PCV7 serotypes and the remaining isolates expressed the additional serotypes included in PCV13 (n = 356, 24%). Non-vaccine types (NVT) were found in 313 isolates (n = 21%) and among these, serotypes 6C, 15A, 16F, 23A and 31 were the most prevalent, together accounting for approximately half of the NVT. Overall, 19% of the isolates presented resistance to erythromycin and penicillin nonsusceptibility was found in 17% of the isolates recovered in 2015–2017.ConclusionAfter several years of pneumococcal conjugate vaccines use in children, PCV serotypes are still frequently responsible for adult IPD. Moreover, serotypes exclusively found in PPV23 were also found to be important causes of invasive disease in this period, suggesting an important role for vaccination in disease prevention in this age group.Disclosures M. Ramirez, Pfizer: Speaker’s Bureau, Speaker honorarium; GlaxoSmithKline: Consultant, Consulting fee; Merck Sharp and Dohme: Consultant, Consulting fee. J. Melo-Cristino, Pfizer: Grant Investigator and Speaker’s Bureau, Research grant and Speaker honorarium; Merck Sharp and Dohme.: Speaker’s Bureau, Speaker honorarium.

330. Head and Spine Injuries Increase Risk of Streptococcus pneumoniae Meningitis in Adults

BackgroundIn the United States, Streptococcus pneumoniae is responsible for 50% of bacterial meningitis cases. However, pneumococcal vaccines were not recommended for routine childhood immunization until pneumococcal conjugate vaccine became available in 2000, and much of the adult population has not received pneumococcal conjugate or polysaccharide vaccine. Limited case reports and series suggest that a history of neurosurgery or skull fractures may be associated with an increased risk for pneumococcal meningitis.MethodsA case–control study was conducted within the Kaiser Permanente Northern California (KPNC) patient population to evaluate the association of prior head injury (HI) or head or spine surgery (H/SS) with pneumococcal meningitis. Cases were pneumococcal meningitis patients ≥18 years of age diagnosed from January 1, 2008 through October 31, 2017. Controls were individually matched 2:1 by age, sex, KPNC facility and membership length. A blinded chart review was done to identify history of HI and H/SS. Analyses were performed using conditional logistic regression.ResultsEighty-four patients were found to have pneumococcal meningitis and were matched with 168 controls. Fifteen of the 84 cases (17.9%) and 6 of the 168 controls (3.6%) had prior HI or H/SS. Case histories included concussion (n = 3), mastoidectomy (n = 2), nasal surgery (n = 3), neurosurgery (n = 3), and spine surgery (n = 5). One case was noted to have two surgical histories. Ten of the 15 cases with HI or H/SS (66.7%) had not received pneumococcal vaccine. Cases had 5.0 times higher odds of having a history of HI or H/SS (95% confidence interval (CI) 1.9–12.9). These odds remained significantly elevated for H/SS only (odds ratio (OR) 10.0, 95% CI 1.2 – 85.6), but not for HI (OR 3.0, 95% CI 0.5 – 18.0). As no skull fractures were detected, HI consisted of concussions only.ConclusionPrior HI or H/SS significantly increased the odds for pneumococcal meningitis. Surveillance data from the Centers of Disease Control and Prevention indicate that 60–75% of invasive pneumococcal disease in adults is due to serotypes included in the pneumococcal vaccines. Given the number of unvaccinated cases, some of these cases may have been vaccine preventable. Such patients may benefit from pneumococcal immunization to reduce the risk of pneumococcal meningitis.Disclosures All authors: No reported disclosures.

Invasive Pneumococcal Disease in Adults in a Private Hospital. Mortality and Serotypes. Revision Period 2013-2016

Invasive Pneumococcal Disease in Adults in a Private Hospital. Mortality and Serotypes. Revision Period 2013-2016

Pneumococcal Disease and the Effectiveness of the PPV23 Vaccine in Adults: A Two-Stage Bayesian Meta-Analysis of Observational and RCT Reports

The efficacy of PPV-23 vaccine on outcomes of pneumococcal disease in adults still remains controversial due mainly to the lack of consistency between the results obtained from observational studies(OSs) and those obtained from randomized controlled trials(RCTs). As a consequence, the complexity in the structure of evidence available, in turn, generates a challenge for combining disparate pieces of evidence quantitatively. In this regard, we used a hierarchical Bayesian inference-based evidence synthesis of RCTs and observational data using a two-stage approach (in addition to a traditional random-effects meta-analysis) to examine the effectiveness of PPV-23 in adults. To this end, 21 studies were included involving 826109 adult participants. By a two-stage Bayesian meta-analysis, which was directly used for combining studies of different designs, the overall log OR (95% credible interval) for IPDs was −0.1048 (−0.3920,−0.0250), indicating a significant protective effect of the vaccination against IPDs. No significant effect of PPV-23 was found on all-cause pneumonia, pneumococcal pneumonia, and death from pneumonia, which confirmed the results obtained by a traditional method followed by stratified and sensitivity analyses. The estimated overall log OR (95% credible interval) was −0.0002 (−0.0241,0.0142), −0.0002 (−0.0110,0.0122), and −6.3912 × 10−5 (−0.0219,0.0131), respectively. The PPV-23 vaccine might be effective in preventing the most severe invasive forms of pneumococcal diseases, but not effective in preventing other clinical outcomes, in the adult population of 18 years and older.

Risk of pneumococcal diseases in adults with underlying medical conditions: a retrospective, cohort study using two Japanese healthcare databases

ObjectivesTo quantify the risk of pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) in adults aged ≥19 years with underlying medical conditions compared with healthy adults of the same age...

Effectiveness of the 13-valent pneumococcal conjugate vaccine against adult pneumonia in Italy: a case–control study in a 2-year prospective cohort

ObjectivesCurrent strategies to prevent adult pneumococcal disease have been recently reviewed in Italy. We did a postlicensure study to estimate the direct vaccine effectiveness (VE) of the 13-valent pneumococcal conjugate...

The Evolving Epidemiology of Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Strains Isolated from Adults in Crete, Greece, 2009-2016.

BackgroundPneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009–2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13).Materials and MethodsAntimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ≥2 non-β-lactam antimicrobials.ResultsA total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively.ConclusionAlthough pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

The pilgrimage and the burden of pneumococcal disease in adults

Pneumococcal disease is responsible for significant morbidity and mortality. All over the world, 1.6 million people die of pneumococcal disease every year; this estimate includes the deaths of 1 million children aged less than 5 years and the deaths of 600.000- 800.000 adults. The burden of pneumococcal disease is high in adults. Increasing age and the presence of comorbidity has a significant affected of the risk of developing the disease. During mass gatherings, such as pilgrimage individuals, is exposed to severe community-acquired pneumococcal infections. Individuals who has Streptococcus pneumoniae in nasopharynx, have the potential to infection and leave exposed to the risk of pneumococcal disease the other Individuals with sneezing, coughing or out of breath, given breath through droplets of these microorganisms. In the present review, the relationship of pneumococcal disease in adults and pilgrimage, vaccination strategies will be considered and then during a visit to Pilgrimate and Umrah pilgrims against the current vaccine recommendations will be summarised.

Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine in adults 50 to 65 years of age in India: An open-label trial

ABSTRACTStreptococcus pneumoniae infection is a major global public health concern in older adults, especially as life expectancy continues to increase in most countries, including India. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) with the ability to enhance immunity (immunologic memory) on natural exposure or revaccination has been shown to protect against community-acquired pneumonia and invasive pneumococcal disease in adults 65 years of age and older. An unconjugated 23-valent pneumococcal polysaccharide vaccine has been available for decades; however, data on protection against pneumonia are inconsistent. For the first time, a multicenter study has been conducted in India to assess the safety and immunogenicity of a single dose of PCV13 in adults aged 50 to 65 years. In this study, PCV13 elicited robust immune responses against all 13 pneumococcal serotypes as reflected by the magnitude of geometric mean fold rises (range, 6.6–102.7) in functional antibody levels from before to 1 month after vaccination. No serious adverse events occurred. These clinical trial findings support the safety and immunogenicity of PCV13 when administered to adults in India and indicate that a single dose of PCV13 has the potential to protect against vaccine-type pneumococcal disease in adults aged 50 to 65 years. ClinicalTrials.gov identifier: NCT02034877

Impact of pneumococcal polysaccharide vaccine on incidence and mortality after pneumonia in adults aged ≥60 years—a population-based retrospective cohort study

ObjectivesThe 23-valent pneumococcal polysaccharide vaccine (PPV) is recommended for prevention of pneumococcal diseases in adults at risk. Few data exist on time-, age- and sex-dependent vaccine effectiveness on outcomes in pneumonia. MethodsWe performed a population-based cohort study including adults ≥60 years of age (n = 738 927) based on statutory health insurance data from 2005 to 2011. Primary outcomes were all-cause pneumonia incidence and 30-day all-cause mortality. Pneumonia was identified by International Classification of Diseases, 10th Revision, German Modification (ICD-10-GM) codes, with ambulatory cases validated by antibiotic prescription within 7 days. The effect of PPV within 5 years was analysed after propensity score–based matching (three controls per case with PPV vaccination) including comorbidities, care status, age, sex and influenza vaccination. Evaluations were stratified by age group, sex and time of PPV. ResultsTwo-year incidence of all-cause pneumonia in 213 431 vaccinated individuals was 7501 (3.51%) of 213 431 vs. 23 243 (3.63%) of 640 293 in matched controls (difference −0.11, 95% confidence interval (CI) −0.22 to −0.002, p 0.046). After sex-dependent analysis, PPV effectiveness on pneumonia incidence was observed only in women (difference −0.15, 95% CI −0.28 to −0.02, p 0.02). Thirty-day mortality in vaccinated individuals with pneumonia was 1302 (17.36%) of 7501 vs. 4267 (18.96%) of 22 503 in matched controls (difference −1.60%, 95% CI −2.83 to −0.38, p 0.011). After analysis according to age group, significant mortality reduction was present only in adults aged 60 to 79 years (difference −2.31, 95% CI −3.79 to −0.83, p 0.002). Year of PPV vaccination showed no effect on outcomes. ConclusionsThe findings support consideration of sex and age dependence of PPV effectiveness in future studies.

Effect of Age on the Manifestations and Outcomes of Invasive Pneumococcal Disease in Adults

BackgroundAlthough a considerable amount is known about the effect of age on the manifestations and outcomes of pneumonia, the same is not true for invasive pneumococcal disease. MethodsThis was a prospective observational study of all cases (2435) of invasive pneumococcal disease in adults in Northern Alberta from 2000 to 2014. Rates of invasive pneumococcal disease per 100,000, sociodemographic variables, clinical characteristics, and invasive pneumococcal disease–related outcomes were compared for the following age groups: 17-54, 55-64, 65-74, and ≥75 years. ResultsThe rate of invasive pneumococcal disease per 100,000 increased with increasing age. Although only 27.3% of the cases were in those aged ≥65 years, they accounted for 48% of the deaths. The case fatality rate increased with increasing age, from 9.6% for those aged 17-54 years to 31.7% for those aged ≥75 years. The rate of meningitis decreased with increasing age, as did admission to intensive care and use of mechanical ventilation. There was a marked reduction in the rate of invasive pneumococcal disease due to protein conjugate vaccine 7 and protein conjugate vaccine 13 serotypes in those aged ≥55 years but a much smaller decline in rates for those aged 17-54 years. Replacement with non-vaccine serotypes constituted approximately 50% of the cases. ConclusionsThe rate of invasive pneumococcal disease is highest in the very elderly, and manifestations of invasive pneumococcal disease are influenced by age.