Invasive Pneumococcal Disease Cases Research Articles

Population-based incidence and serotype distribution of invasive pneumococcal disease prior to introduction of conjugate pneumococcal vaccine in Bangladesh.

BackgroundBangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV-10) in 2015. We measured population-based incidence of invasive pneumococcal disease (IPD) prior to introduction of PCV-10 to provide a benchmark against which the impact of PCV-10 can be assessed.MethodsWe conducted population, facility and laboratory-based surveillance in children 0–59 months of age in three rural sub-districts of Sylhet district of Bangladesh from January 2014 to June 2015. All children received two-monthly home visits with one week recall for morbidity and care seeking. Children attending the three Upazilla Health Complexes (UHC, sub-district hospitals) in the surveillance area were screened for suspected IPD. Blood samples were collected from suspected IPD cases for culture and additionally, cerebrospinal fluid (CSF) was collected from suspected meningitis cases for culture and molecular testing. Pneumococcal isolates were serotyped by Quellung. Serotyping of cases detected by molecular testing was done by sequential multiplex polymerase chain reaction.ResultsChildren under surveillance contributed to 126,657 child years of observations. Sixty-three thousand three hundred eighty-four illness episodes were assessed in the UHCs. Blood specimens were collected from 8,668 suspected IPD cases and CSF from 177 suspected meningitis cases. Streptococcus pneumoniae was isolated from 46 cases; 32 (70%) were vaccine serotype. The population-based incidence of IPD was 36.3/100,000 child years of observations. About 80% of the cases occurred in children below two years of age.DiscussionIPD was common in rural Bangladesh suggesting the potential benefit of an effective vaccine. Measurement of the burden of IPD requires multiple surveillance modalities.

The impact of childhood 13-valent pneumococcal conjugate vaccination on overall invasive pneumococcal disease, including the oldest old

ABSTRACT Objectives: Our aim was to compare serotype distribution in invasive pneumococcal disease (IPD) in the Belgian population before and after introduction of the 13-valent conjugte vaccine (PCV13) in the national childhood vaccination schedule. Methods: Serotyping was performed on 12,534 pleural fluid and bacteraemic Streptococcus pneumoniae isolates sent to the National Reference Centre. We compared the distribution of serotypes (ST)/serogroups (SG) between the periods before (2007–2010) and after (2012–2015) the introduction of PCV13, in children and adults of different age groups, including older individuals (65–84 and ≥85 years). Results: The introduction of PCV13 in the childhood immunization program resulted in a reduction of 16% of all IPD-isolates. The prevalence of PCV13-SG decreased in all age groups: from 81% to 53% (p < 0.0001) in children <18 years, and from 69% to 53% (p < 0.0001) in individuals aged 18–64. This effect was also observed in age groups 65–84 (64% to 50%, p < 0.0001) and ≥85 years (63% to 47%; p < 0.0001). The proportion of IPD cases caused by non-PCV13 SG increased from 31% to 49% between the two periods, indicating replacement with non-vaccine SG. The coverage rate for the 23-valent polysaccharide vaccine (PPV23) in all age groups remains as high as 89% for the total group. Conclusion: After introduction of PCV13, a reduction of PCV13-serotypes occurred in IPD in all age groups. This supports the rationale to combine the effect of PCV13 with the broader coverage of PPV23 as a vaccination strategy for adults.

Estimating the Clinical and Economic Impact of Switching from the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) to the 10-Valent Pneumococcal Conjugate Vaccine (PCV10) in Italy

Background: Invasive and non-invasive pneumococcal diseases are significant health and economic burdens, especially in children and the elderly. Italy included the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the National Immunization Program in 2007 and 2010, respectively, allowing a dramatic reduction in the burden of pneumococcal disease. In the era of budget constraints, decision-makers may consider switching from the higher-valent, more costly PCV13, to the lower-cost PCV10. This study estimated the potential public health and economic impact of changing vaccine programs from PCV13 to PCV10 in Italy. Methods: A decision-analytic forecasting model estimated the impact of PCV programs. Real-world surveillance data were used to forecast serotype distribution and disease incidence among children and the elderly over a specified 5-year time horizon. Costs and outcomes included estimates of cases and deaths avoided, quality-adjusted life years (QALYs) gained, and total costs from a payer perspective, discounted at an assumed rate of 3.0%, and robustness validated through several scenarios and sensitivity analyses. Results: A switch from PCV13 to PCV10 would increase invasive pneumococcal disease (IPD) cases by 59.3% (4317 cases) over a 5-year horizon, primarily due to serotypes 3 and 19A. Pneumonia increased by 8.3% and acute otitis media (AOM) by 96.1%. Maintaining a PCV13 program would prevent a total incremental 531,435 disease cases (1.02M over a 10-year time horizon) and 641 deaths due to invasive pneumococcal disease (IPD), with €23,642 per QALY gained over 5 years versus PCV10. One-way and probabilistic sensitivity analyses showed that a PCV13-based program remained cost-effective in 99.7% of the simulations in Italy as parameters varied within their plausible range; percent vaccinated had the most impact. Conclusions: Maintaining the PCV13 strategy would provide substantial public health and economic benefits in Italy and is cost-effective. Switching from PCV13 to PCV10 would increase the incidence of pneumococcal disease primarily linked to re-emergence of serotypes 3 and 19A.

Who is at risk of 13-valent conjugated pneumococcal vaccine failure?

BackgroundDespite high vaccine coverage rates in children and efficacy of pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) episodes due to serotypes included in the vaccine following completion of the recommended course of immunisation (i.e. vaccine failure) have been reported. MethodsWe used data gathered from a population-based enhanced passive surveillance for IPD in children under 18 years of age in Massachusetts and an ensemble model composed of three machine-learning algorithms to predict probability of 13-valent pneumococcal conjugated vaccine (PCV13) failure and to evaluate potential associated features including age, underlying comorbidity, clinical presentation, and vaccine schedule. Vaccine failure was defined as diagnosis of IPD due to vaccine serotype (VST), in a child who received age recommended doses recommended by Advisory Committee of Immunization Practices. ResultsDuring the 7-year study period, between April 01, 2010 and March 31, 2017, we identified 296 IPD cases. There were 107 (36%) IPD cases caused by VST, mostly serotype 19A (49, 17%), 7F (21, 7%), and 3 (18, 6%). Thirty-seven (34%) were in children who were completely vaccinated representing 13% of all IPD cases. Vaccine failure was more likely among children older than 60 months (predicted probability 0.40, observed prevalence 0.37, model prediction accuracy 79%), children presenting with pneumonia (predicted probability 0.27, observed prevalence 0.31, model accuracy 77%), and children with underlying comorbidity (predicted probability 0.24, observed prevalence 0.23, model accuracy 96%). Vaccine failure probability for those >60 months of age and had an underlying risk factor was 45% (observed prevalence 0.33, model accuracy 82%). The likelihood of vaccine failure was lowest among children who had completed 3 primary doses plus one booster dose PCV13 (predicted probability 0.14, observed prevalence 0.14, model prediction accuracy 100%). ConclusionPCV13 vaccine failure is more frequent among older children with underlying comorbidity, and among those who present with pneumococcal pneumonia. Our study provides a preliminary framework to predict the patterns of vaccine failures and may contribute to decision-making processes to optimize PCV immunization schedules.

Hemophagocytic lymphohistiocytosis complicating invasive pneumococcal disease: a pediatric case report

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

Impact of vaccination on invasive pneumococcal disease in Italy 2007-2017: surveillance challenges and epidemiological changes.

Surveillance of new cases of invasive pneumococcal disease (IPD) in Italy was started in 2007 by the Ministry of Health (MoH). In 2012, pneumococcal childhood vaccination was introduced at the national level and, in 2017, for citizens aged 65 years and over. We describe here IPD epidemiology in Italy over the past 10 years investigating the impact of the vaccine programme on disease burden. Reports of IPD cases, data on serotype and vaccination coverage (VC) data were obtained from MoH annual reports, for the period 2007-2017. IPD notification rate and proportion by year, region, age and serotype were calculated. In 2007, 525 cases were reported (rate 0.88/100 000), rising to 1703 cases (rate 2.82/100 000) in 2017. The distribution of IPD cases by age group over time registered the largest share among individuals aged 65 years and over. A decreasing trend in notification rate was observed among those aged 0-4 years. During the same period, the 24-month VC increased, ranging from 80.9% to 96.7% in 2017. Molecular data indicated re-emergence of PPSV23-specific serotypes and non-vaccine serotypes. We observed an increase in IPD notifications during 2007-2017, likely due to an improved surveillance system, at least in some regions, with the relative quota of IPD notifications decreasing among vaccinated children cohorts. Further strengthening of IPD surveillance system, including molecular and vaccine coverage data, would be needed to assess and inform pneumococcal vaccination strategies in Italy.

Asthma and Invasive Pneumococcal Disease in the Age of Pneumococcal Conjugate Vaccines.

The widespread use of pneumococcal conjugate vaccines (PCVs) in the United States has led to a significant decrease in invasive pneumococcal disease (IPD) and pneumonia in the pediatric population. On the basis of data reported by the Centers for Disease Control and Prevention (CDC), the overall incidence of IPD among children <5 years of age in the United States decreased from 95 cases per 100 000 in 1998 to 9 cases per 100 000 in 2016, and, similarly, the incidence of IPD caused by 13-valent PCV serotypes decreased from 88 cases per 100 000 in 1998 to 2 cases per 100 000 in 2016.1,2 However, IPD still remains a leading cause of morbidity and mortality in the United States and worldwide. In 2017, the CDC’s Active Bacterial Core surveillance network reported that there were 31 000 cases of IPD (meningitis, bacteremia, and bacteremic pneumonia) and 3590 deaths, of which 147 cases and 9 deaths occurred in children <5 years of age.2Asthma has been described as the most common chronic disease of childhood. In the United States, the CDC estimates that 6 million children <18 years of age have asthma, with a higher incidence in boys and African American children.3 Of note, male sex and African American race are also considered risk factors for the development of IPD and pneumonia.4–6 The combination of these risk factors places these children at a significantly higher risk for developing both of these illnesses, the combination of which may lead to more complications and less favorable clinical outcomes.Multiple studies performed in both children and adults with asthma have revealed that these patients are at higher risk for both IPD and pneumococcal pneumonia, with odds ratios between 1.3 and 13.5 for pneumonia and 1.3 and 16.8 for IPD. The risk was found to be substantially higher for persons receiving inhaled or systemic corticosteroid therapy and those with more severe asthma at baseline. These patients are at higher risk not only for IPD and pneumonia but also for the development of complications associated with pneumococcal infections.7–10 In the review being published in this issue of Pediatrics, Castro-Rodriguez et al11 performed a meta-analysis of 4 electronic databases to evaluate the risk of IPD or pneumococcal pneumonia among children who had been diagnosed with asthma compared with children without asthma in the age of widespread use of PCV. Their meta-analysis was based on data from 4 studies, (3 retrospective cohort studies representing an estimated 26 million person-years and 1 case-control study of 3294 children). The meta-analysis revealed that despite widespread PCV use, children with asthma continued to have a substantially higher risk of IPD and pneumococcal pneumonia compared with children without asthma.The findings of this meta-analysis reveal several important facts of which pediatric health care providers need to be cognizant. First, asthma remains a risk factor for IPD and pneumococcal pneumonia even in the era of widespread use of PCV. Second, it is important that all patients, especially those with asthma, are receiving their vaccinations on time and, most notably, are up to date on their pneumococcal vaccinations. This will provide the best protection against pneumococcal infections and their complications for pediatric patients with asthma.

Impact and Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine on Population Incidence of Vaccine and Non-Vaccine Serotype Invasive Pneumococcal Disease in Blantyre, Malawi, 2006-2018: Prospective Observational Time-Series and Case-Control Studies

Background: Population impact of pneumococcal conjugate vaccines (PCV) depend on direct and indirect protection. Following Malawi’s 2011 introduction of the 13-valent PCV (PCV13), we examined impact on vaccine serotype (VT) and non-VT (NVT) invasive pneumococcal disease (IPD) among vaccine-age-eligible and vaccine-age-ineligible children and adults. Methods: Laboratory-based surveillance at a government hospital in Malawi included 6 years before and 7 years after PCV13 introduction. Using negative-binomial regression, we evaluated secular trend-adjusted Incidence Rate Ratio (IRR) in VT- and NVT-IPD prior to and post PCV introduction. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. A case-control study assessed vaccine effectiveness compared PCV uptake among vaccine-age-eligible IPD cases versus matched community controls. Findings: Surveillance covered 10 281 476 person-years observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. IPD decline preceded PCV introduction. Compared to the counterfactually predicted incidence, post-vaccine VT-IPD incidence was 38% (95%CI: 37, 40) lower among infants, 74% (70, 78) among young children, 79% (76, 83) among older children and 47% (44, 51) among adolescents and adults. Though NVT-IPD has increased since 2015 , absolute rates remain low. The case-control study, (19 cases and 76 controls), showed vaccine effectiveness against VT-IPD of 80·7% (-73·7, 97·9). Interpretation: Even with pre-existing declines, infant PCV13 introduction has led to substantial IPD reduction among vaccine-age-eligible children. However, seven years after PCV introduction, indirect effects benefitting unvaccinated infants and adults were more modest. Policy decisions should consider alternative strategies, including targeted vaccination outside infant EP to benefit vulnerable populations. Funding Statement: This work was funded by Bill & Melinda Gates Foundation, USA (OPP117653) to RSH and a Wellcome Trust Programme Grant (WT091909/B/10/Z) to NF, NAC, RSH; National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government (Project number 16/136/46) to RSH. The MLW Clinical Research Programme is supported by a Strategic Award from the Wellcome Trust, UK (206545/Z/17/Z) to SG. Declaration of Interests: NBZ, NAC & NF have received investigator-initiated research grants from GlaxoSmithKline Biologicals. NBZ & NAC received investigator-initiated research grants from Takeda Pharmaceuticals. NAC has received research grant support and honoraria for participation in rotavirus vaccine advisory board meetings from GlaxoSmithKline Biologicals. All other authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by Malawi’s National Health Sciences Research Committee (NHSRC; protocol 867), by the University of Malawi College of Medicine Research and Ethics Committee (COMREC; P.01/08/609 and P.09/09/826) and the University of Liverpool Research Ethics Committee (UoLREC; RETH490). The Centers for Disease Control and Prevention relied on the UoLREC for ethical approval. For the case-control component, the parent/guardian of all child participants provided written informed consent and, in addition, children 8 years or older provided written informed assent. This included consent for publication.

Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015–2017

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages.

The shifting epidemiology and serotype distribution of invasive pneumococcal disease in Ontario, Canada, 2007-2017.

BackgroundOntario, Canada introduced a publicly-funded 13-valent pneumococcal conjugate vaccine (PCV13) for infants in 2010, replacing the 10-valent (PCV10, 2009–2010) and the 7-valent (PCV7, 2005–2009) conjugate vaccine programs; a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been available for older adults since 1996. We examined the epidemiology and serotype distribution of invasive pneumococcal disease (IPD) in Ontario in the context of provincial immunization programs.MethodsWe included confirmed IPD cases reported in Ontario between 2007 and 2017. We grouped serotypes according to Ontario’s current immunization program (PCV13, PPV23, and non-vaccine-preventable) and calculated incidence rates (per 100,000 population) using population data.ResultsBetween 2007 and 2017, annual incidence of IPD in Ontario ranged between 7.3 and 9.7/100,000 per year. Measures of illness severity were high throughout the period of surveillance. After PCV13 program implementation in 2010, incidence due to PCV13 serotypes decreased significantly across all age groups, with the greatest reductions in children <5 years and adults ≥65 years. Conversely, incidence due to PPV23 unique serotypes increased significantly between 2007 and 2017, with the greatest increases observed in adults 50–64 years (1.4 to 3.5/100,000) and ≥65 years (2.3 to 7.2/100,000). Similar increases were observed in incidence due to non-vaccine-preventable serotypes among all age groups, except infants <1 year. Within specific serotypes, incidence due to serotypes 3 (0.42 to 0.98/100,000) and 22F (0.31 to 0.72/100,000) increased significantly between 2007 and 2017, while incidence due to serotypes 19A and 7F decreased significantly during the PCV13 period (2010–2017).ConclusionsEight years after PCV13 implementation in Ontario, our data suggest both direct and indirect effects on serotype-specific incidence in young children and older adults. However, overall provincial rates have remained unchanged, and IPD continues to be a severe burden on the population. The rising incidence of IPD due to PPV23 unique and non-vaccine-preventable serotypes, and the growing burden of serotypes 3 and 22F, require further study.

Serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease isolates from children in mainland China-a systematic review.

This study aimed to review and report the serotype distribution and antimicrobial resistance patterns of invasive pneumococcal disease (IPD) isolates, as this information is important for policy making since China has not adopted any pneumococcal vaccines in the national immunization schedule. A systematic review of the published literature from January 2000 to December 2018 was performed to identify articles that describe the serotype and/or antimicrobial resistance patterns of IPD cases in children in mainland China. Analysis of the extracted data was performed with the Microsoft Excel spreadsheet program. The percentage of the serotypes was calculated by dividing the number of isolates for each serotype with the total number of isolates included in all the studies. The theoretical impact of the vaccine was estimated by calculating the percentage of isolates that exhibited the serotypes included in the vaccines. The prevalence of antimicrobial resistance was defined as the number of isolates that were resistant divided by the total number of isolates tested for resistance to the specific antimicrobial agent. Forty-two articles were screened in the preliminary search, of which sixteen fulfilled inclusion criteria and were included in the final analysis. The predominant serotypes were 19A, 19F, 14, 23F, and 6B, and the estimated impact of PCV13 was 90.4%. The isolates exhibited a high frequency of resistance to cefuroxime, cefaclor, and erythromycin. It is necessary for Chinese children to receive PCV13. Clinical workers should pay attention to the high frequency of resistance to antimicrobial agents.

Factors Associated With Severe Nonmeningitis Invasive Pneumococcal Disease in Adults in France.

BackgroundIn France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death.MethodsWe included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases.ResultsDuring 2014–2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0–1.4) in cases with 1–2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0–7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3–1.9; aRR, 1.3; 95% CI, 1.0–1.5, respectively).ConclusionsWe observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups.

PIN34 A PUBLIC HEALTH AND BUDGET IMPACT ANALYSIS (BIA) OF VACCINATING CHILDREN AGAINST PNEUMOCOCCAL-DISEASES IN AUSTRIA

Around 2 million people die every year from pneumococcal infections world-wide. 50% of them are children. In Austria around 9,000 children (<5 years) develop pneumococcal infections every year. About 20 children develop invasive pneumococcal disease (IPD). Vaccination with a pneumococcal conjugate vaccine (PCV) for all children <2 years is recommended and reimbursed in Austria. Currently PCV10 is being used exclusively but could now be replaced by PCV13. The aim of this BIA is to quantify the monetary impact of an increasing proportion of PCV13 vaccinated children in the different age-groups compared to the present situation, after an observed serotype shift of reported cases. A multi-cohort, population-based model was developed over a 5-year time-horizon, which included the following states: hospitalized and outpatient pneumococcal-disease (pneumonia, meningitis and AOM), IPD, associated complications and mortality in children <5. Within the present vaccination coverage of 80%; 75% receive PCV10; 15% PCV13. The model evaluates PCV10 being replaced by PCV13 with PCV13 achieving 83% market share in year 5. The model includes a serotype shift over time. Results included savings that could be achieved from the health-care-systems perspective. Based on the current vaccination coverage annual savings of 1.1 million € (m€) (1st year) to 3 m€ (5th year) [total: 10.6 m€ over 5 years] could be achieved. A market shift will reduce pneumococcal disease from 1,013 (1st year) to 2,821 (5th year) [total: 9,100 cases over 5 years]. Between 4 (1st year) and 11 (5th year) cases of IPD per year could be prevented [total: 36 over 5 years]. Prevented deaths range from 2 (1st year) to 6 (5th year) per year [total: 19 over 5 years]. An increase in PCV13 vaccinated children – due to a change in the national immunization program – could reduce overall disease-burden substantially and lead to considerable savings.

Invasive pneumococcal disease in Latvia seven years after PCV10 introduction

Abstract Background In 2009 in Latvia, invasive pneumococcal disease (IPD) became notifiable for physicians and in 2010 vaccination of infants with PCV7 commenced. In 2012 PCV10 vaccination was introduced. The objectives of our study were to evaluate trend of incidence and trend serotype distribution of IPD in Latvia and to investigate factors associated with death from IPD. Methods Laboratory confirmed IPD cases are passively notified to the Centre for Disease Prevention and Control of Latvia by laboratories and clinicians. We calculated incidence by age, sex, case fatality and trend in serotypes. Results From 2012 to 2018, 466 cases of IPD were reported, mean annual incidence 3.4/100,000. The notified incidence remained stable from 2012-2014 (2.7), peaked in 2015 (4.4) and fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in elderly (6). The highest mean annual incidence was reported in males (4.5) in comparison to females (2.4) (IR-1.8 95%CI 1.6-2.4). Case fatality was 19% (87/466) and 23% (37/162) in cases aged &amp;gt; =65 years. 90% (421/466) of isolates were serotyped. The proportion of PCV10 vaccine serotypes fell from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend =0.000). Since year 2017, PPV23nonPCV13 and Non-vaccine serotypes become more common. We detected PCV13 serotype (RR 2.04 95%CI 1.37-3.02), S.pneumoniae serotype 3 (RR 1. 91 95% CI 1.25-2.93) significantly associated with IPD death. Conclusions Surveillance data indicate evidence of serotype replacement. Surveillance evaluation should asses the representativeness of notification. Furthermore S. pneumoniae carriage study may be useful to characterise serotype circulation. Serotype 3 and age demonstrate independent and significant association with fatal IPD outcome. Key messages IPD surveillance data analysis indicated evidence of serotype replacement with PPV23nonPCV13, NonVaccine serotypes. Serotype 19A becomes more common with significant increasing trend. Serotype 3 and age independently and significantly associated with fatal IPD outcome. S.pneumoniae carriage study would be very useful providing more evidence of characterizing serotypes circulation.

PIN37 HEALTH AND ECONOMIC BURDEN ASSOCIATED WITH 15-VALENT PNEUMOCOCCAL CONJUGATE VACCINE SEROTYPES IN CHILDREN IN THREE EUROPEAN COUNTRIES

V114, an investigational 15-valent pneumococcal conjugate vaccine (PCV) is under development that contains all serotypes in PCV10 and PCV13 and 2 additional serotypes (22F/33F). This study quantifies the health and economic burden of invasive pneumococcal disease (IPD) associated with V114 serotypes in Finland, the Netherlands and Austria. A Markov model was developed to simulate V114-type IPD cases, deaths and costs in hypothetical unvaccinated birth cohorts over 20 years. All inputs were obtained from the published literature. In the pre-PCV analysis, epidemiological inputs from the pre-PCV7 era were applied to all serotypes. In the post-PCV analysis, pre-PCV7 and pre-PCV10 inputs were applied to PCV7 serotypes and PCV10 not PCV7 (PCV10-PCV7) serotypes. Disease attributable to V114 not PCV10 (V114-PCV10) serotypes were estimated using the most recent data. Costs were estimated from a societal perspective (2017 Euros) and discounted at 3%. In the pre-PCV analysis, 355 V114-type IPD cases would occur: 244 (69%) attributable to PCV7 serotypes, 53 (15%) to PCV10-PCV7 serotypes, and 58 (16%) to V114-PCV10 serotypes. V114 serotypes caused 74 IPD deaths. Costs of V114-type IPD was €9.4 million. In the post-PCV analysis, V114-type IPD increased to 406 cases: 244 (60%) attributable to PCV7 serotypes, 66 (16%) to PCV10-PCV7 serotypes, and 96 cases (24%) to V114-PCV10 serotypes. Compared to the pre-PCV analysis, the additional 13 cases attributable to PCV10-PCV7 serotypes were mainly caused by serotype 1. The additional 38 cases attributable to V114-PCV10 serotypes were from serotypes 3 (33 cases, 91%) and 19A (11 cases, 31%). Costs of V114-type IPD increased to €10.4 million. Deterministic sensitivity analysis will be performed. PCV7 serotypes cause most IPD-related morbidity and costs and should be retained in investigational PCVs. Serotypes contained in PCV10 and PCV13 also contribute to IPD morbidity and cost. Expanding coverage to non-vaccine serotypes can prevent additional disease.

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 &amp;gt;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.

2711. Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Older Adults

BackgroundRoutine use of 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants since early 2010 and for adults ≥65 years since 2014 when KPNC began routine use of PCV13 in adults. PCV13 vaccine effectiveness (VE) against vaccine-type invasive pneumococcal disease (IPD) has been demonstrated; however, recent surveillance data have been interpreted as showing limited population-level impact of PCV13 on serotype 3 IPD. We estimated PCV13 VE against IPD due to vaccine serotypes at Kaiser Permanente Northern California (KPNC).MethodsThe study period spanned September 2014 through September 2018. The cohort included KPNC members who were aged ≥65 years with no record of pneumococcal polysaccharide vaccine (PPV23) receipt before age 65 years. We compared IPD cases with KPNC members who were the same age on the date of the positive pneumococcal culture using conditional logistic regression, conditioned on age and date, and controlled for sex, race, KPNC service area and membership history, prior season influenza vaccine receipt, PPV23 receipt after age 65 years, risk factors for IPD, and healthcare utilization.ResultsFrom September 2014 to September 2018, PCV13 vaccine coverage among persons ≥65 years old increased from < 1% to 77%. During the same period, there was a total of 245 IPD cases. For a variety of reasons, we did not have serotype results for 57 (23%) IPD cases, which were excluded from the analysis. There were 61 (25%) PCV13-type IPD cases included in the analysis, of which 33 (14%) were serotype 3. PCV13 VE against PCV13-type serotypes was 68.0% (95% CI: 37.7%, 83.6%; P-value < 0.01), and 53.4% (95% CI: −10.0%, 80.3%; P = 0.08) against serotype 3.ConclusionDuring the first 4 years of PCV13 vaccination implementation in adults ≥65 years of age at KPNC, PCV13 provided significant protection against PCV13-type IPD. Further surveillance will allow for more precise estimation of PCV13 VE on overall and serotype 3 IPD over time.Disclosures All authors: No reported disclosures.

2708. Genetic Structure of Streptococcus pneumoniae Isolated from Invasive Disease in Korea, 2014–2016

BackgroundThe extended-valency pneumococcal conjugate vaccines (PCVs) were implemented into Korean national immunization program in 2014. This study investigated the change in genetic structures of Streptococcus pneumoniae causing invasive pneumococcal disease (IPD) in Korean children after 10- and 13-valent conjugate vaccine (PCV10 and PCV13, respectively) use.MethodsBetween January 2014 and December 2016, invasive isolates were collected from 23 hospitals throughout Korea. Cases of IPD were defined by isolating pneumococci from normally sterile sites. Each pneumococcal isolate was identified using standard microbiological techniques and serotyped by Quellung reaction. The multi-locus sequence typing (MLST) was analyzed for randomly selected isolates.ResultsA total of 91 pneumococcal isolates were analyzed. Common serotypes were 10A (18.7%), 12F (11.0%), 15A (9.9%), 19A (9.9%), 15B/C (7.7%), 23A (6.6%), 35B (5.5%), and 23B (4.4%). The isolates belonged to 38 sequence types (STs), including 4 newly discovered STs. Of the 4 clonal complexes (CCs), 3 clonal complexes were antibiotic-resistant international clones. CC166 (11.9%) were associated with non-vaccine serotypes (NVTs; 11A, 15B/C, 23A, and 13). Serotypes of CC320 (10.9%) comprised of serotype 19A and 19F. The main serotypes responsible for CC81 (10.9%) were serogroup 15. New serotype-ST combinations were observed, especially in serotype 13 and serogroup 15. Also, a possibility of capsular switch event was noted between serogroup 6 and serogroup 15A.).ConclusionThe introduction of extended-valency PCVs has resulted in the change of the genetic structure of pneumococcal isolates in Korean children. This study demonstrates that selective pressure from PCV10/13 caused predominant serotypes to be NVTs and genetic changes such as capsular switch events.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.

1628. Clinical, Epidemiological and Microbiological Characterization of Invasive Streptococcus pneumoniae Disease in Hospitalized Adults from 5 Tertiary Hospitals in Bogotá, Colombia: A Descriptive Study

BackgroundIn Colombia, clinical characteristics related to invasive pneumococcal disease (IPD) and circulating pneumococcal serotypes (ST) in adults are scarce. We aimed to describe the clinical and microbiological characteristics of IPD in hospitalized adults ≥18 years old in 5 tertiary hospitals in Colombia from 2011 to 2017.MethodsA descriptive, observational, retrospective study was conducted in 5 tertiary care hospitals during a 7-year period. Demographic, clinical data and in-hospital outcomes were collected through chart review from all culture-confirmed invasive S. pneumoniae cases in each hospital. The National Health Institute laboratory database was assessed to obtain information about ST (Quellung) and antimicrobial susceptibility (Broth microdilution).Results128 cases of IPD were included in this interim analysis, 70(54.7%) were males. The median age was 58 ± 16.7 years. Main underlying conditions were cardiovascular disease (32%), smoking (27.9%), diabetes (20.3%), autoimmune diseases (18.8%), and cancer (18%). The main clinical presentation was bacteremic pneumonia (66.4%), followed by meningitis (14.8%), bacteremia (14.1%) and other (3.1%). Critical care management was required in more than half of the patients: ICU (60.2%), mechanical ventilation (53%) and inotropic support (51.6%). The overall in-hospital mortality rate was 43% and was 39%, 52.6% and 61% for pneumonia, meningitis and bacteremia, respectively. ST was known for 82(64%) cases, most frequent ST were: 3(10.9%), 14(7.3%), 19A(6,1%), 1(4.8%), 4/8/11A/22F (3.65% for each one). ST contained in 13-valent conjugate vaccine (PCV13), 23-valent pneumococcal vaccine (PPVS23) and non-vaccine serotypes accounted for 43.9%, 54.9%, and 40.2% of IPD cases, respectively (Figure 1). 83% and 80.7% strains were susceptible to penicillin and ceftriaxone, respectively.ConclusionPneumonia is the most common clinical presentation of IPD among adults. The clinical outcome was severe with high mortality rate and need of critical care management. ST contained in PCV13 and PPVS23 accounted for 43.9% and 54.9% of IPD cases. This study highlights the importance to strengthen local surveillance and the implementation of pneumococcal immunization programs in high-risk population. Disclosures All authors: No reported disclosures.