13-valent Conjugate Vaccine Research Articles

2714. Streptococcus pneumoniae Nasopharyngeal Carriage in Canadian Adults Hospitalized with Community-Acquired Pneumonia from 2010 to 2017

Background Streptococcus pneumoniae can colonizes the human nasopharynx, and can cause life-threatening infections like community-acquired pneumonia (CAP) and invasive pneumococcal diseases (IPD). In Canada, the 13-valent conjugate vaccine (PCV13) was introduced in childhood immunization since 2010, with hopes that it would not only protect the vaccinated, but also confer indirect protection to adults through herd immunity. Given data on S. pneumoniae nasopharyngeal (NP) carriage in adults is scarce, this study reports on S. pneumoniae-positivity and serotype distribution in adult carriage from years 2010 to 2017.MethodsActive surveillance was performed in adults hospitalized with for CAP or IPD from December 2010 to 2017. For assessment of S. pneumoniae carriage, NP swabs were tested using lytA and cpsA real-time PCR. S. pneumoniae-positive NPs were subjected to serotyping using conventional and real-time multiplex PCRs.ResultsOverall, 6472 NP swabs were tested, and Spn was identified in 366 (5.7%). Of the 366 S. pneumoniae-positive NP swabs, a serotype was assigned in 355 (97.0%). From years 2010 to 2017, the proportion of S. pneumoniae-positive NP swabs declined from 8.9% to 4.3%. This was also reflected in the proportion of serotypeable results attributed to PCV13 serotypes, which also declined from 76.9% to 42.2%. The decline was primarily attributed to PCV13 serotypes 7F and 19A. PCV13 serotype 3 remained predominant throughout the study, as did non-PCV13 serotypes like 22F, 33F, and 11A. On the other hand, a proportional rise over time was noted for non-vaccine serotypes (from 15.4% to 31.1%). This was primarily attributed to serotypes 23A, 15A, and 35B.ConclusionMonitoring serotype trends is important to assess the impact of pneumococcal vaccines. While herd immunity from PCV13 childhood immunization was anticipated, few studies have assessed its impact on adult carriage. This study described Spn serotype distribution in adults over years 2010 to 2017, demonstrating not only a reduction of PCV13 serotypes over time, but a proportional rise in non-vaccine serotypes. These emerging serotypes may represent the emergence of serotype replacement. Ongoing serotype surveillance will be needed to compare S. pneumoniae carriage to serotypes associated with pneumococcal CAP and IPD.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.

244. Development, Qualification, and Clinical Validation of an Immunodiagnostic assay for the Detection of 11 Additional S. pneumoniae Serotype-Specific Polysaccharides in Human Urine

BackgroundIdentifying Streptococcus pneumoniae (Sp) serotypes by urinary antigen detection assay (UAD) is the most sensitive and specific way to evaluate the changing epidemiology of non-bacteremic community-acquired pneumonia (CAP) and efficacy of pneumococcal vaccines. We first described an UAD to detect the Sp serotypes 1,-3,-4,-5,-6A,-6B,-7F,-9V,-14,-18C,-19A,-19F,-23F covered by the 13-valent Sp conjugate vaccine PCV13. To assess the pneumococcal disease burden of additional serotypes, a UAD-2 assay was developed to diagnose 11 additional Sp serotypes (-2,-8,-9N,-10A,-11A,-12F,-15B,-17F,-20,-22F,-33F).MethodsUAD-2 specificity was achieved by capturing highly purified pneumococcal polysaccharides with serotype-specific monoclonal antibodies using Luminex technology. Assay qualification assessed accuracy, precision, and sample linearity. Serotype positivity was based on cutoffs determined by non-parametric statistical evaluation of urine samples from individuals without pneumococcal disease. Clinical sensitivity and specificity of the positivity cutoffs were assessed in a clinical validation.ResultsThe UAD-2 was shown to be specific and reproducible. Clinical validation using urine samples from invasive disease patients demonstrated assay sensitivity and specificity of 92.2% and 95.9%, respectively compared with a gold standard of isolating and typing (by Quellung) Sp bacteria from patient samples. Analysis of 11,087 CAP patients showed a UAD-2 and UAD-1 serotype prevalence of 4.33% and 4.60%, respectively (bacteremic and non-bacteremic CAP combined).ConclusionThe qualified/clinically validated UAD-2 method has applicability in understanding the epidemiology of nonbacteremic Sp CAP as well as assessing vaccine efficacy of future pneumococcal conjugate vaccines.Disclosures All authors: No reported disclosures.

Multistate population and whole genome sequence-based strain surveillance of invasive pneumococci recovered in the USA during 2017

ObjectivesWe aimed to provide population-based and whole-genome sequence (WGS) -based characterization of invasive pneumococcal disease isolates collected from multistate surveillance in the USA during 2017. MethodsWe obtained short-read WGS from 2881 isolates with associated bioinformatics pipeline strain feature predictions. For quality control, capsular serotypes and antimicrobial MICs were also obtained conventionally from 442 isolates. Annotated WGS were provided (inclusive of serotypes, MICs, multilocus sequence types, pilus type(s)) from 2723 isolates. For 158 isolates with suboptimal WGS, antimicrobial MICs were obtained conventionally. ResultsThere were 127 isolates from children <5 years of age and 2754 isolates from those ≥5 years old in 2017. One of 43 different serotypes was predicted for 2877 of the 2881 isolates. Serotypes in the 13-valent conjugate vaccine together with 6C (PCV13+6C) accounted for 816 (28.3%) isolates, with PCV13 serotype 3 being the most common serotype overall. Non-PCV13–6C– serotypes accounted for 2065 (71.7%) isolates, comprising 96 (75.6%) isolates from children < 5 years old and 1969 (61.4%) isolates from those aged ≥5 years. Of 36 different categories of recently emerged serotype-switch variants, three showed marked increases relative to 2015–2016 in that the number from 2017 surpassed the number from 2015–2016 combined. Two of these included antimicrobial-resistant serotype 11A and 35B serotype-switch variants of the ST156 clonal complex. ConclusionsPCV13+6C strains are still identified in 2017 but non-PCV13-type strains impose a considerable burden. This well-annotated year 2017 WGS/strain data set will prove useful for a broad variety of analyses and improved our understanding of invasive pneumococcal disease-causing strains in the post-PCV13 era.

Homelessness in Adults with Invasive Pneumococcal Disease (IPD) in Calgary, Canada.

BackgroundHomelessness is uncommon but is frequently a characteristic in adults with invasive pneumococcal disease (IPD). In Calgary, homeless persons comprise approximately 0.2% of the population. We evaluated the relationship of homelessness and IPD in Calgary.MethodsDemographic, clinical, and microbiologic data were collected by the Calgary Streptococcus pneumoniae Epidemiology Research (CASPER) team through prospective, population-based surveillance of all IPD cases. Here, we report on cases in adults (≥18 years) from 2000 to 2016.ResultsOf 1729 IPD cases, 321 (18.8%) occurred in homeless persons. Compared with nonhomeless persons, homeless persons were younger, more often male, smokers, alcohol abusers, illegal drug users, and had a primary diagnosis of pneumonia. In multivariable models of outcomes, homeless persons had lower odds of being admitted to the ICU (odds ratio [OR], 0.7; P = .02) and lower odds of death (OR, 0.6; P = .146). IPD caused by serotypes 4, 5, or 8, which have caused outbreaks in Calgary, was more common in homeless persons (54.4% vs 21.0%; P < .001). In addition, regardless of homeless status, persons with IPD caused by serotypes 4, 5, or 8 had lower odds of ICU admission and mortality (OR, 0.7; P = .017; and OR, 0.4; P = .004; respectively).ConclusionsHomelessness is overrepresented in IPD cases in Calgary, despite most homeless persons having fewer risk factors than the overall population of persons with IPD. Most cases are caused by serotypes in both the 23-valent polysaccharide vaccine and the 13-valent conjugate vaccine. Thus, enhanced efforts are needed to deliver both vaccines to this vulnerable population.

Analysis of Streptococcus pneumoniae using Fourier-transformed infrared spectroscopy allows prediction of capsular serotype

Determination of the capsule type of clinical isolates of Streptococcus pneumoniae is a prerequisite for epidemiological studies and further vaccine development. The Quellung reaction for serotyping is expensive and mostly done in reference centres. We wanted to evaluate whether Fourier-transformed infrared (FT-IR) spectroscopy is suitable for capsular type analysis and prediction of pneumococcal serotypes. We used the IR-Biotyper™ (Bruker) to create a database containing the spectra of 120 strains from invasive disease. The strains covered the 24 vaccine serotypes contained in the 13-valent conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PSV23). Hierarchical clustering analysis was performed. Finally, two different classification sets were created (PCV13 and PSV23). They were used to predict the serotype of 168 different challenge strains (invasive and non-invasive disease) covering 48 different serotypes (vaccine and non-vaccine types). FT-IR spectra from pneumococci (1300–800 cm−1) clustered along their serotype as determined by the Quellung reaction (120 strains, 24 different serotypes). Strains with unknown serotype fell within the cluster of the correct serotype, as long as the latter was represented in the database (168 strains, 48 different serotypes). Concordance between the Quellung reaction and FT-IR spectroscopy was excellent (kappa ≥ 0.75). FT-IR spectroscopy is a fast and cost-effective method to predict the capsular serotype of pneumococci.

Antibody response to the 23-valent pneumococcal polysaccharide vaccine after conjugate vaccine in patients with chronic lymphocytic leukemia

ABSTRACT The 23-valent pneumococcal polysaccharide vaccine (PPV23) given alone is ineffective in patients with chronic lymphocytic leukemia (CLL) and better antibody response is achieved with pneumococcal conjugate vaccines (PCVs). In this study, we determine whether CLL patients would achieve a significant antibody response and broaden their serotype coverage against invasive pneumococcal disease (IPD) with PPV23 given five years after the 7-valent conjugate vaccine (PCV7). A total of 24 patients with CLL and eight controls were vaccinated with PPV23 five years after PCV7. Blood samples for evaluation of antibody response to PCV7 serotypes and PPV23 serotypes 5 and 7 were taken before vaccination and one month after it. Post-vaccination samples were available from 20 patients. IgG antibodies were measured with ELISA. Antibody concentrations after PPV23 were significantly lower in CLL patients for six of the PCV7 serotypes and for both PPV23 serotypes. Only 10% to 15% of CLL patients achieved an antibody response suggested to be protective against IPD. Hence, PCV7 given five years before PPV23 did not improve antibody response in patients with CLL. Based on our results, PPV23 given after a PCV primer is not useful against IPD in CLL patients.

Impact of the introduction of a 13-valent pneumococcal vaccine on pneumococcal serotypes in non-invasive isolates from 2007 to 2016 at a teaching hospital in Japan

To prevent severe invasive pneumococcal infection, pneumococcal conjugate vaccines (PCVs) were introduced in Japan in 2010, and in 2013 a pneumococcal 13-valent conjugate vaccine (PCV13) was included in the routine vaccination schedule for infants. In this study, we analysed the antimicrobial susceptibilities and capsular types of pneumococci isolated from non-invasive patient sites from 2007 to 2016 to assess the impact of the introduction of PCV13. A total of 618 pneumococcal isolates collected at a teaching hospital from 2007 to 2016 were used. These isolates were characterized by capsular typing, multilocus sequence typing and antimicrobial susceptibility testing. Capsular typing indicated that, after the introduction of the PCV, the proportion of PCV13 serotypes decreased (P<0.01), while non-PCV13 serotypes became diverse. In particular, increases in 22 F, 15A and 23A were noted among non-PCV13 serotypes. Regarding antimicrobial susceptibility, the non-susceptibility rate to penicillin of pneumococci that showed higher minimum inhibitory concentrations (MICs) than the susceptibility breakpoint decreased, and pneumococci tended to become susceptible. However, all type 23A pneumococci and 77.8 % of type 15A pneumococci showed the reverse trend, with low susceptibility to penicillin. Furthermore, all 15A and 23A isolates had macrolide resistance genes. These data suggest that PCVs can prevent infections caused by PCV serotypes. However, since non-PCV13-type pneumococci, in particular 15A and 23A, which have acquired multidrug resistance, have already emerged over time, the development of a novel vaccine targeting a broader spectrum of pneumococci is warranted.

Association Between Pneumococcal Surface Protein A Family and Genetic/Antimicrobial Resistance Traits of Non-Invasive Pneumococcal Isolates from Adults in Northern Japan.

Pneumococcal isolates from adult patients in northern Japan in 2016 were subjected to molecular investigation related to pneumococcal surface protein A (PspA) and drug resistance determinants. Of the 51 isolates, serotype 3/ST180 was the most prevalent (17.6%), followed by 35B (ST2755/ST558) (11.8%) and 15A (ST63/ST7874/ST13068/ST13785) (9.8%). Coverage of serotypes by 13-valent conjugate vaccine and 23-valent polysaccharide vaccine was 27.5% and 49%, respectively. All the isolates expressed PspA family 1 or 2 (51% and 49%, respectively). Each serotype was associated with either of the PspA families (e.g., serotype 3, PspA family 1; serotypes 35B and 15A, PspA family 2). Multidrug resistance (MDR) was found in 84.3% of the isolates. Minimum of one altered penicillin-binding protein gene was detected in 82.4% of isolates, indicating 25.5% non-susceptibility to penicillin. Serotypes 15A and 35B were predominant and demonstrated MDR. An isolate of serotype 15A/ST13785 (single-locus variant of ST242) was resistant to fluoroquinolones associated with double mutation in the quinolone resistance-determining regions of gyrA and parC. The present study indicates the spread of MDR pneumococci represented by isolates of serotypes 3, 15A, and 35B, and prevalence of both PspA family 1 and 2 in isolates obtained from adult patients.

Pediatric meningitis due to Neisseria meningitidis, Streptococcus pneumoniae and Group B Streptococcus in Tijuana, Mexico: active/prospective surveillance, 2005–2018

Introduction:In Mexico, Neisseria meningitidis is considered to be a rare cause of bacterial meningitis (BM), however, one national publication using active surveillance has suggested the opposite. Group B Streptococcus (GBS) is also considered to be infrequent in young infants as a cause of BM in central Mexico. Streptococcus pneumoniae vaccination using the 13-valent conjugate vaccine (PCV13) started in our region in May 2012. We focused our research on whether N. meningitidis and GBS are important causes of BM, and to examine the effectiveness of PCV13 on pneumococcal BM.Methods:From October 2005 to September 2018, active/prospective surveillance looking for all patients admitted with suspected BM <16 years of age was performed at the Tijuana, Mexico, General Hospital. Tijuana, Mexico to San Diego, Unites States of America (USA), is the most transited border in the world. Isolation of pathogens was by either conventional culture or Real Time-polymerase chain reaction (RT-PCR), all patients were followed during and 3 months after discharge, and a descriptive analysis was performed. The effectiveness of PCV13 was determined by comparing the proportion of cases per month on pneumococcal BM before and after its implementation.Results:There were 86 confirmed BM cases. N. meningitidis was the leading cause (60.5%, and 61.5% caused by serogroup C), followed by S. pneumoniae (18.6%). PCV13 effectiveness on pneumococcal BM was of 64.3% and was associated with the disappearance of serotype 19A. A total of 22 infants <3 months old had BM; GBS was the leading cause at this age group (27.3%), followed by N. meningitidis (22.7%). The overall mortality was 24%.Conclusions:BM by N. meningitidis is endemic in Tijuana, Mexico, and meningococcal vaccination should be seriously considered in the region. PCV13 is currently showing high effectiveness on pneumococcal BM, and we need to continue active surveillance to see whether maternal screening/prophylaxis for GBS should also be introduced in the region.

12 years active surveillance for pediatric pleural empyema in a Mexican hospital: effectiveness of pneumococcal 13-valent conjugate vaccine, and early emergence of methicillin-resistant Staphylococcus aureus.

Background:Previous publications have proved the effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal pleural empyema (PnPE) in children, with little emergence of other pathogens. We searched the literature to establish whether PCV13 reduces PnPE, and to identify other pathogens causing pleural empyemas (PEs).Material and methods:From October 2005 to January 2018 (12.3 years) we performed active surveillance for all cases of PE at the General Hospital of Tijuana, Mexico. Isolates from pleural fluid (PF) were identified by conventional culture, and since 2014, polymerase chain reaction (PCR) was added for all culture-negative PFs. Streptococcus pneumoniae serotypes were detected by either Quellung reaction (Statens Serum Institute®) or PCR. Clinical, imagenological, laboratorial and microbiological evaluation was performed on each patient. Statistical analysis was purely descriptive.Results:A total of 64 PEs were identified (5.28/year). Median age was 51 months (1–191), hospitalization days 18 (4–35). Decortication was performed in 42%, and two children died (3.2%). Bacterial identification was obtained from 51 (80%). S. pneumoniae was the leading cause (29 = 56.8%), followed by Staphylococcus aureus (14 = 27.4%), Streptococcus pyogenes (3–5 = 9%) and others (5 = 9.8%). PCV13 was initiated in May 2012, and its impact on serotype-specific PnPE was 81% (much fewer than serotype 3) and for all PnPE 56.1%; however, for all PE −2.1% due to an increase of PE caused by S. aureus for all but one methicillin-resistant S. aureus (MRSA).Conclusions:Following 12.3 years of active surveillance, PCV13 has shown impact on both serotype-specific and all PnPEs; however, an increase of PEs by MRSA has emerged. Continuous surveillance is crucial to establish whether this epidemiological finding is transitory or not.

Invasive pneumococcal disease in hospitalised children from Lima, Peru before and after introduction of the 7-valent conjugated vaccine.

The objective of this study was to determine the serotype distribution and antibiotic resistance of invasive pneumococcal disease (IPD) strains in children from Lima, Peru, before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), which was introduced in the national immunisation program on 2009. We conducted a prospective, multicentre, passive surveillance IPD study during 2006-2008 and 2009-2011, before and right after the introduction of PCV7 in Peru. The study was performed in 11 hospitals and five private laboratories in Lima, Peru, in patients &lt;18 years old, with sterile site cultures yielding Streptococcus pneumoniae. In total 159 S. pneumoniae isolates were recovered. There was a decrease in the incidence of IPD in children &lt;2 years old after the introduction of PCV7 (18.4/100 000 vs. 5.1/100 000, P = 0.004). Meningitis cases decreased significantly in the second period (P = 0.036) as well as the overall case fatality rate (P = 0.025), including a decreased case fatality rate of pneumonia (16.3% to 0%, P = 0.04). PCV7 serotypes showed a downward trend. Vaccine-preventable serotypes caused 78.9% of IPD cases, mainly 14, 6B, 5, 19F and 23F. A non-significant increase in erythromycin resistance was reported. Our findings suggest that the introduction of PCV7 led to a significant decrease of IPD in children under 2 years old and in the overall case fatality rate.

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15- and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines.

A multicenter clinical study on 1 138 cases of invasive pneumococcal disease in children from 2012 to 2017

Objective: To explore the clinical features, the serotype distribution and drug resistance of the isolates in patient with invasive pneumococcal disease (IPD). Methods: By retrieving the laboratory information system in 18 children's hospitals from 2012 to 2017, the children with IPD were enrolled. Streptococcus pneumoniae (Spn) must be isolated from the sterile sites (blood, cerebrospinal fluid, hydrothorax and joint effusion etc.). The clinical characteristics, serotype, drug resistance, treatment and prognosis were reviewed and analyzed. According to the telephone follow up results, the patients were divided into death group and recovered group. The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. Results: There were 1 138 children with IPD, including 684 male and 454 female. The proportion of male to female was 1.5∶1. The age ranged from one day to 16 years. The median age was 1 year 3 month. The majority was under 5 years of age (89.3%, n= 1 016), especially under 2 years of age (61.9%, n=704). In all cases, 88.2% (n=1 004) were community acquired infection. The infections included meningitis (n=446, 39.2%), pneumonia with bacteremia (n=339, 29.8%), and bacteremia without focus (n=232, 20.4%). Underlying diseases were found in 242 cases (21.3%). Co-infections were determined in 62 cases (5.4%) with mycoplasma, 27 cases (2.4%) with adenovirus and 34 cases with influenza virus (3.0%). The penicillin insensitivity (PNSP) rates in meningitis and non-meningitis isolates were 69.5% (276/397) and 35.9% (221/615), respectively. There were 81 strains serotyped, in which 93.8% (76/81) were covered by 13-valent protein-polysaccharide conjugate vaccine (PCV13). In the 965 patients who were followed up by phone call, 156 cases (16.2%) were confirmed dead. The independent risk factors for the death were under 2 years of age (OR=2.143, 95%CI 1.284-3.577, P=0.004), meningitis (OR=3.066, 95%CI 1.852-5.074, P<0.01), underlying disease (OR=4.801, 95%CI 2.953-7.804, P<0.01), septic shock(OR=3.542, 95%CI 1.829-6.859, P<0.01), disseminated intravascular coagulation (DIC) (OR=4.150, 95%CI 1.468-11.733, P=0.007), multiple organ failure (OR=12.693, 95%CI 6.623-24.325, P<0.01) and complications of central nervous system (OR=1.975, 95%CI 1.144-3.410, P=0.015). Conclusions: Most children with IPD were under 5 years of age, having underlying diseases and acquired the infection in community. The independent risk factors for death were under two years old, meningitis, underlying diseases and multiple organ failure. The problem of drug resistance was severe. The universal immunization of PCV13 would be effective to prevent IPD in Chinese children.

1438. Uptake of 13-Valent Pneumococcal Conjugate Vaccine in High-Risk Adults Aged 19–64 Years: A Kaplan–Meier Approach

BackgroundCoverage estimates for pneumococcal vaccination in the United States come from the National Health Interview Survey (NHIS) and do not differentiate between 13-valent conjugated vaccine (PCV13) and 23-valent polysaccharide vaccine (PPSV23). This study was conducted to assess coverage of PCV13 among adults aged 19–64 years targeted by the high-risk recommendation issued by the Advisory Committee on Immunization Practices (ACIP) in 2012.MethodsUptake was evaluated from October 2012 through October 2016 in two statistically de-identified databases: Optum’s Clinformatics™ Data Mart (CDM), consisting of administrative health claims, and the Optum-Humedica Electronic Health Record (EHR) dataset, which includes EHR data from providers, primarily integrated delivery networks in the United Statess to cover the continuum of care. Eligibility for the recommendation was determined between October 2011 and October 2016 and served as the index event. Post-index PCV13 uptake was evaluated using prescription and administration codes. Patients with PCV13 prior to the recommendation were excluded to minimize misclassification of PCV13 status. Uptake was calculated using a Kaplan–Meier estimator, with separate estimates for the period before and after the 2014 ACIP age-based recommendation for all adults aged ≥65 years.ResultsUptake of PCV13 was lower among 223,888 patients in the CDM vs. 571,993 patients in the EHR dataset, with <15% of recommended high-risk patients receiving PCV13 in the 4 years following publication of the recommendation. Vaccination among 19- to 64–year-old high-risk patients accelerated after the October 2014 publication of the recommendation for all adults aged ≥65 years. This was consistent in both CDM and EHR databases (Table 1).ConclusionUptake of PCV13 among high-risk adults aged 19–64 years in the US has been very low. Some of the PCV13 vaccination among high-risk patients may have been driven by spillover from the subsequent age-based recommendation for adults aged ≥65 years.Table 1.KM Estimates at the End of the Study with 95% CIUptake Rate95% CIher2012–20140.0420.041–0.0432014–20160.0820.079–0.084CDM (claims)2012–20140.0190.018–0.0202014–20160.0480.045–0.052Disclosures All authors: Employee and Shareholder, Salary.

Paediatric immunisation and chemoprophylaxis in a Ugandan sickle cell disease clinic.

We aimed to assess the receipt of recommended care for young children with sickle cell disease (SCD) in a central SCD clinic in Kampala Uganda, focusing on standard vaccination and antibacterial and antimalarial prophylaxis. A cross-sectional assessment of immunisation status and timeliness and prescribed antibacterial and antimalarial prophylaxis was performed in a sample with SCD aged ≤71 months in Mulago Hospital SCD Clinic. Government-issued immunisation cards and clinic-issued visit records for prescribed prophylaxis were reviewed. Vaccinations were documented by immunisation cards in 104 patients, mean age 31.7 months (range 3-70 months). Only 48 (46.2%) received all doses of each of the four recommended vaccine types, including pneumococcal 10-valent conjugate vaccine (pneumococcal conjugate vaccine (PCV)-10), which became available in 2014. Vaccination completion was associated with younger age and, for polio, maternal employment. PCV-10 series was completed in 54.8% of the sample and in 18.2% of those aged 48-71 months. Of children completing all vaccination types, an average 68.8% were immunised on time, defined as <60 days beyond the recommended age. Only 17 (13.5%) children were both fully and timely vaccinated. In an overlapping sample of 147 children, with a mean age of 38.4 months (4-70 months), 81.6% had ≥1 documented prescription for penicillin and/or antimalarial prophylaxis. Standardised vaccination and antibacterial and antimalarial protective measures for young children at this central SCD clinic were incomplete, especially PCV-10 for age ≥24 months, and often late. Child age, but not general maternal demographics, were associated with vaccination and chemoprophylaxis. Clinic-based oversight may improve timely uptake of these preventative measures.

VACCINATION AGAINST PNEUMOCOCCAL INFECTIONS IN RUSSIAN FEDERATION: SOCIAL AND PHARMACOECONOMIC ASPECTS

Vaccination against pneumococcal infections by 13-valent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality.The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection.Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system.The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level.In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given.The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018.Results.Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided.Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively).In the 15-year-horizon noting the distribution of 65-yearolds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively.Conclusions.Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.

Decreased relative risk of pneumococcal pneumonia during the last decade, a nested case-control study

BackgroundStreptococcus pneumoniae (SP) is one of the most common pathogens of Community-Acquired Pneumonia (CAP), but recent reports suggest that its incidence may be declining in relation to the use of the conjugate 13-valent pneumococcal vaccine in children. We compared the result of the immunochromatographic SP urinary antigen test (SPUAT) and clinical outcomes in patients with CAP admitted in two periods of time: 2001–2002(CAP1) and 2015–2016(CAP2).MethodsThis was a matched nested case-control study of two prospectively recorded cohorts of patients admitted with CAP, with SPUAT and blood culture performed in all patients. CAP2 cases and CAP1 controls were matched for age ± 4 years, sex, and Pneumonia Severity Index (PSI) score ± 10 points. Odds ratios (OR) for having SPUAT positive was estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables.ResultsFour hundred ninety-eight patients were recruited; 307 during the CAP1 and 191 during the CAP2 periods. Comparing both periods we observed differences, in age, PSI score, and the percentage of smokers, outpatients, previously immunized with pneumococcal vaccine, and positive SPUAT. On the other hand, mortality, admission from nursing homes, pneumococcal bacteremia and hospital admission were not different. After matching, pneumonia due to SP per the SPUAT was observed in 34(23.4%) of CAP1 and in 12(8.3%) of CAP2 patients (p < 0.001), and 6/145 CAP1 vs 33/145 CAP2 patients had received pneumococcal immunization before their admission (p < 0.001). A multivariate analysis confirmed that, independent of falling into PSI class 5, having not received the pneumococcal vaccine and having not survived the episode of pneumonia, there were two factors that increased the probability of having SPUAT positive: developing pneumonia during the CAP1 period (OR = 1.23) and having pneumococcal bacteremia (OR = 2.66).ConclusionWe observed a reduction of the role of SP as pathogen, along with an increase in the number of patients who received pneumococcal immunization before admission, in 2015-2016 compared to 2001-2002. In addition, the use of conjugate 13-valent vaccine, starting in 2012 for childhood immunization, could be an additional factor contributing to these changes, as a result of early herd immunity in adults pneumonia.

Trends of invasive pneumococcal disease and its serotypes in the Autonomous Community of Madrid

IntroductionStreptococcus pneumoniae is an important cause of morbidity. Vaccination is the most effective measure to prevent it. The aim of this study is to analyse the evolution of invasive pneumococcal disease (IPD). Material and methodsObservational study of IPD cases notified to the Epidemiological Surveillance Network of the Autonomous Community of Madrid between 2008 and 2015. The IPD case was defined as the disease caused by S. pneumoniae, with isolation and DNA or antigen detection, in samples from normally sterile sites. The isolated strains were sent to the Regional Public Health Laboratory for identification of the serotype. Serotypes were classified according to their inclusion in the 7-valent conjugate vaccine (PCV7), in the 13-valent vaccine, but not in the 7-valent vaccine (PCV13-additional) and not included in the 13-valent vaccine (non-PCV). The incidence rate ratios (IRRs) were calculated comparing the 2011–2012 and 2013–2015 periods with the 2008–2010 period. Results4,307 cases were reported. 86.6% were serotyped. The IRR of IPD was 0.67 and 0.67 for all serotypes; 0.43 and 0.45 for PCV7 serotypes; 0.46 and 0.25 for PCV13-additional serotypes, and 1.01 and 1.32 for non-PCV13 serotypes in the 2011–2012 and 2013–2015 periods. The incidence of serotypes 8, 9N, 10A, 23B, 24F and serogroup 33 increased significantly in the 2013–2015 period. Serotypes 15B and 24F accounted for 24% of non-PCV13 cases in children under 5 years, serotypes 8 and 9N for 51% in the population aged 5–59 years and serotypes 8 and 22F for 25% in the population aged over 59 years. ConclusionsThe incidence of serotypes not included in conjugate vaccines has increased, especially in children under 5 years, but the total incidence of IPD has decreased. It is important to continue with the epidemiological and microbiological surveillance programmes to assess the effect of vaccination on the incidence of IPD.

Retrospective cost-effectiveness of the 23-valent pneumococcal polysaccharide vaccination program in Australia

BackgroundThe Australian infant pneumococcal vaccination program was funded in 2005 using the 7-valent pneumococcal conjugate vaccine (PCV7) and the 13-valent conjugate vaccine (PCV13) in 2011. The PCV7 and PCV13 programs resulted in herd immunity effects across all age-groups, including older adults. Coincident with the introduction of the PCV7 program in 2005, 23-valent pneumococcal polysaccharide vaccine (PPV23) was funded for all Australian adults aged over 65 years. MethodsA multi-cohort Markov model with a cycle length of one year was developed to retrospectively evaluate the cost-effectiveness of the PPV23 immunisation program from 2005 to 2015. The analysis was performed from the healthcare system perspective with costs and quality-adjusted life years discounted at 5% annually. The incremental cost-effectiveness ratio (ICER) for PPV23 doses provided from 2005 to 2015 was calculated separately for each year when compared to no vaccination. Parameter uncertainty was explored using deterministic and probabilistic sensitivity analysis. ResultsIt was estimated that PPV23 doses given out over the 11-year period from 2005 to 2015 prevented 771 hospitalisations and 99 deaths from invasive pneumococcal disease (IPD). However, the estimated IPD cases and deaths prevented by PPV23 declined by more than 50% over this period (e.g. from 12.9 deaths for doses given out in 2005 to 6.1 in 2015), likely driven by herd effects from infant PCV programs. The estimated ICER over the period 2005 to 2015 was approximately A$224,000/QALY gained compared to no vaccination. When examined per year, the ICER for each individual year worsened from $140,000/QALY in 2005 to $238,000/QALY in 2011 to $286,000/QALY in 2015. ConclusionThe cost-effectiveness of the PPV23 program in older Australians was estimated to have worsened over time. It is unlikely to have been cost-effective, unless PPV23 provided protection against non-invasive pneumococcal pneumonia and/or a low vaccine price was negotiated. A key policy priority should be to review of the future use of PPV23 in Australia, which is likely to be more cost-effective in certain high-risk groups.