13-valent Pneumococcal Vaccine Research Articles

Autologous Splenocyte Reinfusion Improves Antibody-Mediated Immune Response to the 23-Valent Pneumococcal Polysaccharide-Based Vaccine in Splenectomized Mice.

Common clinical options, currently, for necessary splenectomy are vaccinations and antibiotic prophylaxis. However, despite these two adjuncts, there still occur numerous cases of overwhelming post-splenectomy infection. To examine whether reperfusion of critical splenic lymphocytes could boost immune response, we harvested splenic lymphocytes, reperfused the autologous lymphocytes, and then administered a pneumococcal vaccine (PNEUMOVAX®23, i.e., PPSV23) in splenectomized mice. We found that splenectomy impaired the immune response in the splenectomized group compared to the non-splenectomized group; the splenectomized group with lymphocyte reinfusion had a higher response to polysaccharide vaccination based on antibody titer than the splenectomized group without lymphocyte reinfusion. The sham group with the native spleen had the most elevated antibody titer against the PPSV23 polysaccharide antigen. This may be additive, resulting from contributions of the splenic structure, along with the phagocytic function of the spleen and its constituent cells affecting the antibody response. Reinfusion of splenic lymphocytes may enhance immunity without the complications associated with splenic fragment autotransplantation, which never gained acceptance. This technique is safe and simple since the splenic lymphocytes are autologous and, therefore, not self-reactive, and very similar to autologous blood transfusion. This concept may be beneficial in cases of unavoidable splenectomy, especially in pediatric cases.

Serotypic distribution and antimicrobial resistance of Streptococcus pneumoniae in Chinese children under 5 years after the introduction of the 13-valent conjugate pneumococcal vaccine: protocol for a scoping review

The World Health Organization (WHO) recommends that pneumococcal conjugate vaccines (PCVs) be included in immunization programs worldwide. In China, the 7-valent pneumococcal conjugate vaccine (PREVNAR 7®) was authorized in 2008 but was not included in the national immunization programs. In 2016, PREVNAR 13®, a 13-valent pneumococcal conjugate vaccine (PCV13), was licensed for optional use in China. We will conduct a scoping review of the distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in children aged under 5 years in China since the introduction of PCV13. We will obtain data from PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Med Online. We will also review epidemiological data from WHO and the China Antimicrobial Surveillance Network (CHINET). Our analysis will include the condition of interest, the intervention, and the geographical region. All types of studies will be eligible for inclusion in the study database if they meet the inclusion criteria. This scoping review is intended to outline how S. pneumoniae serotypes are distributed, and it will map their antimicrobial resistance in children aged under 5 years in China. The results of this study will provide useful information on the impact of PCV13 in China.

A patient-centered medical home model for comprehensive sickle cell care in infants and young children.

The patient-centered medical home (PCMH) has been proposed as a model for comprehensive care coordination and delivery for children with sickle cell disease (SCD), yet little is known regarding the implementation of PCMH core concepts on adherence to preventative care measures, health care utilization, and parent satisfaction. We implemented the newborn cohort clinic (NCC) to explore the application of the PCMH model for infants and children with SCD from birth to age 3years in 2011. In July 2017, we conducted a retrospective chart review to evaluate subjects currently or previously followed in the clinic. We surveyed parents in the NCC to assess their satisfaction with their experience. A total of 112 patients have been managed in the NCC. All patients received penicillin prophylaxis, while 70% and 73% of patients, respectively, received the 23-valent pneumococcal vaccine and an initial transcranial Doppler by age 36months. Most (92 of 112) of the subjects utilized the emergency department (569 encounters), with 86% of encounters for fever or other sickle cell-related complications. The majority of parents indicated satisfaction with the clinic, with 71% saying clinic providers always or usually spent enough time with their child, listened carefully to them (81%) and were sensitive to family values and customs (77%). A comprehensive sickle cell clinic as a component of a PCMH is feasible and can achieve high levels of preventative care. Parents are largely satisfied with this model of care.

Serotypic distribution and antimicrobial resistance of Streptococcus pneumoniae in Chinese children under 5 years after the introduction of the 13-valent conjugate pneumococcal vaccine: protocol for a scoping review.

The World Health Organization (WHO) recommends that pneumococcal conjugate vaccines (PCVs) be included in immunization programs worldwide. In China, the 7-valent pneumococcal conjugate vaccine (PREVNAR 7®) was authorized in 2008 but was not included in the national immunization programs. In 2016, PREVNAR 13®, a 13-valent pneumococcal conjugate vaccine (PCV13), was licensed for optional use in China. We will conduct a scoping review of the distribution of serotypes and antimicrobial resistance of Streptococcus pneumoniae in children aged under 5 years in China since the introduction of PCV13. We will obtain data from PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Med Online. We will also review epidemiological data from WHO and the China Antimicrobial Surveillance Network (CHINET). Our analysis will include the condition of interest, the intervention, and the geographical region. All types of studies will be eligible for inclusion in the study database if they meet the inclusion criteria. This scoping review is intended to outline how S. pneumoniae serotypes are distributed, and it will map their antimicrobial resistance in children aged under 5 years in China. The results of this study will provide useful information on the impact of PCV13 in China.

Development of Next Generation Streptococcus pneumoniae Vaccines Conferring Broad Protection.

Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.

Impact of the 10-valent pneumococcal conjugate vaccine on hospital admissions in children under three years of age in Iceland

IntroductionPneumococcus is an important respiratory pathogen. The 10-valent pneumococcal vaccine (PHiD-CV) was introduced into the Icelandic vaccination programme in 2011. The aim was to estimate the impact of PHiD-CV on paediatric hospitalisations for respiratory tract infections and invasive disease. MethodsThe 2005–2015 birth-cohorts were followed until three years of age and hospitalisations were recorded for invasive pneumococcal disease (IPD), meningitis, sepsis, pneumonia and otitis media. Hospitalisations for upper- and lower respiratory tract infections (URTI, LRTI) were used as comparators. The 2005–2010 birth-cohorts were defined as vaccine non-eligible cohorts (VNEC) and 2011–2015 birth-cohorts as vaccine eligible cohorts (VEC). Incidence rates (IR) were estimated for diagnoses, birth-cohorts and age groups, and incidence rate ratios (IRR) between VNEC and VEC were calculated assuming Poisson variance. Cox regression was used to estimate the hazard ratio (HR) of hospitalisation between VNEC and VEC. Results51,264 children were followed for 142,315 person-years, accumulating 1,703 hospitalisations for the respective study diagnoses. Hospitalisations for pneumonia decreased by 20% (HR 0.80, 95%CI:0.67–0.95) despite a 32% increase in admissions for LRTI (HR 1.32, 95%CI:1.14–1.53). Hospital admissions for culture-confirmed IPD decreased by 93% (HR 0.07, 95%CI:0.01–0.50) and no hospitalisations for IPD with vaccine-type pneumococci were observed in the VEC. Hospitalisations for meningitis and sepsis did not change. A decrease in hospital admissions for otitis media was observed, but did not coincide with PHiD-CV introduction. ConclusionFollowing the introduction of PHiD-CV in Iceland, hospitalisations for pneumonia and culture confirmed IPD decreased. Admissions for other LRTIs and URTIs increased during this period.

Retrospective Study in Children With Necrotizing Pneumonia: Nine Years of Intensive Care Experience.

Although necrotizing pneumonia (NN) is one of the most feared complications of community-acquired pneumonia, data in pediatric patients are scarce. The objective of this article is to describe children admitted to pediatric intensive care unit (PICU) because of NN. Retrospective-prospective observational study in children admitted with NN to PICU (from January 1, 2010, to December 31, 2018). The data collected included information on disease epidemiology, PICU management, respiratory assistance and disease evolution. Fifty-one children were included, 42 of 51 had received 7-valent or 13-valent pneumococcal vaccine. Median age was 3.2 years (1.9-4.2), 15 of 51 had signs of sepsis at admission. Forty-nine patients presented pleural effusion with drainage in 46. The most common respiratory support modality was high-flow oxygen nasal cannula (17/51). Computed tomography was the gold standard for diagnosis. Etiologic diagnosis was obtained in 34 of 51, and pneumococcus was isolated in 29 of 34. In all of these cases, initial detection was made by capsular antigen in pleural fluid. Children with pneumococcal NN had fewer days of evolution prior to PICU admission (P = 0.041). Cefotaxime with clindamycin was used in 49 of 51. Surgery was necessary in 3 of 51 patients. After PICU discharge, only 5 of 51 were readmitted. There were deaths. In our study, the NN was mainly observed in children around 3 years old. The main causal agent was pneumococcus. The evolution towards NN appeared to be faster than in case of other etiologies. Surgery management was unusual. All children required prolonged admissions but had a full clinical recovery.

Practical experience of using pneumococcal thirteen-valent conjugate vaccine among premature infants

Aim. To ground the necessity of premature infants vaccination against pneumococcal infection and estimate the reactogenicity and immune activity of pneumococcal 13-valent conjugate vaccine when vaccinating infants with different degree of prematurity.
 Materials and methods. The clinical study enclosed 88 children including 16 (18.2 0.25 %) infants with extremely low birth body mass (ELBM) and 28 infants (31.8 0.32 %) with very low body mass (VLBM). The mean gestation age was 31 0.41 weeks. The mean birth weight was 1530 66.58 grams. Bronchopulmonary dysplasia was diagnosed in 27 0.25 % of infants. Thirty one infants underwent assessment of the concentration of the total level of specific blood serum IgG antibodies to S. Pneumonia antigens contained in vaccine. The mean age of these infants was 9.71 0.74 months, the mean gestation age at birth 30 0.41 weeks (25 to 41 weeks). The mean birth weight 1441 66.58 grams, ELBM 14 infants, VLBM 18 infants.
 Results. The mild general postvaccinal reactions were noted in 11.3 1.24% of infants, which were arrested for 2 days with no drugs used. The moderate and severe reactions were observed in 2.27 0.62 % of infants. No local postvaccinal reactions were registered. When studying the concentration of the total level of specific IgG antibodies to S. Pneumonia antigens, there was revealed a more than 4- fold increase in geometric mean of pneumococcal antibody titer that proves a high immunogenicity of this vaccine in premature infants. A high level of pneumococcal antibodies after vaccination was reached in 24 infants (75 1.24 % of infants).
 Conclusion. The necessity of immunization of premature infants against pneumococcal infection was scientifically grounded. The application of conjugate 13-valent pneumococcal vaccine among premature infants confirmed a high profile of its safety and high immunogenicity. Improvement of communicative habits between parents and medical personnel regarding the necessity of vaccination of premature infants against pneumococcal infection, as an advanced technology, will permit to provide a timely coverage of infants with immunization (98 %).

The estimated impact of the 5-year national vaccination program on the trend of 23-valent pneumococcal polysaccharide vaccine vaccination rates in the elderly in Japan, 2009–2018

Pneumonia is the third most common cause of death in Japan. Low vaccination rates are thought to be related to low levels of public subsidy. Since 2014, the Japanese government has offered subsidies through a 5-year national routine vaccination program of the 23-valent pneumococcal polysaccharide vaccine (PPV23) for older adults at age ≥65 years with 5-year age intervals. We previously reported that, 2 years into the 5-year program, the estimated vaccination rate was 40.6% at the end of 2015, a significant increase compared with periods before the program introduced. Here, we present an update on the estimated vaccination coverage of the 5-year national routine vaccination program at the end of 2018. The PPV23 vaccination rates were calculated by dividing the cumulative amount shipped to each municipality by the population aged ≥65 years. At the end of 2018, the completion of the 5-year national immunization program, the estimated cumulative vaccination rate was 74%. Stepwise regression analysis revealed that the annual PPV23 vaccination rate significantly increased after 2014 (from 2 to 5% prior to 2014, to 10–11% after 2014), and remained steady for 2014–2018. Our findings suggest that the 5-year national routine vaccination subsidy program was successful in achieving a steady and higher vaccination rate of PPV23 in Japan.

Pneumococcal vaccination in adult patients with comorbidities: a review of the clinical practice guidelines

The review discusses national clinical practice guidelines for pneumococcal vaccination in different countries, existing approaches to adult immunization, and highlights key results of the most significant clinical studies and metaanalyses on the effectiveness of 23-valent polysaccharide pneumococcal vaccine and 13-valent conjugated pneumococcal vaccine in adults, including the elderly and patients with comorbidities.

Obituary of Prof. E. Venkata Rao

Prof. Venkata Rao born on 1st July, 1931 completed his studies in Andhra University during the years 1950- 59. He was one of the founder members of the Department of Pharmaceutical Sciences at Andhra University, Visakhapatnam and instrumental in the growth of institution by way of his rich contributions over a period of 4 decades in different capacities from 1953-91. He visited UK on a Commonwealth Scholarship and worked under Prof. Sir James Baddiley FRS, in Newcastle University, which led to the award of a Ph. D. degree in Bio-Organic Chemistry in 1964 on the topic Studies on the Capsular Polysaccharides of Pneumococcus Type 10A, which work won him K. N. Welch Memorial Prize and this work also formed part of the 23-valent Pneumococcal vaccine (Pneumovax-23rm), which is official to Indian pharmacopeia 2007. Earlier to this significant contribution, Prof. Venkata Rao’s D. Sc. work at Andhra University on Thevetia neriifolia resulted in the discovery of a new clinically useful cardiotonic glycoside, peruvoside, the first modern drug discovery in India acclaimed by the International Scientific Community. This drug was developed for therapeutic use by M/s E. Merck and manufactured by an Italian Pharma Company, Simes, was listed in the Merck Index and Martindale-The Extra Pharmacopeia. Several other compounds his group isolated and worked on have found a place in the Merck Index.

Surveillance of bacterial meningitis in an Angolan pediatric hospital after the introduction of pneumococcal conjugate vaccines

# Background Bacterial meningitis (BM) is a significant cause of mortality in children; with deaths from BM in children aged \<5 years in Angola estimated at 2395 in 2015. *Streptococcus pneumoniae* is one causative agent for BM in young children, and Angola introduced routine immunization with a 13-valent pneumococcal vaccine (PCV13) in 2012. This study assessed BM etiology in children in Angola following introduction of PCV13. # Methods This was a prospective, observational, single-site study conducted from October 2016 to October 2017. Children aged 3 months--15 years were included. Suspected meningitis was defined according to the World Health Organization (WHO) guidelines. Detection and characterization of *S. pneumoniae, Neisseria meningitidis,* and *Haemophilus influenzae* was carried out using polymerase chain reaction (PCR) assay. # Results A total of 1732 patients were enrolled and bacteria were detected in 137 cerebrospinal fluid samples. The most common pathogen detected was *S. pneumoniae* (43/137, 31.4%), followed by *H. influenzae* (21/137, 15.3%) and *N. meningitidis* (16/137, 11.7%) with 48% (10/21) of *S. pneumoniae* cases caused by PCV13 vaccine serotypes. *N. meningitidis* isolates were serogroups B, C and Y, and 67% (10/15) of *H. influenzae* isolates were type b. In patients with meningitis and a pathogen detected, mortality (38% (50/132) vs. 12% (101/818), *P*\<0.0001) and severe neurological sequelae (15% (10/67) vs. 5% (35/667), *P*=0.002) were higher than in those without pathogens detected. # Conclusions These data highlight that strategies to reduce the incidence of BM caused by *N. meningitidis, S. pneumoniae* and *H. influenzae* must continue to reduce mortality and morbidity.

A Japanese nationwide survey of 23-valent pneumococcal capsular polysaccharide vaccine (PPSV23) coverage among patients with chronic medical condition aged 50 and older

ABSTRACT The 23-valent capsular polysaccharide pneumococcal vaccine (PPSV23) was introduced in Japan’s routine immunization schedule October 2014. It was recommended for adults aged 65 years (including those ≥65 during the transition period), and for adults 60–64 with cardiac, renal, or respiratory dysfunction equivalent to Level 1 physical disability. Several studies have shown that patients aged 50+ with chronic medical conditions (CMC) are at elevated risk of pneumococcal infection. Nonetheless, PPSV23 vaccination rates among this population remains low. In our study, we report the results of a survey investigation into PPSV23 vaccination rates among Japanese patients aged 50+ with CMC. Patients aged 50+ comprised the patient population (n = 5,078) and internal medicine physicians comprised the doctor population (n = 400) located all over Japan were asked an array of questions relevant to PPSV23 immunization in June 2018 via Web-based surveys. PPSV23 coverages among chronic patients aged 50–59, 60–64, and 65+ years were respectively 1.3%, 2.9%, and 37.8%. The high disease-specific PPSV23 rates seen in the 65+ group was 50.0% and 49.4%, for chronic liver disease and chronic lung disease, respectively. Doctors most frequently cited a lack of municipal subsidies as justification for recommending the vaccine to patients with CMC aged 50–64 years, and deference to patients’ wishes as justification for patients with CMC aged 65+. In conclusion, PPSV23 has poor coverage among Japanese adults aged 50–64 with CMC. Doctors and local authorities need to raise public awareness to improve the vaccination rate, given the high risk of pneumococcal infectious disease among patients with CMC.

Immunisation status screening in the emergency department: Why are we forgetting the elderly?

BackgroundPneumonia is one of the most common reasons patients over the age of 65 years present to the Emergency Department (ED). There is a 23-valent pneumococcal vaccine (23vPPV) available under the National Immunisation Program (NIP) with demonstrated 61–71% effectiveness against Invasive Pneumococcal Disease (IPD), but only 51% of adults aged over 65 years are vaccinated in Australia. MethodsShort semi-structured interviews were conducted with emergency nurses working across a Local Health District in Sydney New South Wales (n=9) in order to determine their knowledge, behaviour and attitudes towards immunisation status screening in the elderly who present to the ED with pneumonia. Questions were structured to the COM-B Model (capability, opportunity and motivation to change behaviour), and a thematic analysis was conducted. ResultsThere were three major themes identified: (1) The importance of routinisation, (2) Low knowledge levels and, (3) The ‘vaccination is for children’ heuristic, as well as suggestions for future interventions to improve screening. ConclusionsThese findings clarify how to improve vaccine uptake amongst this vulnerable cohort. They suggest that emergency departments should provide education to nurses. In addition, checklists/tick boxes can prompt nurses whilst conducting routine work, which may lead to increased vaccination uptake.

Clinical effectiveness of 13-valent and 23-valent pneumococcal vaccination in middle-aged and older adults: The EPIVAC cohort study, 2015–2016

BackgroundClinical benefits using the 23-valent pneumococcal polysaccharide vaccine (PPsV23) or the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness for both PPsV23 and PCV13 in preventing pneumonia among middle-aged and older adults. MethodsPopulation-based cohort study involving 2,025,730 persons ≥50 years in Catalonia, Spain, who were prospectively followed between 01/01/2015 and 31/12/2016. Primary outcomes were hospitalisation from pneumococcal or all-cause pneumonia and main explanatory variable was PCV13/PPsV23 vaccination status. Multivariable Cox regression models were used to estimate vaccination effectiveness adjusted for age and baseline-risk conditions. ResultsCohort members were followed for 3,897,151 person-years (17,496 PCV13 vaccinated and 1,551,502 PPsV23 vaccinated), observing 3259 pneumococcal pneumonias (63 in PCV13 vaccinated, 2243 in PPsV23 vaccinated) and 24,079 all-cause pneumonias (566 in PCV13 vaccinated, 17,508 in PPsV23 vaccinated). Global incidence rates (per 100,000 person-years) were 83.6 for pneumococcal pneumonia (360.1 in PCV13 vaccinated, 144.6 in PPsV23 vaccinated) and 617.9 for all-cause pneumonia (3235.0 in PCV13 vaccinated, 1128.5 in PPsV23 vaccinated). In the multivariable analyses, the PCV13 appeared significantly associated with an increased risk of pneumococcal pneumonia (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.17–1.97; p = 0.002) and all-cause pneumonia (HR: 1.76; 95% CI: 1.61–1.92; p < 0.001) whereas the PPsV23 did not alter the risk of pneumococcal pneumonia (HR: 1.08; 95% CI: 0.98–1.19; p = 0.132) and slightly increased the risk of all-cause pneumonia (HR: 1.17; 95% CI: 1.13–1.21; p < 0.001). In stratified analyses focused on specific target population subgroups (i.e., elderly people, at-risk and high-risk individuals), protective effects of vaccination did not emerge either. ConclusionData does not support clinical benefits from pneumococcal vaccination (nor PCV13 neither PPsV23) against pneumonia among Catalonian adults in the current era of universal PCV’s childhood immunisation.

A Novel Sickle Cell Outreach Program Improves Access to TCD Screening, Vaccines and Hydroxyurea in a Medically Underserved Area

Background: The Sickle Care Coordination, OutReach, Education Program (SCORE) was created in 2017 to improve access to hematology care and care coordination services for children with sickle cell disease (SCD) in an urban community in Lake County, Indiana. Although Lake County has the second highest prevalence of SCD in Indiana, it lacks a pediatric hematologist, and the closest pediatric hematology practice is 65 miles away. Newborn screening data from 2009-2017 showed that only 25% of children in this underserved area received Transcranial Doppler (TCD) and only 25% received the 23 valent pneumococcal vaccine, compared with 70% for both in other regions of Indiana. The goal of the SCORE clinic is to increase TCD screening and vaccination rates as well as increase the number of children who are prescribed hydroxyurea (HU) at maximum tolerated dosing (MTD). Methods: Quarterly SCORE outreach clinics were established in Lake County, Indiana in August 2017, which is 145 miles Northwest of our center. A multi-disciplinary team (social worker, sickle cell educators, nursing staff) accompanies the pediatric hematologist and physician assistant to clinic. Vaccines are administered in SCORE clinic and laboratory tests are drawn on site. Same day TCD screening was established in May 2018. The state's electronic vaccine record was queried to determine which SCD-specific vaccines the children needed prior to each clinic. Education about SCD, HU, and needed screening tests like TCD was provided by members of the multi-disciplinary team. Results: One hundred thirty-one visits have been made to the 10 SCORE outreach clinics that have been held since August 2017. Forty children have received hematology care in the SCORE clinic; 35 (87.5%) children have had at least 2 visits. Twenty-two children were eligible for HU; sixteen (72.7%) were already taking HU at the time of their first visit to SCORE outreach clinic (mean dose prior to first SCORE visit: 18.6 + 5.9 mg/kg/day). Mean HU dose increased significantly after being followed by the SCORE clinic team (26.5 mg/kg/day, p=0.00002). The remaining 6 children initiated HU after receiving care in the SCORE outreach clinic. Nineteen children were eligible for TCD screening since their first SCORE clinic visit, and fourteen (73.7%) children completed the screening. One hundred twenty-one vaccines have been given in clinic to date: 100% of children who were eligible for the 23 valent pneumococcal, hepatitis A and B vaccines have received them. Seasonal influenza vaccine was given to 76.9% of eligible children. Forty-six of the 54 (85.2%) Menveo doses that were due were given, and 80% of Bexsero doses that were due were given. Conclusion: The SCORE program has increased access to pediatric hematology care for children with SCD in an urban, underserved community in Indiana. In the first 2 years of the program, TCD screening rates and pneumococcal vaccination rates have increased to the level seen in other regions of the state. Children who received care in the SCORE outreach clinic had a significant increase in their HU dosing. Outreach clinics can increase access to specialty care in underserved areas. Disclosures Meier: CVS Caremark: Consultancy. OffLabel Disclosure: Hydroxyurea prescription in children less than 2 years of age.

Viro-immunological outcomes after 13-valent pneumococcal vaccination in HIV-1-infected individuals on stable virological suppression.

Very limited data are available on the immunovirological outcomes after 13-valent pneumococcal conjugate vaccine (PCV13) in antiretroviral therapy (ART)-treated patients. The aim of this study was to assess the immune-virological outcomes in HIV-1-infected ART-treated patients on stable virological suppression who underwent pneumococcal conjugate vaccination. Retrospective, cohort study on ART-treated HIV-1-infected individuals, age at least 18 years, with three consecutive determinations of HIV-RNA less than 50 copies/ml before the administration of PCV13 (baseline) at San Raffaele Hospital and with at least two HIV-RNA values after vaccination. Overall 1197 patients underwent PCV13 vaccination. During 6-month of follow-up (594 person-years of follow-up, PYFU), 12 confirmed virological failure and 35 viral blips were observed; the overall incidence rate of confirmed virological failure was 2.02 (95% confidence interval: 0.88-3.16) per 100-PYFU and the incidence rate of viral blips was 5.89 (95% confidence interval: 3.94-7.84) per 100-PYFU. Median CD4 cell count change from baseline at 6 months was +10 cells/μl (interquartile range -67, +111; P = 0.0002). Median change in CD4/CD8 ratio was +0.02 (interquartile range -0.06, +0.11; P < 0.001). Viral blips and confirmed virological failures were rarely observed in patients on stable virological suppression in the first 6 months following vaccination with PCV13. In addition, no decrease of CD4 cell count and CD4/CD8 ratio was recorded.

An impact of pneumococcal vaccination on exacerbations of occupational lung diseases

Dust-related diseases are the most common occupational diseases with significant economic burden. The purpose of this study was to assess an impact of pneumococcal vaccination on exacerbation rate of occupational lung diseases. Methods. Patients with occupational lung diseases were vaccinated with pneumococcal polysaccharide 23-valent vaccine (PPV23) or pneumococcal conjugate vaccine (PCV13) and then were followed-up for long time. We analyzed the rate of exacerbations of occupational lung diseases at baseline and during 5 years after the vaccination. The immune status, anti-IgG antibodies and antibodies against PPV23 polysaccharides were measured in blood; lactoferrin and IgA were measured in saliva. Exacerbations were determined retrospectively based on outpatient medical records. Results. A rate of exacerbations significantly decreased over two years after the vaccination with PPV-23 followed by an increase to the end of the third year and a significant increase to the end the fourth year; the latter exceeded the pre-vaccination exacerbation rate. After re-vaccination with PPV23, the exacerbation rate decreased and reached the lowest rate two years after the revaccination. This result was maintained over five years with a slight transient decrease during the fourth year. This could be explained by lack of immune memory cells after the re-vaccination compared to primary vaccination and to the risk of B-cell pool depletion. When PCV13 vaccine was used for re-vaccination a year after primary vaccination with PPV23, the exacerbation rate sharply decreased a year after the re-vaccination with maintenance of the effect during three subsequent years and a significant decrease to the end of the fourth year. In a subgroup of patients with pneumoconiosis who were primarily vaccinates with PCV13 without further re-vaccination, the exacerbation rate significantly reduced a year after the vaccination with further reduction during five years. The exacerbation rates were similar in this subgroup and in patients vaccinated sequentially with PCV13 and PPV23. Conclusion. The long-term immune response could be provided by conjugation caused the memory cell formation compared to PPV23 vaccine.

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.

2701. The Impact of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Children in British Columbia, Canada

BackgroundA significant reduction in invasive pneumococcal disease (IPD) has been reported following implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) infant immunization program, but not much has been reported after introduction of the 13-valent vaccine (PCV13). This study represents the effect of PCV13 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 children less than 17 years of age. 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 697 cases were reported over the 14 year period. The overall annual incidence decreased from 10.9 cases per 100,000 population in 2002 to 4.64 cases per 100,000 population in 2015. While overall decline of IPD was 59% (IRR 0.41; 95% CI: 0.35–0.51) compared with baseline, this reduction was greatest after introduction of PCV7 (IRR 0.44; 95% CI: 0.37–0.53); the incremental change after introduction of PCV13 was non-significant (IRR 0.94; 95% CI: 0.78–1.13). The greatest reduction in IPD was in children <2 years of age (PCV13 vs baseline: IRR 0.19; 95% CI: 0.14–0.25), followed by children 3–5 years of age (PCV13 vs baseline: IRR 0.34; 95% CI: 0.21–0.56); no significant change was observed in 6–17 year olds.ConclusionWhile IPD rates have been significantly reduced since the introduction of the PCV vaccines, the impact of the additional 6 serotypes in the PCV13 vaccine is non-significant.Disclosures All authors: No reported disclosures.