bluuebunny/crossref_metadata_2025 huggingface dataset:
2703. Pneumococcal Carriage of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) and Non-PCV13 Serotypes among Greek Children Vaccinated with PCV13 in a 3 + 1 Schedule During the First 6 years after the Fourth Dose of PCV13
Authors: Syrogiannopoulos George A , Grivea Ioanna N , Moriondo Maria , Nieddu Francesco , Michoula Aspasia N , Azzari Chiara
Published: October 2019

Background

We evaluated the long-term impact of full PCV13 vaccination in a 3 + 1 schedule on pneumococcal colonization patterns of children in order to clarify PCV13 serotype persistence/enhancement and re-colonization.

Methods

From January 18 to August 29, 2017, consecutive children who had received the 4-dose course of PCV13, as per the National Immunization Program recommendations, were prospectively enrolled through 45 general pediatric practice facilities in 30 municipalities in Greece. A single oropharyngeal sample was obtained from each subject in a standardized manner (questionnaire, procedure). Based on the time interval since the fourth dose of PCV13, the children sampled were grouped for analysis in 6 groups: 26 days to 11 months; 12–23 months; 24–35 months; 36–47 months; 48–59 months, and 60–71 months. Carriage and distribution of Streptococcus pneumoniae serotypes was detected by RT–PCR.

Results

A total of 1212 children aged 14–83 months were investigated. S. pneumoniae was identified in the pharyngeal swab of 617 children (50.9%); 172/617 (27.9%) children carried > 1 pneumococcal serotypes. As a consequence of co-colonization, a total number of 718 S. pneumoniae (belonging to 28 serotypes) was identified. The carriage rate of non-PCV13 serotypes escalated within 3 years after the fourth dose and plateaued during the fourth and fifth year. The carriage rate of PCV13 serotypes escalated during the 4 years after the fourth dose and declined thereafter. 22/305 children (7.2%) carried one or more PCV13 serotypes in the first year after the fourth vaccine dose, 27/201 (13.4%) in the second year, 34/207 (16.4%) in the third year, 48/224 (21.4%) in the fourth year, 40/191 (20.9%) in the fifth year and 13/84 (15.5%) in the sixth year (P < 0.0001) (Figure 1). The colonization frequency of serotypes 3 and 19A increased with the rise of the vaccination time interval (Figure 2). Changes in the frequency of other PCV13 serotypes were not significant. Serotypes 7F, 14 and 23F were not recovered.

Conclusion

Our study suggests that S. pneumoniae is present in the pharynx of children 26 days to 71 months after the completion of PCV13 vaccination, and that non-PCV13 serotypes predominate throughout this period. The carriage rate of PCV13 serotypes 3 and 19A increases significantly as the time interval from the fourth dose of PCV13 increases.

Disclosures

All authors: No reported disclosures.
2706. Indirect Effects of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Adults in British Columbia, Canada
Authors: Vadlamudi Nirma K , Patrick David , Hoang Linda , Marra Fawziah
Published: October 2019

Background

Many jurisdictions report a significant reduction in invasive pneumococcal disease (IPD) in adults following implementation of the pneumococcal conjugate vaccines, 7-valent (PCV7) and 13-valent (PCV13) in childhood immunization programs. This study evaluates the indirect effect of conjugate vaccines on IPD in British Columbia, Canada over a 14 year period (2002–2015).

Methods

Using provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in adults 18 years of age and older. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.

Results

A total of 3793 cases were reported over the 14 year period. The overall annual incidence increased from 4.32 cases per 100,000 population in 2002 to 8.61 cases per 100,000 population in 2015. Overall, IPD has increased by 80% (IRR: 1.80; 95% CI: 1.59–2.04) compared with baseline, especially in adults ≥ 85 years of age (PCV13 vs baseline: IRR: 1.90; 95% CI: 1.25–03.05). This increase was the highest after introduction of PCV7 (IRR: 1.87; 95% CI: 1.65–2.11); the incremental change after introduction of PCV13 was non-significant (IRR 0.96; 95% CI: 0.90–1.03). While PCV7 type IPD plummeted by 76% (IRR 0.24; 95% CI: 0.18–0.31) since introduction of PCV7 compared with baseline, a modest decline in PCV13 type IPD of 20% was seen (IRR 0.80; 95% CI: 0.71–0.89) since introduction of PCV13.

Conclusion

Although PCV7-type IPD has decreased substantially, only a modest reduction in IPD from the additional 6 serotypes in the PCV13 vaccine was observed.

Disclosures

All authors: No reported disclosures.
2717. The Impact of Pneumococcal Conjugate Vaccine in Nonbacteremic Pneumococcal Pneumonia Among Cancer Patients
Authors: Lee Yeon Joo , Richards Rocco , Su Yiqi , Kaltsas Anna , Papanicolaou Genovefa
Published: October 2019

Background

Invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NB-PNA) are associated with substantial morbidity and mortality in cancer patients. IPD incidence among cancer patients at MSKCC sharply declined after the introduction of routine childhood immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) (1). An indirect effect of PCV on pneumococcal pneumonia incidence has also been reported (2, 3). The impact of PCV on the incidence of NB-PNA in patients with cancer has not been well studied.

Methods

Retrospective review of patients treated at MSKCC, 1993–2012. Unique patient visits (UPV) per year were defined as ≥1 inpatient or outpatient encounter within one calendar year. NB-PNA was defined as Isolation of Streptococcus pneumoniae from sputum or bronchoalveolar lavage (BAL); with associated symptoms (cough, sputum production, and/or fever) and radiographic findings compatible with pneumonia on chest radiograph or computerized chest tomography. NB-PNA incidence was calculated as number of NB-PNA cases per 1000 UPV. Three-time periods were examined: “before PCV7” (1993–2000), “after PCV7” (2001–2010), “after PCV13” (2011–2012).

Results

Of 323 NB-PNA cases, S. pneumoniae was isolated from BAL in 64 (20%) and sputum in 259 (80%). 182 (56%), 121 (37%), and 20 (7%) NB-PNA cases occurred “before PCV7,” “after PCV7,” and “after PCV13,” respectively. The incidence of NB-PNA was highest in patients with hematologic malignancies and in patients ≥65 years during all three periods (Table 1). NB-PNA incidence was lower “after PCV7” compared with “before PCV7” (0.47 vs. 0.13, P < 0.001). A non-statistically significant lower incidence of NB-PNA was noted “after PCV13” vs. “after PCV7” (0.13 vs. 0.09, P = 0.19). The highest decline of NB-PNA after PCV7 introduction was observed in patients ≥65 years (0.67 vs. 0.16, P < 0.001).

Conclusion

(1) The incidence of NB-PNA in adult cancer patient declined after PCV7 compared with before PCV7. (2) The reduction in NB-PNA was highest in patients ≥65 years suggesting an indirect effect from PCV7 childhood immunization. (3) A trend toward decreased incidence in NB-PNA was noted after PCV13; further surveillance is required to ascertain this trend.

Disclosures

All authors: No reported disclosures.
2724. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Healthy Meningococcal Vaccine-Naïve Children (2–9 Years)
Authors: Simon Michael W , Brandon Donald , Christensen Shane , Baccarini Carmen , Jordanov Emilia , Dhingra Mandeep S
Published: October 2019

Background

MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in individuals 6 weeks of age and older. We evaluated the safety and immunogenicity of MenACYW-TT compared with a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-CRM [Menveo®]) in US children 2–9 years of age.

Methods

In a modified double-blind Phase III study (NCT03077438), 1000 children were randomized to receive one dose of either MenACYW-TT vaccine or MenACWY-CRM vaccine. Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure antibodies against representative meningococcal serogroup strains at baseline and 30 days after vaccination. Safety data were collected up to 6 months post-vaccination.

Results

Non-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated for MenACYW-TT compared with MenACWY-CRM at Day 30 compared with baseline. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-CRM administration for all four serogroups (A: 86.4% vs 79.3%; C: 97.8% vs 67.1%; W: 94.8% vs 86.3%; Y: 98.5% vs 90.8%). Similar results were observed in two age substrata (2 to 5 years and 6 to 9 years). Percentages of participants with post-vaccination rSBA titers ≥ 1:128 were comparable between both groups. The safety profiles of MenACYW-TT and MenACWY-CRM were comparable. Reactogenicity at the MenACYW-TT injection site was lower than at the MenACWY-CRM injection site. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study.

Conclusion

MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with that for the licensed MenACWY-CRM vaccine when administered as a single dose to meningococcal vaccine-naïve children.

Disclosures

All authors: No reported disclosures.
2727. Numbers Needed to Vaccinate for Prevention of Adult Pneumonia with Pneumococcal Conjugate Vaccine: Which Values Should Determine Policy?
Authors: Gessner Bradford D , Isturiz Raul E , Snow Vincenza , Jodar Luis
Published: October 2019

Background

At the meeting of the Advisory Committee on Immunization Practices (ACIP) on February 28, 2019, the US Centers for Disease Control and Prevention (CDC) and the Pneumococcal Work Group (PWG) presented data to inform the public health question of whether the 13-valent pneumococcal conjugate vaccine (PCV13) should continue to be recommended for routine immunization of all adults age 65 years and older in the United States.

Methods

We reviewed all three available studies reporting adult PCV13 vaccine effectiveness against all-cause pneumonia, calculated numbers needed to vaccinate (NNV), and compared these results to NNV data presented to the ACIP based on etiologically and radiologically confirmed vaccine-type (VT) disease. Studies included a randomized controlled trial of inpatient pneumonia among Dutch persons age 65+ years, a US CDC-led observational study among the US Medicare population of inpatient pneumonia, and an observational study of inpatient and outpatient pneumonia in Germany.

Results

Based on a background incidence of etiologically and radiologically confirmed VT community-acquired pneumonia of 17–76 per 100,000 per year and PCV13 VE of 43%, the CDC presented to ACIP an annual NNV estimate for preventing one pneumonia case of 3,000 to 14,000. For the three studies we reviewed, VEs were 6% to 12% against all-cause pneumonia and background all-cause pneumonia incidences were 891 to 1776 per 100,000 per year. Assuming a 5-year PCV13 duration of protection, for these three studies NNVs to prevent a case of pneumonia were 95 to 277, or 11- to 147-fold lower than what was presented at ACIP.

Conclusion

To avoid inaccurate conclusions for potentially efficient interventions, calculations of NNVs, rate reductions, and economic benefits should include sensitive outcomes, such as all-cause pneumonia, in addition to more specific but lower sensitivity outcomes such as VT, radiologically confirmed pneumonia.

Disclosures

All authors: No reported disclosures.
2722 B. Efficacy and Safety of a Booster Dose of the MenACWY-TT Vaccine Administered 10 Years After Primary Vaccination with MenACWY-TT or MenACWY-PS
Authors: Quiambao Beatriz , Peyrani Paula , Webber Chris , Van Der Wielen Marie , Bianco Veronique , Perez John L , Cutler Mark W , Li Ping
Published: October 2019

Background

The quadrivalent meningococcal ACWY polysaccharide tetanus toxoid conjugate vaccine (MenACWY-TT; Nimenrix) is licensed in various countries to prevent disease caused by meningococcal serogroups A, C, W, and Y. In a previous study (NCT00464815), subjects aged 11‒17 years received a primary dose of MenACWY-TT or a quadrivalent polysaccharide vaccine (MenACWY-PS). Here, we report the long-term antibody persistence of the primary dose and the immunogenicity and safety of a booster dose given 10 years after primary vaccination of subjects.

Methods

Participants were enrolled from the Philippines and received a booster dose of MenACWY-TT at 10 years postvaccination. Antibody persistence 10 years postprimary vaccination and immunogenicity 1 month after the booster dose were evaluated by serum bactericidal activity assays using rabbit complement (rSBA) to assess the percentages of subjects with titers ≥ 1:8 and ≥ 1:128 and geometric mean titers (GMTs) for each serogroup. Safety was assessed for the booster dose.

Results

Of 229 subjects enrolled in this extension study, 169 and 58 subjects in the MenACWY-TT and MenACWY-PS groups, respectively, completed the booster phase. The percentages of primary MenACWY-TT recipients with prebooster rSBA titers ≥ 1:8 and ≥ 1:128 at year 10 ranged from 71.6%‒90.7% and 64.8%‒85.2% for all serogroups, respectively, compared with 43.1%‒82.4% and 25.5%‒76.5% of primary MenACWY-PS recipients; rSBA GMTs for all serogroups were higher in the MenACWY-TT group than in the MenACWY-PS group at year 10. For the MenACWY-TT and MenACWY-PS groups, respectively, the MenACWY-TT booster dose elicited rSBA titers ≥ 1:8 in 100% and ≥ 98.0% of subjects (figure); 100% and ≥ 96.1% of all subjects had titers ≥ 1:128. For all serogroups, rSBA GMTs at 1 month after the booster dose were higher than before the booster dose. No new safety signals were observed during the booster phase.

Conclusion

Functional antibody responses elicited by MenACWY-TT persisted 10 years after primary vaccination; the booster dose was well tolerated and elicited robust immune responses.

ClinicalTrials.gov

NCT03189745, EudraCT # 2013-001512-29. Funded by Pfizer.

Disclosures

All authors: No reported disclosures.
2729. mRNA Vaccines Encoding Conserved Influenza Antigens Induce Robust and Durable Immunity in Rhesus Macaques
Authors: Flynn Jessica , Cox Kara , Touch Sinoeun , Ou Yangsi , Weber Teresa , Citron Michael , Bahl Kapil , Ciaramella Giuseppe , Espeseth Amy , Zhang Lan
Published: October 2019

Background

In response to immune pressure, influenza virus evolves, producing drifted variants capable of escaping immune recognition. One strategy for inducing a broad-spectrum immune response that can recognize multiple antigenically diverse strains is to target conserved proteins or protein domains. To that end, we assessed the immunogenicity of mRNA vaccines encoding the stem domain of hemagglutinin (HA) or nucleoprotein (NP) in nonhuman primates (NHPs).

Methods

Rhesus macaques were immunized three times intramuscularly, at 28 day intervals, with lipid nanoparticle-encapsulated mRNA encoding either HA stem (Yassine et al, 2015) or NP. Serum and PBMCs were collected up to 14 or 24 weeks, respectively, after the last vaccination. The magnitude and durability of humoral and cell-mediated immunity were evaluated. ELISA, competition ELISA, an in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter bioassay, and microneutralization assays were used to characterize serum immune responses. Intracellular cytokine staining (IFN-gamma and IL-2) was used to assess antigen-specific T-cell responses.

Results

HA stem-immunized NHPs developed a robust anti-stem binding titer after a single vaccine dose, and after two doses, serum antibodies recognized several antigenically distinct Group 1 HA proteins. This broad antibody response persisted for at least 14 weeks post-dose 3 (PD3). Serum antibodies showed ADCC activity and competed with a well-characterized broadly neutralizing antibody, CR9114, for binding to HA stem; however, the polyclonal serum had only minimal activity against a panel of H1N1 viruses in a microneutralization assay. HA-specific CD4+ T-cell responses were detectable PD3. A robust antibody binding response was also detected in NP-vaccinated NHPs, and titers remained high for at least 14 weeks PD3. Additionally, these animals developed robust NP-specific T-cell responses that persisted for at least 24 weeks PD3. On average, 0.5% of CD4+ and 4% of CD8+ T cells produced IFN-gamma in response to NP peptide stimulation at the peak of the response, 2 weeks after the last vaccine dose was administered.

Conclusion

Lipid nanoparticle-encapsulated mRNA vaccines encoding conserved influenza antigens induce a robust and durable immune response in NHPs.

Disclosures

All authors: No reported disclosures.
2733. Association Between Influenza Vaccination Coverage and Ambulatory Antibiotic Prescription Rates in Children in South Carolina
Authors: Younas Mariam , Royer Julie , Rac Hana , Weissman Sharon , Waites Katie , Bookstaver P Brandon , Justo Julie Ann , Bell Linda J , Al-hasan Majdi
Published: October 2019

Background

Prior studies demonstrated an increase in ambulatory antibiotic prescription rates during the peak of Influenza virus activity, which often occurs during the first 4 months of the year in Southeastern United States. However, the impact of Influenza vaccination coverage on antibiotic prescription rates remains undefined. The purpose of this retrospective cohort study is to examine the association between Influenza vaccination coverage and ambulatory antibiotic prescription rates in children in South Carolina from 2012 to 2017.

Methods

Medicaid and State Employee Health Plan pharmacy claims for outpatient oral antibiotics were utilized for estimation of community antibiotic prescription rates in South Carolina population 6 months to 17 years of age from January 1, 2012 to December 31, 2017, which represents approximately 60% of the South Carolina population in this age group. Linear regression was used to examine the association between antibiotic prescription rates in January to April of each year and Influenza vaccine coverage in children 6 months to 17 years old after adjustments for Influenza vaccine effectiveness in that season as obtained from Centers for Disease Control and Prevention (CDC).

Results

During the 6-year study period, the mean antimicrobial prescription rate in children in South Carolina declined from 103 to 79 per 1000 person-months for the months January through April indicating a 26% decline (P < 0.0001). Influenza vaccine coverage also increased from 50.6% during the first Influenza season of the study and peaked at 60.7% in 2014–2015 Influenza season (Figure 1). After adjusting for the vaccine effectiveness, the decline in antibiotic prescription rate was significantly associated with an increase in vaccine coverage in children (P-value < 0.01). Antibiotic prescription rates declined by 3 per 1,000 person-months for each 1% increase in Influenza vaccine coverage in children.

Conclusion

There is a temporal association between the increase in Influenza vaccination coverage and the decline in ambulatory antibiotic prescription rates in children in South Carolina. Achieving the CDC’s set target Influenza vaccination coverage of 70% of the population may be associated with greater decline in ambulatory antibiotic prescription rates in children in the future.

Disclosures

All authors: No reported disclosures.
2734. Lack of Influence of Early Exposure to Influenza A(H3N2) Viruses on Vaccine Effectiveness Against A(H3N2)-Associated Illness in US Children <18 Years, 2016–2018
Authors: Ladva Chandresh N , Belongia Edward , Monto Arnold , Martin Emily T , Gaglani Manjusha , Reis Michael , Jackson Michael L , Jackson Lisa , Zimmerman Richard , Nowalk Mary Patricia , McLean Huong , Patel Manish , Fry Alicia M , Flannery Brendan
Published: October 2019

Background

During 2017–2018, influenza vaccine effectiveness (VE) against A(H3N2) illness was highest among children <5 years compared with all other ages. A child’s first influenza infection can shape later immune responses. The emergence of antigenically distinct influenza A(H3N2) viruses in 2014–2015 provided an opportunity to explore potential effects of first virus infection on vaccine effects. We compared VE against influenza A(H3N2) during 2016–2017 and 2017–2018 among children born after and before 2014.

Methods

Outpatient children aged 6 months–17 years with acute respiratory illness with cough were enrolled in the United States Influenza VE Network and tested for influenza infection by RT–PCR. Vaccination status was derived through medical records and immunization registries. Children with partial or unknown vaccination status were excluded. We used a test-negative design to estimate VE and 95% confidence intervals (CI) from logistic regression, adjusting for potential confounders. Cohorts were defined by birth after or before June 2014; we assumed exposure to the new A(H3N2) virus among children born after June 2014.

Results

During 2016–2017, among 2,545 children, 445 (18%) tested positive for A(H3N2) and 1,809 (71%) tested negative. VE against A(H3N2) did not differ among children born after June 2014 and among those born before June 2014 [49% (95% CI: −12%, 77%) vs. 43% (27%, 55%); interaction P < 0.75]. During 2017–2018, among 2,936 patients, 631 (22%) tested positive for A(H3N2), and 1,852 (63%) tested negative. VE against A(H3N2) was 59% (36%, 74%) among children born after June 2014 vs. 20% (−1%, 37%) among those born before June 2014 (interaction P < 0.01).

Conclusion

We did not consistently see differences in VE against A(H3N2) between children potentially exposed to different A(H3N2) viruses. However, error in exposure assignment to A(H3N2) viruses and few seasons since the emergence of the new A(H3N2) viruses limit our interpretation. Future study will include additional A(H3N2) seasons as initial exposures to current circulating viruses increase among young children. Alternative explanations for age-related differences will also be explored, such as prior seasonal vaccination.

Disclosures

All authors: No reported disclosures.
2753. Induction of Broadly Cross-Reactive Immune Responses Against A(H3N2) Airuses: Results of a Phase 2 Trial of a Novel Recombinant Hemagglutinin Saponin-Adjuvanted Nanoparticle Seasonal Influenza Vaccine
Authors: Shinde Vivek , Cai Rongman , Plested Joyce S , Zhou Bin , Zhou Haixia , Zhu Mingzhu , Wang Nan , Cloney-Clark Shane , Agrawal Sapeck , Spindler Michelle S , Patel Nita , Massare Michael , Smith Gale , Thomas D Nigel , Cho Iksung , Fries Louis F , Glenn Gregory M
Published: October 2019

Background

We developed a recombinant saponin-adjuvanted (Matrix-M1) quadrivalent hemagglutinin nanoparticle influenza vaccine (qNIV; NanoFlu) for older adults to address two impediments to efficacy of current, predominantly egg-derived, seasonal influenza vaccines: (1) limited protection against antigenic drift variants, particularly H3N2 viruses; and (2) antigenic mismatch between vaccine and circulating strains due to egg-adaptive mutations arising during manufacturing. In a prior Phase 1 trial, we showed that qNIV induced robust, broadly cross-reactive antibody responses against multiple antigenically drifted H3N2 viruses, which were 47–64% better than the egg-derived comparator trivalent high-dose inactivated influenza vaccine (IIV3-HD; Fluzone-High Dose). We undertook a Phase 2 trial to optimize the formulation of qNIV, and to compare qNIV immune responses to those of IIV3-HD and quadrivalent recombinant influenza vaccine (RIV4; FluBlok).

Methods

In this phase 2 dose and formulation finding RCT, we randomized 1,375 subjects aged ≥65 years to be immunized with 1 of 7 test vaccines: 5 different formulations of qNIV, IIV3-HD, or RIV4; and assessed wild-type hemagglutinin-inhibition (wt-HAI) and microneutralization (wt-MN) antibody responses (Day 0/28/56).

Results

Matrix-M1-adjuvanted qNIV induced 15–29% higher wt-HAI titers across 5 vaccine homologous or drifted H3N2 strains at Day 28 relative to unadjuvanted qNIV (statistically significantly superior for 5 of 6 strains tested). At Day 28, several qNIV formulations induced significantly superior wt-HAI titers vs. IIV3-HD (39–45%, 17–22%, and 44–48% greater titers for homologous A/Singapore/INFIMH-16–0019/2016—H3N2, historic-drifted A/Switzerland/9715293/2013—H3N2, and forward-drifted A/Wisconsin/19/2017—H3N2, respectively); and comparable HAI titers vs. RIV4. Wt-MN and wt-HAI data showed concordant patterns across treatment groups.

Conclusion

qNIV induced superior wt-HAI antibody responses vs. IIV3-HD against homologous or drifted H3N2 viruses and similar responses to RIV4. qNIV may address several critical challenges confronting current egg-derived influenza vaccines, especially in the older adult population.

Disclosures

All authors: No reported disclosures.
2758. Identifying Populations at High-Risk for Influenza-Related Hospitalization: A Real-World Analysis of Commercially Insured Population in the United States
Authors: Burudpakdee Chakkarin , Near Aimee , Tse Jenny , Young-Xu Yinong , Connolly Lynn , Reyes Carolina M
Published: October 2019

Background

The disease burden of seasonal influenza (flu) is high and contributes to morbidity, mortality and healthcare utilization. While only 1–2% of flu cases are hospitalized, these events are costly. The objective of this study was to describe and quantify risk factors for flu hospitalization.

Methods

Patients with 1 flu diagnosis (Dx) over 4 seasons (October 1, 2014–May 31, 2018) in IQVIA’s Real-World Data Adjudicated Claims – US database were selected into the study; the earliest flu Dx was the index date. Patients were required to have ≥12 months continuous enrollment in their health plan before index (baseline), ≥30 days after index, and either a record of a flu test ± 14 days of index or a flu Dx in the primary position. Comorbidities during a fixed 12-month baseline period were categorized by AHRQ and CDC definitions. The study outcome of interest, flu-related hospitalization during the 30-day follow-up period, was defined as hospitalization with Dx of flu or a pre-defined flu-related complication in any position. A logistic regression model assessed the odds of flu-related hospitalization, adjusting for age, sex, region, payer, season of index Dx, evidence of flu vaccination, and comorbidities.

Results

More than 1.6 million medically-attended flu cases were identified, of which 18,509 (1%) had a hospitalization. 40% of patients were < 18 years of age, 47% were male, and 28%, 15%, 24%, and 33% were identified in the 2014–2017 flu seasons, respectively. More hospitalized patients were ages 50+ compared with non-hospitalized patients (57% vs. 20%) and 44% of hospitalized patients had 4 or more AHRQ/CDC comorbidities vs. 8% of non-hospitalized patients. In adjusted analyses, older age (65+ vs. 5–17; OR = 9.4, 95% CI 8.8–10.1) and leukemia/lymphoma/metastatic cancer (OR = 3.2, 95% CI = 2.9–3.5) were key drivers of hospitalization (Figure 1).

Conclusion

The risk of flu-related hospitalization is high for elderly populations and those with certain underlying co-morbidities among all age groups. While these findings reflect the burden of medically-attended flu in a younger, commercially insured population, additional research is needed to address the flu burden in high-risk populations.

Disclosures

All authors: No reported disclosures.
2759. Immunogenicity of Inactivated Influenza Vaccines Given Early vs. Late After Pediatric Allogeneic Hematopoietic Cell Transplantation
Authors: Schuster Jennifer E , Schuster Jennifer E , Speaker Andrew , Hamdan Lubna , Batarseh Einas , Stewart Laura S , Dulek Daniel , Kitko Carrie L , Munoz Flor M , Munoz Flor M , Bocchini Claire , Danziger-Isakov Lara , Grimley Michael , Goyal Rakesh , Coffin Susan E , Freedman Jason L , Englund Janet A , Carpenter Paul A , Ardura Monica I , Auletta Jeffrey , Wattier Rachel , Truong Kenny , Maron Gabriela , Allison Kim J , Halasa Natasha B
Published: October 2019

Background

Pediatric hematopoietic cell transplant (HCT) recipients often fail to have robust responses to influenza (flu) vaccine. We conducted a blinded phase II trial comparing high-dose (HD) trivalent inactivated vaccine (TIV) vs. standard dose (SD) quadrivalent inactivated vaccine (QIV).

Methods

Children 3–17 years old and 3–35 months post-allogeneic HCT were enrolled at 9 centers and randomized to either 2 doses of HD-TIV or SD-QIV during the 2016–2017 flu season. We compared immune responses by hemagglutination inhibition (HAI) from children 3–11 (early) vs. 12–35 (late) months (m) post-HCT to 3 common flu vaccine antigens, irrespective of vaccine type. HAI responses were evaluated at baseline (visit 1), 1 m post dose 1 (visit 2) and dose 2 (visit 3), and 7 m post dose 2 (visit 4). Geometric mean titers (GMT) were adjusted for baseline log-titer values.

Results

Thirty-one children, median age 11 (7–15) years, were enrolled; 17 (55%) were immunized early and 14 (45%) late. Over 50% of patients had a potentially seroprotective (≥1:40) HAI titer at baseline, with no significant difference post-vaccination between early and late subjects. Table 1 compares early vs late subjects with HAI seroconversion (4-fold HAI titer rise). Post dose 1, late subjects, compared with early, had higher rates of seroconversion to all influenza strains. Post dose 2, early subjects, compared with late, had increased seroconversion. Late subjects had higher GMTs for H1N1 post dose 1 and 2, H3N2 after dose 1, and strain B/VIC post dose 1 and 2 (Figure 1). Although immunogenicity waned throughout flu season, higher seroconversion rates and GMT to H3N2 and strain B/VIC were retained in late subjects.

Conclusion

Compared with subjects in early post-HCT group, late post-HCT subjects had better flu vaccine immune responses as noted by higher GMT and HAI seroconversion. However, 2 doses seemed more beneficial in the early post-HCT group. Future analyses are underway, including comparing immunogenicity of HD vs. SD flu vaccine.

Disclosures

Jennifer E. Schuster, MD, Satchel Health: Shareholder Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.
2768. Does Social Media Contribute to Knowledge About Vaccine Safety?
Authors: Zheteyeva Yenlik , Hannan Jennifer , Goss Mary Ann , Straus Walter
Published: October 2019

Background

Social media is frequently used to share medical information. Current European regulatory guidance for the pharmaceutical industry calls for reporting valid adverse events (AE) derived from social media as well as consideration of non-valid AEs. This guidance is followed when our company utilizes social media related to any company products and interests. Here we evaluate its application to vaccines.

Methods

Posts collected from all screened social media sources (company owned, or company reviewed) were examined (August 1, 2017–February 28, 2019) to identify safety-related information pertaining to any of its 14 licensed vaccines. Posts were classified as valid cases (i.e., containing information about company product, AE, and identifiable reporter), non-valid cases (i.e., company product, AE, but missing an identifiable reporter), or not relevant (no safety-related information; not further analyzed). Valid cases were added to the company’s safety database; non-valid cases were reviewed for trends requiring further analysis. Both, valid and non-valid cases, were analyzed as part of routine safety surveillance

Results

Among 69,682 vaccine-related posts reviewed, 285 (0.4%) were valid; 11,464 (16.5%) were non-valid; 47,966 (83.1%) were not relevant. Most non-valid cases concerned the company’s 4-valent (8,934 [78%]) or 9-valent (1,420 [12%]) human papillomavirus vaccines, followed by its measles-mumps-rubella (336 [2.9%]), pneumococcal (282 [2.5%]), and herpes zoster (246 [2.1%]) vaccines. Review of data from selected temporal spikes in posts demonstrated that they were usually attributable to increased reposts of an original post or to personal views, rather than containing incremental factual new safety data.

Conclusion

Fewer than 1% of posts from relevant social media sources contained sufficient information to be considered valid cases. No new safety signals were identified for any of the vaccines from social media cases (valid or non-valid). Among posts containing safety information, the nature of this information tends to be redundant or sentimental, precluding meaningful safety analyses.

Disclosures

All authors: No reported disclosures.
2779. Efficacy of the Adjuvanted Recombinant Zoster Vaccine According to Sex, Geographic Region, and Geographic Ancestry/Ethnicity: A Post-hoc Analysis
Authors: Willer David O , Wascotte Valentine , Kim Joon Hyung , Zahaf Toufik , Talarico Carla , Gorfinkel Iris , Gervais Pierre , Pharm Pharm, L , Cunningham Anthony L , Oostvogels Lidia , Colindres Romulo , Schuind Anne
Published: October 2019

Background

The risk of herpes zoster (HZ) has been reported to vary by sex and ethnicity. In 2 large-scale clinical trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229), the adjuvanted recombinant zoster vaccine (RZV) demonstrated high vaccine efficacy (VE) against HZ and post-herpetic neuralgia (PHN). We present a post-hoc analysis of RZV efficacy against HZ and PHN in the ZOE-50/70 population stratified by sex, geographic region and geographic ancestry/ethnicity.

Methods

The ZOE-50 and ZOE-70 studies were phase III, observer-blind, placebo-controlled trials conducted across 5 geographic regions. Adults ≥ 50 years of age (YOA; ZOE-50) and ≥ 70 YOA (ZOE-70), randomized 1:1, received 2 doses of RZV or placebo 2 months apart. Here, VE against HZ by sub-population was estimated from the ZOE-50 population (≥ 50 YOA) and the pooled ZOE-50/70 population (pooled ≥ 70 YOA), and VE against PHN by sub-population was evaluated in the pooled ≥ 70 YOA.

Results

VE was evaluated in 7,340 RZV and 7,413 placebo recipients ≥ 50 YOA (mean age: 62.3 [RZV], 62.2 [placebo] YOA) and 8,250 RZV and 8,346 placebo recipients in pooled ≥ 70 YOA (mean age: 75.5 [RZV, placebo] YOA). VE against HZ and PHN was similar for women and men in the ≥ 50 YOA and pooled ≥ 70 YOA (Tables 1 and 2). Point estimates for VE against HZ by geographic region ranged from 95.7% to 97.2% in ≥ 50 YOA and from 87.3% to 95.1% in pooled ≥ 70 YOA (Table 1). Point estimates for VE against PHN by geographic region ranged from 86.8% to 100% in pooled ≥ 70 YOA. VE was similar across geographic ancestry groups in pooled ≥ 70 YOA: VE point estimates against HZ ranged from 89.6% to 100% and VE against PHN ranged from 87.5% to 100% (Tables 1 and 2). VE against HZ was 88.1% and against PHN was 65.9% in Hispanic participants in pooled ≥ 70 YOA (Tables 1 and 2).

Conclusion

Acknowledging the limitations including the post-hoc character of these analyses and the small number of participants and cases available, our data suggest that RZV is efficacious against HZ and PHN irrespective of sex, geographic region, geographic ancestry, and ethnicity.

Funding: GlaxoSmithKline Biologicals SA.

Disclosures

All authors: No reported disclosures.
2781. Statistical Modeling to Predict Maternal RSV Vaccine Efficacy from Neutralizing Titers
Authors: Cai Bing , Chen Yili , Agosti Yasmeen , Swanson Kena , Schmoele-Thoma Beate , Jansen Kathrin U , Gruber William C , Koury Kenneth , Dormitzer Philip R
Published: October 2019

Background

In the United States, respiratory syncytial virus (RSV) is the leading cause of respiratory-related hospitalization in infants. The well-studied efficacy of the prophylactic monoclonal antibody, palivizumab, at preventing RSV disease in the highest risk infants provides proof of mechanism that serum neutralizing antibody protects against RSV. The expense and burden of monthly antibody injections limit the utility of palivizumab, leaving a large unmet medical need. Maternal immunization, with transplacental transfer of antibodies to the fetus, is an alternative, highly practical approach to protect many more infants.

Methods

Levels of protection by known palivizumab serum concentrations provide a basis for predicting maternal RSV vaccine efficacy in infants based on serum neutralizing antibody titers elicited in vaccine clinical trials, using statistical modeling to compensate for differences between palivizumab prophylaxis and maternal immunization. The model adjusts for the dependency of maternal vaccine responses on pre-immunization RSV neutralizing titers, exponential decay of maternal antibodies in infants, and exponentially decreasing airway resistance (reducing RSV disease risk) as infants grow.

Results

The rates of severe RSV disease by age projected from the model match the pattern of US infant hospitalization for RSV, with a peak at 1.5 months of age. The model relates vaccine-elicited increases in maternal RSV neutralizing titers to predicted reductions in severe RSV disease in infants from 0 to 6 months of age.

Conclusion

Statistical modeling of maternal RSV vaccine efficacy based on elicited RSV neutralizing titers provides a rational basis for decision-making during RSV vaccine development.

Disclosures

All authors: No reported disclosures.
2783. Expansion of Monocytic Myeloid-Derived Suppressor Cells in Infants with Severe Respiratory Syncytial Virus (RSV) Infection
Authors: Bedoya Santiago Acero , Ye Fang , Best Victoria , Ramilo Octavio , Ramilo Octavio , Mejias Asuncion
Published: October 2019

Background

RSV remains a leading cause for hospitalization of infants. The mechanisms associated with the ability of RSV to suppress the induction of an adequate immune response are not well understood and represent a challenge for vaccine development. Myeloid-derived-suppressor cells (MDSCs) have been shown to suppress CD8+ T cells in patients with malignancies. These immature myeloid cells are divided into three groups: granulocytic, monocytic, and undifferentiated. Of those, monocytic MDSCs (M-MDSCs) are considered to be key regulators of inflammatory responses during acute infections. Their potential role in the immunopathogenesis of RSV infection in infants is yet to be defined.

Methods

Single-center, prospective cohort study in previously healthy infants hospitalized with severe RSV lower respiratory tract infection (LRTI) and age-matched healthy controls (HC). Nasopharyngeal swabs for RSV detection and blood samples for cell immunophenotyping were analyzed at enrollment (D1), 1-month (D30), and 6-months (D180) follow-up visits. Disease severity was assessed using a clinical disease severity score (CDSS), duration of supplemental O2, and duration of hospitalization.

Results

We enrolled 39 infants with RSV LRTI (median [IQR] age: 3.3 [1.5–5.2] months) and 5 HC (5.9 [4.5–7.2] months). Infants with RSV infection demonstrated an expansion of M-MDSCs during the acute infection (D1) that resolved to numbers comparable to those in HC at follow-up visits (Figure 1A). In addition, numbers of CD8+ T cells were significantly reduced during the acute infection (D1) in RSV-infected infants, but also returned to the HC baseline on D30 and D180 (Figure 1B). Finally, the increase in M-MDSCs numbers and decrease in CD8+ T-cell numbers were associated with worse clinical outcomes as defined by duration of supplemental oxygen (>1 day), hospitalization (>48 hours), and clinical disease severity score (CDSS, > 9) (Figure 2).

Conclusion

These findings suggest that an expansion of M-MDSCs may play a role in T-cell suppression in children with severe RSV disease. As new vaccines are being developed, it is critical to elucidate the immune suppressive mechanisms associated with RSV infection.

Disclosures

Octavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.
2787. Respiratory Syncytial Virus in Elderly Adults
Authors: Mykietiuk Analía , Obed Mora , Cooke Bettina , Fernanda; Alzogaray Maria , Romandetta Agustin , Pablo Balbuena Juan , Galeano Lucia , Chaparro Gustavo , Baumeister Elsa
Published: October 2019

Background

The role of respiratory viruses other than influenza in acute respiratory tract infections (ARTI) among elderly adults has probably been underestimated. Recent advances in molecular diagnosis have made the rapid identification of RSV infection possible.The aim of our study was to assess the role of RSV in patients older than 65 years.

Methods

Prospective observational study (April 2018–February 2019) conducted in a 137-bed institution in Buenos Aires, Argentina. All consecutive elderly patients (>65 years) admitted with ARTI were included. Clinical and laboratory parameters as well as nasopharyngeal swab for respiratory viruses were obtained. Blood cultures and sputum collection, were analyzed. Viral detection was performed according to CDC real-time RT–PCR assay. All patients underwent clinical follow-up during hospitalization and up to 30 days after discharge.

Results

A total of 124 patients were recruited (mean age 82 years; range: 65–98) 58% female. Clinical diagnosis at admission were: community-acquired pneumonia 90 (72%), COPD exacerbation 11 (9%), acute bronchitis 10 (8%), healthcare-associated pneumonia 8 (7%) influenza like síndrome 5 (4%). Blood cultures were obtained in 92 patients: 4 positives for Streptococcus pneumoniae, 3 E. coli, 2 SAMS, 1 Klebsiella pneumoniae. Sputum was obtained in 20 patients, none were positive.The viral results of the124 samples were: RSV 13 (10.4%), Influenza B 9 (7.2%), Influenza A 8 (6.4%).Regarding RSV positive patients, the mean age was 87 years and 69% were female. 30 % had history of heart failure and 30 % had history of COPD. Clinical diagnosis on admission were: CAP 10 (77%), COPD exacerbation 2 (15%) and bronchitis 1 (8%). Non productive cough was present in 46% and bronchospasm in 85%. Mean time of hospitalization was 9 days (R: 4–16) and fever duration 1 day (R: 0–2). The median duration of antibiotic treatment was 9.5 days (R: 4 to 15) No viral nor bacterial coinfections were observed. No early mortality was registered, global mortality was 23% (3 patients). Death was clinically related to RSV infection.

Conclusion

This study suggest that RSV is a relevant respiratory pathogen in the elderly population, with significant associated morbidity and mortality rates. Current treatment is limited to supportive care and prevention to standard infection control practices. A new approach is needed to improve RSV infection management.

Disclosures

All authors: No reported disclosures.
2794. Testing and Treatment in Patients Hospitalized with Suspected Influenza Pneumonia
Authors: Deshpande Abhishek , Klompas Michael , Bartley Patricia , Yu Pei-Chun , Haessler Sarah , Zilberberg Marya , Imrey Peter , Rothberg Michael
Published: October 2019

Background

Influenza is a leading cause of community-acquired pneumonia (CAP). Little is known about the effect of influenza testing on antimicrobial treatment among adult patients hospitalized with CAP. We quantified prevalence of testing and impact of positivity on treatment with antibacterials, antivirals, and outcomes.

Methods

We included adults admitted with pneumonia in 2010–2015 to 179 US hospitals contributing to the Premier database. Patients had CAP if radiographic evidence of pneumonia and antimicrobial treatment were present on day 1. We assessed influenza testing and compared antimicrobial utilization and outcomes of patients who tested positive vs negative vs not tested. Using mixed logistic regression and gamma generalized linear mixed models, we assessed the impact of influenza testing on inpatient mortality, length of stay (LOS) and cost.

Results

Among 166,273 patients with CAP, 38,665 (23.2%) were tested for influenza; 11.5% of these tested positive. The influenza testing rate increased from 15.4% in 2010/7–2011/6 to 35.6% in 2014/7–2015/6, ranging from 28.8% during flu season (October–May) to 8.2% in other months. Positive tests were more common during flu season (12.2% vs. 2.8%, P < 0.001). Patients tested for influenza were younger (66.6 vs. 70.3 years), less likely admitted from SNF (5.4% vs. 7.9%), with fewer comorbidities (2.9 vs. 3.3). Of patients tested for influenza, positive patients were younger (66.3 vs. 68.8 years), less likely admitted from SNF (5.2% vs. 6.8%), with more comorbidities (2.9 vs. 2.7) (all comparisons P < 0.001). Patients testing positive more likely received antivirals, were slightly less likely to receive antibacterials (Figure 1), but received shorter antibacterial courses than negative patients (5.3 vs 6.4 days, P < 0.001). Influenza tests were associated with reduced odds of in-hospital mortality compared with no testing (adjusted OR 0.71, 95% CI 0.63–0.81) and positive vs. negative tests with reduced costs (0.95, 0.92–0.99) and LOS (0.97, 0.94–0.99) (Figure 2).

Conclusion

In a large US inpatient sample hospitalized for pneumonia, only 23.2% of the patients were tested for influenza, but testing varied widely by hospital. A positive influenza test was associated with antiviral treatment but had minimal impact on antibiotic prescribing.

Disclosures

All authors: No reported disclosures.
2796. The Impact of Syndromic Molecular Point-of-Care Testing for Respiratory Viruses on Antibiotic Use in Adults Presenting to Hospital with Exacerbation of Airways Disease: Further Analysis From a Randomized Controlled Trial
Authors: Clark Tristan William , Mills Samuel , Brendish Nathan
Published: October 2019

Background

The ResPOC study demonstrated that syndromic molecular point-of-care testing (POCT) for respiratory viruses was associated with earlier discontinuation of unnecessary antibiotics. Subgroup analysis suggests this occurs predominantly in patients with exacerbation of airways disease. Molecular POCT use is becoming widespread but there is a lack of evidence to inform the choice between multiplex syndromic panels vs. uniplex tests for influenza.

Methods

We evaluated patients with exacerbation of asthma or COPD who were treated with antibiotics. The duration of antibiotics and proportion with early discontinuation were compared between patients testing positive for viruses by POCT (FilmArray Respiratory Panel) those testing negative by POCT and controls. Patients testing positive for viruses by POCT were compared according to virus types detected. Survival curves were generated for duration of antibiotics and compared using the log-rank test.

Results

There were 118 patient with exacerbation of airways disease in the POCT group who received antibiotics and 111 in the controls. In the POCT group 49/118 (42%) patients tested positive for viruses. Of those testing positive for viruses by POCT 17/49 (35%) had early discontinuation of antibiotics vs. 9/81 (13%) in those testing negative and 7/111 (6%) in controls, P < 0.0001. Survival curve analysis showed a reduced time to antibiotic discontinuation in those testing positive for viruses, P = 0.034. Of those positive for viruses by POCT 20% were positive for influenza, 43% for rhinovirus and 37% for other viruses combined. The proportion with early discontinuation of antibiotics was not different between the virus types, P = 0.53.

Conclusion

Syndromic molecular POCT for viruses in adults with exacerbation of airways disease leads to early discontinuation in those positive for viruses. As most viruses detected were non-influenza viruses and there was no difference in antibiotic use between virus types, syndromic molecular POCT for respiratory viruses should be favored over uniplex POCT for influenza.

Disclosures

All authors: No reported disclosures.