bluuebunny/crossref_metadata_2025_split huggingface dataset:
2709. Immune Response After Diphtheria and Tetanus Toxoid Booster in Patients with Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibody
Authors: Tovikkai Dissaruj , Vanichanan Jakapat , Jutivorakool Kamonwan 
Published: October 2019

Abstract

Background
Immunization were the key of prevention in tetanus and diphtherial disease. Nevertheless, in previous observational study, low seroprotection rate of both diphtheria and tetanus were observed in Thai healthy population. Reduced-dose diphtheria and tetanus toxoid vaccine (dT) was recommended to all adult patients regardless of immunologic status. However, data on vaccine efficacy in interferon gamma (IFN-γ) autoantibody were limited. We therefore conducted clinical study to evaluate efficacy and safety of one dose of dT in IFN-γ autoantibody patient compared with healthy individuals at 4 weeks after vaccination.

Methods
Study was conducted from February to April 2019. Total 18 patients with confirmed IFN-γ autoantibody were enrolled. Baseline tetanus and diphtheria serologic study and 4 weeks after vaccination were examined. Antibody levels were measured with a solid-phase IgG-specific ELISAs (EUROIMMUN, Germany). Geometric mean titers (GMTs) were calculated using the log transformation of serological titers and from taking the antilog mean of the transformed values.

Results
Seroprevalence of tetanus was 94.5% in healthy population compared with 60.1% in IFN-γ autoantibody patients. While, seroprevalence of diphtheria was 27.8% and 77.8%, respectively. After vaccination, all healthy adults had reached seroprotection level in both diphtheria and tetanus. For patients with IFN-γ autoantibody, 88.9% and 94.4% had anti-tetanus toxin IgG and anti-diphtheria toxin IgG level above 0.1 IU/mL, respectively. These results indicated seroconversion rate of 71% for tetanus and 75% for diphtheria after dT vaccination. (Table 2). In the subgroup analysis, unboosted IFN-γ autoantibody patient had lower tetanus seroconversion rate compared with previously boosted patient (50% vs 100%). Active infection was also associated with lower immune response after tetanus vaccination. There was no severe adverse event in both group.

Conclusion
This is the first study on immune response after dT vaccination in IFN-γ autoantibody patient. Seroconversion rate of dT vaccine in IFN-γ autoantibody patient were slightly lower than healthy adults. Active infection and previously unboosted patient provided lower immune response of tetanus.

Disclosures
All authors: No reported disclosures.
2716. Persistence of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Serotypes in Invasive Pneumococcal Disease in Adults in Southern Ontario Canada Despite Routine Pediatric Vaccination
Authors: McGeer Allison , Plevneshi Agron , Green Karen , Coleman Brenda , Nayani Sarah , Rudnick Wallis , Simor Andrew , Gold Wayne , Katz Kevin , Kitai Ian , Johnstone Jennie , Martin Irene , Muller Matthew P , Richardson David , Sarabia Alicia 
Published: October 2019

Abstract

Background
In Ontario, Canada, PCV13 is covered for immunocompromised (IC) adults over 50y. PCV13 programs are thought not to be cost-effective in other adults because it is assumed that herd immunity from pediatric vaccination programs (PCV7 since 2005; PCV13 since 2010) will reduce PCV13 disease burden dramatically in adults. We analyzed data from the Toronto Invasive Bacterial Diseases Network (TIBDN) to ask whether PCV13-type invasive pneumococcal disease (IPD) in adults persists in our population.

Methods
TIBDN performs population-based surveillance for IPD in Toronto+Peel Region, Ontario (pop4.1M). All microbiology laboratories receiving specimens from residents report cases of IPD and submit isolates to a central study lab for serotyping; annual audits are conducted. Demographic, medical and vaccination information are obtained from patients, families and physicians. Population data are from Statistics Canada.

Results
Since 1995, 10,365 episodes of IPD have been identified; detailed medical information was available for 9,801 (95%) and serotyping for 9411 (91%). Among 8658 adult cases, 4,273 (49%) were in those aged 15–64 years, and 4,285 (51%) in those aged >645 years. The most common diagnoses were pneumonia (5,978/8,025, 74%) and bacteremia without focus (1,030, 13%); 470 (4.6%) cases had meningitis; the case fatality rate (CFR) was 21%. The incidence of disease due to STs in PCV13 in adults declined from 7.0/100,000/year 2001 to 2.9/100,000/year in 2015–2018 and was stable from 2015–2018 (Figure 1). The incidence was > 5/100,000/year in non-IC patients over 65 years, and younger patients with cancer and kidney disease (Figure 2). In IPD from 2015 to 2018, adult patients with PCV13 ST disease were younger (median age 64 years vs. 67 years, P = .03) than other patients; there was no significant difference in the proportion with at least one underlying chronic condition (253, 69% PCV13ST, vs. 541,74% other ST, P = 0.08), or in CFR (59, 16% PCV13 vs. 145, 20% other, P = 0.13). The ST distribution of cases due to PCV13 STs is shown in Figure 3.

Conclusion
A significant burden of IPD due to PCV13 serotypes persists in adults in our population despite 8 years of routine pediatric PCV13 vaccination. This burden needs to be considered in assessing the value and cost-effectiveness of PCV programs for adults.

Disclosures
All authors: No reported disclosures.
2726. Meningococcal Vaccination Among Patients Newly Diagnosed at High-Risk for Meningococcal Disease in the United States
Authors: Bengtson Lindsay , Marshall Gary S , Buikema Ami R , Koep Eleena , Novy Patricia , Hogea Cosmina 
Published: October 2019

Abstract

Background
Quadrivalent conjugate and polysaccharide meningococcal vaccines (MenACWY) have been recommended in the United States for patients at high-risk due to functional or anatomic asplenia, complement component deficiency (CD) and human immunodeficiency virus (HIV) infection. Serogroup B vaccines (MenB) are recommended for patients ≥10 years of age with asplenia or CD. Little is currently known about meningococcal vaccine uptake and time to vaccination among patients with incident high-risk diagnoses.

Methods
Patients newly diagnosed (1 inpatient or ≥2 outpatient medical claims with evidence of the condition ≥30 days apart) with functional or anatomic asplenia (excluding sickle cell disease), CD or HIV infection were identified in the Optum Research Database. Continuous enrollment for ≥12 months before and ≥6 months after the diagnosis date (index date) was required. Patients with evidence of pre-existing conditions were excluded. MenACWY uptake was assessed among patients ≥2 years of age at index date from January 1, 2010 for asplenia and CD, and January 1, 2016 for HIV infection, through March 31, 2018; and MenB uptake among patients ≥10 years of age at index date from January 1, 2015 through March 31, 2018. Current Procedural Terminology and National Drug Codes on medical claims were used to capture vaccinations. For each condition, Kaplan–Meier analysis was used to estimate uptake and time to receipt of ≥1 dose of each vaccine for up to 5 years post-index date; vaccinations within 90 days before the index date were also included in calculations.

Results
Among asplenia patients, the percentage with receipt of ≥1 dose of MenACWY at 1, 2.5, and 5 years post-index date was 6.6%, 9.4%, and 13.3%, respectively; for CD patients the corresponding percentages were 2.2%, 4.8%, and 8.3%; and for HIV patients at 1 and 2.5 years post-index date the percentages were 10.8% and 19.8% (Figure 1). Receipt of ≥1 dose of MenB at 1 and 2.5 years post-index date was 1.7% and 3.1%, respectively, for asplenia patients and 1.1% and 2.5%, respectively, for CD patients (Figure 2).

Conclusion
Uptake of meningococcal vaccines in patients newly diagnosed with high-risk conditions is very low and the time to vaccination is long, leaving patients vulnerable to invasive meningococcal disease for extended periods of time.

Disclosures
All authors: No reported disclosures.
2728. Proportion of Invasive Pneumococcal Disease Potentially Covered by Current and Next-Generation of Higher-Valency Pneumococcal Conjugate Vaccines in Canada, 2010–2016
Authors: Dion Stephane B , Vojicic Jelena , Major Maria , Nepal Rajeev M , Gessner Bradford D , Cane Alejandro , Suaya Jose A 
Published: October 2019

Abstract

Background
In Canada, routine pediatric immunization with 7-valent pneumococcal conjugate vaccine (PCV7) was introduced between 2002 and 2006. Two of ten provinces transitioned to PCV10 in 2009; by mid-2011, following a national preferential recommendation, PCV13 replaced PCV7/PCV10 across Canada. PCV13 also has been recommended for immunocompromised adults since 2013, and immunocompetent adults aged ≥65 years on an individual basis since 2016. Immunization with 23-valent polysaccharide vaccine (PPV23) is recommended in adults with certain comorbidities, and routinely in those aged ≥65 years. Two higher-valency PCVs, PCV15, and PCV20 are currently under development.

Methods
Case counts of invasive pneumococcal disease (IPD) by serotype and age group were obtained from published annual reports of passive laboratory-based national IPD surveillance conducted by the National Microbiology Laboratory (NML) since April 2010.

Results
In all ages, the proportion of IPD due to PCV13 serotypes declined from 55% in 2010 to 31% in 2016 (Figure 1); in children age < 5 years, from 66% to 19%; in adults age 50–64 years, from 52% to 34%, and in adults age > 65 years from 51% to 25%. While most age groups have experienced declines in the proportion of PCV13-type IPD, this proportion has plateaued since 2014 in all age groups except 2–4 years old. During 2016, among all ages, the proportions of IPD due to PCV13, PCV15, and PCV20 types were 31%, 43%, and 58%, respectively; among children age < 5 years 19%, 35%, and 50%, respectively, among adults 50–64 years, 34%, 47%, and 61%, respectively, and among adults age ≥65 years, 25%, 38%, and 53%, respectively.

Conclusion
The proportion of PCV13-type IPD has declined across all ages since the introduction of PCV13 in children. The plateau in this proportion observed across most age groups since 2014 suggests that herd effect may have been maximized, and additional reductions could be expected primarily from direct PCV13 adult immunization. PCV20 could potentially protect against a large proportion of the remaining IPD burden in Canada.

Disclosures
All authors: No reported disclosures.
2732. Estimate of the Effectiveness of Influenza Vaccine among Children for the 2017–2018 Season
Authors: Powell Lauren , Bégué Rodolfo 
Published: October 2019

Abstract

Background
The 2017–2018 influenza season was one of the deadliest in decades, with 180 pediatric deaths, 80% among children who did not receive the vaccine. Circulating influenza strains change periodically, making it important to determine vaccine efficacy on an annual basis specifically in susceptible populations. The primary aim of our study was to estimate the effectiveness of the influenza vaccine for the 2017–2018 season. Secondary aims were to determine effect of weaning immunity and of previous season vaccination.

Methods
Children 6 months to 17 years tested for influenza during the 2017–2018 season at Children’s Hospital of New Orleans were included. Clinical charts were reviewed, and immunization status confirmed via the Louisiana Immunization Registry. Using a multivariable logistic regression model vaccine effectiveness (VE) was estimated by comparing vaccination status of influenza-positive vs. influenza-negative cases with the formula VE = (1 − OR) × 100%.

Results
4,825 children were included; 22% of them tested positive for influenza, mostly influenza A (61.9%); 21% had received an influenza vaccine prior to illness: 14% among the influenza-positive and 23% among influenza-negative (P < 0.0001). Overall, VE for the 2017–2018 influenza season was 43% (95% CI 30, 53); 44% for influenza A and 38% for influenza B. While receiving current year (2017–2018) vaccine had the most effect, receiving the previous year (2016–2017) vaccine had additional benefit. We found no waning immunity of the vaccine for the 2017–2018 season.

Conclusion
Influenza VE was modest for children in the local area of New Orleans and similar to the CDC’s findings for the nation as a whole. Previous year vaccination had a small, but significant benefit and there was no evidence of waning immunity in our cohort. Ongoing national and local surveillance is important to understand the benefit of influenza vaccination.

Disclosures
All authors: No reported disclosures.
2747. Relative Vaccine Efficacy of High-Dose vs. Standard Dose Influenza Vaccines in Preventing Probable Influenza in a US Medicare Fee-for-Service Population
Authors: Paudel Misti , Mahmud Salah , Buikema Ami R , Korrer Stephanie , Damon Van Voorhis , Brekke Lee , Chit Ayman 
Published: October 2019

Abstract

Background
High dose (HD) influenza vaccine has been shown to be more efficacious than standard dose (SD) vaccine in multiple randomized trials. HD is currently the most commonly used vaccine in US seniors (≥65 years of age). In this study, we evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over 3 influenza seasons.

Methods
This study includes a cohort of Medicare fee-for-service enrollees during influenza seasons 2011–2012 to 2013–2014 who received either HD or SD at a pharmacy or an outpatient clinic. HD recipients were matched 1:1 to SD recipients based on location, date of vaccination, age, and gender. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. The study outcome of probable influenza was defined as any inpatient stay with an influenza diagnosis on the claim, or an outpatient medical encounter with a rapid influenza test/culture followed by an antiviral prescription. Analyses were stratified based on vaccination location (clinic vs pharmacy) as it is expected that physicians carrying both vaccines may prioritize HD to frailer patients, while pharmacists may not exercise clinical judgment.

Results
Over the influenza seasons 2011–2012, 2012/–2013, and 2013–2014, 1.6–2.2 million seniors were immunized at a pharmacy; and 3.3–3.5 million at a clinic. After matching, there were 535,598; 1,017,552; and 1,548,164 in the pharmacy cohort, and 821,662; 1,151,080; and 1,559,488 in the clinic cohort, across study years. The rVE over 2011/12, 2012/13, and 2013/14 during peak influenza circulation was 21.8% (95% CI: −5.9%, 42.3%), 14.8% (9.3%,19.9%), and 16.9% (9.2%, 23.9%), respectively, in the pharmacy cohort; and 16.5% (−5.9%, 34.2%), 15.1% (10.9%, 19.1%), 10.0% (2.9%, 16.6%), respectively, in the clinic cohort.

Conclusion
HD was consistently associated with better protection against probable influenza events requiring outpatient or inpatient care. The slightly lower treatment effects observed in the outpatient clinic cohort could be a result of confounding by indication due to physicians triaging HD to frailer patients.

Disclosures
All authors: No reported disclosures.
2756. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED), Influenza-Like-Illnesses (ILIs) Sub-Study at the Marine Corps Recruit Depot-San Diego, CA (MCRD-SD) During the 2018–2019 Influenza Season
Authors: Maves Ryan , Utz Gregory , Richard Stephanie , Smith Melissa , Collins Limone , Myers Christopher , Graf Paul , Colombo Rhonda , Ganesan Anuradha , Geaney Casey , Lalani Tahaniyat , Markelz Ana E , Mende Katrin , Schofield Christina , Seshadri Srihari , Spooner Christina , Warkentien Tyler , Coles Christian L , Burgess Timothy 
Published: October 2019

Abstract

Background
Military recruits suffer high rates of influenza and influenza-like illness (ILI) during training. ILIs may lead to morbidity, lost training time, and hospitalization. We evaluated the incidence and clinical outcomes of ILI among recruits at Marine Corps Recruit Depot San Diego (MCRD-SD) in a prospective trial of influenza vaccine efficacy.

Methods
Recruits at MCRD-SD were enrolled to compare the effectiveness of 3 types of FDA approved influenza vaccine: Afluria®, an egg-based vaccine; Flucelvax®, a cell-culture-derived vaccine; and Flublok®, a recombinant vaccine. Four companies of recruits were enrolled sequentially from 28 November 2018 to 19 December 2018, then randomized in a 1:1:1 ratio. Participants were followed for 18 weeks at MCRD-SD and Camp Pendleton. All participants who presented with ILI symptoms at medical care sites underwent viral diagnostic testing in addition to immunologic studies. Recruits were excluded from participation if <18 years of age, if previously vaccinated in the 2018–2019 season, or if reporting allergy to the vaccines.

Results
Of 1338 recruits approached, 771 (57.6%) participants consented for enrollment. All recruits were men between 18 and 28 years. There were 182 ILIs amongst 177 recruits (23% of 771 recruits). Nasal swabs were obtained in 180/182 cases (99%). Mean duration of ILI symptoms was 7 days. Mean days of fever was 4. Subjects reported a total 168 days of reduced training (range 0–14 days; mean 0.9 days). There were 47 total days of missed training for all subjects (range of 0–4 days; mean 0.3 days/subject). There were no hospitalizations related to ILIs. Approximately 82% (148/182) of ILIs presented within the first 3 weeks of training; 44% (80/182) of ILIs occurred during the second week of training. PCR- nasal swabs results; race/ethnicity data, and frequency of ILI mapped to week of training are illustrated below.

Conclusion
ILIs can negatively impact training effectiveness. Days lost to training from ILIs and hospitalizations can prevent successful completion of training with impact on military readiness. PAIVED may inform the DoD on future strategies to minimize influenza and other respiratory threats in recruit military populations. Influenza vaccine effectiveness will be reported separately.

Disclosures
All authors: No reported disclosures.
2757. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Immunogenicity Sub-Study
Authors: Colombo Rhonda , Richard Stephanie , Schofield Christina , Collins Limone , Ganesan Anuradha , Geaney Casey , Lalani Tahaniyat , Markelz Ana E , Maves Ryan , Mende Katrin , Seshadri Srihari , Spooner Christina , Utz Gregory , Warkentien Tyler , Coles Christian L , Burgess Timothy 
Published: October 2019

Abstract

Background
Despite greater than 90% of US active duty (AD) military personnel receiving influenza vaccination annually, vaccine effectiveness (VE) among AD members has been substantially lower than in groups with less vaccine uptake. The substrate used in vaccine production may impact immunogenicity and thus VE. The PAIVED study is investigating VE of 3 different influenza vaccine formulations; a sub-study assesses immunogenicity. This analysis compares demographic characteristics and influenza-like illness (ILI) experience among main and sub-study participants for the first year of PAIVED.

Methods
During the 2018–2019 influenza season, PAIVED enrolled participants at 5 military medical centers, recruiting sub-study subjects from the main cohort excluding marine recruits. All participants were randomized (1:1:1) to receive either egg-based, cell-culture based or recombinant influenza vaccine. At enrollment, participants provided key demographic and behavioral data. Weekly surveillance for ILI symptoms was performed electronically. Sub-study volunteers underwent an additional blood draw prior to and at 21–35 days post vaccination ± an optional buccal swab.

Results
200 (23.5%) of 852 non-recruit PAIVED participants enrolled in the immunogenicity sub-study. Similar to the main cohort, 46% of sub-study volunteers were female, 85% were physically active, and 6% smoked tobacco. Sub-study participants were younger (47 ± 16 years vs. 51 ± 17 years, P = 0.004) and more likely to be AD (34% vs. 22%, P = 0.001). Although 70% of both groups identified as White, the percent African American (20% sub-study; 13% main), Asian (3%; 7%), multi-racial (2%; 5%), and unknown (6%; 4%) differed (P = 0.02). More sub-study participants developed an ILI (19% vs. 12%, P = 0.02).

Conclusion
The convenience sampling method used for recruitment into the sub-study was effective. The younger age and higher AD status in the sub-study group may be informative for evaluation of military readiness issues. The greater incidence of ILI in the sub-study increases the chance differences in immune response by vaccine type may be interpretable in the context of circulating influenza strains. Targeted efforts to enhance recruitment of a racially diverse sub-study cohort may be warranted.

Disclosures
All authors: No reported disclosures.
2760. Accounting for Vaccination History in Estimates of Current Season Vaccine Effectiveness in the US Flu VE Network, 2012–2013 Through 2017–2018
Authors: Kim Sara S , Foppa Ivo , Chung Jessie R , Belongia Edward , McLean Huong , Monto Arnold , Petrie, Joshua G , Zimmerman Richard , Nowalk Mary Patricia , Gaglani Manjusha , Murthy Kempapura , Jackson Michael L , Flannery Brendan , Patel Manish 
Published: October 2019

Abstract

Background
Current season vaccine effectiveness (VE) and influenza risk may vary in persons based on vaccination history. United States Influenza Vaccine Effectiveness (US Flu VE) Network studies have explored prior vaccination effects using a single referent group of patients unvaccinated in both the prior and current seasons. We investigated vaccine benefit among those with and without prior season vaccination.

Methods
Our analysis included data from the US Flu VE Network among patients aged ≥9 years old with acute respiratory illness during 6 influenza seasons, 2012–2013 through 2017–2018. We determined current and prior season vaccination status from documented immunizations. Current season VE against laboratory confirmed influenza was estimated using multivariate logistic regression with an interaction term for prior and current season vaccination. Models were adjusted for age, calendar time, high-risk status, and site.

Results
Of 31,819 patients included in the analysis over 6 seasons, 9188 were influenza positive by RT–PCR. Percent flu positivity was greatest among those unvaccinated (34%), followed by those vaccinated in the prior season only (29%), those vaccinated in both seasons (25%), and those vaccinated in the current season only (23%). Among patients with prior season vaccination, current season VE against any influenza was 14% (95% CL: 5, 22) and against A(H3N2), A(H1N1)pdm09, and B was 10% (95% CL: 3, 17), 36% (95%CL: 25, 46), and 40% (95% CL: 33, 46), respectively. Among patients unvaccinated in the prior season, VE was 42% (95% CL: 37, 46) against any influenza in the current season and was 31% (95%CL: 22, 39), 57% (95% CL: 47, 65), and 55% (95% CL: 48, 61) against A(H3N2), A(H1N1)pdm09, and B, respectively. We observed significant interaction of prior season vaccination on current season VE in 4 of 6 seasons (P < 0.20).

Conclusion
Current season vaccination was overall protective regardless of vaccination history. Among those vaccinated in the prior season, current season vaccination may provide some benefit in addition to residual protection from previous vaccination.

Disclosures
All authors: No reported disclosures.