Influenza-related Complications Research Articles

Applying the Lessons of Influenza to COVID-19 During a Time of Uncertainty.

Applying the Lessons of Influenza to COVID-19 During a Time of Uncertainty.

The management of influenza and its complications within the Guy’s and St Thomas’ NHS Foundation Trust

The peak number of admissions to hospital intensive care unit (ICU) for influenza-related complications was higher during the 2015/16 flu season than previous seasons.[1][1] This coincided with a lower uptake of flu vaccination in targeted groups including the elderly, those clinically at risk and

Influenza Therapeutics in Clinical Practice-Challenges and Recent Advances.

In the last few years, several new direct-acting influenza antivirals have been licensed, and others have advanced in clinical development. The increasing diversity of antiviral classes should allow an adequate public health response should a resistant virus to one agent or class widely circulate. One new antiviral, baloxavir marboxil, has been approved in the United States for treatment of influenza in those at high risk of developing influenza-related complications. Except for intravenous zanamivir in European Union countries, no antivirals have been licensed specifically for the indication of severe influenza or hospitalized influenza. This review addresses recent clinical developments involving selected polymerase inhibitors, neuraminidase inhibitors, antibody-based therapeutics, and host-directed therapies. There are many knowledge gaps for most of these agents because some data are not published and multiple pivotal studies are in progress at present. This review also considers important clinical research issues, including regulatory pathways, study designs, endpoints, and target populations encountered during the clinical development of novel therapeutics.

Fractures and Fall Injuries after Hospitalization for Seasonal Influenza - A National Retrospective Cohort Study

Background: Fractures and fall injuries often lead to disability, increased morbidity and mortality. Older adults are at higher risk of influenza related complications such as pneumonia, cardiovascular events and deaths, but the risk of fractures and fall injuries is unclear. The primary objective of this study was to investigate the risk of fractures and fall injuries in older patients after admission with seasonal influenza. Methods: In this retrospective cohort study of 6604 older adults (≥65 years) admitted with seasonal influenza at Swedish hospitals (from December 1st 2015 to December 31st 2017) and 330200 age and sex matched controls from the general population and admitted for other reasons, the risk of fracture or fall injury was investigated. Findings: The mean (SD) age of the 6604 influenza patients was 80·9 (8·1) years and 50·1% were women. During the first year after hospital discharge, there were 680 (10·3%) fractures or fall injuries among the patients with influenza and 25807 (7·8%) among the controls, corresponding to incident rates of 141 (95% CI, 131-152) and 111 (95% CI, 110-112) fractures or fall injuries per 1000 person-years respectively, translating to a significantly increased risk of fracture or fall injury in a Cox regression model (hazard ratio 1·28 (95% CI, 1·19-1·38)). Interpretation: Older adults admitted with influenza diagnosis, have increased risk of fracture or fall injury during the first year after discharge, further supporting the need to prevent influenza by vaccination. Funding: The Swedish Research Council, ALF/LUA grants from the Sahlgrenska University Hospital. Declaration of Interests: Dr Axelsson has received lecture fees from Lilly, Meda/Mylan and Amgen. Prof Lorentzon has received lecture fees from Astellas, Amgen, Lilly, UCB Pharma, Radius Health, Meda/Mylan, GE-Lunar and Santax Medico/Hologic. Mr Litsne has no conflicts of interest. Ethics Approval Statement: The study was approved by the Swedish Ethical Review Authority.

Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, double-blind, active-comparator trial.

Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV). This study was a treatment-stratified, randomised, double-blind trial to compare the immunogenicity and safety of SD-QIV (15 μg of haemagglutinin [HA] per strain) versus HD-TIV (60 μg of HA per strain) in adults with rheumatoid arthritis who are positive for rheumatoid factor or anti-cyclic citrullinated peptide, or both, recruited during the 2016-17 and 2017-18 influenza seasons at three hospitals affiliated with McGill University (Montreal, QC, Canada). Participants had received treatment for rheumatoid arthritis with conventional or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs, or combinations of them, were still on treatment at the time of enrolment, and their treatment had not been modified during the 3 months before enrolment. They were stratified into one of three groups according to treatment. Patients who, at enrolment, were taking conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination were stratified to group 1; those who were taking a biological DMARD (anti-tumour necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 2; and those who were taking abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 3. Participants were randomly allocated (1:1) to receive the SD-QIV or HD-TIV vaccine. Randomisation was based on a computer-generated allocation sequence, and participants, investigators, and research nurses responsible for safety assessments were masked to vaccine assignment. The primary outcome was the seroconversion rate (as measured by haemagglutination-inhibition assay) per strain at day 28. Analysis was done in the modified intention-to-treat population, which included all randomly assigned participants for whom seroconversion status was available. Safety was assessed throughout the surveillance period (day 0-186). This trial is registered at ClinicalTrials.gov, number NCT02936180. Between Oct 24, 2016, and Dec 6, 2017, 696 patients with rheumatoid arthritis were invited to participate in the study and 279 were randomly assigned and vaccinated (140 [50%] received SD-QIV and 139 [50%] HD-TIV). 136 patients who received SD-QIV and 138 who received HD-TIV were included in the modified intention-to-treat anaysis. Patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2·99 (95% CI 1·46-6·11) for seroconversion to strain A/H3N2, 1·95 (1·19-3·22) for seroconversion to strain B/Bris, 3·21 (1·57-6·56) for seroconversion to strain A/H1N1 (in 2016-2017), and 2·44 (1·18-5·06) for seroconversion to strain A/H1N1 (in 2017-2018). Similar results were observed in patients from groups 1 and 2; the number of individuals in group 3 was insufficient to draw conclusions. Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported between days 0 and 28 in any group, and neither vaccine increased rheumatoid arthritis disease activity. Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV. These results are the first evidence to support the use of the HD-TIV in these patients. The Arthritis Society-Canada.

Influenza in patients with cancer after 2009 pandemic AH1N1: An 8-year follow-up study in Mexico.

BackgroundImmunosupressed patients are at high risk of influenza‐related complications. Influenza AH1N1 has been hypothesized to induce worse outcomes in patients with malignancies, but after the A(H1N1)pdm09 few publications have analyzed the presentation and complications related to influenza afterward.ObjectivesWe aimed to describe the characteristics, risk factors, and outcomes of influenza in an oncologic center after the 2009 pandemic and to compare our case distribution to the National community acquired influenza databases in Mexico and the United States.MethodsWe reviewed the cases of confirmed influenza in patients with cancer from an oncological center in Mexico from April 2009 to April 2017. Data on severity and influenza type, malignancy, comorbidities, and outcomes were recorded. We correlated data between the Centers for Disease Control and Prevention (CDC) in the United States and SISVEFLU (Influenza Surveillance Program) in Mexico.ResultsOne hundred eighty‐eight patients were included; 75 (39.9%) had a solid neoplasm and 113 (60.1%) had hematologic malignancies. AH1N1 was the most frequent influenza type (54.2%). Patients with hematologic malignancies had more pneumonia (55% vs 25%, P < .001), needed more hospitalizations (75% vs 39% P < .001), had higher all‐cause mortality at 30 days (20% vs 9% P = .048) and influenza‐associated mortality (17% vs 7% P = .041). Thirty (16%) patients died within 30 days, and 24 (12.7%) were related to influenza. Influenza type was not associated with worse outcomes. Yearly occurrence of influenza reported by the CDC and SISVEFLU showed a significant correlation (ρ = 0.823, P = .006).ConclusionsAH1N1 was the dominant serotype. Patients with hematologic malignancies had more severe influenza and presented worse outcomes. Annual SISVEFLU and CDC surveillance information showed a similar distribution of cases along time but influenza serotypes did not match for all seasons.

Higher frequency of hospitalization but lower relative mortality for pandemic influenza in people with type 2 diabetes.

There is limited evidence linking type 2 diabetes (T2D) to influenza-related complications. To test a set of research questions relating to pandemic influenza vaccination, hospitalization and mortality in people with and without T2D. In this population-based cohort study, we linked individual-level data from several national registers for all Norwegian residents aged 30years or more as of January 2009. People with or without T2D at baseline (n=2992228) were followed until December 2013. We used Cox regression to estimate adjusted hazard ratios (aHRs). Pandemic influenza hospitalization was more common in individuals with T2D (aHR=2.46, 95% CI 2.04-2.98). The mortality hazard ratio associated with hospitalization for pandemic influenza was lower in people with T2D (aHR=1.82, 95% CI 1.21-2.74) than in those without T2D (aHR=3.89, 95% CI 3.27-4.62). The same pattern was observed when restricting to 90-day mortality (aHR=3.89, 95% CI 1.25-12.06 amongst those with T2D and aHR=10.79, 95% CI 7.23-16.10 amongst those without T2D). The rate of hospitalization for pandemic influenza was 78% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR=0.22, 95% CI 0.11-0.39), whilst the corresponding estimate for those without T2D was 59% lower (aHR=0.41, 95% CI 0.33-0.52). Mortality was 25% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR=0.75, 95% CI 0.73-0.77), whilst the corresponding estimate for those without T2D was 9% (aHR=0.91, 95% CI 0.90-0.92). There may have been a lower threshold for pandemic influenza hospitalization for people with T2D, rather than more severe influenza infection. Our combined results support the importance of influenza vaccination amongst people with T2D, especially during pandemics.

2333. Influenza-Related Neurologic Complications in Hospitalized Children with Underlying Neurologic Disorders

BackgroundChildren with underlying neurological and neuromuscular conditions are considered “high risk” for developing severe infection due to influenza. Prior reports highlighted this population’s increased risk for respiratory failure. Little is known about neurological complications experienced by children with pre-existing neurologic disorders (PNDs) when infected with influenza.MethodsRetrospective cohort study of children 0.5–18.0 years old hospitalized at a tertiary care pediatric hospital between August 2010 and June 2017 with laboratory-confirmed influenza. Eligible children were identified by electronic medical record query for influenza assay CPT codes with positive results during an admission; cases were confirmed by chart review. Demographics and clinical data were abstracted.ResultsA total of 1217 immune competent children (median age 5.5 [IQR 2.2–9.8] years) were hospitalized with laboratory-confirmed influenza during the study period. About 28% (341/1217) had at least one PND, including epilepsy (n = 105), developmental delay or intellectual disability (n = 234), neurogenetic or metabolic disorders (n = 77), neuromuscular disorders (n = 22) and others (n = 253). Compared with previously healthy peers, these children were more often admitted to the intensive care unit (31% vs. 16%, P < 0.001), had a longer length of stay (3 vs. 2 days, P < 0.001), and had a higher incidence of neurologic complications (23% vs. 6%, P < 0.001). Seizures (18% vs. 4%, P < 0.001) and encephalopathy (8% vs. 2%, P < 0.001) in particular were more common in children with PNDs, but other neurologic complications occurred in comparable proportions (3% vs. 1%, P = 0.088). Only 49% of the overall cohort had documented annual influenza vaccine; coverage was slightly better for children with PNDs than those without (55% vs. 48%, P = 0.017). The odds of having a neurologic complication in children with documented vaccination was nearly half that of other children when adjusted for age, influenza strain, and any PND (adjusted OR 0.64, 95% CI 0.44–0.94, P = 0.021).ConclusionThe excess risk of neurological complications in children with PNDs highlights the importance of vaccinating this population. Additional consideration should be given to post-exposure prophylaxis for children with PNDs who have not received vaccine. Disclosures All authors: No reported disclosures.

A Forgotten Danger: Burden of Influenza Mortality Among American Indians and Alaska Natives, 1999-2016.

American Indians and Alaska Natives (AI/ANs) are the only racial group in the United States that is identified as having a higher risk for developing influenza-related complications. As such, influenza-related mortality has consistently been one of the leading causes of death among AI/ANs. In addition, estimating influenza-related mortality is hampered by significant degrees of racial misclassification and underreporting of both morbidity and mortality data in the AI/AN population. Using data available from the Centers for Disease Control and Prevention, we analyzed influenza mortality by geography, race, gender, and age group to improve our understanding of the influenza burden on AI/AN communities. We found that while mortality rates generally declined across the AI/AN population, significant disparities exist between AI/ANs and non-Hispanic whites (NHWs). The greatest disparities occurred at the earliest stages of life, with mortality rates for AI/AN children younger than 5 years being more than 2 times higher than for NHW children. Similarly, the burden of influenza-related mortality among AI/AN adults emerged much earlier in life compared with NHWs. Perhaps most important, though, we found significant disparities in the geographic distribution of influenza-related mortality among AI/ANs. Because these are largely vaccine-preventable deaths, these results identify an area for targeted intervention to reduce the overall deaths attributable to influenza.

Coverage and determinants of influenza vaccine among pregnant women: a cross-sectional study

BackgroundPregnant women are at increased risk of influenza-related complications. The World Health Organisation recommends influenza vaccination to this high-risk population as highest priority. However, achieving high influenza vaccine coverage among pregnant women remains challenging. We conducted a cross-sectional survey to estimate the coverage and determinants of influenza vaccination among pregnant women in Singapore.MethodsBetween September and November 2017, pregnant women aged ≥21 years were recruited at two public hospitals in Singapore. Participants completed an anonymous, self-administered online questionnaire assessing participants’ influenza vaccination uptake, knowledge of and attitudes towards influenza and the influenza vaccine, vaccination history, willingness to pay for the influenza vaccine, and external cues to vaccination. We estimated vaccine coverage and used multivariable Poisson models to identify factors associated with vaccine uptake.ResultsResponse rate was 61% (500/814). Only 49 women (9.8, 95% Confidence Interval (CI): 7.3–12.7%) reported receiving the vaccine during their current pregnancy. A few misconceptions were identified among participants, such as the belief that influenza can be treated with antibiotics. The most frequent reason for not being vaccinated was lack of recommendation. Women who were personally advised to get vaccinated against influenza during pregnancy were 7 times more likely to be vaccinated (prevalence ratio (PR) = 7.11; 95% CI: 3.92–12.90). However, only 12% of women were personally advised to get vaccinated. Other factors associated with vaccine uptake were vaccination during a previous pregnancy (PR = 2.51; 95% CI: 1.54–4.11), having insurance to cover the cost of the vaccine (PR = 2.32; 95% CI: 1.43–3.76), and higher vaccine confidence (PR = 1.62; 95% CI: 1.30–2.01).ConclusionsInfluenza vaccination uptake among pregnant women in Singapore is low. There is considerable scope for improving vaccination coverage in this high-risk population through vaccination recommendations from healthcare professionals, and public communication targeting common misconceptions about influenza and influenza vaccines.

EXamining the knowledge, Attitudes and experiences of Canadian seniors Towards influenza (the EXACT survey)

BackgroundOlder adults are at high risk for influenza-related complications including worsening frailty and function. We surveyed older Canadians to explore the impact of influenza and determine how influenza knowledge influences vaccination decision-making.MethodsWe disseminated an online survey through a national polling panel. The survey included questions about the respondents’ influenza vaccination practices and knowledge about influenza. Using validated measures, they reported their frailty and functional status prior to the 2016/17 influenza season, during illness (if applicable), and following the season. Regression analyses were used to examine predictors of poor functional outcomes.ResultsFive thousand and fourteen adults aged 65 and older completed the survey; mean age was 71.3 ± 5.17 years, 42.6% had one or more chronic conditions, 7.8% were vulnerable and 1.8% were frail. 67.9% reported receiving last season’s influenza vaccine. Those who rarely/never receive the influenza vaccine were significantly less likely to correctly answer questions about influenza’s impact than those who receive the vaccine more consistently. Of the 1035 (21.5%) who reported experiencing influenza or influenza-like illness last season, 40% indicated a recovery longer than 2 weeks, and one-fifth had health and function declines during this time. Additionally, 3.1% of those afflicted “never fully recovered”. Older age, significant trouble with memory and having influenza/ILI were among the independent predictors of persistent declines in health and function.ConclusionsGiven that frailty and function are important considerations for older adults’ well-being and independence, healthcare decision-makers must understand the potential for significant temporary and long-term impacts of influenza to make informed vaccine-related policies and recommendations.

Summary of the NACI Seasonal Influenza Vaccine Statement for 2019-2020.

Many different influenza vaccines are authorized for use in Canada and new evidence on influenza and vaccines is continually emerging. The National Advisory Committee on Immunization (NACI) provides annual recommendations regarding the use of seasonal influenza vaccines to the Public Health Agency of Canada (PHAC) for the upcoming influenza season. To summarize NACI recommendations regarding the use of seasonal influenza vaccines for the 2019-2020 influenza season, including conclusions from reviews of evidence on 1) a new split virus quadrivalent inactivated influenza vaccine and 2) the comparative effectiveness and immunogenicity of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older. For both topics, the NACI Influenza Working Group developed a predefined search strategy to identify all eligible studies, assessed their quality, summarized and analyzed the findings and, according to the NACI evidence-based process, proposed recommendations and identified the grade of evidence that supported them. In light of the evidence, the recommendations were then considered and approved by NACI. NACI concluded that the new split virus quadrivalent inactivated influenza vaccine has a safety and immunogenicity profile comparable to the quadrivalent inactivated influenza vaccines already authorized for adults and children 5 years of age and older (Grade B Evidence). Therefore, NACI recommended that this new vaccine may be considered among the quadrivalent inactivated influenza vaccines offered to adults and children five years of age and older (Discretionary NACI Recommendation). However, NACI concluded that the evidence is not sufficient (Grade I Evidence) to support specific recommendations on the differential use of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older. NACI continues to recommend that an age-appropriate influenza vaccine should be offered annually to anyone six months of age and older who does not have contraindications to the vaccine, with focus on the groups for whom influenza vaccination is particularly recommended. This includes people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk, people who provide essential community services and people in direct contact with poultry infected with avian influenza during culling operations.

Evaluating the effectiveness of the influenza vaccine during respiratory outbreaks in Singapore’s long term care facilities, 2017

Influenza outbreaks occur periodically in Long Term Care Facilities (LTCFs) and vaccination is critical in preventing influenza infections. We evaluated the influenza vaccine effectiveness (VE) during respiratory outbreaks in LTCFs reported to the Ministry of Health, Singapore in 2017.A test-negative design was used to estimate the ratio of the odds of testing positive for influenza among vaccinated individuals to the odds among unvaccinated individuals. The VE was calculated as (1-odds ratio) × 100%. For adjusted VE, the estimates were derived using logistic regression adjusted for age group, gender, month of illness, and number of days from date of illness onset till to swab collection date. Estimates by influenza subtypes and post-vaccination time periods (15–180 days & 181–365 days) were also calculated using stratified data.264 individuals, with 118 laboratory-confirmed influenza cases [32 A(H1N1)pdm09, 75 A(H3N2), 11 A(untypable)], were included in the analysis. No one was identified to be infected with influenza B. The overall adjusted VE estimate was 40.5% (95% CI: −12.2–68.5%), while the subtype-specific adjusted VE estimates were −43.4% (95% CI: −312.4–50.2%) against A(H1N1)pdm09 and 57.1% (95% CI: 5.7–80.5%) against A(H3N2). At 15–180 days post-vaccination period, the adjusted VEs were 59.3% (95% CI: 18.0–79.8%) against all influenza, 35.4% (95% CI: −123.5–81.3%) against A(H1N1)pdm09 and 67.9% (95% CI: 22.5–86.7%) against A(H3N2). Estimates were not significant at 181–365 days post-vaccination.The influenza vaccine showed varying effectiveness among individuals in Singapore’s LTCFs in 2017, with a higher effectiveness among those who were more recently vaccinated. It remains an important tool in preventing influenza infections, especially for those who are at high risk of influenza-related complications.

Immune related adverse events in NSCLC patients treated with immune checkpoint therapy who received the influenza vaccination versus no vaccination.

e20657 Background: Influenza vaccination is recommended by the CDC for cancer patients to reduce the risk of influenza-related complications. There is concern that the incidence of immune-related adverse events (irAEs) may be greater in vaccinated patients receiving immune checkpoint inhibitors (ICPI). We sought to interrogate if influenza vaccination in patients with NSCLC receiving ICPI therapy had an increased incidence of irAEs compared to non-vaccinated patients. Methods: We conducted a single-center retrospective analysis of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy between 3/2015 – 12/2018. Influenza immunization records from both institutional and state-wide registries were obtained from 2014 -2019. Comparisons of adverse event incidence between flu vaccinated and control patients were tested using chi-square statistics. Results: 117 patients were included in our analysis, 33 (28%) were vaccinated during ICPI therapy, 19 (58%) received quadrivalent influenza vaccine, 13 (39%) received trivalent influenza vaccine and 1 (3%) was undetermined. 22 (67%) vaccinated patients had an irAE vs 53 (63%) patients who were not vaccinated during ICPI therapy (p = 0.720). 8 (24%) vaccinated patients had an irAE leading to discontinuation of therapy vs 12 (14%) patients who were not vaccinated during ICPI therapy (p = 0.198). The most frequent irAE in both groups was fatigue 16 (48%) vs 28 (33%) (p = 0.128). Notable irAEs included colitis (0 vs 1), pneumonitis (3 vs 3), hepatitis (1 vs 4) in vaccinated patients vs without vaccine, respectively. There were no statistically significant differences in baseline demographics between both groups including age, race, gender, tumor histology or ECOG performance status. Conclusions: Our study suggests that irAEs are not significantly increased with vaccination for influenza during ICPI therapy. However, there is a slight trend toward increased incidence of irAE warranting ICPI discontinuation for which further investigation is needed. Limitations of this study include a small sample size and inability to grade irAE retrospectively.

Influenza-Related Neurologic Complications in Hospitalized Children (S45.006)

Influenza-Related Neurologic Complications in Hospitalized Children (S45.006)

Analysis of influenza vaccination coverage among the elderly in Genoa (Italy) based on a deprivation index, 2009-2013.

SummaryIntroductionThe elderly suffer the most influenza-related complications, and 90% of deaths due to influenza occur in older subjects. Consequently, the elderly are among the main targets of influenza vaccination campaigns. The use of deprivation indexes can help to identify subgroups with lower vaccination uptake. This study analyzed influenza vaccination coverage in elderly persons living in Genoa (Italy) in relation to a local Index of Socio-Economic and Health Deprivation (SEHDI) in order to identify population subgroups needing specific intervention to improve vaccination coverage.MethodsThe study targeted subjects aged ≥ 65 years living in Genoa in the period 2009-2013. Information on vaccination coverage was provided by general practitioners and Local Health Units. A combination of linear regression, factor analysis and cluster analysis was used to construct the SEHDI at Census Tract (CT) level, on the basis of data from the 2011 Italian census.ResultsIn 2011, people aged ≥ 65 years accounted for the 27.7% of the population of Genoa. Most elderly subjects were assigned to either the medium (45.3%) or medium-high (32%) deprivation groups, while the percentages in the extreme tails were low (3.6% high deprivation; 1.3% low deprivation). Significant, non-linear (p < 0.05 NL) relationships were observed in both sexes with regard to mortality due to all respiratory diseases (RD) and chronic obstructive pulmonary disease (COPD), with the highest Standardized Mortality Ratio (SMR) values in women in the high deprivation group of women (1.81, p < 0.05 RD; 1.79, p < 0.05 COPD). The SMRs for influenza and pneumonia showed a positive linear trend in women (p < 0.05) with the highest value in the high deprivation group (1.97, p < 0.05), while in men the trend was NL (p < 0.05). A positive linear trend (p < 0.05) was found with regard to vaccination coverage, which grew weakly as deprivation increased, up to the medium-high deprived group (from 34.6% to 44.4%). However, the high deprivation group showed the lowest value (33.3%).ConclusionsThe results revealed a relationship between deprivation and influenza vaccination coverage in the elderly. This finding should be taken into account in the organization of vaccination campaigns and should prompt differentiated intervention in each local area.

Analysis of influenza vaccination coverage among the elderly living in Rome, based on a deprivation index, 2009-2013.

SummaryIntroductionElderly people are more likely to develop influenza-related complications. However, despite the recommendations, the optimal vaccination coverage is not reached. The use of deprivation indexes can help to identify subgroups with lower vaccination uptake. We analyzed vaccination coverage among elderly subjects living in the city of Rome on the basis of their socioeconomic characteristics by using a local deprivation index.MethodsWe focused on the population aged ≥ 65 years living in the city of Rome from 2009 to 2013. Information on vaccination coverage was collected from general practitioners. A combination of multivariate techniques, including multiple linear regression, factor and cluster analysis, was used to construct a composite area-based Index of Socio-Economic and Health Deprivation (SEHDI). The index was calculated for each census tract on the basis of data from the 2001 Italian census.ResultsThe majority of elderly subjects living in Rome belonged to the medium (40.4%) and medium-high (24%) deprivation groups; only 4.5% of the population was in the low-deprivation group. An inverse relationship was found between influenza vaccination coverage and the deprivation index: elderly subjects in the low-deprivation group displayed lower coverage (55.45%) than those in the high-deprivation group (57.59%). Specifically, vaccination coverage decreased with the increase of replacement index, employment rate and the percentage of: single and divorced individuals; university and high-school graduates; employees, entrepreneurs and freelancers, family assistants, students; foreigners and stateless persons residing in Italy; families consisting of one person.ConclusionsOur results show an inverse relationship between deprivation and vaccination coverage and may help to identify subgroups that could benefit from targeted initiatives to increase vaccination coverage.

Influenza Vaccination Coverage Among Pregnant Women in the U.S., 2012–2015

Pregnant women are at increased risk for severe illness from influenza and influenza-related complications. Vaccinating pregnant women is the primary strategy to protect them and their infants from influenza. This study aims to assess influenza vaccination coverage during three influenza seasons (2012-2015) from a national probability-based sampling survey and evaluate potential factors that influence vaccination uptake among pregnant women. Data from the 2012 through 2015 National Health Interview Surveys were analyzed in 2017. Pregnant women aged 18-49 years were included in the analysis. The Kaplan-Meier survival analysis procedure was used for vaccination coverage in each season. Bivariate and multivariable logistic regression analyses were performed to examine factors associated with vaccination. Adjusted vaccination coverage and adjusted prevalence ratios are reported with corresponding 95% CIs. In the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, 40.4%, 45.4%, and 43.1% of pregnant women were vaccinated, respectively. Multivariable analysis indicated that factors independently associated with a lower likelihood of vaccination included having only a high school education, having three or less provider visits, and having no usual place of care (p<0.05). Less than half of women with ten or more visits were vaccinated (48.6%). Vaccination coverage among pregnant women from this nationally representative sample was suboptimal during recent influenza seasons. Vaccination coverage was lower among certain sociodemographic, access-to-care subgroups. Multifactorial vaccination barriers may exist. Interventions, such as assessing vaccination history at every visit and implementing reminder-recall systems, standing orders, and addressing vaccination hesitancy, are needed to increase vaccination uptake among pregnant women.

Effects of the influenza vaccine on pediatric kidney transplant outcomes.

The influenza vaccine is critical for preventing influenza-related complications in transplant patients. Previous studies demonstrated de novo donor-specific antibody formation and rejection following the influenza vaccination. This risk has not been adequately assessed in the pediatric population. We performed a single-center retrospective analysis of 187 unique pediatric kidney transplant recipients, transplanted from January 1, 2006, to December 31, 2015, assessing for an association of the influenza vaccination with various transplant outcomes. The influenza vaccine was received by 125 of 187 patients within the first year post-transplant. Using log-rank tests and Kaplan-Meier curves, vaccinated patients had a significantly lower risk of mortality (P=0.048). There were no differences in death-censored graft survival (P=0.253), graft survival (P=0.098), or rejection (P=0.195) between vaccinated and unvaccinated groups. To address the problem of multiple exposures for a yearly vaccine, Cox proportional hazards regression was utilized with post-transplant vaccination status considered as a time-dependent covariate; analyses were performed using both a 360- and 180-day vaccination period following any post-transplant influenza vaccination. In this model, being vaccinated did not result in a significant difference in mortality (HR 0.90 [0.16, 5.15], P=0.91), death-censored graft survival (HR 0.70 [0.31, 1.58], P=0.39), graft survival (HR 0.69 [0.32, 1.49], P=0.34), or rejection (HR 0.67 [0.37, 1.19], P=0.17). Eight patients developed de novo donor-specific antibodies following the first post-transplant influenza vaccination; three then developed biopsy-proven rejection. These results suggest influenza vaccination is safe in pediatric kidney transplant recipients, and larger prospective studies are required to conclusively confirm our findings.

LB16. Phase 3 Trial of Baloxavir Marboxil in High-Risk Influenza Patients (CAPSTONE-2 Study)

BackgroundBaloxavir marboxil (BXM), an oral selective cap-dependent endonuclease inhibitor, is effective and safe for treating acute influenza in otherwise healthy patients.MethodWe conducted an international, randomized, double-blind, placebo (PLC)- and oseltamivir (Os)-controlled treatment study in patients at higher risk (HR) of influenza complications. Inclusion criteria included age ≥12 years, fever + influenza symptoms of ≤48 hours duration, and presence of at least 1 HR factor adapted from CDC criteria. Patients were randomized (1:1:1) to a single oral dose of BXM (40/80 mg for BW </≥80 kg), PLC, or 75 mg Os BID for 5 days. The primary endpoint was time to improvement of influenza symptoms (TTIIS) in those with RT-PCR confirmed influenza (ITTI population). Secondary endpoints included infectious virus detection in serial nasopharyngeal swabs, prescription of antibiotics, and influenza-related complications.ResultAmong 2,184 randomized patients, 1,163(53%) comprised the ITTI population (47.9% A/H3N2, 6.9% A/H1N1, 41.6% B). The most common risk factors were asthma or chronic lung disease (39.2%) and age ≥65 years (27.4%). TTIIS was significantly shorter in BXM than PLC (median 73.2 hours vs. 102.3 hours, P < 0.0001) and numerically shorter than Os (81.0 hours, P = 0.8347). TTIIS in BXM patients with A/H3N2 virus (median: 75.4 hours) was significantly shorter than in PLC (100.4 hours; P =0.0141) and was significantly shorter in patients with influenza B (74.6 hours) than in either PLC (100.6 hours; P = 0.0138) or Os (101.6 hours; P = 0.0251). Median time to cessation of viral shedding in BXM patients was 48 hours, significantly less than 96 hours in both PLC and Os patients. Systemic antibiotic use and influenza-related complications were significantly fewer in BXM (3.4% and 2.8%, resp.) than PLC (7.5% and 10.4%; P = 0.0112, and P < 0.0001). The incidence of any (25.1–29.7%) or serious adverse events (0.7–1.2%) did not differ significantly across the groups.ConclusionBXM was well-tolerated and associated with faster recovery and reduced risk of complications in HR influenza patients compared with PLC. It proved superior to Os in shortening the duration of virus replication and in resolving influenza B illness. Oral BXM is a promising treatment option for patients with risk factors for influenza complications.Disclosures M. G. Ison, Romark: Investigator, Research support. Shionogi: Scientific Advisor, Paid DSMB Member. Emergent BioScience: Investigator, Research support. Janssen: Investigator and Scientific Advisor, Consulting fee and Research support. GlaxoSmithKlein: Scientific Advisor, Paid DSMB Member. VirBio: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. S. Portsmouth, Shionogi Inc.: Employee, Salary. Y. Yoshida, Shionogi & Co., Ltd.: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary. F. Hayden, Shionogi & Co., Ltd.: Scientific Advisor, Consulting fee (donated) and travel support for attending 6th ESWI meeting, 10–13 September 2017, Latvia, to present phase 3 OWH results. .T. Uehara, Shionogi & Co., Ltd.: Employee, Salary.