Severe Complications Of Influenza Research Articles

Effectiveness of cocoon strategy vaccination on prevention of influenza-like illness in young infants

ABSTRACT During the initial half-year of their existence, infants cannot receive the influenza vaccine, yet they face the greatest susceptibility to severe influenza complications. In this study, we seek to determine whether influenza vaccination of maternal and household contacts is associated with a reduced risk of influenza-like illness (ILI) and severe acute respiratory infection (SARI) in infants. This work was prospectively conducted during the influenza season. A total of 206 infants were included in this study. The percentage of infants with only the mother vaccinated is 12.6% (n:26), and the percent of infants with all household contacts vaccinated is 16% (n:33). Among the infants with only the mother vaccinated, the effectiveness of influenza vaccine is estimated as 35.3% for ILI and 41.3% for SARI. Among infants with all household contacts vaccinated, the effectiveness is estimated as 48.9% for ILI and 76.9% for SARI. Based on the results of multivariate logistic regression analysis, all-household vaccination is a protective factor against SARI (OR: 0.07 95% CI [0.01–0.56]), household size (OR: 1.75, 95% CI [1.24–2.48]) and presence of secondhand smoke (OR: 2.2, 95% CI [1.12–4.45]) significant risk factors for SARI in infants. The mother alone being vaccinated is not a statistically significant protective factor against ILI (OR: 0.46, 95% CI [0.19–1.18]) or SARI (OR: 0.3, 95% CI [0.11–1.21]). Along with the obtained results and analysis, this study provides clear evidence that influenza vaccination of all household contacts of infants aged 0–6 months is significantly associated with protecting infants from both ILI and SARI.

Immunogenicity of Enhanced Influenza Vaccines Against Mismatched Influenza Strains in Older Adults: A Review of Randomized Controlled Trials.

Antigenic drift is a major driver of viral evolution and a primary reason why influenza vaccines must be reformulated annually. Mismatch between vaccine and circulating viral strains negatively affects vaccine effectiveness and often contributes to higher rates of influenza-related hospitalizations and deaths, particularly in years dominated by A(H3N2). Several countries recommend enhanced influenza vaccines for older adults, who are at the highest risk of severe influenza complications and mortality. The immunogenicity of enhanced vaccines against heterologous A(H3N2) strains has been examined in nine studies to date. In six studies, an enhanced, licensed MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) consistently increased heterologous antibody titers relative to standard influenza vaccine, with evidence of a broad heterologous immune response across multiple genetic clades. In one study, licensed high-dose trivalent inactivated influenza vaccine (HD-IIV3) also induced higher heterologous antibody titers than standard influenza vaccine. In a study comparing a higher dose licensed quadrivalent recombinant influenza vaccine (RIV4) with HD-IIV3 and aIIV3, no significant differences in antibody titers against a heterologous strain were observed, although seroconversion rates were higher with RIV4 versus comparators. With the unmet medical need for improved influenza vaccines, the paucity of studies especially with enhanced vaccines covering mismatched strains highlights a need for further investigation of cross-protection in older adults.

Manfaat Vaksinasi Influenza bagi Pasien Diabetes Melitus

People with diabetes mellitus have a dysregulated immune system and are more susceptible to infection, which poses a higher risk of severe influenza complications. Current evidence for influenza vaccine effectiveness in people with diabetes mellitus indicates a beneficial reduction of morbidity and mortality. In addition, serological studies show antibody levels elicited from influenza vaccination in diabetes patients show comparable results with healthy adults. Although more controlled clinical trials in diabetes mellitus patients with influenza are needed to reflect the effect of vaccination, current data indicate the need for routine influenza vaccination in diabetes mellitus patients, as recommended by guidelines. Efforts should be made to increase vaccination coverage in this risk group.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2022.

For 30 years the Australian Paediatric Surveillance Unit (APSU) has conducted national surveillance of rare communicable diseases and rare complications of communicable diseases. In this report, we describe the results of thirteen such studies surveyed by the APSU in 2022, including reported case numbers and incidence estimates, demographics, clinical features, management and short-term outcomes. Conditions described are: acute flaccid paralysis (AFP); congenital cytomegalovirus (cCMV); neonatal and infant herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV) and paediatric HIV infection; severe complications of influenza; juvenile-onset recurrent respiratory papillomatosis (JoRRP); congenital rubella infection/syndrome; congenital varicella syndrome (CVS) and neonatal varicella infection (NVI); and the new conditions dengue; Q fever; and severe acute hepatitis. In 2022, cases of severe complications of influenza were reported to the APSU for the first time since 2019. This likely reflects the easing of government-mandated restrictions imposed in 2020-2021 to curb the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the re-emergence of a range of infectious diseases. As previously, AFP surveillance by the APSU contributed to Australia achieving a minimum target incidence of one AFP case per 105 children aged less than 15 years. Cases of JoRRP and NVI were reported in 2022. This indicates potential gaps in human papillomavirus (HPV) and varicella vaccination coverage respectively, especially in high-risk groups such as young migrant and refugee women of childbearing age from countries without universal vaccination programs. Paediatric HIV case numbers resulting from mother-to-child-transmission (MTCT) of HIV remain low in Australia due to use of effective intervention strategies. However, there has been an increase in the number of imported cases of HIV in children (mainly perinatally-acquired) from countries with a high HIV prevalence. Without effective vaccines, there has been no decline in the incidence of congenital CMV and neonatal HSV, indicating the importance of early identification and management to reduce morbidity and mortality. The first cases of dengue, Q fever and severe acute hepatitis were received by APSU in 2022, including two cases of acute hepatitis in which aetiology has not been confirmed to date. The APSU has an important ongoing role in monitoring rare childhood infections.

Modeling the impacts of influenza antiviral prophylaxis strategies in nursing homes

Background: Antiviral chemoprophylaxis for influenza is recommended in nursing homes to prevent transmission and severe disease among residents with higher risk of severe influenza complications. Interim CDC guidance recommends that long-term care facilities initiate antiviral chemoprophylaxis with oral oseltamivir for all non-ill residents living in the same unit following the start of an outbreak in a facility (ie, ≥2 patients ill within 72 hours and of whom at least 1 resident has laboratory-confirmed influenza). Prophylaxis continues for a minimum of 2 weeks and for at least 7 days after the last laboratory-confirmed case. However, facilities may not strictly adhere to this guidance, with 1 study showing up to 68% of facilities were nonadherent to national guidance (Silva et al 2020). Here, we model the potential impacts of different antiviral prophylaxis strategies. Methods: We developed a susceptible–exposed–asymptomatic–infected–recovered (SEAIR) compartmental model of an average-sized nursing home comprising short-stay residents, long-stay residents, and healthcare personnel (HCP). Persons treated with antiviral chemoprophylaxis were less susceptible to infection, had a lower probability of symptoms if infected, a reduced viral load, and a shortened duration of infectiousness. We included influenza vaccination for residents and HCP through reduced probability of symptomatic infection. Coverage rates were estimated from CDC FluVaxView and CMS COVID-19 nursing home data. As a base case, we modeled a scenario with prophylaxis implemented according to guidance. We varied uptake by residents and HCP (from 10% to 90%), case thresholds for prophylaxis initiation (1–5 cases identified), and timing of prophylaxis cessation: either time dependent (ie, 10–14 days of prophylaxis) or case-dependent (ie, continuing prophylaxis for 1–7 days with no cases). Results: In the scenario based on current guidance, prophylaxis reduced resident cases by 16% and resident hospitalizations by 45%, compared to no prophylaxis (Fig. 1A). Scenarios that differed from the guidance altered case burden and timing: Time-dependent prophylaxis cessation increased resident cases and hospitalizations (Fig. 1A). Timing of prophylaxis initiation had slight effects on the timing of the epidemic and minimal effects on resident cases and hospitalizations (Fig. 1B). High resident uptake was important for reducing resident cases and hospitalizations (Fig. 1C), but increasing HCP uptake had minimal effect (Fig. 1D). Conclusions: Our findings support the current prophylaxis guidance. Promptly implementing prophylaxis reduces resident cases and hospitalizations. Continuing prophylaxis until cases are no longer identified reduces cases and hospitalizations.Disclosure: None

Early and Increased Influenza Activity Among Children - Tennessee, 2022-23 Influenza Season.

Influenza seasons typically begin in October and peak between December and February (1); however, the 2022-23 influenza season in Tennessee began in late September and was characterized by high pediatric hospitalization rates during November. This report describes a field investigation conducted in Tennessee during November 2022, following reports of increasing influenza hospitalizations. Data from surveillance networks, patient surveys, and whole genome sequencing of influenza virus specimens were analyzed to assess influenza activity and secondary illness risk. Influenza activity increased earlier than usual among all age groups, and rates of influenza-associated hospitalization among children were high in November, reaching 12.6 per 100,000 in children aged <5 years, comparable to peak levels typically seen in high-severity seasons. Circulating influenza viruses were genetically similar to vaccine components. Among persons who received testing for influenza at outpatient clinics, children were twice as likely to receive a positive influenza test result as were adults. Among household contacts exposed to someone with influenza, children were more than twice as likely to become ill compared with adults. As the influenza season continues, it is important for all persons, especially those at higher risk for severe disease, to protect themselves from influenza. To prevent influenza and severe influenza complications, all persons aged ≥6 months should get vaccinated, avoid contact with ill persons, and take influenza antivirals if recommended and prescribed.

Coverage of influenza vaccination of patients with diabetes and determination of barriers for implementation of vaccination

People with diabetes (PWD) are considered to be at high risk of developing severe influenza complications that can lead to hospitalization and sometimes death. It is because of the high risk of developing severe complications that WHO recommends seasonal influenza vaccination (SIV) for PWD.&#x0D; The purpose of the work is to establish the level of coverage of vaccination in PWD and to identify barriers to vaccination in this group in order to overcome obstacles.&#x0D; We analyzed data on the coverage of SIV in PWD and studied the problems of low adherence to vaccination in PWD. We used content analysis, bibliosemantic, analytical, generalizing analyses. An insufficient level of vaccination coverage of PWD has been established. Barriers to vaccination in PWD have been identified. Barriers can be: age, health status, allergic reactions and chronic diseases of people, lower level of education, gender and their employment in economic activities. At the same time, gaps in the knowledge of health care provider, insufficient involvement of endocrinologists and diabetologists in informing PWD about vaccination, a limited number of imported vaccines, and low physical and economic accessibility of vaccines negatively affect the coverage of SIV. A significant factor influencing the level of vaccination coverage of people is their vaccination hesitation. Pharmacists should actively participate in the vaccination campaign by raising public awareness and providing advice to PWD who regularly visit pharmacies. To increase the vaccination coverage of PWD, it is necessary to introduce training programs for doctors and pharmacists to attract them to influenza vaccination companies. Simultaneously conduct educational campaigns and education of PWD. It is advisable to organize a free flu vaccination in medical and diagnostic diabetic hospital (institutions) to increase the physical and economic accessibility of vaccination for PWD. A large number of studies showing the cost-effectiveness of SIV in PWD should be a significant factor for health authorities to improve measures to increase the level of coverage of SIV in patients in this risk group.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2021.

The Australian Paediatric Surveillance Unit (APSU) has been conducting surveillance of rare communicable and non-communicable conditions in children since its inception in 1993. In this report, the results are described of surveillance of ten communicable diseases (and complications) for 2021, including the numbers of cases and incidence estimates; demographics; clinical features; and management and short-term outcomes. The included diseases are: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV); neonatal herpes simplex virus (HSV) infection; paediatric human immunodeficiency virus (HIV) infection; perinatal exposure to HIV; severe complications from influenza; juvenile-onset respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. In 2021, cases of JoRRP were reported to the APSU for the first time since 2017, indicating potential gaps in HPV vaccination. AFP surveillance by APSU again contributed to Australia achieving a minimum target incidence of one AFP case per 100,000 children aged < 15 years. There were no cases of children with severe complications of influenza. No cases of varicella or congenital rubella were reported; however, at-risk populations, especially young migrant and refugee women from countries without universal vaccination programs, need to be screened and prioritised for vaccination prior to pregnancy. Cases of perinatal exposure to HIV continue to increase; however, the rate of mother-to-child-transmission remains at low levels due to the use of effective intervention strategies. Case numbers of congenital CMV and neonatal HSV remain steady in the absence of vaccines, prompting the need for greater awareness and education, with recent calls for target screening of at-risk infants for congenital CMV.

COMPARATIVE ANALYSIS OF CLINICAL AND LABORATORY DATA OF LUNG AFFECTION IN PATIENTS WITH COVID-19 WITH THOSE OF PANDEMIC INFLUENZA A/H1N1

Influenza viruses, in particular A ‒ A(H3N2) and A(H1N1)pdm09, as well as influenza B virus, mainly (98%) of the B/Victoria line, continue to circulate during the current epidemic season. The level of influenza vaccination remains low, about 0.6% of the population of Ukraine, and among occupational and epidemiological risk groups ‒ 22.8%, according to the Public Health Centre of the Ministry of Health of Ukraine. In the COVID-19 pandemic, simultaneous circulation of influenza viruses and SARS-CoV-2 can lead to difficulties in differential diagnosis and treatment. Comparison of clinical and laboratory features of severe influenza complicated by pneumonia caused by pandemic influenza virus A(H1N1)pdm09 in the epidemic season of 2015/2016 Kharkiv RCIDH with COVID-19 on clinical and laboratory data was the aim of the work. Patients and research methods. The analysis of clinical symptoms and laboratory examination data of 19 patients with influenza complicated by community-acquired pneumonia of clinical group IV who were treated at the Kharkiv Regional Hospital and their comparison with those of patients with COVID-19 according to the literature. Results and discussion. Among the studied patients, men predominated ‒ 12 persons (63.2%) aged 50.68±11.95 years. The predominant number had concomitant diseases. At the beginning of the disease, moderate weakness, headache, fever, minor catarrhal phenomena and, as a result, delayed hospitalization prevailed. From 3‒4 days of the disease the condition significantly worsened, shortness of breath and cyanosis joined. Typical initial symptoms of COVID-19 are fever of varying degrees (73%), unproductive cough (59%) and shortness of breath or shortness of breath. Conclusions. In patients with COVID-19 and severe influenza, a more acute onset of the disease was reported, with moderate weakness, headache and fever up to 38°C and symptoms of pharyngitis. Influenza patients often show a delay in seeking medical attention and hospitalization for 6.21±1.46 days of illness. The severity of the disease in influenza is due to the accession of community-acquired pneumonia, in contrast to COVID-19, where the typical features are diffuse, mostly subpleural lung affection. Vaccination of people at risk before the start of the epidemic season is necessary to prevent severe complications of influenza caused by the pandemic virus A(H1N1)pdm09 in the context of the COVID-19 pandemic. Keywords: influenza, pneumonia, COVID-19, diagnosis.

Prediction of Influenza Complications: Development and Validation of a Machine Learning Prediction Model to Improve and Expand the Identification of Vaccine-Hesitant Patients at Risk of Severe Influenza Complications.

Influenza vaccinations are recommended for high-risk individuals, but few population-based strategies exist to identify individual risks. Patient-level data from unvaccinated individuals, stratified into retrospective cases (n = 111,022) and controls (n = 2,207,714), informed a machine learning model designed to create an influenza risk score; the model was called the Geisinger Flu-Complications Flag (GFlu-CxFlag). The flag was created and validated on a cohort of 604,389 unique individuals. Risk scores were generated for influenza cases; the complication rate for individuals without influenza was estimated to adjust for unrelated complications. Shapley values were used to examine the model’s correctness and demonstrate its dependence on different features. Bias was assessed for race and sex. Inverse propensity weighting was used in the derivation stage to correct for biases. The GFlu-CxFlag model was compared to the pre-existing Medial EarlySign Flu Algomarker and existing risk guidelines that describe high-risk patients who would benefit from influenza vaccination. The GFlu-CxFlag outperformed other traditional risk-based models; the area under curve (AUC) was 0.786 [0.783–0.789], compared with 0.694 [0.690–0.698] (p-value < 0.00001). The presence of acute and chronic respiratory diseases, age, and previous emergency department visits contributed most to the GFlu-CxFlag model’s prediction. When higher numerical scores were assigned to more severe complications, the GFlu-CxFlag AUC increased to 0.828 [0.823–0.833], with excellent discrimination in the final model used to perform the risk stratification of the population. The GFlu-CxFlag can better identify high-risk individuals than existing models based on vaccination guidelines, thus creating a population-based risk stratification for individual risk assessment and deployment in vaccine hesitancy reduction programs in our health system.

Antiviral Use and Health Care Use Among US Patients With Rheumatoid Arthritis and Influenza in Three Influenza Seasons, 2016-2019.

ObjectivePatients with rheumatoid arthritis (RA) are vulnerable to severe complications of influenza. We assessed whether health care resource use (HRU) and costs differed between patients with RA and influenza who received antiviral medication compared with matched patients with RA and influenza not receiving antiviral therapy.MethodsThis was a retrospective US health insurance claims analysis over three influenza seasons (each October to April) in 2016‐2019. Adults with RA and a subsequent diagnosis of influenza were included. Treated patients (receiving antiviral influenza treatment within 2 days of diagnosis) and untreated patients were propensity score matched using baseline covariates. HRU and costs were assessed for inpatient, emergency department (ED), and outpatient visits and compared between cohorts using χ2 tests and t tests.ResultsAfter matching, 2638 treated and 1319 untreated patients were included. For treated versus untreated patients, the mean number of all‐cause outpatient visits was 0.96 versus 1.21 during 14 days of follow‐up (P < 0.001) and 1.94 versus 2.24 over 28 days (P = 0.001), respectively. Over 28 days, the mean number of all‐cause ED visits was lower among treated (0.23) than untreated (0.30) patients (P = 0.042). The mean number of respiratory‐related outpatient visits was significantly lower for treated versus untreated patients, and mean costs for these visits were $17.89 versus $35.27 over 14 days (P < 0.001) and $28.92 versus $48.77 over 28 days (P < 0.001) for treated versus untreated patients, respectively.ConclusionOur findings demonstrate that prompt antiviral treatment after influenza diagnosis may reduce HRU and costs in patients with RA.

Identification of Barriers Limiting the Use of Preventive Vaccinations against Influenza among the Elderly Population: A Cross-Sectional Analysis.

Older adults are at a high risk of experiencing severe complications of influenza. Receiving a vaccination is a beneficial strategy to prevent the disease and reduce the severity of influenza illnesses. This cross-sectional questionnaire-based study aimed to evaluate the influence of sociodemographic, clinical, and mental parameters as well as other potential risk factors on refusal to vaccinate against influenza among the elderly population in Poland. Furthermore, due to the prevailing COVID-19 pandemic, we put efforts into finding any statistical correlations between the fear of COVID-19 infection in patients and their attitudes toward receiving an influenza vaccination. The study was conducted in November–December 2020 in Poland on a representative nationwide sample of 500 individuals aged > 60. Of the respondents, 62 (12.4%) and 51 (10.2%) underwent influenza vaccination in 2019 and 2020, respectively. Out of ten different factors analyzed in this study, three were significantly associated with attitudes towards influenza vaccination. Participants with net income below the national average of PLN 3000 (OR = 2.37, CI 95% [1.26–4.47]), compared to those earning more than PLN 3000, had significantly higher odds of having a negative attitude towards influenza vaccination. Furthermore, respondents with <174 cm height (OR = 2.56, CI 95% [1.51–4.33]) and those with strong fear of COVID-19 infection (OR = 1.65, CI95% [1.02–2.66]) were also more likely to refrain from influenza vaccination. We believe the identification of factors limiting the willingness to receive influenza vaccination is an effective way to help clinicians focus their efforts on educating the groups of patients with the highest odds of refusing to receive the vaccine. Moreover, it may aid the design and enforcement of national solutions or the implementation of novel legislative measures and preventive programs, increasing public confidence and promoting vaccination, especially among groups at high risk of developing this disease.

Associated virus-bacterial vaccine based on seasonal LAIV and S. pneumoniae chimeric peptide provide protection against post-influenza pneumococcal infection in mouse model

ABSTRACT Severe influenza complications are often caused by Streptococcus pneumoniae infection, which presents the most common cause of community-acquired pneumonia. We evaluated in a mouse model an associated virus-bacterial vaccine based on seasonal live influenza vaccines (LAIV) and S. pneumoniae chimeric protein comprising flagellin (PSPF). Intranasal immunization of mice with a complex of trivalent LAIV and PSPF caused an increased release of early cytokines in the lungs of mice. The immunogenicity of LAIV and PSPF in the associated vaccine composition was sometimes decreased compared to each vaccine preparation alone. Nevertheless, only vaccination of mice with LAIV+PSPF significantly reduced lethality and the bacterial load in the lungs in a model of post-influenza bacterial pneumonia. The study of the interactions of influenza viruses with bacterial peptides is important during the development of associated virus-bacterial vaccines intended for the prevention of severe post-influenza bacterial complications.

Influenza vaccination uptake and attitudes among adult cancer patients in Japan: a web-based questionnaire survey before the 2020/2021 season

ABSTRACT Influenza vaccination is necessary to reduce severe influenza complications, especially in immunocompromised people such as cancer patients. However, few studies have examined influenza vaccination uptake among adult Japanese patients with cancer; their attitudes toward vaccination, as well as factors related to vaccine hesitancy, are unclear. From September 1 to October 31, 2020, we disseminated a web-based questionnaire to patients with a history of cancer via snowball sampling through e-mails and social media of two Japanese cancer patients associations. A total of 163 surveys were completed. One hundred (61.3%) participants received an influenza vaccination in the 2019/2020 season, and the main reasons for vaccination were as follows: recommendation by medical professionals, positive awareness of vaccination through books or the internet, and provision of vaccination in the workplace. The main reasons for not receiving a vaccination were fear of adverse events, lack of concern about influenza infection, and lack of trust in vaccine effectiveness. In terms of the 2020/2021 season, 120 participants (73.6%) reported their intention to receive an influenza vaccination. Multiple regression analysis showed that significant factors for positive intention were the the treatment without chemotherapy (p = .009), vaccination history in the 2019/2020 season (p < .001), prior experience of influenza infection (p = .043), and the perception that influenza vaccination was more important due to the coronavirus disease pandemic (p = .050). This preliminary survey revealed a relatively modest influenza vaccine coverage among adult Japanese patients with cancer and identified several factors related to positive intention toward vaccination.

Ten Years of National Seasonal Surveillance for Severe Complications of Influenza in Australian Children.

Severe complications of influenza in children are uncommon but may result in admission to hospital or an intensive care unit (ICU) and death. Active prospective surveillance using the Australian Paediatric Surveillance Unit with monthly reporting by pediatricians of national demographic and clinical data on children with <15 years of age hospitalized with severe complications of laboratory-confirmed influenza during ten influenza seasons 2008-2017. Of 722 children notified, 613 had laboratory-confirmed influenza and at least one severe complication. Most (60%) were <5 years of age; 10% were <6 months, hence ineligible for vaccination. Almost half of all cases were admitted to ICU and 30 died. Most children were previously healthy: 40.3% had at least one underlying medical condition. Sixty-five different severe complications were reported; pneumonia was the most common, occurring in over half of all cases. Influenza A accounted for 68.6% hospitalizations; however, influenza B was more often associated with acute renal failure (P = 0.014), rhabdomyolysis (P = 0.019), myocarditis (P = 0.015), pericarditis (P = 0.013), and cardiomyopathy (P = 0.035). Children who died were more likely to be older (5-14 years), have underlying medical conditions, be admitted to ICU, and have encephalitis, acute renal failure, or myocarditis. Only 36.1% of all children reported received antiviral medications, and 8.5% were known to be vaccinated for seasonal influenza. Severe influenza complications cause morbidity and mortality in children, which may increase if coinfection with COVID-19 occurs in the 2020 season and beyond. Increased vaccination rates, even in healthy children, early diagnosis and timely antiviral treatment are needed to reduce severe complications and death.

Effect of Influenza Vaccination in Preventing Laboratory-Confirmed Influenza Hospitalization in Patients With Diabetes Mellitus.

People with diabetes are at high risk of severe influenza complications. The influenza vaccination effect among diabetic patients remains inconclusive. We estimated the average effect of influenza vaccination status in the current and prior seasons in preventing laboratory-confirmed influenza hospitalization in diabetic patients. Patients attended in hospitals and primary healthcare centers with influenza-like illness were tested for influenza from the 2013-2014 to 2018-2019 seasons in Navarre, Spain. A test-negative case-control design in diabetic inpatients compared the influenza vaccination status in the current and 5 prior seasons between laboratory-confirmed influenza cases and negative controls. Vaccination status of influenza-confirmed cases was compared between diabetic inpatients and outpatients. Influenza vaccination effect was compared between diabetic patients and older (≥ 60 years) or chronic nondiabetic patients. Of 1670 diabetic inpatients tested, 569 (34%) were confirmed for influenza and 1101 were test-negative controls. The average effect in preventing influenza hospitalization was 46% (95% confidence interval [CI], 28%-59%) for current-season vaccination and 44% (95% CI, 20%-61%) for vaccination in prior seasons only in comparison to unvaccinated patients in the current and prior seasons. Among diabetic patients with confirmed influenza, current-season vaccination reduced the probability of hospitalization (adjusted odds ratio, 0.35; 95% CI, .15-.79). In diabetic patients, vaccination effect against influenza hospitalizations was not inferior to that in older or chronic nondiabetic patients. On average, influenza vaccination of diabetic population reduced by around half the risk of influenza hospitalization. Vaccination in prior seasons maintained a notable protective effect. These results reinforce the recommendation of influenza vaccination for diabetic patients.

Acute Pulmonary Aspergillosis as a Severe Complication of Influenza, Pneumococcal Pneumonia, and Staphylococcus aureus Bacteremia in ICU

Background. Acute aspergillosis is a disease with dramatic progression and high mortality if not treated rapidly. However, diagnosing and treating is challenging, as the risk factors are not fully understood. Case Presentation. A fifty-three-year-old woman without any comorbidities was admitted to hospital due to high fever. Infections with influenza and pneumonia and Staphylococcus aureus bacteremia were diagnosed. The patient improved at first due to antimicrobial therapy; nine days after admission, her clinical condition deteriorated again, and she was transferred to ICU due to septic shock accompanied by respiratory failure, necessitating mechanical ventilation and high-dose catecholamine support. A CT scan showed a resolving inflammatory infiltrate bilateral caverns with markedly thickened walls. A culture from a bronchoalveolar lavage grew Aspergillus fumigatus. Galactomannan testing was positive in a bronchoalveolar lavage sample, and beta-D-glucan was positive in serum. Antifungal therapy with voriconazole and intermittent isavuconazole due to renal failure was performed, followed by a surgical resection of the caverns. Patient’s recovery was complicated by several severe bleeding episodes in the lungs. However, the patient showed full recovery and was discharged after 109 days in hospital. Conclusions. This case report highlights multiple complications of influenza and the difficulties of diagnosing and treating acute pulmonary aspergillosis. Furthermore, it stresses the importance for further studies to deepen the understanding about the association between influenza and aspergillosis and to shed further light on adequate therapy.

2746. Effectiveness of Influenza Vaccine for Prevention of Influenza-associated Hospitalizations Among Immunocompromised Adults—2017–2018

BackgroundImmunocompromised (IC) individuals are at higher risk for severe complications of influenza. Little literature describes vaccine effectiveness (VE) in this population. We evaluated VE for prevention of influenza-associated hospitalization among IC adults.MethodsWe analyzed data from adults hospitalized with acute respiratory illness (ARI) during the 2017–2018 FLU season at 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Prior year clinical encounter diagnoses and enrollment interviews were used to define IC groups. IC groups were mutually exclusive. VE was evaluated with a test-negative case–control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, race, and other factors, and stratifying by immunocompromising conditions.ResultsOf 3524 adults hospitalized with ARI, 1210 (34%) had an immunocompromising condition. Chronic steroid (n = 397), chemo/radiation therapy (n = 242), hematologic condition (n = 175), and organ transplant (n = 144) were most common. HIV (n = 45) and stem cell transplant (SCT) (n = 28) were least common. IC patients were more likely to be vaccinated than non-IC (60% vs. 55%, P = 0.002). Overall, vaccination reduced risk of influenza hospitalization by 36% (95% CI: 24,46). Among IC adults, VE was 9% (95% CI: −25,34). VE was 32% (95% CI: 5,51) for chemo/radiation therapy, 29% (95% CI: 6,47) for chronic steroids, 29% (95% CI: -6,52) for hematologic conditions, −1% (95% CI: −50,32) for organ transplant, −48% (95% CI: −190,25) for HIV, and −154% (95% CI = −458,−15) for SCT (Figure 1).ConclusionVaccination reduced risk of influenza hospitalization among adults with the most prevalent immunocompromising conditions in our cohort; however, it had little to no effect in other groups, such as in HIV and organ and stem cell transplant recipients. Results support using other preventative strategies in addition to vaccinating adults with immunocompromising conditions, such as vaccination of close contacts. Disclosures All authors: No reported disclosures.

995. Effectiveness of Influenza Vaccine for Prevention of Influenza-Associated Hospitalizations Among High-Risk Adults in the United States, 2015–2016

BackgroundIndividuals with cardiopulmonary and other chronic conditions are at increased risk for severe complications of influenza. Few studies have examined influenza vaccine effectiveness (VE) in high-risk groups. We evaluated VE against influenza-associated hospitalization among adults with specific high-risk conditions.MethodsAdults hospitalized with acute respiratory illness (ARI) during the 2015–2016 influenza season were enrolled at eight hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Respiratory specimens were tested for influenza by reverse transcription PCR. Measures of illness severity, underlying health status, and vaccination were obtained from medical records and enrollment interviews. The presence of high-risk conditions was determined from clinical codes assigned to prior year medical encounters. We estimated VE using a test-negative design as (1 − adjusted odds ratio), comparing odds of PCR-confirmed influenza among vaccinated patients vs. unvaccinated controls. Multivariate logistic regression was adjusted for age, sex, and other factors, stratifying by chronic conditions.ResultsOf 1,467 adults hospitalized with ARI, 236 (16%) had PCR-confirmed influenza; 180 (78%) were A(H1N1)pdm09. In all, 1,358 (93%) had ≥1 high-risk medical condition, and 1,026 (70%) had ≥3 conditions. Cardiovascular (n = 835), metabolic (including diabetes) (n = 773) and lung conditions (n = 692) were most common (figure). Patients with ≥1 high-risk conditions were more likely to be vaccinated (70%) vs. patients not at high risk (31%, P < 0.001). Among all patients, VE against any influenza-associated hospitalization was 50% (95% CI: 31–63). VE was similarly high among patients with neurologic (VE = 64%, 95% CI: 26–83), metabolic (VE = 55%, 95% CI: 30–71), and cardiovascular (VE = 53%, 95% CI: 27–69) conditions, though lower for patients with immunosuppression and malignancy (VE = 20%, 95% CI: −42–54).ConclusionVaccination significantly reduced risk of influenza hospitalization among adults with the most prevalent high-risk cardiovascular, metabolic, and lung conditions. Results support the benefit of vaccinating adults with existing specific chronic conditions. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

Mucosal Administration of Cycle-Di-Nucleotide-Adjuvanted Virosomes Efficiently Induces Protection against Influenza H5N1 in Mice.

The need for more effective influenza vaccines is highlighted by the emergence of novel influenza strains, which can lead to new pandemics. There is a growing population of susceptible subjects at risk for severe complications of influenza, such as the elderly who are only in part protected by current licensed seasonal vaccines. One strategy for improving seasonal and pandemic vaccines takes advantage of adjuvants to boost and modulate evoked immune responses. In this study, we examined the capacity of the recently described adjuvant cyclic di-adenosine monophosphate (c-di-AMP) to serve as an adjuvant for improved mucosal influenza vaccines, and induce effective protection against influenza H5N1. In detail, c-di-AMP promoted (i) effective local and systemic humoral immune responses, including protective hemagglutination inhibition titers, (ii) effective cellular responses, including multifunctional T cell activity, (iii) induction of long-lasting immunity, and (iv) protection against viral challenge. Furthermore, we demonstrated the dose-sparing capacity of the adjuvant as well as the ability to evoke cross-clade protective immune responses. Overall, our results suggest that c-di-AMP contributes to the generation of a protective cell-mediated immune response required for efficacious vaccination against influenza, which supports the further development of c-di-AMP as an adjuvant for seasonal and pandemic influenza mucosal vaccines.