Severe Influenza Disease Research Articles

Obesity uncovers presence of inflammatory lung macrophage subsets with adipose tissue transcriptomic signature in influenza virus infection.

Obesity is a risk factor for increased lung damage and disease severity during influenza virus infection. White adipose tissue (WAT) inflammation is a key driver of disease pathogenesis in obesity. Whether and how obesity modifies lung and WAT immune cell character and function in obesity to amplify influenza disease severity remains unknown. We show that obesity establishes a proinflammatory transcriptome in lung immune cells that is further augmented upon influenza virus infection. Unexpectedly, we also show that influenza virus infection induces expression of inflammatory genes in visceral WAT and modifies WAT immune cell milieu in obesity. Notably, a decrease in WAT macrophage (ATM) populations inversely correlates to increase in infiltrating lung macrophage numbers in obese influenza virus-infected mice. Comparison of both lung and WAT immune cell transcriptional landscapes uncovers a presence of a macrophage subset in the lungs whose transcriptomic signatures matched those of an inflammatory ATM subset preferentially found in obese mice. Adoptive transfer of ATMs from obese mice into lean influenza-virus infected mice promotes host immune cell infiltration to the lungs. Together, our novel findings provide evidence of immune cell transcriptome and character changes in the lungs and WAT of influenza virus infected obese, but not lean, mice and suggest that visceral ATMs may contribute to the overall inflammatory milieu in this setting.

Pediatric Clinical Influenza Disease by Type and Subtype 2015-2020: A Multicenter, Prospective Study.

Previous investigations into clinical signs and symptoms associated with influenza types and subtypes have not definitively established differences in the clinical presentation or severity of influenza disease. The study population included children 0 through 17 years old enrolled at 8 New Vaccine Surveillance Network sites between 2015 and 2020 who tested positive for influenza virus by molecular testing. Demographic and clinical data were collected for study participants via parent/guardian interview and medical chart review. Descriptive statistics were used to summarize demographic and clinical characteristics by influenza subtype. Multivariable logistic regression and Cox proportional hazard models were used to assess effects of age, sex, influenza subtype, and history of asthma on severity, including hospital admission, need for supplemental oxygen, and length of stay. Retractions, cyanosis, and need for supplemental oxygen were more frequently observed among patients with influenza A(H1N1)pdm09. Headaches and sore throat were more commonly reported among patients with influenza B. Children with influenza A(H1N1)pdm09 and children with asthma had significantly increased odds of hospital admission (adjusted odds ratio (AOR): 1.39, 95% CI: 1.14-1.69 and AOR: 2.14, 95% CI: 1.72-2.67, respectively). During admission, children with influenza A(H1N1)pdm09 had significantly increased use of supplemental oxygen compared to children with A(H3N2) (AOR: 0.60, 95% CI: 0.44-0.82) or B (AOR: 0.56, 95% CI: 0.41-0.76). Among children presenting to the emergency department and admitted to the hospital, influenza A(H1N1)pdm09 caused more severe disease compared to influenza A(H3N2) and influenza B. Asthma also contributed to severe influenza disease regardless of subtype.

Development and validation of a nomogram to predict severe influenza.

Influenza is an acute respiratory disease posing significant harm to human health. Early prediction and intervention in patients at risk of developing severe influenza can significantly decrease mortality. A comprehensive analysis of 146 patients with influenza was conducted using the Gene Expression Omnibus (GEO) database. We assessed the relationship between severe influenza and patients' clinical information and molecular characteristics. First, the variables of differentially expressed genes were selected using R software. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis were performed to investigate the association between clinical information and molecular characteristics and severe influenza. A nomogram was developed to predict the presence of severe influenza. At the same time, the concordance index (C-index) is adopted area under the receiver operating characteristic (ROC), area under the curve (AUC), decision curve analysis (DCA), and calibration curve to evaluate the predictive ability of the model and its clinical application. Severe influenza was identified in 47 of 146 patients (32.20%) and was significantly related to age and duration of illness. Multivariate logistic regression demonstrated significant correlations between severe influenza and myloperoxidase (MPO) level, haptoglobin (HP) level, and duration of illness. A nomogram was formulated based on MPO level, HP level, and duration of illness. This model produced a C-index of 0.904 and AUC of 0.904. A nomogram based on the expression levels of MPO, HP, and duration of illness is an efficient model for the early identification of patients with severe influenza. These results will be useful in guiding prevention and treatment for severe influenza disease.

Healthcare personnel acceptance and recommendations for influenza vaccine in twelve low- and middle-income countries: A pooled analysis from 2018 to 2020

BackgroundAlthough healthcare personnel (HCP) are targeted for influenza vaccination they typically underutilize vaccines especially in low- and middle-income countries. We explored knowledge, attitudes, and practices of HCP about seasonal influenza vaccines (SIV) to identify factors associated with and modifiable barriers to SIV uptake. MethodsWe pooled individual-level data from cross-sectional surveys about SIV conducted among health workers in 12 low- and middle- income countries during 2018–2020 (i.e., Albania, Armenia, Cote d’Ivoire, Kenya, Kyrgyzstan, Lao PDR, Lebanon, Morocco, North Macedonia, Tunisia, Tajikistan, and Uganda). Eleven countries used a standard protocol and questionnaire based on the Health Belief Model to measure perceptions of susceptibility and severity of influenza disease, benefits of, barriers to, and motivators for vaccination. We analyzed attitudes and perceptions among HCP, including acceptance of vaccine for themselves and willingness to recommend vaccines to patients, grouped by the presence/absence of a national influenza vaccination program. Models were adjusted for geographic region. ResultsOur analysis included 10,281 HCP from 12 countries representing four of the six World Health Organization regions: African, Eastern Mediterranean, European, and Western Pacific. The sample was distributed across low income (LIC) (3,183, 31 %), lower-middle (LMIC) (4,744, 46 %), and upper-middle income (UMIC) (2,354, 23 %) countries. Half (50 %) of the countries included in the analysis reported SIV use among HCP in both the year of and the year preceding data collection while the remainder had no influenza vaccination program for HCP. Seventy-four percent (6,341) of HCP reported that they would be willing to be vaccinated if the vaccine was provided free of charge. HCP in LICs were willing to pay prices for SIV representing a higher percentage of their country’s annual health expenditure per capita (6.26 % [interquartile range, IQR: 3.13–12.52]) compared to HCP in LMICs and UMICs. HCP in countries with no SIV program were also willing to pay a higher percentage for SIV (5.01 % [IQR: 2.24–8.34]) compared to HCP in countries with SIV programs.. Most (85 %) HCP in our analysis would recommend vaccines to their patients, and those who would accept vaccines for themselves were 3 times more likely to recommend vaccines to their patients (OR 3.1 [95 % CI 1·8, 5·2]). ConclusionIncreasing uptake of SIV among HCP can amplify positive impacts of vaccination by increasing the likelihood that HCP recommend vaccines to their patients. Successful strategies to achieve increased uptake of vaccines include clear guidance from health authorities, interventions based on behavior change models, and access to vaccine free-of-charge.

MUC5AC: A potential biomarker of severity in pediatric patients infected with influenza.

Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, aprospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild diseasecompared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.

A qualitative assessment of influenza vaccine uptake among children in Kenya

BackgroundInfluenza is a significant contributor to acute respiratory infections (ARI), and children < 5 years are at increased risk of severe influenza disease. In Kenya the influenza vaccine is not included in the Kenya Expanded Programme on Immunization (KEPI). To inform roll-out of a national influenza vaccination program, we implemented an influenza vaccine demonstration project in Nakuru and Mombasa counties in Kenya from 2019 to 2021 and set out to establish factors driving influenza vaccine acceptance and hesitancy among caregivers of children aged 6–23 months. MethodsUsing semi-structured questionnaires, we conducted eight focus group discussions among community members and twelve key informant interviews among healthcare workers to elicit both lay and expert opinions. Thematic analysis of the interviews was conducted using the World Health Organization’s “3 Cs” model of vaccine hesitancy to determine reasons for acceptance or hesitancy of the influenza vaccine. ResultsThe influenza vaccine was well received among community members and healthcare workers though concerns were raised. Vaccine hesitancy was fuelled by misconceptions about reasons for introducing the vaccine (confidence), perceptions that influenza was not a serious disease (complacency) and administrative fees required at some facilities (convenience). Despite the use of various advocacy, communication and social mobilisation strategies targeted at educating the community on the influenza disease and importance of vaccination, there remained a perception of inadequate reach of the sensitization among some community members. Contextual factors such as the COVID-19 pandemic affected uptake, and parents expressed concern over the growing number of vaccines recommended for children. ConclusionDespite lingering concerns, caregivers had their children vaccinated indicating that vaccine hesitancy exists, even among those who accepted the vaccine for their children. Efforts targeted at increasing confidence in and reducing misconceptions towards vaccines through effective communication strategies, are likely to lead to increased vaccine uptake.

Mathematical Modeling Suggests That Monocyte Activity May Drive Sex Disparities during Influenza Infection.

In humans, females of reproductive age often experience a more severe disease during influenza A virus infection, which may be due to differences in their innate immune response. Sex-specific outcomes to influenza infection have been recapitulated in mice, enabling researchers to study viral and immune dynamics in vivo in order to identify immune mechanisms that are differently regulated between the sexes. This study is based on the hypothesis that sex-specific outcomes emerge due to differences in the rates/speeds that select immune components respond. Using publicly available sex-specific murine data, we utilized dynamic mathematical models of the innate immune response to identify candidate mechanisms that may lead to increased disease severity in female mice. We implemented a large computational screen using the Bayesian information criterion (BIC), wherein the goodness of fit of the competing model scenarios is balanced against complexity (i.e., the number of parameters). Our results suggest that having sex-specific rates for proinflammatory monocyte induction by interferon and monocyte inhibition of virus replication provides the simplest (lowest BIC) explanation for the difference observed in the male and female immune responses. Markov-chain Monte Carlo (MCMC) analysis and global sensitivity analysis of the top performing scenario were performed to provide rigorous estimates of the sex-specific parameter distributions and to provide insight into which parameters most affect innate immune responses. Simulations using the top-performing model suggest that monocyte activity could be a key target to reduce influenza disease severity in females. Overall, our Bayesian statistical and dynamic modeling approach suggests that monocyte activity and induction parameters are sex-specific and may explain sex-differences in influenza disease immune dynamics.

Diet-induced obesity affects influenza disease severity and transmission dynamics in ferrets.

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesity's impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.

Specific and Nonspecific Effects of Influenza Vaccines.

With the introduction of the influenza vaccine in the official immunization schedule of most countries, several data regarding the efficacy, tolerability, and safety of influenza immunization were collected worldwide. Interestingly, together with the confirmation that influenza vaccines are effective in reducing the incidence of influenza virus infection and the incidence and severity of influenza disease, epidemiological data have indicated that influenza immunization could be useful for controlling antimicrobial resistance (AMR) development. Knowledge of the reliability of these findings seems essential for precise quantification of the clinical relevance of influenza immunization. If definitively confirmed, these findings can have a relevant impact on influenza vaccine development and use. Moreover, they can be used to convince even the most recalcitrant health authorities of the need to extend influenza immunization to the entire population. In this narrative review, present knowledge regarding these particular aspects of influenza immunization is discussed. Literature analysis showed that the specific effects of influenza immunization are great enough per se to recommend systematic annual immunization of younger children, old people, and all individuals with severe chronic underlying diseases. Moreover, influenza immunization can significantly contribute to limiting the emergence of antimicrobial resistance. The problem of the possible nonspecific effects of influenza vaccines remains unsolved. The definition of their role as inducers of trained immunity seems essential not only to evaluate how much they play a role in the prevention of infectious diseases but also to evaluate whether they can be used to prevent and treat clinical conditions in which chronic inflammation and autoimmunity play a fundamental pathogenetic role.

A protectin DX (PDX) analog with in vitro activity against influenza A(H1N1) viruses.

Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections. However, the emergence of drug resistance and the uncontrolled inflammatory response are major limitations in the treatment of severe influenza disease. Protectins D1 (PD1) and DX (PDX), part of a family of pro-resolving mediators, have previously demonstrated anti-influenza activity as well as anti-inflammatory properties in various clinical contexts. Herein, we synthetized a series of simplified PDX analogs and assessed their in vitro antiviral activity against influenza A(H1N1) viruses, including oseltamivir- and baloxavir-resistant variants. In ST6GalI-MDCK cells, the PDX analog AN-137B reduced viral replication in a dose-dependent manner with IC50 values of 23.8 for A/Puerto Rico/8/1934 (H1N1) and between 32.6 and 36.7 µM for susceptible and resistant A(H1N1)pdm09 viruses. In MTS-based cell viability experiments, AN-137B showed a 50% cellular cytotoxicity (CC50 ) of 638.7 µM with a resulting selectivity index of 26.8. Of greater importance, the combination of AN-137B with oseltamivir or baloxavir resulted in synergistic and additive in vitro effects, respectively. Treatment of lipopolysaccharide (LPS)-stimulated macrophages with AN-137B resulted in a decrease of iNOS activity as shown by the reduction of nitrite production, suggesting an anti-inflammatory effect. In conclusion, our results indicate that the protectin analog AN-137B constitutes an interesting therapeutic modality against influenza A virus, warranting further evaluation in animal models.

Differential lung gene expression changes in C57BL/6 and DBA/2 mice carrying an identical functional Mx1 gene reveals crucial differences in the host response

BackgroundInfluenza virus infections represent a major global health problem. The dynamin-like GTPase MX1 is an interferon-dependent antiviral host protein that confers resistance to influenza virus infections. Infection models in mice are an important experimental system to understand the host response and susceptibility to developing severe disease following influenza infections. However, almost all laboratory mouse strains carry a non-functional Mx1 gene whereas humans have a functional MX1 gene. Most studies in mice have been performed with strains carrying a non-functional Mx1 gene. It is therefore very important to investigate the host response in mouse strains with a functional Mx1 gene.ResultsHere, we analyzed the host response to influenza virus infections in two congenic mouse strains carrying the functional Mx1 gene from the A2G strain. B6.A2G-Mx1r/r(B6-Mx1r/r) mice are highly resistant to influenza A virus (IAV) H1N1 infections. On the other hand, D2(B6).A2G-Mx1r/r(D2-Mx1r/r) mice, although carrying a functional Mx1 gene, were highly susceptible, exhibited rapid weight loss, and died. We performed gene expression analysis using RNAseq from infected lungs at days 3 and 5 post-infection (p.i.) of both mouse strains to identify genes and pathways that were differentially expressed between the two mouse strains. The susceptible D2-Mx1r/r mice showed a high viral replication already at day 3 p.i. and exhibited a much higher number of differentially expressed genes (DEGs) and many DEGs had elevated expression levels compared to B6-Mx1r/r mice. On the other hand, some DEGs were specifically up-regulated only in B6-Mx1r/r mice at day 3 p.i., many of which were related to host immune response functions.ConclusionsFrom these results, we conclude that at early times of infection, D2-Mx1r/r mice showed a very high and rapid replication of the virus, which resulted in lung damage and a hyperinflammatory response leading to death. We hypothesize that the activation of certain immune response genes was missing and that others, especially Mx1, were expressed at a time in D2-Mx1r/r mice when the virus had already massively spread in the lung and were thus not able anymore to protect them from severe disease. Our study represents an important addition to previously published studies in mouse models and contributes to a better understanding of the molecular pathways and genes that protect against severe influenza disease.

Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus

Diabetes mellitus is on the rise globally and is a known susceptibility factor for severe influenza virus infections. However, the mechanisms by which diabetes increases the severity of an influenza virus infection are yet to be fully defined. Diabetes mellitus is hallmarked by high glucose concentrations in the blood. We hypothesized that these high glucose concentrations affect the functionality of CD8+ T cells, which play a key role eliminating virus-infected cells and have been shown to decrease influenza disease severity. To study the effect of hyperglycemia on CD8+ T cell function, we stimulated peripheral blood mononuclear cells (PBMCs) from donors with and without diabetes with influenza A virus, anti-CD3/anti-CD28-coated beads, PMA and ionomycin (PMA/I), or an influenza viral peptide pool. After stimulation, cells were assessed for functionality [as defined by expression of IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1β, and lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed that increasing HbA1c correlated with a reduction in TNF-α production by CD8+ T cells in response to influenza stimulation in a TCR-specific manner. This was not associated with any changes to CD8+ T cell subsets. We conclude that hyperglycemia impairs CD8+ T cell function to influenza virus infection, which may be linked with the increased risk of severe influenza in patients with diabetes.

Obesity amplifies influenza virus-driven disease severity in male and female mice

Influenza virus-induced respiratory pneumonia remains a major public health concern. Obesity, metabolic diseases, and female sex are viewed as independent risk factors for worsened influenza virus-induced lung disease severity. However, lack of experimental models of severe obesity in female mice limits discovery-based studies. Here, via utility of thermoneutral housing (30°C) and high-fat diet (HFD) feeding, we induced severe obesity and metabolic disease in female C57BL/6 mice and compared their responses to severely obese male C57BL/6 counterparts during influenza virus infection. We show that lean male and female mice have similar lung edema, inflammation, and immune cell infiltration during influenza virus infection. At standard housing conditions, HFD-fed male, but not female, mice exhibit severe obesity, metabolic disease, and exacerbated influenza disease severity. However, combining thermoneutral housing and HFD feeding in female mice induces severe obesity and metabolic disease, which is sufficient to amplify influenza virus-driven disease severity to a level comparable to severely obese male counterparts. Lastly, increased total body weights of male and female mice at time of infection correlated with worsened influenza virus-driven disease severity metrics. Together, our findings confirm the impact of obesity and metabolic disease as key risk factors to influenza disease severity and present a novel mouse experimental model suitable for future mechanistic interrogation of sex, obesity, and metabolic disease traits in influenza virus-driven disease severity.

Diverse roles of lung macrophages in the immune response to influenza A virus.

Influenza viruses are one of the major causes of human respiratory infections and the newly emerging and re-emerging strains of influenza virus are the cause of seasonal epidemics and occasional pandemics, resulting in a huge threat to global public health systems. As one of the early immune cells can rapidly recognize and respond to influenza viruses in the respiratory, lung macrophages play an important role in controlling the severity of influenza disease by limiting viral replication, modulating the local inflammatory response, and initiating subsequent adaptive immune responses. However, influenza virus reproduction in macrophages is both strain- and macrophage type-dependent, and ineffective replication of some viral strains in mouse macrophages has been observed. This review discusses the function of lung macrophages in influenza virus infection in order to better understand the pathogenesis of the influenza virus.

Impact of Influenza Vaccination on the Burden of Severe Influenza in the Elderly: Spain, 2017-2020.

Annual influenza vaccination is the main strategy to reduce the burden of seasonal influenza epidemics and is recommended for the elderly in most countries with influenza vaccination strategies, with the main objective of preventing hospitalizations and mortality associated with seasonal influenza in this age group. Studies from different countries have estimated the benefits of seasonal influenza vaccination programs in the elderly, preventing a considerable number of cases, hospitalizations and deaths every year. A study measured the number of medically attended confirmed influenza cases in primary care that are prevented annually by vaccination in the population aged 65 and older in Spain, the Netherlands and Portugal, but estimates of the impact of the national influenza vaccination program in the prevention of severe disease in Spain are lacking. The two objectives of this study were to estimate the burden of severe influenza disease in the Spanish population and to measure the impact of influenza vaccination in the prevention of these outcomes in the population aged 65 years and older. Using influenza surveillance systems put in place before the COVID-19 pandemic, we conducted a retrospective observational study to estimate the burden of hospitalizations and ICU admissions in Spain between 2017-18 and 2019-20, by season and age group. Burden estimates for the 65+ group, combined with vaccine effectiveness (VE) and vaccination coverage (VC) data, were used as input data in an ecological, observational study to estimate the impact of the influenza vaccination program on the elderly. We found a higher burden of severe influenza disease in seasons 2017-18 and 2018-19, with A(H3N2) circulation, and in the youngest and oldest age groups. In those aged 65 and older, we estimated an average of 9900 influenza hospitalizations and 1541 ICU admissions averted by vaccination each year. Seasonal influenza vaccination was able to prevent between 11 and 26% influenza hospitalizations and around 40% ICU admissions in the elderly in the three pre-pandemic seasons. In conclusion, our study complements previous analyses in the primary care setting in Spain and demonstrates the benefits of the annual influenza vaccination program in the prevention of severe influenza disease in the elderly, even in seasons with moderate VE.

Group 1 and group 2 hemagglutinin stalk antibody response according to age.

Antibodies elicited by seasonal influenza vaccines mainly target the head of hemagglutinin (HA). However, antibodies against the stalk domain are cross-reactive and have been proven to play a role in reducing influenza disease severity. We investigated the induction of HA stalk-specific antibodies after seasonal influenza vaccination, considering the age of the cohorts. A total of 166 individuals were recruited during the 2018 influenza vaccine campaign (IVC) and divided into groups: <50 (n = 14), 50-64 (n = 34), 65-79 (n = 61), and ≥80 (n = 57) years old. Stalk-specific antibodies were quantified by ELISA at day 0 and day 28 using recombinant viruses (cH6/1 and cH14/3) containing an HA head domain (H6 or H14) from wild bird origin with a stalk domain from human H1 or H3, respectively. The geometric mean titer (GMT) and the fold rise (GMFR) were calculated, and differences were assessed using ANOVA adjusted by the false discovery rate (FDR) and the Wilcoxon tests (p <0.05). All age groups elicited some level of increase in anti-stalk antibodies after receiving the influenza vaccine, except for the ≥80-year-old cohort. Additionally, <65-year-old vaccinees had higher group 1 antibody titers versus group 2 before and after vaccination. Similarly, vaccinees within the <50-year-old group showed a higher increase in anti-stalk antibody titers when compared to older individuals (≥80 years old), especially for group 1 anti-stalk antibodies. Seasonal influenza vaccines can the induction of cross-reactive anti-stalk antibodies against group 1 and group 2 HAs. However, low responses were observed in older groups, highlighting the impact of immunosenescence in adequate humoral immune responses.

Invasive pulmonary aspergillosis in the intensive care unit: current challenges and best practices.

The prevalence of invasive pulmonary aspergillosis (IPA) is growing in critically ill patients in the intensive care unit (ICU). It is increasingly recognized in immunocompetent hosts and immunocompromised ones. IPA frequently complicates both severe influenza and severe coronavirus disease 2019 (COVID-19) infection. It continues to represent both a diagnostic and therapeutic challenge and can be associated with significant morbidity and mortality. In this narrative review, we describe the epidemiology, risk factors and disease manifestations of IPA. We discuss the latest evidence and current published guidelines for the diagnosis and management of IPA in the context of the critically ill within the ICU. Finally, we review influenza-associated pulmonary aspergillosis (IAPA), COVID-19-associated pulmonary aspergillosis (CAPA) as well as ongoing and future areas of research.

Australian hospital paediatricians and nurses' perspectives and practices for influenza vaccine delivery in children with medical comorbidities.

Influenza vaccination of children with medical comorbidities is critical due their increased risks for severe influenza disease. In Australia, hospitals are an avenue for influenza vaccine delivery to children with comorbidities but are not always effectively utilised. Qualitative enquiry sought to ascertainment the barriers and enablers for influenza vaccination recommendation, delivery, and recording of these children at Australian hospitals. Semi-structured interviews and discussion group sessions were conducted with paediatricians and nurses at four tertiary paediatric specialist hospitals and two general community hospitals in three Australian states. Transcripts from interviews and group sessions were inductively analysed for themes. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was used to explore the elements of each theme and identify potential interventions to increase influenza vaccination recommendation and delivery behaviours by providers. Fifteen discussion sessions with 28 paediatricians and 26 nurses, and nine in-depth interviews (five paediatricians and four nurses) were conducted. Two central thematic domains were identified: 1. The interaction between hospital staff and parents/patients for influenza vaccine recommendation, and 2. Vaccination delivery and recording in the hospital environment. Six themes across these domains emerged detailing the importance of dedicated immunisation services, hospital leadership, paediatricians' vaccine recommendation role, the impact of comorbidities, vaccination recording, and cocooning vaccinations. Supportive hospital leadership, engaged providers, and dedicated immunisation services were identified as essential for influenza vaccination of children with comorbidities in Australian hospital. Recommendation of influenza vaccination for Australian children with comorbidities is impacted by the beliefs of paediatricians and the perceived impact of influenza disease on children's comorbidities. Dedicated immunisation services and supportive hospital leadership were drivers for influenza vaccine delivery at hospitals. Future interventions targeting hospital-based influenza vaccine delivery for children with comorbidities should take a rounded approach targeting providers' attitudes, the hospital environment and leadership support.

Pulmonary aspergillosis: diagnosis and treatment.

Aspergillus species are the most frequent cause of fungal infections of the lungs with a broad spectrum of clinical presentations including invasive pulmonary aspergillosis (IPA) and chronic pulmonary aspergillosis (CPA). IPA affects immunocompromised populations, which are increasing in number and diversity with the advent of novel anti-cancer therapies. Moreover, IPA has emerged as a complication of severe influenza and coronavirus disease 2019 in apparently immunocompetent hosts. CPA mainly affects patients with pre-existing lung lesions and is recognised increasingly frequently among patients with long-term survival following cure of tuberculosis or lung cancer. The diagnosis of pulmonary aspergillosis is complex as it relies on the presence of clinical, radiological and microbiological criteria, which differ according to the type of pulmonary aspergillosis (IPA or CPA) and the type of patient population. The management of pulmonary aspergillosis is complicated by the limited number of treatment options, drug interactions, adverse events and the emergence of antifungal resistance.

Vital Signs: Influenza Hospitalizations and Vaccination Coverage by Race and Ethnicity-United States, 2009-10 Through 2021-22 Influenza Seasons.

CDC estimates that influenza resulted in 9-41 million illnesses, 140,000-710,000 hospitalizations, and 12,000-52,000 deaths annually during 2010-2020. Persons from some racial and ethnic minority groups have historically experienced higher rates of severe influenza and had lower influenza vaccination coverage compared with non-Hispanic White (White) persons. This report examines influenza hospitalization and vaccination rates by race and ethnicity during a 12-13-year period (through the 2021-22 influenza season). Data from population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected states participating in the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET) from the 2009-10 through 2021-22 influenza seasons (excluding 2020-21) and influenza vaccination coverage data from the Behavioral Risk Factor Surveillance System (BRFSS) from the 2010-11 through 2021-22 influenza seasons were analyzed by race and ethnicity. From 2009-10 through 2021-22, age-adjusted influenza hospitalization rates (hospitalizations per 100,000 population) were higher among non-Hispanic Black (Black) (rate ratio [RR]=1.8), American Indian or Alaska Native (AI/AN; RR=1.3), and Hispanic (RR=1.2) adults, compared with the rate among White adults. During the 2021-22 season, influenza vaccination coverage was lower among Hispanic (37.9%), AI/AN (40.9%), Black (42.0%), and other/multiple race (42.6%) adults compared with that among White (53.9%) and non-Hispanic Asian (Asian) (54.2%) adults; coverage has been consistently higher among White and Asian adults compared with that among Black and Hispanic adults since the 2010-11 season. The disparity in vaccination coverage by race and ethnicity was present among those who reported having medical insurance, a personal health care provider, and a routine medical checkup in the past year. Racial and ethnic disparities in influenza disease severity and influenza vaccination coverage persist. Health care providers should assess patient vaccination status at all medical visits and offer (or provide a referral for) all recommended vaccines. Tailored programmatic efforts to provide influenza vaccination through nontraditional settings, along with national and community-level efforts to improve awareness of the importance of influenza vaccination in preventing illness, hospitalization, and death among racial and ethnic minority communities might help address health care access barriers and improve vaccine confidence, leading to decreases in disparities in influenza vaccination coverage and disease severity.