Severity Of Influenza Illness Research Articles

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 Influenza Season.

SummaryThis report updates the 2019–20 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2019;68[No. RR-3]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) are expected to be available. Most influenza vaccines available for the 2020–21 season will be quadrivalent, with the exception of MF59-adjuvanted IIV, which is expected to be available in both quadrivalent and trivalent formulations.Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 23, 2019; February 26, 2020; and June 24, 2020. Primary updates to this report include the following two items. First, the composition of 2020–21 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Victoria lineage components. Second, recent licensures of two new influenza vaccines, Fluzone High-Dose Quadrivalent and Fluad Quadrivalent, are discussed. Both new vaccines are licensed for persons aged ≥65 years. Additional changes include updated discussion of contraindications and precautions to influenza vaccination and the accompanying Table, updated discussion concerning use of LAIV4 in the setting of influenza antiviral medication use, and updated recommendations concerning vaccination of persons with egg allergy who receive either cell culture–based IIV4 (ccIIV4) or RIV4.The 2020–21 influenza season will coincide with the continued or recurrent circulation of SARS-CoV-2 (the novel coronavirus associated with coronavirus disease 2019 [COVID-19]). Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient illnesses, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html.This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2020–21 season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration (FDA)–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check this site periodically for additional information.

Clinical characteristics and severity of influenza infections by virus type, subtype, and lineage: A systematic literature review.

AimStudies carried out in the early 2000s found that the number of influenza‐associated hospitalizations and deaths was highest in seasons dominated by A(H3N2), suggesting that the clinical presentation and severity of influenza may differ across virus types, subtypes, and lineages. We aimed to review the studies that examined this hypothesis.MethodWe conducted a literature review of studies published until January 2017 that compared the clinical presentation, disease severity, and case‐fatality ratio of influenza patients infected with different virus types (A, B), subtypes (pre‐pandemic A(H1N1), A(H1N1)p, A(H3N2)), and lineages (Victoria, Yamagata).ResultsThe literature search resulted in over 1700 entries: After applying in‐ and exclusion criteria, 47 studies were included in the literature review. Studies showed a wide diversity in setting and populations. Only a minority of studies provided results adjusted by patient's age and other potential confounders. There were very few differences in the clinical presentation of patients infected with different influenza viruses. We found weak evidence that the A(H1N1)p subtype in the post‐pandemic period was more often associated with secondary bacterial pneumonia, ICU admission, and death, than the other influenza virus (sub)types.ConclusionContrary to what is commonly assumed, the causal virus subtype does not seem to be a major determinant of clinical presentation and severity of influenza illness. However, drawing conclusions was made difficult by the low comparability and methodological shortcomings of included studies, and more well‐designed studies are warranted.

Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study

The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa. We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]). The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02-7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09-11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security). HIV is an important risk factor for influenza-associated ILI and severe presentation in this high-HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.

The impact of HIV infection on the burden and severity of influenza illness in Malawian adults

The impact of HIV infection on the burden and severity of influenza illness in Malawian adults

Impact of HIV on the burden and severity of influenza illness in adults in Malawi: a cohort and case-control study

BackgroundAlthough annual vaccination of at-risk groups is the cornerstone of influenza prevention in many developed settings, it is unavailable in most sub-Saharan African countries. Since 70% of the estimated total population of HIV-infected persons reside in these countries, they might be an important group for whom policy makers could target influenza control strategies. This study aimed to determine the impact of HIV on the burden and severity of influenza illness in adults in a setting with high HIV prevalence. MethodsAt the Queen Elizabeth Central Hospital, Blantyre, Malawi, we conducted a prospective cohort study between April 1, 2013, and March 31, 2015, to compare influenza incidence between HIV-infected and HIV-uninfected adults. We also did a case-control study of adults with mild influenza (influenza-like illness) and severe influenza (admission to hospital with lower respiratory tract infection) to explore risk factors for severe influenza presentation. Poisson and unconditional logistic regression models, respectively, were performed. Findings608 adults were enrolled in the cohort study, of whom 360 (59%) were HIV-reactive (median CD4 count 390 cells per μL [IQR 244–547]). 24 (11%) of 229 episodes of influenza-like illness in HIV-infected and five (4%) of 119 in HIV-uninfected adults were influenza PCR positive (incidence rates 46 vs 15 per 1000 person-years, incidence rate ratio 2·75 [95% CI 1·02–7·44]). In the case-control study, 56 (11%) of 518 patients admitted with lower respiratory tract infection and 88 (14%) of 642 patients with influenza-like illness were influenza PCR positive. HIV prevalence in the influenza-positive cases and controls were 70% (39/56) and 30% (26/88), respectively. HIV was a significant risk factor for severe influenza presentation (odds ratio 4·98 [95% CI 2·09–11·88], population attributable fraction 57%). There was a tendency towards increased incidence and severity in individuals with CD4 count less than 200 cells per μL. InterpretationIn a setting with high HIV prevalence, HIV infection is an important risk factor for acquiring influenza infection and for severe presentation. Individuals with advanced immunosuppression can be particularly vulnerable. These results present a strong case to policy makers to consider targeted vaccination policy in HIV-infected adults in sub-Saharan Africa. However, the optimum mechanism for vaccine introduction and evaluation in overstretched health systems will need to be determined. FundingWellcome Trust.

The impact of HIV on the burden and severity of influenza illness in Malawian adults: The bash-flu study

The impact of HIV on the burden and severity of influenza illness in Malawian adults: The bash-flu study

Disparities in the Severity of Influenza Illness

To investigate the association between socioeconomic status (SES) and hospitalization for 2009 H1N1 influenza, independently of access to care and known risk factors for severe influenza illness, among New York City residents during the 2009-2010 influenza season. We used a 1:2 case-control study design, matching by age group and month of diagnosis. Cases were defined as laboratory-confirmed patients with 2009 H1N1 influenza who were hospitalized during their illness. Controls were defined as nonhospitalized laboratory-confirmed influenza A patients. Participants were contacted for a telephone interview to collect relevant clinical and demographic data. We used conditional logistic regression to analyze the association between SES and hospitalization. New York City. Of the 171 hospitalized cases who were identified between October 2009 and February 2010, a total of 128 completed telephone interviews. A total of 640 nonhospitalized controls were contacted, and of these, 337 completed interviews. The main outcome of interest was whether or not a patient was hospitalized during his or her 2009 H1N1 influenza illness. Socioeconomic status was measured using education and neighborhood poverty. We identified a gradient in the odds of hospitalization for 2009 H1N1 influenza by education level among adults. This association could not be entirely explained by access to care and underlying risk factors. An inverse association between odds of hospitalization and neighborhood poverty was also identified among adults and children. This study suggests that individuals of lower SES were more vulnerable to severe illness during the 2009 H1N1 pandemic. Additional research is needed to help guide interventions to protect this population during future influenza pandemics.

Influenza and HIV: Lessons from the 2009 H1N1 Influenza Pandemic

Influenza is a common respiratory disease in adults, including those infected with HIV. In the spring of 2009, a pandemic influenza A (H1N1) virus (pH1N1) emerged. In this article, we review the existing literature regarding pH1N1 virus infection in HIV-infected adults, which suggests that susceptibility to pH1N1 virus infection and severity of influenza illness are likely not increased in HIV-infected adults without advanced immunosuppression or comorbid conditions. The risk of influenza-related complications, however, may be increased in those with advanced immunosuppression or high-risk comorbid conditions. Prevention and treatment of high-risk comorbid conditions and annual influenza vaccination should continue to be part of HIV clinical care to help prevent influenza illness and complications. Additional information about pH1N1 vaccine immunogenicity and efficacy in HIV-infected patients would be useful to guide strategies to prevent influenza virus infection in this population.

Factors associated with influenza vaccination status of residents of a rural community in Japan

BackgroundThe rate of influenza vaccination in Japan has declined over the past several decades. It is essential to identify community-specific factors that affect attitudes toward vaccination, but such parameters have not yet been fully determined in Japan. The present study used the Health Belief Model (HBM) to identify perceptions of influenza vaccination in a rural Japanese community.MethodsAll subjects were residents of a rural town in the southern part of Kyoto, Japan. An anonymous self-administered questionnaire was mailed to 846 randomly chosen households (containing 2,665 subjects). The survey explored gender, age, history of influenza, and factors associated with obtaining influenza vaccination, based on the HBM.ResultsA total of 1,182 valid responses (response rate, 44.4%) were received. Sources of information that were associated with vaccination decisions were medical facilities for children (OR = 4.21; 95% CI: 1.17-15.1), workplaces for adults (OR = 2.40; 95% CI: 1.22-4.75), medical facilities, town office and family for elderly subjects (OR = 6.18; 95% CI: 2.42-15.7, OR = 5.59; 95% CI: 2.26-13.8 and OR = 3.29; 95%CI: 1.01-10.6). Subjects, in all age groups, who strongly agreed that the vaccine was effective were significantly more likely to be vaccinated (OR = 10.5; 95%CI: 2.68-41.7 for children; OR = 8.85; 95%CI: 4.61-16.9 for adults; OR = 19.9; 95%CI: 8.28-48.0 for the elderly). The vaccination rate of elderly subjects who expressed concerns regarding adverse vaccine effects (OR = 0.34, 95% CI: 0.15-0.78) or who were worried about practical barriers to the vaccination process (OR = 0.13; 95% CI: 0.05-0.31) was significantly lower than in other populations.ConclusionsOur results indicate that vaccination coverage can be increased if accurate information on personal risk, severity of influenza illness, and efficacy of vaccination are provided by responsible information sources that are easily accessible. Such sources include medical facilities and municipal offices. In addition, barriers and inconveniences associated with vaccination should be removed, especially if they impact on elderly people.

Human Genes and Influenza

Why some individuals resist infection or recover quickly, whereas others experience severe disease associated with infection, is a fundamental question that medicine has struggled to answer. Pathogens and host immune factors have been extensively investigated for many infectious diseases, to address these questions. However, limited information is available concerning the influence of host genetics on the response to viral infections. Genetic determinants have the potential to play a role at numerous points during the course of viral infection, including viral attachment and entry, replication, disease progression and development of severity, and, finally, transmission. In this issue of the Journal, Albright et al. [1] propose that the severity of influenza illness may have a heritable component. To investigate this hypothesis, the authors used as a resource the Utah Population Data Base, which contains data from founding families and their descendants, comprised primarily of members of the Church of Jesus Christ of Latter-Day Saints (i.e., Mormons), thus representing a relatively ethnically homogeneous population. Albright et al. [1] estimated the relative risk (RR) of death for relatives of 4855 individuals (spanning 3 generations) who died of influenza. A substantial proportion of deaths occurred during the 1918 influenza pandemic, when a total of 1937 deaths were documented between 1918 and 1921, and 1293 additional deaths occurred between 1922–1932, followed by a dramatic decrease in the number of deaths occurring annually. The RR of death for first-degree relatives was 1.54 (P .0001). The RR was higher for spouses (1.98) and for secondand third-degree relatives (1.22 and 1.16, respectively). The timing of the deaths of third-degree relatives suggests that the deaths were not the result of a common exposure. To control for shared environment, the RR of death for spouses’ relatives was compared and was found to be lower for first-, second-, and third-degree relatives. Excess relatedness among individuals dying of influenza was estimated using the Geneological Index of Familiality, which demonstrated that relatedness among these individuals, including individuals who died during the 1918 pandemic, was greater than expected (P .001). The analysis was repeated with close relatives excluded (to control for shared environment), and the results were consistent with previous findings. Consistent results were not observed when the same analysis was repeated for individuals with diphtheria-associated deaths. For such individuals, excess relatedness was demonstrated; however, when close relationships were excluded, no excess relatedness was detected. Specific genes responsible for the host immune response have been invoked as major determinants of the clinical course of HIV-associated disease and hepatitis B and C virus infections [2, 3]. However, there is very little information with respect to genetic determinants as they relate to severe influenza. Over the past decade, a greater understanding of the immune evasion strategies of influenza virus has developed. This knowledge can be used to propose several candidate genes that may be responsible for severe illness. Clinical and animal studies indicate that cytokine dysregulation is associated with acute respiratory distress syndrome and death among hosts infected with avian influenza virus (H5N1) [4 – 6]. Toll-like receptors (TLRs), particularly TLR3 (which recognizes double-stranded RNA) and TLR7 and TLR8 (which recognize single-stranded RNA), are central to antiviral innate immunity [7]. Singlenucleotide polymorphisms in TLR genes are not uncommon and vary among populations [8]. TLR4 has been implicated in the innate immune response to respiratory syncytial virus (RSV) infection, and polymorphisms in the TLR4 gene have Received 5 July 2007; accepted 5 July 2007; electronically published 7 December 2007. Potential conflicts of interest: none reported. Financial support: W. M. Keck Foundation (to P.P.); National Institutes of Health (grant P01 AI158113 to P.P.); Northeast Biodefense Center (grant U54 AI057158 to P.P.); Center for Investigating Viral Immunity and Antagonism (grants U19 AI62623 and U01 CI 000354 [R21 to P.P.]); Ruth L. Kirschstein Physician Scientist Research Training in Pathogenesis of Viral Diseases Award (to S.M.); Sunnybrook Health Sciences Centre, University of Toronto, Canada (salary support to S.M.). Reprints or correspondence: Dr. Samira Mubareka, Dept. of Microbiology, Mount Sinai School of Medicine, 1 Gustave Levy Pl., Box 1124, New York, NY 10029 (samira.mubareka@mssm.edu). The Journal of Infectious Diseases 2008; 197:1–3 © 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19701-0001$15.00 DOI: 10.1086/524067 E D I T O R I A L C O M M E N T A R Y

Clinical Efficacy and Safety of the Orally Inhaled Neuraminidase Inhibitor Zanamivir in the Treatment of Influenza: a Randomized, Double-blind, Placebo-controlled European Study

Objectives: To assess the clinical efficacy and safety of orally inhaled zanamivir in the treatment of influenza in a European primary care setting.Methods: This was a randomized, double-blind, placebo-controlled trial in primary care and hospital clinics in 11 European countries. Patients aged ≥ 12 years were recruited within 2 days of onset of typical influenza symptoms and received orally inhaled zanamivir 10 mg via a DiskhalerTMtwice daily for 5 days or matching placebo. Influenza symptoms and temperature were recorded daily for 14 days. The primary endpoint was time to alleviation of clinically significant symptoms of influenza. Other endpoints included symptom severity, use of relief medications, time to return to normal activities, complications and investigator’s assessment of symptoms.Results: A total of 356 patients were recruited; 277 (78%) had laboratory-confirmed influenza and 32 (9%) were considered high-risk (i.e. elderly or with underlying medical conditions). Zanamivir significantly reduced the time to alleviation of symptoms versus placebo (median 5 days versus 7.5 days, P< 0.001), a 33% reduction in duration of illness. Zanamivir significantly reduced the severity of several symptoms; improvements versus placebo were discernible after approximately 24 h. The proportion of patients who were afebrile after 24 h increased by 46% versus placebo. Similar treatment benefits were observed in the high-risk patients. Zanamivir was well tolerated, with an adverse event profile similar to that of placebo.Conclusions: Zanamivir is effective in reducing the duration and severity of influenza illness and is well tolerated. Zanamivir should therefore be a clinically valuable intervention in the management of influenza.

Assessment of signs of influenza illness in the ferret model

The ferret model of influenza A infection was evaluated to determine whether physical signs of influenza illness in addition to fever could be adequately followed. Ferrets were evaluated for nasal and systemic signs of influenza infection in a blinded, randomized protocol. Nasal signs were scored depending on the degree of nasal discharge and congestion. Systemic signs were evaluated on the basis of the activity level of ferrets. Nasal and systemic signs in ferrets challenged with influenza began to rise at peak virus shedding. This rise was coincident with the onset of the nasal inflammatory cell response. Nasal and systemic signs were statistically higher in challenged ferrets as compared with controls from 28 to 52 h after infection [ P = 0.002 except at 28 h ( P = 0.01)]. Despite precautions against influenza transmission, controls shed influenza virus associated with mild increases in nasal and systemic signs late in the course of the study. Our results suggest that severity of influenza illness can be adequately assessed in the ferret model using collective measurements of nasal and systemic signs, temperatures, and nasal cellular infiltration.