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December 2013

Co-morbidities associated with influenza-attributed mortality, 1994-2000, Canada.

The elderly and persons with specific chronic conditions are known to face elevated morbidity and mortality risks resulting from an influenza infection, and hence are routinely recommended for annual influenza vaccination. However, risk-specific mortality rates have not been established. We estimated age-specific influenza-attributable mortality rates stratified by the presence of chronic conditions and type of residence based on deaths of persons who were admitted to hospital with a respiratory complication captured in our national database. The majority of patients had chronic heart or respiratory conditions (80%) and were admitted from the community (80%). Influenza-attributable mortality rates clearly increase with age for all risk groups. Our influenza-specific estimates identified higher risk ratios for chronic lung or heart disease than have been suggested by other methods. These estimates identify groups most in need of improved vaccines and for whom the use of additional strategies, such as immunization of household contacts or caregivers should be considered.

Vaccine. 2008 Aug 26;26(36):4697-703

Immunosenescence and Challenges of Vaccination against Influenza in the Aging Population.

Influenza is an important contributor to morbidity and mortality worldwide. Accumulation of genetic mutations termed antigenic drift, allows influenza viruses to inflict yearly epidemics that may result in 250,000 to 500,000 deaths annually. Over 90% of influenza-related deaths occur in the older adult population. This is at least in part a result of increasing dysregulation of the immune system with age, termed immunosenescence. This dysregulation results in reduced capacity to cope with infections and decreased responsiveness to vaccination. The older adult population is in dire need of improved vaccines capable of eliciting protective responses in the face of a waning immune system. This review focuses on the status of immunity, responses to influenza vaccination, and strategies that are currently being explored to elicit enhanced immune responses in this high risk population.

Aging Dis. 2012 Feb;3(1):68-90

Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach.

Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.

Expert Rev Vaccines. 2012 Aug;11(8):985-94

Interim adjusted estimates of seasonal influenza vaccine effectiveness - United States, February 2013.

Early influenza activity during the 2012-13 season enabled estimation of the unadjusted effectiveness of the seasonal influenza vaccine. This report presents updated adjusted estimates based on 2,697 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness (Flu VE) Network during December 3, 2012-January 19, 2013. During this period, overall vaccine effectiveness (VE) (adjusted for age, site, race/ethnicity, self-rated health, and days from illness onset to enrollment) against influenza A and B virus infections associated with medically attended acute respiratory illness was 56%, similar to the earlier interim estimate (62%). VE was estimated as 47% against influenza A (H3N2) virus infections and 67% against B virus infections. When stratified by age group, the point estimates for VE against influenza A (H3N2) and B infections were largely consistent across age groups, with the exception that lower VE against influenza A (H3N2) was observed among adults aged ≥65 years. These adjusted VE estimates indicate that vaccination with the 2012-13 influenza season vaccine reduced the risk for outpatient medical visits resulting from influenza by approximately one half to two thirds for most persons, although VE was lower and not statistically significant among older adults. Antiviral medications should be used as recommended for treatment of suspected influenza in certain patients, including those aged ≥65 years, regardless of their influenza vaccination status.

MMWR Morb Mortal Wkly Rep. 2013 Feb 22;62(7):119-23

Enhancement of antigen-specific immunoglobulin G production in mice by co-administration of L-cystine and L-theanine.

Supplementation with both cystine and glutamic acid increases the synthesis of glutathione (GSH), which has a marked effect on immune cell function, as compared with supplementation with either amino acid alone in human macrophages in vitro. As dietary glutamic acid is metabolized during intestinal transport, oral administration of L-theanine (gamma-glutamylethylamide), which is metabolized to glutamic acid mainly in the liver, may act as a glutamic acid donor in vivo. The present study was performed to investigate the effects of oral administration of L-cystine and/or L-theanine on GSH levels and immune responses. Co-administration of L-cystine (200 mg/kg) and L-theanine (80 mg/kg) for 11 days before immunization significantly increased the levels of total GSH in the liver 6 hr after immunization as compared with the levels in control mice. To examine the effects of administration of L-cystine and/or L-theanine on the balance of T helper (Th) 1/Th2 cell responses, the serum ratios of the Th1 cytokine, interferon (IFN)-gamma, and the Th2 cytokine, interleukin IL-10, were investigated. At 24 hr after immunization, co-administration significantly increased the IL-10/IFN-gamma ratio compared with the ratios of the control and single-administration mice. Furthermore, co-administration before primary immunization significantly enhanced serum antigen-specific IgG levels. Taken together, these findings suggest that co-administration of L-cystine and L-theanine enhances antigen-specific IgG production partly through augmentation of GSH levels and Th2-mediated responses.

J Vet Med Sci. 2007 Dec;69(12):1263-70

Clinical relevance of age-related immune dysfunction.

Immunosenescence is the state of dysregulated immune function that contributes to the increased susceptibility to infection of the elderly. Extensive studies of inbred laboratory animals and very healthy elderly humans have identified changes in immunity; these studies have identified limited phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will attempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza virus vaccination and how chronic illness contributes to increased risk and severity of infection and/or failed vaccine response. Second, key changes in immunity will be reviewed, keeping a perspective of the impact of confounding variables in addition to age but focusing on age-related changes in the interaction of the innate and acquired components of immunity. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology and/or infectious diseases is faced with the tremendous challenge of studying a very diverse population, including mildly immunocompromised/chronically ill individuals and very healthy elderly.

Clin Infect Dis. 2000 Aug;31(2):578-85

Complications of viral influenza.

Viral influenza is a seasonal infection associated with significant morbidity and mortality. In the United States more than 35,000 deaths and 200,000 hospitalizations due to influenza occur annually, and the number is increasing. Children aged less than 1 year and adults aged more than 65 years, pregnant woman, and people of any age with comorbid illnesses are at highest risk. Annual vaccination is the cornerstone of prevention, but some older patients may derive less benefit from immunization than otherwise fit individuals. If started promptly, antiviral medications may reduce complications of acute influenza, but increasing resistance to amantadine and perhaps neuraminidase inhibitors underscores the need for novel prevention and treatment strategies. Pulmonary complications of influenza are most common and include primary influenza and secondary bacterial infection. Either may cause pneumonia, and each has a unique clinical presentation and pathologic basis. Staphylococcus aureus, including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with high mortality. During influenza season, treatment of pneumonia should include empiric coverage for this pathogen. Neuromuscular and cardiac complications are unusual but may manifest in persons of any age.

Am J Med. 2008 Apr;121(4):258-64

Avian influenza virus (H5N1): a threat to human health.

Pandemic influenza virus has its origins in avian influenza viruses. The highly pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry, with attendant economic consequences. It continues to cross species barriers to infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus has rightly received attention as a potential pandemic threat. However, it is noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic influenza viruses, and the next pandemic may well arise from a low-pathogenicity virus. The rationale for particular concern about an H5N1 pandemic is not its inevitability but its potential severity. An H5N1 pandemic is an event of low probability but one of high human health impact and poses a predicament for public health. Here, we review the ecology and evolution of highly pathogenic avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of human H5N1 disease in relation to its epidemiology, clinical presentation, pathogenesis, diagnosis, and management.

Clin Microbiol Rev. 2007 Apr;20(2):243-67

Cardiac findings during uncomplicated acute influenza in ambulatory adults.

BACKGROUND: Previous studies have reported abnormal cardiac findings in up to 43% of ambulatory adults with influenza. This study was conducted to determine the frequency, magnitude, and duration of myocardial dysfunction in such persons. METHODS: We enrolled 30 previously healthy young adults without known cardiovascular disease who presented to the clinic <or=72 h after onset of influenza symptoms and had a positive influenza antigen test. Most patients received antiviral therapy, and all underwent serial electrocardiography and had blood specimens collected on days 1, 4, 11, and 28 after presentation for measurement of total creatine kinase (CK) level, CK isoenzyme MB (CK-MB) level, troponin I level, and selected cytokine levels. Echocardiography was performed on days 4, 11, and 28. RESULTS: None of the patients had an elevated CK-MB index or troponin I level. Abnormal electrocardiogram findings were noted in 53%, 33%, 27%, and 23% of patients on days 1, 4, 11, and 28, respectively, but none of the findings were considered to be clinically significant. No patient had significant changes in the ejection fraction or abnormal wall motions. CONCLUSIONS: Most ambulatory young adults with acute influenza have clinically insignificant abnormal electrocardiogram findings early during the illness. These abnormalities resolve promptly and are not associated with changes in cardiac markers or echocardiogram findings.

Clin Infect Dis. 2005 Feb 1;40(3):415-22

Feeding the immune system.

A well-functioning immune system is key to providing good defence against pathogenic organisms and to providing tolerance to non-threatening organisms, to food components and to self. The immune system works by providing an exclusion barrier, by identifying and eliminating pathogens and by identifying and tolerating non-threatening sources of antigens, and by maintaining a memory of immunological encounters. The immune system is complex involving many different cell types distributed throughout the body and many different chemical mediators some of which are involved directly in defence while others have a regulatory role. Babies are born with an immature immune system that fully develops in the first few years of life. Immune competence can decline with ageing. The sub-optimal immune competence that occurs early and late in life increases susceptibility to infection. Undernutrition decreases immune defences, making an individual more susceptible to infection. However, the immune response to an infection can itself impair nutritional status and alter body composition. Practically all forms of immunity are affected by protein-energy malnutrition, but non-specific defences and cell-mediated immunity are most severely affected. Micronutrient deficiencies impair immune function. Here, vitamins A, D and E, and Zn, Fe and Se are discussed. The gut-associated lymphoid tissue is especially important in health and well-being because of its close proximity to a large and diverse population of organisms in the gastrointestinal tract and its exposure to food constituents. Certain probiotic bacteria which modify the gut microbiota enhance immune function in laboratory animals and may do so in human subjects.

Proc Nutr Soc. 2013 Aug;72(3):299-309