Influenza
Influenza is an important threat to the health of older adults. Each year, it is estimated that 36,000 older adults in the United States die of influenza and pneumonia with the majority of these occurring in persons 65 years and older. Despite immunization, outbreaks of influenza occur regularly in nursing homes and other long-term care facilities. This section of the chapter will summarize the biological, epidemiological, and clinical features of influenza that are relevant to the elderly with a particular emphasis on prevention.
To properly understand the impact of influenza in the elderly, it is important to be familiar with several key characteristics of the virus. The structure of influenza consists of an envelope with a central nucleic acid core comprised of single-stranded RNA. Key structural characteristics of the virus include the presence of hemagglutinin and neuraminidase proteins on the envelope. There are three types of influenza viruses A, B, and C. However only A and B are clinically relevant. Influenza A viruses are characterized by the structure of the hemagglutinin, a surface protein whose function is to bind to a glycoprotein on the surface of respiratory epithelial cells, allowing the virus to enter into the cell by forming an endosome and then using the protein making machinery of the cell to replicate itself. Annually new mutations are selected for resulting in small changes in the hemagglutinin (“antigenic drift”) hence the reason why influenza vaccine needs to be given annually. The other surface projection, neuraminidase, cleaves terminal sialic acid residues from carbohydrate moieties on surfaces of infected cells, promoting the release of virions that go on to infect other cells. As discussed below, this is a key target for neuraminidase inhibitors, thus preventing the influenza virus from replicating.
An important feature of influenza is the segmented structure of the RNA at the core of the virus, with each of eight segments coding for a structural or enzymatic component of the virus. This gives the virus the potential to recombine with influenza viruses of animal origin, forming a virus with a novel genotype and hemaglutinnin to which there is no preexisting immunity. This is known as “antigenic shift” and was responsible for pandemics in 1957–1958 and 1968–1969. A recent concern is the changes in hemaglutinin from animal strains, such as avian influenza or H5N1, maybe able to attach to the human receptors, causing direct transmission from animals to humans. This is believed to have caused the 1918–1919 pandemic and is a current concern with avian influenza (H5N1). Of note is that the highest mortality rate occurring in the 1918–19 pandemic was not in the elderly, but in 18- to 25-year-olds. This may have been because of the fact that there were similar H1 viruses circulating in the early 1900s and individuals older than 50 years of age developed partial immunity with previous exposure. At present, there are only three hemaglutinins (H1, H2, H3) and two neuraminidases (N1, N2) that have developed a stable lineage in humans.
Epidemics of influenza occur annually between November and April in the Northern hemisphere. A typical outbreak of influenza lasts for about 6 weeks, reaching a peak and slowly declining. However, in any given season, there maybe several strains circulating, with several peak periods of activity. It is for this reason that the annual influenza vaccine contains antigen from three influenza strains, two strains of influenza A, and one strain of influenza B.
During the interpandemic period, older adults and particularly residents of long-term care facilities are among those at highest risk for complications of influenza. Rates of hospitalization for influenza in community dwelling elderly persons range from 125 to 228 hospitalizations per 100,000 persons. As with many other infectious diseases, the very old and the very young are at highest risk of complications. Children between the ages of 6 and 23 months similarly have high rates of hospitalization attributable to influenza, ranging from 144 to 187 hospitalizations per 1000 persons. The presence of chronic conditions, such as chronic lung disease, congestive heart failure, conditions that predispose to aspiration, and metabolic disease, increase the risk for complications following infection with influenza. Many of these conditions occur predominately in older age groups. Moreover, studies that have assessed complications have found that age older than 65 years alone is independently associated with increased risk for influenza complications.
Based on our current understanding, the cause of death as a result of influenza in the elderly in the interpandemic period is not viral pneumonia but typically a bacterial infection complicating the influenza infection. Infection with influenza virus therefore predisposes to Streptococcus pneumoniae or Staphylococcus aureus infection, resulting in bacterial pneumonia. Deficits in innate immunity (phagocytes natural killer cells) and acquired immunity (T-cell function, cytokine activity, antibody response) are all felt to play a role, as discussed in Chapter 3.
Young, healthy individuals with influenza characteristically present with a sudden onset of fever, cough, myalgia, sore throat, and headache. Fever and cough have been shown in a systematic review to be the best predictors of influenza in the general population. In the elderly, the presentation usually is more subtle with cough and change in baseline temperature predominating. One of the most important factors in making the diagnosis of influenza, whether on clinical grounds or through diagnostic testing, is the local influenza activity. That is, if a community is experiencing an outbreak of influenza, particularly if the incidence of influenza is at its peak, fever and cough in an older person increase the likelihood of infection with influenza. However, it is important to bear in mind that the majority of studies that have assessed the diagnostic utility of clinical symptoms were done in samples with participants aged from 18 to 45 years, so less is known about the diagnostic utility of clinical signs and symptoms in the elderly.
In the nursing home setting, it is essential to obtain prompt diagnostic testing, because, as consistently demonstrated in longitudinal studies that have compared symptoms to etiologic agents, the clinical presentation is nonspecific. Even when there are peaks of influenza in the community, respiratory syncytial virus (RSV) or other respiratory viruses can circulate. It is essential to obtain testing, because it can lead to a change in management: an outbreak of influenza A in nursing home warrants chemoprophylaxis (see below) as well as immunization of nonimmunized residents in whom it is safe to do so.
The traditional method to detect influenza has been viral culture. The main limitations of culture have been moderate diagnostic accuracy and delay in obtaining results, which may take 2 to 3 days. Rapid tests include direct fluorescent antigen (DFA), or direct immunofluoresence, where monoclonal antibodies labeled with fluorescent material are directed to influenza cell coat antigens. A result can be reported within hours. Rapid enzyme-linked immunoassay (ELISA) tests are commercially available, however they are only available for influenza A and have a sensitivity of 60%. Nucleic acid amplification testing, such as polymerase chain reaction (PCR), is the most promising test since it is over 90% sensitive and specific and the turnaround time is rapid. The drawback however is that most laboratories do not have the resources to perform PCR on a routine basis.
The incubation period of influenza, the period of time from initial infection to development of symptoms, is typically 2 days, but can range from 1 to 4 days. An infected individual becomes contagious 1 day prior to the onset of symptoms. In adults, viral shedding at levels high enough to cause transmission occurs over 5 or 6 days. This is the rationale for keeping patients with influenza in isolation in hospital for 5 days after symptom onset. Although the extent to which influenza can be transmitted by airborne spread is controversial, the majority of spread of influenza is large droplet caused by coughing and sneezing. In terms of practical implications, use of “respiratory etiquette,” coughing, and sneezing into tissues, for example, may help prevent spread to older adults who are susceptible to complications although supporting epidemiologic evidence is limited. In the hospital setting, the use of gloves, gowns, and a mask is recommended prior to entering a patient’s room.
In the United States, there are currently two types of influenza vaccine that are licensed, the inactivated trivalent vaccine, which is a split virus formulation with two strains of influenza A and one B, and a cold-attenuated live intranasal vaccine. Only the inactivated vaccine is licensed for persons older than of 65 years of age. A recent systematic review summarized randomized controlled trial and cohort study evidence for efficacy and effectiveness: 64 studies were included in assessment, resulting in 96 data sets. In nursing homes where there was a good vaccine match and high viral circulation the effectiveness of vaccines against influenza-like illness was 23% (6–36%) but it was not significant against influenza (relative risk [RR] 1.04: 95% CI 0.43–2.51). However, well-matched vaccines had a 46% (30–58%) efficacy for preventing pneumonia, 45% (16–64%) efficacy to prevent hospital, and 42% (17–59%) efficacy for preventing death from influenza or pneumonia.
In elderly individuals living in the community, the review showed that poorly matched vaccines were not significantly effective against influenza (RR 0.19; 95% CI 0.02–2.01), influenza-like illness (RR 1.05: 95% CI 0.58–1.89), or pneumonia (RR 0.88; 95% CI 0.64–1.20). Well-matched vaccines had a 26% (12–38%) efficacy for preventing hospital admission for influenza and pneumonia and a 42% (24–55%) efficacy for preventing all-cause mortality.
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