Update on Prevention and Treatment of Influenza in the Elderly
Influenza, a lower respiratory tract infection caused by influenza viruses infecting ciliated cells, is associated with up to 300,000 hospitalizations annually in the United States.1 The disease occurs in epidemics in both hemispheres during winter months, but summertime outbreaks do exist.2 Persons with chronic illness and those in long-term care (LTC) settings are at increased risk for complications, including secondary pneumonia.3 Influenza and pneumonia consistently rank as a leading cause of death, of which about 90% of victims are over 64 years old.4 Fatality rates from influenza in nursing homes are the highest, reported from 14%5 to 55%.6,7 In addition to primary influenza viral pneumonia or secondary bacterial pneumonia and death, frail older people are at risk of functional decline after acute influenza. Influenza can exacerbate underlying medical conditions (eg, pulmonary or cardiac disease). Concerns for less common complications, such as myositis, myocarditis, and Guillain-Barré syndrome, can be answered by experts at the Clinician Information Line of the Centers for Disease Control and Prevention (CDC) (877-554-4625). The hotline is available 24 hours a day, 7 days a week, and is staffed by registered nurses with access to the latest CDC guidelines and information. Recent review articles provide further background for the interested reader.8,9
Influenza activity records from October 2005 to May 200610 reveal:
• Influenza B viruses predominated in Europe
• Influenza A (H1N1) and influenza B predominated in Asia
• Influenza A (H3N2) predominated overall in the United States, with approximately 75% of isolates antigenically matched to the H3N2 component of the 2005-2006 vaccine
• Influenza B activity was more common late in season in the United States, but only approximately 20% of isolates matched the vaccine antigens
• Influenza activity in the United States peaked in early March, but the number of pneumonia and influenza deaths did not achieve the epidemic level
MAKING THE DIAGNOSIS
The diagnosis of influenza is usually presumptive, based on history consistent with influenza symptoms and knowledge of its presence in a community or facility. Though the clinical presentation of influenza in vaccinated elderly persons may be attenuated, individual symptoms and signs are of some value11 (Table I).
• In patients age 60 years or older, the combination of fever, cough, and acute onset increased the likelihood of influenza to the greatest degree (likelihood ratio [LR] = 5.4). The presence of sneezing among older patients made influenza less likely.12
• Rapid diagnostic tests can yield results within a clinically relevant timeframe of 30 minutes to confirm a diagnosis of influenza A or B.13 Tables II and III show comparisons of commonly available tests. (Sensitivities approximately 60-80% and specificities 90-99%.)
• The virus culture remains the reference standard for diagnosis of influenza.
• In high-risk adults, testing is more cost-effective than empiric treatment with neuraminidase inhibitors only when risk of influenza is between 20% and 40%.14
Both rapid and reference tests should be used on the index or other early cases to confirm the type and to verify that the strain is well matched by the vaccine. Treatment of early cases should not be delayed until results of the reference lab are available. If the results are consistent, then subsequent cases in a community or facility may be assumed to have similar pathogens and should be treated accordingly (see below).
PREVENTION OF INFLUENZA
Primary prevention is best accomplished by widespread compliance with vaccination programs. Secondary prevention involves chemoprophylaxis to treat asymptomatic persons who have risk factors but in whom the condition is not clinically apparent. Tertiary prevention uses drugs and other care of established disease to restore the patient to highest function, minimize the negative effects of disease, and prevent disease-related complications. All three levels of prevention utilize appropriate infection-control measures.
Immunoprophylaxis with vaccines matched to epidemic strains is the most efficacious strategy to prevent influenza in elderly persons. Vaccination is most effective against complications of influenza, especially in LTC facilities, yet the usefulness of vaccines in the community remains modestly effective for at-risk elderly persons.15 The vaccines prepared for the upcoming influenza season are trivalent again, including A (H1N1), and different strains (from last season) of A (H3N2), and B antigens.10 Other relevant changes in recommendations for 2006-200716 for adults from the Advisory Committee on Immunization Practices (ACIP) include:
• Healthy children age 24-59 months and their household contacts and out-of-home caregivers (especially those having routine contact with vulnerable elders) should be vaccinated against influenza. This change extends the recommendations for vaccination of children so that all children age 6-59 months receive annual vaccination.
• To ensure optimal use of available doses of influenza vaccine, projected to be approximately 100 million doses, healthcare providers, those planning organized campaigns, and state and local public health agencies should: (1) develop plans for expanding outreach and infrastructure to vaccinate more persons than during the previous year; and (2) develop contingency plans for the timing and prioritization of administering influenza vaccine if the supply of vaccine is delayed and/or reduced because of the complexity of the production process.
• ACIP emphasizes that influenza vaccine should continue to be offered throughout the influenza season, even after influenza activity has been documented in a community.
• Neither amantadine nor rimantadine should be used for the treatment or chemoprophylaxis of influenza A in the United States because of recent data indicating widespread resistance of influenza virus to these medications.
Only inactivated vaccines should be offered to elderly persons. Live-attenuated intranasal influenza vaccine (LAIV) is contraindicated for persons under age 5 years or over age 50 years, or with asthma, chronic obstructive pulmonary disease, chronic heart conditions, diabetes, renal dysfunction, hemoglobinopathies, or immunocompromised states. Likewise, use of LAIV might not be preferred for close contacts or staff or volunteers caring for high-risk elderly persons, since LAIV allows shedding of live virus for up to 21 days.17 The optimal time to administer influenza vaccine is from late October to mid-November, although vaccine should be offered to high-risk individuals and household contacts as early as September during routine healthcare visits to avoid missed opportunities. Continue to vaccinate eligible persons throughout the influenza season as long as the vaccine is available, even after influenza activity has been documented in the community. Adults develop peak antibody protection against influenza infection 2 weeks after vaccination. The ACIP recently emphasized that all healthcare workers should be vaccinated against influenza annually.18 Physician offices, clinics, hospitals, and LTC facilities should provide vaccines to workers, encouraging maximal immunization rates, which now average 50-60%. Patients with previous reactions, including anaphylaxis, to the influenza vaccine or a known hypersensitivity reaction to eggs should not be vaccinated. Patients should not receive the vaccine during an acute febrile illness. Though suppliers anticipate adequate vaccine supplies for the 2006-2007 season, the CDC recommends a tiered use of inactivated influenza vaccine during shortages. Tier 1 is prioritized (1A, 1B, and 1C treated equally unless there is severe shortage, then the subtiers are prioritized), then tier 2 followed by tier 3.19
• Persons over age 64 years with comorbid conditions
• Residents of LTC facilities
• Persons over age 64 years without comorbid conditions
• Persons age 2-65 years with comorbid conditions
• Children age 6-23 months
• Pregnant women
• Healthcare personnel
• Household contacts and out-of-home caregivers of children under 6 months old
• Household contacts of children and adults at increased risk of influenza-related complications
• Healthy persons age 50-64 years
• Persons age 2-49 years without high-risk conditions
Chemoprophylactic drugs are not a substitute for vaccination. However, effective secondary prevention of influenza with an antiviral agent is reported among at-risk elderly persons given chemoprophylaxis after a household member was diagnosed with influenza.20 The timing and duration of antiviral medications for chemoprophylaxis are weighed against cost, compliance, and potential side effects. The drug must be taken daily for the duration of influenza activity in the community to be maximally preventive. When influenza is discovered in an institution, chemoprophylaxis should be administered to all residents, regardless of vaccination status, and should continue for a minimum of 2 weeks, as this strategy is known to be both clinically and cost-effective21 (see Table IV for dosages). If surveillance indicates that new cases continue to occur, chemoprophylaxis should be continued until approximately 1 week after the end of the outbreak. The CDC published a Health Alert22 on January 17, 2006, reporting that 92% of influenza isolates (H3N2) in the United States had genetically (though not clinically) determined resistance to amantadine and rimantadine, and no longer recommends use of ion channel inhibitors (amantadine or rimantadine) for chemoprophylaxis. No resistance has yet been reported to zanamivir, and only 0.4% resistance has been reported to oseltamivir in adults.23
Treatment, or tertiary prevention, for influenza begins with supportive measures including antipyretics and adequate hydration. Antiviral pharmacotherapy should be started for individuals within 48 hours of symptoms (no evidence of benefit if started after 48 hours), with the choice of agent based upon presumptive etiologic agent (80-90% will be Type A), comorbid conditions, cognitive status (eg, ability to use inhaler), and availability of medication. Neither amantadine nor rimantadine should be used for the treatment of influenza A in the United States until susceptibility has been re-established. The neuraminidase inhibitors oseltamivir or zanamivir can be prescribed if antiviral treatment of influenza is indicated (Table IV). Systematic reviews suggest neuraminidase inhibitors reduce symptoms by 1-2 days,20 and oseltamivir reduces antibiotic use and hospitalizations for complications.24 With the difficulty for elderly persons in using the zanamivir dry powder inhaler device, oseltamivir is arguably the drug of choice for frail elderly patients with influenza.
AVIAN INFLUENZA AND PANDEMIC PLANNING
Three influenza pandemics have occurred since 1900, and all spread globally within 1 year:
• 1918-1919 “Spanish flu” was due to influenza A (H1N1—virus was an avian influenza virus that adapted to humans), causing 20-50 million deaths worldwide (> 0.5 million in United States).
• 1957-1958 “Asian flu” was due to influenza A (H2N2) and caused about 70,000 deaths in United States.
• 1968-1969 “Hong Kong flu” was due to influenza A (H3N2) and caused about 34,000 deaths in United States.
The recent worldwide attention to avian influenza A (H5N1) virus results from the specter of another potential pandemic. Genetic re-assortment of avian influenza and human influenza strains can occur during co-infection, with potential for highly pathogenic strains that can lead to a human pandemic. The World Health Organization (WHO) confirmed a total of 241 human cases with 141 deaths (59% case fatality rate) from December 26, 2003 to August 23, 2006, spread among 10 countries.25 That 90% of these cases are in patients under age 40 years likely reflects local demographics and not resistance by the elderly. Sustained human-to-human transmission of H5N1 has not been documented, although a probable transmission of avian influenza from an infected child to her mother and aunt has been reported.26 Confirmation of avian influenza is based on at least one of the following: positive viral culture for influenza A/H5; positive polymerase chain reaction (PCR) for influenza A/H5; positive immunofluorescence antibody (IFA) test for H5 antigen using H5 monoclonal antibodies; or a fourfold rise in H5-specific antibody titer in paired serum samples. The CDC recommends testing for influenza A (H5N1) in two specific situations in the United States:
1. For hospitalized patients with both radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness without established diagnosis, AND history of travel within 10 days of symptom onset to country with documented H5N1 avian influenza in poultry or humans
2. On a case-by-case basis (in consultation with state and local health departments) for patients with documented temperature higher than 38 degrees C (100.4 degrees F), AND cough, sore throat, or shortness of breath, AND history of contact with domestic poultry or known or suspected case of influenza A (H5N1) in H5N1-affected country within 10 days of symptom onset
Although the development of a vaccine against H5N1 influenza is underway, it is not yet available. The avian H5N1 viruses are resistant to the adamantanes but are usually sensitive to the neura-minidase inhibitors zanamivir and oseltamivir.23 Dosing is the same as for typical influenza, but the CDC recommends isolation for 14 days after symptom onset. Some oseltamivir resistance by H5N1 virus is reported,27 suggesting that zanamivir should be included as part of pandemic preparedness. Finally, physicians caring for elderly world travelers should refer to CDC travel advisories, especially for Southeast Asia destinations (www.cdc.gov/travel/ other/avian_influenza_se_asia_2005.htm).
The authors report no relevant financial relationships.