Management of Influenza in the Nursing Home
Paul J. Drinka, MD, and Stefan Gravenstein, MD

Influenza is a highly infectious, potentially lethal illness; vaccination of residents and staff is the cornerstone of prevention. The Centers for Disease Control and Prevention recommends droplet secretion precautions for influenza; in addition to standard precautions to limit transmission, droplet precautions include wearing a mask within three feet of an infected patient. The use of antiviral medications requires a surveillance system to monitor viral isolates in the community and respiratory illness in the facility, with contingency plans to submit direct immunofluorescence and cultures to confirm the presence of influenza. When M2 channel inhibitors are given simultaneously as treatment and prophylaxis within the close quarters of a household, resistance develops and they become ineffective as prophylaxis. The authors of this report favor neuraminidase inhibitors as treatment of influenza illness and rimantadine as prophylaxis; a possible future role for neuraminidase inhibitors as prophylaxis is being investigated. (Annals of Long-Term Care: Clinical Care and Aging 2000;8[9]:23-30)

Introduction Ninety percent of deaths attributed to pneumonia and influenza occur in adults ages 65 and older.1 Mortality 30 days following isolation of influenza type A or B was 5% in a nursing home study.2 The Centers for Disease Control and Prevention (CDC) tracked influenza mortality over 23 seasons. In six seasons, more than 40,000 excess deaths were attributed to influenza.1 No excess deaths were noted during four of the 23 seasons.

During seven seasons at the Wisconsin Veterans Home with an identical surveillance system, the number of influenza A isolates varied between 154 and 0.3 There was striking annual variability in the influenza attack rate and duration of activity. Thus, activity may be sporadic rather than epidemic. It is difficult to predict influenza illness severity or risk of transmission early in the season. Even within a single, large long-term care facility, the period of influenza activity can vary between floors and buildings.

During the largest outbreak at the Wisconsin Veterans Home in 1997-1998 (a season with a poor vaccine match), influenza was reintroduced into two buildings 40 and 75 days after a period of initial activity. This underscores the need for continued surveillance with contingency plans for reinstitution of outbreak control measures as long as influenza is circulating in the community.3 The annual variation in influenza timing and severity requires that practitioners establish a clinical and laboratory surveillance system to identify cases and respond accordingly.

Many authorities believe that influenza is transmitted via small-particle aerosols.4 A case report suggests transmission of influenza from a single index case to many passengers on an airliner when the ventilation system was turned off.5 Small-particle aerosols can be generated by coughing and sneezing, and can remain airborne long enough to infect a remote individual sharing the airspace. Large-droplet splatter within the three-foot barrier, as well as hand-to-hand or hand-to-doorknob-to-hand contact, may be a factor. The CDC recommends the use of large-droplet secretion precautions for the control of influenza in hospitals.6

Vaccination Vaccination is the cornerstone of prevention. Influenza vaccination is both lifesaving and imperfect. A placebo-controlled study of 1838 community elderly demonstrated a 58% reduction in serologically confirmed illness.7 The efficacy of vaccine in the nursing home was studied in a meta-analysis of 20 observational studies with controls who refused vaccination. The pooled estimates of efficacy varied between 50% and 68% for preventing respiratory illness, pneumonia, hospitalization, and death.8 These adverse endpoints are more common in nursing homes than in the community.

Our experience suggests that a successful nursing home vaccination program should have one individual in charge to avoid diffusion of responsibility. A policy allowing decision makers to give written consent for all subsequent annual vaccinations is helpful. Preprinted physician admission orders including annual influenza vaccination can prompt the physician and avoid extra writing and signatures. Residents should generally not be vaccinated before the last week in October because antibody levels might decline within a few months.1 Influenza activity may extend into April or May.3

Staff vaccination in long-term care facilities is critical in preventing influenza in residents. The "staff" vaccination program should include volunteer workers. Staff illness usually precedes resident illness, and staff may bring influenza into the nursing home following exposure to children and others in the general community. The efficacy of staff vaccination has been demonstrated in controlled studies in English long-term care hospitals. Facilities with staff vaccination programs had a 40% reduction in resident mortality.9,10

One of the goals of every program is to vaccinate enough people to achieve "herd immunity." Herd immunity implies that susceptible residents are protected because the individuals who surround them are barriers to transmission. To achieve "herd" immunity, vaccination rates of both residents and staff should exceed 80%. The vaccine response in individual staff is better than that in frail residents, and should make a more reliable contribution to herd immunity.

One way to improve staff vaccination rates is to have the facility finance and administer vaccine. The facility benefits because of decreased cost of caring for resident illnesses and reduced staff sick leave.11,12 The effectiveness of influenza vaccination was established in a randomized study of 849 healthy working adults. Vaccinated subjects reported 25% fewer upper respiratory infections (URIs) and 43-44% fewer sick days and physician visits for URIs. These percentages were probably diluted by other winter respiratory viruses not covered by the vaccine.12

A successful staff vaccination program should be free and convenient (available on all shifts). Staff need to be educated about vaccine safety, efficacy, and the reasons for targeting health care workers. Vaccine should be reoffered to those who refused it the first time, even after influenza has been documented in the community.

Secretion Precautions and Activity Adaptations to Prevent Influenza Transmission The CDC recommends droplet secretion precautions for hospitalized patients with influenza. Ideally, place residents with influenza in a private room or with other residents who have influenza. Room changes, however, are generally not feasible. Droplet precautions require staff to wear a mask when working within three feet of an infected resident.6

To improve resident compliance, those who are able to understand must be educated about the importance of precautions to protect the community. Residents with suspected influenza should be asked to remain in their rooms and to wear masks if they leave them. It is especially important to isolate residents receiving treatment for presumed influenza infection with amantadine or rimantadine because they may shed resistant virus that may be transmitted to others.1

Activities for asymptomatic residents can be adapted or canceled. Adaptations we have implemented include reducing the size of the group and cohorting activities for asymptomatic residents on outbreak units. In addition, we direct the activity leader to maintain a three-foot space between participants, and to avoid singing or passing objects. We direct coughing residents back to their rooms. Notices are placed on building entrances requesting that visitors with respiratory symptoms postpone their visit. The shortcoming of this approach is the theoretical possibility that there is a period early in influenza illness during which apparently well residents might transmit the virus. Canceling activities is a more aggressive approach that may be poorly tolerated.

During the period of influenza activity in the community, symptomatic staff with viral respiratory infections are encouraged to take sick leave. Nursing homes might consider developing criteria for requiring employees to take sick leave, including information regarding local viral activity and perhaps a temperature threshold. The severity of influenza illness, however, is variable, ranging from that of mild rhinitis or pharyngitis to that of viral pneumonia.13 Vaccine may attenuate influenza illness and make clinical diagnosis difficult.

Staff may wish to work while they are shedding infectious virus. Therefore, staff who work while they have "cold" symptoms (or attenuated influenza symptoms) are encouraged to maintain a barrier between their respiratory secretions and the environment, including wearing masks and frequent hand washing. Nevertheless, working while infected with influenza is a dangerous practice.11 There is a need to develop an institutional program to protect noninfected patients and staff from the transmission of influenza virus (Table I).

Although not all respiratory viruses spread like influenza, we advocate training staff to use the same secretion precautions for all viral respiratory illnesses. Practitioners seldom know the precise organism and are able to initiate organism-specific secretion precautions only if diagnostic tests are obtained and completed. We have documented an approximately 5-6% 30-day mortality rate following isolation of influenza A and B and parainfluenza type 1 (Table II).2 Others have reported fatal outcomes during outbreaks of respiratory syncytial virus and parainfluenza 3. Thus, influenza is not the only potentially lethal viral respiratory infection.

Antiviral Agents Influenza outbreaks often strike swiftly. Therefore, it is important to have plans to facilitate rapid administration of antiviral agents. Plans should include pre-approved, preprinted orders that can be rapidly dated and initialed. The Food and Drug Administration (FDA) has approved two medications for the treatment and prophylaxis of influenza A infection and, more recently, two medications for the treatment but not prophylaxis of influenza A and influenza B.

Amantadine and Rimantadine Amantadine and rimantadine are approved for the treatment and prophylaxis of influenza A. When started before exposure ("seasonal prophylaxis"), amantadine and rimantadine are 70-90% effective in preventing influenza A.1 Treatment of an infected person beginning within 48 hours after onset decreases the duration of symptoms by one to two days in adults with uncomplicated influenza. Rimantadine has gastrointestinal side effects, including anorexia and nausea, similar to those of amantadine; but it has fewer central nervous system (CNS) side effects, which may include anxiety, insomnia, lightheadedness, or even confusion, hallucinations, seizures, and falls in nursing home residents.14

The dose of rimantadine and amantadine generally recommended for nursing home residents is 100 mg per day. Rimantadine is metabolized by the liver before renal excretion; dosage reductions are not recommended until the creatinine clearance falls below 10 mL/minute, or in the presence of severe hepatic dysfunction. Amantadine is excreted by the kidneys, and the dose must be reduced for creatinine clearances of 30 mL/minute or below. The direct cost of rimantadine is greater than that of amantadine. However, excess CNS side effects from amantadine, with their associated indirect costs, may make rimantadine more cost-effective.

Neuraminidase Inhibitors Oseltamivir phosphate, administered orally in capsule form, and zanamivir powder, administered by oral inhalation, are approved for the treatment of influenza A and B infection but not for prophylaxis. Influenza strains are classified by their hemagglutinin (HA) and neuraminidase (NA) surface proteins. NA is a sialidase, and the neuraminidase inhibitors (NAIs) are sialic acid analogs. The NAIs were designed to bind with and inactivate influenza virus NA. Viral HA binds to sialic acid on host cells and facilitates insertion of viral RNA. Viral HA binding also impairs the release of budding viral progeny. NA cleaves sialic acid from the host cell, reversing HA binding, and allows viral release and infection of adjacent cells. Like amantadine and rimantadine, treatment with an NAI should begin within 48 hours of symptom onset. Unlike amantadine and rimantadine, the NAIs are also active against influenza B, a lethal disease in institutionalized elderly.2

When administered to febrile, laboratory-confirmed influenza patients within 36 hours of onset, zanamivir shortened the time to alleviation of clinically important symptoms from 6.5 to 4.5 days. Among 76 "high-risk" patients (age 65 years or more, and/or with cardiopulmonary, metabolic illness or immunocompromised), a reduced requirement for antibiotics to treat secondary complications was noted.15 The dose of zanamivir is two 5-mg oral inhalations twice daily for five days. The inhaled powder is approximately 10% absorbed and excreted unchanged by the kidney. Current labeling cautions that this agent is not generally recommended for those with bronchospasm, asthma, or chronic obstructive pulmonary disease.16 If zanamivir is used in these individuals careful monitoring and short-acting bronchodilators should be available.

Febrile, laboratory-confirmed influenza patients treated with oseltamivir within 36 hours of onset experienced a 30% reduction in the duration of illness.17 Severity of illness was reduced by 38%, and patients were able to return to their usual activities two to three days earlier than patients given placebo. Oseltamivir is well absorbed from the gastrointestinal tract and is converted to the active carboxylate by liver esterases.

The dose of oseltamivir is 75 mg by mouth twice daily for five days. This dose should be reduced to 75 mg daily in those with creatinine clearances below 30 mL/minute. There is little experience administering oseltamivir to those with creatinine clearances below 10 mL/minute or in the presence of severe liver disease. The most common side effect of oseltamivir is nausea and vomiting, which occurs in approximately 7% of subjects in excess of placebo. This may be diminished by routinely administering the medication with food.18

Although nursing home personnel have extensive experience with the use of inhalers, a capsule is easier to administer. The administration of zanamivir requires that residents be able to purse their lips and inhale through a mouthpiece. Neither drug is available as a liquid. There are no clinical data regarding opening oseltamivir capsules.

Influenza Surveillance and the Application of Antiviral Therapy The early recognition of influenza illness is critical to ensure the application of antiviral therapy. In healthy adults, classic influenza presents as an acute febrile respiratory illness with systemic symptoms, including myalgia, headache, and chills, as well as respiratory symptoms, including sore throat, dry cough, nasal congestion, and rhinorrhea. As stated above, the severity of influenza illness varies from that of mild rhinitis or pharyngitis to that of viral pneumonia.13

The clinical presentation of influenza in impaired nursing home residents is not well characterized. Antecedent vaccination attenuates disease severity.19 One cannot assume that the nursing home resident will be febrile at disease presentation. Infectious illness in nursing home residents often has an altered presentation, including functional decline (ie, falls, greater dependency in activities of daily living, disruption of activity, or loss of appetite). During the influenza season, an observation of functional decline should lead to a temperature determination and a focused assessment for respiratory symptoms and signs. When influenza is known to be circulating in the community, the rapid identification of residents with acute respiratory illness affords two benefits. The individual can receive treatment of a potentially lethal disease, and the entire institution can acquire the surveillance information needed to declare an outbreak and initiate control measures.

The CDC recommends that chemoprophylaxis be started as early as possible when influenza A outbreaks are confirmed or suspected.1 Acute respiratory symptoms in nursing home residents have numerous etiologies, both infectious—including parainfluenza, respiratory syncytial virus, and bacterial infections—and noninfectious—including aspiration, heart disease, and allergy.

Outbreak Criteria There is no consensus definition for a suspected or confirmed outbreak. Outbreak criteria, however, can be divided into two parts: clinical and laboratory. One outbreak definition is a cluster of three or more individuals on the same nursing unit with a new onset of respiratory illness and an oral temperature 100ºF or more within a three-day period.20 Such an outbreak can be characterized as explosive because of the concentration of cases, and severe because of temperature elevation. Influenza must then be laboratory-confirmed. The advantage of these criteria is that a clustering of severe cases may improve specificity. The authors of this article include all new respiratory illnesses regardless of temperature to determine the existence of a clinical outbreak.

Prior to the influenza season, clinicians should determine the best source of information about viral respiratory isolates in their community. This might include public health officials or the closest virology laboratory. A nurse should track the new onset of respiratory illnesses, including the highest temperature, whether or not associated with fever. Plans should be made to collect and transport specimens for viral culture and direct immunofluorescence (IF) testing. Sporadic cases of febrile respiratory illness should be subjected to laboratory evaluation after influenza has been identified by a regional laboratory. Confirmation of sporadic influenza will help guide the treatment of symptomatic cases and provide important information if there is a clinical outbreak and widespread chemoprophylaxis is being considered. If there is a clinical outbreak of respiratory illness when influenza is known to be circulating in the community, and laboratory data are not available at that time, antiviral prophylaxis could be applied while laboratory confirmation is pending. Testing offers the advantage of rapid results and might allow laboratory confirmation prior to starting prophylaxis.

Clinicians should be aware of the type of specimens (lavage, swab, nasopharyngeal, pharyngeal) used to validate their test system, as well as sensitivity and specificity. If specificity is cited as 90% and there is no influenza in the community, 10% of tests will be falsely positive, and 90% will be true negatives. The determination of initial sporadic activity should be backed up by culture. The clinician should also consider specificity when determining how many positive rapid tests are required to "confirm" an outbreak. Currently, the CDC recommends a minimum of two weeks of prophylaxis for all residents, regardless of vaccination status, following a confirmed outbreak. In addition, prophylaxis should be continued for one week after the last onset of influenza cases.1 Ongoing surveillance for new cases during prophylaxis is required to follow these recommendations.

Resistant Strains Currently, only amantadine and rimantadine are approved by the FDA for prophylaxis. In 1989, Hayden et al21 reported that when rimantadine is given within the close quarters of a household simultaneously as treatment and prophylaxis, it is ineffective as prophylaxis because of the emergence and transmission of rimantadine-resistant strains. For some time, the CDC has recommended the simultaneous use of amantadine or rimantadine in nursing homes as treatment and prophylaxis. Up to one-third of persons who are treated for influenza A can shed resistant virus. This can occur within two to three days, and especially after five to seven days. Because of the emergence of resistance, the CDC recommends the isolation of nursing home residents who are being treated for influenza and that treatment be limited to three to five days or one to two days after the end of symptoms.1 It is hoped that brief treatment will limit transmission of resistant strains.

During the 1993-1994 season, 68 influenza A isolates were encountered at the Wisconsin Veterans Home over 47 days. Amantadine use started on December 9, 1993. Thirteen of 17 isolates with disease onset after January 8, 1994, underwent amantadine sensitivity determination at the CDC. Ten were resistant.3

A possible use of NAIs in the nursing home is for treatment of influenza infection, saving rimantadine for prophylaxis. Because these two drug classes are active through different mechanisms (M2 channel blockade versus neuraminidase inhibition), the combination could theoretically decrease the emergence of amantadine/rimantadine-resistant strains. There are no data to support this hypothesis. (Both oseltamivir and zanamivir are being investigated as possible agents for prophylaxis in the future.) Facility management should also consider providing NAI therapy to symptomatic staff with influenza. Febrile health care workers with influenza could be expected to return to work earlier and shed virus for a shorter period.15

Summary The following practical steps should be taken to prepare for influenza activity:

1. Educate staff, residents, and decision makers about the dangers of viral respiratory infections, and the benefits of vaccination, secretion precautions, and antiviral agents. 2. Develop policies and preprinted orders to facilitate vaccination of residents and staff, and the use of antiviral agents for early treatment and prophylaxis. 3. Determine the source of information regarding viral isolates in your community. 4. Enlist a nurse to track the onset of new respiratory illnesses along with the highest temperature, and to collect specimens for viral culture and rapid testing.

This information is required to treat infected individuals, to identify an outbreak, to start antiviral prophylaxis, to determine the duration of prophylaxis, and to detect the reintroduction of influenza from the community.

Acknowledgments This work was supported by National Institutes of Health grant AG 00834 (SG). Dr. Drinka has received research funding from Glaxo Wellcome for studies of zanamivir and is a member of the speaker bureaus of Roche Laboratories and Glaxo Wellcome. Dr. Gravenstein receives funding from Glaxo Wellcome for studies of neuraminidase inhibitors and has consulting relationships with Roche and Aventis Pasteur.

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References 1. Advisory Committee on Immunization Practices (ACIP). Prevention and control of influenza: Recommendations of the ACIP. MMWR Morb Mortal Wkly Rep 1999;48(RR-04):1-28. 2. Drinka PJ, Gravenstein S, Langer L, et al. Mortality following isolation of various respiratory viruses in nursing home residents. Infect Control Hosp Epidemiol 1999;20:812-815. 3. Drinka PJ, Gravenstein S, Krause P, et al. Non-influenza respiratory viruses may overlap and obscure influenza activity. J Am Geriatr Soc 1999;47:1087-1093. 4. Treanor JJ. Influenza virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. New York, NY: Churchill Livingstone; 2000:1823-1849. 5. Moser MR, Bender TR, Margolis HS, et al. An outbreak of influenza aboard a commercial airliner. Am J Epidemiol 1979;110:1-6. 6. Garner JS. Hospital Infection Control Practices Advisory Committee. Guideline for isolation precautions in hospitals. Infect Control Hosp Epidemiol 1996;17:53-80. 7. Govaert TM, Thijs CT, Masurel N, et al. The efficacy of influenza vaccination in elderly individuals. JAMA 1994;272:1661-1665. 8. Gross PA, Hermogenes AW, Sacks HS, et al. The efficacy of influenza vaccine in elderly persons: A meta-analysis and review of the literature. Ann Intern Med 1995;123:518-527. 9. Potter J, Stott DJ, Roberts MA, et al. Influenza vaccination of health care workers in long-term-care hospitals reduces the mortality of elderly patients. J Infect Dis 1997;175:1-6. 10. Carman WF, Elder AG, Wallace LA, et al. Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: A randomised controlled trial. Lancet 2000;355:93-97. 11. Wilde JA, McMillan JA, Serwint J, et al. Effectiveness of influenza vaccine in health care professionals: A randomized trial. JAMA 1999;281:908-913. 12. Nichol KL, Lind A, Margolis KL, et al. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med 1995;333:889-893. 13. Cox NJ, Fukuda K. Influenza. Infect Dis Clin North Am 1998;12(1):27-38. 14. Drugs for non-HIV viral infections. Med Lett Drugs Ther 1997;39:69-76. 15. MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. Lancet 1998;352:1877-1881. 16. Glaxo Wellcome Inc. Relenza® (zanamivir) product information; 2000. 17. Treanor JJ, Hayden FG, Vrooman PS, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: A randomized controlled trial. JAMA 2000;283:1016-1024. 18. Roche Laboratories Inc. Tamiflu™ (oseltamivir phosphate) product information; 1999. 19. Gravenstein S, Freund BM, McElhaney JE, et al. Greater effectiveness from zanamivir treatment of influenza with antecedent influenza vaccination in older adults. Abstracts of the 39th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; September 1999; San Francisco, CA. Abstract 1902. 20. Gomolin IH, Leib HB, Arden NH, Sherman FT. Control of influenza outbreaks in the nursing home: Guidelines for diagnosis and management. J Am Geriatr Soc 1995;43:71-74. 21. Hayden FG, Belshe RB, Clover RD, et al. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 1989;321:1696 1702.

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Dr. Drinka is Medical Director, Wisconsin Veterans Home, King, WI; and Clinical Professor of Internal Medicine/Geriatrics, University of Wisconsin-Madison and Medical College of Wisconsin-Milwaukee. Dr. Gravenstein is Medical Director, Beth Sholom Nursing Home, Virginia Beach, VA; John Franklin Chair of Geriatrics and Director, Glennan Center for Geriatrics and Gerontology; and Professor of Medicine, Eastern Virginia Medical School, Norfolk, VA. Address for correspondence: Paul J. Drinka, MD, Wisconsin Veterans Home, County Hwy QQ, King, WI 54946-0620.

Annals of Long-Term Care - ISSN: 1524-7929 - Volume 8 - Issue 09 - September 2000