Topics in Long-Term Care EDITED
BY
DAVID W. BENTLEY, MD
Prevention and Control of Influenza A Outbreaks in Long-Term Care Facilities Stefan Gravenstein, MD; Barbara A. Miller, RN; Paul Drinka, MD
No single virus has the health impact of influenza. Influenza has remained epidemiologically important because it escapes host immune pressure through antigenic variation, is highly contagious, and can cause pneumonia and death in the most susceptible hosts. Viral transmission is most efficient where contact between susceptible hosts is greatest. For humans, this includes institutional settings such as daycare centers, schools, hospitals, and long-term care facilities. Of the three types of influenza, influenza C is relatively nonvirulent. Influenza B is most virulent in children; its antigenic stability presumably allows the adult population to benefit from acquired immunity. Influenza A is virulent in people of all ages, especially in those at the extremes of age or with immunocompromising disease; the attack rate in persons over 70 years of age is four times that of adults under 40 years of age.’ A major factor accounting for recurrent influenza A epidemics is change in the virus (antigenic drift and shift) that renders the vaccine less efficacious. Influenza epidemics cost billions of dollars and result in thousands of deaths annually. This discussion will focus on the prevention and treatment of influenza A in the long-term care facility. CLINICAL INFECTION
The severity of influenza, a typically self-limiting illness, is influenced by viral virulence factors and the health and age of the host. Most cases are sympto-
matic, although 20% of infected persons may be asymptomatic. The initial cases in long-term care facilities are often first diagnosed postmortem or recognized retrospectively. The clinical diagnosis of influenza is more easily made when concurrent cases present with fever and respiratory symptoms such as cough, coryza, and sore throat, and influenza is known to be circulating in the community. Influenza differs from most other viral infections in that it frequently spreads to involve the lower respiratory tract. Influenza A and pneumonia increasingly contribute to morbidity and mortality with advancing age; over 80% of excess deaths attributed to pneumonia and influenza occur among persons 65 years of age or older.2 The tenth leading cause of death in younger individuals, influenza and pneumonia are ranked seventh among individuals 55 to 74 years of age and fourth among those over the age of 74.3 During influenza epidemics, pneumonia is the second leading cause of death among octogenarians.4 Influenza-associated mortality is not only accounted for by pneumonia but also from subsequent events arising from underlying cardiovascular, cerebrovascular, and other chronic or immunocompromising diseases. An institutional influenza A outbreak can result in up to 70% of the population becoming ill, with 22% of those affected developing complications severe enough to result in hospitalization or death.5 Although illness from influenza B virus generally is less severe, case-fatality rates of 10% have been reported in nurs-
From the Section of Geriatrics, Department of Medicine, University of Wisconsin-Madison (Drs. Gravenstein and Drinka and MS Miller), and the William S. Middleton Memorial Veterans’ Hospital, Madison (Drs. Gravenstein and Drinka), and the Wisconsin Veterans’ Home, King, Wisconsin (Dr Drinka). Supported by the NIH, AG00548 and AG09632 (SG). Address reprint requests to Stefan Gravenstein, MD, University of Wisconsin, Institute on Aging and Adult Life, 425 Henry Mall, Room 330, Madison, WI 53706. Gravenstein S, Miller BA, Drinka P. Prevention and control of influenza A outbreaks in long-term care facilities. Infect Control Hosp Epidemiol. 1992;13:49-54.
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IFECTIoN CONTROL
AND
ing home outbreaks6 Even among otherwise healthy elderly persons, studies of interepidemic outbreaks of influenza have shown that hospitalization rates increased sixfold for pneumonia and influenza.4 ANNUAL INFLUENZA VACCINATION
Recurrent institutional influenza A outbreaks are caused by a variety of unique circumstances present in long-term care facilities and may include reduced vaccine efficacy in this population. To reduce the clinical impact of influenza outbreaks in this setting, one must first identify those factors that contribute to the inoculation and subsequent spread of influenza A. The most important factor permitting introduction of infection and subsequent spread of influenza in longterm care facilities is the failure to vaccinate. The Centers for Disease Control (CDC) recommends annual influenza vaccination for any person over 65 years of age with or without underlying medical condition because of increased risk for complications following infection. In addition, healthcare workers and others in close contact with high-risk persons should be vaccinated annually. Employee vaccination programs have the potential to reduce staff-to-patient influenza transmission and illness-associated absenteeism. Epidemiologic studies of several long-term care facility outbreaks identified a long-term care facility employee as the index case (i.e., the individual most likely to have introduced influenza into the long-term care facility) (Personal communication. Centers for Disease Control. 1991.). Unfortunately, fewer than 30% of this population2 and frequently fewer than half of nursing home residents receive the influenza vaccine in any given year.5 Our experience is similar to that reported by others5J; we rarely have seen even 30% vaccination rates in long-term care facility personnel. Influenza vaccination programs are the most cost-effective approach for influenza control.8 Vaccination programs may fail to achieve high vaccination rates because many individuals in the target group fear injections or their side effects, believe that the vaccine does not work or is unnecessary, or simply miss the opportunity to be vaccinated when the program is available.g However, influenza vaccination rarely results in more than local tenderness at the vaccination site; placebo vaccinations (saline solution) cause similar rates of complaints. If tenderness occurs, it rarely lasts more than two days and generally does not interfere with the activities of daily living. Systemic symptoms like coryza or malaise, although less common, may last for a few days postvaccination. Vaccine recipients may need reassurance that such complaints are not caused by the development of an influenza illness, because there is
HOSPITAL EPIDEMIOLOGY
January 1992
no live influenza virus in the modem vaccine capable of causing influenza. The Guillian-Barré, Syndrome complication associated with the 1976 influenza vaccination program is not expected to be repeated.2 The only contraindications to influenza vaccination are anaphylactic hypersensitivity to eggs (these are used in manufacturing the vaccine) and allergy to contact lens solution (the thimerosol preservative in the vaccine is used in many contact lens solutions). Many studies have demonstrated vaccine efficacy even in the elderly and chronically ill.l”J1 The degree of protection conferred by vaccination is dependent on vaccine response.12 Vaccination can reduce the risk for hospitalization, pneumonia, and death in long-term care facilities by two- to six-fold during influenza outbreaks.5J3 Well-matched vaccination has been shown to be effective in reducing clinical illness, viral shedding, and therefore transmission of the virus to others. When enough individuals within a given setting have immunity to a circulating virus (herd immunity), the ability of the virus to infect them is limited.2J4 Although a variety of factors determine the specific number of individuals that need to be immunized, a goal of vaccinating 80% of subjects with the appropriate vaccine may be sufficient for herd immunity in a closed setting.5 Some institutional vaccination programs for the elderly are implemented as soon as the vaccine becomes available, even as early as August. Although it may take six weeks for the elderly to develop optimal antibody titers, vaccinating them in August and September is likely premature because protective antibody titers rarely last more than a few months,15 leaving them unprotected for much of the influenza season. It is advisable to vaccinate the elderly as close to six weeks before the expected influenza season as possible. In most states, the influenza season begins in late December. However, states at higher altitudes and latitudes may have an earlier winter and therefore may enter the influenza season sooner (e.g., Colorado and Alaska). In Wisconsin, we encourage vaccination programs to begin in late October with a goal of finishing in November. This is an appropriate time for most states and is in agreement with CDC recommendations.” Vaccination programs for long-term care facility residents generally require individual physician orders and patient consent.5 This task is simplified by getting patient/guardian consent for annual influenza vaccination upon admission to the long-term care facility and having the order preprinted on medication order sheets as a routine medication renewal prior to the influenza season. Fall and winter long-term care facility admissions that occur after vaccination programs need to have their vaccination status checked
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TOPICS
IN
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LONG-TERM CARE
and updated; nearly half of elderly persons hospitalized in fall and winter are discharged from the hospital unvaccinated.‘6 Hospitals could facilitate the vaccination effort by making seasonal influenza vaccination part of the discharge planning process. Performing all long-term care facility influenza vaccinations within a few weeks while continuing vaccination of new staff and residents seems efficient. When an influenza outbreak is detected, vaccination should be offered again to residents and staff who previously refused vaccination; vaccination throughout the influenza season has potential benefit for the unimmunized.17 Implementing these recommendations may be feasible only if the delivery system is organized and administered by a person such as the infection control practitioner. Despite the general resistance of staff to influenza vaccination, some unique approaches have been successful in achieving the ambitious vaccination rate of 80%. For example, in one Wisconsin long-term care facility, an influenza cart with conspicuous markings proclaiming “Employee influenza vaccination: Protecting our residents” moved between nursing stations during different shifts daily over several weeks achieved a much higher employee vaccination rate than simply offering free vaccination at a central place. Another local long-term care facility holds an annual two-day in-service “fair” that includes a didactic session on influenza immediately followed by a vaccination workshop to immunize the staff while they are “hot” on the idea. Other long-term care facilities send thank you notes to vaccinated staff for doing their part in helping prevent an influenza outbreak. An influenza quiz distributed in September with answers given in October also appears to increase staff awareness. Education of personnel combined with effortless access to vaccine seems to be important in promoting staff vaccination. Despite vaccination programs instituted to prevent influenza and its spread, nursing home outbreaks occur annually. Vaccine failure may leave an institution susceptible to an influenza outbreak. Vaccines may fail because of influenza drift and shift, two different ways that influenza A can undergo antigenic variation and evade immune detection. The annual antigenic drift of influenza results from slight changes in the amino acid sequence on the surface glycoproteins and is one of the reasons that the vaccine formulation changes yearly. Antigenic shift results from influenza A acquiring an entirely different surface glycoprotein, leaving much of the host population without protective immunologic memory and therefore susceptible to the new virus.18 Antigenic shift occurs unpredictably and enables influenza A to cause pandemics.18 Important to recognize, however, is that
despite significant drift in the natural virus from the vaccine strain, the vaccine may still be efficacious. Vaccination may not reduce the incidence of primary infection in the long-term care facility, but it may significantly reduce influenza morbidity and mortality despite antigenic drift.8 Influenza vaccines also may fail to give the desired protection when post-vaccination serum hemagglutination inhibition titers of 40 or greater are not achieved.lg Because of advanced age and underlying disease, only about half of long-term care facility residents develop post-vaccine antibody titers greater than 40, compared with 80% to 90% of young healthy volunteers. Unfortunately, increasing the vaccine dose two or three times the standard commercial dose has not been superior in achieving “protective” titers and is therefore not recommended.21 Booster vaccinations for adults do not substantially improve titers and are therefore also not recommended.22 However, vaccine response may be enhanced by certain adjuvants23 and alternative vaccine formulations, such as conjugation of the influenza hemagglutinin to a carrier molecule like diphtheria toxoid.20 These investigational techniques also appear to result in greater antibody production and superior protection, and provide evidence for potential benefit from the vaccination even when antibody titers are not elevated.20 OUTBREAK
DETECTION
The first step in limiting influenza in the longterm care facility is prevention through compulsory vaccination programs. The next step is early detection with the expectation that earlier intervention can limit its spread. This requires active influenza surveillance. Daily screening of staff and residents is labor intensive, expensive, and therefore impractical. However, if staff are educated and alerted when influenza is in the community, they may voluntarily submit to free culturing and help identify patients with new respiratory symptoms for viral culturing. As many as half of influenza cases can be missed using the strict CDC influenza case definition that requires both fever and a respiratory sign or symptom, because frail subjects in long-term care facilities may not develop fever or have sufficient clinical complaints to compel the clinician to assess for fever.24 The presence of fever makes the clinical diagnosis more certain, but its absence does not exclude it. In our hands, about one (range = 0-4) respiratory illness symptomatic enough to merit documentation in the nursing record occurs per resident per influenza season. Laboratory data on these individuals suggest influenza in 15% to 20% serologically and 5% 10% by culture. Although useful epidemiologically, serologic confirmation of influenza takes several weeks
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AND
(one must wait for the convalescent specimen to perform a meaningful assay) and therefore is impractical for acute management. Cultures currently take two to five days to confirm the diagnosis of influenza; more rapid techniques are under study in long-term care facilities and could provide a diagnosis less than an hour after the specimen is obtained. Laboratory confirmation of influenza is important because the prevention and control measures for influenza are different from those for influenza-like illnesses caused by viruses such as respiratory syncytial and parainfluenza. MANAGEMENT OF OUTBREAKS
Once influenza virus infection is confirmed, there are four strategies for long-term care facilities to consider in their effort to limit its spread: vaccinate unvaccinated residents and staff; isolate infected individuals; treat infected individuals; and initiate chemoprophylaxis in uninfected individuals. Infection Control Practices Experts disagree on how influenza is spread and how long viable virus remains infectious on inanimate objects. Whereas influenza can survive on stainless steel and nonporous plastics for 24 to 48 hours and on paper tissues and other porous items for up to 12 hours, it may be transmitted from stainless steel surfaces for two to eight hours and from tissues for only a few minutes.25 Once transferred to the hands, influenza virus is viable for about five minutes. When influenza is introduced among residents sharing dining facilities, rooms, or caregivers, its transmission becomes increasingly likely because tables, chairs, doorknobs, and other inanimate objects are shared. Because transmission by fomite is possible and respiratory droplet is likely, respiratory isolation of an individual symptomatic with influenza may be insufficient, and secretion precautions also may be indicated. Alternative or additional options include masking asymptomatic residents who have risk factors for severe complicated influenza in order to further protect them, selecting symptomatic patients for placement into respiratory isolation and closing the ward to admissions and visitors, requiring ward visitors to wear masks and possibly gloves, and requiring employees to mask and glove while on an influenza ward. The latter options would be instituted in an effort to limit viral spread from one ward to other parts of the long-term care facility, although they may be difficult to implement. It is not known if negative pressure air flow into isolation rooms (or conversely, into the anterooms) influences the spread of influenza within the longterm care facility as it can with other viruses. In
HOSPItAl EPIdEMIOLOGY
January 1992
addition, few long-term care facilities are equipped to enable isolation of residents from roommates. When long-term care facilities have such provisions available, these interventions may prove appropriate. However, there are no prospective data to indicate if respiratory isolation, secretion precautions, or any other precautions will enable a long-term care facility to contain the outbreak. Such measures may fail because the potential speed at which this virus can spread may outrun antiviral medication, and asymptomatic patients may be able to transmit virus but cannot be isolated because they cannot be identified. Our compromise when influenza season “begins” (i.e., when there is documented influenza A activity within a 90-mile radius) is to post signs at all entrances instructing persons with any upper respiratory tract sign or symptom not to enter the facility before consulting with the infection control practitioner. Resident furloughs into the community are restricted to those medically necessary. Once individuals with symptoms suspicious for influenza (cases) are identified on a ward, the ward is closed to new admissions, and all cases are placed in isolation for the five-day contagious period. This isolation includes restricting the resident to his or her room, keeping the room door shut, and requiring persons to wear masks while in the resident’s room and washing their hands upon exiting. Direct contact for care would require gowns and gloves. The ward puts all nonmedically related in-house appointments on hold and restricts visitors because of the theoretical risk that asymptomatic influenza cases on the ward could transmit influenza to other parts of the long-term care facility. The roommates of all cases are placed in respiratory isolation. As far as possible, personnel are restricted from floating to other wards. We attempt to have only vaccinated staff provide care for suspected influenza cases and avoid concurrent high-risk resident assignments, especially those with chronic heart and lung diseases. Any subsequent staff or resident with upper respiratory signs or symptoms, even if afebrile, are considered possible cases and are screened by viral culture. Role of Amantadine/Rimantadine The CDC recommendations for preventing the spread of influenza are vague but encourage the use of amantadine once influenza A is detected in long-term care facilities.2 This is recommended because influenza activity during outbreaks has declined since the prophylactic introduction of amantadine or its analog rimantadine. Amantadine decreases the duration and severity of influenza symptoms in individuals who have an amantadine-sensitive infection. However, the recommendation needs to be interpreted with caution.
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Topics IN LOng-TErM CaRE
Reports concluding efficacy of antiviral prophylaxis have not been from controlled prospective studies; amantadine toxicity is significant in institutionalized elderly, and rapid emergence and transmission of amantadine-resistant influenza occurs in the longterm care facility setting, thereby potentially limiting the drug’s benefit.8 Amantadine’s side effects are largely related to its action on the central nervous system and occur in up to 33% of recipients.26 For this reason, it may not be well-tolerated in elderly subjects, and its prescription is poorly complied with in the younger professional staff who initially agree to take it. The side effects include hyperexcitability, tremors, slurred speech, insomnia, lightheadedness, irritability, difficulty concentrating, dry mouth, gastrointestinal upset, nocturia, and urinary retention, and occur in 5% to 10% of healthy adults taking this drug.27-2g Nursing home residents tend to be frail, have numerous underlying medical conditions, and receive multiple prescription medications; they are consequently at a high risk for adverse drug events. Of the more serious amantadine-associated adverse drug events, falls have been reported in 3% of elderly amantadine recipients.‘O As in our experience with nearly 900 institutionalized subjects, there is no significant difference between fallers and nonfallers regarding underlying medical disorders, osteoarthritis, or medication use.3o Our data suggest that adverse drug events may be significantly more prevalent in the setting of prophylaxis than previously recognized. Unlike the observations of others,“’ we noted that falls increased four- to eight-fold during prophylaxis,32 an important observation when one considers that 5% of falls result in hip fracture. Patients were more likely to be agitated and physically restrained during the amantadine course, and seizures occurred more frequently (six residents with a seizure history had seizures during the 30-day amantadine prophylaxis but no seizure in the year prior to prophylaxis). Additionally, adverse drug events may mimic other disease states, making it difficult to distinguish a drug effect from exacerbation or progression of existing diseases, which could lead to unnecessary interventions. For example, in a population where confusion is already prevalent, increased confusion may result in the prescription of additional psychoactive medications, which further increases the likelihood of adverse drug events. Adverse drug events also are related to drug accumulation. Renal function declines with age (creatinine clearance declines 1% per year starting at age 30),“” and amantadine is principally cleared by the kidneys. As the extent of drug toxicity is directly related to dose and blood levels,34 risk for toxicity
53
increases with age. The likelihood for adverse reaction is high and the clinical consequences are worrisome when amantadine prophylaxis is indiscriminately prescribed in the long-term care facility. Because of our concerns regarding amantadine’s efficacy and toxicity, we do not adhere to the interpretation of the CDC recommendation that a single case of influenza A in a long-term care facility should declare an influenza outbreak and result in institution-wide prophylaxis.2 Our approach is to begin with careful isolation of ill patients, culture confirmation, and, if the index of suspicion is high, institution of creatinine clearance-adjusted amantadine in ill residents for five days and the roommate for ten days. If the resident has been symptomatic with an influenzalike illness for more than 48 hours, we do not initiate amantadine treatment for that individual, as there are no data suggesting efficacy in this situation. It is advisable to have vaccinated staff care for residents with influenza-like illnesses and no other residents. We also rigorously restrict the ward and the individuals who have regular direct contact with its residents from the rest of the long-term care facility, encourage more frequent handwashing and the wearing of masks, and reinforce reporting of new illnesses to the infection control practitioner. These measures are designed to limit viral transmission. Our threshold for the institution of amantadine prophylaxis is reached when 10% of residents on a ward have influenza-like illness or an upper respiratory illness with cultures pending within a one-week period, and influenza A has been documented in the community or the long-term care facility. Creatinine clearance-adjusted amantadine prophylaxis is then initiated in residents without a seizure history and also in willing staff of that ward, but not in the remainder of the facility. Our interpretation of the CDC recommendation regarding the duration of amantadine prophylaxis also is conservative. We continue amantadine prophylaxis two weeks beyond the last clinical influenza case within the long-term care facility or the neighboring community (population
BY
DAVID W. BENTLEY, MD
Prevention and Control of Influenza A Outbreaks in Long-Term Care Facilities Stefan Gravenstein, MD; Barbara A. Miller, RN; Paul Drinka, MD
No single virus has the health impact of influenza. Influenza has remained epidemiologically important because it escapes host immune pressure through antigenic variation, is highly contagious, and can cause pneumonia and death in the most susceptible hosts. Viral transmission is most efficient where contact between susceptible hosts is greatest. For humans, this includes institutional settings such as daycare centers, schools, hospitals, and long-term care facilities. Of the three types of influenza, influenza C is relatively nonvirulent. Influenza B is most virulent in children; its antigenic stability presumably allows the adult population to benefit from acquired immunity. Influenza A is virulent in people of all ages, especially in those at the extremes of age or with immunocompromising disease; the attack rate in persons over 70 years of age is four times that of adults under 40 years of age.’ A major factor accounting for recurrent influenza A epidemics is change in the virus (antigenic drift and shift) that renders the vaccine less efficacious. Influenza epidemics cost billions of dollars and result in thousands of deaths annually. This discussion will focus on the prevention and treatment of influenza A in the long-term care facility. CLINICAL INFECTION
The severity of influenza, a typically self-limiting illness, is influenced by viral virulence factors and the health and age of the host. Most cases are sympto-
matic, although 20% of infected persons may be asymptomatic. The initial cases in long-term care facilities are often first diagnosed postmortem or recognized retrospectively. The clinical diagnosis of influenza is more easily made when concurrent cases present with fever and respiratory symptoms such as cough, coryza, and sore throat, and influenza is known to be circulating in the community. Influenza differs from most other viral infections in that it frequently spreads to involve the lower respiratory tract. Influenza A and pneumonia increasingly contribute to morbidity and mortality with advancing age; over 80% of excess deaths attributed to pneumonia and influenza occur among persons 65 years of age or older.2 The tenth leading cause of death in younger individuals, influenza and pneumonia are ranked seventh among individuals 55 to 74 years of age and fourth among those over the age of 74.3 During influenza epidemics, pneumonia is the second leading cause of death among octogenarians.4 Influenza-associated mortality is not only accounted for by pneumonia but also from subsequent events arising from underlying cardiovascular, cerebrovascular, and other chronic or immunocompromising diseases. An institutional influenza A outbreak can result in up to 70% of the population becoming ill, with 22% of those affected developing complications severe enough to result in hospitalization or death.5 Although illness from influenza B virus generally is less severe, case-fatality rates of 10% have been reported in nurs-
From the Section of Geriatrics, Department of Medicine, University of Wisconsin-Madison (Drs. Gravenstein and Drinka and MS Miller), and the William S. Middleton Memorial Veterans’ Hospital, Madison (Drs. Gravenstein and Drinka), and the Wisconsin Veterans’ Home, King, Wisconsin (Dr Drinka). Supported by the NIH, AG00548 and AG09632 (SG). Address reprint requests to Stefan Gravenstein, MD, University of Wisconsin, Institute on Aging and Adult Life, 425 Henry Mall, Room 330, Madison, WI 53706. Gravenstein S, Miller BA, Drinka P. Prevention and control of influenza A outbreaks in long-term care facilities. Infect Control Hosp Epidemiol. 1992;13:49-54.
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AND
ing home outbreaks6 Even among otherwise healthy elderly persons, studies of interepidemic outbreaks of influenza have shown that hospitalization rates increased sixfold for pneumonia and influenza.4 ANNUAL INFLUENZA VACCINATION
Recurrent institutional influenza A outbreaks are caused by a variety of unique circumstances present in long-term care facilities and may include reduced vaccine efficacy in this population. To reduce the clinical impact of influenza outbreaks in this setting, one must first identify those factors that contribute to the inoculation and subsequent spread of influenza A. The most important factor permitting introduction of infection and subsequent spread of influenza in longterm care facilities is the failure to vaccinate. The Centers for Disease Control (CDC) recommends annual influenza vaccination for any person over 65 years of age with or without underlying medical condition because of increased risk for complications following infection. In addition, healthcare workers and others in close contact with high-risk persons should be vaccinated annually. Employee vaccination programs have the potential to reduce staff-to-patient influenza transmission and illness-associated absenteeism. Epidemiologic studies of several long-term care facility outbreaks identified a long-term care facility employee as the index case (i.e., the individual most likely to have introduced influenza into the long-term care facility) (Personal communication. Centers for Disease Control. 1991.). Unfortunately, fewer than 30% of this population2 and frequently fewer than half of nursing home residents receive the influenza vaccine in any given year.5 Our experience is similar to that reported by others5J; we rarely have seen even 30% vaccination rates in long-term care facility personnel. Influenza vaccination programs are the most cost-effective approach for influenza control.8 Vaccination programs may fail to achieve high vaccination rates because many individuals in the target group fear injections or their side effects, believe that the vaccine does not work or is unnecessary, or simply miss the opportunity to be vaccinated when the program is available.g However, influenza vaccination rarely results in more than local tenderness at the vaccination site; placebo vaccinations (saline solution) cause similar rates of complaints. If tenderness occurs, it rarely lasts more than two days and generally does not interfere with the activities of daily living. Systemic symptoms like coryza or malaise, although less common, may last for a few days postvaccination. Vaccine recipients may need reassurance that such complaints are not caused by the development of an influenza illness, because there is
HOSPITAL EPIDEMIOLOGY
January 1992
no live influenza virus in the modem vaccine capable of causing influenza. The Guillian-Barré, Syndrome complication associated with the 1976 influenza vaccination program is not expected to be repeated.2 The only contraindications to influenza vaccination are anaphylactic hypersensitivity to eggs (these are used in manufacturing the vaccine) and allergy to contact lens solution (the thimerosol preservative in the vaccine is used in many contact lens solutions). Many studies have demonstrated vaccine efficacy even in the elderly and chronically ill.l”J1 The degree of protection conferred by vaccination is dependent on vaccine response.12 Vaccination can reduce the risk for hospitalization, pneumonia, and death in long-term care facilities by two- to six-fold during influenza outbreaks.5J3 Well-matched vaccination has been shown to be effective in reducing clinical illness, viral shedding, and therefore transmission of the virus to others. When enough individuals within a given setting have immunity to a circulating virus (herd immunity), the ability of the virus to infect them is limited.2J4 Although a variety of factors determine the specific number of individuals that need to be immunized, a goal of vaccinating 80% of subjects with the appropriate vaccine may be sufficient for herd immunity in a closed setting.5 Some institutional vaccination programs for the elderly are implemented as soon as the vaccine becomes available, even as early as August. Although it may take six weeks for the elderly to develop optimal antibody titers, vaccinating them in August and September is likely premature because protective antibody titers rarely last more than a few months,15 leaving them unprotected for much of the influenza season. It is advisable to vaccinate the elderly as close to six weeks before the expected influenza season as possible. In most states, the influenza season begins in late December. However, states at higher altitudes and latitudes may have an earlier winter and therefore may enter the influenza season sooner (e.g., Colorado and Alaska). In Wisconsin, we encourage vaccination programs to begin in late October with a goal of finishing in November. This is an appropriate time for most states and is in agreement with CDC recommendations.” Vaccination programs for long-term care facility residents generally require individual physician orders and patient consent.5 This task is simplified by getting patient/guardian consent for annual influenza vaccination upon admission to the long-term care facility and having the order preprinted on medication order sheets as a routine medication renewal prior to the influenza season. Fall and winter long-term care facility admissions that occur after vaccination programs need to have their vaccination status checked
Vol. 13 No. 1
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IN
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and updated; nearly half of elderly persons hospitalized in fall and winter are discharged from the hospital unvaccinated.‘6 Hospitals could facilitate the vaccination effort by making seasonal influenza vaccination part of the discharge planning process. Performing all long-term care facility influenza vaccinations within a few weeks while continuing vaccination of new staff and residents seems efficient. When an influenza outbreak is detected, vaccination should be offered again to residents and staff who previously refused vaccination; vaccination throughout the influenza season has potential benefit for the unimmunized.17 Implementing these recommendations may be feasible only if the delivery system is organized and administered by a person such as the infection control practitioner. Despite the general resistance of staff to influenza vaccination, some unique approaches have been successful in achieving the ambitious vaccination rate of 80%. For example, in one Wisconsin long-term care facility, an influenza cart with conspicuous markings proclaiming “Employee influenza vaccination: Protecting our residents” moved between nursing stations during different shifts daily over several weeks achieved a much higher employee vaccination rate than simply offering free vaccination at a central place. Another local long-term care facility holds an annual two-day in-service “fair” that includes a didactic session on influenza immediately followed by a vaccination workshop to immunize the staff while they are “hot” on the idea. Other long-term care facilities send thank you notes to vaccinated staff for doing their part in helping prevent an influenza outbreak. An influenza quiz distributed in September with answers given in October also appears to increase staff awareness. Education of personnel combined with effortless access to vaccine seems to be important in promoting staff vaccination. Despite vaccination programs instituted to prevent influenza and its spread, nursing home outbreaks occur annually. Vaccine failure may leave an institution susceptible to an influenza outbreak. Vaccines may fail because of influenza drift and shift, two different ways that influenza A can undergo antigenic variation and evade immune detection. The annual antigenic drift of influenza results from slight changes in the amino acid sequence on the surface glycoproteins and is one of the reasons that the vaccine formulation changes yearly. Antigenic shift results from influenza A acquiring an entirely different surface glycoprotein, leaving much of the host population without protective immunologic memory and therefore susceptible to the new virus.18 Antigenic shift occurs unpredictably and enables influenza A to cause pandemics.18 Important to recognize, however, is that
despite significant drift in the natural virus from the vaccine strain, the vaccine may still be efficacious. Vaccination may not reduce the incidence of primary infection in the long-term care facility, but it may significantly reduce influenza morbidity and mortality despite antigenic drift.8 Influenza vaccines also may fail to give the desired protection when post-vaccination serum hemagglutination inhibition titers of 40 or greater are not achieved.lg Because of advanced age and underlying disease, only about half of long-term care facility residents develop post-vaccine antibody titers greater than 40, compared with 80% to 90% of young healthy volunteers. Unfortunately, increasing the vaccine dose two or three times the standard commercial dose has not been superior in achieving “protective” titers and is therefore not recommended.21 Booster vaccinations for adults do not substantially improve titers and are therefore also not recommended.22 However, vaccine response may be enhanced by certain adjuvants23 and alternative vaccine formulations, such as conjugation of the influenza hemagglutinin to a carrier molecule like diphtheria toxoid.20 These investigational techniques also appear to result in greater antibody production and superior protection, and provide evidence for potential benefit from the vaccination even when antibody titers are not elevated.20 OUTBREAK
DETECTION
The first step in limiting influenza in the longterm care facility is prevention through compulsory vaccination programs. The next step is early detection with the expectation that earlier intervention can limit its spread. This requires active influenza surveillance. Daily screening of staff and residents is labor intensive, expensive, and therefore impractical. However, if staff are educated and alerted when influenza is in the community, they may voluntarily submit to free culturing and help identify patients with new respiratory symptoms for viral culturing. As many as half of influenza cases can be missed using the strict CDC influenza case definition that requires both fever and a respiratory sign or symptom, because frail subjects in long-term care facilities may not develop fever or have sufficient clinical complaints to compel the clinician to assess for fever.24 The presence of fever makes the clinical diagnosis more certain, but its absence does not exclude it. In our hands, about one (range = 0-4) respiratory illness symptomatic enough to merit documentation in the nursing record occurs per resident per influenza season. Laboratory data on these individuals suggest influenza in 15% to 20% serologically and 5% 10% by culture. Although useful epidemiologically, serologic confirmation of influenza takes several weeks
52
INFEcTIOuS CONTrOl
AND
(one must wait for the convalescent specimen to perform a meaningful assay) and therefore is impractical for acute management. Cultures currently take two to five days to confirm the diagnosis of influenza; more rapid techniques are under study in long-term care facilities and could provide a diagnosis less than an hour after the specimen is obtained. Laboratory confirmation of influenza is important because the prevention and control measures for influenza are different from those for influenza-like illnesses caused by viruses such as respiratory syncytial and parainfluenza. MANAGEMENT OF OUTBREAKS
Once influenza virus infection is confirmed, there are four strategies for long-term care facilities to consider in their effort to limit its spread: vaccinate unvaccinated residents and staff; isolate infected individuals; treat infected individuals; and initiate chemoprophylaxis in uninfected individuals. Infection Control Practices Experts disagree on how influenza is spread and how long viable virus remains infectious on inanimate objects. Whereas influenza can survive on stainless steel and nonporous plastics for 24 to 48 hours and on paper tissues and other porous items for up to 12 hours, it may be transmitted from stainless steel surfaces for two to eight hours and from tissues for only a few minutes.25 Once transferred to the hands, influenza virus is viable for about five minutes. When influenza is introduced among residents sharing dining facilities, rooms, or caregivers, its transmission becomes increasingly likely because tables, chairs, doorknobs, and other inanimate objects are shared. Because transmission by fomite is possible and respiratory droplet is likely, respiratory isolation of an individual symptomatic with influenza may be insufficient, and secretion precautions also may be indicated. Alternative or additional options include masking asymptomatic residents who have risk factors for severe complicated influenza in order to further protect them, selecting symptomatic patients for placement into respiratory isolation and closing the ward to admissions and visitors, requiring ward visitors to wear masks and possibly gloves, and requiring employees to mask and glove while on an influenza ward. The latter options would be instituted in an effort to limit viral spread from one ward to other parts of the long-term care facility, although they may be difficult to implement. It is not known if negative pressure air flow into isolation rooms (or conversely, into the anterooms) influences the spread of influenza within the longterm care facility as it can with other viruses. In
HOSPItAl EPIdEMIOLOGY
January 1992
addition, few long-term care facilities are equipped to enable isolation of residents from roommates. When long-term care facilities have such provisions available, these interventions may prove appropriate. However, there are no prospective data to indicate if respiratory isolation, secretion precautions, or any other precautions will enable a long-term care facility to contain the outbreak. Such measures may fail because the potential speed at which this virus can spread may outrun antiviral medication, and asymptomatic patients may be able to transmit virus but cannot be isolated because they cannot be identified. Our compromise when influenza season “begins” (i.e., when there is documented influenza A activity within a 90-mile radius) is to post signs at all entrances instructing persons with any upper respiratory tract sign or symptom not to enter the facility before consulting with the infection control practitioner. Resident furloughs into the community are restricted to those medically necessary. Once individuals with symptoms suspicious for influenza (cases) are identified on a ward, the ward is closed to new admissions, and all cases are placed in isolation for the five-day contagious period. This isolation includes restricting the resident to his or her room, keeping the room door shut, and requiring persons to wear masks while in the resident’s room and washing their hands upon exiting. Direct contact for care would require gowns and gloves. The ward puts all nonmedically related in-house appointments on hold and restricts visitors because of the theoretical risk that asymptomatic influenza cases on the ward could transmit influenza to other parts of the long-term care facility. The roommates of all cases are placed in respiratory isolation. As far as possible, personnel are restricted from floating to other wards. We attempt to have only vaccinated staff provide care for suspected influenza cases and avoid concurrent high-risk resident assignments, especially those with chronic heart and lung diseases. Any subsequent staff or resident with upper respiratory signs or symptoms, even if afebrile, are considered possible cases and are screened by viral culture. Role of Amantadine/Rimantadine The CDC recommendations for preventing the spread of influenza are vague but encourage the use of amantadine once influenza A is detected in long-term care facilities.2 This is recommended because influenza activity during outbreaks has declined since the prophylactic introduction of amantadine or its analog rimantadine. Amantadine decreases the duration and severity of influenza symptoms in individuals who have an amantadine-sensitive infection. However, the recommendation needs to be interpreted with caution.
Vol. 13 No. 1
Topics IN LOng-TErM CaRE
Reports concluding efficacy of antiviral prophylaxis have not been from controlled prospective studies; amantadine toxicity is significant in institutionalized elderly, and rapid emergence and transmission of amantadine-resistant influenza occurs in the longterm care facility setting, thereby potentially limiting the drug’s benefit.8 Amantadine’s side effects are largely related to its action on the central nervous system and occur in up to 33% of recipients.26 For this reason, it may not be well-tolerated in elderly subjects, and its prescription is poorly complied with in the younger professional staff who initially agree to take it. The side effects include hyperexcitability, tremors, slurred speech, insomnia, lightheadedness, irritability, difficulty concentrating, dry mouth, gastrointestinal upset, nocturia, and urinary retention, and occur in 5% to 10% of healthy adults taking this drug.27-2g Nursing home residents tend to be frail, have numerous underlying medical conditions, and receive multiple prescription medications; they are consequently at a high risk for adverse drug events. Of the more serious amantadine-associated adverse drug events, falls have been reported in 3% of elderly amantadine recipients.‘O As in our experience with nearly 900 institutionalized subjects, there is no significant difference between fallers and nonfallers regarding underlying medical disorders, osteoarthritis, or medication use.3o Our data suggest that adverse drug events may be significantly more prevalent in the setting of prophylaxis than previously recognized. Unlike the observations of others,“’ we noted that falls increased four- to eight-fold during prophylaxis,32 an important observation when one considers that 5% of falls result in hip fracture. Patients were more likely to be agitated and physically restrained during the amantadine course, and seizures occurred more frequently (six residents with a seizure history had seizures during the 30-day amantadine prophylaxis but no seizure in the year prior to prophylaxis). Additionally, adverse drug events may mimic other disease states, making it difficult to distinguish a drug effect from exacerbation or progression of existing diseases, which could lead to unnecessary interventions. For example, in a population where confusion is already prevalent, increased confusion may result in the prescription of additional psychoactive medications, which further increases the likelihood of adverse drug events. Adverse drug events also are related to drug accumulation. Renal function declines with age (creatinine clearance declines 1% per year starting at age 30),“” and amantadine is principally cleared by the kidneys. As the extent of drug toxicity is directly related to dose and blood levels,34 risk for toxicity
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increases with age. The likelihood for adverse reaction is high and the clinical consequences are worrisome when amantadine prophylaxis is indiscriminately prescribed in the long-term care facility. Because of our concerns regarding amantadine’s efficacy and toxicity, we do not adhere to the interpretation of the CDC recommendation that a single case of influenza A in a long-term care facility should declare an influenza outbreak and result in institution-wide prophylaxis.2 Our approach is to begin with careful isolation of ill patients, culture confirmation, and, if the index of suspicion is high, institution of creatinine clearance-adjusted amantadine in ill residents for five days and the roommate for ten days. If the resident has been symptomatic with an influenzalike illness for more than 48 hours, we do not initiate amantadine treatment for that individual, as there are no data suggesting efficacy in this situation. It is advisable to have vaccinated staff care for residents with influenza-like illnesses and no other residents. We also rigorously restrict the ward and the individuals who have regular direct contact with its residents from the rest of the long-term care facility, encourage more frequent handwashing and the wearing of masks, and reinforce reporting of new illnesses to the infection control practitioner. These measures are designed to limit viral transmission. Our threshold for the institution of amantadine prophylaxis is reached when 10% of residents on a ward have influenza-like illness or an upper respiratory illness with cultures pending within a one-week period, and influenza A has been documented in the community or the long-term care facility. Creatinine clearance-adjusted amantadine prophylaxis is then initiated in residents without a seizure history and also in willing staff of that ward, but not in the remainder of the facility. Our interpretation of the CDC recommendation regarding the duration of amantadine prophylaxis also is conservative. We continue amantadine prophylaxis two weeks beyond the last clinical influenza case within the long-term care facility or the neighboring community (population
