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Zanamivir use during transmission of amantadine-resistant influenza A in a nursing home
International Congress Series 1219 (2001) 823 – 828
Zanamivir use during transmission of amantadineresistant inf luenza A in a nursing home Yan Lia, Christine Leeb, Mark Loebc, Anne Phillipsd, Judy Nesbitte, Karen Smithe, Margaret Fearonf, Margaret M. McArthurb, Tony Mazzullib, Allison McGeerb,* a
National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba, Canada Department of Microbiology, Mount Sinai and Princess Margaret Hospitals, University of Toronto, Toronto, Ontario, Canada c Department of Pathology and Molecular Medicine, McMaster University, , Hamilton, Ontario, Canada d Glaxo-Wellcome, Inc., Toronto, Ontario, Canada e Aurora Resthaven Nursing Home, Newmarket, Ontario, Canada f Ministry of Health and Long Term Care, Laboratory Branch, Ontario, Canada b
Abstract Background: Nursing home influenza outbreaks are common. Amantadine is effective for prophylaxis, but fails to control all outbreaks. We describe an outbreak of influenza A which continued due to amantadine resistance. Zanamivir use was associated with termination of the outbreak. Outbreak: The outbreak occurred in a 176-bed residential home for the elderly. Cases of respiratory illness started on March 5, and three of four nasopharyngeal swabs tested positive for influenza A. Amantadine was given to residents from 9 to 19 March; however, new cases continued to occur. The number of new cases increased to 11 on March 25, and five of six nasopharyngeal swabs tested were positive for influenza A. Despite re-initiation of amantadine, new cases continued. Nine nasopharyngeal swabs yielded amantadine-resistant influenza A. Intervention: Prophylactic zanamivir inhalations were initiated on April 2. Despite the level of dementia, 95% of residents cooperated, 74% had no difficulty with inhalations. Results: In the 2 weeks after the initiation of zanamivir, two new cases of respiratory illness occurred, neither confirmed as influenza A. No side effects were associated with zanamivir. Conclusion: Zanamivir use was associated with termination of an outbreak which amantandine had failed to control. Zanamivir was well tolerated and effective in the control of influenza A. D 2001 Elsevier Science B.V. All rights reserved. Keywords: Zanamivir; Nursing home; Influenza A
* Corresponding author. Department of Microbiology, Mount Sinai Hospital, Room 1460, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. Tel.: +1-416-586-3118. E-mail address: [email protected] (A. McGeer).
0531-5131/01/$ – see front matter D 2001 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 3 6 2 - 4
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1. Introduction Despite vaccination of residents and staff, as many as 40% of nursing homes in Canada report at least one influenza outbreak in any given year [1,2]. Both the US and Canadian expert bodies recommend antiviral prophylaxis for the control of nursing home outbreaks of influenza A [3,4]. Only amantadine is licensed in Canada. Amantadine is now used to control more than 80% of influenza A outbreaks in Ontario long-term care facilities [1,2]. However, use of amantadine may be limited by side effects, and by the emergence of resistance [5– 8]. Zanamivir is a new antiviral agent shown to be effective for treatment [9] and prophylaxis [10,11] of influenza. In the winter of 1999, the continuation of a nursing home outbreak of influenza A despite amantadine prophylaxis led us to study the feasibility of using zanamivir as prophylaxis in this setting.
2. Background Aurora Resthaven is a 176-bed residential long-term care facility for the elderly (median age 84 years). Seventy percent of staff and 90% of residents received the 1998 –1999 influenza vaccine in the fall of 1998.
Fig. 1. Epidemic curve of influenza A outbreak in a long-term care facility. Closed bars represent those cases from whom amantadine-resistant influenza A was isolated; dotted bars, those from whom amantadine susceptible virus was isolated; hatched bars, those from whom no virus was isolated; and open bars, those for whom no nasopharyngeal swab was tested.
Y. Li et al. / International Congress Series 1219 (2001) 823–828
825
On March 8/9, rapid antigen testing of nasopharyngeal swabs identified influenza as the cause of a cluster of respiratory illness. Outbreak control measures included case finding, recommending vaccine to unimmunized residents and staff, droplet isolation precautions for ill residents, restriction of ill staff and visitors, and cancellation of communal activities. In addition, a 10-day course of amantadine hydrochloride was offered to all residents and unimmunized staff. Five days after the completion of this course of amantadine, in response to an increasing number of cases and rapid antigen testing indicating continuing influenza A transmission (Fig. 1), a second course of amantadine prophylaxis was offered to asymptomatic residents. Cases of influenza continued to occur, and on April 2, zanamivir prophylaxis was recommended.
3. Methods A case was defined as an episode of acute respiratory illness (at least two of: temperature >37.4 °C, cough, sore throat, myalgia, coryza, new wheezes or crackles on chest exam) occurring between March 1 and April 16. Cases were classified as confirmed if influenza A was identified from a nasopharyngeal swab by culture or antigen detection, and probable if viral culture and antigen detection were not done or negative. Residents were assessed daily for respiratory symptoms from March 9 – April 16. Nasopharyngeal swabs were obtained from four new cases on March 25, six new cases on March 30, and all new cases from March 31 onward. Resident charts were reviewed for medical and demographic information. Zanamivir prophylaxis (10 mg once daily) was offered to asymptomatic residents, and treatment (10 mg twice daily) to case residents ill for < 48 h. Nursing staff categorized each resident’s ability to comply with instructions for zanamivir inhalations (sealing lips around the device and taking a deep breath) as able to comply without difficulty, able to comply but with difficulty, and not able to comply. Investigators (CL and AM) assessed compliance ability in a sample of residents. Rapid antigen detection for influenza A was performed on nasopharyngeal swabs from residents using a membrane ELISA (Directigen, Becton-Dickinson, Cockeysville, MD), or an in-house direct fluorescent antigen detection method. Specimens were inoculated into monolayer rhesus monkey kidney and Hep2 cells, and incubated for 2 weeks. Viral isolates were subtyped by hemagglutination inhibition, and tested for amantadine susceptibility testing by RT-PCR restriction and sequence analysis of the M2 gene [12].
4. Results Thirteen definite and 66 probable cases occurred (Fig. 1). Twelve (15%) developed pneumonia, seven (9%) were hospitalized and two (2.6%) died. Vaccine efficacy was estimated to be 14% (95% confidence limits, 39%, 53%) for prevention of respiratory illness, 71% (95% CL, 38%, 94%) for prevention of hospitalization, and 88% (95% CL, 1%, 100%) for prevention of death. All of the 12 influenza A isolates were similar to
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A/Sydney/05/97, the H3N2 component of the 1998 – 1999 vaccine. Three isolates obtained from residents before amantadine use were susceptible to amantadine. In contrast, all nine isolates obtained between March 25th and 30th were resistant to amantadine, and had the same point mutation resulting in a change from leucine to phenylalaline at amino acid position 26 in the transmembrane region of the M2 protein. One of these isolates was from a case-resident who did not receive amantadine during the initial phase of the outbreak. On April 2, 10 residents were eligible for treatment with zanamivir, and 130 for prophylaxis. Eleven of these (8%) were unwilling or unable to attempt inhalations ( P = 0.11 compared to amantadine). Of the remaining 129 residents, 100 (78%) were considered by staff to have no difficulty complying with instructions regarding inhalations. Twenty-nine (22%) residents attempted inhalations but had some difficulty (e.g. weak inhalation, incomplete seal of lips on device). Study staff agreed with the nursing home staff assessment in all residents assessed. Difficulty complying with inhalations was associated with poor functional status, and increasing dementia (Table 1). In the 2 weeks after the initiation of zanamivir, only two new cases of respiratory illness occurred. No residents required hospitalization, and none died. Nasopharyngeal swabs taken the day of onset in both cases were negative for all respiratory viruses by direct immunofluorescence and culture. None of the 128 residents had side effects associated with zanamivir inhalation.
Table 1 Relationship between long-term care facility resident characteristics and observational assessment of difficulty complying with instructions for zanamivir inhalations Characteristic
No. (%) of residents with difficulty inhaling zanamivir
P value *
Age group < 70 years 70 – 79 years 80 – 89 years 90 years
1/7 (14%) 3/25 (12%) 19/64 (30%) 6/32 (19%)
Functional statusa Dependent in 0 – 3 ADL Dependent in 4 – 5 ADL Dependent in 6 ADL Dependent in all 7 ADL
2/24 6/38 6/38 15/26
(8%) (16%) (16%) (58%)
< 0.001
Orientation to person/place/timeb All three Two of three One of three Not oriented
1/33 2/19 4/25 22/49
(3%) (11%) (16%) (45%)
< 0.001
0.25
* Analysis of variance. Functional status assessed by Katz score [13]; ADL = activities of daily living. b Orientation to person, place, and time as assessed by facility staff at most recent three monthly assessment. a
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5. Discussion This outbreak demonstrates that, although vaccination of residents and staff in longterm care facilities reduces mortality in residents and the risk of influenza outbreaks [1,14], the poor efficacy of vaccine in nursing home residents means that outbreaks will continue to occur, and outbreak management continues to be important [2,15]. The reported efficacy of amantadine and rimantadine is 75 –90% in influenza A prophylaxis in individuals [16], and several outbreak investigation reports provide convincing evidence of their efficacy in controlling outbreaks [6,17 – 20]. However, amantadine resistance emerges readily during therapy [21], and several previous reports document the emergence and transmission of amantadine-resistant viruses during nursing home influenza outbreaks [6– 8]. The isolation of an amantadine-resistant virus from a resident who had not previously received amantadine confirms transmission of resistant virus in this nursing home. Difficulty in isolating case-residents effectively and the treatment of case residents likely increased selective pressure in this facility. Several studies have shown that neuraminidase inhibitors, including zanamivir, are effective in treatment and prevention of influenza [9– 11]. Zanamivir is delivered topically to the respiratory tract by inhalation. Although minimal respiratory pressure is required to deliver the medication, some nursing home residents may not be able to fully cooperate with use of the Diskhaler1. In this facility, the majority (78%) of residents attempting inhalations complied without difficulty. Difficulty with inhalations was greatest in residents who were not oriented and were totally dependent in activities of daily living. As expected, zanamivir was well tolerated and no side effects were observed. Because zanamivir was introduced late in the outbreak, it is not possible to be sure that zanamivir was responsible for the termination of transmission of influenza A. Nonetheless, the use of zanamivir was temporally associated with control of transmission of amantadine-resistant influenza A, and has been associated with protection against influenza and termination of outbreaks in other reports [11,22]. Neuraminidase inhibitors may be useful adjuncts to the management of influenza in long-term care facilities.
References [1] C. Stevenson, M.A. McArthur, M. Naus, E. Abraham, A. McGeer, Respiratory disease prevention in Canadian long term care facilities: can we do better? CMAJ 64 (2001) 1413 – 1419. [2] B. Henry, Summary report of the Ontario influenza 1998/9 season, Public Health Epidemiol. Rep., Ont. 10 (1999) 144 – 159. [3] Advisory Committee on Immunization Practices, Prevention and control of influenza, MMWR 48 (1999) RR-4. [4] National Advisory Committee on Immunization. Statement on influenza vaccination for the 1999 – 2000 season, CCDR 25:ACS-2. [5] W.L. Atkinson, N.H. Arden, P.A. Patriarca, et al., Amantadine prophylaxis during an institutional outbreak of type A (H1N1) influenza, Arch. Intern. Med. 146 (1986) 1751 – 1756. [6] E.E. Mast, M.W. Harmon, S. Gravenstein, S.P. Wu, N.H. Arden, et al., Emergence and possible transmission of amantadine-resistant viruses during nursing home outbreaks of influenza A (H3N2), Am. J. Epidemiol. 134 (1991) 988 – 997.
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[7] J. Degelau, S. Somani, S. Cooper, D. Guay, K. Crossley, Amantadine-resistant influenza A in a nursing facility, Arch. Intern. Med. 152 (1992) 390 – 392. [8] P. Houck, M. Hemphill, S. LaCroix, D. Hirsh, N. Cox, Amantadine-resistant influenza A in a nursing homes, Arch. Intern. Med. 155 (1995) 533 – 537. [9] F.G. Hayden, A.D.M.E. Osterhaus, J.J. Treanor, Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections, N. Engl. J. Med. 337 (1997) 874 – 880. [10] A.S. Monto, D.P. Robinson, M.L. Herlocher, et al., Zanamivir in the prevention of influenza among healthy adults, JAMA 282 (1999) 31 – 35. [11] M. Schilling, L. Povinelli, P. Krause, et al., Efficacy of zanamivir for chemoprophylaxis of nursing home outbreaks, Vaccine 16 (1998) 1771 – 1774. [12] A.I. Klimov, E. Rocha, F.G. Hayden, R.A. Schult, L.F. Roumillat, N.J. Cox, Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients: detection by polymerase chain reactionrestriction analysis, J. Infect. Dis. 172 (1995) 1352 – 1355. [13] S. Katz, T.D. Downs, H.R. Cash, R.D. Frotz, Progress in the development of the index of ADL, Gerontologist 10 (1970) 20 – 30. [14] W.F. Carman, A.G. Elder, L.A. Wallace, K. McAulay, et al., Effects of influenza vaccination of health-care workers on mortality of elderly people in long-term care: a randomized controlled trial, Lancet 355 (2000) 93 – 97. [15] P.A. Gross, A.W. Hermogenes, H.S. Sacks, J. Lau, R.A. Lenadowski, The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature, Ann. Intern. Med. 123 (1995) 518 – 527. [16] R. Dolin, R.C. Reichman, H.P. Madore, et al., A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A in humans, N. Engl. J. Med. 307 (1982) 580 – 584. [17] K. Staynor, G. Foster, M. McArthur, A. McGeer, M. Petric, A.E. Simor, Influenza A outbreak in a nursing home: value of early diagnosis and the use of amantadine hydrochloride, Can. J. Infect. Control 9 (1994) 109 – 111. [18] N.H. Arden, P.A. Patriarca, M.B. Fasano, et al., The roles of vaccination and amantadine prophylaxis in controlling an outbreak of influenza A (H3N2) in a nursing home, Arch. Intern. Med. 148 (1988) 865 – 868. [19] N.L. Peters, S. Oboler, C. Hair, L. Laxson, J. Kost, G. Meiklejohn, Treatment of an influenza A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control, J. Am. Geriatr. Soc. 37 (1989) 210 – 218. [20] Anonymous, Control of influenza A outbreaks in nursing homes: amantadine as an adjunct to vaccine — Washington, 1989 – 90, MMWR 40 (1991) 841 – 844. [21] H.G. Hayden, R.B. Belshe, R.D. Clover, et al., Emergence and apparent transmission of rimantadineresistant influenza A virus in families, N. Engl. J. Med. 321 (1989) 1696 – 1702. [22] W. Lee, M. McArthur, A. Kam, P. Friedman, A. Phillips, A. Simor, M. Loeb, A. McGeer, Use of Zanamivir to Control an Outbreak of Influenza A in a Nursing Home, Abstract presented at: Community and Hospital Infection Control Association of Canada 2000, Toronto, Ontario, May 29 – 31 2000.
Zanamivir use during transmission of amantadineresistant inf luenza A in a nursing home Yan Lia, Christine Leeb, Mark Loebc, Anne Phillipsd, Judy Nesbitte, Karen Smithe, Margaret Fearonf, Margaret M. McArthurb, Tony Mazzullib, Allison McGeerb,* a
National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba, Canada Department of Microbiology, Mount Sinai and Princess Margaret Hospitals, University of Toronto, Toronto, Ontario, Canada c Department of Pathology and Molecular Medicine, McMaster University, , Hamilton, Ontario, Canada d Glaxo-Wellcome, Inc., Toronto, Ontario, Canada e Aurora Resthaven Nursing Home, Newmarket, Ontario, Canada f Ministry of Health and Long Term Care, Laboratory Branch, Ontario, Canada b
Abstract Background: Nursing home influenza outbreaks are common. Amantadine is effective for prophylaxis, but fails to control all outbreaks. We describe an outbreak of influenza A which continued due to amantadine resistance. Zanamivir use was associated with termination of the outbreak. Outbreak: The outbreak occurred in a 176-bed residential home for the elderly. Cases of respiratory illness started on March 5, and three of four nasopharyngeal swabs tested positive for influenza A. Amantadine was given to residents from 9 to 19 March; however, new cases continued to occur. The number of new cases increased to 11 on March 25, and five of six nasopharyngeal swabs tested were positive for influenza A. Despite re-initiation of amantadine, new cases continued. Nine nasopharyngeal swabs yielded amantadine-resistant influenza A. Intervention: Prophylactic zanamivir inhalations were initiated on April 2. Despite the level of dementia, 95% of residents cooperated, 74% had no difficulty with inhalations. Results: In the 2 weeks after the initiation of zanamivir, two new cases of respiratory illness occurred, neither confirmed as influenza A. No side effects were associated with zanamivir. Conclusion: Zanamivir use was associated with termination of an outbreak which amantandine had failed to control. Zanamivir was well tolerated and effective in the control of influenza A. D 2001 Elsevier Science B.V. All rights reserved. Keywords: Zanamivir; Nursing home; Influenza A
* Corresponding author. Department of Microbiology, Mount Sinai Hospital, Room 1460, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. Tel.: +1-416-586-3118. E-mail address: [email protected] (A. McGeer).
0531-5131/01/$ – see front matter D 2001 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 3 6 2 - 4
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1. Introduction Despite vaccination of residents and staff, as many as 40% of nursing homes in Canada report at least one influenza outbreak in any given year [1,2]. Both the US and Canadian expert bodies recommend antiviral prophylaxis for the control of nursing home outbreaks of influenza A [3,4]. Only amantadine is licensed in Canada. Amantadine is now used to control more than 80% of influenza A outbreaks in Ontario long-term care facilities [1,2]. However, use of amantadine may be limited by side effects, and by the emergence of resistance [5– 8]. Zanamivir is a new antiviral agent shown to be effective for treatment [9] and prophylaxis [10,11] of influenza. In the winter of 1999, the continuation of a nursing home outbreak of influenza A despite amantadine prophylaxis led us to study the feasibility of using zanamivir as prophylaxis in this setting.
2. Background Aurora Resthaven is a 176-bed residential long-term care facility for the elderly (median age 84 years). Seventy percent of staff and 90% of residents received the 1998 –1999 influenza vaccine in the fall of 1998.
Fig. 1. Epidemic curve of influenza A outbreak in a long-term care facility. Closed bars represent those cases from whom amantadine-resistant influenza A was isolated; dotted bars, those from whom amantadine susceptible virus was isolated; hatched bars, those from whom no virus was isolated; and open bars, those for whom no nasopharyngeal swab was tested.
Y. Li et al. / International Congress Series 1219 (2001) 823–828
825
On March 8/9, rapid antigen testing of nasopharyngeal swabs identified influenza as the cause of a cluster of respiratory illness. Outbreak control measures included case finding, recommending vaccine to unimmunized residents and staff, droplet isolation precautions for ill residents, restriction of ill staff and visitors, and cancellation of communal activities. In addition, a 10-day course of amantadine hydrochloride was offered to all residents and unimmunized staff. Five days after the completion of this course of amantadine, in response to an increasing number of cases and rapid antigen testing indicating continuing influenza A transmission (Fig. 1), a second course of amantadine prophylaxis was offered to asymptomatic residents. Cases of influenza continued to occur, and on April 2, zanamivir prophylaxis was recommended.
3. Methods A case was defined as an episode of acute respiratory illness (at least two of: temperature >37.4 °C, cough, sore throat, myalgia, coryza, new wheezes or crackles on chest exam) occurring between March 1 and April 16. Cases were classified as confirmed if influenza A was identified from a nasopharyngeal swab by culture or antigen detection, and probable if viral culture and antigen detection were not done or negative. Residents were assessed daily for respiratory symptoms from March 9 – April 16. Nasopharyngeal swabs were obtained from four new cases on March 25, six new cases on March 30, and all new cases from March 31 onward. Resident charts were reviewed for medical and demographic information. Zanamivir prophylaxis (10 mg once daily) was offered to asymptomatic residents, and treatment (10 mg twice daily) to case residents ill for < 48 h. Nursing staff categorized each resident’s ability to comply with instructions for zanamivir inhalations (sealing lips around the device and taking a deep breath) as able to comply without difficulty, able to comply but with difficulty, and not able to comply. Investigators (CL and AM) assessed compliance ability in a sample of residents. Rapid antigen detection for influenza A was performed on nasopharyngeal swabs from residents using a membrane ELISA (Directigen, Becton-Dickinson, Cockeysville, MD), or an in-house direct fluorescent antigen detection method. Specimens were inoculated into monolayer rhesus monkey kidney and Hep2 cells, and incubated for 2 weeks. Viral isolates were subtyped by hemagglutination inhibition, and tested for amantadine susceptibility testing by RT-PCR restriction and sequence analysis of the M2 gene [12].
4. Results Thirteen definite and 66 probable cases occurred (Fig. 1). Twelve (15%) developed pneumonia, seven (9%) were hospitalized and two (2.6%) died. Vaccine efficacy was estimated to be 14% (95% confidence limits, 39%, 53%) for prevention of respiratory illness, 71% (95% CL, 38%, 94%) for prevention of hospitalization, and 88% (95% CL, 1%, 100%) for prevention of death. All of the 12 influenza A isolates were similar to
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A/Sydney/05/97, the H3N2 component of the 1998 – 1999 vaccine. Three isolates obtained from residents before amantadine use were susceptible to amantadine. In contrast, all nine isolates obtained between March 25th and 30th were resistant to amantadine, and had the same point mutation resulting in a change from leucine to phenylalaline at amino acid position 26 in the transmembrane region of the M2 protein. One of these isolates was from a case-resident who did not receive amantadine during the initial phase of the outbreak. On April 2, 10 residents were eligible for treatment with zanamivir, and 130 for prophylaxis. Eleven of these (8%) were unwilling or unable to attempt inhalations ( P = 0.11 compared to amantadine). Of the remaining 129 residents, 100 (78%) were considered by staff to have no difficulty complying with instructions regarding inhalations. Twenty-nine (22%) residents attempted inhalations but had some difficulty (e.g. weak inhalation, incomplete seal of lips on device). Study staff agreed with the nursing home staff assessment in all residents assessed. Difficulty complying with inhalations was associated with poor functional status, and increasing dementia (Table 1). In the 2 weeks after the initiation of zanamivir, only two new cases of respiratory illness occurred. No residents required hospitalization, and none died. Nasopharyngeal swabs taken the day of onset in both cases were negative for all respiratory viruses by direct immunofluorescence and culture. None of the 128 residents had side effects associated with zanamivir inhalation.
Table 1 Relationship between long-term care facility resident characteristics and observational assessment of difficulty complying with instructions for zanamivir inhalations Characteristic
No. (%) of residents with difficulty inhaling zanamivir
P value *
Age group < 70 years 70 – 79 years 80 – 89 years 90 years
1/7 (14%) 3/25 (12%) 19/64 (30%) 6/32 (19%)
Functional statusa Dependent in 0 – 3 ADL Dependent in 4 – 5 ADL Dependent in 6 ADL Dependent in all 7 ADL
2/24 6/38 6/38 15/26
(8%) (16%) (16%) (58%)
< 0.001
Orientation to person/place/timeb All three Two of three One of three Not oriented
1/33 2/19 4/25 22/49
(3%) (11%) (16%) (45%)
< 0.001
0.25
* Analysis of variance. Functional status assessed by Katz score [13]; ADL = activities of daily living. b Orientation to person, place, and time as assessed by facility staff at most recent three monthly assessment. a
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5. Discussion This outbreak demonstrates that, although vaccination of residents and staff in longterm care facilities reduces mortality in residents and the risk of influenza outbreaks [1,14], the poor efficacy of vaccine in nursing home residents means that outbreaks will continue to occur, and outbreak management continues to be important [2,15]. The reported efficacy of amantadine and rimantadine is 75 –90% in influenza A prophylaxis in individuals [16], and several outbreak investigation reports provide convincing evidence of their efficacy in controlling outbreaks [6,17 – 20]. However, amantadine resistance emerges readily during therapy [21], and several previous reports document the emergence and transmission of amantadine-resistant viruses during nursing home influenza outbreaks [6– 8]. The isolation of an amantadine-resistant virus from a resident who had not previously received amantadine confirms transmission of resistant virus in this nursing home. Difficulty in isolating case-residents effectively and the treatment of case residents likely increased selective pressure in this facility. Several studies have shown that neuraminidase inhibitors, including zanamivir, are effective in treatment and prevention of influenza [9– 11]. Zanamivir is delivered topically to the respiratory tract by inhalation. Although minimal respiratory pressure is required to deliver the medication, some nursing home residents may not be able to fully cooperate with use of the Diskhaler1. In this facility, the majority (78%) of residents attempting inhalations complied without difficulty. Difficulty with inhalations was greatest in residents who were not oriented and were totally dependent in activities of daily living. As expected, zanamivir was well tolerated and no side effects were observed. Because zanamivir was introduced late in the outbreak, it is not possible to be sure that zanamivir was responsible for the termination of transmission of influenza A. Nonetheless, the use of zanamivir was temporally associated with control of transmission of amantadine-resistant influenza A, and has been associated with protection against influenza and termination of outbreaks in other reports [11,22]. Neuraminidase inhibitors may be useful adjuncts to the management of influenza in long-term care facilities.
References [1] C. Stevenson, M.A. McArthur, M. Naus, E. Abraham, A. McGeer, Respiratory disease prevention in Canadian long term care facilities: can we do better? CMAJ 64 (2001) 1413 – 1419. [2] B. Henry, Summary report of the Ontario influenza 1998/9 season, Public Health Epidemiol. Rep., Ont. 10 (1999) 144 – 159. [3] Advisory Committee on Immunization Practices, Prevention and control of influenza, MMWR 48 (1999) RR-4. [4] National Advisory Committee on Immunization. Statement on influenza vaccination for the 1999 – 2000 season, CCDR 25:ACS-2. [5] W.L. Atkinson, N.H. Arden, P.A. Patriarca, et al., Amantadine prophylaxis during an institutional outbreak of type A (H1N1) influenza, Arch. Intern. Med. 146 (1986) 1751 – 1756. [6] E.E. Mast, M.W. Harmon, S. Gravenstein, S.P. Wu, N.H. Arden, et al., Emergence and possible transmission of amantadine-resistant viruses during nursing home outbreaks of influenza A (H3N2), Am. J. Epidemiol. 134 (1991) 988 – 997.
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