Volume 27-05
1 March 2001

[Table of Contents]

EXPERIENCE WITH OSELTAMIVIR IN THE CONTROL OF A NURSING HOME INFLUENZA B OUTBREAK

Introduction

An influenza B outbreak began on 13 December, 2000, in a 300-bed extended care nursing home in the Simon Fraser Health Region (SFHR) in New Westminster, British Columbia (B.C.), Canada. We report this as the first influenza B strain outbreak to our knowledge in Canada where oseltamivir (Tamiflu^®) prophylaxis was implemented for control purposes.

The SFHR provides integrated health services to over 500,000 residents in the lower mainland of B.C., immediately adjacent to the city of Vancouver. The care facility involved has four 75-bed wards, which were occupied by 286 residents at the onset of the outbreak. The residents' mean age was 78 years. Extended care is the uppermost category of long-term care in B.C. for those who are wheelchair bound and need assistance in transferring.

Immunization coverage records in this facility estimate that 77% of the residents received publicly-funded influenza immunization in the Fall of 2000, with 90% of the immunizations delivered between 1 and 10 November. Thirty-six percent of the residents' records confirmed pneumococcal immunization at some point in the past. The staff influenza immunization rate was 57% (358/627).

Outbreak Identification

A nasal swab taken from a resident with influenza-like illness (ILI) symptoms on 13 December, 2000, was reported by the B.C. Provincial Laboratory on 17 December to be positive for influenza B on direct fluorescent antigen (DFA) testing. Earlier community influenza B isolates had been strain identified as B/Yamanashi-like. This strain is included as a current vaccine component. On 17 December, the facility reported additional residents with ILI to public health authorities.

All eight initial ILI cases with onset between 13 and 20 December occurred within a geographically separate area of one ward, Three West (3W). Six of these eight ILI cases were DFA laboratory-confirmed as influenza B. Cohorting and room restriction of ill residents was implemented on 17 December. An influenza outbreak was declared on 20 December, and restrictions were placed on new admissions and resident transfers to this geographically separate section of Three West.

Control Using Oseltamivir

On 22 December, a single case of ILI was identified elsewhere on this ward. A course of limited oseltamivir prophylaxis of residents on Three West was attempted in order to restrict the outbreak to this ward. This decision was based on recent recommendations to consider new antiviral medications in the control of influenza outbreaks in long term care settings⁽¹⁾, and on oseltamivir's safety and efficacy profile in seniors^(2,3). However, published literature on the effectiveness of oseltamivir in the control of influenza B outbreaks in nursing homes is limited. Residents without ILI symptoms underwent prophylaxis with oseltamivir 75 mg po od. However, it was observed that while this prophylactic regimen had successfully arrested the outbreak on Three West within a couple days; over the next 10 days residents elsewhere in the facility who had not undergone prophylaxis showed signs of ILI. Therefore, on 3 January, 2001 it was decided that oseltamivir prophylaxis would be extended to all residents of the facility who had not yet developed ILI and who had estimated creatinine clearances of >= 10 mL/min. With this intervention, the last ILI case occurred on 7 January, and the outbreak was declared over on 15 January, 2001.

A total of 28 resident cases of ILI occurred during the outbreak (Figure 1), with an overall attack rate of 10%. The attack rate among immunized residents was 9% (20/220), and 12% (8/66) among non-immunized residents. The facility did not track ILI cases among staff in detail, although the facility director reported that over the course of the outbreak many staff members were away on sick-leave.

On 10 January, a positive influenza A culture was reported on a case with an ILI symptom onset date of 30 December - this case had initially been DFA negative. In total, 10 residents had positive influenza B nasal swabs, with symptom onset dates ranging from 13 to 31 December, 2000. There was only a single influenza A result.

Clinical experience with oseltamivir

Of the 286 residents in the facility, 263 were eligible to be started on oseltamivir prophylaxis on the date it was offered (Figure 1). Of the eventual 28 residents with ILI, 23 developed symptoms before prophylaxis was offered.

Of the 263 residents started on prophylaxis, four developed ILI during the first 48 hours of prophylaxis and one resident developed ILI after 96 hours of prophylaxis. Thus oseltamivir worked very well in preventing ILI after 48 hours of prophylaxis. The five residents who developed ILI after initiating oseltamivir prophylaxis were converted to a treatment protocol of oseltamivir 75 mg bid for 5 days (75 mg od if estimated creatinine clearance < 30 mL/min).

The 263 residents who initiated prophylaxis received oseltamivir for an average of 15 days, with a range of 11 to 23 days for those who continued prophylaxis until the outbreak was declared over. Three residents discontinued prophylaxis prior to the end of the outbreak. One resident was transferred to acute care for unrelated medical reasons after 5 days of prophylaxis, at which time it was discontinued. Another resident accepted 2 days of prophylaxis and then refused further medication, but denied symptoms of any kind. The third resident received 8 days of prophylaxis after which, the regimen was discontinued due to difficulty swallowing.

Two residents on oseltamivir prophylaxis complained of nausea; one, on initiation of prophylaxis, and the other, after 13 days (the last day of prophylaxis). Neither resident had to discontinue prophylaxis because of this symptom. No other symptoms were noted by staff or attributed to oseltamivir prophylaxis.

One resident with ILI onset prior to prophylaxis was hospitalized because of chest infection. Three residents, all of whom had ILI onset prior to prophylaxis, died during the outbreak. The average age of these three residents was 83 years. Two died of pneumonia, however the cause of death was not available for the third resident.

Throughout the outbreak, staff continued to be shared between wards. It was recommended that non-immunized staff should be excluded from the facility; however, since much of the staff were non- immunized (43%), full implementation was impossible. Instead, attempts were made to cohort the care of ill residents by immunized direct-care staff.

Summary

Oseltamivir prophylaxis was very effective in protecting nursing home residents from ILI and in halting this outbreak of influenza B. A portion of the total ILI cases may have been due to influenza A, as this strain was isolated in one resident.

The 10% attack rate in this facility, controlled with oseltamivir, compares favourably with another influenza B outbreak in a similar facility in the same region, over the same time frame (ILI onset 27 December to 17 January). Oseltamivir prophylaxis was not used to manage this second outbreak of laboratory-confirmed influenza B. Of the 236 residents, 45 developed ILI for an overall attack rate of 19%, nearly double the rate in the oseltamivir-controlled setting (10%).

While oseltamivir was effective in controlling influenza B in this outbreak, further experience and evaluation is required before it can be routinely recommended for prophylaxis of influenza in nursing home outbreaks. Although earlier attempts by others using oseltamivir in the control of influenza A outbreaks have also met with success⁽³⁾, it is not yet licensed for this purpose. Compared to amantadine, oseltamivir has a relatively high cost for the control of influenza A outbreaks and this may continue to limit its wider acceptance. The cost-effectiveness of oseltamivir in the control of influenza B outbreaks needs to be specifically addressed given the typically milder nature of influenza B strains⁽⁴⁾. However, such a distinction is not clinically reliable and elderly residents of long-term care facilities remain vulnerable to serious complications associated with influenza infection in general. An alternate agent for influenza chemoprophylaxis that is effective against both influenza A and B, is easily administered and has few side effects, could greatly enhance current prevention and control measures and warrants serious assessment.

The spread of this outbreak from the geographically separate ward to other areas of the facility in which residents had not received prophylaxis, underscores the likely role of staff as a vehicle for transmission during facility outbreaks. While accurate staff ILI rates could not be determined, their immunization rates were low, and many staff were ill during the outbreak. Isolation of residents with ILI and prophylaxis of non-ill residents on the initial outbreak wards was insufficient to prevent the spread of the outbreak, although it was subsequently halted once prophylaxis was extended to all residents.

In view of the uncertainty over this medication's widespread use, in the absence of licensure or previous studies demonstrating its effectiveness in the prophylaxis and control of influenza B outbreaks, initiation of oseltamivir prophylaxis was staggered by ward. In a declared influenza A outbreak, the protocol in a long term care facility is to initiate amantadine prophylaxis on all residents, rather than ward-by-ward.

While anti-viral prophylaxis may be an effective secondary control measure in the management of influenza outbreaks, optimal primary prevention would be more effective. This would require increased vaccine coverage of residents and particularly of staff, who play an important role in the importation and transmission of influenza within these facilities^(5,6).

Acknowledgements

The authors would like to acknowledge the co-operation and contribution of staff and directors at the involved facilities, and the expert consultation provided by Dr. Allison McGeer of Mount Sinai Hospital, Toronto.

References

1. Couch RB. Prevention and treatment of influenza. N Engl J Med 2000;343:1778-85.

2. Lee C. Use of zanamivir to control an outbreak of influenza A. ICAAC September 2000, San Francisco.

3. Bowles SK, Vearncombe M, McGeer A et al. Use of oseltamivir in outbreaks of influenza in Ontario long term care facilities. CACMID November 2000, Ottawa.

4. Nicholson KG. Human influenza. In: Nicholson KG, Webster RB, Hay AJ (eds). Textbook of influenza oxford. Blackwell Science, 1998:358-72.

5. Van Voris LP, Belshe RG, Shaffer JL. Nosocomial influenza B virus infection in the elderly. Ann Intern Med 1982;96:153-58.

6. Pachuck CT, Walsh Pappas SA, Fuller GF et al. Influenza A among hospital personnel and patients. Arch Intern Med 1989;149:77-80.

Source:  Robert Parker, MD, Nadine Loewen, MD, Simon Fraser Health Region; Danuta Skowronski, MD, FRCPC, Epidemiology Services, B.C. Centre for Disease Control, Vancouver, British Columbia.

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