Infection Control & Hospital Epidemiology
interval [CI], 1.21–1.46). Thus, for every day that passes from the second case to the initiation of oseltamivir, the odds of a resident at risk of infection in the facility developing ILI increased by 33%.
Discussion
These data indicate that the sooner oseltamivir chemoprophylaxis is initiated, the lower the odds of secondary infection with influenza in LTCFs during outbreaks caused by influenza A H3N2 in Manitoba. The data also indicate that the number of residents in a facility and the number of days from the first case to the second case are negatively associated with the odds of secondary infection in LTCFs with influenza A H3N2 outbreaks. In the study preceding this one, these associations were not statistically significant in the adjusted model, but we observed a trend toward significance.22 The results of these 2 variables may have become statistically significant because of the increased power of the current study.22 The timing of oseltamivir chemoprophylaxis was statistically significant in both studies.22 This study provides strong evidence supporting the rapid
detection of influenza A H3N2 outbreaks and the rapid admin- istration of oseltamivir chemoprophylaxis in a LTC resident population. Delays in this process can occur at many key points, including collection of nasopharyngeal specimens, transport of specimens to the laboratory, identification of viruses present, communication of results, making the decision to administer oseltamivir chemoprophylaxis, and the actual administration of oseltamivir.
Strengths and limitations
This study has several strengths. First, this is the largest study examining the effect of the timing of oseltamivir chemoprophy- laxis in influenza A H3N2 outbreaks in LTC facilities to date, and we employed a common provincial approach to oseltamivir prophylaxis. Second, we examined the secondary attack rate, which is a much more accurate approach to examine the impact of oseltamivir chemoprophylaxis than total attack rate. Third, vaccination rates were not a significant confounder for infection in the 2014–2015 influenza season for influenza A H3N2 because of lack of effectiveness of the vaccine for that strain of circulating virus.23 Fourth, oseltamivir resistance is likely not a confounder because none of the 73 influenza A H3N2 samples tested in Manitoba for oseltamivir resistance were positive.13 In addition, only 1 of the 913 influenza A H3N2 samples tested in Canada for oseltamivir resistance was positive.13 Fifth, some discrepancies between LTCFs are controlled for by including hand hygiene audits, staff vaccination rates, public versus private operation, and time between declaring an outbreak and the start of chemopro- phylaxis. After an outbreak is declared, chemoprophylaxis of its residents should occur immediately. When this is not the case, a difference in the operations and preparedness of these facilities may be indicated. Sixth, several other potentially significant variables are included in the analysis. Finally, a hierarchical model was used, accounting for both the number of outbreaks and the size of the facilities involved. This study also has several limitations. First, not all cases of ILI
received a nasopharyngeal swab. Therefore, some cases of ILI that developed during the outbreaks may have been caused by other respiratory viruses. However, this lack of specificity likely affected all institutions equally at random, so only the magnitude of the result should be affected not the presence of an effect. Second,
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although this study attempts to control for some of the dis- crepancy between how various facilities operate, some of these differences may not be accounted for by the control variables and may confound the results in an unpredictable way. Third, the analysis does not control for individual factors, such as age, comorbidities, smoking status, or mobility, among the various LTCF residents. Therefore, differences such as the number and types of comorbidities and other demographic differences could theoretically be present and could affect the results. Fourth, this study does not examine hospitalization or mortality. However, these variables are less sensitive measures of effectiveness and the decision to hospitalize a patient can be very subjective. Fifth, many outbreaks were missing data to the extent that they could not be included in the analysis (27 influenza A H3N2 outbreaks of 94 total). If these facilities were significantly different in character from those with sufficient information for analysis, the results may not be as generalizable. However, given the variation in institutional characteristics present in the 53 institutions in the analysis, these results are likely widely applicable to LTCFs.
Generalizability of findings
The findings presented should be applicable across North America and Europe. All of these areas have similar LTC resident populations, infection control precautions, and institutional standards,24,25 and they all use oseltamivir for chemoprophylaxis in influenza outbreaks.6,9,10,16,19
Future research
Future research regarding the effect of the timing of oseltamivir chemoprophylaxis in LTCFs should be targeted at influenza B and influenza A H1N1, as these have not yet been studied in a rigorous way. Due to the relatively large amount of missing data common to many retrospective cohort studies, a prospective study may be more beneficial. However, the advantages of a prospective study will need to be weighed against the need for increased time and resources. Eventually, separate strategies regarding chemopro- phylaxis may be employed based on the circulating type or subtype of influenza in the community. Other outcomes, such as hospi- talization and mortality, could also be examined. This would be valuable since these are the outcomes that infection prevention and control programs are ultimately striving to prevent.
Acknowledgments. The authors thank the Regional Health Authority Ethics Review Boards and Infection Prevention and Control Coordinators from the Winnipeg Regional Health Authority (WRHA), Interlake-Eastern Regional Health Authority (IERHA), Northern Regional Health Authority (NRHA), Prairie Mountain Health (PMH), and Southern Health – Santé Sud (SH) for their assistance in accessing the necessary data and for their helpful colla- boration. No drug manufacturers had any involvement, direct or indirect, with any portion of the planning or production of this manuscript.
Financial support. No financial support was provided relevant to this article.
Conflicts of interest. All authors report no conflicts of interest relevant to this article.
References 1. National Advisory Committee on Immunization. Statement on Seasonal Influenza Vaccine for 2015–2016. Government of Canada website. https://
www.canada.ca/en/public-health/services/immunization/national-advisory- committee-on-immunization-naci/statement-on-seasonal-influenza-vaccine-
2015-2016.html. Published 2015. Accessed May 1, 2018.
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