Estimated impact of aggressive empirical antiviral treatment in containing an outbreak of pandemic influenza H1N1 in an isolated First Nations community

Abstract

Background: The 2009 influenza A (H1N1) pandemic was mild by historical standards, but was more severe in isolated Canadian Indigenous communities. Oseltamivir was used aggressively for outbreak control in an isolated northern Ontario First Nations community. We used mathematical modeling to quantify the impact of antiviral therapy on the course of this outbreak.

Methods: We used both a Richards growth model and a compartmental model to evaluate the characteristics of the outbreak based on both respiratory visits and influenza-like illness counts. Estimates of best-fit model parameters, including basic reproductive number (R0 ) and antiviral efficacy, and simulations, were used to estimate the impact of antiviral drugs compared to social distancing interventions alone.

Results: Using both approaches, we found that a rapidly growing outbreak slowed markedly with aggressive antiviral therapy. Richards model turning points occurred within 24 hours of antiviral implementation. Compartmental models estimated antiviral efficacy at 70-95%. Plausible estimates of R from both modeling approaches ranged from 4·0 to 15·8, higher than published estimates for southern Canada; utilization of aggressive antiviral therapy in this community prevented 962-1757 cases of symptomatic influenza and as many as 114 medical evacuations in this community.

Conclusion: Although not advocated in other settings in Canada, aggressive antiviral therapy markedly reduced the impact of a pandemic-related influenza A (H1N1) outbreak in an isolated Canadian First Nations community in northern Ontario, Canada. The differential risk experienced by such communities makes tailored interventions that consider risk and lack of access to medical services, appropriate.

Keywords: Epidemiology; Indigenous health; influenza; mathematical modeling; oseltamivir.

Figure 1

Demographic characteristics of 16 initial virologically confirmed cases of influenza A (H1N1)‐2009 in Sandy Lake.

Figure 2

Epidemic curves for influenza A (H1N1)‐2009 outbreak in Sandy Lake. Epidemic curves from June 1 to June 21, 2009. Solid curve denotes epidemic curve for all healthcare visits related to influenza‐like illness; dashed curve represents visits meeting case definition for respiratory symptoms possibly compatible with influenza. The first vertical line denotes implementation of social distancing measures, while the second denotes actual implementation of aggressive antiviral treatment.

Figure 3

Actual and model‐predicted cumulative case counts by day of outbreak. Data are represented by hollow circles; model projections are denoted by solid curves (for large‐scale least squares, L‐S) or diamonds (Levenberg–Marquardt (L‐M). Models fit well for time series restricted to individuals meeting influenza‐like illness case definition (see text) (A) and for all individuals with symptomatology suggestive of possible influenza (B).

Figure 4

Compartmental model fits to Sandy Lake outbreak data. Ranges of model‐projected cumulative case counts by date (dashed lines) plotted against observed case counts for influenza‐like illness (black) and respiratory illness (gray). The blue vertical line denotes initiation of social distancing measures; the red vertical line denotes implementation of aggressive antiviral drug therapy.

Figure 5

Model‐based estimates of reproductive numbers plotted against generation times. Estimates generated using Richards models are plotted as solid lines with 95% confidence limits (dashed lines). Red lines represent late‐scale least squares fit models for all respiratory symptoms; blue lines are based on cases meeting case definition for influenza‐like illness (blue curves). Mean basic reproductive number estimates generated using compartmental SEIR models are presented as hollow triangle (respiratory visits) or hollow square (influenza‐like illness). The estimated reproductive number and from southern Ontario, derived from Tuite et al.,1 is shown as a hollow circle. Note that reproductive numbers are plotted on a natural log scale.