The impact of case diagnosis coverage and diagnosis delays on the effectiveness of antiviral strategies in mitigating pandemic influenza A/H1N1 2009

Abstract

Background: Neuraminidase inhibitors were used to reduce the transmission of pandemic influenza A/H1N1 2009 at the early stages of the 2009/2010 pandemic. Policies for diagnosis of influenza for the purposes of antiviral intervention differed markedly between and within countries, leading to differences in the timing and scale of antiviral usage.

Methodology/principal findings: The impact of the percentage of symptomatic infected individuals who were diagnosed, and of delays to diagnosis, for three antiviral intervention strategies (each with and without school closure) were determined using a simulation model of an Australian community. Epidemic characteristics were based on actual data from the A/H1N1 2009 pandemic including reproduction number, serial interval and age-specific infection rate profile. In the absence of intervention an illness attack rate (AR) of 24.5% was determined from an estimated R(0) of 1.5; this was reduced to 21%, 16.5% or 13% by treatment-only, treatment plus household prophylaxis, or treatment plus household plus extended prophylaxis antiviral interventions respectively, assuming that diagnosis occurred 24 hours after symptoms arose and that 50% of symptomatic cases were diagnosed. If diagnosis occurred without delay, ARs decreased to 17%, 12.2% or 8.8% respectively. If 90% of symptomatic cases were diagnosed (with a 24 hour delay), ARs decreased to 17.8%, 11.1% and 7.6%, respectively.

Conclusion: The ability to rapidly diagnose symptomatic cases and to diagnose a high proportion of cases was shown to improve the effectiveness of all three antiviral strategies. For epidemics with R(0)< = 1.5 our results suggest that when the case diagnosis coverage exceeds ∼70% the size of the antiviral stockpile required to implement the extended prophylactic strategy decreases. The addition of at least four weeks of school closure was found to further reduce cumulative and peak attack rates and the size of the required antiviral stockpile.

Figure 1. Age-specific infection rate profiles for seasonal and A/H1N1 2009 influenza used to calibrate age-specific susceptibility.

The proportion of each age group infected in a baseline (unmitigated) epidemic is shown for seasonal influenza and for A/H1N1 2009. In both cases age demographics are those of the Albany model, and final infection rates are 17% (corresponding to a 13% final illness attack rate).

Figure 2. Outcome of six antiviral intervention strategies as a function of diagnosis delay.

Three outcomes are reported: (A) cumulative illness attack rate, (B) peak daily incidence (per 10,000 population), and (C) number of antiviral courses used as a percentage of the population size. We assumed that antiviral treatment or prophylaxis began at the time diagnosis was made and that 50% of symptomatic cases would be diagnosed.

Figure 3. Outcome of six antiviral intervention strategies as a function of diagnosis coverage.

Three outcomes are reported: (A) cumulative illness attack rate, (B) peak daily incidence (per 10,000 population), and (C) number of antiviral courses used as a percentage of the population size. We simulated percentages of symptomatic individuals being diagnosed ranging from 10% to 100% in 10% increments. We assumed that the delay between symptoms appearing and antiviral treatment or treatment plus prophylaxis was 24 hours.

Figure 4. Daily incidence epidemic curves for various delays in antiviral treatment and/or prophylaxis.

Interventions are abbreviated as follows: treatment only (T), household prophylaxis (H), extended prophylaxis (E), 4 weeks school closure (SC). We assumed that 50% of symptomatic cases would be diagnosed. Schools were assumed to close upon the diagnosis of 3 cases in the school for a period of two weeks. Each school closed a maximum of 2 times for a total of 4 weeks.

Figure 5. Daily incidence epidemic curves for various diagnosis coverages.

Interventions are abbreviated as follows: treatment only (T), household prophylaxis (H), extended prophylaxis (E), 4 weeks school closure (SC). We assumed that the delay between symptoms appearing and antiviral treatment or treatment plus prophylaxis was 24 hours. Schools were assumed to close upon the diagnosis of 3 cases in the school for a period of two weeks. Each school closed a maximum of 2 times for a total of 4 weeks.