Assessing the role of basic control measures, antivirals and vaccine in curtailing pandemic influenza: scenarios for the US, UK and the Netherlands

Abstract

An increasing number of avian flu cases in humans, arising primarily from direct contact with poultry, in several regions of the world have prompted the urgency to develop pandemic preparedness plans worldwide. Leading recommendations in these plans include basic public health control measures for minimizing transmission in hospitals and communities, the use of antiviral drugs and vaccination. This paper presents a mathematical model for the evaluation of the pandemic flu preparedness plans of the United States (US), the United Kingdom (UK) and the Netherlands. The model is used to assess single and combined interventions. Using data from the US, we show that hospital and community transmission control measures alone can be highly effective in reducing the impact of a potential flu pandemic. We further show that while the use of antivirals alone could lead to very significant reductions in the burden of a pandemic, the combination of transmission control measures, antivirals and vaccine gives the most 'optimal' result. However, implementing such an optimal strategy at the onset of a pandemic may not be realistic. Thus, it is important to consider other plausible alternatives. An optimal preparedness plan is largely dependent on the availability of resources; hence, it is country-specific. We show that countries with limited antiviral stockpiles should emphasize their use therapeutically (rather than prophylactically). However, countries with large antiviral stockpiles can achieve greater reductions in disease burden by implementing them both prophylactically and therapeutically. This study promotes alternative strategies that may be feasible and attainable for the US, UK and the Netherlands. It emphasizes the role of hospital and community transmission control measures in addition to the timely administration of antiviral treatment in reducing the burden of a flu pandemic. The latter is consistent with the preparedness plans of the UK and the Netherlands. Our results indicate that for low efficacy and coverage levels of antivirals and vaccine, the use of a vaccine leads to the greatest reduction in morbidity and mortality compared with the singular use of antivirals. However, as these efficacy and coverage levels are increased, the use of antivirals is more effective.

Figure 1

Flowchart diagram describing the high- and low-risk populations considered in model (2.1), where the index i denotes the high- (i=h) and low-risk $(i=\ell )$ classes. The implementation of antiviral prophylactically is only available to susceptibles (S_i), while therapeutic antivirals may be given to exposed (L_i), early-stage infectious $(I_{i_1})$ and asymptomatic (A_i) individuals. C and D classes are the populations of protected (via vaccination) and deceased cases, respectively.

Figure 2

The final number of deaths (dotted line), hospitalizations (dashed line) and infections (solid line) for varying reduction factors in hospital (1−ζ_i) and community settings (1−π_i). (a,b) Single control measures either in hospitals (a, π_i=1) or in community (b, ζ_i=1). (c,d) Control measures in both of these settings. We assume $\mathcal{R}$₀=1.9.

Figure 3

Baseline scenarios illustrating the final number of deaths (dotted line), hospitalizations (dashed line) and infections (solid line) for varying levels of hospital control measures. We assume a fixed 10% (π_i=0.9) reduction in community control measures and vary hospital control measures from 0 to 100% (ζ_i) for ${\mathcal{R}}_0$=1.6, 1.9, 2.1 and 2.4.

Figure 4

Contour plot of ${\mathcal{R}}_{\text{a}\text{v}}^i$ as a function of antiviral efficacy (ϵ_A). (a) An average time before antiviral intervention to latent and early-infectious individuals within 24 h (${\theta }_i^{-1}={\xi }_i^{-1}$=1 day). (b, c) The case in which therapeutic antivirals are implemented in 48 (${\theta }^{-1}={\xi }_i^{-1}=2$ days) and 72 h (${\theta }_i^{-1}={\xi }_i^{-1}=3$ days), respectively. The remaining parameters used in this simulation are provided in table 1.

Figure 5

Contour plot of ${\mathcal{R}}_{\text{v}}^i$ as a function of antiviral efficacy (ϵ_A) for fixed susceptible $(S_0^0=0.99)$ and vaccinated $(V_0^0=0.01)$ population proportions at the beginning of the outbreak. The remaining parameter values are provided in table 1.

Figure 6

Contour plot of ${\mathcal{R}}_{\text{eff}}^i$ as a function of infection control measures via hospital (1−ζ_i) and community (1−π_i) transmission reduction factors. (a) Results when the antiviral medications are administered within 24 h to latent, asymptomatic and early-infectious individuals (${\theta }_i^{-1}={\xi }_i^{-1}=1$ day). (b,c) The case in which therapeutic antivirals are implemented within 48 h (${\theta }_i^{-1}={\xi }_i^{-1}=2$ days) and 72 h (${\theta }_i^{-1}={\xi }_i^{-1}=3$ days), respectively. The remaining parameters used in this simulation are provided in table 1.

Figure 7

Contour plot of ${\mathcal{R}}_0^i$ as a function of infection control measures via hospital (1−ζ_i) and community (1−π_i) transmission reduction factors.