A comparative analysis of influenza vaccination programs

Abstract

Background: The threat of avian influenza and the 2004-2005 influenza vaccine supply shortage in the United States have sparked a debate about optimal vaccination strategies to reduce the burden of morbidity and mortality caused by the influenza virus.

Methods and findings: We present a comparative analysis of two classes of suggested vaccination strategies: mortality-based strategies that target high-risk populations and morbidity-based strategies that target high-prevalence populations. Applying the methods of contact network epidemiology to a model of disease transmission in a large urban population, we assume that vaccine supplies are limited and then evaluate the efficacy of these strategies across a wide range of viral transmission rates and for two different age-specific mortality distributions. We find that the optimal strategy depends critically on the viral transmission level (reproductive rate) of the virus: morbidity-based strategies outperform mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. These results hold for a range of mortality rates reported for prior influenza epidemics and pandemics. Furthermore, we show that vaccination delays and multiple introductions of disease into the community have a more detrimental impact on morbidity-based strategies than mortality-based strategies.

Conclusions: If public health officials have reasonable estimates of the viral transmission rate and the frequency of new introductions into the community prior to an outbreak, then these methods can guide the design of optimal vaccination priorities. When such information is unreliable or not available, as is often the case, this study recommends mortality-based vaccination priorities.

Figure 1. Network Model

(A) A schematic of a network model for an urban population. Each individual is a vertex in the network, and edges represent potentially disease-causing contacts between individuals. Directed edges (with arrows) represent transmission occurring in only one direction. (B) We model vaccination in a population by removing nodes from the population network, and the edges that are attached to them. HCW, health-care worker.

Figure 2. Vaccination Strategies

The demographic distribution of vaccines according to each of the strategies: the black bars reflect the fraction of available vaccines given to each age group (and thus will always sum to one). The gray bars reflect the proportion of each demographic that is effectively immunized, and thus take into account the size of the demographic and the demographic-specific vaccine efficacy. HCW, health-care worker.

Figure 3. Morbidity and Mortality for Influenza Epidemics and Pandemics

Expected (A) attack rate and (B) mortality rate as a function of T for annual influenza epidemics. Expected (C) attack rate and (D) mortality rate as a function of T for an influenza pandemic. The dots in (A) show simulation results for comparison. Estimates of R ₀ for interpandemic and pandemic flu are shown as gray lines in (B) and (D), respectively.

Figure 4. Model Validation

Comparison of predicted to observed age-specific attack rates for (A) the 1977–1978 influenza season and (B) the 1918 influenza pandemic.

Figure 5. Direct versus Indirect Intervention

The figure shows the proportions of the adult and elderly populations that are infected, not infected (neither vaccinated nor infected), and vaccinated for two different values of T for the mortality-based strategy versus the morbidity-based strategy.

Figure 6. The Epidemiological Impact of Multiple Introductions of Disease

(A) The morbidity-based strategy is more effective than the mortality-based strategy when T is less than 0.13 only if there is only a single introduction of disease. With four introductions of disease, however, the morbidity-based strategy becomes less effective (and is the preferred strategy only when T is less than 0.12.) (B) At T = 0.125, the morbidity-based strategy is superior to the mortality-based strategy when there is a single introduction, but inferior when there is more than one introduction.

Figure 7. The Epidemiological Impact of Delayed Vaccination

(A) The morbidity-based strategy is more effective than the mortality-based strategy when T is less than 0.13 only if there is there is no delay in vaccination. When vaccines are given after 10% of the population has already been infected, the morbidity-based strategy becomes relatively less effective (and is the preferred strategy only when T is less than 0.11). (B) At T = 0.125, the morbidity-based strategy is superior to the mortality-based strategy when there is no delay, but inferior for any amount of delay. Each of the values is an average taken across 500 epidemic simulations on the contact network.