In the spring of 2009, the novel H1N1 influenza virus first emerged in Mexico and later spread widely throughout the world within just a few months. The World Health Organization (WHO) announced on June 11 the start of 2009 influenza pandemic [1
], and further issued an advisory on August 28 for countries in the northern hemisphere to prepare for a second wave of pandemic spread in the coming fall/winter [2
]. As of November 8, more than 206 countries and overseas territories or communities worldwide have reported laboratory confirmed cases of the pandemic pH1N1 virus, including over 6250 deaths [3
To lessen the severity of this pandemic, developing an effective flu vaccine and a global vaccination strategy is considered to be among the most important medical interventions [4
]. However, to have the greatest impact, pandemic vaccines need to be available quickly and in large quantities, and to be delivered to the population optimally. Moreover, vaccines against a novel pandemic strain might take up to six months to manufacture and deliver, even in developed countries [5
]. Given the potential threat of drug-resistance resulting from widespread use of antiviral treatment against pandemic flu, vaccine appears to be our primary weapon to prevent and to mitigate a pandemic. However, in addition to the need to consider the logistics of implementing large-scale vaccination, distinctly different age-specific mortalities had also been observed during some past flu pandemics (e.g., in 1918 [6
]), which require different priorities when large-scale vaccination is to be implemented.
Moreover, vaccine for influenza is known to have different efficacy (i.e., reduction in the number of infectives) and effectiveness (i.e., reduction in symptomatic case number) for different age groups, see e.g., [7
]. Setting priority for vaccination by targeting age groups most vulnerable (the elderly, infants, etc.) to prevent mortalities is commonly employed in most countries. However, when vaccinating those at greatest risk of mortality becomes impractical (if, e.g., medical care is relatively inaccessible) or inefficient (if, e.g., immune response is deficient), targeting those most likely to expose them to infection might be more preferable [10
]. In this way, the very young and the old might be better protected by vaccinating those who are most likely to be in contact with them (thereby reducing their risk of exposure), rather than by being vaccinated. Comparison of influenza mortality among elderly Japanese during time periods when schoolchildren were and were not vaccinated suggests that the infected children pose a risk to others [11
], including the elderly. Moreover, several past US experiences (as summarized in [12
]) also are consistent with this conclusion. Nonetheless, influenza policymakers have typically advocated protecting those individuals of ages 6-24 months and >65 years directly.
Bansal et al. [13
] recently carried out a comparative analysis of two classes of suggested vaccination strategies, namely, the mortality-based strategies that target the high-risk populations and the morbidity-based strategies that target the high-prevalence populations, by applying the methods of contact network epidemiology to a model of disease transmission in a large urban population. Using a range of mortality rates reported previously for past influenza epidemics and pandemics, they concluded that the optimal strategy depends critically on the viral transmission level (or reproduction number) of the virus. That is, the morbidity-based strategies outperform the mortality-based strategies for moderately transmissible strains, while the reverse is true for highly transmissible strains. However, they also cautioned that when information pertaining to viral transmission rate of a particular disease and the frequency of new introductions into the community prior to an outbreak is unreliable or not available, a mortality-based vaccination priority is recommended. This further demonstrates the importance of targeting and, moreover, the uncertainty surrounding this issue.
To further the uncertainties regarding influenza pandemic preparedness planning, it is widely believed that asymptomatic cases (i.e., individuals who had been infected but showed little or no symptoms) and asymptomatic infection of influenza (i.e., infection caused by an asymptomatic case) do indeed occur regularly (e.g., [14
Model with only asymptomatic infections, by either asymptomatic or subclinical infectives, during their infectivity period had been recently studied in [14
]. In this current study, we will consider a traditional compartmental model which incorporates both pre-symptomatic and asymptomatic infections, in order to explore the role which they could play in the overall spread of disease, if any. Moreover, the age-group structure of the model, by dividing the population into seven groups of the very young, preschool children, younger and older schoolchildren, young adults, adults, and the elderly, allows us to study targeted public health policies (e.g., immunization) aimed at different age groups. Our model also allows for inclusion of immunity and other age-dependent intervention measures such as quarantine and voluntary home withdrawal (see e.g., [15
]). A full model will be proposed to take into account of the above-mentioned factors that may be important in determining the best vaccine strategy.