# **DETERMINANTS OF A PANDEMIC INFLUENZA OUTBREAK AND ITS CONTROL**

The properties of a future pandemic influenza virus relevant to the containment and mitigation of outbreaks may be uncertain, but studies have attempted to create scenarios for policy analysis based on three sources of information. First, clinical, epidemiological, and laboratory data exist in the form of tissue samples from patients, records of public health measures, as well as overall morbidity and mortality estimates from influenza pandemics of the 20<sup>th</sup> century: in 1918‐20, 1957‐58, and 1968‐69. Second, researchers have been tracking the evolution of the current avian influenza A (subtype H5N1) virus and the associated human cases. This virus is considered the prime candidate for generating a pandemic capable strain. Predicting potential mutations in the H5N1 strain helps create new scenarios of the properties of a pandemic virus and inform prevention and control measures. Third, there are extensive studies of the transmission of seasonal influenza (various subtypes), which can help model the transmission of a more efficient human communicable strain of any avian influenza A virus that attacks people.

A discussion of how an avian virus of subtype H5N1 may potentially mutate to pandemic capable form is omitted. Assuming that this mutation occurs, a substantial proportion of the world population – some studies assume 60%<sup>62</sup> – would be susceptible. The two basic properties of a pandemic influenza virus relevant to prevention and mitigation are considered below: _infectivity_ and _virulence_ . Thereafter, some concepts related to infectivity – or more generally, transmissibility – used in modeling outbreaks are discussed with reference to pandemic influenza viruses (e.g., the effective contact rate, the basic reproduction number). Connected to both infectivity and virulence, the current science on antiviral, vaccine, and personal protective equipment efficacy is discussed.

**_Infectivity_** : The more intrinsically infectious a virus, the higher the likelihood that when an infected person meets an average uninfected person, a second infection will occur. Here, an infection is defined as developing antibodies to the viral presence in the body – also known as ‘exposure’ – and is prior to developing a clinical case of the disease (i.e., symptoms). Given a level of base infectivity of the virus, the likelihood of a secondary infection is modified by several factors ‐ the effectiveness of the contact between infected and uninfected, environmental conditions, and the presence of preventive barriers (i.e., prophylaxis via pharmaceuticals, or physical protection). The issue of effective contact is briefly considered after _virulenc e_ below.

There are three types of human influenza viruses: A, B, and C. Of these, only influenza A viruses, which have subtypes based on the hemagglutinin (HA) and neuraminidase (NA) protein combinations on the viral surface, have caused pandemics. Influenza B virus strains may be widely transmitted in seasonal epidemics, but usually do not cause pandemics. Influenza C virus generally causes mild illnesses in humans<sup>2</sup> . In this review, only influenza A is considered. The base infectivity of influenza A viruses depends on the rate at which the average infected person ‘sheds’ the virus, the timing of the ‘peak shedding’ period, the mode of transmission for the shed virus, minimum size of an infectious dose of virus, and survivability of the virus on surfaces and in the air.

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