Medical Information

• What is Influenza?
• What is Pandemic Influenza?
• Prevention Strategies
• Vaccines
• Antiviral Drugs

What is Pandemic Influenza?

An influenza pandemic is a global outbreak of disease that occurs when a new influenza A virus appears or “emerges” in the human population, causes serious illness, and then spreads easily from person to person worldwide. Pandemics are different from seasonal outbreaks or “epidemics” of influenza. Seasonal outbreaks are caused by subtypes of influenza viruses that already circulate among people, whereas pandemic outbreaks are caused by new subtypes, by subtypes that have never circulated among people, or by subtypes that have not circulated among people for a long time. Generally we all get some level of immunity to the different subtypes circulating each season, as the subtypes are very similar. In pandemic influenza, an entirely new subtype appears and we have no inherent immunity. Past influenza pandemics have led to high levels of illness, death, social disruption, and economic loss.

Emergence of Pandemic Influenza Viruses

There are many different subtypes of influenza or “flu” viruses. The subtypes differ based upon certain proteins on the surface of the virus (the hemagglutinin or “H” protein and the neuraminidase or the “N” protein). Pandemic viruses emerge as a result of a process called "antigenic shift,” which causes an abrupt or sudden major change in influenza A viruses. These changes are caused by new combinations of the HA and/or NA proteins on the surface of the virus. Changes results in a new influenza A virus subtype. The appearance of a new influenza A virus subtype is the first step toward a pandemic; however, to cause a pandemic, the new virus subtype also must have the capacity to spread easily from person to person. Once a new pandemic influenza virus emerges and spreads, it usually becomes established among people and moves around or “circulates” for many years as seasonal epidemics of influenza. The World Health Organization (WHO) has large surveillance programs to monitor and detect influenza activity around the world, including the emergence of possible pandemic strains of influenza virus. Factors that influence the likelihood of a pandemic include: the emergence of a new viral subtype; the capacity for the virus to spread efficiently from person to person; and the virus being virulent enough to cause disease. It is not possible to predict when the next pandemic will occur or how long it will last. It is over 35 years since the last pandemic.

Influenza Pandemics during the 20th Century

During the 20th century, the emergence of several new influenza A virus subtypes caused three pandemics, all of which spread around the world within a year of being detected.

• 1918-19, "Spanish flu" [A (H1N1)], caused the highest number of known influenza deaths. (However, the actual influenza virus subtype was not detected in the 1918-19 pandemic). It is estimated that between 20-40 million people may have died worldwide. Many people died within the first few days after infection, and others died of secondary complications. Nearly 60% of those who died in Australia were young, healthy adults. Influenza A (H1N1) viruses still circulate today after being introduced again into the human population in 1977.
• 1957-58, "Asian flu" [A (H2N2)], caused a milder pandemic, as the disease was milder and spread slower, and focussed on children and the elderly. First identified in China in late February 1957, the Asian flu spread rapidly around the world. There was clear evidence of spread through mass gatherings.
• 1968-69, "Hong Kong flu" [A (H3N2)], caused a mild pandemic, possibly because many people had been exposed to H2N2 before and had some partial immunity. This virus was first detected in Hong Kong in early 1968. Influenza A (H3N2) viruses still circulate today.

Both the 1957-58 and 1968-69 pandemics were caused by viruses containing a combination of genes from a human influenza virus and an avian influenza virus. The 1918-19 pandemic virus appears to have an avian origin.

Lessons from previous pandemics

Not knowing which influenza virus strain is going to cause the next pandemic makes planning for it very challenging. The likely impact of a pandemic depends upon characteristics of the virus such as its infectivity, attack rates in different ages (the proportion of the population infected for each age group) and the severity of disease it causes. A description of the three pandemics of the 20th century demonstrates the variation in mortality, severity of illness and patterns of spread that can occur.

Consistent features of pandemics include sudden increases in morbidity and mortality, with rapid spread around the world (due to being caused by a highly contagious virus to which the population has little immunity). Pandemics usually spread to all parts of the globe within less than a year and affect more than a quarter of the total population. The ability of health and emergency systems to respond can be overwhelmed by the rapid increase in illness in the community. There is a tendency for pandemics to recur in second and sometimes third waves, which may begin simultaneously in different parts of the world.

Estimates of morbidity and mortality in Australia

If a pandemic with an attack rate of 25% (25% of the population affected) were to occur again in Australia and there was no pandemic vaccine or treatment available, over a 6-8 week period it could lead to:

• 13,000 - 44,000 deaths
• 57,900 - 148,000 hospitalisations
• 2,600,000 - 7,500,000 outpatient visits

The figures are estimates only and the likely outcomes associated with a pandemic will depend upon many factors such as the transmissibility and virulence of the virus, and the availability and success of health and social interventions.

In the absence of actual data on the potential pandemic virus, mathematical modelling, whereby various assumptions about the virus are included in a theoretical model to test various research questions and proposed strategies (such as school closures and quarantine measures), can provide a useful pandemic planning tool.

Stages of a Pandemic

WHO has developed a global influenza preparedness plan which defines the stages of a pandemic, outlines the role of WHO, and makes recommendations for national measures before and during a pandemic. The phases are:

Interpandemic period:

Phase 1: No new influenza virus subtypes have been detected in humans. An influenza virus subtype that has caused human infection may be present in animals. If present in animals, the risk of human infection or disease is considered to be low.

Phase 2: No new influenza virus subtypes have been detected in humans. However, a circulating animal influenza virus subtype poses a substantial risk of human disease.

Pandemic alert period

Phase 3: Human infection(s) with a new subtype, but no human-to-human spread, or at most rare instances of spread to a close contact. This is the current situation.

Phase 4: Small cluster(s) with limited human-to-human transmission but spread is highly localized, suggesting that the virus is not well adapted to humans.

Phase 5: Larger cluster(s) but human-to-human spread still localized, suggesting that the virus is becoming increasingly better adapted to humans but may not yet be fully transmissible (substantial pandemic risk).

Pandemic period

Phase 6: Pandemic: increased and sustained transmission in general population.

Notes: The distinction between phases 1 and 2 is based on the risk of human infection or disease resulting from circulating strains in animals and birds. The distinction is based on various factors and their relative importance according to current scientific knowledge. Factors may include pathogenicity in animals and humans, occurrence in domesticated animals and livestock or only in wildlife, whether the virus is enzootic or epizootic, geographically localized or widespread, and other scientific parameters.

The distinction among phases 3 and 4 is based on an assessment of the risk of a pandemic. Various factors and their relative importance according to current scientific knowledge may be considered. Factors may include rate of transmission, geographical location and spread, severity of illness, presence of genes from human strains (if derived from an animal or bird strain), and other scientific parameters.

The SARS Experience

Severe acute respiratory syndrome (SARS) is a newly identified acute viral respiratory syndrome caused by a novel coronavirus, the SARS coronavirus (SARS-CoV) which is believed to have crossed the species barrier recently from animals to humans. The first case was retrospectively recognized as having occurred in Guangdong Province, China, in November 2002. By July 2003, the international spread of SARS-CoV resulted in 8098 SARS cases in 26 countries, with 774 deaths. At the time of its emergence, it was unknown as a cause of human disease. The epidemic caused significant social and economic disruption in areas with sustained transmission of SARS, and on the travel industry internationally, in addition to the impact on health services directly.

The natural reservoir of SARS-CoV has not been identified but a number of wildlife species - the Himalayan masked palm civet, the Chinese ferret badger, and the raccoon dog - consumed as delicacies in southern China have shown laboratory evidence of infection with a related coronavirus. Domestic cats have been shown to be infected with SARS-CoV. These findings indicate that the reservoir for this pathogen may involve a range of animal species.

On 5 July 2003, the World Health Organization (WHO) reported that the last human chain of SARS transmission had been broken, so the world is in an inter-epidemic period for SARS. At this time the most probable sources of infection with SARS-CoV are exposure in laboratories where the virus is used or stored for diagnostic and research purposes, or from animal reservoirs of SARS-CoV-like viruses. Since July 2003 there have been four occasions when SARS has reappeared. Three of these incidents were attributed to breaches in laboratory biosafety and resulted in one or more cases of SARS. The fourth incident in Guangzhou, China, resulted in four sporadic community-acquired cases arising over a six-week period. Three of those cases were attributed to exposure to animal or environmental sources while the source of exposure is unknown in the other case.

It remains very difficult to predict when or whether SARS will re-emerge in epidemic form. The 2002-2003 epidemic was characterized rapid international spread. Health-care systems in areas with sustained transmission of SARS were rapidly overburdened and public health systems in countries free of SARS investigating cases of SARS-like illness were also severely stressed by the increased workload. If SARS does recur, early detection of infected individuals will be crucial to contain the spread of infection and prevent international spread.

The emergence of SARS has taught some very valuable lessons for public health, and the need for coordinated international responses with integrated action at all levels within countries. It is clear too that health resources are relatively easily overloaded, and that public perceptions, media use and education on basic health matters are all important considerations for countries and organisations.

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