About pandemic influenza

Influenza is an illness of the respiratory tract caused by one of a number of influenza viruses. There are three virus types: influenza A, B and C. Influenza C causes only mild and usually sporadic respiratory illness. Regional and widespread epidemics are most often attributed to influenza A or B. Influenza A – which is found in humans and animals – causes the most severe disease and is the only type known to cause influenza pandemics.

Influenza A and B viruses have two main proteins on the outside of the virus: haemagglutinin (HA), which helps the virus enter the host respiratory cells, and neuraminidase (NA), which facilitates the release of virus particles from infected host cells. These proteins (also called antigens) are used in naming various viruses; for example, H5N1 is avian influenza or ‘bird flu’. H1N1 is also known as ‘swine flu’ and was the cause of the 2009 pandemic.

Influenza viruses have a high mutation rate – where the H and N antigens undergo change. Small mutations (called antigenic drift) are common and every 1–2 years virus change is seen. These changes are the cause of seasonal flu epidemics. The changes to the virus mean that little immunity is gained from previous infection, exposure or vaccination. This is why a new seasonal influenza vaccine is required each year.

Large mutations (called antigenic shift) cause the emergence of a new virus and the potential for a pandemic as there is no immunity in the population. Without any immunity, the virus can spread quickly from person to person, worldwide.

Three distinct influenza scenarios may be encountered in general practice:

• seasonal influenza, which occurs each winter. Most people experience 1–2 weeks of symptoms that are unpleasant but not usually life-threatening, except in the very young, pregnant women, or people with chronic health diseases
• epidemic influenza, which occurs when a new highly pathogenic and more severe influenza strain emerges. This can result in increased mortality and morbidity in local populations, especially in at-risk groups
• pandemic influenza, which occurs when a new highly pathogenic influenza strain emerges and spreads globally.

Seasonal influenza and pandemic influenza cause the same (or very similar) signs and symptoms. However, how often the influenza occurs, who gets ill and the severity of the disease may be quite different. Table 1 shows similarities and differences between seasonal and pandemic flu.

Seasonal influenza imposes a moderate but variable burden every year. The WHO estimates that seasonal influenza causes between 250,000 and 500,000 deaths worldwide each year.⁷

Unlike seasonal influenza, it is impossible to predict when and where the next pandemic will start, how quickly it will spread and what impact it will have on public health. The majority of deaths from seasonal influenza occur among people aged 65 years or older, but in a pandemic the proportion of deaths among the young increases.⁸
 

As was seen with the 2009 H1N1 pandemic, high death rates are not necessarily a feature of all influenza pandemics. Australia experienced 20-fold less mortality than several countries in the Americas.⁸

A number of factors may influence the mortality rate, including:

• the strength (virulence) of the virus
• the number of people infected
• the vulnerability of the affected populations
• implementation of public health mitigation strategies
• the effectiveness of preventive measures
• the number and duration of pandemic waves
• influenza vaccination coverage in preceding seasons
• the use of antivirals (where indicated) 
• access to intensive care

At a national level, Australia experienced only a mild pandemic with H1N1 causing fewer deaths than seasonal influenza.9 However, not all Australians were affected equally. Aboriginal and Torres Strait Islander peoples were found to be more vulnerable than the general Australian population. Aboriginal and Torres Strait Islander peoples had a mortality rate six times higher than non-Indigenous Australians.2 Research suggests that Aboriginal and Torres Strait Islander peoples may be particularly vulnerable to future infections (eg H7N9) due to a lack of preexisting T-cell immunity.10

A pandemic is a global infectious disease outbreak. The term ‘pandemic’ relates to how the disease spreads, not how widespread it is or how many deaths occur (eg. cancer is widespread and kills many people but is not a pandemic).

From studies done by the WHO, pandemic influenza develops in three stages (also see Figure 3):

Stage 1: An influenza virus in an animal develops the ability to infect humans and cause serious disease. During this phase, the virus is not able to transmit efficiently between humans. Contact with infected animals is needed for human infection to occur.

Stage 2: Following a genetic change, the virus becomes more efficient at passing from human to human, first within small groups (eg. families or community networks) and later over wider but still localised areas.

Stage 3: Finally, the virus is able to transmit readily between humans. It spreads rapidly due to a short incubation period, period of communicability and the infectious nature of influenza. Rapid global spread is aided by extensive international travel, which takes place every day between virtually every country in the world.

Novel influenza viruses such as avian influenza (H5N1) continue to circulate globally and are a potential source for a pandemic.

Influenza symptoms develop 1–3 days after the patient becomes infected and can include:

• fever, chills and sweating
• sore throat
• weakness
• headache and generalised muscle and joint pains (legs and back)
• a nonproductive cough that can later become severe and productive.

These symptoms can last up to approximately 1 week.

Influenza is more than a ‘bad cold’. Colds cause a runny nose, occasional mild fever but no muscle pains. Colds usually last 1–2 days. 

The influenza virus is highly infectious. This combined with a short incubation period (likely 1–3 days, maximum 7 days) and a period of viral shedding (when a person can infect others – 1 day before symptoms and up to 7 days after onset of illness in adults and up to 21 days in young children),¹² accounts for the rapid spread of the influenza virus.

The primary mode of transmission is by large respiratory droplets, which can be propelled up to 1 metre from an infected person who is coughing or sneezing, onto the mouth, nose or eyes (mucous membranes) of another person.

Spread is also by direct or indirect (fomite) contact, when a person touches respiratory droplets that are on either another person or an object and then touches their own mouth or nose.

Airborne (small particles) transmission can occur in the general practice setting by particles being dispersed during the use of nebulisers, oxygen administration and intubation. These procedures should not be undertaken without appropriate personal protective equipment (PPE).

Evidence shows that physical barriers, especially hand hygiene, wearing a mask, and using social distancing or isolation of potentially infected people, are effective in preventing the spread of respiratory virus infections.¹³

Animal studies regarding the transmission of influenza viruses have pointed to a number of environmental factors, including relative humidity and temperature, that may influence transmission.¹⁴

Vaccines are the leading pharmacological measure for limiting the impact of pandemic influenza in the community.¹⁵

While pandemic influenza vaccines are only available some months after an outbreak starts, seasonal influenza vaccinations are developed each year. Candidate pandemic vaccines are also available for particular strains.

Seasonal influenza vaccination will not protect an individual against a pandemic influenza strain; however, it can reduce circulating influenza virus in the community and the chances that seasonal influenza will be confused with an outbreak of a novel strain.

Seasonal influenza vaccination is encouraged according to the current immunisation guidelines as outlined in the  Australian Immunisation Handbook.

Influenza vaccine is the only vaccine reformulated each year to optimise the match between vaccine and circulating virus strains. The WHO issues recommendations for the different strains of influenza viruses (type A and type B) which are included in the vaccine based on the prevailing strains in the northern and southern hemispheres. Once the recommendation is made, vaccine producers require at least 6 months to manufacture and distribute the vaccine.¹⁶ Unfortunately, not all influenza vaccines (especially influenza A) have high vaccine effectiveness.¹⁷

In the case of pandemic influenza, once the viral strain has been identified it takes at least 3–6 months for vaccination development.

The development of a vaccine that could block all strains of influenza virus is an intense area of research. There have been some promising leads but there is no vaccine for the foreseeable future.¹⁸

There were three influenza pandemics during the 20th century:

• Spanish flu (H1N1) swept across the world in three waves in 1918 and 1919. It caused an estimated 50 million deaths worldwide (1–2% of the global population) and approximately 10,000 Australians died. The highest number of deaths was in young and healthy people aged 15–35 years; pregnant women were especially vulnerable.
• Asian flu (H2N2) in 1957 caused approximately 2 million deaths worldwide. During the first wave, school children, young adults and pregnant women were mainly affected. In the second wave, the elderly had the highest death rates.
• Hong Kong flu (H3N2) occurred in 1968 and 1969 and caused approximately 1 million deaths worldwide. It mainly affected the elderly.

Along with millions of deaths, these influenza pandemics caused social disruption and profound economic losses worldwide.

The first influenza pandemic this century was in 2009; it was referred to as ‘swine flu’ (H1N1). The virus contained genetic material of swine, avian and human origin.¹⁸ The virus has also been isolated in turkeys, cats and domestic ferrets.¹⁹ While the infection rate was high, there was a comparatively low mortality rate (18,449 laboratory-confirmed deaths as of 31 August 2010 by the WHO).

However, laboratory-confirmed deaths greatly underestimate the real mortality burden; for example, deaths from secondary bacterial infections and exacerbation of pre-existing chronic conditions are not recorded as being in any way related to influenza infection.⁸

Global mortality estimates by the Global Pandemic Mortality project suggest that there were between 123,000 and 203,000 pandemic respiratory deaths for the last 9 months of 2009 (which is approximately 10-fold higher than the WHO mortality count). The majority (62–85%) were attributed to persons under 65 years of age.⁸

There are more factors that are not known about a future influenza pandemic than that are known (see Table 2). The uncertainty factor makes preparedness particularly challenging.

While the 2009 pandemic was considered mild, future emerging pandemic virus strains may be highly pathogenic.¹⁸ The impact of a future pandemic will depend on its transmissibility and severity.²⁰