What makes the flu turn deadly?

What is influenza?

The influenza virus is a microscopic pathogen – around a thousandth the width of a human hair in size – that packs an outsized deadly punch. It is responsible for up to 500,000 deaths each year, according to World Health Organisation estimates. 

To understand how the virus can kill, we first need to understand what it wants and what it does in the body.

Unlike bacteria, viruses require a host cell to replicate. They lack the biological ‘machinery’ to copy themselves, instead hijacking the host cell to instruct it to make copies of the virus.

The influenza virus is particularly fond of the cells of the respiratory tract (nasal cavity, pharynx, larynx) and lungs. Using a special protein called hemagglutinin, it binds to hosts cells and break inside. There it replicates before using an enzyme called neuraminidase to open the cell and release the newly formed viruses, which often has the side-effect of killing the host cell.

The immune system tries to fight off the virus, and if it succeeds, all is well. If it doesn’t, things aren’t so rosy.

Secondary infections

At this point a number of deadly outcomes can occur.

One is that the tissue damage caused by the virus killing host cells and triggering an inflammatory response lets bacteria invade, resulting in a secondary infection. 

Another effect of the viral infection can be to break down the physical barriers (cell walls, membranes) and immune activity that would normally prevent the invading bacteria from proliferating. The immune system, facing two kinds of pathogen at once, is in trouble. 

Secondary infections are often caused by opportunistic bacteria including Streptococcus pneumoniae (nasopharynx) and Staphylococcus aureus (skin), which live in or on our body, waiting until conditions are right to attack. 

If these bacteria spread into the bloodstream, a condition known as sepsis, they can cause infection throughout the body, damaging organs and potentially making them fail, leading to death. 

Viral pneumonia

Another potentially deadly outcome can occur in the lungs if the influenza virus infects the alveoli, the transfer hubs that exchange oxygen and carbon dioxide between air and the bloodstream.

When influenza viruses infect the alveoli, they trigger a ‘cytokine storm’, a wave of inflammatory signallers that trigger an influx of immune cells. The storm also triggers the production of fluid that clogs the alveoli, preventing it from functioning properly, leading to life-threatening pneumonia.

The age factor

While any person can present with either a secondary infection or viral pneumonia, some age groups are more susceptible.

In younger patients, usually less than half of cases are associated with bacterial infections, says Ian Barr, deputy director of the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne, Australia. “In the elderly it’s probably a much larger proportion that have secondary infections with bacteria.”

Barr explains a lower overall immune status may contribute to why particular groups have higher rates of influenza infection, the elderly and the young often have immune systems that are reduced or not fully developed respectively.

A deadly season

So why has 2017 been particularly deadly?

It will take time to understand and explain why it has been a particularly severe year for influenza infections, says Barr. One factor is the particular strain of virus prevalent this year: “Whenever H3N2 viruses crop up in the community they cause more problems.” 

Different forms of influenza are constantly arising under the pressure to evade our immune systems. Changes to the hemagglutinin (H) and neuraminidase (N) proteins help the virus hide from immune cells. The H3N2 sub-type Barr refers to is one of many types that infect humans; pigs, birds and other animals also have a variety of sub-types moving through their species. 

In total 18 H and 11 N proteins have been found and listed, of which around half affect humans, resulting in a range of combinations. H3N2 is particularly virulent, meaning it causes a more severe flu and is more easily spread.

What makes the H3 subtype particularly lethal, Barr explains, is that it is dangerous to both the very young and the very elderly, meaning that these vulnerable populations are even more at risk than usual.

Vaccine trouble

Another reason why this year has seen more flu cases and deaths is to do with the vaccine. 

Each year, vaccine manufacturers must decide months in advance which strains to protect against. They do this by using information from more than 100 influenza monitoring centres around the world, which study which strains are making people sick, how prevalent each is and how effective the previous season’s vaccine was.

Typically, the influenza vaccine protects around 40% to 50% of the population from infection, however preliminary data suggests that this year’s vaccine only protected between 15% to 20%, according to Peter Collignon, an infectious diseases physician and microbiologist at Canberra hospital.

Protection tips

So how can we protect ourselves from getting the flu?

While vaccination is not totally protective, it does reduce the likelihood of catching the flu. According to Barr, only around 20% of people get the flu shot each year. Increasing this percentage would help to protect against the virus spreading, particularly into communities that are not able to receive the vaccine including the very young, very old and immunocompromised.

Staying home when sick, limiting your exposure to people who are already sick and taking antiviral medications like Tamiflu and Relenza as soon as symptoms begin are some ways to reduce the severity of the flu, says Barr.

The antiviral drugs inhibit the virus from from spreading through the body by blocking neuraminidase, which the virus needs to break out of its host cell.

One approach being used for ‘at risk’ groups like the elderly is the provision of a high dosage vaccine, which Barr says is around four times as strong as the regular vaccine. This makes it easier for the immune system to ‘learn’ what the virus looks like and prepare for its arrival.