The Spanish flu pandemic killed more than WWI. Are we prepared for the next?

by Sally Blundell / 17 June, 2018

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Photo/Getty Images/Listener illustration

Photo/Getty Images/Listener illustration

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This year marks a century since the Spanish flu pandemic killed 9000 New Zealanders. In the years since, three more such plagues have swept the world – and another is inevitable. Sally Blundell looks at how we can protect ourselves against the latest strain, which is expected to be severe. 

November 1918 is a month engraved in the collective memory: an armistice, signed in France, marked the end of war and brought to an end four years of misery and death in Europe. But a new war, against a more insidious enemy, was already wreaking havoc on these islands.

That same November, Maurice O’Callaghan, a St John ambulance man, attended a call-out to a home in the central Auckland suburb of Grey Lynn. Inside, he found a man lying in bed. He’d been dead for three days. O’Callaghan would tell a government commission the next year that the man’s wife was lying in the same bed, “not dead but driven out of her mind by the fact that she was lying in bed with a dead husband and could not get up”.

The man in the Grey Lynn house was one of the early victims of a vicious influenza pandemic that would kill thousands of New Zealanders and tens of millions worldwide. Often neglected in national commemorations, the impact of the 1918-19 Spanish flu (which was variously dubbed the Brazilian flu, the German flu, the Bolshevik disease and the sumo flu in different parts of the world) continues to ring a chilling note in cemeteries and family histories.

Anthony Burgess describes in his autobiography how his father came home to Manchester on military furlough in 1919 to find the novelist’s mother and sister dead in bed from the flu, while the young Anthony lay chuckling in his cot in the same room. This was proof, Burgess said, of a god: “Only a supreme being could contrive so brilliant an afterpiece to four years of unprecedented suffering and devastation.”

Viennese painter Egon Schiele wrote to his mother in October 1918 that his pregnant wife, Edith, had the flu, which developed into pneumonia. “The illness is exceptionally severe and critical; I am preparing myself for the worst.” She and their unborn child died on October 28 and he died three days later.

The 1918-19 Spanish flu killed about 9000 here, including an estimated 2500 Māori, almost 5% of that population.

Viennese painter Egon Schiele on his deathbed. Photo/Getty Images

Viennese painter Egon Schiele on his deathbed. Photo/Getty Images

It remains, says retired history professor Geoffrey Rice, “New Zealand’s worst natural disaster, both in terms of mortality and the extent of disruption to everyday life. No event has killed so many New Zealanders in so short a space of time.”

Globally, at least 50 million people – by some estimates as many as 100 million – died from influenza A/H1N1 and secondary bacterial infections, more than twice the number killed in the war that had just ended. If a similar deadly infection were to hit New Zealand today, writes Rice in his book Black Flu 1918, we could expect more than 30,000 deaths.

Although outbreaks of other diseases, such as Sars (Sudden Acute Respiratory Syndrome) and Ebola have caused more deaths than influenza in recent years, scientists are saying another influenza pandemic is inevitable.

A 2016 United Nations report warns a new, highly pathogenic influenza virus, resulting in millions of deaths, “is not an unlikely scenario”. The world does not have the millions of troops on the move and spreading the disease, as it did a century ago; but it faces other risks unknown then: a growing population; ever closer proximity between humans and animals; intensive farming of genetically identical birds with no “immune firebreak” and faster and more frequent travel (almost four billion passenger air movements last year). Meanwhile, climate change is also increasing the risk of respiratory infections.

The UN report quoted mathematical modelling by the Bill and Melinda Gates Foundation that showed a virulent strain of a new airborne influenza virus could spread to all major global capitals within 60 days and kill more than 33 million people. According to the World Bank, such a pandemic would cost about US$3 trillion ($4.3 trillion) in global economic losses.

Balclutha-born virologist Robert Webster, described by the journal the Smithsonian as the “flu hunter”, has been saying all his life that we are overdue for a pandemic.

“We don’t fully understand influenza severity,” he says. “Whatever you say about flu, it will do the opposite. If we say we are overdue, the virus will prove you wrong and take another 10 years to come around – but it will come.”

New Zealand-born, US-based virologist Robert Webster.

New Zealand-born, US-based virologist Robert Webster.

The shapeshifter virus

It will come because influenza viruses, such as the H1N1 subtype that blasted across the world in 1918, are skilled shapeshifters.

A virus needs a host cell – it cannot live on its own. Once inside the host cell, the virus is replicated thousands of times, the cell bursts open and the viruses swarm around the body. However, during this process of replication, genetic mutations can and often do happen. This is called antigenic drift. The mutated virus copy then sails past our immune system unrecognised, unchallenged and much faster than the four to six months it takes to develop and distribute a new vaccine.

Once the virus has taken hold, these microscopic envelopes of single-stranded ribonucleic acid (RNA) molecules, which carry all the genetic information needed to make new influenza virus particles, are easily spread, transmitted from person to person in droplets of mucus flung through the air on a cough or a sneeze or picked up from cold surfaces, where they can survive for up to 48 hours.

Even if our bodies have been primed to fight a particular strain of virus through an earlier encounter, our immune system may not recognise a slightly altered subtype, thanks to the dramatically named “original antigenic sin” response.

But viruses have another, more insidious way of adapting to new hosts. Through a process called antigenic shift, animal and human viruses can exchange or “reassort” genetic material, creating a whole new strain of influenza that its human hosts have never encountered before. Once this happens, says Sue Huang, a virologist at the Government’s Institute of Environmental Science and Research (ESR), the new virus is able to transmit efficiently throughout the human population. “Then, boom, you have a pandemic.”

In the past century, we have had four such booms: the 1918 A/H1N1 Spanish flu; the A/H2N2 Asian pandemic in 1957 (two million dead); the 1968 A/H3N2 Hong Kong pandemic (one million); and the 2009 swine flu pandemic, a slightly altered A/H1N1 strain, thought to have caused around 18,500 deaths, although some scientists say the death toll could be closer to 300,000.

Like the virus that caused the 1918-19 pandemic, this last strain is unusual in that it hits healthy young adults; New Zealand’s first reported cases were three Rangitoto College students returning from a study trip in Mexico. Resistance was strongest in the elderly, presumably due to their exposure to earlier A/H1N1 strains.

ESR virologist Sue Huang.

Now based at St Jude Children’s Research Hospital in Memphis, Tennessee, Webster has traced these “monster viruses” to migratory seabirds, particularly wild ducks. These, he says, are the natural reservoirs of influenza A, transporting strains of the virus across the world and, in some cases, across species.

In some instances, the successful transfer of these viruses to humans is facilitated by mammals. Pigs, Webster says, can work as mixing bowls for new pandemic flu outbreaks: if a human flu and an avian flu infect a pig cell at the same time and exchange genetic material, the resulting new strain can be both highly infectious and deadly.

There have been other instances when a virus has moved directly from bird to human. In 1997, a three-year-old boy in Hong Kong was found to have been the first to die from the A/H5N1 bird flu. The virus went on to kill six of the 18 people it infected – a death ratio far higher than in the 1918 pandemic. Between 2003 and 2007 it hit again in Thailand and Vietnam, killing 201 of the 329 people it infected.

So far, the H5N1 strain has shown no ability to pass from human to human, but it could be just a matter of time. Laboratory testing of ferrets to gauge the pathogenicity (the capacity to cause disease) of the virus found that in just five tweaks of the genetic material the virus could be transmitted from animal to animal.

Webster is also keeping a weather eye on the H7N9 bird flu, again caught from poultry. So far it has caused over 1000 deaths but the virus remains confined to China; it hasn’t moved to migratory water birds and it has not been passed from human to human. Of those it infects, 60% die, but out of the millions of people who go through poultry markets in Asia, he says, very few appear to have caught the virus.

However, if the virus becomes more adept at infecting humans, and once it is able to be transmitted from human to human, “we scream bloody murder and try and stop it, but it takes six months to make a vaccine and we don’t have decent drugs for flu; we have one and it is not enough”.

Even without the “monster viruses” spreading through whole populations, seasonal flu can knock us down. New research by Trang Khieu and Michael Baker from the University of Otago shows that the influenza virus is “probably” New Zealand’s biggest single infectious-disease killer, claiming 500 lives each year. Of these, 37% are caused by secondary circulatory conditions such as heart attacks and strokes, many of which are not recognised as having been caused by the flu. Older Māori and Pasifika people are two to three times more likely to die prematurely from the flu; men, especially in the older age group, are also more vulnerable.

But three relatively mild winters may have made us complacent. The chief medical officer for the Nelson Marlborough District Health Board, Nick Baker, predicts this winter will be worse, “because of what the Northern Hemisphere has been through and because we have a health system already under pressure”.

Chief medical officer for the Nelson Marlborough District Health Board, Nick Baker, predicts a tough winter ahead “because of what the Northern Hemisphere has been through and because the health system is under pressure”. Photo/Fairfax

Chief medical officer for the Nelson Marlborough District Health Board, Nick Baker, predicts a tough winter ahead “because of what the Northern Hemisphere has been through and because the health system is under pressure”. Photo/Fairfax

The mean season

The 2017-18 winter flu season did hit the Northern Hemisphere hard. In England, GPs grappled with a 78% increase in the numbers of patients presenting with flu-like illness. In the US, it was the deadliest flu season for children since 2013. New Zealand was not hit too badly in 2017, but in Australia there were 745 confirmed flu-related deaths, the highest for eight years, although the data is patchy because influenza-related deaths are reported differently in each state. But in anybody’s terms it was a bad year.

The main culprit? In many cases, influenza A/H3N2, a nasty strain, says Baker, associated with more complications, hospitalisations and deaths, especially among children, those older than 65 and people with certain chronic conditions.

There are two main reasons for this: first, people have had less exposure to the strain – when the same flu strain strikes repeatedly, it builds up immunity in the population – and the vaccine for A/H3N2, grown inside egg cells, acquired a new mutation, reducing its effectiveness to about 20-30%.

This winter, the Government is rolling out a new vaccine, containing four strains rather than the usual three – an updated A/H3N2, A/H1N1 and two strains of influenza B – the Yamagata and the Victoria lineages. It is free for pregnant women, people aged 65 and over, those with certain medical conditions and those under 18 living in certain areas affected by recent earthquakes or flooding.

Whether this vaccine will be an exact match to our winter flus is not guaranteed. There is no way of knowing for sure, says clinical virologist Lance Jennings, which viruses will circulate in the coming year and how severe the outbreak will be. “What the Northern Hemisphere countries experienced over their last winter may be very different from what we experience here.”

People who have had previous exposure to the prevailing virus, either by getting the flu or by being vaccinated previously, will have some protection, because it will have cranked up their immune system to put up a good fight. Once the immune system has a particular type of antibody, says Baker, “the memory cells linger on so when you are next exposed to it you get a much more agile immune response”.

And even if the vaccine is only 50-60% effective, says Nikki Turner, director of the Immunisation Advisory Centre, it can still reduce the spread of the virus and prevent more serious infections. “This is individual protection, but it’s also community protection; if enough people in the community are vaccinated, the virus doesn’t spread so much.”

In some cases, however, vaccination after previous exposure to a similar but not identical flu virus can blunt, rather than boost, our immune response. This is where the “original antigenic sin” kicks in: the body will put up a robust response to the first virus you encounter, but when a second, slightly different one strikes, the body relies on its memory of the earlier infection, rather than mounting a new response.

Nikki Turner, director of the Immunisation Advisory Centre. Photo/Hagen Hopkins

Nikki Turner, director of the Immunisation Advisory Centre. Photo/Hagen Hopkins

“It’s about pattern recognition,” says Turner. “If, in the past, the pattern recognition was similar but not identical, the body might not have such a vigorous response. It does not mean the vaccine is not working; it just means it might not work quite as well.”

But a vaccine’s effectiveness does depend to a certain extent on your pre-existing health status. Those who are most at risk of flu complications are those who are least likely to mount a strong immune response, “so we cannot guarantee that even when they are vaccinated they are well protected”.

Social factors have a role to play, too. The Khieu and Baker research found those living in the most deprived 20% of neighbourhoods are almost twice as likely to die of the infection.

“Stress, poor nutrition, poor housing – when you look at any of our illnesses, children who come from backgrounds of deprivation are more likely to get sick,” says Turner. “It doesn’t mean that healthy, well-nourished kids don’t get sick and die – they do – but you are way more likely when you come from a background of deprivation.”

A good diet and a healthy lifestyle are key to a strong immune system, she says (obesity and smoking are both risk factors for infection). Likewise, moderate exercise, good housing and good support networks.

“There’s a lot of old wives’ tales out there, and a lot of medication and pills, but a healthy lifestyle, laughing, having good family support – they all make a difference to your response to any virus.”

In the meantime, trials for a universal flu vaccine – one jab to rule them all – are under way. They are aimed at parts of the flu virus that are common to all influenza A strains, rather than the more strain-specific haemagglutinin cap of the virus that current vaccines target. Webster predicts that vaccine is about five years away, but even then, eradication is unlikely. We have rid the world of smallpox; polio and measles may eventually be banished; but so-called zoonotic illnesses – diseases that can be passed from animals to humans – such as influenzas are much harder to eradicate – and still difficult to predict.

“Influenza is like the weather report,” says Webster. “Seventy years ago, when I was young, the weather reports on the radio weren’t worth a cracker. The weather reports nowadays are 99% spot on. What has changed? The weather people have satellites, they have all the information about what is coming and they can make useful predictions. Influenza is similar, in that once we have all the information on the genetic susceptibility of the human and the multiple viruses that are out there in wild birds, we can start to make predictions about which one of this mass of viruses really matters when it comes to pandemics.”

When the next “monster virus” does come, says Jennings, we will be ready, thanks to our improved diagnostic laboratories, well-organised and well-informed general practices and easily managed borders (although our reliance on trade and tourism makes closing these borders tricky). We have better surveillance – ESR scientists have recently launched an online dashboard to provide real-time information on the spread and severity of the flu virus – and we are part of an active global surveillance programme.

New Zealand was one of first countries to have a draft influenza pandemic plan, which was used during the 2002-03 Sars outbreak. We were first to carry out a pandemic readiness exercise, and we now have a Government Influenza Pandemic Plan.

In terms of capacity-building and education of the community, says Jennings, “we are one of the better-prepared countries in the world, should we have another emergency.”

This article was first published in the June 9, 2018 issue of the New Zealand Listener.

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