The many faces of flu

Influenza is underestimated. As a seasonal infection that strikes most of the world’s population, it’s an expected part of winter life. People with a slight temperature and runny nose will often say they have the flu, though a true infection would leave them bedridden for at least a week. Many actually are bedridden for a week or more but know they will recover; many receive a newly designed vaccine each year, targeting that year’s strains, in hope of damping the effects of the virus to keep them healthy during the colder months; some keep a watchful eye, almost expecting it to strike at any minute. Parlance around influenza is commonplace in our society, but it could be said that the majority of people don’t appreciate the potential lethality of an infection. If it strikes the elderly or young, or if a pandemic strain emerges, people know to worry and seek immediate help. But for anyone aged in between who contracts the seasonal virus, it’s assumed bed rest and liquids will see them through. Influenza, however, is a complex beast.

Seasonal influenza causes extensive damage to a population’s health. The annual epidemics are estimated to cause about 3–5 million severe cases of disease each year, and between 290,000 and 650,000 deaths. The United States sees between 12,000 and 61,000 deaths annually, and Europe 15,000 to 70,000. The wide range in these figures is because there are different types and subtypes of the virus and each year new strains of these circulate, and their virulence, their potency, is hugely variable. For example, the 2017–18 season was the most damaging in recent years, with two flu subtypes circulating and the vaccine being less effective than usual, causing more than 44 million cases and 61,000 deaths in the United States and an estimated 152,000 deaths in Europe. Severe cases and deaths are predominantly among high-risk groups, such as the elderly, immunocompromised (people with weakened immune systems) or chronically ill, but it’s fair to say the harm caused by influenza is far greater than people realise. The number of deaths worldwide is often greater than deaths from malaria, for example.

Before going further, and before exploring the P-word – pandemic – it’s important to understand the basic biology of influenza. The airborne respiratory virus has four types: A, B, C, and D, with the first two being the cause of seasonal epidemics and type A causing the greatest burden. Type A further divides up into subtypes, based on the combinations of two proteins found on its surface, haemagglutinin and neuraminidase, examples being A(H1N1), which circulates every year, but a version of which was behind the 2009 swine flu pandemic. Type C is less common and when it does arise, causes mild illness, meaning it is not a public health priority, while type D is known to infect cattle, not humans, for now. A mix of type A and type B viruses circulate at any one time and they change over time, due to genetic mutations and gene reassortment, meaning we see different strains of the virus types each flu season. This explains why people need to get vaccinated every year, as a new vaccine will have been developed to match the strains currently circulating. In fact, the vaccine is updated twice a year, for flu seasons in the northern and southern hemisphere, which occur six months apart. The WHO Global Influenza Surveillance and Response System, a system of National Influenza Centres  and WHO Collaborating Centres around the world, continuously monitor what’s circulating and determine the vaccine’s composition.

The majority of infections are uncomplicated, meaning people recover after a few days or weeks. Symptoms in these cases include fever, tiredness, a runny nose, headache and muscle pain. Some studies estimate that as many as 75% of infections are asymptomatic. But away from these milder infections, a great many severe infections and fatalities occur, as earlier numbers show. More severe infections can cause pneumonia and inflammation of heart muscles and the brain, exacerbated by any underlying conditions a person may have, such as diabetes or heart disease. As a result, they typically affect the elderly, pregnant women and the chronically ill, which is why these groups, as well as children, are prioritised to receive vaccines each season.

The flu vaccine itself is complex and its effectiveness extremely variable, because it depends if the correct strains for the upcoming season have been chosen, based on what is circulating in advance and when the vaccines need to be designed and made. Any protection individuals may have against some types or subtypes, from previous infection or vaccination, do not confer immunity to other types and subtypes. On average the flu vaccine reduces the risk of developing flu symptoms by between 40 % and 60 % in the population as a whole. During the more severe epidemic of winter 2017–18, the vaccine was just 40% effective, according to the US Centers for Disease Control and Prevention. This is overall protection against all flu strains, with percentages varying for each strain included in the vaccine. For example, the 2017–18 vaccine protected against A(H3N2), A(H1N1) and influenza B viruses and reduced risk of disease from each type by 25 %, 65% and 49% respectively. Vaccination remains the best means of prevention though, in addition to good hygiene and isolation once symptoms develop. Treatment is also an option, particularly for people at risk of severe disease, using antivirals such as oseltamivir, sold as Tamiflu. These can also be used as a means of prevention in some circumstances.

The endless cycle of influenza leaves no time to be complacent. Prevention efforts are continuous and responsive and require extensive resources, leaving significant economic burden. In the United States, for example, one study estimated the annual economic burden to be over $11-billion, accounting for costs to both healthcare and society from not only the severe cases and deaths, but the mild to moderate cases which result in time off work and losses to productivity. This significant cost is for a regularly occurring infection that we see coming each year, so imagine the cost when it comes as a surprise. When that happens, the global cost is estimated to be almost six times this figure, at $60-billion a year. It is in this scenario that populations truly fear the damage influenza can bring. And so we reach the P-word, the event in which the spread of a novel influenza virus across the globe is most feared.

In 1918, more than 50 million people died from an H1N1 influenza pandemic that spread across the world. In 2009, the same flu subtype returned. In both cases it emerged from pigs, but in 2009 times were very different; healthcare was a lot stronger, people were healthier overall and the virus strain was less virulent than experts had predicted. Nonetheless, very rough estimates suggest more than  280,000 people died worldwide, close to the minimum number that die from seasonal strains each year. But novel strains that underlie a potential pandemic spark worry because they are a surprise, they are unknown, and teams have not predicted their arrival so as to at least have a partially effective vaccine available ahead of time. Many countries faced the first wave of the 2009 H1N1 pandemic without a vaccine, because it arrived late, explains Sylvie Briand of the World Health Organisation. “Then when it arrived, some countries had too much, others had none,” she says, which led to those with more donating their extra supplies to the WHO, by which point it was “too little too late”.

Influenza viruses that go on to cause pandemics are always type A and so invariably have a subtype designation referencing the proteins found on the surface (such as H1N1). They are able to cause pandemics because of large genetic changes the virus undergoes, due in part to the fact this virus type is also found in birds and swine. Influenza A is transmitted interchangeably between humans and swine, and also from birds to humans. Surface proteins from avian or swine influenza viruses can become incorporated into human viruses, through gene reassortment. This is a common occurrence, but not all reassortments lead to viable viruses and even ones that are viable may not be able to infect humans, or enable ongoing human-to-human transmission. They may also be a strain to which humans harbour some immunity. A perfect storm of factors must come together, but on occasion they will and this is when a pandemic strikes.

In 2009, H1N1 crossed over from swine to readily infect humans. Prior to that, in 1997, H5N1 crossed over for the first time from birds, causing the first human case of avian influenza (bird flu). H5N1 went on to infect people around the world, with over 250 cases and 150 deaths across at least 55 countries, but it was not virulent enough to cause a pandemic. In 2003 it re-emerged, reaching many countries in Asia, but with fewer cases: 23 confirmed cases, of which eighteen died, and around 100 suspected cases, according to the US Centers for Disease Control and Prevention. Avian influenza remains a regular threat among birds, with farmers worldwide monitoring and culling their flocks accordingly, and human cases still occur most years, albeit in cases totalling single figures, among people in prolonged close contact with the birds, most often in China. But its emergence and re-emergence left countries scared, leading to intensive work on preparedness, explains Briand. “Countries were really frightened to have a true pandemic,” she says.

Be it a crossover from pigs or from birds, global health experts around the world know the chances of another pandemic strain emerging are high. There is no reason why one of the many gene reassortments that occur will not result in a virus with the potential to infect thousands worldwide, so health authorities must increase their capacity to predict and their ability to react. But whether it’s a pandemic or seasonal influenza, it’s all a guessing game using the information to hand, with everyone hoping they guess right. DM/ML

Extracted from Outbreaks and Epidemics: Battling Infection from Measles to Coronavirus by Meera Senthilingam (Icon books, June 2020, R215). Visit The Reading List for South African book news – including excerpts! – daily.