Australia has just gone through, and the northern hemisphere is in throes of, one of the most severe influenza seasons for some years. One of the reasons is that the particularly virulent A(H3N2) flu strain is circulating. These events are costly. They burden health systems from the GP offices to intensive care. On top of the costs of treatment and care, there are the indirect costs of absenteeism; due to illness, for prophylactic reasons, or to care for one’s relatives. But there is an influenza vaccine. Perhaps if more people were vaccinated, we would do better?

Background

Recent reports from the UK indicate that the death rate from flu this season is three time the rate of last year. 30,000 patients visited their GP last week with flu like symptoms, compared to 9,000 in the same week in the previous year. 600 people were admitted to hospital with flu in the week, 200 of whom required intensive care. 120 people have died from the disease in the season to date. Apparently, it is not yet an epidemic, but it is nevertheless the worst since 2010/11.[1] Australia, too, had a tough influenza season last winter. The personal costs can be enormous, the economic costs no less so.

But there is a vaccine against flu, so why do we get these periodic crises? There are a number of reasons.

The influenza virus itself

The influenza virus is extraordinarily protean. Through the processes of antigenic shift and drift it continually evolves into new strains as it spreads through the population. Some of these strains will be new to the body’s immune system. Influenza is highly infectious and easily spread, so these new strains will land upon people with limited or no immunity who will get flu.

For any patient but particularly for those at risk — the aged, those with respiratory conditions, or compromised immune systems[2] — the infection can lead to pneumonia, a major cause of hospitalisation, which can be fatal. From time to time, perhaps twice each century, seasonal influenza will be overtaken by a pandemic event which can be particularly destructive, where a virulent and entirely new strain emerges for which few have immunity. These new strains arise in bird populations and make the jump to humans. In these rare pandemic events, for some healthy adults the vigorous immune response to the infection itself, resulting in massive neutrophil infiltration into the lungs, can be deadly.

The vaccine manufacturing challenge

The vaccine manufacturers are in a constant race to keep up with this shifting target so that they can minimize the harm.

The World Health Organisation keeps track of the most common strains of the virus in circulation. Just before vaccine manufacturing must start (to get the vaccine into the clinics and pharmacies on time), the WHO selects the strains that should go into final vaccine. They do this twice a year, separately for the northern and southern hemispheres.

Even when manufacturers know the strains, there is a deal of work to be done. They must grow the virus, and then inactivate[3] it for use in the vaccine. For a disease that is so infectious, it is remarkably difficult to grow outside the body. There are two main approaches: in live fertilized chicken eggs, the predominant approach, and in cell culture (essentially, individual mammalian cells grown in large tanks in a nutrition medium). If you think that one egg, which must be fertilized, will provide about one dose of vaccine and 400m doses of vaccine are supplied to the northern hemisphere each year, you get a flavour of the size of the egg supply challenge.

The manufacturers must grow the three or four strains of vaccine indicated by the WHO in time for the forthcoming season. But some of the strains are especially hard to grow, so the virus strains sometimes need to be ‘adapted’ so that they can be grown more quickly. Some take longer than others to grow in sufficient volumes. The viruses must then be separated from the growth medium, inactivated, purified, tested, put into vials or syringes and packaged, all under the most exacting aseptic conditions and under the watchful eyes of a multiplicity of international regulators. Finally, the vaccine must get to the patient, and stay refrigerated until the moment it goes into your arm. All this, twice a year, every year.

With the passing of time

All the while, the circulating virus continues to evolve, so by the time that the vaccine is administered, the three or four strains in the syringe may not precisely match the main circulating strains. When this happens, the vaccine is less effective. The Centres for Disease and Prevention (CDC) in the US puts the average effectiveness of the vaccine at around 41%.[4]

Some changes in vaccine, for example moving from three to four strains, higher antigen doses, adjuvants, and changes in manufacturing technology, may raise this average. But inevitably the vaccine will work better in some seasons than others. Vaccine suppliers tied to current technologies will never be able to guarantee that the strains they provide match the specific strain that has infected the victim.

Putting these numbers in context

So vaccination will not always stop infection, illness, hospitalisation or even death. But it does reduce the risk of these substantially. And if enough of the population gets vaccinated, it will stop the spread of the strains that are included in the vaccine, often quite virulent strains. This is the basis of herd immunity; if enough people get vaccinated, that will stop the spread of the virus and confer protection on those that, for some reason, are not. This is a huge benefit of high vaccination rates, and a huge cost if it is not achieved.

There is nothing mysterious about preventative measures that are not 100% successful. Everyone now wears a seat belt in their car. It does not stop accidents, nor dying in accidents, but it does make it less likely. For a very rare few, wearing a seat belt might cause harm (think, it jams and traps you in a sinking car), but for the vast majority of accidents, it saves lives. The same can be said with anti-lock brakes; they don’t stop people dying in accidents, but they make accidents less likely and possibly less severe.

How, then, do we assess whether to make seat belts compulsory, whether to fit ant-lock brakes, or whether to get vaccinated? If we are policy makers, we see whether the benefits outweigh the costs. If we are individuals, we wear a seat belt because we are taught that it makes driving safer (and if we don’t know or don’t believe it, we know we can avoid a fine). We buy cars with anti-lock brakes because we know they are safer — the car manufacturers tell us — and because the technology has become much cheaper over time. Anti-lock brakes are now close to ubiquitous.

We can take the same approach with influenza vaccine. The evidence indicates that the benefits outweigh the costs,[5] even when you take account of all the costs of manufacture, transport and administration. With the possible exception of the US, we have been less good at teaching the public that this is so.

The benefits are largest for the at-risk population. But there are also benefits for the rest of the population, particularly when health care is expensive, but also in richer economies where the absenteeism results in a loss of valuable production; and when health systems are stressed; and if the cost of supply and administration is low. Vaccination that frees up scarce hospital and intensive care beds from pneumonia can prevent health systems from grinding to a halt. The National Health Service in the UK, stressed as it is, can ill afford the extra woes and cancellations that can arise in a severe flu season.

So how are we going on vaccination?

If you look at the data that the WHO collects, you would have to say that our performance is patchy. The US does best, vaccinating close to half its population. It achieves this through education — the CDC has worked hard to raise vaccination rates — and because pharmacies make profits from giving the vaccine, so they promote it and make it easy. And recipients don’t usually have to pay, it is covered by their health insurers who know that their costs will fall if those they cover get the jab.

No doubt the coverage rate could be higher, but even so the US tops the list. This makes sense. Health costs in the US are the highest in the world, so health cost savings from reduced hospitalisation are similarly large. The average American worker contributes more to GDP than workers in most other countries, so reduced absenteeism is similarly valuable. But some other rich economies, no less prone to influenza, have vaccination rates one third of the US. Whatever the reasons, this is bizarre. Their economies would undoubtedly be better off if they followed the US lead, so too their influenza victims.

So, don’t be misled. Ignore the old wives’ tales. Influenza vaccine does not give you flu. Don’t listen to the anti-vaxers, any more than you would listen to the anti-seat belters; both are wrong. Just because influenza vaccine does not work as well as we would like in some years, that does not mean it doesn’t work. Sadly, seat belts won’t always save you, but you should still wear one.

Influenza vaccination is good for you. And if that’s not a good enough reason, it is also good for your economy!

 

Additional information on Sam Lovick’s work in the health area.

[1]             https://www.theguardian.com/society/2018/jan/18/flu-outbreak-gps-under-huge-pressure-as-deaths-soar-to-120

[2]             There are some vaccine formulations that elicit a stronger immune response from these at-risk populations.

[3]             There are vaccines based on an attenuated live virus rather than inactivated virus or virus particles.

[4]             Source: CDC at https://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm

[5]             See, for example, Muennig P, Kahn K (December 2001) Cost-Effectiveness of Vaccination versus Treatment of Influenza in Healthy Adolescents and Adults, Clinical Infectious Diseases, 33 11, 1879–1885.