The endless hunt for the perfect flu vaccine | New

VAccinas are one of the great success stories of modern medicine. Thanks to them, we are no longer vulnerable to smallpox, polio or measles. The flu shot, however, is a different story. Its effectiveness varies from one patient to another, from one population to another and from one year to the next. It must be updated every season and, even in a good year, its effectiveness is usually not more than 50%. We can count on him to avoid getting the flu, but his story shows how far we are from a reliable vaccine.

Vaccination, which involves infecting a healthy person with a microbe to prevent disease, is at least a thousand years old. But the beginning of the vaccination as we think it today is generally attributed to the work of Edward Jenner, a British doctor born in 1749. Jenner was an attentive observer, deeply interested in the natural world, and having found the time to seriously study artistic game. He studied everything from hydrogen balloons to the cuckoo's life cycle, he wrote poetry and played the violin, but smallpox – or rather its eradication – is his legacy. Because of Jenner, this virus is not one of our current concerns.

Smallpox was a vicious disease that killed more than 30% of people who contracted it. In the 1700s, however, a demographic group appeared to be immune: the dairy. It had been observed that, as part of their cow milking work, women came into contact with the milder cowpox virus called cowpox.

These women are then immunized against the deadly human smallpox virus. There was something in smallpox that protected against smallpox, and in 1796 Edward Jenner took the material of the fresh pustules on the hand of a milkman and inserted it under the skin of a young boy named James Phipps. After a brief and mild illness, Phipps is fully recovered. Jenner then infected him with scrapings of a smallpox injury over and over again, but the boy was never sick. Jenner named this process "vaccination" after vaccinated smallpox, Latin term for cowpox. His technique quickly spread in nineteenth century England and beyond, saving countless people, inspiring changes in technique and altering the course of history.

Jenner's smallpox vaccine has been improved and modified in the coming decades and soon joined by others. Louis Pasteur has developed vaccines against animal diseases such as chicken cholera and anthrax, but he is best remembered for his anti-rabies vaccine. Rabies was a common and uniformly fatal disease in the 19th century. Once the victim is bitten by a rabid animal, the virus multiplies slowly and infects the brain and nervous system. Pasteur did not know the viral cause, but that did not matter. He dissected and dried the spinal cord of the infected animals and then injected the remains with test animals, which showed immunity against rabies. What Pasteur did, in fact, weakened the virus into a version of Goldilocks. He was not strong enough to kill, and he was not weak enough to be ignored by our immune system.

One hundred years ago, during the 1918 influenza pandemic, there were no flu shots. We did not know exactly what the cause of the disease was, so we could not make a vaccine to protect ourselves. But that did not stop scientists and doctors from doing something to fight the epidemic. In 1919, Edward Rosenow of the Mayo Clinic in Rochester, Minnesota, isolated several bacteria from the sputum and lungs of Rochester patients, formulated a vaccine containing five different types of bacteria and distributed it to 100,000 people. At Tufts College Medical School in Boston, Timothy Leary (whose nephew and namesake would also become a doctor and experiment with psychedelic substances) produced his own vaccine mixed with the help of drug strains. Naval hospital in Chelsea, from a nurse's nose to Carney Hospital and infected rooms of the camp. Devens. Leary mixed these samples, cultivated them on agar plates and then sterilized the mixture. His vaccine was sent to San Francisco, where at least 18,000 people were vaccinated.

These and other efforts have given hope to a ravaged nation. A health official at the time wrote that the most important badet of an influenza vaccine was that it was reducing "fluphobia". Anxiety and fear spread as quickly as the disease itself, and any vaccine offering at least mental relief was welcome. Of course, there is no indication that any of these vaccines actually worked. Today, doctors are struggling to ensure that vaccine trials meet strict standards, but these did not exist a century ago. Many vaccine trials were conducted on influenza survivors after the end of the initial outbreak, meaning that the pool was tainted with a degree of immunity.

In 1933, the flu virus was identified and scientists could then face the culprit rather than the mess. The Russians led the field, weakening the virus by grafting it between chicken eggs. About one billion people in the USSR were vaccinated with the live but weakened influenza virus, which was still used in the late twentieth century. Although this vaccine appeared to be successful, the live flu vaccine has never been rigorously tested and it remained a constant danger. Since he was using a live virus, he could cross with other strains and turn into a more virulent version.

Vaccine researchers have therefore focused their attention on creating a vaccine containing what they have called "inactive" strains. The virus was still grown in chicken embryos, but this time it was rendered inactive by dipping it in a bath of formalin disinfectant. Although a higher dose of the inactive vaccine is needed to produce an immune response, replication of the virus was not a problem.

During the early years, the influenza vaccine contained only one strain, the influenza A virus, because, to the best of all, it was the only type of influenza existing. In 1940, influenza B was identified, which launched the perpetual task of calibrating vaccines to treat several strains in evolution. In the 1950s, we had an effective vaccine against A and B, but the virus, as always, was ahead of us. In the late 1970s, we had to make a vaccine against three strains. For the 2016-7 influenza season, most vaccine doses manufactured in the United States were for four different strains. The last 100 years have been an incessant arms race against an enemy with whom we can not negotiate.

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TThe key to a good influenza vaccine is to adapt it to strains in circulation during a given season. The challenge is that it takes about six months to produce the vaccine. Manufacturers must therefore rely on clever detective work led by the World Health Organization.

In approximately 80 countries, approximately 110 WHO Influenza Centers distribute swabs from the nose and throat of patients with influenza-like illnesses. These centers identify influenza strains in circulation and sometimes find a new one. When this happens, they send it to one of the five collaborating centers in London, Atlanta, Melbourne, Tokyo and Beijing for a more detailed molecular badysis. Twice a year (in February for the northern hemisphere and in September for the south), WHO organizes a meeting to gather all the information and to recommend a vaccine recipe for the coming season. In the United States, the Atlanta Centers for Disease Control and Prevention (CDC) provide additional national data, and the Food and Drug Administration makes the final decision on vaccine use. Manufacturers then have about six months to market the recommended flu shot.

Because the flu virus can mutate so quickly, it is difficult to exactly define the recipe. In some seasons, the match is almost perfect, but it is not always the case. If the virus drifts after the February WHO meeting, there will be a mismatch between the vaccine and the virus. The larger the shift, the less effective the vaccine is. In a good year, the vaccine can be expected to be 50-60% effective. During the 2004-2005 influenza season, this figure was only 10%, which means that the vaccine was a big failure. We also missed the 2014-5 season, when new strains were not included in the vaccine. This season, the vaccine was effective at 19%, against more than 50% the previous year. At the start of the 2017-8 influenza season, the number of hospitalizations was almost record and, although the performance of the last vaccine has improved throughout the season, its overall effectiveness is estimated at 40%.

Even if the vaccine reaches the target, different demographic responses react differently. Children respond very well to the vaccine. The situation is more complicated in elderly patients, whose immune system is generally weaker, but whose natural immunity accumulates throughout life. After having supported many influenza seasons, their immune system is wiser, you would say, than that of young people.

The United States and most other developed countries urge older people to be vaccinated against influenza. One study compared 18 different groups in 10 influenza seasons and found that the vaccine reduced the overall rate of winter mortality in the elderly by 50%. But epidemiologists at the CDC have shown that the rate of flu-related death among older people is increasing along with the vaccination rate, which raises questions about the urgency of vaccinating them. The bottom line is that while seniors are vaccinated, they are still the most likely population to die of influenza.

One of the ways to better protect the elderly is to vaccinate a totally different demographic group: schoolchildren. This notion has been elegantly demonstrated in a natural experiment in Japan. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza; At one point, the vaccine was mandatory for a solid decade. The vaccination rate was about 85%, but the mandatory vaccination program was discontinued in 1994. Over the next few years, the number of deaths among seniors has increased during the influenza season. In the United States, where immunization policy has not changed, deaths of older persons in the same influenza season have remained unchanged. To vaccinate part of the population, in other words, benefits another.

Data can be interpreted in many ways and each country has developed its own policy accordingly. The CDC has been recommending influenza vaccine for all healthy children in the United States since 2008. In 2013, the UK has gradually adopted a flu vaccination policy, unlike most European countries. Germany provides free vaccines only to the elderly, letting parents pay for their children. In Europe, the vaccination rate of children is 15%, against nearly 60% in the United States.

If influenza vaccines are indeed the biggest weapon of mankind against influenza, why are they used in very different doses?

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WWhen my colleagues gave each other the influenza vaccine at the George Washington University hospital, we followed the advice of the CDC. A few months later, when flu patients began to enter the emergency room, I asked them if they had received a flu shot. Many had them, and yet they were in the hospital. I knew what they felt. My only visit to the emergency department as a patient – the year I had an ugly case of influenza – occurred after the flu shot.

Despite the regular failure of the vaccine, Americans are bombarded each year with reminders and opportunities to get vaccinated against the flu. At the end of August, pharmacies display signs and doctors' offices are preparing. The vaccine is available in many workplaces and places of worship, and hospitals require all their health care providers to be vaccinated.

Behind this effort lies the CDC, which recommends the flu vaccine to all people over six months old. A CDC poster that caught my attention asked, "Who needs a flu shot? a) you, b) you, c) you, d) all the above ". (In case you're wondering, the correct answer is d.) The poster reminds us that "even healthy people can catch the flu and that it can be serious." The message became clearer: "All people 6 months and older should get the flu shot. It means you. "

The Immunization Practices Advisory Committee (Acip), made up of more than a dozen experts specializing in immunization research, public health and health policy, makes recommendations on the use of vaccines in the United States. United. It meets three times a year to review any new evidence and advise the CDC Director on the use of vaccines. As recently as 2006, the committee recommended influenza vaccine for people at high risk for influenza complications and adults over 50 years of age. A few years later, he expanded his recommendations to include all people over six months old. And this recommendation has remained in place ever since.

The CDC's public health campaign to immunize everyone is not shared by other countries. Europe and Australia recommend the vaccine only to the very young, the elderly and people with underlying diseases. Healthy adults are simply not targeted. It is very difficult to compare the death rates from influenza in different countries because the definition of an influenza case varies, as does the way a country collects its own statistics. Often, deaths from viral influenza and bacterial pneumonia are listed together. It is therefore difficult to compare data from the United States and the United Kingdom. However, in the United Kingdom, the 2014 flu mortality rate was 0.2 per 100,000 population. And in the United States it was 1.4 per 100,000. That's seven times more than in the UK, a country that vaccinates much less of its population. These figures should be interpreted with caution, but they suggest at least that the approach to the UK is reasonable.

How can we correctly determine whether a "vaccination for all" program, like the one implemented in the United States, saves more lives and protects more people than the English version of "vaccination for some"? Perhaps we could encourage everyone to be vaccinated for an influenza season, and for the next season, we would only encourage people at increased risk. We could compare the death rates from influenza between the two groups and get our answer. Of course, it's more complicated than that. Because the flu mortality rate is so low, hundreds of thousands of patients should be enrolled to see if the vaccine is making a difference. However, such an experience could be compromised by influenza strains circulating each year. If the tension of a year were more contagious or more lethal than the next, our experience would tell us nothing.

We could instead collect evidence from small trials and look for trends. This method was used by the Cochrane Collaboration, an international group of 37,000 medical contributors, in 2014, when they reviewed all studies evaluating the effects of influenza vaccine in healthy American adults. It was a big company. 90 studies compared the administration of the vaccine to its retention, and 8 million patients in total were involved.

The Cochrane review found that the effect of influenza vaccine in healthy adults was "small". About 2.5% of unvaccinated people became ill, compared to 1.1% of those who were ill. It's very small. In other words, 71 people should be vaccinated to prevent a single case of influenza. The vaccine did not reduce the number of days of work lost or the number of hospitalizations. So yes, the vaccine does prevent influenza in young and healthy adults, but in a very modest way. So why is the United States still recommending universal vaccination, unlike the UK?

It comes back to the language. The CDC describes the flu in a poster for doctors' offices: "The flu can cause coughs, sore throats and fever. They may also have runny nose or stuffy nose, feel tired, have sore body or show other signs indicating that they are not doing well. Influenza occurs every year and is more common in the fall and winter in the United States. People of all ages can get the flu, babies and young adults to the elderly. "

Not so bad. It's then on the CDC's home page on the flu: "It can cause serious to serious illness. Serious consequences of an influenza infection can result in hospitalization or death. Some people, such as the elderly, young children, and people with certain health conditions, are at high risk of serious influenza complications. The best way to prevent the flu is to get vaccinated every year. "

The CDC's approach to influenza is that it is a life-threatening disease that can be prevented by a vaccine. The British take another approach. Here's the advice on the NHS flu: "The flu is an infectious viral disease spread by coughing and sneezing. This can be very unpleasant, but you will usually start feeling better in about a week … [If you are an otherwise healthy adult] you do not usually need to see a doctor if you have flu-like symptoms. The best medicine is to stay at home, stay warm and drink plenty of water to avoid dehydration. "

At most, according to the British, the flu can be a bit of a nuisance: "Most people will recover completely and will not have any more problems, but older people and people with certain long-term health problems are more likely to suffer. A serious flu or develop a serious complication, such as an infection of the chest. There is no mention of death as a complication. Everything remains very calm and continue, as during the 1918 pandemic.

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IIs the flu a killer or an irritant? We know for sure that every year he kills many people in the United States and Britain. And we know with the same certainty that for almost everyone in good health, the flu is only a minor inconvenience. Both are correct. This is the nature of the flu. It is delicate and mysterious, causing discomfort among some of its victims and death in others. It's just that the United States and the United Kingdom quantify them in different ways.

The UK version of the CDC Advisory Committee on Vaccines is called the Joint Committee on Immunization and Immunization (JCVI). It meets three times a year, reviews the scientific evidence and makes recommendations to the Secretary of State for Health when it is necessary to modify the vaccination policy. Andrew Pollard, head of JCVI, has studied pediatrics and is currently a professor of pediatric infection and immunity at Oxford University. Pollard is extremely aware of the many effects of the flu, but for JCVI, the most important measure is profitability.

It may seem cold or foolish to focus on costs when lives are at stake, but money and resources are limited, and reckless or misdirected spending can lead to poor medical practice or more damage. important. For example, spending $ 1 million on drugs for those who have had a heart attack could save 1,000 lives each year. That same $ 1 million may have been spent on cervical cancer screening, saving the lives of 60,000 women each year. What's more important: saving 1,000 lives or 60,000 lives? It often comes down to who is asking the question (and what illness you have).

Andrew Pollard and his JCVI team reviewed studies evaluating the cost-effectiveness of the influenza vaccine. They concluded that, given the extremely small number of healthy young adults who become seriously ill or die of the flu, it is not cost-effective to vaccinate this segment of the population.

The Pollard Committee measures the cost to the health system itself: how much the vaccine costs and how much it reduces the number of days that patients spend in hospital or intensive care. They also estimate the effect of the vaccine on the number of physician office visits related to influenza. What they do not measure is the general cost to society, which includes the loss of work, the loss of pay, or the amount of time a parent has to take care of their child. These are also a burden to society, but they do not enter the JCVI deliberations. The vaccine is cost-effective for the health system when it is given to children, the elderly, people with health problems and pregnant women. This is not cost effective when it is administered to healthy young adults.

In the United States, the cost-effectiveness of the vaccine is less important. What is more important is whether it works or not. This approach has resulted in another difference in vaccination policy between the United States and the United Kingdom, this time compared to the chickenpox vaccine. The varicella vaccine can prevent both chicken pox and shingles, a subsequent complication of the disease. In the US, the chickenpox vaccine is recommended for all children; the first dose is administered at the age of 12 months and one booster injection four years later. In the United Kingdom, chicken pox is not on the list of childhood vaccines. In the United States, if a vaccine is safe to use, the CDC generally recommends it.

At the beginning of the 1976 flu epidemic, President Gerald Ford had to choose between two perfectly sound recommendations. One was to quickly vaccinate as many people as possible, while the other was to store the vaccine and wait for the situation to worsen. Ford rejected the wait-and-see attitude. "We can not afford to try our luck with the health of our country," he said. "It's better to err on the side of reaction than under-reaction."

This is the dominant approach to health care in the United States. They are always willing to do more, try the latest drugs or surgical procedures, because, why take a chance? Compared to other Western countries, the United States carries out more invasive heart studies in patients with chest pain, without improving their outcomes. In the United States, we place more patients in the intensive care unit, even though they are on average less sick than their counterparts abroad. We give more chemotherapy to cancer patients close to the end of their illness, even if it does not improve the quality and duration of their life. We do these things because we can, because acting otherwise would be considered a renunciation – even if doing less would be an extremely sensible and benevolent decision.

Influenza is not cancer or heart disease. But the American approach in this area is emblematic of how it treats most diseases: doing more is better. If there is an option not exhausted, exhaust it. And since many vaccines have had tremendous success in preventing and eradicating some horrific infectious diseases, the flu shot is expected to do the same. It's another high tech solution. For most people, the word "vaccine" equals the guarantee that an illness will leave you alone.

It's hard to make a catchy public service announcement that reflects the intricacies it contains. "Vaccinate all people over six months old" is the current message. It is easy to understand and easy to remember. A more precise message is much more clumsy: "Vaccinate school-aged children, pregnant women and probably the elderly (but the evidence is mixed) and those with chronic diseases, but did not need to vaccinate adults. young and healthy. mount on a sign board. In this case, the shades can be dangerous.

The quest for a better flu shot is continuing. The Holy Grail would be a vaccine covering all possible influenza strains (so there would be no problem of inadequate vaccination) and should be administered only once, not every year as it is. the case now. Dozens of research laboratories around the world have been working on the creation of this so-called universal vaccine, but without success so far. The flu virus is simply too adept at changing disguise and is still a step ahead of our efforts to neutralize it with a single-action vaccine. Although influenza is a common disease, finding an effective vaccine to prevent it is a major challenge.

Adapted from Influenza: In Search of the Most Deadly Illness in History, by Jeremy Brown, published by Text on Jan. 31 at £ 12.99. To order a copy for £ 10.99, go to guardianbookshop.com or call 0330 333 6846

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