To be vaccinated or not to be vaccinated against influenza? This question usually stirs up far less emotion than the discussion about vaccinations against childhood diseases. Those refraining from flu vaccinations do so not because of strong opposition to it, but because they did not get around to it, or because they are not sure that it is necessary. Why even go to a clinic full of viruses? The people who do get vaccinated, on the other hand, do not get angry. No one tells people avoiding vaccination that they are knowingly spreading diseases that threaten children's lives.
Is this indifference justified? Dr. Tomer Hertz, senior lecturer at the Ben Gurion University of the Negev Shraga Segal Department of Microbiology, Immunology, and Genetics, and the National Institute for Biotechnology in the Negev, a systems immunologist and flu researcher, wants to get rid of some popular superstitions.
Only 22% of people get vaccinated
There are several reasons for the difference in people's attitudes towards different types of vaccinations. One is that flu is not considered a deadly disease. This is an error, of course, because flu kills old people, babies, people with suppressed immune systems, and here and there also a healthy young person. 60-70 people a year in Israel have died of the disease in recent years.
This tolerant attitude has been somewhat undermined this winter, following stories of young people and children dying from flu, but Dr. Hertz says that the same thing happens every year. "Why was there a shortage of vaccine last week that made the headlines? Because people get vaccinated each year only when stories are published about apparently healthy young people and babies who died," he says. "Even after the hysterical response, which takes place in most years, the rate of vaccination is now 22%."
Other reasons for the low vaccination rates are inconvenience - it is necessary to get vaccinated every year, an action that requires planning and proactive action, and the varying effectiveness of the vaccine. While vaccines for childhood diseases provide vaccinated people with protection of over 90%, and vaccinating everyone can completely eliminate the disease, this is not the case with flu. Government health ministries around the world are the first to admit this. Vaccination against flu reduces the likelihood of getting the disease by 10-70%, depending on the year. Furthermore, we all know people who are willing to swear that that they got flu only a day or two after getting vaccinated. Is it possible that the vaccination causes the disease?
Dr. Hertz dismisses this claim. "The vaccination that is administered now is mainly the inactivated vaccination," he explains. "The virus is raised in eggs, which makes it free of infectious activity, and it is eventually broken down into particles, none of which is a complete virus. In response to the vaccine, the body generates antibodies that identify parts of the virus that can be connected to it when necessary, and prevent it from spreading in the body. You can't get flu from the vaccine, and you obviously can't infect anyone else with flu after the vaccine. The vaccine sometimes creates a local pain response in the area of the injection, and sometimes muscle pain or a low temperature. This is a response by the activated immune system, but it isn't a disease.
"Furthermore, at least three weeks are required for the immune system to generate the antibodies, and people are liable to contract the disease during that time. In addition, the incubation period of the virus between the time a person becomes infected and the appearance of symptoms is one-to-four days, and it is therefore possible for a person to become infected with flu a day or two before getting vaccinated, and for the symptoms to appear only afterwards."
"Globes": Why is the vaccine only partially effective?
Hertz: "Every year, the vaccine companies try to guess which strain of flu will be prevalent in the Northern Hemisphere, after monitoring what happened in the Southern Hemisphere during the past summer (winter in the Southern Hemisphere). Sometimes they make a good guess, and sometimes their guess isn't so good. The effectiveness of the vaccine can therefore vary between a few percent in some years to 70% in other years. The correspondence this year to the strains now infecting people in Israel is fairly close, but a complete assessment of effectiveness takes place only after the year ends."
If no one got vaccinated, what would the risk be of getting the disease?
"About 8% in an average year."
What is the greatest risk of the vaccination?
"The smallest risk, one-to-two cases per one million vaccinations, is of paralysis, sometimes temporary, which is called the Guillain-Barre syndrome. The risk of getting this syndrome, however, is substantially greater than the risk of getting the syndrome after vaccination."
Hertz says that in general, "Vaccination is the medical invention that has saved the most lives. Childhood vaccinations are the main reason that there are so many children in the world today. I think that this invention is so successful because it is modest. We're essentially using a process that happens in nature in any case - exposure to a virus creates immunity."
Vaccination as a community act
Hertz says that just as getting infected with flu increases our resistance to other strains of the disease, getting vaccinated against it also expands our immunity profile, sometimes simultaneously for several strains, thereby protecting us from flu the next time without contracting the disease. Even if we get a strain of flu that is not in the vaccine in that year, we may get a less serious case. "When the strain of flu is deadly, or when we get old, it could be the difference between surviving and not surviving the disease," he says.
"Getting vaccinated against flu is a community act," Hertz adds. "We do it mainly for the weaker people in society. But if we want a more egotistical reason, current studies have found that during a period of flu, the risk of a heart attack increases six-fold in the week following infection, and doubles in the month following infection. For a healthy young person, this risk isn't a big one, but it's greater during and after flu. For an old person who is already sick, it can have a significant effect, and that doesn't happen when a person is vaccinated. We don't know exactly why this happens. Maybe flu affects the heart, and maybe it's related to an added respiratory burden.
"Furthermore, there are many studies showing that a person who contracts flu after being vaccinated usually gets a milder and shorter case of the disease. Only one of the 17 people who died of the disease in Israel in the current season had been vaccinated against flu, and only 12 of the 167 severe cases."
What do you think can be done to increase the proportion of people vaccinated?
"Make it more convenient. If we send nurses to workplaces and offer an available vaccine on a specific day, or if we make it possible to get vaccinated quickly at no cost at a pharmacy in a shopping mall, there's no doubt that we'll increase the number of vaccinated people.
"If vaccination becomes a social norm, it will have positive consequences. For example, certain workplaces in the US offer people a sticker saying, 'I've already been vaccinated.' Such a sticker helps make vaccination an accepted and desirable social act, and makes the vaccinated person proud. In the US, the proportion of vaccinated people is 60%."
According to Hertz, the proportion of vaccination among medical staff in Israel is only slightly higher than among the rest of the population, in contrast to medical staff in other countries, where vaccination is compulsory in many cases. "They have the same problems as the rest of the population," Hertz explains. "They don't have time to think about it. They don't really believe that something very bad will happen to them if they get infected, and they don't understand the benefit of prevention. I think that this is because many doctors don't really learn much about vaccinations in their training. The subject of vaccinations takes up such a small part of a doctor's time. In general, only in recent years have the health funds and doctors begun to spend more effort on preventative medicine."
In rare cases, flu can spread as an infection caused by the appearance of a new strain originating in animals, such as poultry or pigs. Such cases can kill a large proportion of the population, as happened in 1918, when a flu pandemic killed 50-100 million people worldwide in an 18-month span. "If such a powerful virus comes and develops into a disease, it can kill millions of people today and really change the population's composition," Hertz says.
In such a case, vaccination will probably be of no help. "We usually prepare with vaccinations against flu that we've already seen in human beings, while the deadly flu first ravages animals, undergoes mutation, and then spreads to us," Hertz says.
With time, medicine manages to also catch up to the new strain. This year, one of the four flu strains included in the vaccine, which has been the dominant strain in Israel so far, is a type of swine flu that also broke out in Israel a decade ago. Hertz now fears a certain strain of H7N9 flu widespread in poultry that has killed 40% of the infected poultry. Once this disease begins spreading from one person to another, it is liable to become deadly flu.
Is the usual flu in human beings this year, which comes from pigs, more deadly than the usual seasonal flu?
"We think so. In a study we're conducting now at Soroka Medical Center in cooperation with Dr. Lior Nesher, in which we recruit flu patients hospitalized in internal medicine wards, we found a large number of patients with alarming speed. It seems that the number of hospitalized patients is larger than usual, and there are more patients hospitalized with pneumonia."
The search for a universal vaccine
If we want to reduce the risk of infection with flu among both vaccinated and unvaccinated people, hygiene plays an important role. "People used to sneeze and cough into their hand; now they know that it's better to do it into their elbow. Even something like this helps. It's also recommended staying at home when you're sick, but since the virus spreads in the body before there are any symptoms, this won't solve the entire problem," Hertz says.
"At Soroka Medical Center, they carried out a project that used a rapid test for detecting viruses to identify flu patients within half an hour of their arriving at the emergency room," Hertz explains. "If flu is detected, great efforts are made to release them from the hospital quickly, or to put them in isolation. This procedure dramatically reduced the burden on the internal medicine wards, because one flu patient infects all of the others.
"A study we conducted in elite IDF units, in which 50% of the soldiers were vaccinated and 50% were not, because they came from other units and were conscripted during the summer, showed that in crowded conditions like those in which soldiers live, everyone who was not vaccinated developed antibodies to the disease, meaning that everyone was exposed. We understand from this that people in crowded places, such as the army, kindergartens, old and age homes, are very likely to be infected.
"At the same time, although all of the unvaccinated people whom we examined developed antibodies, this doesn't mean that the disease put all of them were out of action for a week. Some people have a more severe response to the disease, and there are people who are naturally resistant."
What causes the difference between people at risk of contracting the disease?
"There's an enormous difference between people in the response of their immune systems that results from genetics and congenital characteristics, and also from their exposure profile. It's easier for them to develop antibodies to diseases similar to those to which they've already been exposed.
"In my laboratory, we're investigating 'healthy people' who contract diseases infrequently, and whom diseases affect less when they are contracted, as well as people who are unfortunately at the other end of the scale - those who get every virus they meet, and who are liable to get sick even if they are vaccinated - not just flu, but other diseases, too. These people appear to have a problem with creating immunity memory.
"Incidentally, there are diseases that strengthen the immune response to diseases that come after them, and some that work in the other direction. For example, a recently published study on measles showed that it 'erased' the immune memory for other diseases, and made people more sensitive to them. The measles vaccine doesn't do this."
How does lifestyle affect the likelihood of getting infected, and the immune system in general?
"Many studies have shown that physical activity probably changes the immune profile for the better. Exercise creates small inflammation processes that strengthen the immune system. The biggest benefit is among people who exercise regularly and moderately. As for nutrition, there is apparently an effect via the microbiome, i.e. there are certain foods that interact with intestinal bacteria and a certain immune profile in a certain person, and which can also affect the immune system's effectiveness against a specific pathogen, but we don't know yet exactly what and how. Other studies showed that extreme obesity probably has a negative impact on the immune system and increases the risk of being infected with flu and other respiratory viruses."
Are we close to seeing a universal vaccine for all types of flu that we can take once and not have to worry about it any more?
"This is something that great effort and huge sums have been invested in by various countries, and by large funds such as the Bill and Melinda Gates fund and the US National Institutes of Health. The saving in lives and money from such a vaccine would be huge. I myself belong to a group of people from higher education institutions and industry that is trying to develop such a vaccine. Unfortunately, we have more questions than answers right now.
"At the same time, there are developments in this field. For example, they have succeeded in isolating an antibody that connects to and neutralizes many flu strains from a person who contracted swine flu in 2009 and recovered. They're now trying to turn this antibody into a passive vaccine, so that instead of injecting an inactivated and fabricated virus, we'll inject people directly with the antibody. A new vaccination would probably still be necessary each year, but the protection would be broader, including against unexpected viruses.
"Another approach is to develop a conventional vaccine, with an emphasis on areas in the vaccine that are supposed to be evolutionary. People are working on several such approaches."
What about the vaccination being developed by Israeli company BiondVax Pharmaceuticals?
"Their approach differs from the two I told you about. They're not developing antibodies for the proteins wrapped around the virus; they're developing T cells for the virus's internal proteins against which conventional vaccinations aren't aimed. They're in a Phase III human trial now, and we're all certainly waiting to hear about their results."
Published by Globes, Israel business news - en.globes.co.il - on January 15, 2020
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