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Monday, September 4, 2017

The Fight Against Antibiotic-Resistant Bacteria Might Start With Vaccines 09-04



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It seems like a major part of keeping kids healthy these days is managing their microbial exposure. On the one hand, we’re told that letting our kids get dirty and tempering our use of hand sanitizer can help cultivate a healthy population of good microbes in and on the body, which is associated with lower rates of chronic maladies like asthma and allergies. On the other hand, we know that among all the benign and beneficial bacteria in the world lurk some that are deadly, causing diseases such as whooping cough, pneumonia and meningitis.

To treat these diseases, we need antibiotics, but the downside is that antibiotics indiscriminately kill bacteria in the body, including the ones that contribute to our health. Meanwhile, every course of antibiotics gives bacteria that are resistant to the drugs a chance to grow and thrive. That makes for more antibiotic-resistant infections, all of which are harder to treat and some of which can’t be treated at all.

Ideally, we want to protect our kids from deadly bacteria without disturbing the good ones or worsening the trend of antibiotic resistance. And this is exactly what vaccines do. They give us exposure to the pathogen — be it bacterial or viral — in a weakened, killed or partial form so that we can develop immunity to it without getting the full-blown illness. If we’re exposed to the real thing later, our bodies have antibodies specific to that pathogen ready to fight back. No antibiotics needed, and our friendly microbes can continue to live in peace. But when parents choose not to vaccinate their kids, they’re increasing the kids’ chances of not only becoming seriously ill, but also of needing antibiotic treatment and other medical interventions down the road.

Dr. Joel Amundson, a pediatrician in Portland, Oregon, finds himself frequently talking about vaccines and antibiotics in the same breath. Oregon has one of the lowest immunization rates in the nation, and Amundson said many of the parents he counsels want to keep their kids “all-natural” and see vaccines as an unnecessary medical intervention. But when he explains that vaccines are a tool for decreasing medical interventions, including antibiotic use, that often changes their perspective. “That’s a huge benefit to my families,” he said, “It definitely has them more interested in doing vaccines when they understand that.”

Some parents who are reluctant to vaccinate worry about side effects, and though some kids will experience short-lived, minor reactions such as swelling at the injection site, serious side effects are extremely rare. Side effects from antibiotics, including diarrhea, rashes and allergic reactions, are generally more common and severe, Amundson said. “I see far more harm from antibiotics than I do from vaccines, by a huge margin. It’s not subtle,” he said.

Of course, when a person has a serious bacterial infection, the benefits of antibiotics far outweigh those risks, because these diseases can be deadly. “When we need them, we really need them,” said Janet Gilsdorf, professor emerita of pediatric infectious diseases at the University of Michigan. But in a world where antibiotic-resistant infections are thought to kill 50,000 people each year in the U.S. and Europe alone, a problem that the United Nations has called “the greatest and most urgent global risk,” reducing our use of antibiotics helps preserve their value. “The fewer infections we have, the fewer antibiotics we need to use, and we know that the use of antibiotics is what drives antibiotic resistance,” Gilsdorf said.

Vaccines have prevented millions of illnesses
Estimated number of infections prevented by vaccines over the lifespan of children born in the U.S. in 2009
INFECTIOUS DISEASECAUSED BYCASES PREVENTED
VaricellaVirus3,942,546
MeaslesVirus3,835,825
PertussisBacteria2,950,836
Pneumococcus-related diseasesBacteria2,323,952
MumpsVirus2,312,275
RubellaVirus1,981,066
RotavirusVirus1,582,940
DiphtheriaBacteria275,028
HepBVirus239,993
HepAVirus153,164
PolioVirus67,463
HibBacteria19,606
Congenital rubella syndromeVirus632
TetanusBacteria169
Source: Pediatrics

We don’t yet have research on whether emphasizing this benefit of vaccines might encourage parents to immunize their kids. While the vast majority of parents vaccinate their kids on schedule, the number of parents who are reluctant to do so does seems to be increasing in the U.S., despite a mountain of evidence supporting the efficacy and safety of vaccines. Reasons for parents’ concerns about vaccines are varied, and each type of concern will likely need to be addressed differently to improve vaccination rates. But there’s some evidence that parents are becoming more aware of the problem of antibiotic resistance, and a study of Austrian adults found that those with more knowledge about antibiotics were more likely to get the flu vaccine.

There’s no question that vaccines have dramatically reduced the burden of disease. A study published in 2014 estimated that among U.S. children born in 2009, following the recommended childhood vaccine schedule (not including the flu vaccine) would prevent 20 million cases of disease across their lifespans, and about 30 percent of these are bacterial diseases that would likely require antibiotic treatment. These are diseases like diphtheria and pertussis, both of which were major causes of childhood illness and death before their vaccines were developed in the first half of the 20th century.

More recently, the vaccine for Haemophilus influenzae type b (Hib), which the Food and Drug Administration approved for use in toddlers starting in 1985 and infants in 1990, nearly eliminated the dangerous blood and brain infections caused by this bacteria.

Pneumococcal vaccines have also reduced our dependence on antibiotics. The first was recommended in the U.S. for infants and young children in 2000, followed in 2010 by an updated version covering more strains of the bug. Like Hib, pneumococcus bacteria can cause pneumonia and invasive blood and brain infections, but it’s also a major cause of ear infections, which are one of the biggest reasons that children are prescribed antibiotics. Before the vaccine was added to the infant immunization schedule, up to 40 percent of invasive pneumococcal infections — meaning infections that spread to parts of the body, such as the bloodstream, that are normally germ-free — were resistant to at least one antibiotic, making them more difficult and costly to treat. The first pneumococcus vaccine decreased antibiotic-resistant invasive pneumococcal infections in young children by 81 percent, and the second vaccine caused an additional 61 percent drop. (These studies looked at different age groups, however; the first included only children younger than 2, and the second looked at children up to age 4.)

Pneumococcal vaccines have also reduced our dependence on antibiotics. The first was recommended in the U.S. for infants and young children in 2000, followed in 2010 by an updated version covering more strains of the bug. Like Hib, pneumococcus bacteria can cause pneumonia and invasive blood and brain infections, but it’s also a major cause of ear infections, which are one of the biggest reasons that children are prescribed antibiotics. Before the vaccine was added to the infant immunization schedule, up to 40 percent of invasive pneumococcal infections — meaning infections that spread to parts of the body, such as the bloodstream, that are normally germ-free — were resistant to at least one antibiotic, making them more difficult and costly to treat. The first pneumococcus vaccine decreased antibiotic-resistant invasive pneumococcal infections in young children by 81 percent, and the second vaccine caused an additional 61 percent drop. (These studies looked at different age groups, however; the first included only children younger than 2, and the second looked at children up to age 4.)
The U.S., Israel and the U.K. have also observed big drops in kids’ ear infections coinciding with the introduction of pneumococcal vaccines. (Other factors, such as increased breastfeeding and tightened diagnostic criteria for ear infections, have likely contributed to these improvements, but researchers believe that the vaccines have played an important role.) In a paper published last year, researchers estimated that making the pneumococcal vaccine universally available to children in the 75 countries they looked at could not only prevent disease but also avert 11.4 million days of antibiotic treatment each year, a 47 percent drop in current antibiotic use for pneumonia.

Less obviously, vaccines that protect against illnesses caused by viruses rather than bacteria can also help cut antibiotic use. For example, influenza is viral, but flu season always brings an uptick in antibiotic prescriptions. In many cases, the antibiotics are being inappropriately prescribed, but some are necessary treatments for secondary bacterial infections, like pneumonia and ear infections, that can move in when a person’s immune system is busy fighting the virus. When Ontario, Canada, started offering free flu vaccines, the province’s rate of antibiotic prescriptions associated with the flu dropped by 64 percent.

The vaccine against measles, another viral infection, also probably decreases antibiotic use. A 2015 paper showed that a measles infection weakens a person’s immune system for two to three years, which explains why the measles vaccine reduces childhood mortality by 30 percent to 50 percent in poor countries, which can’t be explained by measles prevention alone. “Not having measles is a really good thing for your immune system in terms of preventing other infections,” said Marc Lipsitch, professor of epidemiology at Harvard T.H. Chan School of Public Health.

In a paper published last year, Lipsitch argued that development of new vaccines should be considered an important strategy in the fight against antibiotic-resistant bacteria. He believes that it would be most useful to have vaccines against certain bacterial strains that patients tend to pick up in hospitals — those strains are often resistant to multiple antibiotics. A more effective flu vaccine and a vaccine for respiratory syncytial virus, known as RSV, which sends more than 57,000 young children and 177,000 elderly people in the U.S. to the hospital each year, could also reduce antibiotic use. Potential vaccines for a number of these diseases are in various stages of clinical trials.

Lipsitch envisions vaccines that go even further. “I actually think one of the most interesting ideas I’ve had is the idea of using vaccines directly to target [antibiotic] resistant bacteria, not just all bacteria, but directly aiming at the targets that are the resistant genes.” This type of vaccine would be especially helpful for bacteria like pneumococcus and Staphylococcus aureus, which are so ubiquitous that they’re unlikely to be eliminated; keeping drug resistance at bay would help us coexist with them more peacefully. “The idea of these resistance-targeted vaccines is to try to make life extra hard for the resistant organisms,” Lipsitch said.

But would it be tough to sell people on more vaccines for both kids and adults when some people are refusing to get the vaccines we already have? “I think it ought to be a pretty easy sell, actually,” said David Salisbury, associate fellow at the Chatham House Centre on Global Health Security in London and former director of immunization at the U.K. Department of Health. “Imagine if an ear infection, which happens so commonly in children, became untreatable. You can fantasize about false risks of the vaccines, but they turn to nothing when you compare them with untreatable infections. Would you seriously prefer your child not to have a vaccine and risk an infection to which there was no treatment?”

A global challenge as big as antibiotic resistance will require multiple solutions, including reducing the use of antibiotics in agriculture and developing new antibiotics, but Salisbury says that vaccines deserve more attention and investment. Gilsdorf is on board with that. “What we need is more good science, which means we need more funding for the National Institutes of Health, the National Science Foundation, and these federal agencies that support scientists to learn the nitty-gritty of these bacteria,” she said.

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