National Institute of Allergy and Infectious Diseases

A new flu vaccine is made out of self-assembling nanoparticles. This images shows what the particle looks like - to the immune system, it looks like a flu virus.

Researchers have developed a “stripped down” synthetic flu vaccine that they believe will not only work better than current vaccines, but might last longer, too -- saving people from having to get a fresh flu shot every year.

They say it’s the first step toward a new generation of influenza vaccines, designed entirely in the lab, using nanoparticles instead of the decades-old approach that uses chicken eggs. The nanoparticles assemble themselves into an imposter of the flu virus -- one that seems to excite the immune system far more than the real thing.

“This is, I believe, an important advance,” says Dr. Tony Fauci, head of the National Institute of Allergy and Infectious Diseases, where the research was done.

Current flu vaccines are clunky at best. Most are still grown in eggs, an uncertain technology that takes months. Entire factories full of vaccine can be shut down because of contamination. Researchers have figured out how to make synthetic versions of the flu virus to use as a basis for the vaccine, but many still use real viruses, either killed or weakened so they don’t make people sick.

And it’s never certain from one year to the next how well the vaccine will work. No one is precisely sure why, but the virus mutates every year, and a variety of strains circulate at any given time. The result is that some years the vaccine protects people well, and in others, it doesn’t.

For instance, this past season’s influenza vaccine reduced the chances of illness by just 9 percent in people older than 65, the Centers for Disease Control and Prevention says, and reduced illness for the population as a whole by 56 percent.

And then every few years, a new strain pops up to infect people. Health officials are currently keeping a wary eye on two strains of bird flu, H5N1 and H7N9, either of which could mutate just a bit more to cause a pandemic.

The new vaccine uses a key part of the flu virus, called hemagglutinin, which gives flu the “H” in its name.  Dr. Gary Nabel, who was at NIAID at the time, fused a bit of hemagglutinin to a piece of a compound called ferritin. Ferritin naturally makes itself into little nanoparticles, and the result was a nano-sized spiky ball that looked a lot like a natural bit of hemagglutinin.

Nabel says it’s a stripped-down version of flu virus that the immune system recognizes even better than it does real flu. Tests on animals showed the nanoparticles caused the body to produce 10 times as many virus-fighting antibodies as the current seasonal flu vaccine, Nabel’s team reports in the journal Nature.

“They look like flu. They react with antibodies like flu,” Nabel, who now works for vaccine maker Sanofi, said in a telephone interview.

The vaccine protected ferrets against H1N1 flu viruses, an H3 flu virus and an influenza B virus, too. Ferrets are the animals that react most like humans to flu.

Now researchers are working to make a version that can be tested in people.

Nabel thinks the vaccine will provide broader immunity than current vaccines, as well as a stronger immune response. But humans have unique immune systems and it’s not yet clear how it will work in people.

It may also speed up the convoluted process for making vaccines, which starts with growing the virus in the lab, something that can take months. “We don’t need the virus to replicate. We just put the gene into a cell and make the particle. It is rather an amazing process,” Nabel says.

“In theory it could be very fast.” If it takes three months now to make a “seed” virus for a vaccine, the new process would only take a week or two, he estimates.

It took months to make and roll out vaccine against H1N1 swine flu when it first broke out in 2009 and thousands of people died during the delay. CDC doesn’t count how many adults die from flu each year, because it’s so variable -- anywhere from 4,000 to 49,000 a year.

The new technology might not just work against flu. “This is a platform that could be used for other viruses,” Nabel said. That could include the AIDS virus or herpes, or even coronaviruses like the new MERS virus that has killed more than 20 people in Saudi Arabia and other middle east countries.

Fauci said in theory, a vaccine made from this new technology could last longer than the current seasonal flu vaccine. “To me, this is an important step toward the development of a universal flu vaccine,” Fauci said. “The definition of a universal flu vaccine is it covers wide range (of virus strains) and you wouldn’t necessarily need to get a new one each year.”

Dr. John Treanor, a flu vaccine researcher at the University of Rochester Medical Center, said the approach resembled some newer-generation vaccines that use synthetic technology and that have been shown to work in people.  “It certainly is a very technically advanced approach,” said Treanor, who was not involved in the research.

Related:

• CDC says flu vaccine barely worked in seniors this year
• New technology speeds process against bird flu vaccine
• Doctors are making an H7N9 vaccine, just in case
• Ouch free vaccines in the works

A drug that flopped in tests to treat sepsis may offer a new way to treat influenza, researchers reported on Wednesday.

If it works in people, it might provide a new defense against emerging new viruses such as the H7N9 bird flu virus circulating in China, other experts said.

Tests in rodents show the drug appears to stop the immune system overreaction that so often kills people infected with influenza and other viruses, the researchers report in the journal Nature. And because it acts on the patient, and not on the virus, it may be immune to the mutations that make so many viruses resistant to drugs.

“We hope it’s a new flu drug,” says Stefanie Vogel, a researcher at the University of Maryland school of medicine who led the research. “This is the first drug to come along for flu where you are not focusing on the virus… What was exciting about our paper is we showed that even starting the drug as late as six days after the infection gave us significant improval in the life of the mice.”

Most strains of influenza have already evolved resistance to the first two flu drugs – amantadine and rimantadine. There are two newer drugs on the market – a pill called Tamiflu and an inhaled powder called Relenza. But there are strains of flu that already elude the effects of Tamiflu.

There’s a third drug, called peramivir, but it’s not widely used. And viruses can evolve resistance to that drug, too.  It’s the same problem that plagues antibiotics, the drugs used to fight bacterial infections. So-called “superbugs” have evolved that can resist the effects of many different drugs.

Health experts are keen for an antiviral drug that will work no matter how the virus mutates. One way to do this is to affect the immune response of the patient.

The new drug, called Eritoran, was originally developed by the Japanese drug company Eisai Co. to fight sepsis. Doctors believe sepsis is a form of immune system overreaction that can kill after an infection or injury.  Eritoran was shown to be safe in people, but it didn’t work well against sepsis.

Vogel’s team had noticed that the drug worked against a particular part of immune system cells called TLR4. They also knew that lab mice genetically engineered to lack TLR4 seemed particularly immune to flu. Could blocking TLR4 make people immune to flu’s effects on the immune system, too, they asked?

It did. Tests in a second rodent called a cotton rat showed this, too. Vogel’s team wants to do further tests but they hope this may provide a new and better way to treat influenza.

Flu usually doesn’t kill people, of course. It just causes unpleasant symptoms such as fever, cough and muscle aches. But it can cause pneumonia and in some people, including perfectly healthy young people, it can cause an immune system overreaction called a cytokine storm. Vogel calls it a cytokine avalanche.

“You need a certain amount of imflammation to be able to fight off the attacking agent,” Vogel said. “But when the inflammation spins out of control, then you end up hurting yourself.”

Joan Nichols, a flu expert at the University of Texas Medical Branch in Galveston, says the study shows Eritoran has a lot of potential. “One of the things we need is a broad-spectrum influenza drug,” she said in telephone interview.

One of the weaknesses of Tamiflu is that it must be taken within a day or two of symptoms showing up to be effective. The new drug might work after people become seriously ill with flu. “This drug could be used to treat people who are already symptomatic,” Nichols said. “You might not see as many deaths.”

A new strain of bird flu called H7N9 avian influenza has already infected more than 120 people in China and killed 27 of them. Tamiflu seems to help, but if the new virus spread and mutated into a form that infected people more easily, it could cause a pandemic. It would take months to make a vaccine, and drugs would be the best defense until one was ready.

“This would be useful in outbreaks like the H7N9,” Nichols said. “No matter what strain of influenza you see emerge, we have got a drug that could buy us some time.”

The approach might also be useful against other viruses that also cause an immune system overreaction, such as severe acute respiratory syndrome (SARS), says John Teijaro, senior research associate at The Scripps Research Institute who specializes in studying these cytokine storms. “Aberrant immune responses have been implicated in the pathogenesis of acute respiratory viral infections including influenza, SARS and hantavirus,” he said in a statement.

SARS, a so-called coronavirus, swept around the world in 2003, infecting around 8,000 people and killing 800 before it was stopped. Health experts are keeping a wary eye on a new type of coronavirus first seen in the Middle East that has killed at least 16 people.

And, said Nichols, the drug has already gone through clinical trials to show it’s safe in people. “Say we needed it tomorrow. They could probably push this,” she said.

Related:

• A long, tough flu season
• New analysis show bird flu a mixture of duck, chicken viruses
• Teen's death shows flu can kill in a flash

Less than two weeks after Chinese officials released the genetic sequence of a new type of bird flu, U.S. vaccine experts are well on the way to making a vaccine to protect people against it.

There’s no evidence the H7N9 virus would ever threaten the U.S. It’s been diagnosed in fewer than three dozen people, all restricted to eastern China. People don’t appear to be infecting one another, at least not in large numbers.

But it’s already killed nine of them. Scientists said Wednesday that the virus seems to have been the result of genetic reassortment of wild birds from east Asia and chickens from east China, Xinhua, the official Chinese news agency reported. Still, it doesn’t seem to be making birds sick -- which means authorities don’t have tell-tale die-offs of poultry to warn them when it’s circulating.

And it takes months to make influenza vaccines, so every day may count.

“It puts flu back on people’s minds,” said Dr. Amesh Adalja, an emergency physician at the Center for Biosecurity at the University of Pittsburgh Medical Center.

It’s just the kind of situation that flu experts have been been rehearsing for. They hope to do better than in 2009, when it took until October to deliver the first vaccines against the pandemic of H1N1 swine flu.

“The virus was identified in March,” notes flu expert Dr. Arnold Monto of the University of Michigan. Six long months ticked by with the virus spreading and no vaccine against it.

The U.S. government was battered by criticism from confused Americans who tried hard to get flu vaccine but couldn’t, and then gave up trying just about the time that vaccines started being produced and delivered in quantity.

Vaccine makers ended up throwing away about 70 million doses. “We can do it faster,” Monto said.

Two seasonal flu vaccines that use new technology approved within the past six months should help speed up the process. That same techonology can be used to make other vaccines, including one to protect against H7N9. And Dr. Robin Robinson of the Biomedical Advanced Research and Development Authority (BARDA), part of the Health and Human Services Department, says H7N9 is giving his department the chance for what he hopes will be a dry run.

“I think we are in a much better place than we were before the pandemic of 2009,” Robinson told NBC News. “We have some ongoing initiatives that are starting to provide real results.”

Most flu vaccines are made using technology that dates back to the 1940s. Doctors isolate the virus from a patient, combine it with another virus used to make the a “seed” for the vaccine, grow it in specially fertilized chicken eggs, strain it out and purify it – a process that takes months and that is fraught with dangers, not the least of which is contamination of the eggs.

Newer technology dumps the eggs. One new vaccine is grown in insect cells, and another is grown in cells taken from a single cocker spaniel’s kidney decades ago. That speeds things up a bit. And now scientists can make vaccine based on the genetic sequence, because they can make artificial genes in the lab.

So they can go straight from a genetic sequence published online to starting to make a vaccine. This method, called recombinant technology, shaves a few weeks off the process. Last summer, when a new strain of swine flu called H3N2v infected about 300 people and killed one, mostly via state fairs, drug maker Novartis and experts at the J. Craig Venter Institute in California made a seed virus for the vaccine in a week, Robinson says.

“Now with the H7N9 outbreak in China, the nucleotide (genetic) sequence was available Saturday, March 30,” Robinson said. Scientists at Novartis, with the federal government and the Venter Institute synthesized the necessary genes by the following Tuesday. By Wednesday, they had inserted the artificial gene sequences into dog cells and were growing new virus.

“Now we are characterizing that … virus to see if we have the right seed strains,” Robinson said. If they are, they’ll be tested and prepared to make a vaccine.

“We have been able to shave weeks off the method,” Robinson said.

When samples of the actual virus are released later this week, vaccine makers using old-fashioned methods will go to work on those, Robinson added.

“We have talked to all the manufacturers that make egg- based, cell-based and recombinant-based vaccines to ask what their manufacturing capabilities are,” Robinson said. HHS will know by the end of this week how much vaccine the companies can make and when they could have it ready, he says.

In any pandemic, the goal is to vaccinate every American. What's not clear is how many doses would be needed for protection and whether manufacturers could create enough in time.

The United States has invested heavily in vaccine technology since about 2004, when it became clear that H5N1 bird flu was a threat. So far, H5N1 has been an expensive nuisance, forcing the culling of hundreds of millions of birds, and killing 60 percent of the 600 or so human victims who have been infected.

But it could mutate into a form that passes easily from human to human. So could H7N9. Or another type of flu could emerge. Seasonal flu vaccines provide no protection at all against these new strains.

Some people have criticized the U.S. government’s reliance on commercial flu vaccines. It’s spent $147 million in five years to help companies that were struggling to develop new vaccine technology.

Seven companies make flu vaccines for the U.S. market, and the CDC and HHS are heavily invested in encouraging people to get vaccinated each year, not only to protect themselves from flu, but to keep a market incentive for companies to make flu vaccine.

But Monto says it’s the only way. “If the companies were not involved in producing a vaccine and taking risks each year, we wouldn’t have vaccines,” he says. And seasonal flu is nothing to sneeze at -- killing upwards of 40,000 people in a bad year.

Robinson says these preparedness efforts have been spared so far from budget cuts hitting other areas of government.

“We plan for these kinds of things to happen,” he said. “So far we are OK in developing the actual vaccine candidate. Where we get into trouble and will have to ask Congress for more money is if we have to have a large vaccine campaign like we had in 2009.”

Related:

Government investment gives flu vaccine a shot in the arm

New virus not transmitted person to person

Flu vaccine barely worked in elderly this year

Brian Snyder/Reuters

Chihn Ha, 8, gets an influenza vaccine injection from nurse Nho Nguyen, right, during a flu shot clinic at Dorchester House, a health care clinic, in Boston, Mass., in January 2013.

The longer-than-average flu season finally appears to be ending, federal officials said on Friday, but it’s not quite done yet. Only six states, mostly in the Northeast, are now reporting widespread influenza.

The deaths of another five children were reported this past week, bringing the total for the season to 110, the Centers for Disease Control and Prevention reports. That’s just around the unfortunate average for influenza in any given year, the CDC says, although it varies a lot.

The viruses circulating this year were especially hard on people 65 and older and CDC is still trying to work out just how well vaccines may or may not have protected people, especially the elderly, against serious illness and death from flu. So many adults die of flu every year that the CDC can’t keep a precise count, but estimates that it ranges from a low of 3,000 to as many as 49,000.

This year was a “moderately severe” flu year, CDC says in a review of the 2012-2013 influenza season.

“This season, influenza activity started about 4 weeks early and was intense. Influenza-like-illness rose quickly to well above the baseline of expected activity and remained elevated for 15 consecutive weeks, making this season slightly longer than average,” the agency says in a statement.

“Flu-associated hospitalizations began to rise in mid-December with sharp increases seen among people 65 years and older.”

Half of the patients sick enough to be hospitalized with flu were 65 or older, CDC said. “While hospitalization rates have leveled off, this is the highest proportion of persons 65 and older hospitalized for flu that has been measured since this kind of record-keeping began during the 2005-2006 season,” it said.

Sadly, a few were children, and most had not been vaccinated, CDC said. “CDC reported an additional five pediatric deaths this week for a total of 110 to date for the 2012-2013 season. The number of pediatric deaths is likely to climb further as additional deaths are reported,” CDC said. Reports of deaths can take weeks to collate -- some of the five deaths reported this week dated back to December.

Experts have done a batch of studies to see how well the flu vaccine worked this year. That varies from year to year and scientists still are not sure why flu vaccination protects more strongly in some years than in others.

Flu vaccines have to be formulated freshly each year to protect against the most common circulating strains of virus. This year’s vaccine protected against three strains – one called H3N2, one called H1N1 – a descendant of the H1N1 “swine flu” that emerged in 2009 – and one influenza B strain.

Next year’s vaccines are just being formulated now, based on what’s circulating, and some will protect against four strains of flu.

“February results showed the 2012-2013 flu vaccine reduced the risk of flu-associated medical visits from influenza A (H3N2) viruses by one half and from influenza B by two-thirds for most of the population,” the CDC said.

 “This means that vaccinated people reduced their risk of having to go to the doctor for influenza by more than half, thus providing significant benefit to the person getting vaccinated and to public health in general.”

But it only prevented the risk of severe disease by 27 percent among people 65 and older this year. “It’s possible that some people 65 and older did not mount a good immune response to H3N2 from vaccination,” CDC said.

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• Why it's so hard to get the flu vaccine supply right
• Flu spreads to all 50 states

If all the coughing and sneezing associated with this year’s severe flu season have you worried you’ll catch the bug, consider boosting the humidity in the rooms around you.

Moderate to high humidity can actually reduce the ability of the flu virus to infect folks, according to a new study published in the journal PLOS One. Maintaining relative indoor humidity at 43 percent or higher could cut the bug’s threat to about 15 percent, researchers found.

The flu is often spread through the air, said John D. Noti, team leader of the infectious disease transmission program at the National Institute for Occupational Safety and Health. When we cough or sneeze, bits of virus hitch a ride on droplets of mucous or water, explained Noti, the report’s lead author.

While the large droplets hit the floor and other surfaces fairly quickly, the smallest ones can remain in the air for hours -- just waiting for you to breathe them in.

“Typically they stay in the air for an hour or so, but we have caught them as long as five hours out,” Noti says. “If you’re a health care worker in a room full of coughing patients there could be a lot of them.”

Earlier studies had suggested that the flu virus might be sensitive to humidity. So Noti and his colleagues set up an ingenious experiment, one that simulated a real-life situation, but exposed no humans to the nasty virus.

The researchers put two manikins about six feet apart in a closed-off room. One of the manikins was designed to “cough” flu particles into the air, while the one on the other side of the room “breathed” them in.

Noti and his colleagues collected samples from the inhaling manikin every few minutes and then deposited them in a cell culture to see if the virus particles would be able to infect the tissue cells.

The researchers ran their experiment at varying levels of humidity.

They found that when the humidity was less than 23 percent, the virus retained between about 71 percent of its ability to infect. When the humidity was boosted to 43 percent or higher, the infectivity dropped to about 15 percent.

And that drop-off in infectivity happened fast -- within 15 minutes of the initial cough.

The experiment may explain why we see so much more flu in the fall and winter months, Noti says. “In the winter months when the heat is on, the air is really dry,” he says. “It’s often down around 10 percent or less. So that may be what is driving all that February activity.”

The new study might offer interesting insight into the biology of the virus itself, says E. John Wherry, director of the Institute for Immunology at the University of Pennsylvania School of Medicine.

“There are lots of theories as to why the flu seasonally cycles: More people are inside, the weather is colder, mucous membranes might be more sensitive because of the dry conditions inside,” says Wherry. “But this suggests that humidity influences the virus itself rather than making our mucous membranes more susceptible.”

The researchers don’t address what happens to the virus, Wherry says. “But this virus is not very hardy. Changes in humidity, concentrations of salt or protein could have a major impact on it. The next step might be to look at what features of the virus change when the humidity is high. Those might offer targets for intervention. If you can show the weak point of the virus, that might be more broadly useful.”

In the meantime, it might make sense for folks to invest in a humidifier for their homes.

“Given that there’s very little downside to humidifying houses in the winter -- that looks like a good idea based on their data.”

Related stories: 

• CDC says flu vaccine barely worked in over-65s this year
• Nasty flu season sparks spotty vaccine shortages

REUTERS/Lisi Niesner

Paramedics dressed in protective attire enter a German cruise ship quarantined in December after an outbreak suspected to be norovirus. A new strain is making people miserable around the world this year.

It gets in your food, in your laundry, it sticks to plates and it might even float into the air when you flush your toilet. A new strain of norovirus -- often called stomach flu -- is going around and it’s going to be very hard to avoid it, experts say.

Federal health officials say a new strain, called the Sydney strain, is now causing most of the misery across the United States and the world. The virus, sometimes known as Norwalk virus or winter vomiting disease, causes vomiting, diarrhea and that someone-just-hit-me-with-a-plank feeling.

There’s no real treatment for it except for waiting it out, no vaccine, and recent studies show it’s one of the hardest viruses to get rid of. Simple cleaning alone doesn’t always kill it, and it takes just a few particles of virus to sicken a person.

“It is pretty difficult to get rid of,” says Allison Aiello, who studies how viruses spread at the University of Michigan. “It is pretty stable. It lives quite some time on surfaces. It is hard to kill.”

For instance, a few recent studies show that a quick application of hand sanitizer won’t get rid of it, Aiello says. And most people don’t wash their hands properly, either -- it takes about 30 seconds of vigorous rubbing using hot water and soap to wash away the tiny bits of virus, and that means getting under the nails, too.

Perhaps worst of all, people start spreading norovirus before they actually feel sick, and they can spread it for as long as two weeks after they start getting better. 

“Imagine you have a food handler who uses the bathroom and they haven’t washed their hands thoroughly,” Aiello said in a telephone interview. “They can end up preparing a salad for the diners that evening and end up infecting a lot of people because the food isn’t cooked. You can’t really do anything about that.”

Raw shellfish is a notorious source of norovirus and other foodborne germs, but at least one recent study suggests norovirus may be even more insidious than that. In December, a team at Ohio State University found the virus stuck to plates that had been washed in restaurant-like conditions -- and they found sticky dairy products like cheese helped the virus stay there.

Hand-washed dishes are especially likely to carry the virus, the Centers for Disease Control and Prevention says in its website -- which could be one reason norovirus causes so many outbreaks on cruise ships. “You cannot get the water hot enough if you wash by hand,” says Aiello.

Norovirus is spread fecally -- in the poop -- and that means it can get into laundry. Studies show that fecal matter spreads even in ordinary laundry, so if someone is sick, it’s important to use very hot water and bleach to destroy virus that could be on any clothing, sheets or towels.

And regular cleaner won’t get the virus off surfaces. CDC recommends using bleach, including chlorine bleach or hydrogen peroxide.

Complicating the problem, most restaurant workers don’t get paid sick leave, so if they miss work, they don’t get paid. This means many workers come in sick, and they can spread the virus to hundreds of customers. Food handlers, dishwashers, even staff who bus and clear tables, all can spread the germ.

“If they have to go back to work there has to be complete and utter vigilance about washing your hands,” Aiello says.

In June, the Food Chain Workers Alliance issued a report showing that only 21 percent of workers surveyed could take a paid sick day off work. More than half said they come to work sick because they cannot take time off.

The problem extends to the home, too. There, Aiello said, several factors make it hard to keep one sick family member from infecting others.

“It could be the door handle. It could be the toilet tank cover. Some studies show it can be aerosolized. If you throw up and then flush the toilet, how much of the spray gets into the air?” she asked. One study last year showed how the virus spread on a plastic bag that had been in a bathroom where a norovirus patient threw up. 

Norovirus is the most common cause of acute gastroenteritis -- stomach upset -- in the United States. It makes 21 million people sick every year in the United States – 70,000 on average sick enough to go to the hospital. As many as 800 people die, mostly elderly patients who become dehydrated. It’s the the most common cause of foodborne-disease outbreaks, CDC says.

Dr. John Treanor of the University of Rochester Medical Center in New York is working on a vaccine against norovirus. But the same properties that make norovirus so hard to kill also make it hard to make a vaccine.

For one thing, it’s simple. Like all viruses, norovirus hijacks live cells, turning them into virus factories that kick out particles called virions. “There is only one protein they use to make virions,” Treanor says. “If you have that one protein, it will self-assemble.”

The virus is also surrounded by a case called a capsid, which makes it hard to kill. The viruses infect the epithelial cells which line the digestive tract, causing cramps, diarrhea and vomiting, but it’s not understood exactly why.

And the virus mutates. “You typically see a specific strain, and then that strain is replaced by a new strain,” Treanor said. In this case, a strain called New Orleans has been replaced by the Sydney strain. Like with influenza, people who may have had some immunity against one strain aren’t protected agaisnt the new one.

So until there is a vaccine, what can people do? “There really isn’t very much you can do,” says Treanor. “Clearly, washing your hands is important.”

Related stories:

• New strain of norovirus on the rise
• Norovirus vaccine shows promise
• It's not always the flu

Don’t miss the latest health news on NBCNews.com

Mario Tama/Getty Images

Phamacist Prakash Deshpande injects Judith Echevarria with influenza vaccine at a Manhattan pharmacy. Americans are clamoring for influenza vaccine thanks an an unusually early flu season this year.

Drugs stores running out of vaccine. One company’s supply nearly sold out. An unusually early flu season has Americans clamoring for vaccines and all of a sudden they are scarce.

Yet back in September, public health officials were begging people to get vaccinated. Why the disconnect?

There are four main reasons:

• Flu vaccine is hard to make and it takes months
• Americans are ambivalent about vaccines in general and only want flu vaccines when they are scared (like now)
• Doctors are not paid to encourage and remind patients to get a flu shot, and they are afraid to order too much in case they’re stuck with the extra
• Vaccine makers only want to make as much as they can sell and last year the U.S. threw away 30 million doses

It may be 2013, but the United States still uses technology developed in the 1940s to make flu vaccines. In fact, the process for making next year’s flu vaccine is just starting to gear up right now, even though this year’s flu season is nowhere near to being over.

Experts have to first predict which strains of flu virus will be circulating next year. Influenza mutates all the time and there are different strains, so this is tricky. It’s also the reason people have to get a new flu vaccine every year.

The virus must be isolated from patients’ blood, purified, and injected into chicken eggs to grow. These aren’t just any chicken eggs, either – they have to be fertilized, have a chicken embryo inside and they need to be a certain size. The process is fraught with danger and often breaks down if eggs don’t develop right or if there’s contamination.

Then the virus is purified and made into vaccine. New technology is in the works and Novartis now makes flu vaccine at a factory in Holly Springs, North Carolina, using dog cells instead of eggs—a process that’s slightly faster, easier to control and that can be scaled up more quickly.

The hope is for a universal flu vaccine – one that would work against all strains of flu and protect people for years at a time, but progress is slow.

“A vaccine that would provide protection against all of the known strains of influenza has been a goal since flu vaccine was discovered,” says Dr. John Treanor, a vaccine researcher at the University of Rochester in New York. “It’s not going to be a straightforward, easy shot.”

In the meantime, companies predict how much demand there will be months before flu season even starts, and there’s no way to ramp up production when a season like this one hits and there’s suddenly a surge in demand.

This leads to the next problem: Americans don’t like getting flu shots. It’s the main reason demand is hard to predict. About 128 million people, or about 42 percent of the U.S. population, got immunized against influenza last year. That’s even though the Centers for Disease Control and Prevention says everyone over the age of six months should get a vaccine – every year. More than 30 million doses of flu vaccine never got used and were almost certainly thrown away, according to CDC.

“If people followed the recommendations every year, there would be no shortages,” says Dr. Walter Orenstein of Emory University’s Emory Vaccine Center and a former head of the CDC’s immunization program.

“The first issue is that Americans are pretty deeply divided on whether they think flu vaccination is a good idea,” says Katherine Harris, a RAND Corporation economist who studies flu vaccine issues.

“There are the people that get it and the people that don’t, and the people that don’t get it have pretty bad attitudes about it.”

And people aren’t afraid of the flu, even though it kills as many as 36,000 people in a bad year, including 100 children every year. Flu puts as many as 200,000 people into the hospital every year. But in some years it may be a mild season and kill 4,000 people. This variation lulls people into thinking flu isn’t a problem. “Many people who don’t get flu vaccine don’t get it because they don’t feel they, personally, are at risk,” Treanor says.

The flu vaccine isn’t perfect, either, leading many to think it’s a waste of time to get one. This year’s is only 62 percent effective. On top of that. lots and lots of viruses act like flu – causing coughing, headache, muscle aches and so on – so  many people believe they have flu even if they don’t. But Orenstein says if 80 percent of Americans got vaccinated with this vaccine, it would provide “herd immunity” against flu.

“I have had in the last three weeks two respiratory illnesses,” Orenstein says. “And I was vaccinated. But even if one was the flu, the other one was not. Maybe neither of them was flu.” But such uncertainty can make people doubtful about the value of vaccination.

The belief that flu vaccine causes flu is still rampant, although doctors all agree it’s not true. Many people also fear side-effects from the vaccine. Vaccine regulators and public health experts still remember the 1976 swine flu debacle, when the U.S. government rushed out a mass immunization against a swine flu virus that never spread off one military base.

Several hundred cases of a rare neurological disease called Guillain-Barre syndrome were reported afterward and the incident made many people mistrustful of immunizations.  More recent fears center on a mercury-based preservative called thimerosal, which was taken out of most vaccines after activists claimed it could cause autism. The link is discredited by many scientific studies but suspicion persists among some parents and activists.

Harris says people do trust their personal physicians, but doctors are not usually paid by health insurance companies to talk people into getting flu vaccines, and they aren’t paid much to administer them. Doctors have to compete with pharmacies, big companies that buy up vaccine to give to their employees, and large stores like Wal-Mart and Target to even get vaccine to stock, and they have to eat the cost if they don’t sell all the vaccines they buy to patients.

“It is a cost that comes right off their books,” Harris says. So many don’t even bother.

“We don’t really have a way for compensating health care providers for encouraging us to take preventive steps,” she said. The 2010 Affordable Care Act does have provisions for rewarding preventive medicine, however, which take effect in 2014.

Harris believes that if doctors’ offices worked harder to remind people to get a flu shot, more people would get it, vaccine makers would provide more supply, and flu shot shortages would ease up.

The Trust for America's Health agrees. It recommends that insurers be required to cover flu vaccines under public and private insurance without cost-sharing.  "For instance, currently, 12 states and Washington, D.C. do not require Medicaid to cover flu shots with no co-payment requirements for beneficiaries under the age of 65," the group said in a statement released Tuesday.

The federal government is trying to help in other ways, too. Ten years ago, just four companies made flu vaccines. This year, the U.S. government has licensed vaccines made by seven manufacturers. They include a nasal spray that’s been shown to work especially well in children and a special formulation for older people, whose immune sytems don’t respond as well to vaccines.

The idea is to spread the risk as well as to increase availability. Sanofi Pasteur, which provides about half of the flu vaccine in the U.S., says it has sold out of four of its six formulations of its Fluzone seasonal flu vaccine because of late-season demand.

Companies are wary of making too much vaccine, however, because they can’t re-sell it next year. The flu strains will likely have changed enough to make this year’s vaccine out of date for next year. “It’s not like you can carry it over if you don’t use it,” says Orenstein.

In 2008-2009 the U.S. government shipped 162 million doses of vaccine, but only 90 million were used. And last year 30 million doses or more went unused – most at a loss to the drug makers.

As a result, this year the seven companies made 135 million doses of flu vaccine. So far 128 million have been distributed to pharmacies, doctors’ offices and other providers.

“We have received reports that some consumers have found spot shortages of the vaccine,” Food and Drug Administration commissioner Dr. Margaret Hamburg says in her blog. “We are monitoring this situation and will update you at our Website and at www.flu.gov.” There’s a flu vaccine finder on those websites.

“The flu season usually peaks in January or February, but can extend as late as May,” Hamburg adds – meaning it’s not too late to get a vaccine if you can find one.

“All of us should be encouraging our friends, our neighbors – everyone – to get vaccinated,” Orenstein said. 

• Related links:
• Nasty flu season sparks shortages
• Flu shot isn't perfect
• Flu shot still a hard sell
• Teen death shows flu can kill

MIXA via Getty Images stock

You may think your cough ought to last no more than a week, but the actual duration of a typical cough is nearly 18 days, and could be more than three weeks, a study finds.

If you’re a victim of this year’s terrible flu, or any of the other nasty bugs causing general respiratory distress, Dr. Mark Ebell sends his sympathies.

But if you’re tempted to head to the doctor to demand drugs for the hacking cough that came with your illness, he’s got another message: Wait a little longer.

A new study shows that although most people think a cough ought to last no more than a week or so, the duration of the most annoying symptom of winter illness is about 18 days -- and could be more than three weeks.

Taking antibiotics in the interim is not only ineffective, it could also prompt dangerous side effects -- and contribute to the country’s growing problem with bugs becoming resistant to the drugs used to treat them.

That’s according to a new study by Ebell, an associate professor at the University of Georgia College of Public Health, which sought to define the gulf between public perception and reality when it comes to coughing.

“A lot of times patients will come to me and they’ve been coughing for four or five days and they’re not getting any better, so they ask for an antibiotic,” he said. “After eight or nine days, they’re still not feeling better, so they ask for an even stronger antibiotic. Then they’ll say, ‘The only thing that really works for me is this really strong antibiotic.’”

The trouble is, antibiotics aren’t actually the solution for most of the 3 million outpatient cases in the U.S. each year in which cough is the chief complaint, or for the more than 4.5 million outpatient cases diagnosed as acute bronchitis or bronchiolitis. More than 90 percent of such cases are viral, not bacterial, which means they won’t respond to the drugs most folks request, according to the Centers for Disease Control and Prevention.

Ebell decided to pursue the study, published Monday in the journal Annals of Family Medicine, after noticing the disconnect between how long people thought coughs should last and how long they actually lingered.

When he surveyed nearly 500 Georgia residents by phone, he found that they predicted that a cough would last between five days and nine days, but generally about a week, depending on the scenario.

A review of 19 published medical studies, however, revealed that the mean duration of any cough was 17.8 days, with a range of 15.3 to 28.6 days.

If a person demanded -- and received -- an antibiotic after he or she had been sick for a week,  the condition might improve several days later -- but not because of the drug, Ebell said.

“Although this outcome may reinforce the mistaken idea that the antibiotic worked, it is merely a reflection of the natural history of acute cough,” he said.

Convincing people of that fact is tough. In Ebell’s study, a quarter of participants thought that antibiotics were "always helpful" and about 44 percent said they were "always or usually" helpful. 

That ignores the reality that antibiotics won't affect viral infections, and also that they can cause harmful side effects, including allergic reactions and the life-threatening gut condition called C. difficile, Ebell said. Plus, overuse of antibiotics is contributing to conditions such as drug-resistant pneumonia and other infections.

Crystal Thompson, a 34-year-old kindergarten teacher in Fort Worth, Texas, says that she’d start to become concerned if a cough lasted more than a few days.

“I would think no longer than a week,” said Thompson, whose family is just now getting over this year’s severe flu. “If it lasted longer than a week, I’d be in to the doctor.”

But Thompson said she also understands the difference between a viral infection and a bacterial one and that she’d follow her doctor’s advice about antibiotics.

In general, Ebell said he tells patients that they likely don’t need an antibiotic unless symptoms turn serious, with shortness of breath, high fever or bloody or rusty phlegm.

It’s important to get the message out about the actual duration of a normal cough, said Dr. Gustavo Ferrer, director of the new cough clinic at the Cleveland Clinic’s Weston, Fla., site. Ferrer, who was not involved with Ebell’s study, praised it as “beautiful” way to remind the public that there’s not a drug solution for every symptom.

“We have come to the conclusion as a population that we don’t want to be sick for one hour,” he said. "In reality, people want those symptoms to go away right away."

Still, cough docs know that patients come for some relief. Ferrer said that antihistamines such as Benadryl can help dry up airways, reduce coughing and help people sleep. Cough drops – especially those with honey and herbs – can help during the day, he added.

Ebell said he and other docs have come up with a range of ways to discourage demand for antibiotics. They’ll call the infection a “chest cold” instead of acute bronchitis. They’ll agree to write an antibiotic prescription -- but then tell patients to wait.

“If you feel that you’re really not going to get them out of the office without a prescription, give them one and say ‘Don’t fill it for a few days,’” he said. “About half never fill it at all.”

Related stories: 

• 5 things do to (and 5 not to do) when you have the flu
• Flu spreads to 47 states, but may be waning
• Flu jab isn't perfect by a long shot, health officials admit

Patients can refuse a flu shot. Should doctors and nurses have that right, too? That is the thorny question surfacing as U.S. hospitals increasingly crack down on employees who won't get flu shots, with some workers losing their jobs over their refusal.

"Where does it say that I am no longer a patient if I'm a nurse," wondered Carrie Calhoun, a longtime critical care nurse in suburban Chicago who was fired last month after she refused a flu shot.

Hospitals' get-tougher measures coincide with an earlier-than-usual flu season hitting harder than in recent mild seasons. Flu is widespread in most states, and at least 20 children have died.

Most doctors and nurses do get flu shots. But in the past two months, at least 15 nurses and other hospital staffers in four states have been fired for refusing, and several others have resigned, according to affected workers, hospital authorities and published reports.

In Rhode Island, one of three states with tough penalties behind a mandatory vaccine policy for health care workers, more than 1,000 workers recently signed a petition opposing the policy, according to a labor union that has filed suit to end the regulation.

Why would people whose job is to protect sick patients refuse a flu shot? The reasons vary: allergies to flu vaccine, which are rare; religious objections; and skepticism about whether vaccinating health workers will prevent flu in patients.

Dr. Carolyn Bridges, associate director for adult immunization at the federal Centers for Disease Control and Prevention, says the strongest evidence is from studies in nursing homes, linking flu vaccination among health care workers with fewer patient deaths from all causes.

"We would all like to see stronger data," she said. But other evidence shows flu vaccination "significantly decreases" flu cases, she said. "It should work the same in a health care worker versus somebody out in the community."

Related stories:
CDC reports flu in 47 states
Bioethicist says: Don't be selfish, get the shot

Cancer nurse Joyce Gingerich is among the skeptics and says her decision to avoid the shot is mostly "a personal thing." She's among seven employees at IU Health Goshen Hospital in northern Indiana who were recently fired for refusing flu shots. Gingerich said she gets other vaccinations but thinks it should be a choice. She opposes "the injustice of being forced to put something in my body."

Medical ethicist Art Caplan says health care workers' ethical obligation to protect patients trumps their individual rights.

"If you don't want to do it, you shouldn't work in that environment," said Caplan, medical ethics chief at New York University's Langone Medical Center. "Patients should demand that their health care provider gets flu shots — and they should ask them."

For some people, flu causes only mild symptoms. But it can also lead to pneumonia, and there are thousands of hospitalizations and deaths each year. The number of deaths has varied in recent decades from about 3,000 to 49,000.

A survey by CDC researchers found that in 2011, more than 400 U.S. hospitals required flu vaccinations for their employees and 29 hospitals fired unvaccinated employees.

At Calhoun's hospital, Alexian Brothers Medical Center in Elk Grove Village, Ill., unvaccinated workers granted exemptions must wear masks and tell patients, "I'm wearing the mask for your safety," Calhoun says. She says that's discriminatory and may make patients want to avoid "the dirty nurse" with the mask.

The hospital justified its vaccination policy in an email, citing the CDC's warning that this year's flu outbreak was "expected to be among the worst in a decade" and noted that Illinois has already been hit especially hard. The mandatory vaccine policy "is consistent with our health system's mission to provide the safest environment possible."

The government recommends flu shots for nearly everyone, starting at age 6 months. Vaccination rates among the general public are generally lower than among health care workers.

According to the most recent federal data, about 63 percent of U.S. health care workers had flu shots as of November. That's up from previous years, but the government wants 90 percent coverage of health care workers by 2020.

The highest rate, about 88 percent, was among pharmacists, followed by doctors at 84 percent, and nurses, 82 percent. Fewer than half of nursing assistants and aides are vaccinated, Bridges said.

Some hospitals have achieved 90 percent but many fall short. A government health advisory panel has urged those below 90 percent to consider a mandatory program.

Also, the accreditation body over hospitals requires them to offer flu vaccines to workers, and those failing to do that and improve vaccination rates could lose accreditation.

Starting this year, the government's Centers for Medicare & Medicaid Services is requiring hospitals to report employees' flu vaccination rates as a means to boost the rates, the CDC's Bridges said. Eventually the data will be posted on the agency's "Hospital Compare" website.

Several leading doctor groups support mandatory flu shots for workers. And the American Medical Association in November endorsed mandatory shots for those with direct patient contact in nursing homes; elderly patients are particularly vulnerable to flu-related complications. The American Nurses Association supports mandates if they're adopted at the state level and affect all hospitals, but also says exceptions should be allowed for medical or religious reasons.

Mandates for vaccinating health care workers against other diseases, including measles, mumps and hepatitis, are widely accepted. But some workers have less faith that flu shots work — partly because there are several types of flu virus that often differ each season and manufacturers must reformulate vaccines to try and match the circulating strains.

While not 100 percent effective, this year's vaccine is a good match, the CDC's Bridges said.

Several states have laws or regulations requiring flu vaccination for health care workers but only three — Arkansas, Maine and Rhode Island — spell out penalties for those who refuse, according to Alexandra Stewart, a George Washington University expert in immunization policy and co-author of a study appearing this month in the journal Vaccine.

Rhode Island's regulation, enacted in December, may be the toughest and is being challenged in court by a health workers union. The rule allows exemptions for religious or medical reasons, but requires unvaccinated workers in contact with patients to wear face masks during flu season. Employees who refuse the masks can be fined $100 and may face a complaint or reprimand for unprofessional conduct that could result in losing their professional license.

Some Rhode Island hospitals post signs announcing that workers wearing masks have not received flu shots. Opponents say the masks violate their health privacy.

"We really strongly support the goal of increasing vaccination rates among health care workers and among the population as a whole," but it should be voluntary, said SEIU Healthcare Employees Union spokesman Chas Walker.

Supporters of health care worker mandates note that to protect public health, courts have endorsed forced vaccination laws affecting the general population during disease outbreaks, and have upheld vaccination requirements for schoolchildren.

Cases involving flu vaccine mandates for health workers have had less success. A 2009 New York state regulation mandating health care worker vaccinations for swine flu and seasonal flu was challenged in court but was later rescinded because of a vaccine shortage. And labor unions have challenged individual hospital mandates enacted without collective bargaining; an appeals court upheld that argument in 2007 in a widely cited case involving Virginia Mason Hospital in Seattle.

Calhoun, the Illinois nurse, says she is unsure of her options.

"Most of the hospitals in my area are all implementing these policies," she said. "This conflict could end the career I have dedicated myself to."

__

Online:

R.I. union lawsuit against mandatory vaccines: http://www.seiu1199ne.org/files/2013/01/FluLawsuitRI.pdf

CDC: http://www.cdc.gov

Joe Raedle / Getty Images file

Russell Waddley of Miami received a flu shot in early December from Alina Pastoriza Garcia at a CVS pharmacy's MinuteClinic. Government health officials say new data show that the flu vaccine is about 62 percent effective at preventing illness this year.

Flu activity remains high across the United States, but there are signs this year's bad season may be waning in some areas, government health officials said Friday.

Forty-seven states reported widespread flu activity as of the week ending Jan. 5, up from 41 the previous week. Twenty-four states and New York City reported high levels of flu-like illness, but that was down from 29 states and NYC the week before, according to new data released by the Centers for Disease Control and Prevention.  

Still, flu is unpredictable and illness could rebound or worsen, said CDC Director Dr. Tom Frieden.

"Really, only the next week or two will show whether we have, in fact, crossed the peak," Frieden told reporters in a conference call. "Nationally, it's likely that influenza will continue for several more weeks."

Flu activity was elevated all across the U.S., except in the far west region that includes Arizona, California, Guam, Hawaii and Nevada, the new report showed. 

More than 3,700 people have been hospitalized for the flu since October, and 20 children have died, the CDC says. Most of the hospitalizations have been in people older than 65. For the first time this season, deaths associated with the flu rose into the epidemic category, though just barely, CDC officials said.

Vaccines given to fight this year's flu appear to be about 62 percent effective overall , according to data from some 1,155 children and adults with acute respiratory infections. Of people who got the flu, 32 percent were vaccinated. CDC officials characterize that level as "moderate" effectiveness and infection control experts say it's about what they expect from the shots. 

"That's normal," said Dr. William Schaffner, chairman of the department of preventive medicine at Vanderbilt University in Nashville, Tenn. "It's a good but not a perfect vaccine." 

This year's vaccines appear to be about 55 percent effective against influenza A strains, which are responsible for most illness and more severe cases, and about 70 percent effective against influenza B, which is usually less serious, the report showed.

That helps explain why some people who've received flu shots -- which are recommended for everyone older than six months -- say they've still gotten sick. It argues in favor of using antiviral drugs such as Tamiflu to help bolster vaccine effectiveness, or VE, CDC's report said. 

"These early VE estimates underscore that some vaccinated persons will become infected with influenza; therefore, antiviral medications should be used as recommended for treatment in patients, regardless of vaccination status," the report concluded. 

Related stories: 

• Flu jab isn't perfect by a long shot, officials admit
• Bioethicist: Don't be selfish. Get a flu shot.
• Nasty flu season sparks spotty vaccine shortages
• Not always the flu; some may have other viruses
• Who gave you the flu? New app, docs help place blame

An early flu season, complicated by an aggressive strain of a stomach virus, has spread misery across the United States.

Boston’s mayor Thomas Menino declared a public health emergency and hospitals in some cities reported their already stretched emergency rooms were filling up with patients. More than 2,200 people have been hospitalized with the flu since October nationwide, according to the Centers for Disease Control and Prevention, and at least 18 children have died nationwide -- a reminder that flu can be deadly and unpredictable.

Public health officials said while the season is off to an early start, the influenza virus doesn’t so far seem to be doing anything especially unusual. They’ve been urging people since last fall to get vaccinated against the flu and to take precautions, such as frequent handwashing, to avoid infection. 

But this year, in addition to the usual colds, there's also a strain of a virulent stomach bug, called norovirus, making people sick around the world and in the United States. Patients who are sick may have a hard time telling the difference. Norovirus causes flu-like symptoms as well as vomiting and diarrhea. In the past few weeks, 250 people at a Mormon missionary training center in Provo, Utah, became sick with norovirus, the Associated Press reports. In Mill Valley Calif., two died after an outbreak of norovirus at a senior care facility over Christmas sickened 60. 

Data from the Centers for Disease Control and Prevention shows only about a third of all people with flu-like symptoms actually are testing positive for influenza. So two-thirds of the sick people have something else.

Unlike for flu, there's no vaccine for norovirus. There's also no treatment except what health professionals call supportive care – rest, fluids and ibuprofen or acetaminophen for muscle aches. Some patients with influenza can take a pill called Tamiflu. It doesn’t cure the virus but it can cut a few days off the week or so that flu usually makes people ill, if it’s taken within 48 hours of the first symptoms. 

Twenty-nine states and New York City are now reporting high levels of influenza-like-illness and more than nine states are reporting moderate levels of flu-like disease, according to the Centers for Disease Control and Prevention. 

CDC says about 8 out of every 100,000 people are being hospitalized for flu. “This is high for this time of year,” says Dr. Joe Bresee of the Centers for Disease Control and Prevention’s Influenza Division.

In a severe year, as many as 36,000 Americans die from influenza and 200,000 go into the hospital. While most who die are elderly, every year previously healthy children and young adults can also die.

“While we can’t say for certain how severe this season will be, we can say that a lot of people are getting sick with influenza and we are getting reports of severe illness and hospitalizations,” Bresee added. “Anyone who has not already been vaccinated should do so now.”

Vaccine makers have distributed 128 million doses out of about 135 million doses that they plan to make. 

The vaccine protects against three strains of the flu virus, but there’s a fourth strain circulating at low levels that is not affected by the vaccine.

CDC will update its statistics on flu Friday. It said last week that more than five percent of people seeing their doctors complained of flu-like symptoms, which is more than twice as many as this time last year. But last year was an unusually mild flu season.

“While the timing of influenza seasons also is impossible to predict, based on past experience it’s likely that flu activity will continue for some time,” the CDC cautions. Flu season usually lasts at least three months and the United States typically gets hit the worst in January and February.

Influenza-associated pediatric deaths have been reportable to CDC since the 2004-2005 season. To date, CDC has received reports of 18 pediatric deaths this season. More information about reported pediatric deaths is available at the Influenza-Associated Pediatric Mortality web application.

One factor that may indicate increased severity this season is that the predominant circulating type of influenza virus is influenza A (H3N2) viruses, which account for about 76 percent of the viruses reported. Bresee explains “typically ‘H3N2 seasons’ have been more severe, with higher numbers of hospitalizations and deaths, but we will have to see how the season plays out.”

So far this season, more than 90 percent of the influenza viruses that have been analyzed at CDC are like the viruses included in the 2012-2013 influenza vaccine. The match between the vaccine virus and circulating viruses is one factor that impacts how well the vaccine works. But Bresee cautions that other factors are involved.

Related stories:

Bad flu season worsens; Boston declares a state of emergency

Who gave you the flu? New app, docs place blame

How to protect yourself from the flu? Wash your hands