U.S. Department of Health and Human Services
National Institute of General Medical Sciences (NIGMS)
National Heart, Lung, and Blood Institute

For Release: Wednesday, February 18, 2009

New Research Says Yes-Now for the Clinical Trial

In a large-scale study and an upcoming clinical trial, scientists supported by the National Institutes of Health address one of the trickiest issues in prescribing medicine — how to quickly optimize each patient’s dosage of the common blood-thinning drug warfarin.

One of the most widely prescribed drugs in the world, warfarin is used to prevent dangerous blood clots that can lead to heart attacks, strokes or even death. The drug is challenging for doctors to prescribe because the ideal dosage for each person varies widely and is hard to predict, yet is crucial for the patient’s safety.

Every year, an estimated 2 million Americans with certain heart conditions or other risk factors start taking warfarin. Getting the wrong amount of warfarin can be dangerous — if the dose is too high, patients could bleed profusely; if it’s too low, they could develop life-threatening clots.

Using information from thousands of genetically and geographically diverse patients, an international team of researchers developed a way to use genetic information from patients that could help doctors better determine optimal warfarin doses. The results of the analysis are published in an article titled “Warfarin Dosing Using Clinical and Pharmacogenetic Data” in the Feb. 19 issue of The New England Journal of Medicine.

The article is accompanied by an editorial by Janet Woodcock and Lawrence Lesko of the Center for Drug Evaluation and Research at the Food and Drug Administration.

In an important step toward putting these findings into clinical practice, NIH is launching the largest prospective, multi-center, randomized clinical trial in the United States to test whether a gene-based strategy for prescribing the initial warfarin dose will improve patient outcomes. The clinical trial will use a dosing strategy similar to that developed in the international study. The trial will enroll 1,200 participants of diverse backgrounds and ethnicities at twelve clinical sites, and is scheduled to begin next month.

“In these investigations, NIH-funded basic research and clinical trials are working hand in hand to improve the care of the millions of patients on warfarin therapy,” said Raynard S. Kington, M.D., Ph.D., acting NIH director. “More broadly, these efforts showcase NIH’s firm commitment to building a future of personalized medicine — a future in which doctors will be able to prescribe the optimal dosage of medicine for each patient right from the start.”


Each person responds differently to warfarin. One person may need 10 times more of the drug than another, so it’s challenging to figure out where to start. Doctors typically select the initial dose based on standard clinical factors — such as age, weight and gender — then fine tune the dosage over a few weeks in response to periodic tests of the blood’s ability to clot.

In 2007, the FDA worked with the makers of warfarin drug products to modify the product label to indicate that a patient’s genetic makeup may affect how he or she responds to the drug. Researchers know that two genes, CYP2C9 and VKORC1, which vary slightly among different individuals, can influence warfarin’s effectiveness. However, scientists do not know whether information about these genes can improve optimal dosage prediction for a wide range of patients, regardless of race, ethnicity or other genetic differences.

To investigate this issue, researchers from more than 20 teams in nine countries on four continents voluntarily joined to form the International Warfarin Pharmacogenetics Consortium (IWPC). The consortium was spearheaded by scientists involved in the NIH Pharmacogenetics Research Network and PharmGKB (http://www.pharmgkb.org), an online pharmacogenomics resource where data from the study is now freely available to scientists.

By pooling their data, the consortium members had access to anonymized information from about 5,700 people on stable dosages of warfarin. The patients came from around the globe, including Taiwan, Japan, Korea, Singapore, Sweden, Israel, Brazil, Britain and the United States. This kind of study — one that includes a large, diverse data set — is essential to draw conclusions that are applicable to a wide range of patients.

For each patient, the data included demographic information like age, gender and race; CYP2C9 and VKORC1 variants; and initial, as well as optimized, warfarin dosages.

The scientists calculated warfarin dosages in three ways — one that relied on the standard, clinical information, one that included additional information about individual patient variation in CYP2C9 and VKORC1, and one that used a fixed dose per day. Then they checked how closely their computational predictions matched the actual, clinically derived stable warfarin dosage for each patient.

The results revealed that when genetic information was included, the predictions of ideal dosages were more accurate, especially for patients at the low or high ends of the dosing range. This is meaningful because nearly half of those on warfarin are at the extremes of the range, and these patients are typically at the greatest risk for excessive bleeding or clotting. By quickly optimizing dosages for these patients, doctors could minimize dangerous complications and improve the effectiveness and safety of warfarin treatment.

“By sharing information and expertise, the consortium researchers developed a way to dose warfarin that is based on data from patients around the world,” said Jeremy M. Berg, Ph.D., director of the National Institute of General Medical Sciences (NIGMS), which supported the study. “This is a highly commendable example of international cooperation and data sharing and should increase the potential utility of the results.”

In addition to NIGMS, the following NIH components supported the consortium’s research: the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Center for Research Resources (NCRR).


Although genetic tests are now available for doctors to use to help determine the initial dose of warfarin, a large, randomized clinical trial — the gold standard for testing medical therapies — is needed to determine if the more precise, gene-based prescribing strategy is the best option.

“With growing evidence on how certain genes affect the way individual patients respond to warfarin, we are now ready to move forward with a major clinical trial to test these strategies in patients who are starting warfarin therapy,” said Elizabeth G. Nabel, M.D., director of NHLBI, which is supporting the new study.

Called Clarification of Optimal Anticoagulation through Genetics (COAG), the new clinical trial will test two approaches to determining the initial dose of warfarin in patients who are expected to need therapy for three months or longer. The trial will be conducted at 12 sites, with one site each in California, Florida, Maryland, Michigan, Minnesota, Missouri, New York, Pennsylvania, Tennessee, Texas, Utah and Wisconsin. The COAG Coordinating Center is at the University of Pennsylvania School of Medicine.

COAG researchers will apply prescribing strategies for initial dosing similar to those used in the IWPC analysis. About one-half of the participants will be randomly selected to have their initial dose determined by clinical information alone. For the other half of the participants, the initial dose will be determined by using the clinical factors as well as information about the participant’s genetic makeup, specifically his or her variants of the CYP2C9 and VKORC1 genes. All participants will be monitored for six months.

“The COAG study will provide important evidence to determine if genetic information gives added benefit for determining initial warfarin doses above and beyond what can be obtained with clinical information,” added Nabel.

Researchers will assess how long participants in each group maintain the desired level of blood thinning, as determined by a blood test, at two and four weeks after starting therapy, as well as at three and six months. Researchers will also review bleeding problems and other complications, quality of life and cost of therapy.

“This new body of research and the prospective clinical trial that will soon be launched by NIH builds on the warfarin labeling changes that FDA put in place in 2007 to reduce the number of adverse events associated with this dose-sensitive drug,” said Frank M. Torti, M.D., acting commissioner of Food and Drugs. “The NIH research is precisely what is needed to advance the promise of personalized medicine, ensuring that patients receive the safest and most effective drug dose.”

The COAG trial is supported by NHLBI, with additional funding for genome analyses from the National Human Genome Research Institute (NHGRI). Warfarin will be donated by Bristol-Myers Squibb, New York City. The COAG trial is also working with the Critical Path Institute, an independent, non-profit organization that fosters partnerships between academia, government and the healthcare industry.

A cancer patient, given just months to live, stages a miraculous recovery. Doctors dismiss it as a fluke. Yet the mystery may offer crucial clues to fighting cancer.

Charles Burrows was given two months to live in 2005. Then, with no treatment, his liver tumor vanished. ‘I won a lottery,’ he says.

Forbes.com, March 2, 2009, by Robert Langreth — Charles Burrows noticed a strange lump on his stomach in the summer of 2005. By November the pain was so bad it felt like a knife was stabbing him in the stomach. A ct scan and a biopsy confirmed Burrows’ worst fears: He had inoperable liver cancer.

Few cancers have a worse prognosis. His tumor, the size of a baseball, was already starting to strangle the portal vein going into the liver. Doctors at the Phoenix Veterans Affairs Health Care System told Burrows, then 56 years old, there was nothing they could do. “They said, ‘Get your affairs in order because you have 30 days to live, maybe 60,'” recalls Burrows, who is divorced with three grown kids.

Burrows quit his carpentry job and spent the next two months in a fog. Then things got very strange. In February 2006 Burrows developed abdominal bloating, shaking, chills and nausea. Soon after that he noticed that the lump on his stomach was gone. By then his daughter had found a doctor in private practice willing to consider treating him. But the doctor couldn’t find a tumor. He went back to the VA, where gastroenterologist Nooman Gilani was flabbergasted when computed tomography and magnetic resonance imaging scans showed no sign of cancer. Where the tumor had once been, there was “literally empty space,” Gilani says.

Burrows remains free of cancer three years later and still seems dazed by the turn of events. “I won a lottery, and I don’t understand why,” he says. “I would like someone to explain to me what the heck happened.”

Ole Nielsen Schou also looked like a goner. In 2002 the Danish pharmaceutical production manager (now 69 and retired) found out that his melanoma had spread to his liver, abdomen, lungs, bones and ten spots in his brain. The abdominal tumor was surgically removed, but doctors at Rigshospitalet in Copenhagen had no treatment for his other tumors. He took a strange cocktail of 17 vitamins and supplements, including shark cartilage pills, and imagined the metastases were rats and he was chasing them with a club. In Depth: 6 Miracle Cancer Survivors.

Four months later he went back for a new scan and found that 90% of his tumors had melted away. Soon they were gone. Co-workers hugged and kissed him when they heard the news. Plastic surgeon Vennegaard Kalialis, who detailed his case last year in Melanoma Research, doubts it was the vitamins. “It is a complete mystery,” she says. “Nobody has seen anything like this.”

Spontaneous tumor regressions are among the rarest and most mysterious events in medicine, with only several hundred cases in the literature that can be considered well documented. Regressions have most often been reported in melanoma and in kidney cancer. But the phenomenon may, in fact, be an everyday one, taking place beyond doctors’ eyes. A recent study suggests that as many as 1 in 3 breast tumors may vanish on their own before being detected by a doctor.

Why do some patients get lucky? Scientists are finding tantalizing evidence that the immune system, the body’s defense against disease-causing microbes, kicks in to play a critical role in combating cancer. If that’s the case, then Schou and Burrows are more than just lucky patients. They are clues to how doctors may someday save thousands of lives.

The evidence includes the fact that some unexplained remissions have occurred after infections, which may propel the immune system into high gear–possibly attacking the cancer tumor as well as the infection. Burrows’ remission seemed to begin after his strange illness. Schou’s abdominal tumor when removed was swarming with white blood cells, the lead weapon in the body’s immune system. It’s also possible that ordinary cancer survivors, people who beat the disease after getting radiation, chemotherapy or surgery, get an assist from their own immune systems.

Big drug companies, including Pfizer, Bristol-Myers Squibb and Sanofi-Aventis, are doggedly pursuing drugs that aim to boost the immune system to fight cancer. GlaxoSmithkline is in final-stage tests of a vaccine to prevent lung cancer from coming back after surgery. In an early trial it slashed the probability of cancer recurrence by 27%. “It is all about educating the patients’ natural defenses against cancer,” says GlaxoSmithkline’s Vincent Brichard. Easier said than done, of course. Some patients, apparently, need only a small trigger to propel a massive anticancer attack. With nearly all others, however, the cancer cells fight back successfully and even co-opt immune cells to aid their growth. Why some patients respond better than others to certain drugs is a focus of furious scrutiny.

The role of the immune system in controlling cancer has been hotly debated for decades–and indeed many scientists remain unconvinced. But Jedd D. Wolchok, an oncologist at New York’s Memorial Sloan-Kettering Cancer Center, thinks there is a connection. A spontaneous remission, he says, is “either divine intervention or the immune system.” While few researchers directly study such cases–they are far too rare–they provide hints of what the immune system might be able to do if we could harness it.

The immune system work is part of a new twist on the war on cancer. For decades cancer researchers have focused mostly on killing cancer cells with drugs and radiation, or removing them with surgery. But this is often impossible to accomplish. So scientists are studying the environment around tumors in order to invent drugs that will halt their spread. Such drugs, like Genentech’s Avastin, would be the medical equivalent of cutting terrorist-cell supply lines or putting up security checkpoints to stop them from getting into vital areas.

One of the first scientists to try to trigger the immune system to attack cancer was the New York surgeon William Coley. He was inspired by a patient with sarcoma who recovered after suffering an acute bacterial infection. In the 1890s Coley started vaccinating other patients with killed bacteria. He claimed that his toxins spurred the immune system to destroy tumors in a minority of cases.

In the 1980s the natural immune protein interleukin-2 was touted as a breakthrough. But it turned out to help only a small minority of cancer patients and to sport an array of nasty side effects. Over the years numerous trials of anticancer vaccines designed to train the immune system to recognize cancer have shown mostly lackluster results. None of these new therapeutic vaccines is approved in the U.S.

But intriguing data suggest that the immune system can combat cancer sometimes. “To the body, a tumor looks like the biggest bacteria it has ever seen,” says Robert Schreiber, an immunologist at Washington University School of Medicine in St. Louis. He has found that mice lacking key components of their immune system are far more likely to develop cancers. In one experiment 60% of mice missing something called the gamma interferon receptor on their cells got tumors after being exposed to a carcinogen, versus only 15% of normal mice.

Schreiber theorizes that many early cancers arising in the body are killed off by the immune system. Over time, however, some develop mutations that allow them to thwart the immune system, and a long stalemate ensues. Eventually some tumors escape the control of the immune system entirely.

Moreover, a 2006 study by the University of Paris Descartes’ Wolf H. Fridman found that the number of certain kinds of white blood cells inside colon tumors is a stronger predictor of a relapse than criteria pathologists traditionally use, such as whether cancer cells have spread to the lymph nodes. He analyzed tumor samples from 415 people who had been operated on for early-stage colon cancer over the last two decades. Those with the highest number of these cells in their tumor rarely relapsed; those with few immune cells almost always did.

No broad-based anticancer antidotes have emerged from the immune system work yet. In trials to date, immune-boosting drugs have generally helped only a minority of patients, particularly those with melanoma. But when they do work, it can be spectacular.

By the odds, 27-year-old Sharon Belvin should no longer be alive. The North Carolina resident found out that she had melanoma in her lung a week before her wedding when she was only 22. That sort of tumor usually sprouts like a weed once it has migrated beyond the skin to internal organs, and it resists most chemotherapy. By the time she turned 24 the few standard treatments had failed, and she had tumors in both lungs.

But then Memorial’s Wolchok put her on an experimental drug called ipilimumab that aims to trigger the immune system. Within four months her lung tumors started to shrivel. By late 2006 they were gone. Today Belvin remains free of cancer and off treatment. She spends her time caring for her husband and 1-year-old daughter, whom she calls “a miracle baby, after all we have been through.” Her case is so unusual that during a recent appointment the radiologist called Wolchok in disbelief. “He said, ‘What did you do for this patient? Am I reading the diagnosis correctly?'”

Seven years ago Los Angeles high school social studies teacher Joseph Rick spotted a purple pimple on the small of his back. Too late: The melanoma soon spread into his colon. Nine surgeries and 40 chemo rounds over two years failed to stop it. By fall 2004 dozens of tumors riddled his body. Doctors gave Rick, then 43, four months to live. Rick bought a grave site for himself and went home to his L.A. condo to die. By December his weight had plummeted to 90 pounds from 240. He could barely walk.

Then he heard about a new immune-system-boosting drug being tested at UCLA, similar to the one Belvin received. A week after his first infusion visible brown tumors on his neck and thigh began to fade and his appetite returned. By March his tumors had shrunk 25%, and by early 2006 they were gone. When he could go back to work, he broke into tears watching the sunrise. Says Rick: “I would have been dead [years ago] without this drug.”

Belvin’s drug, from Bristol-Myers Squibb and Medarex, shrank tumors in about 10% of melanoma patients in a 2007 trial–not enough to get approval without more study. A larger trial that could lead to approval will wrap up late this year. Rick’s drug is being tested by Pfizer. In a recent final-stage trial it failed to beat chemotherapy, and Pfizer sent it back a grade; the drug will start over at an earlier stage of trials. Both drugs turn off a natural brake on immune system activity called CTLA4 (cytotoxic T-lymphocyte antigen 4). They are part of a new breed of drugs that hit specific molecular components of the immune system.

Other treatments that aim to amplify the immune system report similar patterns–scattered amazing success stories combined with a failure on the broad stage. Last summer Cassian Yee at the Fred Hutchinson Cancer Research Center reported eradicating tumors in a 52-year-old man with advanced melanoma by plucking out the rare white cells from his blood that seemed to be active against cancer, painstakingly growing them in the lab and then injecting billions of them back into him. The man is free of cancer three years later. On eight other patients the procedure helped temporarily or not at all. “It’s the hallmark of immune therapy–it doesn’t happen often, but once it happens, those patients live years,” says UCLA oncologist Antoni Ribas.

One famous researcher, the National Cancer Institute’s Steven Rosenberg, says his immune cell therapy, roughly similar to Yee’s, helps 72% of melanoma patients when given after chemo and radiation. Rosenberg, whose work was inspired by a patient whose stomach cancer vanished on its own, is now expanding the method to colon and breast cancer. But his procedure is far too complex for most hospitals to do.

What is special about the miracle survivors? Why do a minority of outliers live years longer than most? Is it something in their blood? Their genes? Are their tumors weaker than some? Or do they have unusually strong immune systems that just need a slight nudge?

The immune system is “phenomenally complicated,” says oncologist Jeffrey Weber of the H. Lee Moffitt Cancer Center in Tampa. “Nobody knows how to pick out the patients that will respond.” Complicating matters further: Some people get mysteriously delayed responses to immune-boosting drugs, as if a trigger has finally gone off. In the past some responses may have been missed because therapy was stopped too soon, says Bristol-Myers Squibb Vice President Renzo Canetta.

Some patients’ tumors have mutations that make them particularly sensitive to one drug or another. Another reason that drugs get spotty results may be that some tumors are simply more visible to the immune system than others. Some 30% to 40% of melanoma tumors contain a rare protein called NY-ESO-1 that looks particularly suspicious to the immune system. Wolchok at Memorial has analyzed blood from eight patients for whom Bristol-Myers’ CTLA4 drug worked; in five of them it appeared to rouse or amplify an immune response against this particular protein.

Another reason for perplexing results is that there are numerous molecular brakes inside the body that keep the immune system from rampaging out of control; cancer cells evade the immune system by manipulating these brakes. The drugs that Belvin and Rick took release one of those brakes (CTLA4), thereby allowing the fury of the immune system to be unleashed on the tumor. But tumors can quell the immune system by activating other brakes. Patients who don’t respond to the CTLA4 drugs may have other brakes that are still engaged. Researchers may have to do many small trials of various combinations of immune-boosting drugs until they find which combos work best on which patients, says Dana Farber Cancer Institute’s Glenn Dranoff.

Even as some researchers puzzle over the mystery of rare responders, others are finding that the immune system may play a crucial role in how patients react to bestselling antibody drugs. These drugs–such as Herceptin for breast cancer (Genentech) and Erbitux for colon cancer (Eli Lilly)–were designed to bind to signaling molecules on tumors and disrupt cell growth signals. But it turns out that they perform a second role, which drug companies have paid scant attention to until recently: flagging the immune system to kill cancer.

Rockefeller University researcher Jeffrey Ravetch has shown that antibody drugs like Herceptin no longer work well in lab mice when the portion of the antibody that flags the immune system is damaged–even through they still bind perfectly well to the tumor. Genetic differences in people’s immune systems may also explain why some people respond much better to antibody drugs than others. Last year an Italian study of 54 breast cancer patients found that patients whose white blood cells had certain gene variants were far more likely to respond to Herceptin than those who had different variants. Similar results have been found with some other antibody drugs.

Biotech company researchers are now trying to devise second-generation antibodies that send stronger signals to the immune system, in hopes that far more cancer patients will benefit. “We are very intrigued by this,” says Genentech biochemist Mark Sliwkowski, who cautions that the precise role of the immune system in the response to antibody drugs is unclear.

If the new thrust in immune system research goes somewhere, it could mean there will be more survivors like Barbara Bradfield of Puyallup, Wash. In 1992 her breast cancer came roaring back only two years after she’d had a double mastectomy. She had a marshmallow-size tumor on her neck and 16 spots in her lungs. She refused more heavy-duty chemotherapy and faced the fact she was going to die. Then she found out she qualified for a trial of a drug called Herceptin, which targets 25% of patients whose breast tumors have a certain mutation. She was one of the first patients to take it. Typically, it extends life by five months. But within six months of when she started Herceptin in 1992, Bradfield’s tumors had all melted away. They have never come back, and now, at age 66, she is considered cured.

Robert Langreth, 02.11.09, 06:00 PM EST
Forbes Magazine dated March 02, 2009

A cancer patient, given just months to live, stages a miraculous recovery. Doctors dismiss it as a fluke. Yet the mystery may offer crucial clues to fighting cancer.

Forbes.com, February 18, 2009, by Julie Steenhuysen — U.S. scientists proposed a new theory on Wednesday of how Alzheimer’s disease kills brain cells they said opens new avenues of research into treatments for the fatal, brain-wasting disease.

They believe a chemical mechanism that naturally prunes away unwanted brain cells during early brain development somehow gets hijacked in Alzheimer’s disease.

‘The key player we’re focusing on is a protein called APP,’ said Marc Tessier-Lavigne, executive vice president of research drug discovery at the U.S. biotechnology company Genentech Inc (nyse: DNA – news – people ) , whose study appears in the journal Nature.

Tessier-Lavigne said amyloid precursor protein, or APP — a key building block in brain plaques found in Alzheimer’s disease — is the driving force behind this process.

‘We know that APP is a bad actor in Alzheimer’s, but it has been unclear how it participates,’ he said in a telephone interview.

Tessier-Lavigne thinks that somehow this self-destruction mechanism gets switched on in Alzheimer’s disease and starts killing healthy brain cells.

The finding provides new clues about potential treatments for Alzheimer’s, a disease that gets worse over time and is marked by memory loss, confusion and eventually the inability to care for oneself.

The researchers made the Alzheimer’s connection by accident while studying a process of nerve cell self-destruction that occurs as a part of normal embryonic development.

When the brain and spinal cord are being formed, excess nerve cells are generated that have to be removed to refine the pattern of nerve cell connections.

They discovered a biochemical mechanism that activates when nerve cells are pruned back. ‘A key component of this self-destruction program was none other than APP, this bad actor in Alzheimer’s disease,’ Tessier-Lavigne said.

‘We were stunned,’ he added.

‘This immediately raised the possibility that in Alzheimer’s disease, where we know APP is involved, it is involved by virtue of this mechanism.’

In Alzheimer’s disease, enzymes snip APP into beta amyloid pieces, which form the basis of beta amyloid plaques that are thought to be toxic.

Many companies are working on drugs to remove beta amyloid from the brain, but so far have had little success in altering the course of the disease.

Tessier-Lavigne’s theory suggests targeting APP and other components of this mechanism may help. In tests on human embryonic cells, the team showed it was able to interfere with the mechanism and block the degeneration of nerve cells.

The researchers now plan to see if they can disrupt this mechanism in adult brain cells.

‘The key question is, if we interfere with it, can we halt the progression of the disease?’ Tessier-Lavigne said.

There is no cure for Alzheimer’s, and current drugs merely delay symptoms. It affects 5.2 million people in the United States and 26 million globally, according to the Alzheimer’s Association.

The flu season got a late start this year, but it is finally picking up speed, according to activity on Google Flu Trends, which tracks search terms plugged into Google, not actual flu cases.

Google Flu Trends sees spike in flu-related search terms about two weeks before CDC gets surveillance reports.

Overall, 17 U.S. states have high flu activity, 28 have moderate activity, and only five have low activity, according to the search engine. The Centers for Disease Control and Prevention (CDC), which tracks flu cases reported from local health departments, typically picks up on cases a couple of weeks after Google Flu Trends.

The most recent CDC report, from early February, showed widespread activity in 16 states, up from five the previous week. (That same week Google Flu showed high activity in 18 states). In addition, the agency says, four children have died of flu-related complications this flu season, with deaths in Texas, Colorado, New York, and Tennessee.

Using Google Flu to check for activity in your region is “quite a reasonable thing,” says Anthony Fiore, M.D., a medical epidemiologist and infectious disease specialist at the CDC. “They are typically ahead of us,” he says. For example, the state of Maine has only regional activity according to flu cases reported to the agency but high activity according Google Flu.

Google Flu Trends was launched to the public in November 2008 as a new way to track flu activity. The site monitors search terms for words such as influenza and flu. In constructing the site, Google engineers checked hundreds of billions of searches over a five-year period to find those that most correlated with actual cases reported to the CDC.

“They’ve been careful with developing the model, back-checking it against what we have, and refining as they need to,” says Fiore. During last year’s flu season, Google Flu Trends picked up a significant rise in such search terms on January 28, 2008, and two weeks later the CDC saw a rise in cases reported from local health departments.

“So far, it works pretty well,” says Fiore. However, he says, “It’s important to remember that it’s data based on people’s searches for symptoms and information and not actual disease reporting. We’re always concerned that it could be perturbed by some event that causes people to look for things but who don’t necessarily have flu.”

Google reports only on flu cases, and only those in the United States, but the search engine hopes to expand to other countries and illnesses, says Google spokesperson Katy Bacon.

“This is really a first step, and we’re definitely very excited about where this will go,” she says.

This year’s flu season may be getting a later start than last year’s, but it’s no surprise that cases are picking up, says Fiore. February has been the peak month for flu activity in 11 of the last 20 seasons, he says.

The good news is that it’s still not too late to get a flu shot, he says, and indeed it is a good idea. Experts recommend you get a flu shot as soon as it’s available, typically in November, because the virus can sometimes get its start before Thanksgiving.

However, most people get sick in January and February. While it takes two weeks after you’re vaccinated to get full protection, you probably get at least some protection soon after getting a flu shot, Fiore says.

“So it’s worth still getting vaccinated at this point, especially in a season that’s starting somewhat late,” he says. Even if everyone around you is sick and you’ve stayed healthy, a second wave of flu almost always sweeps through communities, and peak activity can last for six to eight weeks, he says.

“You have to remember, there are three strains of flu virus,” says Fiore. “Widespread activity right now may be entirely due to one strain, and you could see another sweep through three or four weeks from now.”

Overall, this year’s flu vaccine is a “good match” in terms of protection against the viruses circulating in the community, he says. The vaccine is designed to combat two A-type viruses and one B-type virus. The vaccine is turning out to be good protection against A-types, but not B-type, he says.

“It’s a mixed picture, but I think overall it looks so far like it will be a good match year,” he says. “About this time last year we were finding a lot of differences amongst even the influenza A strains, but it’s looking at this point to be better than last year.”

As for Google Flu Trends, Fiore says, “If its something that makes people more interested in preventing flu because they have a sense that it’s coming soon, then it’s all good.”

Google Flu Trends


MayoClinic.com — Influenza is a viral infection that attacks the respiratory system, including your nose, throat, bronchial tubes and lungs. Influenza, commonly called the flu, is not the same as the stomach viruses that cause diarrhea and vomiting.

Anyone can get the flu, but young children, older adults, people with weakened immune systems and those with chronic illnesses are especially vulnerable. If you’re at high risk of flu, your first line of defense is an annual flu shot.

Approximately 50 million people died worldwide in the 1918 influenza pandemic. Today, according to the Centers for Disease Control and Prevention, as many as 36,000 people in the United States die each year of complications of influenza and more than 200,000 are hospitalized.

Expand Arrow DownSymptoms

Initially, the flu may seem like a common cold with a runny nose, sneezing and sore throat. But colds usually develop slowly, whereas the flu tends to come on suddenly. And although a cold can be a nuisance, you usually feel much worse with the flu.

Common signs and symptoms of the flu include:

· Fever over 101 F (38 C) in adults, and often as high as 103 to 105 F (39.5 C to 40.5 C) in children

· Chills and sweats

· Headache

· Dry cough

· Muscular aches and pains, especially in your back, arms and legs

· Fatigue and weakness

· Nasal congestion

· Loss of appetite

· Diarrhea and vomiting in children

When to see a doctor
If you have flu symptoms and are at risk of complications, see your doctor right away. Taking antiviral drugs within the first 48 hours after you first notice symptoms may reduce the length of your illness by a day or two and may help prevent more serious problems. Seek immediate medical care if you have signs and symptoms of pneumonia. These include a severe cough that brings up phlegm, a high fever and a sharp pain when you breathe deeply. If you have bacterial pneumonia, you’ll need treatment with antibiotics.

Expand Arrow DownCauses

Flu viruses travel through the air in droplets when someone with the infection coughs, sneezes or talks. You can inhale the droplets directly, or you can pick up the germs from an object, such as a telephone or computer keyboard, and then transfer them to your eyes, nose or mouth.

The flu is caused by three types (strains) of viruses — influenza A, B and C. Type A can be responsible for the deadly influenza pandemics (worldwide epidemics) that strike every 10 to 40 years. Type B can lead to smaller, more localized outbreaks. And either types A or B can cause the flu that circulates almost every winter. Type C has never been connected with a large epidemic.

Type C is a fairly stable virus, but types A and B are constantly changing, with new strains appearing regularly. Once you’ve had the flu, you develop antibodies to the strain that caused it, but those antibodies won’t protect you from new strains. That’s why doctors recommend getting a flu shot every year.

Expand Arrow DownRisk factors

You’re at increased risk of influenza or its complications if you:

· Are an infant or young child

· Are over age 50

· Are a resident of a nursing home or other long term care facility

· Have a chronic disorder, such as diabetes or heart, kidney or lung disease

· Have a weakened immune system, such as from medications or HIV infection

· Will be pregnant during flu season

· Work in a health care facility where you’re more likely to be exposed to the flu virus

· Are in regular, close contact with infants or young children

Children on long-term aspirin therapy also may be at greater risk.

The flu vaccine is safe for children 6 months and older. If your child isn’t at risk of the flu but lives with someone who is, you still may want to have your child vaccinated. That way, your child is less likely to infect others. The more people immunized, the less likely it is that the flu will spread through a community.

Expand Arrow DownComplications

If you’re young and healthy, influenza usually isn’t serious. Although you may feel miserable while you have it, the flu usually goes away with no lasting effects. But high-risk children and adults may develop complications such as:

· Ear infections

· Acute sinusitis

· Bronchitis

· Pneumonia

· Encephalitis

Of these, pneumococcal pneumonia, a serious bacterial infection of the lungs, is the most common and most serious. For older adults and people with a chronic illness, pneumonia can be deadly. The best protection is vaccination against both pneumococcal pneumonia and influenza.

Expand Arrow DownTreatments and drugs

Usually, you’ll need nothing more than bed rest and plenty of fluids to treat the flu. But in some cases, your doctor may prescribe an antiviral medication such as oseltamivir (Tamiflu) or zanamivir (Relenza).

These drugs, which treat both influenza A and B, work by deactivating an enzyme the virus needs to grow and spread. If taken soon after you notice symptoms, they may shorten your illness by a day or so. Oseltamivir is an oral medication, but zanamivir is inhaled through a device similar to an asthma inhaler and shouldn’t be used by anyone with respiratory conditions, such as asthma and lung disease.

Both medications can cause side effects, including lightheadedness, nausea, vomiting, loss of appetite and trouble breathing. They can also lead to the development of antiviral-resistant viruses.

In November 2006, the Food and Drug Administration (FDA) required the maker of Tamiflu to include a warning that people with the flu, particularly children, may be at increased risk of self-injury and confusion after taking Tamiflu. The FDA recommends that individuals with the flu who take Tamiflu be closely monitored for signs of unusual behavior. Discuss possible side effects with your doctor before starting any antiviral medication.

Expand Arrow DownLifestyle and home remedies

If you do come down with the flu, these measures may help ease your symptoms:

· Drink plenty of liquids. Choose water, juice and warm soups to prevent dehydration. Drink enough so that your urine is clear or pale yellow.

· Rest. Get more sleep to help your immune system fight infection.

· Try chicken soup. It’s not just good for your soul — it really can help relieve flu symptoms by breaking up congestion.

· Consider pain relievers. Use an over-the-counter pain reliever such as acetaminophen (Tylenol, others) or ibuprofen (Advil, Motrin, others) cautiously, as needed. Remember, pain relievers may make you more comfortable, but they won’t make your symptoms go away any faster and may have side effects. Ibuprofen may cause stomach pain, bleeding and ulcers. If taken for a long period or in higher than recommended doses, acetaminophen can be toxic to your liver. Talk to your doctor before giving acetaminophen to children. And don’t give aspirin to children or teens because of the risk of Reye’s syndrome, a rare but potentially fatal disease.

Expand Arrow DownPrevention

These steps can help you stay healthy, even at the height of flu season:

· Get an annual flu vaccination. The best time to be vaccinated is October or November. This allows your body time to develop antibodies to the flu virus before peak flu season, which in the Northern Hemisphere is usually December through March. However, getting a flu shot later in the flu season may still protect you. It takes up to two weeks to build immunity following a flu shot.

Keep in mind that the flu vaccine doesn’t offer complete protection, especially for older adults, but it can reduce the risk and severity of illness. According to the Centers for Disease Control and Prevention (CDC), when the match between flu vaccine and circulating strains of flu virus is close, a flu shot is between 70 and 90 percent effective in warding off illness in healthy people under age 65. It is less effective in older adults. Health experts recommend vaccinations for people over 50 because the flu shot may reduce the risk of flu-related complications, hospitalizations and deaths.

Healthy people ages 2 to 49 alternatively may receive the flu vaccine via a nasal spray called FluMist. It protects against the same strains of influenza that the flu shot does. Like the flu shot, FluMist is given every year. Because FluMist contains live, but weakened, flu viruses, it shouldn’t be given to pregnant women, people with weakened immune systems and those with chronic illnesses. A study published in 2006 found that FluMist was only between 30 and 57 percent effective in preventing the flu in adults. However, another study in 2006 found that giving nasal spray vaccine to school-age children helped to reduce the spread of flu in the community. And in 2007, researchers compared the effectiveness of FluMist with the flu shot in children ages 6 months to 5 years. The children treated with FluMist experienced about half as many cases of flu as did those treated with the shot. However, FluMist increases the risk of wheezing in this age group — especially in those who already have asthma or recurrent wheezing and in all children under age 2. In 2007, the Food and Drug Administration (FDA) therefore approved FluMist for children older than 2 years who don’t have asthma or recurrent wheezing. Consult with your doctor about which form of vaccination may be best for you or your child.

You can get the flu vaccine from your doctor, at public health centers and many pharmacies. In some areas, flu vaccines are also available at senior or community centers and at supermarkets.

· Wash your hands. Thorough and frequent hand washing is the best way to prevent many common infections. Scrub your hands vigorously for at least 15 seconds, rinse well and turn off the faucet with a paper towel. Or use an alcohol-based hand gel containing at least 60 percent alcohol.

· Eat right, sleep tight. A poor diet and poor sleep both lower your immunity and make you more vulnerable to infections. A balanced diet that emphasizes fresh fruits and vegetables, whole grains, and small amounts of lean protein works best for most people. On the other hand, the amount of sleep needed for a healthy immune system varies from person to person. In general, adults seem to do best on seven to eight hours of sleep a night. Older children and teens need more rest — between nine and 10 hours every night.

· Exercise regularly. Regular cardiovascular exercise — walking, biking, aerobics — boosts your immune system. Exercise won’t prevent infection, but if you do come down with the flu, you may have less severe symptoms and recover more quickly than do people who aren’t as fit.

· Avoid crowds during flu season. Flu spreads easily wherever people congregate — in child care centers, schools, office buildings, auditoriums and public transportation. By avoiding crowds whenever possible during peak flu season, you reduce your chances of infection.