FLU vaccines may be far less effective at combating seasonal outbreaks than previously thought, researchers say, adding that they may not be worth the cost and effort required to produce them.

According to a review published today, there is little clinical evidence that the vaccines reduce deaths significantly, hospital stays and time off work among those most at risk from seasonal flu, including the over-65s and those with chronic heart and lung conditions.

Public policy worldwide recommends the use of inactivated influenza vaccines — those that contain dead viruses and are given with a needle in the arm — to prevent outbreaks. More than 15 million doses of vaccine have been ordered for use this winter in Britain.

But according to Tom Jefferson, a vaccines expert, vaccines given to children under 2 have the same effect as if they were given a dummy drug. He is calling for an urgent re-evaluation of vaccination campaigns.

Writing in the British Medical Journal, he says that because influenza viruses mutate and vary from year to year, it is difficult for scientists to study the precise effects of vaccines and that most existing studies are of poor quality.

Responding to Dr Jefferson’s comments, David Salisbury, director of immunisation at the Department of Health, said: “In older people, protection against infection may be less, but there is good evidence showing that immunisation reduces broncho- pneumonia, hospital admissions and mortality.”

TAMIFLU RESISTANC AND AVIAN FLU

By Steven Reinberg

HealthDay ReporterWed Dec 21,11:48 PM ET

WEDNESDAY, Dec. 21 (HealthDay News) -- One of the few drugs known to be effective against the potentially pandemic avian flu is the antiviral drug Tamiflu, but a new report finds further evidence that some patients may develop resistance to it.

A report issued last October outlined one such case in Vietnam. Now, a new article gives more details on two Vietnamese patients who were resistant to Tamiflu (oseltamivir) and died from the H5N1 avian flu virus despite treatment with the drug.

According to the report, six surviving patients who were also treated with the drug appeared to respond well to the therapy, which was associated with a rapid decline of viral load to undetectable levels in the blood.

The report appears in the Dec. 22 issue of The New England Journal of Medicine.

A research team from the Oxford University Clinical Research Unit and Hospital for Tropical Diseases, in Ho Chi Minh City, believes the failed cases show that in some H5N1-infected patients, the recommended dose of Tamiflu is unable to stop the virus from replicating.

In these cases, not only does the virus spread, but a viral resistance to Tamiflu may develop.

The study's lead author, Dr. Menno D. de Jong, said the resistance is unsurprising, but added, "this does not automatically extrapolate to the situation in the event of an influenza pandemic."

"While our study shows that the drug seems to be effective in suppressing viral replication in at least some patients, it also clearly shows that oseltamivir resistance in H5N1 can develop, and if this happens it may render the drug not effective," de Jong said.

"The availability of alternative antiviral drugs, which remain active against oseltamivir-resistant virus, is important," de Jong said. "One such drug is zanamivir. In addition, strategies to prevent or delay resistance development, for example, higher dosing or combination therapy needs to be explored."

"My advice to patients is to remain calm," de Jong added. "High resistance rates have been observed in human flu as well, generally without detrimental clinical effects."

The reasons for Tamiflu's ineffectiveness in some patients is unclear, however. The researchers speculated that the virus may be replicating too fast for the drug to stop it, or somehow the drug becomes altered in these patients.

One expert believes, however, that Tamiflu resistance may not be the reason the two patients died. Instead, their deaths could be due to the virulence of the particular virus.

"There is no telling that the development of resistance has anything to do with the fatal outcome of these patients," said Dr. Arnold S. Monto, a professor of epidemiology at the University of Michigan School of Public Health, Ann Arbor. "We do not suspect that with this virus that we are going to get 100 percent cure."

Monto noted that the H5N1 virus may not be able to spread easily, since it seems to take a very large amount of the virus to move from birds and then infect people. "This virus is somewhat lacking in fitness -- its ability to infect and transmit [to people]," he said. "On a population basis, this virus might not take off."

According to Monto, a new report about to be issued shows that Japan, where Tamiflu is widely used, has not seen an emergence of a resistant flu virus. "Appropriate use of Tamiflu in treating seasonal influenza should not be inhibited because you are worried that you may be enhancing the emergence of a resistant virus," he said.

Despite this, Monto believes that other antiviral drugs to treat the flu are needed. "It's an unhealthy situation to have the whole world dependent on one drug for treating a very important infection," he said. "We can't ensure that this resistance will not emerge. We need to be sure that we have a backup if it does."

Faced with the growing fear of a pandemic of deadly avian flu, the number of requests by patients for prescriptions for Tamiflu has increased dramatically. In increasing numbers, patients have been asking their doctors for Tamiflu so they can be sure they have a supply should an outbreak occur.

One expert, writing in the same journal issue, cautions doctors not to let patients stockpile Tamiflu as a way of being prepared for an outbreak of avian flu.

Physicians are receiving requests by patients to give them prescriptions for Tamiflu, and in many cases, doctors are acceding to these requests, because it's easier than arguing with patients, said Dr. Allan S. Brett, a professor of medicine at the University of South Carolina School of Medicine, Columbia.

"Physicians should not yield to requests for Tamiflu, when the purpose is personal stockpiling," Brett said. "The patient is asking it for some hypothetical event in the future that may or may not even come," he said.

Brett also cautioned that allowing patients to have the drug may encourage them to take it when they think they have the flu, but only have a bad cold. "People may say, 'This could be influenza, so I'll just start taking the drug,' and then it becomes a real waste," he said. "In addition, widespread unnecessary use will increase the chance of resistant virus."

Another expert, writing in the journal, agreed with Brett.

"I focus on the issue of the development of resistance in influenza to Tamiflu," said Dr. Anne Moscona, a professor in the departments of pediatrics and microbiology and immunology at the Weill Medical College of Cornell University in New York City. "This means that the influenza may develop to [a point] where it is no longer able to be killed, to be treated by Tamiflu."

Moscona isn't surprised that resistance to Tamiflu is developing in the H5N1 virus. "We expected resistance to develop," she said. "Resistance is developing in seasonal flu and now resistance is developing in avian flu."

"There is no pandemic flu right now," Moscona said. "Really, Tamiflu remains an effective and important drug in seasonal influenza. Physicians should not be prescribing Tamiflu to people who just want to stockpile it. We should use these drugs to treat people who are sick."

More information

For moe on avian flu, head to the U.S. Centers for Disease Control and Prevention.

Flu Shots May Not Save Lives -- Study

CHICAGO (Reuters) - The flu vaccinations that doctors hoped would save the lives of fragile elderly people have apparently failed to lower death rates, U.S. researchers said on Monday.

More people whose health could be put at risk by influenza have heeded the call to get vaccinated before flu season, but the death rate during the winter flu season remained the same rather than declining, they said.

Based on U.S. mortality rates from 1968 to 2001, the study by the National Institute of Allergy and Infectious Diseases (news - web sites) found no correlation between increasing vaccination rates after 1980 and declining death rates in any age group.

"We conclude, therefore, that there are not enough influenza-related deaths to support the conclusion that vaccination can reduce total winter mortality among the U.S. elderly population by as much as half," study author Lone Simonsen wrote in The Archives of Internal Medicine (news - web sites).

Previous studies have estimated that vaccine programs have cut mortality rates among the elderly by about half.

While the vaccination rate in 2001 rose to 65 percent among elderly Americans from around 20 percent before 1980, the rate of excess winter deaths has remained flat instead of declining by an expected 40 percent.

Because deaths spiked in some years when a virulent form of flu was epidemic, the findings may not be conclusive, the researchers said.

The report suggested earlier observational studies may have had skewed data. For one thing, influenza sufferers may have died from secondary complications brought on by flu after their symptoms had passed, it said. In addition, vaccines often fail to activate antibodies in the elderly.

Further evidence may come after this flu season since an initial U.S. shortage of flu vaccine should have an effect on mortality rates, one way or the other, the report said.

"Either way, this vast disconnect between conclusions from different studies must be sorted out," it said.

Study Suggests Flu Vaccine Didn't Work Well

Thu Jan 15, 4:10 PM ET Add Health - Reuters to My Yahoo!

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) - The influenza vaccine that many Americans clamored for this year was not very good at protecting people against influenza, colds and similar viruses, a preliminary report published on Thursday shows.

The study is the first attempt to show whether the vaccine that many sought after a flu scare this autumn and winter actually worked.

The study of hospital workers in Colorado, a state that was hit early and hard by influenza, showed the vaccine had "no or low effectiveness against influenza-like illness," the U.S. Centers for Disease Control and Prevention (news - web sites) said in its report.

Many experts did not expect the vaccine to work well, although the CDC had hoped it would at least prevent some of the worst illnesses caused by this year's strain of influenza.

The vaccine is only meant to protect against true influenza. Without a test, it is often difficult to distinguish between influenza and other, similar viruses.

CDC spokesman Tom Skinner said that for this reason the report only shows part of the story.

"This is the first of a number of studies that we are going to do to try to answer the question, 'did this year's vaccine offer protection against flu?' This study in and of itself does not answer this question," he said in a telephone interview.

However, the study shows that people who were vaccinated against influenza came down with colds, flu and similar viruses at the same rate as people who were not vaccinated. This would presumably include true influenza.

The vaccine is formulated each year in February or March, at the end of the northern hemisphere's flu season, and did not include the Fujian strain of influenza, a new, mutated strain that turned out to be the predominant type of flu in the United States and several other countries this year.

The epidemic appears to be on the wane -- this past week only 2.8 percent of hospital visits were for influenza-like illnesses, compared to 5.5 percent the week before.

News coverage of the early start to the flu season sent many people rushing to get vaccinated. There were shortages in some places and the U.S. government bought 625,000 doses of flu vaccine from makers Chiron and Aventis .

It also negotiated a discount price for states to buy up to 3 million unsold doses of Wyeth and MedImmune's FluMist vaccine, which is given nasally.

Experts knew the vaccines did not include the Fujian strain, but they did contain the related Panama strain, which they hoped would provide at least some protection.

The study, done among hospital workers at the Children's Hospital in Denver, suggests it did not.

Of the 1,000 people vaccinated before Nov. 1, 149 developed influenza-like illness, or just under 15 percent. Of the 402 people who were not vaccinated, 68 got a flu-like illness, or just under 17 percent.

JAMA Patient Page:

Do You Have The Flu?

The common cold and influenza (commonly called flu) are both respiratory infections caused by viruses. But the flu is considered more serious because of more severe symptoms that can lead to pneumonia and even death in persons who have other chronic diseases.

With both the cold and flu, you may experience a stuffy nose, sore throat, and sneezing. Tiredness, fever, chills, headache, and major aches and pains may mean you have the flu. Neither the common cold nor flu need to be treated with antibiotics. Consult your doctor if your symptoms get worse or persist for more than a few days.

One of the best ways to prevent flu infection is to get a flu vaccine from your doctor. A study in the March 10, 1999, issue of The Journal of the American Medical Association shows that the vaccine is 88 percent effective in preventing influenza type A infection and 89 percent effective in preventing influenza type B infection. A second study in the same issue shows that it may be especially advisable for certain groups of people, such as women younger than age 65 with certain chronic medical conditions, to get an annual flu vaccine.

Who Should Get a Flu Shot?

All people aged 65 years or older

People of any age with chronic diseases of the heart, lung or kidneys, diabetes, compromised immune systems, severe forms of anemia, or asthma

Residents of nursing homes and other facilities where patients with chronic medical conditions live

Children or teenagers who are receiving long-term aspirin therapy and who therefore may be at risk for developing Reye syndrome (a neurologic disorder characterized by brain or liver damage) after a flu infection

Women who will be in the second or third trimester of pregnancy during the flu season

Health care professionals and volunteers who work with high-risk patients

People who live in a household with a person who fits into any of the categories above

LEADING CAUSES OF DEATH, UNITED STATES, 1995:
1	Heart disease	737,563
2	Cancer	538,455
3	Cerebrovascular disease	157,991
4	Chronic obstructive lung disease	102,899
5	Unintentional injury	93,320
6	Pneumonia and influenza	82,923
7	Diabetes	59,254
8	HIV and AIDS	43,115
9	Suicide	31,284
10	Chronic liver diseases	25,222
Sources: National Foundation for Infectious Diseases, 1996-97, and Injury Chartbook, Hyattsville, Maryland, 1997

What to Expect:

The flu shot contains no live virus, so you cannot get the flu from the shot. In the United States, flu season usually occurs from about November to April, and the best time to get the vaccine is between September and mid-November. Flu viruses continually change, so it is important that you receive the flu vaccine every year. Most people do not experience side effects from the flu vaccine; however, some people may feel sore at the vaccination site, and other minor, uncommon side effects include headache or low-grade fever for about a day after vaccination.

What is Influenza?

Influenza is a highly contagious respiratory infection. It is spread person-to-person through infectious droplets, such as when an infected person coughs or sneezes. It causes symptoms that include headache, chills, and dry cough, followed by body aches, fever, nasal congestion and sore throat. Symptoms usually appear within two days to four days days of being infected, and a person is considered contagious for another three days to four days after symptoms appear. There are three types of influenza viruses (types A, B and C), with type A being the most prevalent and associated with the most serious epidemics.

For More Information:

National Institute of Allergy and Infectious Diseases

Building 31, Room 7A50

31 Center Drive, MSC 2520

Bethesda, MD 20892-2520

http://www.niaid.nih.gov

American Lung Association

(800) LUNG-USA

http://www.lungusa.org

Additional Sources: National Center for Infectious Diseases, National Institute for Allergy and Infectious Diseases, Food and Drug Administration, AMA's Encyclopedia of Medicine

Mi Young Hwang, Writer

Richard M. Glass, Editor

Jeff Molter, Director of Science News

(JAMA. 1999; 281:962)

Published in JAMA: March 10, 1999

The JAMA Patient Page is a public service of The Journal of the American Medical Association and the American Medical Association. The information and recommendations appearing on this page are appropriate in most instances; but they are not a substitute for medical diagnosis. For specific information concerning your personal medical condition, JAMA and AMA suggest that you consult your physician. This page may be reproduced noncommercially by physicians and other health care professionals to share with patients. Any other reproduction is subject to AMA approval.

Flu Shot Works Best in Well-Rested Individuals

Tue Sep 24, 5:38 PM ET

By Charnicia E. Huggins

NEW YORK (Reuters Health) - An annual vaccination may be the best way to protect against the influenza bug, but to guarantee its effectiveness, people should also be sure to get a good night's sleep before they get their flu shot, new study findings show.

"Getting your flu shot after not having enough sleep may not offer the same protection as getting it when well-rested," study author Dr. Eve Van Cauter of the University of Chicago in Illinois told Reuters Health.

"Chronic partial sleep loss, as experienced by millions of Americans today, has an adverse effect on immune function," she added.

To investigate, Van Cauter and her team studied 25 healthy young men. Eleven had their sleep restricted to just 4 hours a night on 6 nights of the week, followed by 12 hours of sleep per night for a full week. They were vaccinated against the flu on the morning of the fifth day during their sleep-deprived week. The remaining 14 men maintained their usual bedtimes before they were vaccinated.

At follow-up, 10 days after the vaccinations, the investigators found that the men who were immunized while sleep-deprived had an immune response to the flu that was less than half of that shown by their better-rested peers.

At both the 3- and 4-week follow-ups, however, there were no great differences in immune response between the two groups, the researchers note. Their findings are published in a letter to the editor in the September 25th issue of The Journal of the American Medical Association ( news - web sites).

"These findings add to a growing body of evidence indicating that sleep curtailment has adverse health effects," such as making people more prone to colds and other illnesses, Van Cauter said.

The study was partially funded by grants from the National Institutes of Health ( news - web sites).

SOURCE: The Journal of the American Medical Association 2002;288:1471-1472.

Classic signs and symptoms of influenza

Rapid onset of symptoms

Fever (temperature usually > 37.7°C [100°F])

Nonproductive cough

Headache

Myalgia

Chills and/or sweats

Sore throat

Potentially severe, persistent malaise

Substernal soreness, photo-phobia, and ocular problems

From Cox NJ, Fukuda K. Infect Dis Clin North Am. 1998.[6]

FLU VS COLD

Signs and symptoms	Influenza	Cold
Onset	Sudden	Gradual
Fever	Characteristically high, lasting 3 or 4 days	Uncommon
Cough	Frequent, early in onset, often marked, sometimes mucoid	Less frequent, less severe, later in onset
Headache	Prominent	Common but usually not disabling
Myalgia	Usual, often severe	Slight
Fatigue or weakness	May last up to 2 to 3 weeks	Mild
Extreme exhaustion	Early and prominent	Rare
Chest discomfort	Common	Uncommon
Stuffy nose	Sometimes	Hallmark symptom
Sneezing	Sometimes	Hallmark symptom
Sore throat	Sometimes	Sore or scratchy throat typically first symptom noted

Influenza Vaccine Recommendations

The most important control measure for the prevention of influenza outbreaks in any population is annual vaccination with the influenza vaccine. The Advisory Committee on Immunization Practices (ACIP) has prioritized target groups for influenza vaccination.[1] People who are included in the highest priority group are those most at risk for complications of influenza (see Table 1). This group includes: (1) persons aged 65 years or older; (2) residents of nursing homes and other facilities where people with chronic illnesses reside; (3) adults and children who have chronic disorders, especially pulmonary or cardiovascular illness, chronic metabolic diseases (eg, diabetes), renal dysfunction, hemoglobinopathies, or immunosuppression such as HIV; (4) children and teenagers who receive long-term aspirin therapy and are therefore at risk for Reye syndrome following an influenza infection; and (5) women who will be in their second or third trimester of pregnancy during the influenza season.

People who are between the ages of 50 and 64 years are also included in the ACIP's recommendation for vaccination, because this age group has a high prevalence of chronic medical conditions. People who have close contact with at-risk individuals (eg, healthcare workers, family caregivers) should also be vaccinated. Finally, any healthy person who wishes to be protected from influenza should receive an annual vaccine. Since many office workers are at risk for a worksite epidemic, employers often encourage them to be vaccinated. The vaccination of apparently healthy children may also be warranted because encephalitis and encephalopathy have been reported with increased frequency among children who have an influenza infection.[8]

The Influenza Vaccine

Vaccine Protection

Protection from influenza is dependent on how closely the strains approximate the circulating strains of the virus. Elderly and immunocompromised people may not be as protected as younger adults because their postvaccination antibody titers tend to be lower.[4] Protective antibody levels are achieved in 70% to 90% of immunized healthy adults younger than 65 years of age.[9] The antibody titer begins to decline within 7 months, and, therefore, annual vaccination is needed. The vaccine may reduce the severity and complications that follow the onset of influenza. Therefore, vaccine protection can decrease the risks of illness, hospitalization, and death.

Adverse Reactions and Contraindications

Local reactions, which occur in approximately one third of recipients, include pain, erythema, and induration at the vaccine site. For the first 2 days after the intramuscular injection, the recipient may experience systemic reactions consisting of fever, malaise, and myalgia. Because influenza virus is killed during the manufacturing process, people cannot get influenza from the vaccine. Guillain-Barré syndrome has not been associated with the vaccine since the 1976 swine influenza vaccine. However, Wyeth Laboratories recommends that the vaccine not be administered to persons with a history of Guillain-Barré syndrome.[7] Although the vaccine can be given to people with minor illnesses, persons with acute febrile illnesses should not receive it. Because animal reproduction studies have not been conducted to determine fetal harm from the vaccine, caution should be used when making decisions to give the vaccine to pregnant women. The vaccine contains a small amount of egg protein and therefore is contraindicated for individuals with a severe anaphylactic sensitivity to eggs.

Chemoprophylaxis With Antiviral Compounds