Even when the flu does not reach pandemic proportions, it is the source of misery, illness, and death every flu season, which runs roughly through the fall and early winter months in North America. Since the early 1970s, researchers estimate that influenza has caused more than 40,000 deaths in the United States every year (Dushoff J et al 2006). It is estimated that flu outbreaks cost about $12 billion annually in the United States (Kasper DL et al 2004).
Everyone is susceptible to infection with the flu virus, which is usually spread by direct contact with contaminated secretions (Nicholson KG et al 2003). It can also be spread when the virus is sneezed or coughed into the air, although influenza is not typically spread by aerosol (being dissolved in air), as are other respiratory viruses (Bridges CB et al 2003; Goldmann DA 2000). This means that the flu can spread only short distances between people—simply being in a room with someone who has the flu is not a major risk factor. The severity of the infection and the duration of the illness, however, depend on several factors, including:
■Resistance of the respiratory tract to oxidative stress associated with influenza infection, as well as its ability to mount a local immune/inflammatory response and its ability to manufacture and secrete antibodies (Beck MA et al 1998; Mileva M et al 2002b; Muller F et al 2000; Nicholson KG et al 2003).
■Level of immunity against that particular strain of influenza (Dolin R 2004; Glezen WP 2004; Nicholson KG et al 2003; Wareing MD et al 2002; Zambon MC 2001).
■Overall health of the person’s immune system (Brandtzaeg P 2003; Chandra S et al 1986; Nicholson KG et al 2003).
■Antioxidant status (Hennet T et al 1992).
■Overall nutritional and general health status.
Nutrition has recently been singled out as the most important factor in resistance to influenza infection (Beck MA et al 2004).
Infection: The Flu Virus at Work
There are two main types of flu viruses: influenza A and influenza B. The most serious and deadly flu outbreaks are caused by influenza A because of its ability to genetically shift into new forms against which no person has developed immunity. H5N1, the avian flu, is caused by an influenza A virus. Influenza B generally causes less severe infection. Outbreaks of influenza B commonly occur in schools and military camps, where many people live or work in close contact.
Infection with the flu begins with exposure of the upper respiratory tract to the virus. In infected cells, viral replication occurs 4 to 6 hours after infection, after which time the infected cell bursts, spreading the virus to nearby cells. The cycle then repeats, infecting more and more cells each time. This accounts for the incubation period for the flu, which ranges from about 18 to 72 hours, depending on the strain and the effectiveness of the body’s immune response. The more virulent the strain, and/or the weaker the host's immunity, the sooner the cycle of cell death and viral spread produces noticeable symptoms. People who have weak immune systems, such as the elderly, sick people, or young children, can therefore be quickly overwhelmed by strong strains of the virus.
The immune response to the flu is complex and comprehensive. Almost immediately after sensing the virus, the body mounts a response that calls upon all facets of the immune system. This includes natural immune responses, such as the release of proinflammatory cytokines and enhanced natural killer cell activity, which includes the release of antiviral interferons. White blood cells called neutrophils and macrophages also flood the site of infection, producing yet more proinflammatory and fever-causing cytokines. This rapid, indiscriminate immune response is responsible for the sudden onset and continuation of symptoms, which usually peak by the second day of infection (Wright PF et al 2001; Yuen KY et al 2005).
At the same time that this nonspecific response is occurring, the body is creating specific antibodies to recognize and destroy that particular strain of flu virus in the future. The body’s immune system relies on T-cells and B-cells, which are coded to identify specific antigens (invaders) and stimulate a more effective and rapid immune response in the event of future infection. In the case of the influenza virus, antibodies against the flu are detected in the second week after primary infection. These antibodies will help protect against similar strains of the flu in the future. New strains, such as those created by genetic shifting, retain their full power. For more information on a healthy immune system, please see the chapter "Immune System Enhancement."
Ideally, the best approach to the flu is to avoid getting sick in the first place. This may mean using a vaccine to help bolster the immune response against specific strains, or taking nutrients such as lactoferrin that have been shown to enhance the immune system.
Once infection has occurred, the goal of flu therapy is to stop the virus before it replicates enough to cause illness. Flu vaccines, which contain dead or inactivated flu viruses, help people ward off illness by enabling their bodies to recognize and fight a specific strain of flu virus early in the infection process. Every year, doctors try to determine which variety of the flu is likely to cause an outbreak, then vaccines against that particular strain are manufactured. Vaccination against influenza is often recommended for at-risk populations, especially the elderly (Cox RJ et al 2004; Glezen WP 2004; Kilbourne ED 2004; Langley JM et al 2004; Munoz FM 2003; Nicholson KG et al 2003; Pfleiderer M et al 2001; Sandhu SK et al 2001; Wareing MD et al 2002). Additionally, animal studies suggest that supplementing with dehydroepiandrosterone (DHEA) may restore the aging immune system sufficiently to allow normal response to the vaccine (Daynes RA et al 1994).
In many cases of flu infection, the onset of symptoms is so abrupt that people can pinpoint the hour when they began to feel ill. Body temperature rises rapidly, and can reach 100ºF to 106ºF within the first 24 hours; a sharp headache may occur (Dolin R 2004). These symptoms are not characteristic of other, less serious, respiratory infections such as the common cold, so they are reliable indicators that the person is infected with the flu. Respiratory symptoms, such as coughing and congestion, appear later in the illness. In the absence of complications, influenza symptoms typically resolve within a week, although, in a significant number of elderly people, general weakness and fatigue may persist for several weeks (Dolin R 2004).
The most common and dangerous complication of influenza is pneumonia, which can affect people of all ages and may be life-threatening. The people most commonly affected by complications of influenza are 65 years or older or those who have chronic disorders such as diabetes. Newborn infants, like the elderly, are at increased risk of serious complications because of their incompletely developed immune systems. These complications include pneumonia and other lung conditions, as well as occasional heart diseases such as myocarditis. Minor complications of influenza in infants and young children can include ear infections, while the fever itself may be responsible for febrile convulsions in children 6 months to 6 years.
You Should Get a Flu Vaccine If You …
■Are age 65 or older.
■Have a chronic medical condition, such as a cardiovascular, pulmonary, metabolic, or renal disease.
■Have a weak immune system.
■Are a pregnant woman in her second or third trimester (Cox RJ et al 2004).
■Smoke.
■Are a health-care provider or a volunteer in a health-care setting.
Conventional Antiviral Drugs
Although good nutrition and flu vaccines are first-line treatments for the prevention of the flu, antiviral drugs also may be given to prevent infection or reduce the severity of illness. If given quickly enough, antiviral drugs have been shown to reduce the duration of symptoms by about 50 percent, although some people experience unpleasant side effects of the central nervous system with these drugs. Some of the adverse effects from using these drugs can include nervousness, jitters, insomnia, or difficulty concentrating (Kasper DL et al 2004). Everyone (including people who have been vaccinated against the flu) can receive antiviral drugs.
Common antiviral drugs include:
■Amantadine and rimantadine. In the United States, amantadine and rimantadine are approved by the US Food and Drug Administration (FDA) for treatment of influenza infection. Amantadine is approved for prevention and treatment in adults and in children older than 1 year; rimantadine is approved for prevention and treatment in adults and for prevention in children (Jefferson T et al 2004). The effectiveness of amantadine in the treatment of influenza in people who are at high risk of complications has not been proved in clinical trials. Also, influenza A rapidly develops resistance to amantadine (Dolin R 2004; Nicholson KG et al 2003).
■Oseltamivir. In October 1999, the antiviral drug oseltamivir (Tamiflu) was approved in the United States for treatment of uncomplicated influenza in adults. People who take oseltamivir usually recover 1.3 days (30 percent) faster than those who do not. The most common adverse effects are mild to moderate transient nausea or vomiting. Other side effects include bronchitis, insomnia, and vertigo. Less than 1 percent of people who take oseltamivir in clinical trials discontinued the drug early because of nausea or vomiting (McClellan K et al 2001; Treanor JJ et al 2000).
In 2000, oseltamivir was approved for prevention of influenza in people who have been exposed to the virus. It is up to 92 percent effective in preventing influenza when taken once daily (Peters PH Jr et al 2001). In one clinical trial involving 548 patients (276 taking oseltamivir, 272 taking placebo), a daily dose of 1.75 milligrams (mg) of oseltamivir was given for up to 42 days to a group of elderly nursing home residents. In the placebo group, oseltamivir reduced the incidence of influenza from 4.4 to 0.4 percent (Peters PH Jr et al 2001). Oseltamivir shortened the duration of influenza by 1.5 days (26 percent) in children age 1 to 12 years when given within 2 days of symptom onset (Whitley RJ et al 2001).
■Zanamivir. The antiviral zanamivir (Relenza) is delivered through an inhaler. In the United States, zanamivir is approved only for prevention of influenza. Several clinical trials have demonstrated efficacy comparable to that of oseltamivir. Seasonal prevention with 10 mg of zanamivir daily in unvaccinated healthy subjects reduced the incidence of influenza from 69 to 81 percent (Nicholson KG et al 2003).
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