Flu

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses), that affects birds and mammals. The most common symptoms of the disease are chills, fever, sore throat, muscle pains, severe headache, coughing, weakness/fatigue and general discomfort. Sore throat, fever and coughs are the most frequent symptoms. In more serious cases, influenza causes pneumonia, which can be fatal, particularly for the young and the elderly. Although it is often confused with other influenza-like illnesses, especially the common cold, influenza is a much more severe disease than the common cold and is caused by a different type of virus. Influenza may produce nausea and vomiting, particularly in children, but these symptoms are more common in the unrelated gastroenteritis, which is sometimes called "stomach flu" or "24-hour flu".

Typically, influenza is transmitted through the air by coughs or sneezes, creating aerosols containing the virus. Influenza can also be transmitted by direct contact with bird droppings or nasal secretions, or through contact with contaminated surfaces. Airborne aerosols have been thought to cause most infections, although which means of transmission is most important is not absolutely clear. Influenza viruses can be inactivated by sunlight, disinfectants and detergents. As the virus can be inactivated by soap, frequent hand washing reduces the risk of infection.

Influenza spreads around the world in seasonal epidemics, resulting in the deaths of hundreds of thousands worldwide annually, and millions in pandemic years. On average 41,400 people died each year in the United States between 1979 and 2001 from influenza. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new strain of the virus in humans. Often, these new strains appear when an existing flu virus spreads to humans from other animal species, or when an existing human strain picks up new genes from a virus that usually infects birds or pigs. An avian strain named H5N1 raised the concern of a new influenza pandemic, after it emerged in Asia in the 1990s, but it has not evolved to a form that spreads easily between people. In April 2009 a novel flu strain evolved that combined genes from human, pig, and bird flu, initially dubbed "swine flu" and also known as influenza A/H1N1, emerged in Mexico, the United States, and several other nations. The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009 (see 2009 flu pandemic). The WHO's declaration of a pandemic level 6 was an indication of spread, not severity.

Vaccinations against influenza are usually given to people in developed countries and to farmed poultry. The most common human vaccine is the trivalent influenza vaccine (TIV) that contains purified and inactivated material from three viral strains. Typically, this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain. The TIV carries no risk of transmitting the disease, and it has very low reactivity. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and new strains quickly replace the older ones. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.

Signs and symptoms

Symptoms of influenza can start quite suddenly one to two days after infection. Usually the first symptoms are chills or a chilly sensation, but fever is also common early in the infection, with body temperatures ranging from 38-39 °C (approximately 100-103 °F). Many people are so ill that they are confined to bed for several days, with aches and pains throughout their bodies, which are worse in their backs and legs. Symptoms of influenza may include:

• Fever and extreme coldness (chills shivering, shaking (rigor))
• Cough
• Nasal congestion
• Body aches, especially joints and throat
• Fatigue
• Headache
• Irritated, watering eyes
• Reddened eyes, skin (especially face), mouth, throat and nose
• In children, gastrointestinal symptoms such as diarrhea and abdominal pain, (may be severe in children with influenza B)

It can be difficult to distinguish between the common cold and influenza in the early stages of these infections, but a flu can be identified by a high fever with a sudden onset and extreme fatigue. Diarrhea is not normally a symptom of influenza in adults, although it has been seen in some human cases of the H5N1 "bird flu" and can be a symptom in children. The symptoms most reliably seen in influenza are shown in the table to the right.

Since antiviral drugs are effective in treating influenza if given early (see treatment section, below), it can be important to identify cases early. Of the symptoms listed above, the combinations of fever with cough, sore throat and/or nasal congestion can improve diagnostic accuracy. Two decision analysis studies suggest that during local outbreaks of influenza, the prevalence will be over 70%, and thus patients with any of these combinations of symptoms may be treated with neuraminidase inhibitors without testing. Even in the absence of a local outbreak, treatment may be justified in the elderly during the influenza season as long as the prevalence is over 15%.

The available laboratory tests for influenza continue to improve. The United States Centers for Disease Control and Prevention (CDC) maintains an up-to-date summary of available laboratory tests. According to the CDC, rapid diagnostic tests have a sensitivity of 70–75% and specificity of 90–95% when compared with viral culture. These tests may be especially useful during the influenza season (prevalence=25%) but in the absence of a local outbreak, or peri-influenza season (prevalence=10%).

Transmission

People who contract influenza are most infective between the second and third days after infection, and infectivity lasts for around ten days. Children are much more infectious than adults and shed virus from just before they develop symptoms until two weeks after infection. The transmission of influenza can be modeled mathematically, which helps predict how the virus will spread in a population.

Influenza can be spread in three main ways: by direct transmission (when an infected person sneezes mucus directly into the eyes, nose or mouth of another person); the airborne route (when someone inhales the aerosols produced by an infected person coughing, sneezing or spitting) and through hand-to-eye, hand-to-nose, or hand-to-mouth transmission, either from contaminated surfaces or from direct personal contact such as a hand-shake. The relative importance of these three modes of transmission is unclear, and they may all contribute to the spread of the virus. In the airborne route, the droplets that are small enough for people to inhale are 0.5 to 5 µm in diameter and inhaling just one droplet might be enough to cause an infection. Although a single sneeze releases up to 40,000 droplets, most of these droplets are quite large and will quickly settle out of the air. How long influenza survives in airborne droplets seems to be influenced by the levels of humidity and UV radiation: with low humidity and a lack of sunlight in winter probably aiding its survival.

As the influenza virus can persist outside of the body, it can also be transmitted by contaminated surfaces such as banknotes, doorknobs, light switches and other household items. The length of time the virus will persist on a surface varies, with the virus surviving for one to two days on hard, non-porous surfaces such as plastic or metal, for about fifteen minutes from dry paper tissues, and only five minutes on skin. However, if the virus is present in mucus, this can protect it for longer periods (up to 17 days on banknotes). Avian influenza viruses can survive indefinitely when frozen. They are inactivated by heating to 56 °C (133 °F) for a minimum of 60 minutes, as well as by acids (at pH <2).

Prevention

Vaccination
 
Giving an influenza vaccination.Vaccination against influenza with an influenza vaccine is often recommended for high-risk groups, such as children and the elderly, or in people who have asthma, diabetes, heart disease, or are immuno-compromised. Influenza vaccines can be produced in several ways; the most common method is to grow the virus in fertilized hen eggs. After purification, the virus is inactivated (for example, by treatment with detergent) to produce an inactivated-virus vaccine. Alternatively, the virus can be grown in eggs until it loses virulence and the avirulent virus given as a live vaccine. The effectiveness of these influenza vaccines are variable. Due to the high mutation rate of the virus, a particular influenza vaccine usually confers protection for no more than a few years. Every year, the World Health Organization predicts which strains of the virus are most likely to be circulating in the next year, allowing pharmaceutical companies to develop vaccines that will provide the best immunity against these strains. Vaccines have also been developed to protect poultry from avian influenza. These vaccines can be effective against multiple strains and are used either as part of a preventative strategy, or combined with culling in attempts to eradicate outbreaks.

It is possible to get vaccinated and still get influenza. The vaccine is reformulated each season for a few specific flu strains but cannot possibly include all the strains actively infecting people in the world for that season. It takes about six months for the manufacturers to formulate and produce the millions of doses required to deal with the seasonal epidemics; occasionally, a new or overlooked strain becomes prominent during that time and infects people although they have been vaccinated (as by the H3N2 Fujian flu in the 2003–2004 flu season). It is also possible to get infected just before vaccination and get sick with the very strain that the vaccine is supposed to prevent, as the vaccine takes about two weeks to become effective.

The 2006–2007 season was the first in which the CDC had recommended that children younger than 59 months receive the annual influenza vaccine. Vaccines can cause the immune system to react as if the body were actually being infected, and general infection symptoms (many cold and flu symptoms are just general infection symptoms) can appear, though these symptoms are usually not as severe or long-lasting as influenza. The most dangerous side-effect is a severe allergic reaction to either the virus material itself or residues from the hen eggs used to grow the influenza; however, these reactions are extremely rare.

In addition to vaccination against seasonal influenza, researchers are working to develop a vaccine against a possible influenza pandemic. The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at non-egg-based options for vaccine production. Live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles) could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate. As of July 2009, more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration approved four vaccines against the 2009 H1N1 influenza virus (the current pandemic strain), and expect the initial vaccine lots to be available within the following month.

Infection control

Reasonably effective ways to reduce the transmission of influenza include good personal health and hygiene habits such as: not touching your eyes, nose or mouth; frequent hand washing (with soap and water, or with alcohol-based hand rubs); covering coughs and sneezes; avoiding close contact with sick people; and staying home yourself if you are sick. Avoiding spitting is also recommended.

Although face masks might help prevent transmission when caring for the sick, there is mixed evidence on beneficial effects in the community. Smoking raises the risk of contracting influenza, as well as producing more severe disease symptoms. Thus, according to the laws of mathematical modelling of infectious diseases, smokers raise the exponential growth rates of influenza epidemics and may indirectly be responsible for a large percentage of influenza cases.

Since influenza spreads through both aerosols and contact with contaminated surfaces, surface sanitizing may help prevent some infections. Alcohol is an effective sanitizer against influenza viruses, while quaternary ammonium compounds can be used with alcohol so that the sanitizing effect lasts for longer. In hospitals, quaternary ammonium compounds and bleach are used to sanitize rooms or equipment that have been occupied by patients with influenza symptoms. At home, this can be done effectively with a diluted chlorine bleach.

During past pandemics, closing schools, churches and theaters slowed the spread of the virus but did not have a large effect on the overall death rate. It is uncertain if reducing public gatherings, by for example closing schools and workplaces, will reduce transmission since people with influenza may just be moved from one area to another; such measures would also be difficult to enforce and might be unpopular. When small numbers of people are infected, isolating the sick might reduce the risk of transmission.

Treatment

People with the flu are advised to get plenty of rest, drink plenty of liquids, avoid using alcohol and tobacco and, if necessary, take medications such as acetaminophen (paracetamol) to relieve the fever and muscle aches associated with the flu. Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin during an influenza infection (especially influenza type B), because doing so can lead to Reye's syndrome, a rare but potentially fatal disease of the liver. Since influenza is caused by a virus, antibiotics have no effect on the infection; unless prescribed for secondary infections such as bacterial pneumonia. Antiviral medication can be effective, but some strains of influenza can show resistance to the standard antiviral drugs.

The two classes of antiviral drugs used against influenza are neuraminidase inhibitors and M2 protein inhibitors (adamantane derivatives). Neuraminidase inhibitors are currently preferred for flu virus infections since they are less toxic and more effective. The CDC recommended against using M2 inhibitors during the 2005–06 influenza season due to high levels of drug resistance. As pregnant women seem to be more severely affected than the general population by the 2009 H1N1 influenza virus, prompt treatment with anti-influenza drugs has been recommended.

Neuraminidase inhibitors

Antiviral drugs such as oseltamivir (trade name Tamiflu) and zanamivir (trade name Relenza) are neuraminidase inhibitors that are designed to halt the spread of the virus in the body. These drugs are often effective against both influenza A and B. The Cochrane Collaboration reviewed these drugs and concluded that they reduce symptoms and complications. Different strains of influenza viruses have differing degrees of resistance against these antivirals, and it is impossible to predict what degree of resistance a future pandemic strain might have.

M2 inhibitors (adamantanes)

The antiviral drugs amantadine and rimantadine block a viral ion channel (M2 protein) and prevent the virus from infecting cells. These drugs are sometimes effective against influenza A if given early in the infection but are always ineffective against influenza B because B viruses do not possess M2 molecules. Measured resistance to amantadine and rimantadine in American isolates of H3N2 has increased to 91% in 2005. This high level of resistance may be due to the easy availability of amantadines as part of over-the-counter cold remedies in countries such as China and Russia, and their use to prevent outbreaks of influenza in farmed poultry.

Prognosis

Influenza's effects are much more severe and last longer than those of the common cold. Most people will recover completely in about one to two weeks, but others will develop life-threatening complications (such as pneumonia). Influenza, thus, can be deadly, especially for the weak, young and old, or chronically ill. People with a weak immune system, such as people with advanced HIV infection or transplant patients (whose immune systems are medically suppressed to prevent transplant organ rejection), suffer from particularly severe disease. Other high-risk groups include pregnant women and young children.

The flu can worsen chronic health problems. People with emphysema, chronic bronchitis or asthma may experience shortness of breath while they have the flu, and influenza may cause worsening of coronary heart disease or congestive heart failure. Smoking is another risk factor associated with more serious disease and increased mortality from influenza.

According to the World Health Organization: "Every winter, tens of millions of people get the flu. Most are only ill and out of work for a week, yet the elderly are at a higher risk of death from the illness. We know the worldwide death toll exceeds a few hundred thousand people a year, but even in developed countries the numbers are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness." Even healthy people can be affected, and serious problems from influenza can happen at any age. People over 50 years old, very young children and people of any age with chronic medical conditions are more likely to get complications from influenza, such as pneumonia, bronchitis, sinus, and ear infections.

In some cases, an autoimmune response to an influenza infection may contribute to the development of Guillain-Barré syndrome. However, as many other infections can increase the risk of this disease, influenza may only be an important cause during epidemics. This syndrome can also be a rare side-effect of influenza vaccines, with an incidence of about one case per million vaccinations