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Influenza (Flu) Print E-mail

Dr. Kennedy

Influenza, aka "flu," is an infectious disease of mammals and birds caused by RNA viruses of the family Orthomyxoviridae (the influenza viruses). The word "influenza" is Italian meaning "influence," (L. influentia) and comes from a time when astrological influences wre considered relevant, even in the scientific community of the tijme. Later the disease came to be called influenza del freddo ("influence of the cold") deriving from another myth which persists to this day outside of medical science. The word influenza was first used in English in 1743 when it was used to refer to an outbreak of the disease in Europe.

In humans, common symptoms of the disease are the chills, fever, sore throat, muscle pains, severe headache, coughing, weakness and general malaise (discomfort, just plain feeling bad). In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Although sometimes confused with the common cold, influenza is a more severe illness and is caused by a different type of virus. Influenza can produce nausea and vomiting, especially in children, but these symptoms are more characteristic of the unrelated gastroenteritis, which is sometimes called "24-hour flu" or"stomach flu."

Influenza is usually transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections also occur through contact with these body fluids or with contaminated surfaces. Flu viruses remain infectious for about one week at human body temperature, over 30 days at freezing (32 °F and 0 °C), and for much longer periods at very low temperatures which explains why epidemics of inflenza tend to occur in cold weather. Most influenza strains can be inactivated easily by disinfectants and detergents.

In the modern age flu spreads around the world in seasonal epidemics thanks fo the ease of travel, killing millions of people in pandemic years and hundreds of thousands in non-pandemic years. Three 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 result from the spread of an existing flu virus to humans from other animal species. A deadly avian strain named H5N1 has posed the greatest risk for a new influenza pandemic since it first killed humans in Asia in the 1990s. Fortunately, this virus has not yet mutated to a form that spreads easily between people. Here are the major pandemics with estimated numbers of fatalities of the recent past:

  • Asiatic (Russian) Flu 1889-90 1 million (possibly H2N2)
  • Spanish Flu 1918-20 40 million (H1N1)
  • Asian Flu 1957-58 1 to 1.5 million (H2N2)
  • Hong Kong Flu 1968-69 0.75 to 1 million (H3N2)

    Symptoms and Diagnosis

    Influenza spreads by aerosols created by coughs or sneezes.In humans. The effects are much more severe and last longer than those of the common cold. Recovery takes about one to two to three weeks. Furthermore, influenza can be fatal, especially for the weak, old or chronically ill, except for H5N1 (the 1918-19 pandemic) which selectively took out people with robust immune systems. Influenza can worsen chronic health problems. People with emphysema, chronic bronchitis or asthma may experience increased shortness of breath while they have the flu, and influenza may cause worsening of coronary heart disease or congestive heart failure. Smoking increases mortality from influenza. Symptoms can start begin suddenly one to two days after infection. Usually the first symptom is a chill, but fever is also common early in the infection with body temperatures as high as 103 °F (approximately 39 °C). Many people are so ill that they are confined to bed for several days, with aches and pains throughout their bodies, worst in the backs and legs. Symptoms of influenza may include:

    • Extreme coldness and fever
    • Body aches, especially joints and throat
    • Fatigue
    • Headache
    • Coughing and sneezing
    • Irritated watering eyes
    • Nasal congestion
    • Reddened eyes, skin (especially face), mouth, throat and nose
    • Abdominal pain (in children with influenza B)

    Most people who get influenza will recover in one to two weeks, but others will develop life-threatening complications (such as pneumonia). The world-wide death toll exceeds a few hundred thousand people a year.

    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.

    Mutation and Spread

    New influenza viruses are constantly being produced by mutation or by reassortment of genetic information. Mutations can cause small changes in the hemagglutinin and neuraminidase antigens on the surface of the virus which is called antigenic drift, and this creates an increasing variety of strains over time until one of the variants eventually achieves higher fitness, becomes dominant, sweeps through the human population. When influenza viruses reassort, they may acquire new antigens - for example by reassortment between avian strains and human strains; this is called antigenic shift. If a human influenza virus is produced with entirely novel antigens, everyone will be susceptible, and the new influenza will spread uncontrollably, causing a pandemic.

    Vaccinations against influenza are usually given to people in developed countries with a high risk of contracting the disease as well as to farmed poultry. The most common human vaccine is the trivalent influenza vaccine that contains purified and inactivated material from three viral strains. Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance Network. The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time, and different strains become dominant. The efficacy of flu vaccine is a matter of debate with many health professionals having the opinion that the risks of flu vaccine outweigh the benefits.

    History

    The symptoms of influenza were described by Hippocrates about 2400 years ago. Since then, the virus has caused numerous pandemics. Historical data are difficult to interpret because the symptoms can be similar to those of other diseases. The first convincing record of an influenza pandemic was of an outbreak in 1580, which began in Asia and spread to Europe via Africa. In Rome, over 8,000 people were killed, and several Spanish cities were almost wiped out. Pandemics continued sporadically throughout the 17th and 18th centuries, with the pandemic of 1830–1833 being particularly widespread; it infected approximately 1/4 of the people exposed.

    The most famous and deadly outbreak was the Spanish flu pandemic (type A, H1N1), of 1918 - 1919. Current estimates say place the cost of that event at 50 million to 100 million people worldwide. This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death (Bubonic Plague) of the middle ages (widely thought to have been caused by the bacterium Yersinia pestis. The monstrous death toll of 1918-19 was caused by an extremely high infection rate of up to 50% combined with extreme severity of symptoms, suspected to be caused by cytokine storms in which a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various inflammatory agents called cytokines. In other words, the virus induces to patient to kill himself. Usually pneumonia intervened to cause death, but the virus also provoked people directly, causing massive hemorrhages and edema in the lung.

    The Spanish flu pandemic was global, spreading even to remote islands and to the Arctic killing a high percentage (up to 20%, about one in five) of those infected, as opposed to the more usual flu epidemic mortality rate of one in 1000. It mostly killed young adults, with 99% of deaths occurring in people under 65, and more than 50% of infected young adults 20 to 40 years of age. This is unusual since influenza is normally most deadly ing the very young (under age 2) and the very old (over age 70), but it makes sense because the disease kills by over-stimulating the immune system. Naturally, those with the strongest immune systems would over-react most effectively. It is estimated that 2.5% to 5% of the world's population was killed by the Spanish flu pandemic of 1918-19. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 years.

    Later flu pandemics were not so devastating, but even these smaller outbreaks killed millions. In later pandemics antibiotics were available to control secondary infections and this may have helped reduce mortality compared to the Spanish Flu. Although there were scares in New Jersey in 1976 with the Swine Flu, worldwide in 1977 with the Russian Flu, and in Hong Kong and other Asian countries in 1997 (with H5N1 avian influenza), there have been no major pandemics since the 1968 Hong Kong Flu. Immunity to previous pandemic influenza strains and vaccination may have limited the spread of the virus and may have helped prevent further pandemics or we may have just been lucky to this point.

    Discovery of Causative Agents

    The cause of influenza, the Orthomyxoviridae family of viruses, was first discovered in pigs by Richard Schope in 1931. Schope's discovery was shortly followed by the isolation of the virus from humans by a group at the Medical Research Council of the United Kingdom in 1933. Wendell Stanley first crystallized tobacco mosaic virus in 1935 and for the firs time the non-cellular nature of viruses was discerned. The first killed-virus vacccine was developed in 1944 by Thomas Francis, Jr at the University of Michigan with the support of the U.S. Army which was deeply involved in this research due to its experience of influenza in World War I when thousands of troops were killed by the virus in just a few months.

    Microbiology

    The type A viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. The influenza A virus can be subdivided into different serotypes based on the antibody response to these viruses. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:

    • H1N1 caused Spanish Flu
    • H1N2 is endemic in humans and pigs
    • H2N2 caused Asian Flu
    • H3N2 caused Hong Kong Flu
    • H5N1 is a pandemic threat in the 2007–08 flu season
    • H7N7 has unusual zoonotic potential (refers to a disease that normally exists in animals but that can infect humans)
    • H7N2 a subtype of bird flu A virus rarely infeccting humans (4 cases, fully recovered)
    • H7N3 a subtype of bird flu A virus rarely infeccting humans (2 cases, fully recovered)
    • H9N2 a subtype of bird flu A virus rarely infeccting humans (3 cases, fully recovered)
    • H10N7 a subtype of bird flu A virus rarely infeccting humans (2 cases, infants, outcome unknown)

    Influenza B virus is almost exclusively a human pathogen and is less common in humans than influenza A. The only other animal known to be susceptible to influenza B infection is the seal. This type of influenza mutates at a rate 2–3 times slower than type A and consequently is less genetically diverse, with only one influenza B serotype. Therefore, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that permanent immunity is not possible. This reduced rate of mutation, combined with its limited host range ensures that pandemics of influenza B do not occur. Influenza C virus infects humans and pigs and can cause severe illness and localized epidemics. However, influenza C is less common than the other types and usually seems to cause mild disease in children.

    Prevention

    Vaccination against influenza with an influenza vaccine is often recommended for high-risk groups, such as children and the elderly. 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. Also, 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 is variable. Due to the high mutation rate of the virus, a particular influenza vaccine usually confers protection for no more than a few years. Each 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.

    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.

    Since influenza spreads through aerosols and contact with contaminated surfaces, it is important to educate people to cover their mouths while sneezing and to wash their hands regularly. Surface sanitization is recommended in areas where influenza may be present on surfaces. Alcohol is an effective sanitizer against influenza viruses, while quaternary ammonium compounds can be used with alcohol to increase the duration of the sanitizing action. In hospitals, quaternary ammonium compounds and halogen-releasing agents such as sodium hypochlorite are commonly used to sanitize rooms or equipment that have been occupied by patients with influenza symptoms. 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.

    Treatment

    The most effective treatment I have found for influenza in large dose intravenous vitamin C. Routine recommendation for influenza include rest, plenty of liquids, avoid alcohol and tobacco and, if necessary, take medications such as paracetamol (acetaminophen) to relieve fever and muscle aches. Children and teenagers with flu symptoms (especially fever) should avoid taking aspirin (especially influenza type B), because it 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, and furthermore they can lead to resistant bacterial infection. Antiviral medication is sometimes effective, but viruses can develop resistance to the standard antiviral drugs. The two classes of anti-virals are neuraminidase inhibitors and M2 inhibitors (adamantane derivatives). Neuraminidase inhibitors are currently preferred for flu virus infections. Antiviral drugs such as oseltamivir (trade name Tamiflu) and zanamivir (trade name Relenza) are neuraminidase inhibitors designed to halt the spread of the virus within the body. These drugs are often effective against both influenza A and B. The M2 inhibitors (adamantanes) are amantadine and rimantadine and are designed to block a viral ion channel (M2 protein) and thus prevent the virus from infecting cells. These drugs are sometimes effective against influenza A if given early in the infection but are ineffective against influenza B. Resistance to amantadine and rimantadine in American isolates of H3N2 has increased to 91% in 2005.



The information in this article is not meant to be medical advice.�Treatment for a medical condition should come at the recommendation of your personal physician.

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