Influenza
Encyclopedia
Influenza, commonly referred to as the flu, is an infectious disease
caused by RNA virus
es of the family Orthomyxoviridae
(the influenza viruses), that affects bird
s and mammal
s. The most common symptoms of the disease are chills, fever
, sore throat
, muscle pains
, severe headache
, cough
ing, weakness/fatigue and general discomfort
.
Although it is often confused with other influenza-like illness
es, especially the common cold
, influenza is a 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, inaccurately, referred to as "stomach flu." Flu can occasionally cause either direct viral pneumonia or secondary bacterial pneumonia.
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 detergent
s. 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 between 250,000 and 500,000 people every year, up to millions in some pandemic
years. On average 41,400 people died each year in the United States
between 1979 and 2001 from influenza. In 2010 the Centers for Disease Control and Prevention
(CDC) in the United States
changed the way it reports the 30 year estimates for deaths. Now they are reported as a range from a low of about 3,300 deaths to a high of 49,000 per year.
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 gene
s 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, the strain actually having a lower mortality rate than common flu outbreaks.
Vaccinations against influenza are usually made available to people in developed countries
. Farmed poultry is often vaccinated to avoid decimation of the flocks. The most common human vaccine is the trivalent influenza vaccine (TIV) that contains purified and inactivated antigens against 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 drug
s can be used to treat influenza, with neuraminidase inhibitor
s (such as Tamiflu or Relenza) being particularly effective.
In virus classification
influenza viruses are RNA viruses that make up three of the five genera
of the family Orthomyxoviridae
:
These viruses are only distantly related to the human parainfluenza viruses
, which are RNA viruses belonging to the paramyxovirus
family that are a common cause of respiratory infections in children such as croup
, but can also cause a disease similar to influenza in adults.
s.
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:
This genus has one species, influenza B virus. Influenza B almost exclusively infects humans and is less common than influenza A. The only other animals known to be susceptible to influenza B infection are the seal
and the ferret
. 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. As a result of this lack of antigen
ic diversity, a degree of immunity
to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift
), ensures that pandemics of influenza B do not occur.
s in diameter and usually roughly spherical, although filamentous forms can occur. These filamentous forms are more common in influenza C, which can form cordlike structures up to 500 micrometer
s long on the surfaces of infected cells. However, despite these varied shapes, the viral particles of all influenza viruses are similar in composition. These are made of a viral envelope
containing two main types of glycoprotein
s, wrapped around a central core. The central core contains the viral RNA
genome
and other viral proteins that package and protect this RNA. RNA tends to be single stranded but in special cases it is double. Unusually for a virus, its genome is not a single piece of nucleic acid
; instead, it contains seven or eight pieces of segmented negative-sense RNA, each piece of RNA containing either one or two gene
s, which code for a gene product (protein). For example, the influenza A genome contains 11 genes on eight pieces of RNA, encoding for 11 protein
s: hemagglutinin (HA), neuraminidase
(NA), nucleoprotein
(NP), M1
, M2
, NS1
, NS2(NEP: nuclear export protein), PA, PB1 (polymerase basic 1), PB1-F2 and PB2.
Hemagglutinin (HA) and neuraminidase (NA) are the two large glycoproteins on the outside of the viral particles. HA is a lectin
that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. Thus, these proteins are targets for antiviral drugs. Furthermore, they are antigen
s to which antibodies can be raised. Influenza A viruses are classified into subtypes based on antibody responses to HA and NA. These different types of HA and NA form the basis of the H and N distinctions in, for example, H5N1. There are 16 H and 9 N subtypes known, but only H 1, 2 and 3, and N 1 and 2 are commonly found in humans.
Viruses can replicate only in living cells. Influenza infection and replication is a multi-step process: First, the virus has to bind to and enter the cell, then deliver its genome to a site where it can produce new copies of viral proteins and RNA, assemble these components into new viral particles, and, last, exit the host cell.
Influenza viruses bind through hemagglutinin
onto sialic acid
sugars on the surfaces of epithelial cells
, typically in the nose, throat, and lung
s of mammals, and intestine
s of birds (Stage 1 in infection figure). After the hemagglutinin is cleaved
by a protease
, the cell imports the virus by endocytosis
.
The intracellular details are still being worked out. It is known that virons converge to the microtubule
organizing center, interact with acidic endosomes and finally enter the target endosomes for genome release.
Once inside the cell, the acidic conditions in the endosome
cause two events to happen: First, part of the hemagglutinin protein fuses the viral envelope
with the vacuole's membrane, then the M2 ion channel
allows proton
s to move through the viral envelope and acidify the core of the virus, which causes the core to dissemble and release the viral RNA and core proteins. The viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase
are then released into the cytoplasm
(Stage 2). The M2 ion channel is blocked by amantadine
drugs, preventing infection.
These core proteins and vRNA form a complex that is transported into the cell nucleus
, where the RNA-dependent RNA polymerase begins transcribing complementary positive-sense vRNA (Steps 3a and b). The vRNA either is exported into the cytoplasm and translated (step 4) or remains in the nucleus. Newly synthesized viral proteins are either secreted through the Golgi apparatus
onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotide
s for vRNA synthesis and also inhibiting translation of host-cell mRNAs.
Negative-sense vRNAs that form the genome
s of future viruses, RNA-dependent RNA polymerase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core
proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane
, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase
has cleaved sialic acid residues from the host cell. Drugs that inhibit neuraminidase, such as oseltamivir
, therefore, prevent the release of new infectious viruses and halt viral replication. After the release of new influenza viruses, the host cell dies.
Because of the absence of RNA proofreading
enzymes, the RNA-dependent RNA polymerase that copies the viral genome makes an error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, the majority of newly manufactured influenza viruses are mutants; this causes antigenic drift
, which is a slow change in the antigens on the viral surface over time. The separation of the genome into eight separate segments of vRNA allows mixing or reassortment
of vRNAs if more than one type of influenza virus infects a single cell. The resulting rapid change in viral genetics produces antigenic shift
s, which are sudden changes from one antigen to another. These sudden large changes allow the virus to infect new host species and quickly overcome protective immunity. This is important in the emergence of pandemics, as discussed below in the section on Epidemiology.
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:
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 drug
s 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%).
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 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).
The mechanisms by which influenza infection causes symptoms in humans have been studied intensively. One of the mechanisms is believed to be the inhibition of adrenocorticotropic hormone (ACTH) resulting in lowered cortisol levels.
Knowing which genes are carried by a particular strain can help predict how well it will infect humans and how severe this infection will be (that is, predict the strain's pathophysiology
).
For instance, part of the process that allows influenza viruses to invade cells is the cleavage
of the viral hemagglutinin
protein by any one of several human protease
s. In mild and avirulent viruses, the structure of the hemagglutinin means that it can only be cleaved by proteases found in the throat and lungs, so these viruses cannot infect other tissues. However, in highly virulent strains, such as H5N1, the hemagglutinin can be cleaved by a wide variety of proteases, allowing the virus to spread throughout the body.
The viral hemagglutinin protein is responsible for determining both which species a strain can infect and where in the human respiratory tract
a strain of influenza will bind. Strains that are easily transmitted between people have hemagglutinin proteins that bind to receptors in the upper part of the respiratory tract, such as in the nose, throat and mouth. In contrast, the highly lethal H5N1 strain binds to receptors that are mostly found deep in the lungs. This difference in the site of infection may be part of the reason why the H5N1 strain causes severe viral pneumonia in the lungs, but is not easily transmitted by people coughing and sneezing.
Common symptoms of the flu such as fever, headaches, and fatigue are the result of the huge amounts of proinflammatory cytokine
s and chemokine
s (such as interferon
or tumor necrosis factor) produced from influenza-infected cells. In contrast to the rhinovirus
that causes the common cold
, influenza does cause tissue damage, so symptoms are not entirely due to the inflammatory response
. This massive immune response might produce a life-threatening cytokine storm
. This effect has been proposed to be the cause of the unusual lethality of both the H5N1 avian influenza, and the 1918 pandemic strain. However, another possibility is that these large amounts of cytokines are just a result of the massive levels of viral replication produced by these strains, and the immune response does not itself contribute to the disease.
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.
In 2011, there has been some research success towards a “universal flu vaccine” that produces antibodies against proteins on the viral coat which mutate less rapidly, and thus a single shot could potentially provide longer-lasting protection.
s 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.
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.
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, antibiotic
s 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. In a November 2009 press conference, the World Health Organization recommended that persons in high risk groups, including pregnant women, children under two, and persons with respiratory problems, begin taking antivirals as soon as they start experiencing flu symptoms. Antivirals include oseltamivir (Tamiflu) and zanamivir (Relenza).
(trade name Tamiflu) and zanamivir (trade name Relenza) are neuraminidase inhibitor
s 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.
s 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.
. 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 has been believed to also be a rare side effect of influenza vaccines. Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in the NEJM covering close to 100 million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain-Barre syndrome
, (0.1%) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects; "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." Getting infected by influenza itself increases both the risk of death (up to 1 in 10,000) and increases the risk of developing GBS to a much higher level than the highest level of suspected vaccine involvement (approx. 10 times higher by recent estimates).
and Southern Hemisphere
s have winter at different times of the year, there are actually two different flu seasons each year. This is why the World Health Organization (assisted by the National Influenza Centers
) makes recommendations for two different vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere.
A long-standing puzzle has been why outbreaks of the flu occur seasonally rather than uniformly throughout the year. One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this promotes transmission from person to person. Increased travel due to the Northern Hemisphere winter holiday season may also play a role. Another factor is that cold temperatures lead to drier air, which may dehydrate mucus, preventing the body from effectively expelling virus particles. The virus also survives longer on surfaces at colder temperatures and aerosol transmission of the virus is highest in cold environments (less than 5 °C) with low relative humidity. Indeed, the lower air humidity in winter seems to be the main cause of seasonal influenza transmission in temperate regions.
However, seasonal changes in infection rates also occur in tropical regions, and in some countries these peaks of infection are seen mainly during the rainy season. Seasonal changes in contact rates from school terms, which are a major factor in other childhood diseases such as measles
and pertussis
, may also play a role in the flu. A combination of these small seasonal effects may be amplified by dynamical resonance with the endogenous disease cycles. H5N1
exhibits seasonality in both humans and birds.
An alternative hypothesis to explain seasonality in influenza infections is an effect of vitamin D
levels on immunity to the virus. This idea was first proposed by Robert Edgar Hope-Simpson
in 1965. He proposed that the cause of influenza epidemics during winter may be connected to seasonal fluctuations of vitamin D, which is produced in the skin under the influence of solar (or artificial) UV radiation
. This could explain why influenza occurs mostly in winter and during the tropical rainy season, when people stay indoors, away from the sun, and their vitamin D levels fall.
As influenza is caused by a variety of species and strains of virus
es, in any given year some strains can die out while others create epidemic
s, while yet another strain can cause a pandemic
. Typically, in a year's normal two flu season
s (one per hemisphere), there are between three and five million cases of severe illness and up to 500,000 deaths worldwide, which by some definitions is a yearly influenza epidemic. Although the incidence of influenza can vary widely between years, approximately 36,000 deaths and more than 200,000 hospitalizations are directly associated with influenza every year in the United States. Roughly three times per century, a pandemic occurs, which infects a large proportion of the world's population and can kill tens of millions of people (see history section). Indeed, one study estimated that if a strain with similar virulence
to the 1918 influenza emerged today, it could kill between 50 and 80 million people.
New influenza viruses are constantly evolving
by mutation
or by reassortment
. Mutations can cause small changes in the hemagglutinin
and neuraminidase
antigen
s on the surface of the virus. This is called antigenic drift
, which slowly creates an increasing variety of strains until one evolves that can infect people who are immune to the pre-existing strains. This new variant then replaces the older strains as it rapidly sweeps through the human population—often causing an epidemic. However, since the strains produced by drift will still be reasonably similar to the older strains, some people will still be immune to them. In contrast, when influenza viruses reassort, they acquire completely new antigens—for example by reassortment between avian strains and human strains; this is called antigenic shift
. If a human influenza virus is produced that has entirely new antigens, everybody will be susceptible, and the novel influenza will spread uncontrollably, causing a pandemic. In contrast to this model of pandemics based on antigenic drift and shift, an alternative approach has been proposed where the periodic pandemics are produced by interactions of a fixed set of viral strains with a human population with a constantly changing set of immunities to different viral strains.
From a public health point of view, flu epidemics spread rapidly and are very difficult to control. Most influenza virus strains are not very infectious and each infected individual will only go on to infect one or two other individuals (the basic reproduction number for influenza is generally around 1.4). However, the generation time for influenza is extremely short: the time from a person becoming infected to when he infects the next person is only two days. The short generation time means that influenza epidemics generally peak at around 2 months and burn out after 3 months : the decision to intervene in an influenza epidemic therefore has to be taken early, and the decision is therefore often made on the back of incomplete data. Another problem is that individuals become infectious before they become symptomatic, which means that putting people in quarantine after they become ill is not an effective public health intervention.
meaning "influence" and refers to the cause of the disease; initially, this ascribed illness to unfavorable astrological
influences. Changes in medical thought led to its modification to influenza del freddo, meaning "influence of the cold". The word influenza was first used in English to refer to the disease we know today in 1703 by J. Hugger of the University of Edinburgh in his thesis De Catarrho epidemio, vel Influenza, prout in India occidentali sese ostendit.
Archaic terms for influenza include epidemic catarrh, grippe (from the French, first used by Molyneaux in 1694 ), sweating sickness, and Spanish fever (particularly for the 1918 flu pandemic strain).
The symptoms of human influenza were clearly described by Hippocrates
roughly 2,400 years ago. Although the virus seems to have caused epidemics throughout human history, historical data on influenza are difficult to interpret, because the symptoms can be similar to those of other respiratory diseases. The disease may have spread from Europe to the Americas as early as the European colonization of the Americas
; since almost the entire indigenous population of the Antilles was killed by an epidemic resembling influenza that broke out in 1493, after the arrival of Christopher Columbus
.
The first convincing record of an influenza pandemic was of an outbreak in 1580, which began in Russia 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 a quarter of the people exposed.
The most famous and lethal outbreak was the 1918 flu pandemic (Spanish flu pandemic) (type A influenza
, H1N1
subtype), which lasted from 1918 to 1919. It is not known exactly how many it killed, but estimates range from 20 to 100 million people. This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death
. This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storm
s. Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera
, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membrane
s, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages
in the skin also occurred." The majority of deaths were from bacterial pneumonia
, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages
and edema
in the lung.
The 1918 flu pandemic (Spanish flu pandemic) was truly global, spreading even to the Arctic
and remote Pacific islands
. The unusually severe disease killed between 2 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate
of 0.1%. Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65, and more than half in young adults 20 to 40 years old. This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918–1919 pandemic is not known, but it is estimated that 2.5% to 5% of the world's population was killed. 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. They included the 1957 Asian Flu
(type A, H2N2
strain) and the 1968 Hong Kong Flu
(type A, H3N2
strain), but even these smaller outbreaks killed millions of people. In later pandemics antibiotic
s were available to control secondary infections and this may have helped reduce mortality compared to the Spanish Flu of 1918.
The first influenza virus to be isolated was from poultry, when in 1901 the agent causing a disease called "fowl plague" was passed through Chamberland filter
s, which have pores that are too small for bacteria
to pass through. The etiological
cause of influenza, the Orthomyxoviridae family of viruses, was first discovered in pig
s by Richard Shope
in 1931. This discovery was shortly followed by the isolation of the virus from humans by a group headed by Patrick Laidlaw
at the Medical Research Council
of the United Kingdom
in 1933. However, it was not until Wendell Stanley first crystallized tobacco mosaic virus
in 1935 that the non-cellular
nature of viruses was appreciated.
The first significant step towards preventing influenza was the development in 1944 of a killed-virus vaccine for influenza by Thomas Francis, Jr.
. This built on work by Australian Frank Macfarlane Burnet
, who showed that the virus lost virulence when it was cultured in fertilized hen's eggs. Application of this observation by Francis allowed his group of researchers at the University of Michigan
to develop the first influenza vaccine, with support from the U.S. Army
. The Army 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 a matter of months. In comparison to vaccines, the development of anti-influenza drugs has been slower, with amantadine
being licensed in 1966 and, almost thirty years later, the next class of drugs (the neuraminidase inhibitor
s) being developed.
due to lost productivity
and associated medical treatment, as well as indirect costs
of preventative measures. In the United States, influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs. However, the economic impacts of past pandemics have not been intensively studied, and some authors have suggested that the Spanish influenza
actually had a positive long-term effect on per-capita income growth, despite a large reduction in the working population and severe short-term depressive
effects. Other studies have attempted to predict the costs of a pandemic as serious as the 1918 Spanish flu on the U.S. economy
, where 30% of all workers became ill, and 2.5% were killed. A 30% sickness rate and a three-week length of illness would decrease the gross domestic product
by 5%. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.
Preventative costs are also high. Governments worldwide have spent billions of U.S. dollars
preparing and planning for a potential H5N1 avian influenza pandemic, with costs associated with purchasing drugs and vaccines as well as developing disaster drills
and strategies for improved border control
s. On 1 November 2005, United States President
George W. Bush
unveiled the National Strategy to Safeguard Against the Danger of Pandemic Influenza backed by a request to Congress
for $7.1 billion to begin implementing the plan. Internationally, on 18 January 2006, donor nations pledged US$2 billion to combat bird flu at the two-day International Pledging Conference on Avian and Human Influenza held in China.
In an assessment of the 2009 H1N1 pandemic on selected countries in the Southern Hemisphere, data suggest that all countries experienced some time-limited and/or geographically isolated socio/economic effects and a temporary decrease in tourism most likely due to fear of 2009 H1N1 disease. It is still too early to determine whether the H1N1 pandemic has caused any long-term economic impacts.
Research on influenza includes studies on molecular virology
, how the virus produces disease (pathogenesis
), host immune responses, viral genomics
, and how the virus spreads (epidemiology
). These studies help in developing influenza countermeasures; for example, a better understanding of the body's immune system response helps vaccine
development, and a detailed picture of how influenza invades cells aids the development of antiviral drugs. One important basic research
program is the Influenza Genome Sequencing Project
, which is creating a library of influenza sequences; this library should help clarify which factors make one strain more lethal than another, which genes most affect immunogenicity
, and how the virus evolves
over time.
Research into new vaccines is particularly important, as current vaccines are very slow and expensive to produce and must be reformulated every year. The sequencing of the influenza genome and recombinant DNA
technology may accelerate the generation of new vaccine strains by allowing scientists to substitute new antigens into a previously developed vaccine strain. New technologies are also being developed to grow viruses in cell culture
, which promises higher yields, less cost, better quality and surge capacity. Research on a universal influenza A vaccine, targeted against the external domain of the transmembrane viral M2 protein
(M2e), is being done at the University of Ghent by Walter Fiers
, Xavier Saelens
and their team and has now successfully concluded Phase I clinical trials.
A number of biologics
, therapeutic vaccines and immunobiologics are also being investigated for treatment of infection caused by viruses. Therapeutic biologics are designed to activate the immune response to virus or antigens. Typically, biologics do not target metabolic pathway
s like anti-viral drugs, but stimulate immune cells such as lymphocytes, macrophages, and/or antigen presenting cells, in an effort to drive an immune response towards a cytotoxic effect against the virus. Influenza models, such as murine influenza, are convenient models to test the effects of prophylactic and therapeutic biologics. For example, Lymphocyte T-Cell Immune Modulator
inhibits viral growth in the murine model of influenza.
s are thought to be the main animal reservoirs
of influenza viruses. Sixteen forms of hemagglutinin
and nine forms of neuraminidase
have been identified. All known subtypes (HxNy) are found in birds, but many subtypes are endemic in humans, dog
s, horse
s, and pig
s; populations of camel
s, ferret
s, cat
s, seals
, mink
, and whale
s also show evidence of prior infection or exposure to influenza. Variants of flu virus are sometimes named according to the species the strain is endemic in or adapted to. The main variants named using this convention are: Bird Flu, Human Flu
, Swine Flu
, Horse Flu
and Dog Flu. (Cat flu
generally refers to Feline viral rhinotracheitis
or Feline calicivirus
and not infection from an influenza virus.) In pigs, horses and dogs, influenza symptoms are similar to humans, with cough, fever and loss of appetite
. The frequency of animal diseases are not as well-studied as human infection, but an outbreak of influenza in harbor seals caused approximately 500 seal deaths off the New England
coast in 1979–1980. On the other hand, outbreaks in pigs are common and do not cause severe mortality.
combined with minor respiratory disease
. Since these mild symptoms can make diagnosis in the field difficult, tracking the spread of avian influenza
requires laboratory testing of samples from infected birds. Some strains such as Asian H9N2
are highly virulent to poultry and may cause more extreme symptoms and significant mortality. In its most highly pathogenic form, influenza in chicken
s and turkeys
produces a sudden appearance of severe symptoms and almost 100% mortality within two days. As the virus spreads rapidly in the crowded conditions seen in the intensive farming
of chickens and turkeys, these outbreaks can cause large economic losses to poultry farmers.
An avian-adapted, highly pathogenic strain of H5N1 (called HPAI A(H5N1), for "highly pathogenic avian influenza virus of type A of subtype H5N1") causes H5N1 flu
, commonly known as "avian influenza" or simply "bird flu", and is endemic
in many bird populations, especially in Southeast Asia
. This Asian lineage strain of HPAI A(H5N1) is spreading globally
. It is epizootic
(an epidemic in non-humans) and panzootic (a disease affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling
of hundreds of millions of other birds in an attempt to control its spread. Most references in the media to "bird flu" and most references to H5N1 are about this specific strain.
At present, HPAI A(H5N1) is an avian disease, and there is no evidence suggesting efficient human-to-human transmission of HPAI A(H5N1). In almost all cases, those infected have had extensive physical contact with infected birds. In the future, H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. The exact changes that are required for this to happen are not well understood. However, due to the high lethality and virulence
of H5N1, its endemic
presence, and its large and increasing biological host reservoir, the H5N1 virus was the world's pandemic threat in the 2006–07 flu season, and billions of dollars are being raised and spent researching H5N1 and preparing for a potential influenza pandemic.
In pigs swine influenza produces fever, lethargy, sneezing, coughing, difficulty breathing and decreased appetite. In some cases the infection can cause abortion. Although mortality is usually low, the virus can produce weight loss and poor growth, causing economic loss to farmers. Infected pigs can lose up to 12 pounds of body weight over a 3 to 4 week period. Direct transmission of an influenza virus from pigs to humans is occasionally possible (this is called zoonotic
swine flu). In all, 50 human cases are known to have occurred since the virus was identified in the mid-20th century, which have resulted in six deaths.
In 2009, a swine-origin H1N1
virus strain commonly referred to as "swine flu" caused the 2009 flu pandemic
, but there is no evidence that it is endemic to pigs (i.e. actually a swine flu) or of transmission from pigs to people, instead the virus is spreading from person to person. This strain is a reassortment of several strains of H1N1 that are usually found separately, in humans, birds, and pigs.
Information concerning flu research can be found at:
History
Microbiology
Pathogenesis
Epidemiology
Treatment and prevention
Research
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
caused by RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es of the family Orthomyxoviridae
Orthomyxoviridae
The Orthomyxoviridae are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described...
(the influenza viruses), that affects bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s and mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s. The most common symptoms of the disease are chills, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, sore throat
Sore throat
A sore throat or throat pain is a common physical symptom usually caused by acute pharyngitis, or throat inflammation, though it also occurs in a number of other situations, such as post trauma and in diphtheria. It can cause mild to extreme pain....
, muscle pains
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, severe headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
ing, weakness/fatigue and general discomfort
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
.
Although it is often confused with other influenza-like illness
Influenza-like illness
Influenza-like illness , also known as acute respiratory infection and flu-like syndrome, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms, with SARI referring to Severe Acute Respiratory Infection.Symptoms commonly include fever, shivering, chills,...
es, especially the common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
, influenza is a more severe disease than the common cold and is caused by a different type of virus. Influenza may produce nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, particularly in children, but these symptoms are more common in the unrelated gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...
, which is sometimes, inaccurately, referred to as "stomach flu." Flu can occasionally cause either direct viral pneumonia or secondary bacterial pneumonia.
Typically, influenza is transmitted through the air
Airborne disease
Airborne diseases refers to any diseases which are caused by pathogenic microbial agents and transmitted through the air. These viruses and bacteria can be aerosolized through coughing, sneezing, laughing or through close personal contact...
by coughs or sneezes, creating aerosols containing the virus. Influenza can also be transmitted by direct contact with bird droppings or nasal secretions
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
, 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
Sunlight
Sunlight, in the broad sense, is the total frequency spectrum of electromagnetic radiation given off by the Sun. On Earth, sunlight is filtered through the Earth's atmosphere, and solar radiation is obvious as daylight when the Sun is above the horizon.When the direct solar radiation is not blocked...
, disinfectants and detergent
Detergent
A detergent is a surfactant or a mixture of surfactants with "cleaning properties in dilute solutions." In common usage, "detergent" refers to alkylbenzenesulfonates, a family of compounds that are similar to soap but are less affected by hard water...
s. As the virus can be inactivated by soap, frequent hand washing reduces the risk of infection.
Influenza spreads around the world in seasonal epidemics
Flu season
Flu season is a annually-recurring time period characterized by the prevalence of outbreaks of influenza . The season occurs during the cold half of the year in each hemisphere. Influenza activity can sometimes be predicted and even tracked geographically...
, resulting in the deaths of between 250,000 and 500,000 people every year, up to millions in some pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
years. On average 41,400 people died each year in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
between 1979 and 2001 from influenza. In 2010 the Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
changed the way it reports the 30 year estimates for deaths. Now they are reported as a range from a low of about 3,300 deaths to a high of 49,000 per year.
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
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
of the virus in humans. Often, these new strains appear when an existing flu virus spreads to humans from other animal species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
, or when an existing human strain picks up new gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s from a virus that usually infects birds or pigs. An avian strain named H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
raised the concern of a new influenza pandemic
Influenza pandemic
An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in...
, after it emerged in Asia in the 1990s, but it has not evolved
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
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
Swine flu
Swine influenza, also called pig influenza, swine flu, hog flu and pig flu, is an infection by any one of several types of swine influenza virus. Swine influenza virus or S-OIV is any strain of the influenza family of viruses that is endemic in pigs...
" and also known as influenza A/H1N1, emerged in Mexico, the United States, and several other nations. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
officially declared the outbreak to be a pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
on June 11, 2009 (see 2009 flu pandemic
2009 flu pandemic
The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...
). The WHO's declaration of a pandemic level 6 was an indication of spread, not severity, the strain actually having a lower mortality rate than common flu outbreaks.
Vaccinations against influenza are usually made available to people in developed countries
Developed country
A developed country is a country that has a high level of development according to some criteria. Which criteria, and which countries are classified as being developed, is a contentious issue...
. Farmed poultry is often vaccinated to avoid decimation of the flocks. The most common human vaccine is the trivalent influenza vaccine (TIV) that contains purified and inactivated antigens against three viral strains. Typically, this vaccine includes material from two influenza A virus
Influenzavirus A
Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
subtypes and one influenza B virus
Influenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
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 drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s can be used to treat influenza, with neuraminidase inhibitor
Neuraminidase inhibitor
Neuraminidase inhibitors are a class of antiviral drugs targeted at the influenza virus, which work by blocking the function of the viral neuraminidase protein, thus preventing the virus from reproducing by budding from the host cell....
s (such as Tamiflu or Relenza) being particularly effective.
Types of virus
Virus classification
Virus classification is the process of naming viruses and placing them into a taxonomic system. Similar to the classification systems used for cellular organisms, virus classification is the subject of ongoing debate and proposals. This is mainly due to the pseudo-living nature of viruses, which...
influenza viruses are RNA viruses that make up three of the five genera
Genera
Genera is a commercial operating system and development environment for Lisp machines developed by Symbolics. It is essentially a fork of an earlier operating system originating on the MIT AI Lab's Lisp machines which Symbolics had used in common with LMI and Texas Instruments...
of the family Orthomyxoviridae
Orthomyxoviridae
The Orthomyxoviridae are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described...
:
- Influenzavirus AInfluenzavirus AInfluenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
- Influenzavirus BInfluenzavirus BInfluenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
- Influenzavirus CInfluenzavirus CInfluenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza...
These viruses are only distantly related to the human parainfluenza viruses
Human parainfluenza viruses
Human parainfluenza viruses are a group of four distinct serotypes of enveloped single-stranded RNA viruses belonging to the paramyxovirus family.Parainfluenza viruses can be detected via cell culture, immunofluorescent microscopy, and PCR....
, which are RNA viruses belonging to the paramyxovirus
Paramyxovirus
Paramyxoviruses are viruses of the Paramyxoviridae family of the Mononegavirales order; they are negative-sense single-stranded RNA viruses responsible for a number of human and animal diseases.-Genera:*Subfamily Paramyxovirinae**Genus Avulavirus Paramyxoviruses (from Greek para-, beyond, -myxo-,...
family that are a common cause of respiratory infections in children such as croup
Croup
Croup is a respiratory condition that is usually triggered by an acute viral infection of the upper airway. The infection leads to swelling inside the throat, which interferes with normal breathing and produces the classical symptoms of a "barking" cough, stridor, and hoarseness...
, but can also cause a disease similar to influenza in adults.
Influenzavirus A
This genus has one species, influenza A virus. Wild aquatic birds are the natural hosts for a large variety of influenza A. Occasionally, viruses are transmitted to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemicPandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
s.
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
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
response to these viruses. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
- H1N1H1N1'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
, which caused Spanish FluSpanish fluThe 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
in 1918, and Swine FluSwine fluSwine influenza, also called pig influenza, swine flu, hog flu and pig flu, is an infection by any one of several types of swine influenza virus. Swine influenza virus or S-OIV is any strain of the influenza family of viruses that is endemic in pigs...
in 2009 - H2N2H2N2H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
, which caused Asian FluAsian fluAsian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus...
in 1957 - H3N2H3N2Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...
, which caused Hong Kong FluHong Kong fluThe Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...
in 1968 - H5N1H5N1Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
, which caused Bird FluBird fluBird flu may refer to:Biology and disease* Avian influenza, influenza endemic to birds and pigeons.* Influenzavirus A, the causative agent for bird flu; the genus of the Orthomyxoviridae family...
in 2004 - H7N7H7N7H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies...
, which has unusual zoonotic potential - H1N2H1N2H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans....
, endemic in humans, pigs and birds - H9N2H9N2H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...
- H7N2H7N2H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...
- H7N3H7N3H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been...
- H10N7H10N7H10N7 is a subtype of the species Influenza A virus . In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.The first reported H10N7 outbreak in the US occurred in...
Influenzavirus B
Pinniped
Pinnipeds or fin-footed mammals are a widely distributed and diverse group of semiaquatic marine mammals comprising the families Odobenidae , Otariidae , and Phocidae .-Overview: Pinnipeds are typically sleek-bodied and barrel-shaped...
and the ferret
Ferret
The ferret is a domesticated mammal of the type Mustela putorius furo. Ferrets are sexually dimorphic predators with males being substantially larger than females. They typically have brown, black, white, or mixed fur...
. 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. As a result of this lack of antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
ic diversity, a degree of immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible. This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift
Antigenic shift
Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains...
), ensures that pandemics of influenza B do not occur.
Influenzavirus C
This genus has one species, influenza C virus, which infects humans, dogs and pigs, sometimes causing both severe illness and local epidemics. However, influenza C is less common than the other types and usually only causes mild disease in children.Structure, properties, and subtype nomenclature
Influenzaviruses A, B and C are very similar in overall structure. The virus particle is 80–120 nanometerNanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
s in diameter and usually roughly spherical, although filamentous forms can occur. These filamentous forms are more common in influenza C, which can form cordlike structures up to 500 micrometer
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...
s long on the surfaces of infected cells. However, despite these varied shapes, the viral particles of all influenza viruses are similar in composition. These are made of a viral envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
containing two main types of glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s, wrapped around a central core. The central core contains the viral RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
and other viral proteins that package and protect this RNA. RNA tends to be single stranded but in special cases it is double. Unusually for a virus, its genome is not a single piece of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
; instead, it contains seven or eight pieces of segmented negative-sense RNA, each piece of RNA containing either one or two gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s, which code for a gene product (protein). For example, the influenza A genome contains 11 genes on eight pieces of RNA, encoding for 11 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s: hemagglutinin (HA), neuraminidase
Viral neuraminidase
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell...
(NA), nucleoprotein
Influenza virus nucleoprotein
Influenza virus nucleoprotein is a structural protein which encapsidates the negative strand viral RNA. NP is one of the main determinants of species specificity. The question of how far the NP gene can cross the species barrier by reassortment and become adapted by mutation to the new host has...
(NP), M1
M1 protein
The M1 protein is a matrix protein of the influenza virus. It forms a coat inside the viral envelope.The M1 protein binds to the viral RNA. The binding is not specific to any RNA sequence, and is performed via a peptide sequence rich in basic amino acids....
, M2
M2 protein
The M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer , where the units are helices stabilized by two disulfide bonds...
, NS1
NS1 Influenza Protein
The NS1 Influenza Protein is created by the internal protein encoding, linear negative-sense, single stranded RNA, NS gene segment; which found in Influenzavirus A, Influenzavirus B and Influenzavirus C; and which also codes for the nuclear export protein or NEP, formerly referred to as the NS2...
, NS2(NEP: nuclear export protein), PA, PB1 (polymerase basic 1), PB1-F2 and PB2.
Hemagglutinin (HA) and neuraminidase (NA) are the two large glycoproteins on the outside of the viral particles. HA is a lectin
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
that mediates binding of the virus to target cells and entry of the viral genome into the target cell, while NA is involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. Thus, these proteins are targets for antiviral drugs. Furthermore, they are antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s to which antibodies can be raised. Influenza A viruses are classified into subtypes based on antibody responses to HA and NA. These different types of HA and NA form the basis of the H and N distinctions in, for example, H5N1. There are 16 H and 9 N subtypes known, but only H 1, 2 and 3, and N 1 and 2 are commonly found in humans.
Replication
Influenza viruses bind through hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
onto sialic acid
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
sugars on the surfaces of epithelial cells
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
, typically in the nose, throat, and lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s of mammals, and intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
s of birds (Stage 1 in infection figure). After the hemagglutinin is cleaved
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
by a protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
, the cell imports the virus by endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
.
The intracellular details are still being worked out. It is known that virons converge to the microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
organizing center, interact with acidic endosomes and finally enter the target endosomes for genome release.
Once inside the cell, the acidic conditions in the endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
cause two events to happen: First, part of the hemagglutinin protein fuses the viral envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
with the vacuole's membrane, then the M2 ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
allows proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
s to move through the viral envelope and acidify the core of the virus, which causes the core to dissemble and release the viral RNA and core proteins. The viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA polymerase
RNA-dependent RNA polymerase
RNA-dependent RNA polymerase , , or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template...
are then released into the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
(Stage 2). The M2 ion channel is blocked by amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
drugs, preventing infection.
These core proteins and vRNA form a complex that is transported into the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where the RNA-dependent RNA polymerase begins transcribing complementary positive-sense vRNA (Steps 3a and b). The vRNA either is exported into the cytoplasm and translated (step 4) or remains in the nucleus. Newly synthesized viral proteins are either secreted through the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
s for vRNA synthesis and also inhibiting translation of host-cell mRNAs.
Negative-sense vRNAs that form the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s of future viruses, RNA-dependent RNA polymerase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7). As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
has cleaved sialic acid residues from the host cell. Drugs that inhibit neuraminidase, such as oseltamivir
Oseltamivir
Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...
, therefore, prevent the release of new infectious viruses and halt viral replication. After the release of new influenza viruses, the host cell dies.
Because of the absence of RNA proofreading
Proofreading (biology)
The term proofreading is used in genetics to refer to the error-correcting processes, first proposed by John Hopfield and Jacques Ninio, involved in DNA replication, immune system specificity, enzyme-substrate recognition among many other processes that require enhanced specificity...
enzymes, the RNA-dependent RNA polymerase that copies the viral genome makes an error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, the majority of newly manufactured influenza viruses are mutants; this causes antigenic drift
Antigenic drift
The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific receptors, which prevent...
, which is a slow change in the antigens on the viral surface over time. The separation of the genome into eight separate segments of vRNA allows mixing or reassortment
Reassortment
Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting...
of vRNAs if more than one type of influenza virus infects a single cell. The resulting rapid change in viral genetics produces antigenic shift
Antigenic shift
Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains...
s, which are sudden changes from one antigen to another. These sudden large changes allow the virus to infect new host species and quickly overcome protective immunity. This is important in the emergence of pandemics, as discussed below in the section on Epidemiology.
Signs and symptoms
| Symptom: | sensitivity | specificity |
|---|---|---|
| Fever | 68–86% | 25–73% |
| Cough | 84–98% | 7–29% |
| Nasal congestion | 68–91% | 19–41% |
|
||
- FeverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
and extreme coldness (chills shiveringShiveringShivering is a bodily function in response to early hypothermia in warm-blooded animals. When the core body temperature drops, the shivering reflex is triggered to maintain homeostasis. Muscle groups around the vital organs begin to shake in small movements in an attempt to create warmth by...
, shaking (rigorRigor (medicine)Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
)) - CoughCoughA cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
- Nasal congestionNasal congestionNasal congestion is the blockage of the nasal passages usually due to membranes lining the nose becoming swollen from inflamed blood vessels. It is also known as nasal blockage, nasal obstruction, blocked nose, stuffy nose, or stuffed up nose.Nasal congestion has many causes and can range from a...
- Body achesMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, especially joints and throat - Fatigue
- HeadacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
- Irritated, watering eyesTearsTears are secretions that clean and lubricate the eyes. Lacrimation or lachrymation is the production or shedding of tears....
- Reddened eyes, skin (especially face)Flushing (physiology)For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
, mouth, throat and nose - Petechial RashPetechiaA petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
- In children, gastrointestinal symptoms such as diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
and abdominal painAbdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, (may be severe in children with influenza B)
It can be difficult to distinguish between the common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
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
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
"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 drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s 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
Decision analysis
Decision analysis is the discipline comprising the philosophy, theory, methodology, and professional practice necessary to address important decisions in a formal manner...
studies suggest that during local outbreaks of influenza, the prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
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
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(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
Viral culture
Viral culture is a laboratory test in which samples are placed with a cell type that the virus being tested for is able to infect. If the cells show changes, known as cytopathic effects, then the culture is positive....
. 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
Influenza virus shedding (the time during which a person might be infectious to another person) begins the day before symptoms appear and virus is then released for between 5 to 7 days, although some people may shed virus for longer periods. People who contract influenza are most infective between the second and third days after infection. The amount of virus shed appears to correlate with fever, with higher amounts of virus shed when temperatures are highest. 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
Humidity
Humidity is a term for the amount of water vapor in the air, and can refer to any one of several measurements of humidity. Formally, humid air is not "moist air" but a mixture of water vapor and other constituents of air, and humidity is defined in terms of the water content of this mixture,...
and UV radiation: with low humidity and a lack of sunlight in winter 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).
Pathophysiology
Knowing which genes are carried by a particular strain can help predict how well it will infect humans and how severe this infection will be (that is, predict the strain's pathophysiology
Pathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
).
For instance, part of the process that allows influenza viruses to invade cells is the cleavage
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
of the viral hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
protein by any one of several human protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s. In mild and avirulent viruses, the structure of the hemagglutinin means that it can only be cleaved by proteases found in the throat and lungs, so these viruses cannot infect other tissues. However, in highly virulent strains, such as H5N1, the hemagglutinin can be cleaved by a wide variety of proteases, allowing the virus to spread throughout the body.
The viral hemagglutinin protein is responsible for determining both which species a strain can infect and where in the human respiratory tract
Respiratory tract
In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
a strain of influenza will bind. Strains that are easily transmitted between people have hemagglutinin proteins that bind to receptors in the upper part of the respiratory tract, such as in the nose, throat and mouth. In contrast, the highly lethal H5N1 strain binds to receptors that are mostly found deep in the lungs. This difference in the site of infection may be part of the reason why the H5N1 strain causes severe viral pneumonia in the lungs, but is not easily transmitted by people coughing and sneezing.
Common symptoms of the flu such as fever, headaches, and fatigue are the result of the huge amounts of proinflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s (such as interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
or tumor necrosis factor) produced from influenza-infected cells. In contrast to the rhinovirus
Rhinovirus
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33–35 °C , and this may be why it occurs primarily in the nose...
that causes the common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
, influenza does cause tissue damage, so symptoms are not entirely due to the inflammatory response
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. This massive immune response might produce a life-threatening cytokine storm
Cytokine storm
A cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
. This effect has been proposed to be the cause of the unusual lethality of both the H5N1 avian influenza, and the 1918 pandemic strain. However, another possibility is that these large amounts of cytokines are just a result of the massive levels of viral replication produced by these strains, and the immune response does not itself contribute to the disease.
Vaccination
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, diabetes, heart disease
Heart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
, or are immuno-compromised. Influenza vaccines can be produced in several ways; the most common method is to grow the virus in fertilized hen
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
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
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
and the avirulent virus given as a live vaccine. The effectiveness of these influenza vaccines are variable. Due to the high mutation rate
Mutation rate
In genetics, the mutation rate is the chance of a mutation occurring in an organism or gene in each generation...
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
Pharmaceutical company
The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
to develop vaccines that will provide the best immunity against these strains. Vaccines have also been developed to protect poultry
Poultry
Poultry are domesticated birds kept by humans for the purpose of producing eggs, meat, and/or feathers. These most typically are members of the superorder Galloanserae , especially the order Galliformes and the family Anatidae , commonly known as "waterfowl"...
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
Culling
Culling is the process of removing animals from a group based on specific criteria. This is done either to reinforce certain desirable characteristics or to remove certain undesirable characteristics from the group...
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
Fujian flu
Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus...
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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
is a severe allergic reaction
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
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.
In 2011, there has been some research success towards a “universal flu vaccine” that produces antibodies against proteins on the viral coat which mutate less rapidly, and thus a single shot could potentially provide longer-lasting protection.
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 maskFace mask
Strictly, the expression face mask is tautological and means "mask", because masks by definition go on the face; but it is sometimes used to mean:*Respirator*Among divers, diving mask...
s 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.
Since influenza spreads through both aerosols and contact with contaminated surfaces, surface sanitizing may help prevent some infections. Alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
is an effective sanitizer against influenza viruses, while quaternary ammonium compounds
Quaternary ammonium cation
Quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure NR4+, R being an alkyl group or an aryl group. Unlike the ammonium ion and the primary, secondary, or tertiary ammonium cations, the quaternary ammonium cations are permanently charged,...
can be used with alcohol so that the sanitizing effect lasts for longer. In hospitals, quaternary ammonium compounds and bleach
Bleach
Bleach refers to a number of chemicals that remove color, whiten, or disinfect, often via oxidation. Common chemical bleaches include household chlorine bleach , lye, oxygen bleach , and bleaching powder...
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 alcoholAlcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
and tobacco
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
and, if necessary, take medications such as acetaminophen (paracetamol
Paracetamol
Paracetamol INN , or acetaminophen USAN , is a widely used over-the-counter analgesic and antipyretic . It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies...
) to relieve the fever and muscle aches associated with the flu. Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
during an influenza infection (especially influenza type B
Influenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
), because doing so can lead to Reye's syndrome
Reye's syndrome
Reye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar . The classic features are liver damage, aspirin use and a viral infection...
, a rare but potentially fatal disease of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Since influenza is caused by a virus, antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s have no effect on the infection; unless prescribed for secondary infections such as bacterial pneumonia
Bacterial pneumonia
Bacterial pneumonia is a type of pneumonia caused by bacterial infection.-Sign and symptoms:*Fever*Rigors*Cough*Dyspnea*Chest pain*Pneumococcal pneumonia can cause Hemoptysis-Gram positive:...
. 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
M2 protein
The M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer , where the units are helices stabilized by two disulfide bonds...
inhibitors (adamantane
Adamantane
Adamantane is a colorless, crystalline chemical compound with a camphor-like odor. With a formula C10H16, it is a cycloalkane and also the simplest diamondoid. Adamantane molecules consist of three cyclohexane rings arranged in the "armchair" configuration. It is unique in that it is both rigid...
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
Drug resistance
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...
. 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. In a November 2009 press conference, the World Health Organization recommended that persons in high risk groups, including pregnant women, children under two, and persons with respiratory problems, begin taking antivirals as soon as they start experiencing flu symptoms. Antivirals include oseltamivir (Tamiflu) and zanamivir (Relenza).
Neuraminidase inhibitors
Antiviral drugs such as oseltamivirOseltamivir
Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...
(trade name Tamiflu) and zanamivir (trade name Relenza) are neuraminidase inhibitor
Neuraminidase inhibitor
Neuraminidase inhibitors are a class of antiviral drugs targeted at the influenza virus, which work by blocking the function of the viral neuraminidase protein, thus preventing the virus from reproducing by budding from the host cell....
s 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
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
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 drugAntiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
and rimantadine
Rimantadine
Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug...
block a viral ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
(M2 protein
M2 protein
The M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer , where the units are helices stabilized by two disulfide bonds...
) 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
H3N2
Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...
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 coldCommon cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
. Most people will recover completely in about one to two weeks, but others will develop life-threatening complications (such as pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
). Influenza, thus, can be deadly, especially for the weak, young and old, or chronically ill. People with a weak immune system
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
, such as people with advanced HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
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
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
while they have the flu, and influenza may cause worsening of coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...
or congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
. Smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
is another risk factor
Risk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...
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
Bronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
, sinus
Paranasal sinus
Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity , above and between the eyes , and behind the ethmoids...
, and ear infections.
In some cases, an autoimmune response to an influenza infection may contribute to the development of Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
. However, as many other infections can increase the risk of this disease, influenza may only be an important cause during epidemics. This syndrome has been believed to also be a rare side effect of influenza vaccines. Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in the NEJM covering close to 100 million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain-Barre syndrome
Guillain-Barré syndrome
Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
, (0.1%) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects; "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." Getting infected by influenza itself increases both the risk of death (up to 1 in 10,000) and increases the risk of developing GBS to a much higher level than the highest level of suspected vaccine involvement (approx. 10 times higher by recent estimates).
Seasonal variations
Influenza reaches peak prevalence in winter, and because the NorthernNorthern Hemisphere
The Northern Hemisphere is the half of a planet that is north of its equator—the word hemisphere literally means “half sphere”. It is also that half of the celestial sphere north of the celestial equator...
and Southern Hemisphere
Southern Hemisphere
The Southern Hemisphere is the part of Earth that lies south of the equator. The word hemisphere literally means 'half ball' or "half sphere"...
s have winter at different times of the year, there are actually two different flu seasons each year. This is why the World Health Organization (assisted by the National Influenza Centers
National Influenza Centers
National Influenza Centers are institutions which are formally recognized as such by the World Health Organization ."The WHO Global Influenza Surveillance Network was established in 1952...
) makes recommendations for two different vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere.
A long-standing puzzle has been why outbreaks of the flu occur seasonally rather than uniformly throughout the year. One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this promotes transmission from person to person. Increased travel due to the Northern Hemisphere winter holiday season may also play a role. Another factor is that cold temperatures lead to drier air, which may dehydrate mucus, preventing the body from effectively expelling virus particles. The virus also survives longer on surfaces at colder temperatures and aerosol transmission of the virus is highest in cold environments (less than 5 °C) with low relative humidity. Indeed, the lower air humidity in winter seems to be the main cause of seasonal influenza transmission in temperate regions.
However, seasonal changes in infection rates also occur in tropical regions, and in some countries these peaks of infection are seen mainly during the rainy season. Seasonal changes in contact rates from school terms, which are a major factor in other childhood diseases such as measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
and pertussis
Pertussis
Pertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...
, may also play a role in the flu. A combination of these small seasonal effects may be amplified by dynamical resonance with the endogenous disease cycles. H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
exhibits seasonality in both humans and birds.
An alternative hypothesis to explain seasonality in influenza infections is an effect of vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
levels on immunity to the virus. This idea was first proposed by Robert Edgar Hope-Simpson
Robert Edgar Hope-Simpson
Robert Edgar Hope-Simpson was a general practitioner. He showed that shingles was caused by reactivation of the chickenpox virus.He also pioneered research into a possible relationship between influenza and Vitamin D....
in 1965. He proposed that the cause of influenza epidemics during winter may be connected to seasonal fluctuations of vitamin D, which is produced in the skin under the influence of solar (or artificial) UV radiation
Ultraviolet
Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
. This could explain why influenza occurs mostly in winter and during the tropical rainy season, when people stay indoors, away from the sun, and their vitamin D levels fall.
Epidemic and pandemic spread
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, in any given year some strains can die out while others create epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
s, while yet another strain can cause a pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
. Typically, in a year's normal two flu season
Flu season
Flu season is a annually-recurring time period characterized by the prevalence of outbreaks of influenza . The season occurs during the cold half of the year in each hemisphere. Influenza activity can sometimes be predicted and even tracked geographically...
s (one per hemisphere), there are between three and five million cases of severe illness and up to 500,000 deaths worldwide, which by some definitions is a yearly influenza epidemic. Although the incidence of influenza can vary widely between years, approximately 36,000 deaths and more than 200,000 hospitalizations are directly associated with influenza every year in the United States. Roughly three times per century, a pandemic occurs, which infects a large proportion of the world's population and can kill tens of millions of people (see history section). Indeed, one study estimated that if a strain with similar virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
to the 1918 influenza emerged today, it could kill between 50 and 80 million people.
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
by mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
or by reassortment
Reassortment
Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting...
. Mutations can cause small changes in the hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
and neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s on the surface of the virus. This is called antigenic drift
Antigenic drift
The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific receptors, which prevent...
, which slowly creates an increasing variety of strains until one evolves that can infect people who are immune to the pre-existing strains. This new variant then replaces the older strains as it rapidly sweeps through the human population—often causing an epidemic. However, since the strains produced by drift will still be reasonably similar to the older strains, some people will still be immune to them. In contrast, when influenza viruses reassort, they acquire completely new antigens—for example by reassortment between avian strains and human strains; this is called antigenic shift
Antigenic shift
Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains...
. If a human influenza virus is produced that has entirely new antigens, everybody will be susceptible, and the novel influenza will spread uncontrollably, causing a pandemic. In contrast to this model of pandemics based on antigenic drift and shift, an alternative approach has been proposed where the periodic pandemics are produced by interactions of a fixed set of viral strains with a human population with a constantly changing set of immunities to different viral strains.
From a public health point of view, flu epidemics spread rapidly and are very difficult to control. Most influenza virus strains are not very infectious and each infected individual will only go on to infect one or two other individuals (the basic reproduction number for influenza is generally around 1.4). However, the generation time for influenza is extremely short: the time from a person becoming infected to when he infects the next person is only two days. The short generation time means that influenza epidemics generally peak at around 2 months and burn out after 3 months : the decision to intervene in an influenza epidemic therefore has to be taken early, and the decision is therefore often made on the back of incomplete data. Another problem is that individuals become infectious before they become symptomatic, which means that putting people in quarantine after they become ill is not an effective public health intervention.
Etymology
The word Influenza comes from the Italian languageItalian language
Italian is a Romance language spoken mainly in Europe: Italy, Switzerland, San Marino, Vatican City, by minorities in Malta, Monaco, Croatia, Slovenia, France, Libya, Eritrea, and Somalia, and by immigrant communities in the Americas and Australia...
meaning "influence" and refers to the cause of the disease; initially, this ascribed illness to unfavorable astrological
Astrology
Astrology consists of a number of belief systems which hold that there is a relationship between astronomical phenomena and events in the human world...
influences. Changes in medical thought led to its modification to influenza del freddo, meaning "influence of the cold". The word influenza was first used in English to refer to the disease we know today in 1703 by J. Hugger of the University of Edinburgh in his thesis De Catarrho epidemio, vel Influenza, prout in India occidentali sese ostendit.
Archaic terms for influenza include epidemic catarrh, grippe (from the French, first used by Molyneaux in 1694 ), sweating sickness, and Spanish fever (particularly for the 1918 flu pandemic strain).
Pandemics
Hippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
roughly 2,400 years ago. Although the virus seems to have caused epidemics throughout human history, historical data on influenza are difficult to interpret, because the symptoms can be similar to those of other respiratory diseases. The disease may have spread from Europe to the Americas as early as the European colonization of the Americas
European colonization of the Americas
The start of the European colonization of the Americas is typically dated to 1492. The first Europeans to reach the Americas were the Vikings during the 11th century, who established several colonies in Greenland and one short-lived settlement in present day Newfoundland...
; since almost the entire indigenous population of the Antilles was killed by an epidemic resembling influenza that broke out in 1493, after the arrival of Christopher Columbus
Christopher Columbus
Christopher Columbus was an explorer, colonizer, and navigator, born in the Republic of Genoa, in northwestern Italy. Under the auspices of the Catholic Monarchs of Spain, he completed four voyages across the Atlantic Ocean that led to general European awareness of the American continents in the...
.
The first convincing record of an influenza pandemic was of an outbreak in 1580, which began in Russia 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 a quarter of the people exposed.
The most famous and lethal outbreak was the 1918 flu pandemic (Spanish flu pandemic) (type A influenza
Influenzavirus A
Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
, H1N1
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
subtype), which lasted from 1918 to 1919. It is not known exactly how many it killed, but estimates range from 20 to 100 million people. This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the Black Death
Black Death
The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350. Of several competing theories, the dominant explanation for the Black Death is the plague theory, which attributes the outbreak to the bacterium Yersinia pestis. Thought to have...
. This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storm
Cytokine storm
A cytokine storm, or hypercytokinemia is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells, with highly elevated levels of various cytokines.-Symptoms:...
s. Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera
Cholera
Cholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membrane
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages
Petechia
A petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
in the skin also occurred." The majority of deaths were from bacterial pneumonia
Bacterial pneumonia
Bacterial pneumonia is a type of pneumonia caused by bacterial infection.-Sign and symptoms:*Fever*Rigors*Cough*Dyspnea*Chest pain*Pneumococcal pneumonia can cause Hemoptysis-Gram positive:...
, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
in the lung.
Arctic
The Arctic is a region located at the northern-most part of the Earth. The Arctic consists of the Arctic Ocean and parts of Canada, Russia, Greenland, the United States, Norway, Sweden, Finland, and Iceland. The Arctic region consists of a vast, ice-covered ocean, surrounded by treeless permafrost...
and remote Pacific islands
Pacific Islands
The Pacific Islands comprise 20,000 to 30,000 islands in the Pacific Ocean. The islands are also sometimes collectively called Oceania, although Oceania is sometimes defined as also including Australasia and the Malay Archipelago....
. The unusually severe disease killed between 2 and 20% of those infected, as opposed to the more usual flu epidemic mortality rate
Mortality rate
Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
of 0.1%. Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65, and more than half in young adults 20 to 40 years old. This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918–1919 pandemic is not known, but it is estimated that 2.5% to 5% of the world's population was killed. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
has killed 25 million in its first 25 years.
Later flu pandemics were not so devastating. They included the 1957 Asian Flu
Asian flu
Asian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus...
(type A, H2N2
H2N2
H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
strain) and the 1968 Hong Kong Flu
Hong Kong flu
The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...
(type A, H3N2
H3N2
Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...
strain), but even these smaller outbreaks killed millions of people. In later pandemics antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s were available to control secondary infections and this may have helped reduce mortality compared to the Spanish Flu of 1918.
| Name of pandemic | Date | Deaths | Case fatality rate | Subtype involved | Pandemic Severity Index Pandemic Severity Index The Pandemic Severity Index is a proposed classification scale for reporting the severity of influenza pandemics in the United States. The PSI was accompanied by a set of guidelines intended to help communicate appropriate actions for communities to follow in potential pandemic situations... |
|---|---|---|---|---|---|
| Asiatic (Russian) Flu | 1889–1890 | 1 million | 0.15% | possibly H3N8 H3N8 H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs.-Introduction:Equine influenza is a highly contagious respiratorydisease of horses and related animals such as donkeys,... |
NA |
| 1918 flu pandemic (Spanish flu) |
1918–1920 | 20 to 100 million | 2% | H1N1 H1N1 'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of... |
5 |
| Asian Flu | 1957–1958 | 1 to 1.5 million | 0.13% | H2N2 H2N2 H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds... |
2 |
| Hong Kong Flu | 1968–1969 | 0.75 to 1 million | <0.1% | H3N2 H3N2 Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains... |
2 |
| 2009 flu pandemic 2009 flu pandemic The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version... |
2009–2010 | 18,000 | 0.03% | H1N1 H1N1 'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of... |
NA |
The first influenza virus to be isolated was from poultry, when in 1901 the agent causing a disease called "fowl plague" was passed through Chamberland filter
Chamberland filter
A Chamberland filter, also known as a Pasteur-Chamberland filter, is a porcelain water filter invented by Charles Chamberland in 1884. It is similar to the Berkefeld filter in principle.-Design:...
s, which have pores that are too small for bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
to pass through. The etiological
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
cause of influenza, the Orthomyxoviridae family of viruses, was first discovered in pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s by Richard Shope
Richard Shope
Richard Shope was an American virologist who was first to isolate an influenza virus and first to vaccinate animals against influenza. In the 1930s, Shope, a physician at the Rockefeller Institute for Medical Research, identified the causative agent as a virus in the 1918-19 Spanish influenza...
in 1931. This discovery was shortly followed by the isolation of the virus from humans by a group headed by Patrick Laidlaw
Patrick Laidlaw
Patrick Playfair Laidlaw was a British virologist.He was one of the scientists working at the Medical Research Council at Mill Hill who first isolated influenza virus from humans. This happened when ferrets they were working on to develop a distemper vaccine caught influenza from one of the...
at the Medical Research Council
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...
of the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
in 1933. However, it was not until Wendell Stanley first crystallized tobacco mosaic virus
Tobacco mosaic virus
Tobacco mosaic virus is a positive-sense single stranded RNA virus that infects plants, especially tobacco and other members of the family Solanaceae. The infection causes characteristic patterns on the leaves . TMV was the first virus to be discovered...
in 1935 that the non-cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
nature of viruses was appreciated.
Thomas Francis, Jr.
Thomas Francis, Jr. was an American physician, virologist, and epidemiologist. Francis was the first person to isolate influenza virus in America, and in 1940 showed that there are other strains of influenza, and took part in the development of influenza vaccines.- Life and achievements :Francis...
. This built on work by Australian Frank Macfarlane Burnet
Frank Macfarlane Burnet
Sir Frank Macfarlane Burnet, , usually known as Macfarlane or Mac Burnet, was an Australian virologist best known for his contributions to immunology....
, who showed that the virus lost virulence when it was cultured in fertilized hen's eggs. Application of this observation by Francis allowed his group of researchers at the University of Michigan
University of Michigan
The University of Michigan is a public research university located in Ann Arbor, Michigan in the United States. It is the state's oldest university and the flagship campus of the University of Michigan...
to develop the first influenza vaccine, with support from the U.S. Army
United States Army
The United States Army is the main branch of the United States Armed Forces responsible for land-based military operations. It is the largest and oldest established branch of the U.S. military, and is one of seven U.S. uniformed services...
. The Army was deeply involved in this research due to its experience of influenza in World War I
World War I
World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...
, when thousands of troops were killed by the virus in a matter of months. In comparison to vaccines, the development of anti-influenza drugs has been slower, with amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
being licensed in 1966 and, almost thirty years later, the next class of drugs (the neuraminidase inhibitor
Neuraminidase inhibitor
Neuraminidase inhibitors are a class of antiviral drugs targeted at the influenza virus, which work by blocking the function of the viral neuraminidase protein, thus preventing the virus from reproducing by budding from the host cell....
s) being developed.
Society and culture
Influenza produces direct costsVariable cost
Variable costs are expenses that change in proportion to the activity of a business. Variable cost is the sum of marginal costs over all units produced. It can also be considered normal costs. Fixed costs and variable costs make up the two components of total cost. Direct Costs, however,...
due to lost productivity
Productivity
Productivity is a measure of the efficiency of production. Productivity is a ratio of what is produced to what is required to produce it. Usually this ratio is in the form of an average, expressing the total output divided by the total input...
and associated medical treatment, as well as indirect costs
Indirect costs
Indirect costs are costs that are not directly accountable to a cost object . Indirect costs may be either fixed or variable. Indirect costs include taxes, administration, personnel and security costs, and are also known as overhead.There are two types of Indirect Costs...
of preventative measures. In the United States, influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs. However, the economic impacts of past pandemics have not been intensively studied, and some authors have suggested that the Spanish influenza
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
actually had a positive long-term effect on per-capita income growth, despite a large reduction in the working population and severe short-term depressive
Recession
In economics, a recession is a business cycle contraction, a general slowdown in economic activity. During recessions, many macroeconomic indicators vary in a similar way...
effects. Other studies have attempted to predict the costs of a pandemic as serious as the 1918 Spanish flu on the U.S. economy
Economy of the United States
The economy of the United States is the world's largest national economy. Its nominal GDP was estimated to be nearly $14.5 trillion in 2010, approximately a quarter of nominal global GDP. The European Union has a larger collective economy, but is not a single nation...
, where 30% of all workers became ill, and 2.5% were killed. A 30% sickness rate and a three-week length of illness would decrease the gross domestic product
Gross domestic product
Gross domestic product refers to the market value of all final goods and services produced within a country in a given period. GDP per capita is often considered an indicator of a country's standard of living....
by 5%. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.
Preventative costs are also high. Governments worldwide have spent billions of U.S. dollars
United States dollar
The United States dollar , also referred to as the American dollar, is the official currency of the United States of America. It is divided into 100 smaller units called cents or pennies....
preparing and planning for a potential H5N1 avian influenza pandemic, with costs associated with purchasing drugs and vaccines as well as developing disaster drills
Emergency management
Emergency management is the generic name of an interdisciplinary field dealing with the strategic organizational management processes used to protect critical assets of an organization from hazard risks that can cause events like disasters or catastrophes and to ensure the continuance of the...
and strategies for improved border control
Border control
Border controls are measures used by a country to monitor or regulate its borders.The control of the flow of many people, animals and goods across a border may be controlled by government Customs services. Security is enforced by various kinds of Border Guards and Coast Guards...
s. On 1 November 2005, United States President
President of the United States
The President of the United States of America is the head of state and head of government of the United States. The president leads the executive branch of the federal government and is the commander-in-chief of the United States Armed Forces....
George W. Bush
George W. Bush
George Walker Bush is an American politician who served as the 43rd President of the United States, from 2001 to 2009. Before that, he was the 46th Governor of Texas, having served from 1995 to 2000....
unveiled the National Strategy to Safeguard Against the Danger of Pandemic Influenza backed by a request to Congress
United States Congress
The United States Congress is the bicameral legislature of the federal government of the United States, consisting of the Senate and the House of Representatives. The Congress meets in the United States Capitol in Washington, D.C....
for $7.1 billion to begin implementing the plan. Internationally, on 18 January 2006, donor nations pledged US$2 billion to combat bird flu at the two-day International Pledging Conference on Avian and Human Influenza held in China.
In an assessment of the 2009 H1N1 pandemic on selected countries in the Southern Hemisphere, data suggest that all countries experienced some time-limited and/or geographically isolated socio/economic effects and a temporary decrease in tourism most likely due to fear of 2009 H1N1 disease. It is still too early to determine whether the H1N1 pandemic has caused any long-term economic impacts.
Research
Molecular Virology
Molecular Virology is the study of viruses at the molecular level.In particular, this includes the analysis of individual viral genes and gene products, and their interaction with host cellular proteins....
, how the virus produces disease (pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
), host immune responses, viral genomics
Genomics
Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
, and how the virus spreads (epidemiology
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
). These studies help in developing influenza countermeasures; for example, a better understanding of the body's immune system response helps vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
development, and a detailed picture of how influenza invades cells aids the development of antiviral drugs. One important basic research
Research
Research can be defined as the scientific search for knowledge, or as any systematic investigation, to establish novel facts, solve new or existing problems, prove new ideas, or develop new theories, usually using a scientific method...
program is the Influenza Genome Sequencing Project
Influenza Genome Sequencing Project
The Influenza Genome Sequencing Project is an American-based genome project aimed at improving the availability of genomic sequence data from influenza viruses and related information....
, which is creating a library of influenza sequences; this library should help clarify which factors make one strain more lethal than another, which genes most affect immunogenicity
Immunogenicity
Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.- Immunogenicity :The ability to induce humoral and/or cell-mediated immune responses....
, and how the virus evolves
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
over time.
Research into new vaccines is particularly important, as current vaccines are very slow and expensive to produce and must be reformulated every year. The sequencing of the influenza genome and recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
technology may accelerate the generation of new vaccine strains by allowing scientists to substitute new antigens into a previously developed vaccine strain. New technologies are also being developed to grow viruses in cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
, which promises higher yields, less cost, better quality and surge capacity. Research on a universal influenza A vaccine, targeted against the external domain of the transmembrane viral M2 protein
M2 protein
The M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer , where the units are helices stabilized by two disulfide bonds...
(M2e), is being done at the University of Ghent by Walter Fiers
Walter Fiers
Walter Fiers is a Belgian molecular biologist.He obtained a degree of Engineer for Chemistry and Agricultural Industries at the University of Ghent in 1954, and started his research career as an enzymologist in the laboratory of Laurent Vandendriessche in Ghent. In 1956-57, he worked with Heinz...
, Xavier Saelens
Xavier Saelens
Xavier Saelens is a Belgian scientist and currently his main research interest is finding a universal influenza vaccine. He is a Lecturer in Virology and Group Leader of the Molecular Virology Unit at the University of Ghent...
and their team and has now successfully concluded Phase I clinical trials.
A number of biologics
Biologics
A biologic is a medicinal product such as a vaccine, blood or blood component, allergenic, somatic cell, gene therapy, tissue, recombinant therapeutic protein, or living cells that are used as therapeutics to treat diseases...
, therapeutic vaccines and immunobiologics are also being investigated for treatment of infection caused by viruses. Therapeutic biologics are designed to activate the immune response to virus or antigens. Typically, biologics do not target metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
s like anti-viral drugs, but stimulate immune cells such as lymphocytes, macrophages, and/or antigen presenting cells, in an effort to drive an immune response towards a cytotoxic effect against the virus. Influenza models, such as murine influenza, are convenient models to test the effects of prophylactic and therapeutic biologics. For example, Lymphocyte T-Cell Immune Modulator
Lymphocyte T-Cell Immune Modulator
Lymphocyte T-Cell Immune Modulator is an immune regulating polypeptide manufactured by T-Cyte Therapeutics and distributed by . Lymphocyte T-Cell Immune Modulator is a potent regulator of CD-4 lymphocyte production and function. It has been shown to increase lymphocyte numbers and Interleukin-2 ...
inhibits viral growth in the murine model of influenza.
Infection in other animals
Influenza infects many animal species, and transfer of viral strains between species can occur. BirdBird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s are thought to be the main animal reservoirs
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
of influenza viruses. Sixteen forms of hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
and nine forms of neuraminidase
Neuraminidase
Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
have been identified. All known subtypes (HxNy) are found in birds, but many subtypes are endemic in humans, dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s, horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s, and pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s; populations of camel
Camel
A camel is an even-toed ungulate within the genus Camelus, bearing distinctive fatty deposits known as humps on its back. There are two species of camels: the dromedary or Arabian camel has a single hump, and the bactrian has two humps. Dromedaries are native to the dry desert areas of West Asia,...
s, ferret
Ferret
The ferret is a domesticated mammal of the type Mustela putorius furo. Ferrets are sexually dimorphic predators with males being substantially larger than females. They typically have brown, black, white, or mixed fur...
s, cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s, seals
Pinniped
Pinnipeds or fin-footed mammals are a widely distributed and diverse group of semiaquatic marine mammals comprising the families Odobenidae , Otariidae , and Phocidae .-Overview: Pinnipeds are typically sleek-bodied and barrel-shaped...
, mink
Mink
There are two living species referred to as "mink": the European Mink and the American Mink. The extinct Sea Mink is related to the American Mink, but was much larger. All three species are dark-colored, semi-aquatic, carnivorous mammals of the family Mustelidae, which also includes the weasels and...
, and whale
Whale
Whale is the common name for various marine mammals of the order Cetacea. The term whale sometimes refers to all cetaceans, but more often it excludes dolphins and porpoises, which belong to suborder Odontoceti . This suborder also includes the sperm whale, killer whale, pilot whale, and beluga...
s also show evidence of prior infection or exposure to influenza. Variants of flu virus are sometimes named according to the species the strain is endemic in or adapted to. The main variants named using this convention are: Bird Flu, Human Flu
Human flu
Human flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...
, Swine Flu
Swine flu
Swine influenza, also called pig influenza, swine flu, hog flu and pig flu, is an infection by any one of several types of swine influenza virus. Swine influenza virus or S-OIV is any strain of the influenza family of viruses that is endemic in pigs...
, Horse Flu
Horse flu
Equine influenza is the disease caused by strains of Influenza A that are enzootic in horse species. Equine influenza occurs globally, and is caused by two main strains of virus: equine-1 and equine-2...
and Dog Flu. (Cat flu
Cat flu
Cat flu is the common name for a feline upper respiratory tract disease. It is a misnomer, since it usually does not refer to an infection by an influenza virus...
generally refers to Feline viral rhinotracheitis
Feline viral rhinotracheitis
Feline viral rhinotracheitis is an upper respiratory infection of cats caused by feline herpesvirus 1, of the family Herpesviridae. It is also known as feline influenza and feline coryza. Viral respiratory diseases in cats can be serious, especially in catteries and kennels...
or Feline calicivirus
Feline calicivirus
Feline calicivirus is a virus of the family Caliciviridae that causes disease in cats. It is one of the two important viral causes of respiratory infection in cats, the other being feline herpesvirus. FCV can be isolated from about 50 percent of cats with upper respiratory infection...
and not infection from an influenza virus.) In pigs, horses and dogs, influenza symptoms are similar to humans, with cough, fever and loss of appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
. The frequency of animal diseases are not as well-studied as human infection, but an outbreak of influenza in harbor seals caused approximately 500 seal deaths off the New England
New England
New England is a region in the northeastern corner of the United States consisting of the six states of Maine, New Hampshire, Vermont, Massachusetts, Rhode Island, and Connecticut...
coast in 1979–1980. On the other hand, outbreaks in pigs are common and do not cause severe mortality.
Bird flu
Flu symptoms in birds are variable and can be unspecific. The symptoms following infection with low-pathogenicity avian influenza may be as mild as ruffled feathers, a small reduction in egg production, or weight lossWeight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
combined with minor respiratory disease
Respiratory disease
Respiratory disease is a medical term that encompasses pathological conditions affecting the organs and tissues that make gas exchange possible in higher organisms, and includes conditions of the upper respiratory tract, trachea, bronchi, bronchioles, alveoli, pleura and pleural cavity, and the...
. Since these mild symptoms can make diagnosis in the field difficult, tracking the spread of avian influenza
Avian flu
Avian influenza, sometimes avian flu, and commonly bird flu, refers to "influenza caused by viruses adapted to birds." Of the greatest concern is highly pathogenic avian influenza ....
requires laboratory testing of samples from infected birds. Some strains such as Asian H9N2
H9N2
H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...
are highly virulent to poultry and may cause more extreme symptoms and significant mortality. In its most highly pathogenic form, influenza in chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
s and turkeys
Turkey (bird)
A turkey is a large bird in the genus Meleagris. One species, Meleagris gallopavo, commonly known as the Wild Turkey, is native to the forests of North America. The domestic turkey is a descendant of this species...
produces a sudden appearance of severe symptoms and almost 100% mortality within two days. As the virus spreads rapidly in the crowded conditions seen in the intensive farming
Intensive farming
Intensive farming or intensive agriculture is an agricultural production system characterized by the high inputs of capital, labour, or heavy usage of technologies such as pesticides and chemical fertilizers relative to land area....
of chickens and turkeys, these outbreaks can cause large economic losses to poultry farmers.
An avian-adapted, highly pathogenic strain of H5N1 (called HPAI A(H5N1), for "highly pathogenic avian influenza virus of type A of subtype H5N1") causes H5N1 flu
Transmission and infection of H5N1
Transmission and infection of H5N1 from infected avian sources to humans is a concern due to the global spread of H5N1 that constitutes a pandemic threat....
, commonly known as "avian influenza" or simply "bird flu", and is endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
in many bird populations, especially in Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
. This Asian lineage strain of HPAI A(H5N1) is spreading globally
Global spread of H5N1
The global spread of highly pathogenic H5N1 influenza in birds is considered a significant pandemic threat.While other H5N1 influenza strains are known, they are significantly different from a current, highly pathogenic H5N1 strain on a genetic level, making the global spread of this new strain...
. It is epizootic
Epizootic
In epizoology, an epizootic is a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience . Epidemic is the analogous term applied to human populations...
(an epidemic in non-humans) and panzootic (a disease affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling
Culling
Culling is the process of removing animals from a group based on specific criteria. This is done either to reinforce certain desirable characteristics or to remove certain undesirable characteristics from the group...
of hundreds of millions of other birds in an attempt to control its spread. Most references in the media to "bird flu" and most references to H5N1 are about this specific strain.
At present, HPAI A(H5N1) is an avian disease, and there is no evidence suggesting efficient human-to-human transmission of HPAI A(H5N1). In almost all cases, those infected have had extensive physical contact with infected birds. In the future, H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. The exact changes that are required for this to happen are not well understood. However, due to the high lethality and virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
of H5N1, its endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
presence, and its large and increasing biological host reservoir, the H5N1 virus was the world's pandemic threat in the 2006–07 flu season, and billions of dollars are being raised and spent researching H5N1 and preparing for a potential influenza pandemic.
Swine flu
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...
swine flu). In all, 50 human cases are known to have occurred since the virus was identified in the mid-20th century, which have resulted in six deaths.
In 2009, a swine-origin H1N1
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
virus strain commonly referred to as "swine flu" caused the 2009 flu pandemic
2009 flu pandemic
The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...
, but there is no evidence that it is endemic to pigs (i.e. actually a swine flu) or of transmission from pigs to people, instead the virus is spreading from person to person. This strain is a reassortment of several strains of H1N1 that are usually found separately, in humans, birds, and pigs.
See also
- List of epidemics
- List of viruses
- Vitamin D and influenzaVitamin D and influenzaNumerous studies link vitamin D and influenza, as well as vitamin D and respiratory infections more generally. This vitamin up-regulates genetic expression of various endogenous antimicrobial peptides , which exhibit broad-spectrum microbicidal activity against bacteria, fungi, and viruses...
Information concerning flu research can be found at:
Further reading
General- Bernd Sebastian Kamps, Christian Hoffmann and Wolfgang Preiser (Eds.) Influenza Report, 225 pp, PDF, free download. Flying Publisher 2006
- ISBN 978-3-211-80892-4 The Influenza Viruses Hoyle L 1968 Springer Verlag
History
Microbiology
Pathogenesis
Epidemiology
Treatment and prevention
Research
- WHO (PDF) contains latest Evolutionary "Tree of Life" for H5N1 article Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as pre-pandemic vaccines published 18 August 2006
- WHO's assessment of Flu Research as of November 2006.
External links
- ERS Online Course on Influenza
- Swine and Seasonal Flu, Institute for Good Medicine at the Pennsylvania Medical Society
- Info on influenza at CDCCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
- Summary of the disease at the NYTimes.
- 10 Genes, Furiously Evolving NYTimes May 2009
- Outbreak Alerts United States based communicable disease notification website
- Influenza (Mayo Clinic)
- Fact Sheet Overview of influenza at World Health Organization
- The Multinational Influenza Seasonal Mortality Study (MISMS) Fogarty International Center
- Influenza Virus Resource from the NCBINational Center for Biotechnology InformationThe National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
- European Influenza Surveillance Scheme
- Flu Trends – flu activity across the U.S.
- Cold and flu advice (NHS Direct)
- Online video discussing influenza outbreaks and spread of other infectious diseases (Vega Science Trust)
- Flu.gov: Know What To Do About the Flu
- PATH Vaccine Resource Library influenza resources
- Influenza Research Database – Database of influenza genomic sequences, serotypes, polymorphisms, structures, epitopes, drugs and related tools.
- Recombinomics - What's New : Up to date details of circulating strains.