Ricerche Simili:
Infobox_Disease
Name=Influenza
Image=EM of influenza virus.jpg
Caption=
TEM of negatively stained influenza virions, magnified approximately 100,000 times
Width=226
DiseasesDB=6791
ICD10=
ICD9=
MedlinePlus=000080
eMedicineSubj=med
eMedicineTopic=1170
eMedicine_mult=
MeshID=D007251
Influenza''', commonly referred to as the '''flu , is an
infectious disease caused by
RNA viruses of the
family Orthomyxoviridae (the influenza viruses), that affects
birds and
mammals. The most common symptoms of the disease are
chills,
fever,
sore throat,
muscle pains, severe
headache,
coughing, weakness/
fatigue and
general discomfort.
cite web
url=http://www.merck.com/mmhe/sec17/ch198/ch198d.html
title=Influenza: Viral Infections: Merck Manual Home Edition
publisher=www.merck.com
accessdate=2008-03-15
last=
first=
Sore throat, fever and coughs are the most frequent symptoms. In more serious cases, influenza
causes pneumonia, which can be fatal, particularly for the young and the elderly. Although it is often confused with other
influenza-like illnesses, especially the
common cold, influenza is a more severe disease than the common cold and is caused by a different type of virus.
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.
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 people every year,
Vaccinations against influenza are usually given to people in
developed countries
The TIV carries no risk of transmitting the disease, and it has very low reactivity. A vaccine formulated for one year may be ineffective in the following year, since the influenza virus evolves rapidly, and new strains quickly replace the older ones.
Antiviral drugs can be used to treat influenza, with
neuraminidase inhibitors being particularly effective.
Classification
Types of influenza virus
. The
hemagglutinin (HA) and
neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the
genome are shown as red coils inside the particle and bound to Ribonuclear Proteins (RNPs).
In
virus classification influenza viruses are
RNA viruses that make up three of the five
genera of the family
Orthomyxoviridae:
Influenzavirus A Influenzavirus B Influenzavirus C
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,
=
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
pandemics.
The type A viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. The influenza A virus can be subdivided into different
serotypes based on the
antibody response to these viruses. The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
H1N1, which caused
Spanish flu in 1918, and the
2009 flu pandemic H2N2, which caused
Asian Flu in 1957
H3N2, which caused
Hong Kong Flu in 1968
H5N1, a current
pandemic threat
H7N7, which has unusual
zoonotic potential
H1N2, endemic in humans and pigs
H9N2 H7N2 H7N3 H10N7
=
Influenzavirus B
=
(for a
Fujian flu virus)
This genus has one species, influenza B virus. Influenza B almost exclusively infects humans
=
Influenzavirus C
=
This genus has one species, influenza C virus, which infects humans, dogs and pigs, sometimes causing both severe illness and local epidemics.
Structure, properties, and subtype nomenclature
Influenzaviruses A, B and C are very similar in overall structure.
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.
Replication
Viruses can only replicate in living cells.
Influenza viruses bind through
hemagglutinin onto
sialic acid sugars on the surfaces of
epithelial cells; typically in the nose, throat and
lungs of mammals and
intestines of birds (Stage 1 in infection figure).
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
protons 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.
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).
Negative-sense vRNAs that form the
genomes 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 shifts, 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
_
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 filters, which have pores that are too small for
bacteria to pass through.
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.
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 inhibitors) being developed.
Society and culture
Influenza produces
direct costs 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.
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 controls.
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
virus in a
biosafety level 3 environment.
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.
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 pathways 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. Infuenza 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.
Infection in other animals
Influenza infects many animal species, and transfer of viral strains between species can occur.
Birds are thought to be the main
animal reservoirs of influenza viruses.
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.
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.
Swine flu
In pigs
swine influenza produces fever, lethargy, sneezing, coughing, difficulty breathing and decreased appetite.
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.
See also
List of epidemics List of viruses Vitamin D and influenza
;Information concerning flu research can be found at:
References
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
Epidemiology of WHO-confirmed human cases of avian influenza A(H5N1) infection
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
CDC Summary of the disease at the
NYTimes.
10 Genes, Furiously Evolving NYTimes May 4, 2009
Outbreak Alerts United States based communicable disease notification website.
Influenza Research Database – Database of influenza genomic sequences, serotypes, polymorphisms, structures, epitopes, drugs and related tools.
Influenza (Mayo Clinic) Fact Sheet Overview of influenza at
World Health Organization The Multinational Influenza Seasonal Mortality Study (MISMS) Fogarty International Center Health encyclopedia entry at
NHS Direct Orthomyxoviridae The Universal Virus Database of the
International Committee on Taxonomy of Viruses Influenza Virus Resource from the
NCBI European Influenza Surveillance Scheme Flu Trends – flu activity across the U.S.
[https://www.nhsdirect.nhs.uk/Sat/Topics/ColdsAndFlu.aspx?Host=Nhsd&SyndicationPartnerGuid=d19370ea-a100-407d-9695-b73407f701c7&TopicGuid=8c903315-a302-412a-bfae-9cb576d4b4cd 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