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Influenza - causes, symptoms, diagnosis, treatment, pathology

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Influenza, the virus that causes the flu, is one of the most common infectious diseases.

Now, there are three types of influenza that infect humans, called type A, type B, and

type C, each one with slightly different genome and proteins.

Influenza belongs to the virus family Orthomyxoviridae - and type A and B have genomes that are made

up of eight RNA segments, whereas type C, has a seven-segment RNA genome, with each

segment containing a few genes.

Now, type A, the most common type of influenza virus, can be further subdivided based on

two of the glycoproteins on its protective envelope surface; H protein, or Hemagglutinin,

and N protein, or neuraminidase.

Hemagglutinin and Neuraminidase can vary a bit in their structure, so different versions

are identified by a number.

For example, type A subtype H3N2, sometimes just called H3N2, has hemagglutinin number

3 and neuraminidase number 2 on its surface.

H3N2 and H1N1 are the most common type A subtypes to infect humans, but they both also infect

various animals.

To give the full name of a virus, we use the type, the original host that it came from,

the location where the virus was first identified, which is usually a city, the strain number,

the year of origin, and—for type A influenza—the subtype named by the H and N glycoproteins.

For example, an H1N1 type A flu virus of duck origin from the province of Alberta, Canada,

that is the 35th strain discovered in 1976 would be called A/duck/Alberta/35/76 (H1N1).

Type B influenza is less common, it only infects humans and doesn't mutate as often as type

A. Type B influenza only has a few types of H and N glycoproteins on its surface.

Therefore the naming pattern is similar to type A influenza without the H and N subtype

included at the end or the host type, since it only infects humans.

For example, a type B virus found in Yamagata, Japan, which is the 16th strain discovered

in 1988 would be called B/Yamagata/16/88.

Finally, there's type C influenza which is only one species, and is the least common

and least likely to mutate of the three.

Influenza C usually causes mild disease in children, and unlike type B, it can affect

both humans and pigs.

Rather than hemagglutinin and neuraminidase, type C influenza uses a hemagglutinin-esterase-fusion

protein to enter and exit cells.

So, type C influenza is named without the HN subtype, similar to how type B's written.

For example, a type C virus found in Sao Paulo, Brazil which is the 37th strain discovered

in 1982 would be called C/Sao Paulo/37/82.

Of the three types, type A is the most common and causes the most severe illness.

One reason is that the virus has a tendency to mutate its H and N glycoproteins during

replication, and this allows daughter viruses to form that are slightly different from one

another and from the parent virus.

Over time, if enough of these small changes happen, even if somebody's immune to the original

virus, the mutated virus may have H and N glycoproteins that are different enough to

allow it to evade antibodies, and therefore infect people who were immune to previous

strains.

This process is called genetic drift, and is why individuals can get sick from influenza

year after year or from two different strains of influenza in the same year.

In addition, a process called antigenic shift, is where sometimes a virus will be circulating

among animal populations like pigs or chickens and then will suddenly change in a way that

allows the virus to infect humans as well.

This happens when the same cell, let's say a pig cell, gets infected with two similar

flu viruses, for example a flu strain that usually infects humans and one that usually

infects pigs.

Since the viral genome is in segments of RNA, the pieces might reassort, or mix, allowing

new viruses to have a mix of RNA segments in them.

Reassortment results in viruses that have entirely new hemagglutinin, neuraminidase,

or both.

When a virus is produced that can infect human cells and has entirely new proteins, people

have little or no protection against it, and it can rapidly spread through the population.

This antigenic shift process is responsible for three major influenza pandemics in the

20th century, including the Spanish Flu in 1918, which killed 3 percent of the world's

entire population at the time.

The flu is transmitted when an infected person sneezes or coughs, which spreads thousands

of droplets containing the virus into the local area, up to about two meters or six

feet away.

These droplets can then land in the mouths or noses of people nearby, or get inhaled

into the lungs.

The virus can also survive on surfaces for a few hours, so it's possible to get the virus

by touching a surface, like a contaminated doorknob, and then touching your own eyes,

nose, or mouth.

When the flu virus enters the body, it uses hemagglutinin to bind to sialic acid sugars

on the surface of epithelial cells in the upper respiratory tract.

Once bound, the cell swallows up the virus in a process called endocytosis.

That viral RNA is negative-sense, meaning that each piece first has to be transcribed

by RNA polymerase into positive-sense mRNA strands, before it can be translated into

proteins and assembled into viruses.

These viruses leave the cell by simply budding out from it by using the neuraminidase, which

cleaves the sialic acid sugars in the membrane, releasing the newly created viruses from the

cell.

Influenza symptoms start 1-4 days after infection and include fever, headache, runny nose, sore

throat, and a cough.

Most of these symptoms get better in a week, but the cough often persists for up to two

weeks.

There can be sometimes be complications, though, like acute otitis media, bronchiolitis, croup,

sinusitis, and pneumonia, including antibiotic-resistant strains caused by Staphylococcus aureus and

Streptococcus pneumoniae.

The highest risk of complications is among high-risk groups like young children under

6 months of age, pregnant women, adults over 65 years old, and those with chronic medical

conditions, like chronic heart or lung disease.

Young children in particular are more likely to have neurologic complications like encephalitis

and febrile seizures.

One unique complication is Reye syndrome, which is a condition where a after taking

aspirin while fighting off a viral infection like the flu, a child develops encephalopathy

and liver disease.

Although less common, all of these complications can occur in previously healthy individuals

as well.

Although most people don't show symptoms until a few days after infection, the disease can

be spread to other people 1 day before symptoms even begin, and up to a week or two afterwards.

This means that a person can pass the flu to someone else even before they have symptoms

and feel sick.

There are many tests used to detect if an individual is infected with influenza.

Rapid influenza diagnostic tests can detect the flu virus from nasal secretions within

minutes, but often vary in their reliability and often can detect a certain type of influenza,

but not the specific strain of influenza A, like H1N1, for example.

There are two more accurate and reliable ways to identify influenza.

The first is a viral culture, which involves growing the virus and identifying it, and

the second is to use polymerase chain reaction to detect even a tiny amount of viral RNA.

Medical treatment for influenza is usually used for high-risk patients or if the illness

is severe.

There are two classes of medicines: the first is neuraminidase inhibitors, which inhibit

neuroaminidase...and stops the viruses from breaking out of the host cells.

The second are M2 proton channel inhibitors, which are made of a compound called adamantane

and prevent viruses from replicating inside the host cell.

It turns out, though, that the virus's M2 gene mutates frequently, allowing it to become

resistant to the M2 proton channel inhibitors.

The most effective way to prevent influenza is through vaccination, and there are two

that are commonly offered.

One option is a trivalent inactivated influenza vaccine, TIV, which is a killed virus that

is injected into a muscle, and the other is a live, attenuated influenza vaccine, or LAIV,

which is a weakened virus that is sprayed into the nose so that it can infect the epithelial

cells.

Both of them are actually trivalent meaning they contain a mixture of the three strains

that are predicted to be the ones that will dominate the coming season.

This prediction is based on what strains typically dominate year after year - like H1N1, H3N2,

and influenza B - as well as real-time data on which strains are circulating during the

winter season on the other side of the planet, since these ones are likely to spread and

cause trouble.

This is because countries in the northern hemisphere, like the US and Canada, experience

winter—and therefore the flu season—at the opposite time than countries, like Australia,

in the southern hemisphere!

Now, there are a few risks associated with getting the flu vaccine.

Most flu vaccines are produced by growing the virus inside of a chicken embryo and therefore

the vaccine contain small amounts of egg protein, which can be a problem for individuals with

a food allergy.

Guillain-Barre syndrome, an autoimmune disorder of the peripheral nervous system, is another

side effect believed to be associated with the influenza vaccine.

Lastly, children under 6 months old are in the pediatric group at highest risk of serious

influenza complications, but they are too young to get the flu vaccine.

That said, the best way to protect these young infants is to make sure their caregivers are

vaccinated - which creates a natural barrier to infection.

On average, the flu vaccine reduces the risk of illness by half, roughly falling from 10%

to 5% in terms of likelihood of getting sick over the entire winter season, and two factors

play an important role in determining if the flu vaccine will protect a person from illness.

First, a person's characteristics—like being in a high-risk category—can make that person

more susceptible to the virus despite being vaccinated.

Second, the vaccine must match the circulating flu virus of the season.

Since flu viruses are constantly mutating, the flu vaccine formulation is reviewed each

year to keep up with any changes.

Finally, it's important to be vaccinated each year before the start of flu season to ensure

protection against the circulating virus.

Now, getting vaccinated is super important for both yourself as well as the community,

since if the majority of a community is vaccinated against influenza, or any other contagious

diseases, it actually protects the other members of the community, even those few that aren't

vaccinated!

Alright, so let's say one everyone's not vaccinated, and one person gets the flu and then comes

in contact with two other people.

Those two people then get it and each spread it to two other people.

This chain reaction goes on and on, maybe even causing an influenza outbreak in that

community.

But now let's say that the majority of people are vaccinated, in this case the chain reaction

can't spread through the whole community, so even if a few people aren't vaccinated,

they're still protected.

This is called herd immunity, because the herd is protecting the weakest members.

This is especially important for people who can't get certain vaccines—like infants,

pregnant women, or immunocompromised individuals—because they still get some protection when the spread

of contagious disease is contained.

Alright, as a quick recap, influenza, also known as the flu, is a common infectious disease,

and can spread from person to person through tiny droplets in the air or on surfaces.

Most people recover from the flu without complications, though sometimes antiviral treatments can

be used.

The most effective way to prevent the flu is through seasonal flu vaccination.