Influenza A virus subtype H1N1
Influenza A (H1N1) virus is the subtype of influenza A virus that was the most common cause of human influenza (flu) in 2009, and is associated with the 1918 outbreak known as the Spanish Flu.
It is an orthomyxovirus that contains the glycoproteins haemagglutinin and neuraminidase.
For this reason, they are described as H1N1, H1N2 etc. depending on the
type of H or N antigens they express with metabolic synergy.
Haemagglutinin causes red blood cells to clump together and binds the
virus to the infected cell. Neuraminidase are a type of glycoside
hydrolase enzyme which help to move the virus particles through the
infected cell and assist in budding from the host cells.[1]
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 small percentage of all human flu infections in 2004–2005.[2] Other strains of H1N1 are endemic in pigs (swine influenza) and in birds (avian influenza).
In June 2009, the World Health Organization (WHO) declared the new strain of swine-origin H1N1 as a pandemic. This strain is often called swine flu
by the public media. This novel virus spread worldwide and had caused
about 17,000 deaths by the start of 2010. On August 10, 2010, the World
Health Organization declared thaf the H1N1 influenza pandemic over,
saying worldwide flu activity had returned to typical seasonal patterns.[3]
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Swine influenza
Swine
influenza (swine flu or pig flu) is a respiratory disease that occurs
in pigs that is caused by the Influenza A virus. Influenza viruses that
are normally found in swine are known as swine influenza viruses (SIVs).
The known SIV strains include influenza C and the subtypes of influenza
A known as H1N1, H1N2, H3N1, H3N2 and H2N3. Pigs can also become infected with the H4N6 and H9N2 subtypes.[4]
Swine influenza virus is common throughout pig
populations worldwide. Transmission of the virus from pigs to humans is
not common and does not always lead to human influenza, often resulting
only in the production of antibodies in the blood. If transmission does
cause human influenza, it is called zoonotic swine flu
or a variant virus. People with regular exposure to pigs are at
increased risk of swine flu infection. The meat of an infected animal
poses no risk of infection when properly cooked.
Pigs experimentally infected with the strain of swine
flu that caused the human pandemic of 2009–10 showed clinical signs of
flu within four days, and the virus spread to other uninfected pigs
housed with the infected ones.[5]
During the mid-20th century, identification of
influenza subtypes became possible, allowing accurate diagnosis of
transmission to humans. Since then, only 50 such transmissions have been
confirmed. These strains of swine flu rarely pass from human to human.
Symptoms of zoonotic swine flu in humans are similar to those of
influenza and of influenza-like illness in general, namely chills, fever, sore throat, muscle pains, severe headache, coughing, weakness, and general discomfort. The recommended time of isolation is about five days.
Notable incidents
Spanish flu
The Spanish flu, also known as la grippe, La Gripe Española, or La Pesadilla, was an unusually severe and deadly strain of swine influenza, a viral infectious disease,
that killed some 50 to 100 million people worldwide over about a year
in 1918 and 1919. It is thought to be one of the deadliest pandemics in human history.
The 1918 flu caused an unusual number of deaths, possibly due to it causing a cytokine storm in the body.[6][7] (The current H5N1 bird flu, also an Influenza A virus, has a similar effect.)[8] The Spanish flu virus infected lung cells, leading to overstimulation of the immune system via release of cytokines into the lung tissue. This leads to extensive leukocyte
migration towards the lungs, causing destruction of lung tissue and
secretion of liquid into the organ. This makes it difficult for the
patient to breathe. In contrast to other pandemics, which mostly kill
the old and the very young, the 1918 pandemic killed unusual numbers of
young adults, which may have been due to their healthy immune systems
mounting a too-strong and damaging response to the infection.[9]
The term "Spanish" flu was coined because Spain was at the time the only European country where the press were printing reports of the outbreak, which had killed thousands in the armies fighting World War I. Other countries suppressed the news in order to protect morale.[10]
Fort Dix outbreak
In 1976, a novel swine influenza A (H1N1) caused
severe respiratory illness in 13 soldiers with 1 death at Fort Dix, New
Jersey. The virus was detected only from January 19 to February 9 and
did not spread beyond Fort Dix.[11]
Retrospective serologic testing subsequently demonstrated that up to
230 soldiers had been infected with the novel virus, which was an H1N1
strain. The cause of the outbreak is still unknown and no exposure to
pigs was identified.[12]
Russian flu
The 1977–1978 Russian flu epidemic was caused by strain Influenza A/USSR/90/77 (H1N1).
It infected mostly children and young adults under 23 because a similar
strain was prevalent in 1947–57, causing most adults to have
substantial immunity. Because of a striking similarity in the viral RNA
of both strains – one which is unlikely to appear in nature due to antigenic drift
– it was speculated that the later outbreak was due to a laboratory
incident in Russia or Northern China, though this was denied by
scientists in those countries.[13][14][15] The virus was included in the 1978–1979 influenza vaccine.[16][17][18][19]
2009 A(H1N1) pandemic
In the 2009 flu pandemic, the virus
isolated from patients in the United States was found to be made up of
genetic elements from four different flu viruses – North American swine
influenza, North American avian influenza, human influenza, and swine
influenza virus typically found in Asia and Europe – "an unusually mongrelised mix of genetic sequences."[20] This new strain appears to be a result of reassortment of human influenza and swine influenza viruses, in all four different strains of subtype H1N1.
Preliminary genetic characterization found that the hemagglutinin (HA) gene was similar to that of swine flu viruses present in U.S. pigs since 1999, but the neuraminidase (NA) and matrix protein
(M) genes resembled versions present in European swine flu isolates.
The six genes from American swine flu are themselves mixtures of swine
flu, bird flu, and human flu viruses.[21]
While viruses with this genetic makeup had not previously been found to
be circulating in humans or pigs, there is no formal national
surveillance system to determine what viruses are circulating in pigs in
the U.S.[22]
In April 2009, an outbreak of influenza-like illness (ILI) occurred in the United States and then in Mexico; the CDC
reported seven cases of novel A/H1N1 influenza. By April 24 it became
clear that the outbreak of ILI in Mexico and the confirmed cases of
novel influenza A in the southwest US were related and WHO issued a
health advisory on the outbreak of "influenza-like illness in the United
States and Mexico".[23]
The disease then spread very rapidly, with the number of confirmed
cases rising to 2,099 by May 7, despite aggressive measures taken by the
Mexican government to curb the spread of the disease.[24] The outbreak had been predicted a year earlier by noticing the increasing number of replikins, a type of peptide, found in the virus.[25]
On June 11, 2009, the WHO declared an H1N1 pandemic, moving the alert level to phase 6, marking the first global pandemic since the 1968 Hong Kong flu.[26] On October 25, 2009, U.S. President Barack Obama officially declared H1N1 a national emergency[27] Despite President Obama's concern, a Fairleigh Dickinson University
PublicMind poll found in October 2009 that an overwhelming majority of
New Jerseyans (74%) were not very worried or not at all worried about
contracting the H1N1 flu virus.[28]
However, the President’s declaration caused many U.S. employers to take
actions to help stem the spread of the swine flu and to accommodate
employees and / or workflow which may be impacted by an outbreak.[29]
A study conducted in coordination with the University
of Michigan Health Service — scheduled for publication in the December
2009 American Journal of Roentgenology — warned that H1N1 flu can cause pulmonary embolism,
surmised as a leading cause of death in this pandemic. The study
authors suggest physician evaluation via contrast enhanced CT scans for
the presence of pulmonary emboli when caring for patients diagnosed with
respiratory complications from a "severe" case of the H1N1 flu.[30]
However pulmonary embolism is not the only embolic manifestation of
H1N1 infection. H1N1 may induce a number of embolic events such as
myocardial infarction, bilateral massive DVT, arterial thrombus of
infrarenal aorta, thrombosis of right external Iliac vein and common
femoral vein or cerebral gas embolism. The type of embolic events caused
by H1N1 infection are summarized in a recently published review by
Dimitroulis Ioannis et al.[31]
The March 21, 2010 worldwide update, by the U.N.'s
World Health Organization (WHO), states that "213 countries and overseas
territories/communities have reported laboratory confirmed cases of
pandemic influenza H1N1 2009, including at least 16,931 deaths."[32]
As of May 30, 2010, worldwide update by World Health Organization(WHO)
more than 214 countries and overseas territories or communities have
reported laboratory confirmed cases of pandemic influenza H1N1 2009,
including over 18,138 deaths.[33] The research team of Andrew Miller MD showed pregnant patients are at increased risk.[34]
It has been suggested that pregnant women and certain populations such
as native North Americans have a greater likelihood of developing a T helper type 2 response to H1N1 influenza which may be responsible for the systemic inflammatory response syndrome that causes pulmonary edema and death.[35]
On 26 April 2011, an H1N1 pandemic preparedness alert was issued by the World Health Organization for the Americas.[36]
In August 2011, according to the U.S. Geological Survey and the CDC,
northern sea otters off the coast of Washington state were infected with
the same version of the H1N1 flu virus that caused the 2009 pandemic[when?] and "may be a newly identified animal host of influenza viruses".[37] In May 2013, seventeen people died during an H1N1 outbreak in Venezuela, and a further 250 were infected.[38]
As of early January 2014, Texas health officials have confirmed at
least thirty-three H1N1 deaths and widespread outbreak during the
2013/2014 flu season,[39]
while twenty-one more deaths have been reported across the US. Nine
people have been reported dead from an outbreak in several Canadian
cities,[40] and Mexico reports outbreaks resulting in at least one death.[41] Spanish health authorities have confirmed 35 H1N1 cases in the Aragon region, 18 of whom are in intensive care.[42] On March 17, 2014, three cases were confirmed with a possible fourth awaiting results occurring at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada.[43]
2015 India outbreak
Swine flu was reported in India in early 2015. The disease affected more than 31,000 people and claimed over 1,900 lives.[44]
2017 Maldives outbreak
Total number of people who passed away due to this disease is so far unknown. Patient zero was never identified.[47]
Schools were closed for a week due to the disease,
but were ordered by the Ministry of Education to open after the holidays
even though the disease was not fully under control. [48]
After widespread rumors about Saudi Arabia going to
purchase an entire atoll from Maldives, Saudi Arabian embassy in
Maldives issued a statement against the rumors. [49] [50] However the trip of the Saudi monarch was going forward until it was cancelled later due to the H1N1 outbreak in Maldives. [51]
2017 Myanmar outbreak
Myanmar reported H1N1 in late July 2017. As of 27 July, 30 confirmed cases and 6 people had died.[52] The Ministry of Health and Sports
of Myanmar sent official request to WHO to provide help to control the
virus; and also mentioned that government would be seeking international
assistance, including from the UN, China and the United States.[53]
In pregnancy
Pregnant
women who contract the H1N1 infection are at a greater risk of
developing complications because of hormonal changes, physical changes
and changes to their immune system to accommodate the growing fetus.[54]
For this reason the Center for Disease Control and Prevention
recommends that those who are pregnant to get vaccinated to prevent the
influenza virus. The vaccination should not be taken by people who have
had a severe allergic reaction to the influenza vaccination.
Additionally those who are moderately to severely ill, with or without a
fever should wait until they recover before taking the vaccination.[55]
Pregnant women who become infected with the influenza
are advised to contact their doctor immediately. Influenza can be
treated using antiviral medication, which are available by prescription.
Oseltamivir (trade name Tamiflu) and zanamivir (Relenza) are two neuraminidase inhibitors
(antiviral medications) currently recommended. It has been shown that
they are most effective when taken within two days of becoming sick.[56]
Since October 1, 2008, the CDC has tested 1,146
seasonal influenza A (H1N1) viruses for resistance against oseltamivir
and zanamivir. It was found that 99.6% of the samples were resistant to
oseltamivir while none were resistant to zanamivir. In 853 samples of
2009 Influenza A (H1N1) virus only 4% showed resistance to oseltamivir,
while none of 376 samples showed resistance to zanamivir.[57]
A study conducted in Japan during the 2009 H1N1 pandemic concluded that
infants exposed to either oseltamivir or zanamivir had no short term
adverse effects.[58] Both amantadine and rimantadine have been found to be teratogenic and embryotoxic (malformations and toxic effects on the embryo) when given at high doses in animal studies.[59]
Additional images
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