Saturday, May 9, 2009

Influenza A virus subtype H1N1

Wikipedia



Influenza A virus subtype H1N1, also known as A(H1N1), is a subtype of influenza virus A and the most common cause of influenza (flu) in humans. Some strains of H1N1 are endemic in humans, including the strain(s) responsible for the 1918 flu pandemic which killed 50–100 million people worldwide. Less virulent H1N1 strains still exist in the wild today, worldwide, causing a small fraction of all influenza-like illness and a large fraction of all seasonal influenza. H1N1 strains caused roughly half of all flu infections in 2006. Other strains of H1N1 are endemic in pigs and in birds.

In March and April 2009, hundreds of laboratory-confirmed infections and a number of deaths were caused by an outbreak of a new strain of H1N1.





The 2009 outbreak of influenza A (H1N1) virus is an epidemic of a new strain of influenza virus identified in April 2009, and is commonly referred to as "swine flu." The source of the outbreak in humans is still unknown but cases were first discovered in the U.S. and officials soon suspected a link between this and an earlier outbreak of late-season flu cases in Mexico. Within days, hundreds more suspected cases, many resulting in death, were discovered in Mexico, with more cases found in the U.S. and several other countries. Soon after, the U.N.'s World Health Organization (WHO), along with the U.S. Centers for Disease Control and Prevention (CDC), became concerned that it could become a worldwide flu pandemic, and WHO then raised its pandemic alert level to "Phase 5" out of 6 maximum, as a "signal that a pandemic is imminent".

Although virologists have noted that the outbreak is so far relatively mild and less fatal than previous pandemics, other health officials, including CDC Director Richard Besser, worry about what might happen later in the year, saying that "we are not seeing any sign of this petering out. We are still on the upswing of the epidemic curve. The number of cases is expected to rise as the new flu spreads across the country."

The new strain is an apparent reassortment of four strains of influenza A virus subtype H1N1. Analysis by the CDC identified the four component strains as one endemic in humans, one endemic in birds, and two endemic in pigs (swine). However, other scientists have stated that analysis of the 2009 swine flu (A/H1N1) viral genome suggests that all RNA segments are of swine origin, and "this preliminary analysis suggests at least two swine ancestors to the current H1N1, one of them related to the triple reassortant viruses isolated in North America in 1998." One swine influenza strain was widespread in the United States, the other in Eurasia. In a step towards understanding the outbreak, and developing a vaccine, Canadian scientists have completed the full genetic sequencing of H1N1 swine flu virus.

Symptoms and severity

The symptoms seen in U.S. cases resemble those normally seen in influenza, with fever, cough, sore throat, runny nose, headache, and muscle soreness. However, about 38% of patients had vomiting or diarrhea, which is unusual in infections with other strains of influenza.

The CDC does not fully understand why the U.S. cases' symptoms were primarily mild while the Mexican cases had led to multiple deaths. However, research on previous pandemic strains has suggested that mortality can vary widely between different countries, with mortality being concentrated in the developing world.Differences in the viruses or co-infection are also being considered as possible causes. In 1918, influenza weakened the infected, and it was then lung infections such as pneumonia which killed 3% of them. In the current outbreak, the first deaths (13 and 21 April) were diagnosed as 'atypical pneumonias', a pneumonia which, helped by the flu, becomes more dangerous. The CDC's flu chief Nancy Cox said that genetic analysis of the swine flu strain did not reveal the markers for virulence found in the 1918 flu virus.

Colourised transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green). Courtesy of CDC/ Cynthia Goldsmith, Jacqueline Katz, and Sharif R. Zaki, Public Health Image Library, http://phil.cdc.gov/Phil/home.asp

At a press briefing on April 27, acting CDC director Richard Besser stated that out of 40 confirmed cases in the United States at that point, only one individual was hospitalized. He also revealed that the median age was 16 years "with a range in age of 7 to 54 years". By May 5, with 642 confirmed cases in the U.S., the age of the patients ranged from 3 months to 81 years, with 60% of cases occurred in people less than eighteen years old. In all, 36 patients (9%) required hospitalization and two people died.

Whereas most influenza strains affect the elderly and young children worst, most early deaths from this strain were in people aged 25–50, and the WHO expressed some concern over the unusual age profile of the deaths. However, more recent cases have a younger age profile, with more than half of Mexico's confirmed cases being in people aged under 20. By May 6, almost half of Mexico's confirmed swine flu deaths were in people aged under 30.

MIT Team Solves Mystery of 1918 Pandemic that Killed 50-100 Million Worldwide

1918_pandfemic MIT researchers have explained why two mutations in the H1N1 avian flu virus were critical for viral transmission in humans during the 1918 pandemic outbreak that killed at least 50 million people -believed more than that taken by the Black Death, and higher than the number killed in World War I.

The 1918 flu pandemic -commonly knownas the Spanish flu- was an influenza pandemic that started in the United States, appeared in West Africa and France and then spread to nearly every part of the globe in three waves lasting from March 1918 to June 1920, spreading to the Arctic and remote Pacific islands. It was caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. In contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients, the Spanish Flue also claimed healthy young adults, resulting from infection rates of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms.

The disease was first discovered at Fort Riley, Kansasand Queens, New York , in 1918. In August 1918, a more virulent strain appeared simultaneously in Brest, France, in West Africa at Freetown, Sierra Leone, and in the U.S. at Boston, Massachusetts. The Allies of World War I came to call it the Spanish Flu, primarily because the pandemic received greater press attention after it moved from France to Spain in November of 1918.



The MIT team showed that the 1918 influenza strain developed two mutations in a surface molecule called hemagglutinin (HA), which allowed it to bind tightly to receptors in the human upper respiratory tract.

"Two mutations dramatically change the HA binding affinity to receptors found in the human upper airways," said Ram Sasisekharan, MIT's Underwood Prescott Professor of Biological Engineering and Health Sciences and Technology.

In January, Sasisekharan and colleagues reported in Nature Biotechnology that flu viruses can only bind to human respiratory cells if they match the shape of sugar (or glycan) receptors found on those cells.

The glycan receptors found in the human respiratory tract are known as alpha 2-6 receptors, and they come in two shapes-one resembling an open umbrella, and another resembling a cone. To infect humans the MIT team found that avian flu viruses must gain the ability to bind to the umbrella-shaped alpha 2-6 receptor.

In the current study, the team discovered that two mutations in HA allow flu viruses to bind tightly or with high affinity to the umbrella-shaped glycan receptors.

"The affinity between the influenza virus HA and the glycan receptors appears to be a critical determinant for viral transmission," said Sasisekharan.

The researchers used the 1918 influenza virus as a model system to investigate the biochemical basis for hemagglutinin binding to glycans, which leads to viral transmission.


Click to Enlarge Image

This new work could aid researchers in monitoring the HA mutations in the H5N1 avian flu strains currently circulating in Asia. These mutations could enable the virus to jump from birds to humans, as many epidemiologists fear will occur.

Researchers from the Centers for Disease Control and Prevention reported on the varying infectiousness of these strains last year, but the PNAS study is the first that explains the exact biochemical reason underlying these differences.


Table 1: Antigenic Shifts and Pandemics*


Designation

Resulting Pandemic

Death Toll

1889

H3N2

Moderate

?

1918

H1N1 ("Spanish")

Devastating

50-100 million

1957

H2N2 ("Asian")

Moderate

1 million

1968

H3N2 ("Hong Kong")

Mild

1 million

2009




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* H = haemagglutinin; N = neuraminidase




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