How is swine flu (H1N1) diagnosed?

Swine flu is presumptively diagnosed clinically by the patient’s history of association with people known to have the disease and their symptoms listed above. Usually, a quick test (for example, nasopharyngeal swab sample) is done to see if the patient is infected with influenza A or B virus. Most of the tests can distinguish between A and B types. The test can be negative (no flu infection) or positive for type A and B. If the test is positive for type B, the flu is not likely to be swine flu (H1N1). If it is positive for type A, the person could have a conventional flu strain or swine flu (H1N1). However, the accuracy of these tests has been challenged, and the U.S. Centers for Disease Control and Prevention (CDC) has not completed their comparative studies of these tests. However, a new test developed by the CDC and a commercial company reportedly can detect H1N1 reliably in about one hour; as of October 2009, the test is only available to the military.

Swine flu (H1N1) is definitively diagnosed by identifying the particular antigens associated with the virus type. In general, this test is done in a specialized laboratory and is not done by many doctors’ offices or hospital laboratories. However, doctors’ offices are able to send specimens to specialized laboratories if necessary. Because of the large number of novel H1N1 swine flu cases (as of October 2009, the vast majority of flu cases [about 99%] are due to novel H1N1 flu viruses), the CDC recommends only hospitalized patients’ flu virus strains be sent to reference labs to be identified.

What are the symptoms of swine flu (H1N1)?

Symptoms of swine flu are similar to most influenza infections: fever (100F or greater), cough, nasal secretions, fatigue, and headache, with fatigue being reported in most infected individuals. Some patients also get nausea, vomiting, and diarrhea. In Mexico, many of the patients are young adults, which made some investigators speculate that a strong immune response may cause some collateral tissue damage. Some patients develop severe respiratory symptoms and need respiratory support (such as a ventilator to breathe for the patient). Patients can get pneumonia (bacterial secondary infection) if the viral infection persists, and some can develop seizures. Death often occurs from secondary bacterial infection of the lungs; appropriate antibiotics need to be used in these patients. The usual mortality (death) rate for typical influenza A is about 0.1%, while the 1918 “Spanish flu” epidemic had an estimated mortality rate ranging from 2%-20%. Swine flu in Mexico (as of April 2009) has had about 160 deaths and about 2,500 confirmed cases, which would correspond to a mortality rate of about 6%, but these initial data have been revised and the mortality rate currently in Mexico is estimated to be much lower. By June 2009, the virus had reached 74 different countries on every continent except Antarctica, and by September 2009, the virus had been reported in most countries in the world. Fortunately, the mortality rate as of October 2009 has been low but higher than for the conventional flu (average conventional flu mortality rate is about 36,000 per year; projected novel H1N1 flu mortality rate is 90,000 per year in the U.S. as determined by the president’s advisory committee).

Why is swine flu (H1N1) now infecting humans?

Many researchers now consider that two main series of events can lead to swine flu (and also avian or bird flu) becoming a major cause for influenza illness in humans.

First, the influenza viruses (types A, B, C) are enveloped RNA viruses with a segmented genome; this means the viral RNA genetic code is not a single strand of RNA but exists as eight different RNA segments in the influenza viruses. A human (or bird) influenza virus can infect a pig respiratory cell at the same time as a swine influenza virus; some of the replicating RNA strands from the human virus can get mistakenly enclosed inside the enveloped swine influenza virus. For example, one cell could contain eight swine flu and eight human flu RNA segments. The total number of RNA types in one cell would be 16; four swine and four human flu RNA segments could be incorporated into one particle, making a viable eight RNA segmented flu virus from the 16 available segment types. Various combinations of RNA segments can result in a new subtype of virus (known as antigenic shift) that may have the ability to preferentially infect humans but still show characteristics unique to the swine influenza virus (see Figure 1). It is even possible to include RNA strands from birds, swine, and human influenza viruses into one virus if a cell becomes infected with all three types of influenza (for example, two bird flu, three swine flu, and three human flu RNA segments to produce a viable eight-segment new type of flu viral genome). Formation of a new viral type is considered to be antigenic shift; small changes in an individual RNA segment in flu viruses are termed antigenic drift and result in minor changes in the virus. However, these can accumulate over time to produce enough minor changes that cumulatively change the virus’ antigenic makeup over time (usually years).

Second, pigs can play a unique role as an intermediary host to new flu types because pig respiratory cells can be infected directly with bird, human, and other mammalian flu viruses. Consequently, pig respiratory cells are able to be infected with many types of flu and can function as a “mixing pot” for flu RNA segments (see Figure 1). Bird flu viruses, which usually infect the gastrointestinal cells of many bird species, are shed in bird feces. Pigs can pick these viruses up from the environment and seem to be the major way that bird flu virus RNA segments enter the mammalian flu virus population.

What is swine flu (novel H1N1 influenza A swine flu)?

Swine flu (swine influenza) is a respiratory disease caused by viruses (influenza viruses) that infect the respiratory tract of pigs and result in nasal secretions, a barking-like cough, decreased appetite, and listless behavior. Swine flu produces most of the same symptoms in pigs as human flu produces in people. Swine flu can last about one to two weeks in pigs that survive. Swine influenza virus was first isolated from pigs in 1930 in the U.S. and has been recognized by pork producers and veterinarians to cause infections in pigs worldwide. In a number of instances, people have developed the swine flu infection when they are closely associated with pigs (for example, farmers, pork processors), and likewise, pig populations have occasionally been infected with the human flu infection. In most instances, the cross-species infections (swine virus to man; human flu virus to pigs) have remained in local areas and have not caused national or worldwide infections in either pigs or humans. Unfortunately, this cross-species situation with influenza viruses has had the potential to change. Investigators think the 2009 swine flu strain, first seen in Mexico, should be termed novel H1N1 flu since it is mainly found infecting people and exhibits two main surface antigens, H1 (hemagglutinin type 1) and N1 (neuraminidase type1). Recent investigations show the eight RNA strands from novel H1N1 flu have one strand derived from human flu strains, two from avian (bird) strains, and five from swine strains.

Common herb has flavonoids that fight flu virus

CM NEWS – A commonly used Chinese herb for cold and fever contains ingredients that can fight influenza viruses, a study in China suggests.

Elsholtzia rugulosa (野拔子 ye ba zi), a common Chinese herb, is widely used in the treatment of cold and fever. A group of researchers of the Chinese Academy of Medical Sciences and Peking Union Medical College, as well as University of Macau investigated the anti-flu functions of the ingredients of this plant.
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In order to elucidate the action mechanism and the active principles from the plant against anti-influenza virus, the influenza virus neuraminidase (NA) activity assay and in vitro antiviral activity assay were established, and the isolation of the active principles was guided by NA activity.

Their study established that five active constituents were found in ye ba zi and they are all flavonoids.

What are flavonoids? Flavonoids (or bioflavonoids) are a class of plant secondary metabolites fulfilling many functions including producing yellow or red/blue pigmentation in flowers and protection from attack by microbes and insects. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been referred to as “nature’s biological response modifiers” because of strong experimental evidence of their inherent ability to modify the body’s reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory, anti-microbial and anti-cancer activity.

Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins.

The five constituents are:

1. apigenin
2. luteolin
3. apiin
4. galuteolin
5. luteolin 3′-glucuronyl acid methyl ester

According to the researchers, these constituents all possessed anti-influenza virus activity. Among them, apigenin and luteolin exhibited the highest activities against influenza virus (H3N2).

What is apigenin? Apigenin is described as a nonmutagenic bioflavonoid which is presented in leafy plants and vegetables (e.g., parsley, artichoke, basil, celery) and has significant chemopreventive activity against UV-radiation. Current research trials indicate that it may reduce DNA oxidative damage; inhibit the growth of human leukemia cells and induced these cells to differentiate; inhibit cancer cell signal transduction and induce apoptosis (cell death); act as an anti-inflammatory; and as an anti-spasmodic or spasmolytic.

Apigenin is also reported to be useful in fighting against antiestrogen-resistant breast cancer.

Apigenin is a bioflavone, considered to have a bioactive effect on human health as antioxidant, radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, immunity system modulater.

What is luteolin? Luteolin is a flavonoid thought to play an important role in the human body as an antioxidant, a free radical scavenger, an agent in the prevention of inflammation, a promoter of carbohydrate metabolism, and an immune system modulator. These characteristics of luteolin are also believed to play an important part in the prevention of cancer. Multiple research experiments describe luteolin as a biochemical agent that can dramatically reduce inflammation.

Luteolin inhibited the excess production of TNF-alpha, which directly causes inflammation and apoptosis. Luteolin also offers hope to develop a novel type of anti-inflammatory and anti-allergic drugs.

Luteolin is most often found in leaves, but it is also seen in rinds, barks, clover blossom and ragweed pollen. It has also been isolated from Salvia tomentosa. Dietary sources include celery, green pepper, perilla and camomile tea.

Herbal soup fights flu A, perhaps useful to guard off swine flu too?

CM NEWS – Swine flu outbreak has scared the world recently, with death toll reaching 100 and counting. While scientists are racing to understand the flu and in full effort to formulate a new vaccine against it, the only things ordinary folks like us can do is to keep ourselves healthy and strong to guard off infection. In traditional Asian medicine, a decoction called Ma Huang Tang (麻黃湯) in Chinese or Mao-to in Japanese.

What’re in Ma Huang Tang?

The main ingredients of Ma Huang Tang are:


In a Japanese study conducted to evaluate the effect of oral Mao-to (麻黃湯) administration in children with type A influenza, the Mao-to powder was more effective in controlling fever due to flu A than administering an antiviral drug commonly used to fight flu A, Oseltamivir, alone.

What is Oseltamivir? Oseltamivir is an antiviral drug that is used in the treatment and prophylaxis of both Influenzavirus A and Influenzavirus B infection. Like zanamivir, oseltamivir is a neuraminidase inhibitor. It acts as a transition-state analogue inhibitor of influenza neuraminidase, preventing progeny virions from emerging from infected cells.

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In the Japanese study, the scientists performed a controlled trial of 60 children, from 5 months through 13 years of age, with fever and influenza-like symptom of up to 48 h duration. Patients assigned into the following 3 groups: oral Mao-to powder 0.06 g/kg body wt. three times daily; Oseltamivir 2 mg/kg body wt. dose twice daily; or both oral Mao-to plus Oseltamivir.

The results indicated that the median duration of fever after treatment was significantly shorter in the Mao-to and Mao-to plus Oseltamivir groups, compared with the Oseltamivir only group. It was thus concluded by the scientists that oral Mao-to administration was effective in the control of fever due to type A influenza infection in children.

Pandemic is a blink away

U of Maryland – A new study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu

pandemic is greater than previously thought. Results also illustrate how the current swine flu outbreak likely came about.

As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However, in research recently published in the Proceedings of the National Academy of Sciences, Associate Professor Daniel Perez from the

University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an

avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.

“This is similar to the method by which the current swine influenza strain likely formed,” said Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project, AICAP. “The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing.”

In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human

pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together, Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface

avian flu genes from the H9N2 virus. Though it comes from a different strain of

avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez’s research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.

Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.

When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, they concluded that after an animal-human hybrid influenza virus forms in nature, a human

pandemic of this virus is potentially just a few mutations away.

“We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets,” Perez said. “We will be doing more research on the current swine flu strain to study its specific genetic mutations.”

Perez found that one of the two of the genetic mutations in his lab strain that enabled respiratory transmission between mammals was on the tip of the HA surface protein, one of the sites where human antibodies created in response to current vaccines would bind.

“Because the binding site of the mutant virus is different from the virus upon which the vaccine is modelled, it may mean that current vaccine stocks would not be as effective against the H9N2 mutant strain as previously anticipated,” said Perez. “We should keep this in mind when designing vaccines for an

avian flu

pandemic in humans.”

However, scientists cannot predict what the actual mutations will look like if and when they occur in nature, or even which strain of avian influenza will mutate to infect mammals.

“This is just the tip of the iceberg,” said Perez. “Many more studies have to be done to see which combinations of mutations cause this type of transmission before we can design the appropriate vaccines.”

Perez will be talking this week with the NIH and the CDC to discuss his team’s role in researching the current swine flu virus strain. Perez will likely do studies related to vaccine development, virus transmission between humans and animals, and the pathogenesis of the virus.

A virus vaccine is derived from the virus itself. The vaccine consists of virus components or killed viruses that mimic the presence of the virus without causing disease. These prime the body’s immune system to recognize and fight against the virus. The immune system produces antibodies against the vaccine that remain in the system until they are needed. If that virus, or in some cases a closely similar one is later introduced into the system, those antibodies attach to viral particles and remove them before they have time to replicate, preventing or lessening symptoms of the virus.

The immune system also retains antibodies to a virus after being infected with it, so humans have general immunity to human strains of avian influenza strains. But humans do not generally have immunity to

avian flu strains because they have not been infected by them before. The surface proteins are sufficiently different to escape the human immune response.

Avian flu strains are therefore more dangerous for humans because the human immune system cannot recognize the virus or protect against it.

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