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.

Is swine flu (H1N1) a cause of an epidemic or pandemic in 2009?

An epidemic is defined as an outbreak of a contagious disease that is rapid and widespread, affecting many individuals at the same time. The swine flu outbreak in Mexico fit this definition. A pandemic is an epidemic that becomes so widespread that it affects a region, continent, or the world. As of April 2009, the H1N1 swine flu outbreak did not meet this definition. However, as of June 11, 2009, WHO officials determined that H1N1 2009 influenza A swine flu reached WHO level 6 criteria (person-to-person transmission in two separate WHO-determined world regions) and declared the first flu pandemic in 41 years. To date, the flu has reached over 74 different countries on every continent except Antarctica in about three month’s time; fortunately, the severity of the disease has not increased.

Can novel H1N1 swine flu be prevented with a vaccine?

The best way to prevent novel H1N1 swine flu would be the same best way to prevent other influenza infections, and that is vaccination. The CDC has multiple recommendations for vaccination based on who should obtain the first doses when the vaccine becomes available (to protect the most susceptible populations) and according to age groups. The CDC based the recommendations on data obtained from vaccine trials and infection reports gathered over the last few months. The current (October 2009) vaccine recommendations from the CDC say the following groups should get the vaccine as soon as it is available:

* pregnant women,

* people who live with or provide care for children younger than 6 months of age,

* health-care and emergency medical services personnel,

* people between 6 months and 24 years of age, and

* people from the ages of 25 through 64 who are at higher risk because of chronic health disorders such as asthma, diabetes, or a weakened immune system.

Currently, the CDC is stating that people ages 10 and above are likely to need only one vaccine shot to provide protection against novel H1N1 swine flu and further suggest that these shots will be effective in about 76% of people who obtain the vaccine. New vaccine trial data showed that healthy adults produce protective antibodies in about 98% of people in 21 days. Unfortunately, the vaccine shot in children ages 6 months to 9 years of age is not as effective as it is in older children and adults. Consequently, the CDC currently recommends that for ages 6 months up to and including 9 years of age, the children obtain two shots of the novel H1N1 vaccine, the second shot 21 days after the first shot.

Pregnant women are strongly suggested to get vaccinated as stated above. Although some vaccine preparations (multidose vials) contain low levels of thimerosal preservative (a mercury-containing preservative), the CDC still considers the vaccine safe for the fetus and mother. However, some vaccine preparations that are in single-dose vials will not have thimerosal preservative, so those pregnant individuals who are concerned about thimerosal can get this vaccine preparation when it is available.

Another type of vaccine (currently named Influenza A [H1N1] 2009 Monovalent Vaccine Live, Intranasal) has been made available during the first week in October 2009. It is a live attenuated novel H1N1 flu vaccine that contains no thimerosal, is produced by MedImmune, LLC, and is sprayed into the nostrils. This vaccine is only for healthy people 2-49 years of age, and some data suggest that it is less effective in generating an immune response in adults than the vaccine injection. The dosing schedule is as follows:

* Children 2-9 years of age should receive two doses (0.1 ml in each nostril; total equals 0.2 ml per dose) — the second dose should be given the same way about one month after the first dose

* Children, adolescents and adults, 10-49 years of age should receive one dose — (0.1 ml in each nostril; total equals 0.2 ml per dose)

The CDC occasionally makes changes and updates its information on vaccines and other recommendations about the current flu pandemic. The CDC states, “for the most accurate health information, visit http://www.cdc.gov or call 1-800-CDC-INFO, 24/7.” Caregivers should check the vaccine package inserts for more detailed information on the vaccines when they become available. This article has an updated timeline for novel H1N1 swine flu attached (see below) and provides the reader with current details about the pandemic. The following is a list of the CDC-approved H1N1 vaccines and the companies that name and manufacture them as of 10/29/09:

* Influenza A (H1N1) 2009 Monovalent Vaccine by Sanofi Pasteur

* Influenza A (H1N1) 2009 Monovalent Vaccine by Novartis

* Influenza A (H1N1) 2009 Monovalent Vaccine Live, Intranasal by MedImmune, LLC

* Influenza A (H1N1) 2009 Monovalent Vaccine by CSL Limited

The CDC says that a good way to prevent any flu disease is to avoid exposure to the virus; this is done by frequent hand washing, not touching your hands to your face (especially the nose and mouth), and avoiding any close proximity to or touching any person who may have flu symptoms. Since the virus can remain viable and infectious for about 48 hours on many surfaces, good hygiene and cleaning with soap and water or alcohol-based hand disinfectants are also recommended. Some physicians say face masks may help prevent getting airborne flu viruses (for example, from a cough or sneeze), but others think the better use for masks would be on those people who have symptoms and sneeze or cough. The use of Tamiflu or Relenza may help prevent the flu if taken before symptoms develop or reduce symptoms if taken within about 48 hours after symptoms develop. Some investigators say that administration of these drugs is still useful after 48 hours, especially in high-risk patient populations .However, taking these drugs is not routinely recommended for prevention for the healthy population because investigators suggest that as occurs with most drugs, flu strains will develop resistance to these medications. Recently, the CDC made further suggestions about the use of these antiviral medications. Dr. Schuchat, a CDC official, indicated that three modifications were being suggested (Sept. 8, 2009) to the interim guidelines for use of Tamiflu and Relenza:

1. Patients with high-risk factors should discuss flu symptoms and when to use antiviral medications; doctors should provide a prescription for the antiviral drug for the patient to use if the patient is exposed to flu or develops flu-like symptoms without having to go in to see the doctor.

2. “Watchful waiting” was added as a response to taking antiviral medications, with the emphasis on the fact that those people who develop fever and have a preexisting health condition should then begin the antiviral medication.

3. The antiviral medications are the first-line medicines for treatment of novel H1N1 swine flu, and most current cases of flu are novel H1N1 and are, to date, susceptible to Tamiflu and Relenza.

Your doctor should be consulted before these drugs are prescribed.

In general, preventive measures to prevent the spread of flu are often undertaken by those people who have symptoms. Symptomatic people should stay at home, avoid crowds, and take off from work or school until the disease is no longer transmittable (about two to three weeks) or until medical help and advice is sought. Sneezing, coughing, and nasal secretions need to be kept away from other people; simply using tissues and disposing of them will help others. Quarantining patients is usually not warranted, but such measures depend on the severity of the disease. The CDC recommends that people who appear to have an influenza-like illness upon arrival at work or school or become ill during the day be promptly separated from other people and be advised to go home until at least 24 hours after they are free of fever (100 F [37.8 C] or greater), or signs of a fever, without the use of fever-reducing medications. The novel H1N1 swine flu disease takes about seven to 10 days before fevers stop, but new research data (Sept. 14, 2009) suggests waiting until the cough is gone since many people are still infectious about one week after fever is gone. The CDC has not yet extended their recommendations to stay home for that extra week.

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.

READ ALSO:

* Common herb has flavonoids that fight flu virus
* New tech licensed to combat deadly swine flu virus
* Pandemic is a blink away
* Ginger does ward off flu: study

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.

This graphic shows why the Type A virus can’t be eradicated. (U of Maryland)
READ ALSO:

* Herbal soup fights flu A, perhaps useful to guard off swine flu too?
* Common herb has flavonoids that fight flu virus
* New tech licensed to combat deadly swine flu virus
* Ginger does ward off flu: study

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.”

This is the influenza A virus. (U of Maryland)

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 hybridinfluenza 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,” saidPerez. “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 ofavian 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 ofavian 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.