Bird Flu Fears

by Carole Nickerson

Remember the good old days when a cold consisted of a runny nose, stuffed up sinuses, and a few aches & pains?

Or how about the flu? I remember as a kid, the worst horror story I ever heard of was someone having a week of diarrhea & vomiting. That was scary stuff, and not even so much in the fact that you would feel downright rotten, but the embarassment of it all.

Times have changed....

It seems every year you hear about some crazy new viral mutation or "superbug" sweeping into the population, ready and willing to not just make us sick, but to outright kill us.

Infectious diseases have always been a threat to mankind. In the past 10 years we have seen many new & reemerging diseases come to the surface - SARS, Monkeypox, Malaria, Tuberculosis, West Nile Virus, and the most popular of our time - HIV/AIDS. A report from the National Institute of Allergy and Infectious Diseases published a 10-year perspective where it showed that nearly 25% of all worldwide deaths are caused by infectious & parasitic diseases. That's about 15 million out of some 57 million annual deaths.

In comes "Bird Flu"......

Technically known as "avian influenza" H5N1, it is the latest infectious threat on the scene, making headlines around the world - and for good reason. There have been reports that it could kill anywhere between 50% - 90% of those infected. It's important to remember that opinions & theories are going to vary because there just isn't enough data to work with in establishing a true perspective on what h5N1 could do. We do know that out of 117 reported human cases, 60 were fatal. That is indeed a scary number.

There is a lot of controversy over the numbers though. Some scientists claim the threat of bird flu is much lower, while others predict a global outbreak in the very near future that could kill millions. It appears to be yet another issue where the "experts" can only guess.

People become infected when they come into contact with infected poultry and poultry feces, usually during the process of slaughtering and preparing meat. The World Health Organization reports though that this does not occur in everyone exposed though. For many years it has essentially been a disease affecting birds, but over time managed to cross over into a threat to humans.

So why the worry?

What worries scientists is that if given the right conditions, the H5N1 virus could mutate into a new form which would allow human-to-human infection, sparking a global pandemic. There has been at least one reported case of human-to-human infection in Thailand already, so the question now is not "if", but "when" it will occur. H5N1 is now firmly established in large parts of Asia, with each human infection giving the virus more opportunity to adapt and mutate. Based on it's history, makeup and what we've learned from it's cousins & past pandemics, it's ability & likelihood of mutating is very high, making the risk for a global pandemic a very real possibility.

Don't they have anything to treat this?

Unfortunately, there is no commercially available product which can prevent H5N1 infection in humans. It is under development in several countries, but no vaccines are expected to be available for several months until after the onset of a pandemic. The problem is that they can only guess as to what the virus will look & behave like in a mutated form. It's like trying to figure out what a 2 month old child will look like when they are 20 and buying the clothes long before you even know if they'll fit.

Most recently, a drug called Tamiflu was being stockpiled by some countries to combat H5N1, but there are reports that it may not be very effective at all. Tamiflu was really designed for your "average joe" flu that we all have has at some point. In higher doses, it may work to some degree. Then again, it might not. We just don't know that yet. As with everything - there is controversy, mixed messages & conflicting expert opinions. There have been a number of other vaccines (old & new) being discussed in the news recently. To keep up on the vaccine situation, it probably best to keep your eye on the WHO website at: http://www.wpro.who.int/health_topics/avian_influenza/

If there is one thing everyone can agree on is that the world is not prepared. WHO has urged all countries to establish preparedness plans, but only around 40 have done so and most developing countries simply don't have the resources to prepare themselves and even fewer have access to vaccines.

How ironic that "chicken soup" has been the choice for curing colds and flus for so many generations.

About the Author
Carole Nickerson is a writer & web developer who has been writing on various topics of interest since 1998. To read more on the avian bird flu topic, visit http://www.GlobalBirdFlu.com

Bird Flu: Diagnosis

by Bradford Frank

Central to the problem of dealing with bird flu is diagnosis. A number of upper respiratory infections have similar symptoms—at least at the onset of the illness, including the common cold, seasonal influenza, and bird flu. Seasonal flu and bird flu have almost identical symptoms—including fever, cough, malaise (feeling unwell), nausea, vomiting, and diarrhea. This is, needless to say, a gigantic problem in accurately diagnosing bird flu—which is critical to beginning appropriate treatment as well as initiating infection control procedures and public health measures.

Currently, accurate testing for bird flu and other vial infections that can cause similar symptoms is difficult and requires specialized testing. This testing is time consuming and only available in specialized reference laboratories, which are few and far between. Fortunately, this may change in the near future.

According to Richard Janeczko, Ph.D., executive vice-president and chief scientific officer, Tm Bioscience, located In Toronto, Canada, is feverishly working to complete the final stage of development of an amazing test—not only for bird flu, but for more than 15 other viral infections (including severe acute respiratory syndrome or SARS), many of which can mimic the symptoms of bird flu (personal communication). (Tm Bioscience is a DNA-based diagnostics company developing a suite of genetic tests. Tm Bioscience’s product pipeline includes tests for genetic disorders, drug metabolism, and infectious diseases.

The test, called the Multiplexed Respiratory Test, discriminates influenza A from influenza B and identifies the H5-subtype of influenza A (bird flu is “H5N1”) from all other H subtypes. In addition, it can identify almost all the other common—and some uncommon—viruses that cause influenza-like illnesses. This is extremely important in managing patients, communities and economic issues. Other tests have lower clinical sensitivities and specificities which can lead to both false positives and false negatives.

By incorrectly identifying an outbreak as due to H5N1, patients could be treated with anti-virals unnecessarily (thus raising the chances of selecting for drug-resistant strains), unneeded vaccination programs in asymptomatic individuals could be initiated, and damage to local and national economies—through such measures as culling of commercial poultry operations—could occur. Conversely a false-negative test result could lead to catastrophic outcomes, including a pandemic.

The assay utilizes swab specimens taken from the nose and takes less than 5 hours to perform. It was developed for use as a diagnostic tool and for infection control in hospitals. The assay has been slated for expedited review by the Food and Drug Administration (FDA), and TM Bioscience is hoping to have an FDA-cleared test available by the end of January 2006. If this assay delivers what it claims, it will have huge applicability on a global basis and save many lives.

About the Author
Bradford Frank, M.D., M.P.H., M.B.A. The Frank Group. P.O. Box 138 Lakewood, NY 14750 http://www.AvoidBirdFlu.com

Discovery of new drug candidates to combat bird flu

As the specter of a worldwide outbreak of avian or "bird flu" lingers, health officials recognize that new drugs are desperately needed since some strains of the virus already have developed resistance to the current roster of anti-flu remedies.
Now, a team of UC San Diego scientists - with the help of resources at the San Diego Supercomputer Center (SDSC), also at UC San Diego - have isolated more than two dozen promising and novel compounds from which new "designer drugs" might be developed to combat this disease. In some cases, the compounds appeared to be equal or stronger inhibitors than currently available anti-flu remedies.

"If those resistant strains begin to propagate, then that's when we're going to be in trouble, because we don't have any anti-virals active against them," said Rommie Amaro, a postdoctoral fellow in chemistry at UC San Diego. "So, we should have something as a backup, and that's exactly why we're working on this."

Avian flu has provoked considerable concern since humans have little or no immune protection against the virus. While flu vaccines are being developed, it could take up to nine months for an effective vaccine to be developed against any new strains, and could still be rendered ineffective if any new strains arise over that time. Should the virus gain the capacity to spread from person to person, the result could be a worldwide outbreak or pandemic.

"In light of the urgency to find drugs to combat this virus, we're hopeful that our results will assist in that effort," said J. Andrew McCammon, holder of the Joseph Mayer Chair of Theoretical Chemistry at UC San Diego and a Howard Hughes Medical Institute Investigator.

Also participating in this study were researchers from the National Biomedical Computation Resource (NBCR), part of the Center for Research on Biological Systems and the California Institute for Telecommunications and Information Technology at UC San Diego, including Lily S. Cheng, co-first author; Don Xu; Wilfred Li; and Peter W. Arzberger.

The study, published in the Journal of Medicinal Chemistry, builds on prior work that captured the nanosecond-by-nanosecond movements of a protein called neuraminidase 1 (or N1), needed by the avian flu virus to spread infection to new cells. To help reveal the often-spasmodic motion of proteins, scientists work with molecular dynamics codes that simulate their movements as they obey the fundamental laws of physics. Such is the complexity of the mathematical calculations needed for these simulations that scientists often require the use of supercomputers. In this case, the researchers ran their data through a molecular dynamics program called NAMD - developed at the University of Illinois at Urbana-Champaign - on supercomputers at SDSC and the National Center for Supercomputing Applications in Illinois.

Some surprising details emerged as the scientists watched the protein gyrate and wiggle over time. In particular, one region - dubbed a "hot pocket" - appeared to be quite dynamic and flexible. Amaro said the topology of this region and the amino acids linking the pocket are significantly different from what the scientists previously observed in a static image of the protein's crystal structure.

"Crystal structures are very important," she said. "They give us a real picture of the protein. But it's just one picture."

Over the past decade or so, scientists have come to realize that the sometimes colorful structures gleaned from standard crystallography studies are limited. Instead of a still-life painting, proteins act more like a moving picture, constantly twitching and jiggling, making the goal of finding a specific inhibitor somewhat daunting. It's somewhat like a baseball pitcher attempting to throw strikes to a catcher who's doing handsprings behind home plate.

Molecular dynamics simulations already have proved their value for other drug designs, said McCammon, one of the pioneers in the field. For example, the route to the development of raltegravir, an anti-integrase inhibitor recently approved by the U.S. Food and Drug Administration to combat HIV, was discovered in McCammon's lab.

"The treatment of receptor flexibility with molecular dynamics simulations played a critical role in understanding the mechanism of action for this new class of inhibitors," said McCammon, a professor of Pharmacology at UC San Diego.

In their latest work, the scientists conducted a "virtual screen" of an ensemble of 1,883 compounds selected from the National Cancer Institute Diversity Set, using a computational tool called AutoDock that predicts how small molecules, such as drug candidates, bind to a receptor of a known three-dimensional structure. The goal was to try to determine which compounds fit best into the "hot pocket" region of N1. Generally, compounds that most easily bind to the site are considered to be top hits for validation and further optimization as drug candidates.

Five other compounds known to experimentally bind to avian influenza N1 were also screened, including drugs now available or in clinical trials.

The results were intriguing. About 27 compounds showed significant promise, all having potentially the same or stronger bonding affinity than current anti-flu drugs now available, including Tamiflu and Relenza. Several looked like particularly good candidates, Amaro said, since they bound to both the regular active site and an additional side pocket that opened during the computer simulation.

"The general idea is that we will be able to make a better drug through the strategic targeting of multiple active site pockets," said Amaro.

Added Cheng, former Pacific Rim Experience for Undergraduate student and NBCR researcher: "Importantly, half of these compounds would have been neglected based on the crystal structure simulations alone. Many of these drug leads would only have been found through the use of this computational method."

The research now moves into the lab, where the compounds will undergo testing against the virus. Researchers at The Scripps Research Institute in La Jolla, Calif., led by Dr. Ian Wilson, will lead this phase of the research.

http://www.ucsd.edu/

Bird Flu And You: How Will The Flu Affect You?

by Niall Cinneide

Flu is a common disease nowadays, with most people having developed the antibodies to fight against the disease. So the mention of "flu" doesn’t really create any alarm. However, say "bird flu" and there’s likely to be a pandemonium.

Bird flu, or avian influenza, is a highly pathogenic virus of 15 types. The virus spreads to poultry through direct or close contact with nasal secretions, saliva and feces of infected birds. What is alarming about this virus is that it has the ability to rapidly mutate into different forms that can affect human beings. Believed to be worse than the SARS outbreak, the bird flu outbreak brought millions of dead birds worldwide and at least 70 people dead in Asia.

From a not-so-harmful H5N2 virus strain, it can mutate into a killer virus with a low spread rate once the virus is transmitted to a bird. The virus has an incubation period of six to nine months before it becomes a full-blown, deadly pathogen. A bird that has been infected with the virus but has survived the disease continues to carry the virus in its body for more than week. When this happens, the bird passes on the disease to other birds that come in close contact with its secretions, saliva and feces.

Bird flu and ordinary human flu have the almost the same symptoms. These symptoms are fever, muscle pains and cough. This is the reason that a person who is actually infected with bird flu may be mistakenly diagnosed as simply having ordinary flu. However, bird flu symptoms can escalate into several life-threatening conditions. Some of these life-threatening conditions are lung inflammation, eye infections and pneumonia.

Because of the severity of symptoms of bird flu infection, the World Health Organization (WHO) is in the midst of a widespread effort to prevent the virus from infecting humans, particularly those whose who depend on poultry and livestock as their livelihood.

Bird flu virus and its subtypes can easily mutate into other forms. For example, the virus that was transferred from one animal to another is the H5N2 strain. However, the virus mutated into the H5N1 strain, which has been responsible for the death of at least 50 people. It is a very surprising discovery how these viruses can mutate itself from pathogens that can harm humans as it had started with birds.

In Asia, the countries plagued by the avian flu are Vietnam, Japan, Cambodia, South Korea, China, Indonesia, Laos, Thailand, Kazakhstan, Malaysia, Mongolia, Russia, Thailand. In Europe, Turkey, Romania and Croatia are the hardest hit by the disease.

WHO has issued a warning to travelers to these countries to avoid going to live poultry markets, getting close contact to any farms and having direct exposure to feathers, feces or droppings, eggs and poultry meat products. Travelers need to know that most contamination occurs during the slaughtering of poultry and being in direct contact with fecal matter.
No travel advisory has been issued restricting anyone from going to countries with the H5N2 strain. Travelers coming from afflicted countries are also not being screened. However, precautionary measures are in place, particularly in the media. Information is being disseminated in order to make people aware of the bird flu, its effects and what to do to avoid getting infected.

To date, no vaccines have been developed or available to fight the illness. However, anti-viral medicines are being used as alternatives in helping alleviate the severity of symptoms on those infected. While M2 inhibitors would be helpful, the body tends to develop resistance to those, diminishing the efficiency and effectivity of inhibitors.

The bird flu problem is both a government and global issue. Governments are in charge of making reliable declarations, initiating studies and putting objective measures in place. There is no reason to panic if the virus has not reached your area yet. The best thing you can do is to take practical steps in taking of your body and helping it build resistance to any kind of illnesses.

About the Author
Niall Cinneide publishes the bird flu news site http://www.birdfluinfo.org, and an informational site with reports and articles about bird flu transmission at http://www.bird-flu-alert.info This article may be reprinted in full so long as the resource box and the live links are included intact. All rights reserved. Copyright http://Bird-Flu-Alert.info