WHO: Indonesia H5N1 spread by humans

Geneva (dpa) - A cluster of seven human bird-flu cases in Indonesia may have been caused by multiple person-to-person transmission, the World Health Organization (WHO) said Tuesday.

The apparent infection chain among an extended family in North Sumatra began with a woman who is believed to have passed on the H5N1 to relatives who were with her "in a small room" when she was sick and coughing, a WHO statement said.

The woman's 10-year-old nephew subsequently got bird flu and is considered a possible source of infection for her brother, who was "closely involved in caring for his son," WHO said. The three people are among six family members who have died since May 4.

"All confirmed cases in the cluster can be directly linked to close and prolonged exposure to a patient during a phase of severe illness," a WHO statement said.

Human-to-human transmission "cannot be ruled out," though a possible alternative source of exposure is still being investigated, WHO said.

Indonesia is second only to Vietnam in human cases and deaths in the current outbreak of bird flu. Worldwide, 218 people in 10 countries have been confirmed with bird flu, of which 124 have died, according to WHO.

The disease's spread has raised fears that the virus could mutate to spread easily among humans, threatening a pandemic with millions of infections.

WHO said there is no evidence of "efficient human-to-human transmission" in the cluster of cases in Indonesia's Kubu Sembelang village, a reference to the fact that the infections appear to have happened at close quarters.

But Indonesia's health ministry and WHO are concerned about the cases, and health experts are searching for any cases among other relatives or the wider community, the Geneva-based agency said.

A rather frightening possibility.

Let us hope that, if human-to-human transmission occurred, it was largely due to the "small room" factor. This would mean that it is not very contagious, and that quarantine of the sick would be an effective measure to combat its spread.

This piece has nice analysis.

H5N1 Pandemic Increase to Phase Four?

Recombinomics Commentary
May 23, 2006

In cases dating back to late April, three of the man's siblings, two nephews, and two of his children became infected with the H5N1 virus. Only one family member who fell ill, a brother, has recovered from the infection.

The man's older sister, believed to be the first case in this cluster, died without being tested and is not on the WHO's official case count. With this latest case, the number of confirmed H5N1 cases in this family rises to seven, with six deaths.

The man, 32, is said to have nursed his son while the boy was dying, putting him in the path of blasts of virus-laced droplets.

The above information may be used as "proof" of human-to-human transmission of H5N1 (H2H) in North Sumatra, Indonesia, which could lead to the raising of the pandemic alert level to phase 4. Technically, the pandemic level has been at phase 4 or higher since early 2005. At that time the number of H5N1 clusters in northern Vietnam began to be reported at a greater frequency and the size of the clusters began to grow.

However. WHO discounted most of these clusters because each bird flu cluster was analyzed individually, and most had a bird connection, which was used to discount the proof of H2H. When there are clusters of H5N1 cases, distinguishing a common source from the alternative explnation of H2H is heavily dependent on disease onset dates. By definition, clusters are two or more cases linked by time and space, so the sequence of the H5N1 usually does not provided conclusive evidence because the cases are closely related in time and a similar sequence would be expected regardless of source.

However, since most cases develop symptoms 2-4 days after exposure, gaps of 5-10 days in disease onset dates suggests two or more independent infections. Since transmission from birds to humans is very rare, two independent infections in the same family is unlikely to be linked to birds. Family members have frequent contact with infected family member(s), and therefore transmission within families is far more common than transmission from a bird source to a human.

Familial clusters were reported as early as the beginning of 2004 and the most cited case was in Thailand in August of 2004. The cluster has been cited as H2H because the mother of the index case was an office worker in Bangkok, far from her daughter who was on a farm with her aunt hundreds of miles away. The mother became infected after visiting her daughter in the hospital and the aunt was infect after the mother, supporting the infection of one or both by the index case. The adults did not develop symptoms until the daughter died, and the gap in disease onset dates was in the 5-10 day range.

Most other clusters involved a potential bird source, so the "proof" was not conclusive. However, familial clusters accounted for about 1/3 of H5N1 cases in 2004 and early 2005 and almost all of the clusters had the 5-10 gap in onset dates.

Thus, the clusters as a group provided overwhelming evidence for H2H. This evidence became stronger when H5N1 human cases in Indonesia began to be reported in July of 2005. Most cases were in clusters and overwhelming majority had the gap in onset dates.

In 2006, larger clusters were being reported in Turkey and Azerbaijan, and these cluster had the same gap with evidence of growing transmission chains, including evidence for cluster-to-cluster transmission. The current cluster in North Sumatra may have the transmission chain increased to H2H2H2H, providing more proof of H2H, which may now cause an increase in the pandemic level because the concurrent cluster in Iran may be signaling a widespread increase in larger clusters in multiple regions by multiple versions of H5N1.

The deployment of Tamiflu from the United Staes to Asia is another signal of a potentional pandemic phase increase.

And also the prolonged exposure. It looks to me like this is a very containable outbreak, but it serves as a warning that we're running out of time to prepare. Hopefully this will also speed up getting at least a reasonable vaccine.

This is the most hopeful thing I've read in a long, long time about avian influenza. Looks like these guys have figured out predictable rules in how viruses evolve via recycling old mutations and apparently this will enable them to prepare vaccines for viruses that haven't emerged yet. If all that is true, that is a very, very hopeful development.


Paradigm Shift


The analysis of recombination will generate a paradigm shift in the way molecular evolution is viewed. Influenza is an ideal system for studying molecular evolution. Viruses are generally thought to evolve via shifting and drifting. Shifting occurs when viruses swap genes and drifting was thought to be due to a steady accumulation of mutations.

However, rapidly evolving viruses simply recycle old mutations via recombination. This method is much more efficient and follows specific rules. These rules appear to be followed by all viruses, including influenza, HIV, SARS, WNV. These rules allow vaccines to be prepared before viruses emerge. These observations will produce a paradigm shift in the study of molecular evolution via recombination, which will provide solutions for unmet health needs

Hopefully, they'll be able to contain this, Jeff. And looks like there are several more H2H transmissions - another one brewing in Iran. Hopefully they can contain them locally.

Wow, just coincidentally in Iran???

Hope one of these people leads to a vaccine and a window of a half year or whole year so everyone can get a shot quickly when it is mass made
(instead of waiting they should ramp it up with these people)

WHO Coordinator of Epidemic and Pandemic Alert and Response, Keiji Fukuda, says influenza pandemics occur at least a couple of times each century. "We are in a period in which the risk both elevated and more visible and this is because of the H5N1 virus. And, this is because this virus has the ability to persist and to spread and also to infect people. Now the WHO assessment at this period is that we remain at phase three. This is a period in which we may see examples of limited human-to-human transmission. But, we definitely have not seen sustained human-to-human transmission," he said.

Dr. Fukuda says WHO's early efforts in raising global awareness have been very successful. He notes one and one half years ago, a WHO survey found fewer than 50 countries had pandemic preparedness plans. Now, he says, more than 176 countries have either a draft or a completed national pandemic plan.

Egypt's Minister of Health, Mostafa El-Gabaly describes how even a developing country, with limited resources, can get control of the H5N1 virus if it responds immediately to the threat. He says after Egypt's first reported cases of H5N1 in birds and humans, his government sprang into action. It vaccinated tens of thousands of birds and culled those infected with the disease. "Training at the grassroots level, I think is the most important and most effective way of fighting this disease. Whether training people to cull birds. Whether training people to educate families. Whether training people to protect themselves from the dangers of the disease," he said.

The biggest problem with vaccines is that they are still being made using eggs. This process has a high chance of contamination (remember 2 years ago?) and takes 6 months to make a commercial product. More modern (quicker turnaround) techniques exist, but the PharmCorps aren't interested because that's not where the big bucks are.

Life in BushWorld.

Wash frequently. Don't let anybody cough on you. Elect some smart people in DC.

WHO: Wont' Get Fooled Again

We'll be fighting in the streets
With our children at our feet
And the morals that they worship will be gone
And the men who spurred us on
Sit in judgement of all wrong
They decide and the shotgun sings the song

I'll tip my hat to the new constitution
Take a bow for the new revolution
Smile and grin at the change all around
Pick up my guitar and play
Just like yesterday
Then I'll get on my knees and pray
We don't get fooled again

The change, it had to come
We knew it all along
We were liberated from the fold, that's all
And the world looks just the same
And history ain't changed
'Cause the banners, they are flown in the next war

I'll tip my hat to the new constitution
Take a bow for the new revolution
Smile and grin at the change all around
Pick up my guitar and play
Just like yesterday
Then I'll get on my knees and pray
We don't get fooled again
No, no!

I'll move myself and my family aside
If we happen to be left half alive
I'll get all my papers and smile at the sky
Though I know that the hypnotized never lie
Do ya?

There's nothing in the streets
Looks any different to me
And the slogans are replaced, by-the-bye
And the parting on the left
Are now parting on the right
And the beards have all grown longer overnight

I'll tip my hat to the new constitution
Take a bow for the new revolution
Smile and grin at the change all around
Pick up my guitar and play
Just like yesterday
Then I'll get on my knees and pray
We don't get fooled again
Don't get fooled again
No, no!

Yeaaaaaaaaaaaaaaaaaaaaaaaaah!

Meet the new boss
Same as the old boss

3 days ago a young (relatively) doctor who was one of heads of
WHO died. I put a post up asking a questoin about why.
Could he have been murdered.

Two days later they announce this

and one of the people is in Iran

coincidence again???

WE WON'T GET FOOLED AGAIN

Last night my daughter said, "There are five letters in my name, and I'm five years old. That's amazing!"

Graham, do you think my mother was murdered? She was traveling with the dog, a Springer Spaniel, when she was stricken by her aneurism. (Gee, the dog of Bush the Elder, Millie, was also a Springer Spaniel. Is that too much of a coincidence?)

WHO says no plans to raise bird flu alert level
Wed 24 May 2006 9:27 AM ET
(Adds more detail, background)

GENEVA, May 24 (Reuters) - The World Health Organisation (WHO) said on Wednesday it had no immediate plans to call a meeting of experts to discuss raising its global bird flu alert.

A WHO spokeswoman was asked to comment on press reports that the U.N. agency could convene a meeting of experts within the next few days because of concern about Indonesia where seven members of a family died this month.

"Right now it does not look like the task force will need to meet immediately, but this is subject to change depending on what comes out of Indonesia," WHO spokeswoman Maria Cheng told Reuters.

Under WHO's action plan for dealing with bird flu, the panel will be consulted before any change is made to the level of alert, which currently stands at three on a six-point scale.

There needs to have been increased human-to-human transmission, along with signs that the deadly virus is becoming more easily transmissible for a change in readiness to be made.

"Today we have no indication that the virus is more efficient," said Cheng.

In the Indonesian case -- which set international alarm bells ringing because it is the biggest cluster of human infections yet -- there was no indication that the virus had spread beyond the family members, she said.

"This is the biggest cluster we have seen, there may have been human-to-human transmission, and all this is something that needs to be responded to as quickly as possible," Cheng said.

maybe when 20 million have it they will say, OK there are enough people who have it, it must be here...

I just hope that the UN, the world governments and others are doing what they need to prepare for this. I would rather see them developing adequate plans than trying to instill the maximum amount of fear about this.

I think they are planning for this Arne. I can't imagine any government NOT developing plans for this.

Graham, I think this is still limited H2H transmission. All in close quarters, I mean. But it's stepping up, a bit.

I'm sure that there is planning, but I wonder how adequate it is.

I don't know a lot about what's going on in this arena, but I have to say that I don't start off with a lot of confidence that the Administration which flubbed Katrina is necessarily doing all that can be done on this. I am sure that there is a lot of good work being done by government professionals at all levels, but you need leadership from the top.

WHO panel may weigh worldwide bird flu alert
After deaths of at least 6 in Indonesia, officials stress virus unchanged

08:38 PM CDT on Wednesday, May 24, 2006
The Washington Post


JAKARTA, Indonesia – The World Health Organization might soon convene an expert panel to decide whether an unprecedented human outbreak of bird flu in Indonesia requires the world to go on higher alert for a possible pandemic, health officials said Wednesday.



DIAZ RIDHO/AP
Joned Ginting, the only remaining member of a family wiped out by bird flu, is treated for the disease. If the global alert status were increased, international stockpiles of antiviral drugs would probably be shipped to Indonesia, and travel from the country would be monitored to contain the outbreak.

Indonesian health authorities confirmed this week that the virus had killed at least six members of a single extended family on Sumatra island, including a 32-year-old man who died Monday.

A seventh family member also died from what investigators suspect was bird flu, but she was buried before samples could be taken. Another relative is hospitalized with a confirmed case but is recovering.

Maria Cheng, a WHO spokeswoman in Geneva, said the outbreak in the North Sumatran village of Kubu Sembilang was not only the largest bird flu cluster in the world but also the first in which investigators believe the virus was passed from one person to another and then to a third.

I Nyoman Kandun, Indonesia's director for disease control, said this week that the evidence from Sumatra was "suggestive of a third generation" of infection because of the long intervals between the earliest, middle and most recent cases. The timing of the infections makes it unlikely that the family members contracted bird flu from the same source, for instance sick chickens.

While the outbreak is exceptional, international and Indonesian health officials in Jakarta stressed that the virus appears unchanged. Laboratory analysis of virus samples shows that it has not mutated or developed into a form more easily passed among people.

Top international health investigators dispatched to Sumatra have uncovered no signs that the disease has spread beyond the one extended family, indicating that broader transmission of bird flu remains difficult.

Any decision to convene the expert panel, Ms. Cheng said, "depends on what we see in Indonesia. Our investigation is still incomplete."

How much should we believe the hype about bird flu? Is there cause for concern or are we being led down a garden path? What are we really doing about this?


The False Bird Flu Scare

by DR. MARC SIEGEL

[from the June 5, 2006 issue] The Nation

In 2003 concerns about the SARS coronavirus prompted the Centers for Disease Control (CDC) to work with the World Health Organization to encourage reporting and isolation of cases and contacts while at the same time cordoning off parts of Asia and Toronto. Health officials spoke publicly of a new era of cooperation. But the media-saturated advisories and pronouncements resulted in the loss of billions of tourist dollars to the Asian and Canadian economies. Ultimately, SARS infected about 8,400 people worldwide. There was never any objective evidence that regional quarantine helped squelch the virus, and follow-up studies found SARS to be not nearly as infectious as had been originally thought. Yet public health officials continued to speak of that global action as an unqualified success.

The same pattern of CDC/WHO involvement has been followed in the US-fueled worldwide overreaction to H5N1 avian influenza. This bird flu cannot routinely affect humans in its current form (114 deaths to date in nine years). But the priority being placed on it as a potential threat to humans is obscuring diseases that are already worldwide killers: malaria, which kills more than 1 million people a year; tuberculosis, more than 2 million; and HIV/AIDS, more than 3 million. As the worldwide health network grows, promoted by US healthcare officials but involving public health agencies all over the world, I am concerned that there will be a simultaneous export of the American obsession with certain diseases while others are excluded.

Worldwide spending on AIDS was $8.3 billion in 2005, with almost half of this coming from George W. Bush's Emergency Plan for AIDS Relief. But a 2005 WHO/UNAIDS report estimates that AIDS treatment coverage is $18 billion below global needs for 2005-07, with a projected $22 billion annual requirement by 2008. The WHO has not come close to its goal of treating 3 million AIDS patients by the end of 2005. Currently just over a million are receiving antiretroviral therapy.

Meanwhile, here in the United States, Bush has proposed cutting $15 million in AIDS research at the National Institutes of Health, while increasing funds for studying avian flu and bioterrorism. Bush's proposed 2007 budget calls for increasing by 0.3 percent funding for the NIH's Institute of Allergy and Infectious Diseases. The money will be targeted for avian flu and biodefense. Bush is also calling for a 6.2 percent increase for other NIH biodefense projects, according to the American Association for the Advancement of Science's analysis of the President's budget. This is in addition to the $5.6 billion already being largely wasted on Project Bioshield, which is supposed to help provide medical countermeasures against a chemical, biological, radiological or nuclear attack, with much more to come in Bioshield II. Almost $1 billion has gone to the manufacture of 75 million doses of anthrax vaccine, for example, despite the fact that anthrax is not contagious and has not recurred since the twenty-two cases in 2001 thought to be linked to terror.

Some public health officials have argued that avian flu should be at least as high a priority as AIDS because of the theoretical worst case, in which it could cause a severe human pandemic, but it is not even clear that the money allocated for bird flu will be used effectively for real prevention. Ron De Haven of the Animal and Plant Inspection Service of the Department of Agriculture says that although H5N1 is still a major threat to birds, only $4.4 million of his department's $1.1 billion budget for 2005-06 was earmarked for biosecurity outreach, to keep infected birds from coming here. And though $3.6 billion has already been approved for emergency pandemic preparedness against bird flu, with an additional $2.6 billion proposed, Dr. Andrea Gambotto, the creator of a new bird flu vaccine using modern genetic techniques (adenovirus) that has been effective in mice and birds, has been unable to get NIH funding to test this vaccine in humans. Newer approaches could lead to more potent vaccines with a quicker turnaround time--a much more effective tool for reacting to a pandemic as it is happening than current attempts to anticipate one that may never happen. But the President's new budget cuts 4.5 percent from the CDC's core programs while adding no funds for NIH. There is clearly no priority for key research programs. It is true that as part of his "worst case" pandemic flu preparedness plan announced in May, Bush awarded $1 billion in contracts to vaccine manufacturers to upgrade flu vaccine technology over the next five years. Of course, there is no guarantee that this goal will actually be met or that the money will reach the right hands.

Overseas, the biggest health problems that could benefit from our attention are malnutrition and the lack of clean water and proper sewage. Diseases like schistosomiasis and malaria thrive because of poor public health conditions. But our outreach does not emphasize them. Our public health system appears to be much more concerned about a disease like bird flu transforming into something that could threaten us than it does in helping the world with diseases that already threaten poor people everywhere. More than 16 million people die every year of malnutrition. Eight hundred million people worldwide currently suffer from hunger and malnutrition. How many people who survive mainly on poultry will have this food taken from them if worldwide health authorities--their perceived need to act in a hurry fueled by media reports--continue to kill domestic fowl indiscriminately whenever H5N1 appears?

A TV movie that aired in May, Fatal Contact: Bird Flu in America, capitalizes on fear by depicting a crippling loss of basic services and mass graves. This movie wasn't made in a vacuum--many scientists and journalists have been doomsaying on bird flu to such an extent that they have created a fear terrain even Disney could exploit. Sadly, hyperbole is not a method of discourse exclusive to TV drama; a public health blog for bird flu fanatics recently suggested the United States should pull out of Iraq and use the resources we save for bird flu preparation. On the surface this sounds like a terrific idea. On further reflection, it seems clear that going into Iraq in the first place was based on the same kind of argument--in which a remote but scary risk is exaggerated so it appears to be looming--that has characterized the public health reaction to bird flu.



http://www.thenation.com/docprint.mhtml?i=20060605&s=siegel

Dozens of people quarantined in Indonesian village struck by bird flu

Last Updated 25/05/2006, 20:39:46 Select text size:


Health experts in an Indonesian village hit by an unprecedented bird flu outbreak have asked more than 30 people to quarantine themselves to contain any potential further spread.

World Health Organisation (WHO) spokesman Dick Thompson says people who had close contact with any of seven relatives who have died since last month in the North Sumatran village are being monitored for signs of illness.

Mr Thompson also says that contact with an infected bird is now considered the likely cause of the outbreak.

His comments come a day after another WHO spokesman, Peter Cordingly, said the UN body was "stumped" about the original source of the infection.

Mr Thompson has stressed there is evidence the virus has not mutated into a form that can be more easily spread from humans to humans.

He says samples of the virus taken from the cluster of victims have been sequenced in a Hong Kong laboratory and have not shown any signs of mutation into a more contagious form.

Since late 2003, outbreaks of bird flu have killed 124 people in nine countries worldwide, 33 of them in Indonesia.

WHO invokes flu rules a year early

May 26, 2006 (CIDRAP News) – Member states of the World Health Organization (WHO) agreed today to invoke a set of health regulations related to influenza a year early because of the threat that H5N1 avian flu will trigger a flu pandemic.

The voluntary regulations are part of the International Health Regulations (IHR), which were approved by the World Health Assembly a year ago but are not scheduled to take effect until June 2007.

"The provisions identified for early voluntary compliance include those relating to rapid and transparent notification, support to countries that request it in investigating and controlling [influenza] outbreaks, and providing essential information including recommendations for control measures," the WHO said in a news release today.

The resolution passed by the WHA notes that rapid detection and reporting of human cases of avian flu "underpin WHO's ability to issue a reliable risk assessment and declare an appropriate phase of pandemic alert."

Among other things, the voluntary measures adopted under the resolution call on countries to:

Promptly report to the WHO any probable or confirmed human illnesses caused by any new flu virus subtype
Designate an official IHR "focal point" to communicate information and collaborate with the WHO on risk assessment (the language doesn't specify whether this would be an individual or an agency)
Designate IHR "contact points"
Provide WHO collaborating centers with information and biological materials related to highly pathogenic avian influenza and other novel flu strains in a timely manner
The resolution also covers regulations related to surveillance, information-sharing, consultation, verification, public health response, and public health measures for travelers.

The measure calls on the WHO director-general to "further accelerate steps" to set up a roster of experts [on avian and pandemic flu] and to invite proposals for its membership."

In addition, the WHO chief is asked to help mobilize international help for needy countries affected by avian flu and to search for solutions to the shortage of, and unequal access to, flu vaccines.

Anders Nordstrom, acting WHO director-general, said the agency has increased its ability to provide on-the-ground help to avian-flu–affected countries in the past year, according to an Agence France-Presse (AFP) report published today.

"The number of missions from WHO has gone up since the last year," said Nordstrom. "And now we expect with this decision, which is more of a political commitment, that we will be able to accelerate even more."

Nordstrom, who was appointed after the death of Dr. Lee Jong-wook on May 22, said the WHO and affected countries need more people and money to cope with avian flu, according to AFP.

At a conference in Beijing last January, donor countries pledged $1.9 billion to help poor countries prepare for a pandemic. Nordstrom could not provide details on how much of the promised money has been given so far. But he said that only $12 million of $89 million promised to the WHO has come in, according to AFP.

Bird Flu Kills 2 More in a Possible Case of Human Infection
By THE ASSOCIATED PRESS
Published: May 27, 2006

MEDAN, Indonesia, May 26 (AP) — Preliminary tests have identified two new fatal human cases of avian influenza in Indonesia, officials said Friday.

The latest victims, an 18-year-old man and his 10-year-old sister, died within hours of each other on Tuesday in a hospital in Bandung, where they had arrived the day before.

The Health Ministry said laboratory tests had found that the siblings were infected with the A(H5N1) bird flu virus. The tests will be sent to a World Health Organization laboratory for confirmation. Agency officials have so far confirmed 33 deaths from bird flu in Indonesia, out of 124 worldwide.

In Geneva, the 192-nation World Health Assembly, the agency's main decision-making body, agreed to speed up preparations for a possible bird flu pandemic by allowing member nations to establish a global warning system immediately. The system had been scheduled to start June 15, 2007.

The assembly cited "serious risk to human health, including the possible emergence of a pandemic virus, arising from ongoing outbreaks in poultry of highly pathogenic avian influenza."

Health officials in Indonesia continued to investigate a family cluster of human cases of avian influenza in Kubu Sembilang, a village in northern Sumatra where at least six of seven family members have died of the disease, the most recent on Monday.

W.H.O. officials have said human-to-human transmission in the Kubu Sembilang cases cannot be ruled out.

Indonesia, a sprawling nation of 17,000 islands, has refused to carry out mass slaughters of poultry in all infected areas _ a basic containment guideline _ saying it cannot afford to compensate farmers. And bio-security measures are virtually nonexistent in the densely populated countryside, with its hundreds of millions of backyard chickens.

A common situation in third (or even many second) world counties.

When you read all these articles, one thing is clear-the money allocated does not appear to be going where it is suppose to
(d'uh, with this administraiton, big surprise.)

It probably is time to see who's pockets are being enriched at the expense of all the fear of the population.

3 million dead a year by AIDS, yet nobody cares.
And all that money for anthrax...bet it went to manufacture bio-terror weapon anthrax or something like that

Imagine if they stopped the war and used all that money to science to find cures for cancer and other diseases worldwide.
Or to give clean drinking water to poorer countries instead of throwing bombs at them for oil.
If we did that , those countries would probably throw free oil at us, of course, that would not enrich and inflate the pockets of Bush, just make for a better world, not their concern of course.

Lemmeseenow.

Since 2003, here in Amerika, about 150,000 people have been killed in car accidents.

"The only thing we have to fear is fear itself" - - FDR

"The only thing we have is fear itself" - - GWB

I think this article below is very important. It shows how people will respond to this initially. People are not going to want to cooperate with a lot of medical cares out of fear the medicines are tainted, and they will form opinions as to what is happening to them that are not always rooted in reality. It's an important look into how this might go down in the larger world community.

Indonesian villagers blame magic, not flu

By MARGIE MASON
AP MEDICAL WRITER



Villagers walk out of a church after they finished Sunday service in Kubu Simbelang village, North Sumatra, Indonesia, Sunday, May 28, 2006. An extended family in the village had died of bird flu and no links to sick birds could be found, raising fear of possible human-to-human infection, thus locals blame black magic, not the virus, for the deaths. (AP Photo/Binsar Bakkara)

KUBU SIMBELANG, Indonesia -- The three brick-and-clapboard houses stand along the village's muddy dirt road, empty and forlorn. A naked light bulb hangs from a wire over one door, still burning. A white pet bird cries for food from its cage. But no one dares to go near.

Health experts have focused on the houses since an extended family started dying from bird flu and no links to sick birds could be established. They suspect limited human-to-human transmission, but say there is no need to panic because no one else in this mountain farming village has fallen ill and the virus has not mutated.

Some neighbors insist, however, that bird flu is not to blame. They are convinced black magic is at work, that ghosts now haunt their quiet Christian community of about 1,500 people.

Many are too scared to even pass by the family's houses, and some who live nearby are awakened by nightmares that they will be the next to die.

"We are so afraid just to step into that house," said a 37-year-old woman who identified herself only as Sembining. "We can't tell what we're afraid of - we're just afraid."

She lived near the victims and said the first woman who died was like a daughter to her. She recalled feeding and caring for her friend as she lay burning with fever before bird flu was ever suspected. Sembining can't understand why she, too, didn't fall ill.

"I think the family was cursed," she said. "It must be, because if it's bird flu, why only their family? Their blood?"

This is the largest cluster in a handful of cases involving bird flu passing from human to human, but scientists think it has always done so between blood relatives - not spouses. That has led some to theorize there may be a genetic susceptibility to the disease, but there is no evidence yet to support that.

Tests found no trace of the H5N1 virus in the village's poultry, and dozens of hens, roosters and chicks run freely in backyards. Pigs, cows, buffalo, dogs and barefoot children roam along the rutted road and across fields of chilies, oranges and limes.

Whatever the source of the infection, six of seven family members who tested positive for H5N1 have died. An eighth was buried before samples could be taken, but the World Health Organization considers her part of the cluster.

As their neighbors started dying, confusion and mistrust prompted villagers to stop cooperating with officials. Many refused to give blood samples, fearing they would later fall ill and suffer the fate of their neighbors.

The case has been a powerful lesson for WHO officials in understanding the importance of early communication and education.

"We're seeing what problems we're going to run into on the ground," WHO spokesman Dick Thompson said. "We're learning with every step."

Jules Pieters, manager of WHO's rapid response and containment group in Geneva, said it is clear that people familiar with the culture, language and customs of this area should have been involved earlier to help villagers understand what was happening, how to protect themselves and the importance of allowing treatment if they develop symptoms.

Instead, many people who were never scared of doctors before are now terrified of them.

"We are afraid to be sent to an isolation room. You know an isolation room is a slaughtering room - a room for the people who want to die," said villager Caranta Perangin-Angin. "Therefore we are afraid of (letting doctors) take blood. Taking the blood, for me, symbolizes going to die."

Indonesian officials reported that at least one patient had fled the hospital to seek traditional medicine and was later caught and returned. In the event H5N1 should mutate into a form easily passed among humans, such behavior would likely spread the illness further - a serious worry for experts who fear the possibility of a bird flu pandemic.

"In these situations, we need to first earn the trust of the people most directly at risk," Thompson said. "I think one of the lessons we're learning from this outbreak is that you can't just drive truckloads of Tamiflu into this area and expect that the problem is solved."

He said some villagers began associating Tamiflu, the chief drug to treat bird flu, with death because members of the infected family - most of whom were given the medicine too late to help - were dying after taking the pills.

Not everyone in the village is spooked.

Parked on a bench outside his tiny shop and strumming a guitar, Bapak Karunia Sembiring smiled when asked about bird flu. "If the doctors said it's bird flu, then so be it."

He said he is happy officials are monitoring the villagers' health and spraying disinfectant. But the 60-year-old fears his village will be shunned.

"I'm a little bit worried about what will happen in the future to the village," he said. "The worst is that the world will hate us, will judge us."

That's actually a very common reaction in any tribal area, when there's a serious threat people rely on traditions and personal observations.

I got this as a CME. I thought you all might like to read it as well. I definitly recommend N95 masks. I have already bought some. Both for adult sized faces as well as pediatric sized faces. And I might also buy some more. I think this is going to be one of the most important things you can do to help limit the spread of disease (other than good hand hygiene). I'll find the names of the places I found the pediatric N95 masks as these are more difficult to find. And they're not baby pediatric - just kid sized - or more kid sized than the adult sized N95 masks.


Avian Flu Practical Strategies to Prepare for and Respond to Pandemic Influenza

Although the major population with avian influenza is in Southeas Asia, spread of the virus through migratory birds means that the virus is getting closer and closer.
Critical Discussion & Commentary

Predicting and Planning for Influenza Epidemics

This will probably be the year of influenza A, probably H3N2, as an epidemic strain

By John G. Bartlett, MD

To determine the scope of the problem of avian flu we must look at influenza as we expect it to occur in the United States this year.This will probably be the year
of influenza A, probably H3N2, as an epidemic strain. It will attack a large number of people and will cause a lot of school absenteeism. There will be somewhere between 30,000 and 40,000 deaths as a result of influenza.

However, almost all of those who die will be people who have major co-morbidities or who are what we call the elderly-elderly (people who are over the age of 75 or 85 years).This is a morbid disease in young, previously healthy people, but it is not a lethal disease.

The Spanish flu in 1918 to 1919 was an avian strain. It is now called H1N1. In the United States, it had a mortality rate of approximately 2%.The total mortality was 675,000. It traversed the world in about six months. The average age of death was somewhere between 25 and 35 years. In other words, this was not an influenza of the elderly-elderly. This was an influenza in which the mortality
was primarily in young, previously healthy adults.As a matter of fact, older people fared better with this influenza than did younger people, which is testimony to the probability that the inflammatory reaction is an important part of this equation.

Avian influenza, the H5N1 strain, is currently in Southeast Asia. However, the mortality rate is not 2%; it is 50%, and that is with the best medical technology and medicines we currently have. It has not become a pandemic. There are approximately 64 deaths so far. Its limitation appears to be the inability to have
sustained transmission person to person.The average age of death is approximately 15 years, which again means that it is the young and previously healthy that are apparently most vulnerable.

In terms of the scope of the problem, we can say first of all that this is well placed permanently in the bird population. No one thinks we are going to be able to remove this from the bird population. Part of the reason is because the migratory birds—ducks, geese, swans, etc—are asymptomatic carriers.They fly thousands of miles and honor no borders.There is no way to prevent the spread of this disease in that bird population. It is also almost impossible to control the backyard chicken farms, which are part of the culture in much of the world where this virus is a big problem today.

The major population with avian influenza is located or restricted to Southeast Asia. However, the bird problem (the extension by migratory birds) has reached many other areas of the world, including Russia, Romania,Turkey, and Greece, which means it is getting closer and closer.

Human-to-Human Transmission

The avian flu remains a problem with regard to human-to-human transmission in terms of its ability to cause a major epidemic. There are two ways to look at this. One is that it will eventually get the two mutations that are necessary to make it efficiently transmitted from person to person. After all, influenza is a very fragile organism in terms of its mutation pattern.

The reason we must have a new influenza vaccine every year is due to that fact we have a different strain every year because it mutates so frequently. The virus has been called fickle and fragile, and some have even said promiscuous.That is the pattern of influenza. It could mutate as a result of spontaneous mutations, or it could mutate as a result of mixing of human influenza and avian influenza in the same patient. If that happens, then those who are predicting that this will become a global pandemic could be correct.

The alternative point of view is that this is a virus that has been around since 1997. Since that time, it has not yet learned to go efficiently from person to person. It may be that this particular virus does not want to do that and somehow has a mechanism to avoid it. In this case, it will be endemic in the bird population but will cause infection in people only once in a while, which is the pattern we have right now.

For planning purposes, most of the authorities in the field have said that it may turn out to be nothing except for a few sporadic cases. On the other hand, we have to be prepared for the possibility that it could become a global pandemic.
Therefore, the issue before us right now is preparedness.

Which Neuraminidase Inhibitors Are Most Effective for Avian Flu?

A newer set of antiviral drugs called neuraminidase inhibitors are advocated
for the treatment of influenza because these drugs cover both influenza A and B

By Paul G.Auwaerter, MD, MBA

The Centers for Disease Control and Prevention has made a distinction between
chemoprophylaxis and treatment. For chemoprophylaxis for routine influenza, older drugs such as amantadine and rimantadine are favored because they are less expensive.These drugs may be taken on a long-term basis and at
generally half of regular treatment doses. Although these drugs are less expensive, they tend to have more central nervous system (CNS) side effects, especially in the elderly, although rimantadine is considered to have a better CNS
and gastrointestinal side effect profile compared with amantadine.

A newer set of antiviral drugs called neuraminidase inhibitors are advocated for the treatment of influenza because these drugs cover both influenza A and B.The older drugs such as amantadine and rimantadine treat only influenza A because they use a specific N-protein that is not found in influenza B and, interestingly, is also not seen in avian flu.Therefore, the drugs are not effective for avian influenza strains.

However, the neuraminidase inhibitors are effective and are believed to be effective in vitro against avian influenza strains.To date, it is unclear whether the neuraminidase inhibitors are truly effective in human cases of avian influenza. This is, in part, because the drugs typically have been employed several days into these severe avian influenza cases in Southeast Asia.Typically, as with any antiviral drug, the recommendations are to start within 48 hours of
symptom onset to have efficacy.

The most popular neuraminidase inhibitor is oseltamivir (Tamiflu®).This is an oral capsule taken at a 75-mg dose twice daily for five days for treatment, or one pill daily for chemoprophylaxis.This drug has approximately a 20% incidence of gastrointestinal side effects. Some experts have advocated higher doses in avian influenza suspects, such as 150 mg twice a day for 10 days.

A less commonly used neuraminidase inhibitor is zanamivir(Relenza®).This is an inhaled powder, which is a bit tricky to coach people into taking properly.The dosage is 10 mg inhaled twice a day for treatment.The drug is not approved by the Food and Drug Administration for chemoprophylaxis, although Tamiflu is. However, it seems to work effectively for prophylaxis as just one puff inhaled daily.The main side effect of the inhaled powder is bronchospasms, so typical use in patients with pulmonary disorders such as asthma should be done with caution.

Given the attention to the neuraminidase inhibitors, I would like to make several points clear.The first is that the older drugs, amantadine and rimantadine, do not have activity against avian influenza.The second is that it is quite unclear whether Tamiflu will prove effective, especially in an avian strain that has evolved to become more competent in human populations.The third is that the exact dosing is a bit unclear, and for prophylaxis, patients may need to take this drug for four weeks at a time.

If an epidemic were to occur, so-called social distancing would have to be initiated.This would involve closing public facilities with large populations such as schools and businesses and imposing quarantines, along with epidemiologic
measures in an attempt to isolate contacts and prevent potentiation of cases.

Governments worldwide are beginning to stockpile Tamiflu in preparation for such a potential pandemic until a useful vaccine can be produced in sufficient quantities.There have been manufacturing issues with regard to Tamiflu such that
significant amounts of the drug will not be produced in the short term, although the manufacturer (Roche) has considered licensing the product to other drug manufacturers in an effort to stave off significant shortfalls in the next one to
two years.

One thorny question that many physicians face is the so-called request for a private stockpile of Tamiflu or Relenza. Public health authorities have generally discouraged health care providers from prescribing either oseltamivir (Tamiflu) or zanamivir (Relenza) for either stockpiling or travel to Southeast Asia.The rationale for this is that the actual clinical effectiveness for these drugs is unproven against avian influenza, and we have no guidelines at the moment on how to instruct people to use these drugs from their own personal stockpile and/or when to
take them and for how long. Personal stockpiling has also placed a significant strain on the manufacturer, and there may be little of the drug available for routine influenza cases this winter for patients and families who may actually
require the drug.

One concern is that if people take the drug indiscriminately,there may be a loss of effectiveness. Evidence of resistance seems to arise fairly commonly, as studies in Japan have indicated.Therefore, at this time, prescription of the neuraminidase inhibitors has been recommended only for people suffering from influenza. Efficacy is best if used within 48 hours of symptom onset, or for chemoprophylaxis for current influenza strains in a community in which an epidemic has occurred in patients who have not received the traditional vaccine.

It should also be emphasized that prescribing Tamiflu for people traveling to Southeast Asia is also not recommended. There has been little experience that people traveling to Southeast Asia have come down with avian influenza, and
there have been no recommendations regarding limiting travel issued by the State Department or the Centers for Disease Control and Prevention at this time.A routine influenza immunization would be recommended, however, during the winter season.

If going to endemic regions, travelers should be advised to avoid poultry contact and avoid eggs and undercooked poultry. They may wish to bring along alcohol-based sanitizers to frequently cleanse their hands. If a traveler comes down
with a febrile illness within 10 days of leaving an endemic region, I would suggest that avian influenza should be on your differential diagnosis at this time.

How to Proceed Without a Vaccine

Vaccines are our premier prevention strategy for an outbreak of any kind of flu, and this is an area in which we need to put maximum efforts

By Trish M. Perl, MD, MSc

What kinds of issues and considerations must we deal with if we have a pandemic with avian flu? First, we will briefly address vaccination. After we have a situation in which we have avian flu, it will take four to six months before the first doses of vaccine will be available. Therefore, we will have to function without the comfort of having an effective avian flu vaccine for four to six months.

This is worsened by the fact that in the United States, we have a limited vaccine production capacity. If there is a global problem—intrinsic in the concept of a pandemic— many countries will be competing for the limited supplies of vaccine.This current shortage and inadequate production capacity are important caveats in our preparation for a possible pandemic.Vaccines are, of course, our premier prevention strategy for an outbreak of any kind of flu, and this is
an area in which we need to put maximum efforts.

Without vaccine, how shall we proceed? At a community level, we would see such things as discussion about isolation and quarantine, travel restrictions, and restrictions of social mixing in order to curtail the spread. In health care settings,
we would have a genuine shift from freedom to enter a health care setting to a more active screening process, looking for symptoms, and a much more aggressive, proactive use of respiratory precautions in order to exclude people
who are potentially incubating the virus from high-risk settings.
Quite possibly, mask usage would be made mandatory
around the clock.

Defining a Pandemic

There are three required criteria for a pandemic. First, there must be a strain for which there is little immunity existing in the human population; that criterion has been met. Second, there must be a strain that can replicate in humans; this criterion has also been met.Third, for a pandemic to occur, there must be human-to-human transmission causing disease in subsequently affected people, which
is calculated using a respiratory coefficient; that criterion
has not yet been met.

Currently, this virus is not efficiently transmitted among humans. Because of this, we have a little time to prepare. Avian flu can cause a pandemic.There is no natural immunity, and we do not have a vaccine. There is a very high mortality
associated with this disease.We have learned from the SARS experience that health care is a hot zone, and the control of this disease will hinge on effective management within the health care setting.

Considering community control measures, what kinds of isolation and quarantine measures should be performed? We could envision closing of schools. Mass gatherings of people, such as at football games, could be interdicted.
Reduction of hospital visits would be required because of the risk of transmission of the virus.We may have to implement respiratory etiquette beyond health care settings, such as in grocery stores.There could be restrictions in the use
of public transportation. Mask advisories could be issued. There could be requests for voluntary or mandatory isolation of people who have been exposed.We could see a shift toward home care as opposed to care in office settings.

Vaccinations Must Be Prioritized

It is important to prioritize the use of vaccine to patients who will respond to it, and not use it in patients who are unlikely to respond. It is likewise important to vaccinate health care workers.They also must be educated on how to use personal protective equipment, including masks, gowns, and gloves.

Challenges will occur on what to do with family members of health care workers. How can we reassure health care workers that they and their families will be adequately protected? Two studies recently reported some models that looked at transmission. One study showed that quarantine increased the effectiveness of other measures.A second study reflected the importance of vaccination in decreasing transmission. Consider this:Vaccinating just 50% of the targeted population would adequately reduce transmission of avian flu.

To summarize, we acknowledge that, at this time, we really do not know what we should be doing at a community level; we do not know the relative importance of various strategies.Therefore, we must implement all of the strategies. This is a wonderful opportunity to prepare for avian influenza, as well as to prepare for our annual epidemic of influenza.

We recognize the importance of handwashing, not only around patients but also in any gathering.We need to think about putting alcohol gels in waiting rooms.We need to educate health care workers on the use of personal protective equipment. Also, we should think about the gathering of patients in waiting rooms and other places.There must be adequate supplies of materials needed for isolation, prophylaxis, and treatment. I emphasize that, at this time, there is absolutely no reason to stockpile antivirals. I emphasize, too, the importance of communication.This is a great opportunity to establish and try out communication networks that we will need in order to support maximum effectiveness.

Diagnosing Avian Flu Takes Time

Enteric symptoms such as nausea, vomiting, and diarrhea appear to be more common in patients infected with avian influenza

By Paul G.Auwaerter, MD, MBA

I would like to review some of the typical symptoms as well as diagnostic issues of avian influenza, as well as concerns regarding vaccines and therapeutics. Lastly, I will review frequent questions that have arisen by both physicians and patients in the hope of providing some clarification to this fast-moving topic.

The first point is that a pandemic of avian influenza currently does not exist, nor does a pandemic of routine influenza. Who might be at risk for contracting avian influenza? At the moment, most cases have been found in Southeast Asia, Indonesia, and countries where avian influenza has been found in domesticated poultry flocks.

There is a possible risk from coming into contact with infected birds.To date, no more than 130 to 140 total human cases have been described, although millions of birds have been infected. So far, the ability to transmit avian influenza to humans seems limited, and there have been only a very few cases of human-to-human transmission of this H5N1 avian influenza strain.

Therefore, most of the discussion to date has centered on the theoretical concerns that the current avian influenza strain may further mutate slightly and become better adapted to mammalian hosts and quickly facilitate a human pandemic.

Avian Influenza Symptoms

What are the typical avian influenza symptoms? There seems to be some differences with the avian influenza human infection in the cases described to date compared with routine influenza. First, only about half of the patients described so
far seem to have typical flu-like symptoms, such as fever, cough, sore throat, or muscle aches. Enteric symptoms such as nausea, vomiting, and diarrhea appear to be more common in patients infected with avian influenza.The pneumonitis
that occurs from the influenza seems to be severe and, at times, hemorrhagic. What is most concerning is that the mortality rates of this avian influenza strain appear to approach 50% to 60%.

Avian Flu May Take Time to Be Diagnosed

At this time, if individuals come from Southeast Asia with a febrile illness, one could be concerned whether they may be harboring avian influenza. Unfortunately, influenza diagnostics do not allow for rapid assessment of whether
someone may be carrying the avian influenza strain. Routine influenza subtyping is generally performed by public health departments weeks after the actual viruses are collected from human samples.

Currently, a positive diagnosis for H5N1 would depend on paired convalescent serum, with acute serum showing a 4-fold rise in the H5N1 specific titer, or the use of a polymerase chain reaction assay on a respiratory isolate, which some commercial laboratories have begun offering.

Currently, there have been no cases of avian influenza among humans in the United States. However, if concerns arise in an individual patient, the local public health authorities should be contacted to help investigate the case.

What vaccines are available for avian influenza?

Significant attention has been directed toward producing an H5N1-specific vaccine. Although a vaccine does exist for poultry, there is no currently available vaccine to protect humans against the H5N1 virus. A significant number of strategies
are underway, and preliminary tests have already been performed in humans dating to this past April. However, most experts believe that a widely available avian-specific vaccine will be at least two to four years away.This is, in part, due to
the challenges of producing this vaccine by recombinant cell technology instead of the traditional use of chick embryos to manufacture vaccine.The current influenza vaccine will not protect against avian strains. However, traditional immunization
against influenza is recommended as it will help distinguish routine influenza from the potential avian influenza if an outbreak were to occur.

This year, although influenza vaccine is available, there has again been some shortage in supply due to manufacturing difficulties.Therefore, if enough vaccine is not sufficient, the Centers for Disease Control and Prevention has again recommended using routine influenza vaccine for so-called high-risk groups, which include persons aged 65 years and older with or without chronic health conditions, any resident of a long-term health care facility, anyone between the ages of two and 64 years with chronic health problems, children between the ages of six and 23 months, pregnant women, health care personnel who provide direct patient
care, and household contacts and home caregivers for children under six months of age. Since an effective vaccine against an avian influenza strain may be several years in the future, much attention has been directed toward antiviraltherapy as a stopgap measure if an epidemic with an avian
strain were to occur.

Warning Signs of a Pandemic

Although there are many challenges in terms of preparing for a potential influenza pandemic, we are far better prepared than we were in prior epidemics, with advanced medicine and newer drugs

By Paul G.Auwaerter, MD, MBA

Some patients have asked,“When will I know there is a pandemic, or what will be the warning signs that a pandemic may occur?” Many people believe that the first
evidence would be an increase in cases in other animals such as swine or evidence of relatively facile human-to-human transmission of a novel influenza strain.

Although H5N1 has garnered considerable focus because the virus appears to behave very similarly to the 1918 influenza strain that wiped out millions of people, it could be that other avian strains or an as yet undiscovered virus could be the driver of the next pandemic.

Generally, pandemics have occurred in anywhere from 20- to 40-year spans.With the last major pandemic occurring in the late 1960s, many people who study influenza believe that we are past due for a pandemic. What are some of the takehome points regarding avian influenza? First and foremost, there is no current pandemic, and we can reassure our patients on this point.Travelers do not need to take any special measures at this time.

Although a vaccine is not yet available in the foreseeable future, governments have taken to starting a stockpiling of neuraminidase inhibitors. Many people have questioned whether there will be sufficient supply. However, personal
stockpiling has not been advocated, and this might cause significant problems in the setting of a routine influenza epidemic during the winter if drugs are in short supply. Last, the drug should be taken within 48 hours. If you were treating
influenza or avian influenza, this should be done on a twice-a-day basis. However, for prophylaxis of influenza, the drug should be taken only once a day.The older anti-influenza drugs (amantadine and its newer cousin rimantadine) are
not effective against avian influenza but still have a role in the chemoprophylaxis for, or treatment of, influenza A.

Although there are many challenges in terms of preparing for a potential influenza pandemic, we are far better prepared than we were in prior epidemics, with advanced medicine and newer drugs. Fears and anxieties can be easily
stoked.

Although the United States is considered by many to be unprepared, efforts are being made to stockpile neuraminidase inhibitors and produce an H5 vaccine.
Authorities have suggested that there is enough drug for 20% to 25% of the population, but in an avian influenza pandemic, the rate of hospitalizations would be reduced anywhere between 50% and 77%.

Avian influenza will certainly remain in the news. In a field where additional information is being learned continuously, frequent updating and issuance of guidelines will help manage the medical response. Detailed information can be found on both the Centers for Diseases Control and Prevention and
the World Health Organization websites.

Should You Advise Against Chicken in Diet?

Some additional questions that have come up from both physicians and patients include concerns that avian influenza has spread to Europe and the Middle East.What has actually happened is that poultry flocks have become infected in
these regions, but there have not yet been human cases. It appears that avian influenza is spread rather rapidly by migratory waterfowl that may land in domesticated poultry flocks and spread the infection.The rate of spread is alarming
but has not yet triggered concerns that the virus is mutating or becoming more likely to infect humans.

Countries have taken a variety of approaches but have generally focused on culling flocks as being the most effective method to handle the avian influenza. Although China has recently initiated a large-scale campaign to vaccinate all of
the poultry in the country, many veterinarians feel that this will be a difficult task to perform logistically.

Another question has been this: Should I avoid chicken in my diet? During the avian influenza outbreak, people have tended to eat less chicken in certain countries. According to an article in the Wall Street Journal, Kentucky Fried Chicken franchises in Southeast Asia have switched in some cases to serving fish rather than chicken. Although handling live birds or birds contaminated with avian influenza could pose a potential risk, it appears that cooking chicken to 140 to 150
degrees is sufficient to render the virus noninfectious.

Therefore, travelers to Southeast Asia may not wish to be around any areas where uncooked chicken or live poultry are located.There appear to be no such concerns here in the United States that should warrant taking chicken or
other poultry meats out of our diet.

www.cdc.gov/flu/avian or www.who.int/en/

Symptomatology of Avian Flu Differs From Traditional Flu

Differing markedly from traditional flu, 40% to 70% of reported patients with avian flu have had diarrhea

By Trish M. Perl, MD, MSc

No one really knows what to expect with avian influenza.There will be great challenges to the public health specialists and difficult problems for the health
care industry.With the effective shrinking of our globe and shortening of travel times, for the first time we may encounter a pandemic that can spread rapidly and appear unpredictably, so that resources and ingenuity will be maximally
taxed.

Currently, there are approximately 150 human cases of avian flu, and it has been carrying a mortality rate of approximately 50%. Updates can readily be obtained from the WHO website (www.who.int/en/).

Avian flu has an incubation period of six to 10 days, a bit longer than traditional influenza. The symptomatology is importantly different from traditional influenza. Every reported patient has had fever. All have had cough, which is productive
in one-third to three-fourths of the patients. Every reported patient has had an abnormal chest x-ray with lobar infiltrates, usually unilateral.The pneumonia is very advanced in its manifestations. Dyspnea has been present in 75% to 100% of reported patients. Differing markedly from traditional flu, 40% to 70% of reported patients with avian flu have had diarrhea.

Laboratory findings are generally nonspecific. Thrombocytopenia is common, and leukopenia is present. Increased ASTs and ALTs are found, consistent with a viral
process.These manifestations are in reported and examined individuals. Patients with milder disease may have fewer severe manifestations.

Diagnosis Difficult

The diagnosis of avian flu can be challenging.When we see a patient with pneumonia or acute respiratory distress syndrome without a defined etiology, it is important to obtain a travel history to determine if the patient has been in an
endemic or epidemic area. The rapid antigen test commonly used in influenza has been insensitive. Currently, polymerase chain reaction is being used in clinical specimens (from bronchial alveolar lavage or nasopharyngeal aspirate).The
specimens should be handled in BSL-3+ conditions defined by the Centers for Disease Control and Prevention (CDC).

Transmission occurs by respiratory droplet as well as by direct contact. It is anticipated that the CDC will soon be requiring droplet precautions. Droplet precautions require the use of a surgical mask, gown, and gloves when entering
the room. Droplets can be acquired from surfaces in the room because of sneezing and coughing.There is no current requirement for any specially engineered room. Droplets can be transmitted only three to six feet.

Most important is strict hand hygiene. Patients should be in private rooms or, if necessary, be placed with similarly sick patients with at least six feet separating the beds. Health care workers must use standard precautions.The importance
of hand washing should not be understated. In a study of military recruits, there was a 45% reduction in outpatient visits for respiratory illness following utilization of aggressive hand hygiene practices.There are similar data in college students.
Some data show that if good hand hygiene is practiced in a school setting, there would be a 10% to 45% reduction in absenteeism in teachers as well as students.
Hand hygiene includes not only washing the hands, but also the use of alcohol gel as an additional agent.

Droplet Precautions Important in Control of Avian Flu

The use of droplet precautions is an important component in the control of avian flu, as well as respiratory syncytial virus, influenza, rhinovirus, adenoviruses, and coronavirus

By Trish M. Perl, MD, MSc

The use of droplet precautions is an important component in the control of avian flu, as well as respiratory syncytial virus, influenza, rhinovirus, adenoviruses, and
coronavirus.We now have documentation of human-tohuman transmission of avian influenza.

Following the SARS outbreak, the Centers for Disease Control and Prevention promoted a concept of respiratory hygiene and cough etiquette.The observation of this concept will be critical in outpatient as well as inpatient management in order to abort any transmission of the disease. This includes education of staff on the importance of source control in order to prevent transmission of respiratory
pathogens.

Signs must be posted instructing persons with symptoms of respiratory infection to cover their noses and mouths with tissue when they cough in order to minimize spread of droplets, and then dispose of the tissues appropriately. In health care settings, we must provide alcohol gel wipes and instructions on how to wash hands and use alcoholwipes. If influenza does appear, we could offer masks for patients as well as health care workers to use while they are in any setting.

Cohort studies (done initially with meningococcemia) indicate that respiratory droplets are hazardous if patients are separated by less than three feet. One study involved an outbreak of meningococcemia in an elementary school.The
researchers in this study found that if there was less than 102 cm (40 inches) between the chairs of children in the room where there was a case of meningococcal disease, 27% of the children became meningococcal carriers. If the
distance was greater than 102 cm, only 7% became carriers. This is the basis for current recommendations.

Masks to Prevent Transmission

There has been documentation of human-to-human transmission of avian flu virus. Because of this, studies have been made of the effectiveness of personal protective equipment that health care workers should be wearing.We now must
look at what we need to do with health care workers.

To date, there has been no recently documented transmission of avian flu virus, H5N1, to any health care worker. A survey showed that 95% of health care workers wore masks. Most wore N95 masks, although 73% report having
worn surgical masks, which supports our move for droplet precautions. Only 30% wore eye protection, which is alarming. This raises concern over the possibility of transmission. As we move to droplet precautions, we should recognize
that part of the standard precautions would be covering all mucous membranes. We also know, from the SARS experience, that the particular barrier that health care workersused that was shown to be effective in aborting transmission
was the use of mask, either a surgical mask or an N95 mask. Masks were much more important than gowns or gloves.This experience can help us focus on where we should put our efforts.

Quality of Care Overseas Not an Issue

In approximately 80% of cases of the avian flu, young adults and children had contact with poultry

By John G. Bartlett, MD

The mortality rate of avian flu is approximately 50%. Some people might think that patients who are in another part of the world probably would not receive
very good care, and that it would be quite different in the United States with all of our medical facilities.When reviewing the cases, however, you will find that these patients were on ventilators and received a full menu of antibacterial agents; they received oseltamivir most of the time and also received steroids. In the majority of cases, they had essentially everything there that we would use in this country.

As mentioned, most of these young adults and children had contact with poultry. That applies to approximately 80% of cases.There has been one clear case of human-to-human transmission. To date, however, there is no sustained transmission, and that appears to be the major limitation.

What about the science of this virus? To look at this, we must first look at the history of influenza and influenza epidemics. In the last 100 years, there have been three epidemics: the epidemic of Spanish influenza in 1918 to 1919;
the Asian influenza in 1957 to 1958; and the Hong Kong flu in 1968 to 1969. Each of these introduced an antigenically distinct form of influenza that resulted in a global pandemic. However, the mother of all pandemics was the Spanish flu of
1918 to 1919. That is thought to have caused somewhere between 40 and 50 million deaths in the world. That actually decreased the average life expectancy in the United States by 15 years. There has not been another epidemic anything
like this in the last 100 years. It is for that reason that many have worried about the possibility of another pandemic.

The influenza watchers have always said,“We don’t know when, we don’t know where, we don’t know if it will be this one, but we do know, predictably, there will be another big pandemic of influenza.”

Exploring the History of the Avian Flu

The first human isolate of avian influenza A, H5N1, was in a child in Hong Kong in 1997

By John G. Bartlett, MD

Avian influenza started in 1997 in Hong Kong when there was a death due to influenza in a three-year-old child.This alarmed the Hong Kong health authorities
because they felt it was an unusual case and sent the strain to be identified. It turned out to be what we call avian influenza, or influenza A, type H5N1.That was the first human isolate. It was also thought to be the first time that an
influenza virus had been transmitted directly from poultry to a person. Subsequently, that theory was disproven.

The health authorities reviewed the situation at the time, and during the rest of 1997, there were 18 cases of influenza and six deaths due to this organism.This was obviously a clinically unique form of influenza.A review of the epidemiology
by health authorities at the Hong Kong Health Department, the Centers for Disease Control and Prevention, and World Health Organization concluded that
there needed to be three properties to cause a pandemic influenza outbreak: (1) it had to have a strain of influenza that would infect people; this situation clearly did that because there were 18 cases; (2) it needed a population of susceptible hosts; that was clearly true because no human had ever had this influenza; and (3) it had to be transmitted from person-to-person; that was the Achilles heel for this
epidemic and outbreak in Hong Kong.

It continues to be the major limitation of this strain of influenza for causing pandemic influenza.The reason we know that it did not go from person to person is because authorities performed good serologic testing of the families,
the close contacts, and the health care workers who took care of the 18 patients.They saw little or no evidence that this virus was transmitted from person to person.

On December 31, 1997, a group of experts met in downtown Hong Kong and discussed the situation further. The geneticists said that there needed to be only two mutations in order to make this virus capable of being transmitted
person to person.They also decided that it was appropriate to limit the further epidemic of this strain of influenza by culling, or killing, all of the poultry in Hong Kong, which they did over the next three days.That seemed to take care of
the problem, at least for the next five years.

In December 2003, the virus recurred in poultry in eight Asian countries, and it became a rampant epidemic in poultry. In January 2004, cases were beginning to occur in people. Four countries (Vietnam,Thailand, Cambodia, and most
recently, Indonesia) had cases.The current total number of cases is 125, and of these individuals, 64 have died, for a mortality rate of approximately 50%.

This was a very virulent form of influenza. It attacked people who were young and previously healthy, very much unlike the kind of influenza that we call seasonal flu that we have every year.The typical patient was a young adult or child who had direct contact with poultry, often sick poultry. Then, after an incubation period of two to five days, the patient developed symptoms of flu and lower respiratory
tract infection symptoms. They were then hospitalized, quickly went into acute respiratory distress syndrome, and often died.The average age of death in the cases that have been tracked so far is 15 years.

A hemorrhagic pneumonia has been found at autopsy, and the pathophysiologic mechanism appears to be a cytokine storm, which is the inflammatory response. It is not necessarily the virus itself, but the cytokine storm, or the inflammatory
response to the virus, that causes the hemorrhagic pneumonia.

The most exciting part of the history of the science of this virus involves the work of Jeff Taubenberger and colleagues at the American Forces Institute of Pathology at the Centers for Disease Control and Prevention. They wanted to study the influenza virus of 1918 to 1919. Obviously, they did not save strains at that time.Therefore, a crew went to Alaska and exhumed the bodies of patients who had died of influenza and remained in frozen state for the next 80 years.
As a result, they could recover fragments of the virus and could then reconstruct the virus with reverse transcriptase and eventually reproduce the virus of 1918 to 1919.

Researchers needed to understand what the virus was and how it caused isease.They found several things that are relevant to the avian flu and are important for our understanding of influenza. First, they found that this was an avian flu that had genes of a bird.Therefore, it seems to represent transmission from poultry to person.The other pandemics of this century have not involved avian strains. Second, they obviously had a virus that could easily be transmitted from human to human.Third, by virtue of sequencing the virus, they could then study virulence factors; they showed that several of the sequences in the hemagglutinin part of the virus were apparently responsible for the pathophysiologic effects, the hemorrhagic pneumonia.These researchers are using an animal model (both ferrets and mice) as objects of studies of influenza
virus, so it is a long-standing process.They also noted that some (but not all) of those sequences were similar or identical to those noted with H5N1.Therefore, it turns out that that science has now given validity to the concern that the
avian influenza, H5N1, does have some but not all of the properties of the virus of 1918 to 1919.

This article really disturbs me.

May 29, 2006, 1:25PM
Sole Bird Flu Survivor Shuns Treatment



A medical worker with protective gear, left, checks the health condition of Johannes Ginting while relatives support his weakened body at a hospital in Medan, north Sumatera, Indonesia, Monday, May 29, 2006. At least six of Ginting's relatives from tiny Kubu Simbelang village in North Sumatra have died of the virus. A seventh was buried before samples could be taken, but the WHO considers her part of the cluster _


By MARGIE MASON AP Medical Writer
© 2006 The Associated Press

MEDAN, Indonesia — The sole survivor in a cluster of Indonesian relatives infected with bird flu lies in an open-air hospital room, chickens pecking outside his door and visitors shuffling in and out without masks or protective gear.

The patient, Johannes Ginting, is still very weak but seems unconcerned. He even fled the hospital when he first fell ill with the H5N1 virus, and has since resisted treatment, balking at the bird flu drug Tamiflu and other medicine.

"We had actually given masks and gloves to the family, and we informed them how dangerous this disease is, but they didn't cooperate with us," said Nurrasyid Lubis, deputy director of Adam Malik Hospital. "We also informed him how dangerous it is, but he didn't believe us."

On the other side of the hospital, health workers got a briefing on the importance of infection control. Posters depicting chickens and a burning globe are on walls throughout the building warning of bird flu, which has killed at least 124 people worldwide since it began ravaging Asian poultry in late 2003.

A quarter of the human deaths have been Indonesia, which has been criticized for acting too slowly to stop the spread of the disease.

Lack of public awareness is part of the problem, health experts say, noting that many people in the sprawling countryside have never heard of bird flu. Others, like 25-year-old Ginting, deny it is a problem.

At least six of Ginting's relatives from tiny Kubu Simbelang village in North Sumatra have died of the virus. A seventh was buried before samples could be taken, but the World Health Organization considers her part of the cluster _ the largest ever reported.

The case has drawn much attention because the infections have not been linked to contact with birds. Experts suspect limited human-to-human transmission may have occurred, but say no one else outside the family has fallen ill.

The disease remains hard for people to catch and most human cases so far have been traced to contact with infected birds. But experts fear the virus will mutate into a highly contagious form that passes easily among people, possible sparking a pandemic. They stress, however, that has not happened in Kubu Simbelang.

Ginting's mother, who declines to reveal her name, sits on a straw mat on a grassy patch outside her son's hospital room, at the end of a row of ground-floor rooms that open to the outside.

Despite losing three children and four grandchildren, she is not afraid to care for her son, who must be fed and is too weak to sit unaided since falling ill May 4.

She said he is slowly recovering, but still suffers a cough and struggles to speak.

"I'm not afraid. I don't even wear a mask or anything," she said. "If it spreads, I will be the first one to die."

Ginting's mother chewed on betel nut, a mild natural stimulant, as hens, roosters and chicks scratched the ground just feet away. Several cats also roamed outside her son's door.

"Why would I have to be afraid of chickens around here," she said. "The ones who died, they didn't eat chicken, after all."

The family, which has spoken to few outsiders, has been the subject of intense international interest because of the number of its members who were infected. WHO officials say it marks an important development with the H5N1 virus, which is thought to have been transmitted among people in a handful of other cases.

So far, scientists think, all such case have involved passing the virus between blood relatives. Some experts theorize that may mean some people have a genetic susceptibility to the disease, but there is no evidence to support that.

Many people in Ginting's farming village do not believe bird flu caused the deaths because no spouses or neighbors also got sick. Many, including Ginting and his family, have been uncooperative with health authorities.

"Johannes doesn't want to be injected, doesn't want to take Tamiflu or other antibiotics," Lubis said, although he added that the patient ha become more agreeable since first being hospitalized.

There is also a lack of knowledge about preventative steps, as shown by Ginting's uncovered visitors.

Lubis said the hospital held a seminar for the staff Monday to discuss infection control measures.

As he spoke, a woman outside Ginting's room picked through his garbage without gloves or other germ-protective gear. Family members of patients in the adjoining room lounged on the floor near his open door.

WHO guidelines call for health workers to wear masks, gloves, gowns, goggles and special boots when coming into contact with a bird flu patient, WHO spokesman Dick Thompson said.

Nurses and doctors who entered Ginting's room did wear protective gear, but no one interfered with the unprotected visitors.

Lubis said the hospital has done the best it can to isolate Ginting.

"For the room, we've done the maximum effort we can do," he said. "We don't know what more we can do beyond that."

Crucell tests three flu vaccines in humans
1st June 2006
By Tom Neilson
Dutch biotechnology company Crucell has commenced a large dose-ranging study to test a vaccine against avian influenza in humans.
The trial, performed in collaboration with a team based in Leicester, UK, will oversee the vaccination of 560 healthy adult individuals.

Conventional vaccines against H5 and H9 avian influenza subtypes work only at much higher doses than in seasonal vaccines, making it impossible to meet the world's vaccine requirements in the event of an H5 or H9 pandemic.

Formulations of H9 vaccine that are expected to enhance the immune response while enabling the vaccine to be used sparingly are being tested in the trial, with different dose levels also being studied. The intradermal route of immunization will be tested as it may also allow a reduction in the amount of antigen used.

The study will allow Crucell to choose the best vaccine modality to be tested in further clinical studies with pandemic vaccines, including vaccines against H5N1 avian influenza. First results of the study are expected by the end of 2006.

"We are proud to be involved in the testing of different production methods and ways to improve protection against pandemic flu," said Jaap Goudsmit, CSO of Crucell.