First, the good news:  The "Medan Eight" suspected H5N1 patients have all tested negative.  This was done using conventional PCR testing.  The photo at left, by the way, was taken in June in Medan, where several suspected human cases of H5N1 occurred in May and June of this year.

The good news about Medan is tempered by the apparent revelation that 44-year old Riau H5N1 victim Linda Tismeri actually traveled to Jakarta while suffering from bird flu symptoms (and, hypothetically and probably, was shedding virus all the way there and all the way back).  intrepid FluTrackers and Flu Wiki poster Commonground has reworked, via ToggleText, a translation from Malay into English of a Riau newspaper's story.  Here it is:

Investigation, he said, also will be carried out down to Jakarta, where being known in the period of casualties's illness, had departed for Jakarta to visit to the family's house at the same time taking medicine there.
In Jakarta there, the increase, also will be found out by the possibility of the occurrence of the spread of the virus.
‘’Saat this we still could not answer from where the source of his spread.
All the possibilities could happen, good in the house, in the place of his activity or arrived at Jakarta the place that had been visited by him.
This that will be investigated by us more jauh,’’ said he.

More: http://www.riautoday.com/new/index.php?option=com_content&task=view&id=2821&Itemid=1

So the Indonesian authorities are dutifully following up on the dead woman's family in Jakarta, to see if the woman brought more than glad tidings to her family's home.  This is precisely the nightmare scenario we all fear:  An infected person in a remote part of a nation travels to a densely populated city to visit family or go shopping.  The end result is a plague of unmentionable lethality, let loose without warning.  Folks, this is no longer the stuff of horror fiction.  Stay tuned.  And thanks to Commonground. http://www.flutrackers.com/forum/showthread.php?t=37702&page=2

As we have learned over the weekend, the suspected bird flu death of 44-year old Linda Tismery of Pekanbaru, Riau Province, Indonesia, has been confirmed as H5N1.  This is the second H5N1 death in a week for the nation of Indonesia; the first was a male 21-year old West Jakarta shopkeeper who apparently was exposed to chickens.  The fact that, according to the Jakarta Post, some 26 deaths of the 87 now-confirmed H5N1 deaths in Indonesia come from the Greater Jakarta area (its capital) has apparently passed unnoticed.

Interesting.  If you read that 26 deaths in, say, Atlanta, Georgia since 2005 were from bird flu, would you take the news passively?  But I digress.

From the Jakarta Post:

Riau woman dies of suspected bird flu

- October 06, 2007

Rizal Harahap, The Jakarta Post, Pekanbaru

A woman believed to be suffering from bird flu died Friday morning in Pekanbaru, Riau province, after having received treatment in Arifin Achmad Hospital's isolation ward since Thursday.

The 44-year-old housewife, identified only as L, lived in a housing complex in Rumbai, Pekanbaru.

"The patient died at dawn. Our diagnosis indicated she was suffering from bird flu," the head of the hospital's bird flu mitigation team, Azizman Saad, told journalists Friday.

Before being transferred to Arifin Achmad Hospital, she had received treatment at several other hospitals in Pekanbaru.

"She was even treated at a hospital in Jakarta," Azizman said.

She was moved to Arifin Achmad Hospital after doctors at Awal Bros hospital noticed her symptoms were similar to those of bird flu victims.

"There is an indication her condition was detected late. As a consequence, she was already in bad shape when she was moved to this hospital," Azizman said.

Members of the woman's family declined to comment on whether she had come into contact with poultry recently.

L's death brings the number of bird flu fatalities in Riau this year to three. The other two victims lived in the Kampar and Indragiri Hulu regencies.

The Health Ministry confirmed Tuesday that a West Jakarta shop attendant died from bird flu last Friday, increasing the country's human death toll from the virus to 86.

Originally a disease carried by poultry, the H5N1 virus was first detected in humans in 1995 in Hong Kong.

Indonesia first reported human bird flu cases in 2005, but since has recorded the most human bird flu cases in the world at 107.

Now the Indonesian press is reporting that two of the nurses who attended to Ms. Tismery have also begun exhibiting bird flu symptoms.  This translation is courtesy of Dutchy and Theresa42 of FluTrackers.com:

Pekanbaru -- the media: (the media): two nurses from hospital early bross Pekanbaru, on Monday (8/10), suffered fever after have handled the victim who died from positive bird flu b Linda Tismery, 44, that died on Friday (5/10) last in RSUD Arifin Ahmad, Pekanbaru.

The identity of the two, to now still was kept secret . Together 63 other immediate contact. the amalgam of the team body perusal and expansion the health (balitbangkes) the Department of Health RI and the health service (dinkes) Riau still did check and appropriation blood the serum all the contacts.

Two nurses victim bird flu putative infected
Written by: Rudi Kurniawansyah

PEKANBARU -- MEDIA: (Media): Two nurses Hospital Awal Bross Pekanbaru, Monday (8/10), experience fever after ever handle victim died positive bird flu Linda Tismery, 44, who died Friday (5/10) previously in RSUD Arifin Ahmad Pekanbaru.

Identities both, until now still kept in secret with 63 contacts nearest rest. Team combination Body Research & Pengembangan Health (Balitbangkes) Depkes RI and Department of Health (Dinkes) Riau still perform checkup/surveillance and take serum blood everyone contact aforementioned.

The nurses had duties over some 63 patients.  All 63 are appearing to be OK, but the two nurses are quite ill.  This is always a cause for concern, because human-to-human transmission is becoming less and less rare in Indonesia, and any preliminary report of health care staff becoming ill causes ashen faces and worried looks both in Jakarta and in Geneva.

According to "boots on the ground" health care workers, taken from from a previous blog, http://www.scottmcpherson.net/journal/2007/9/24/indonesian-cases-continue-to-pile-up.html :

"Bird flu in Riau is a horrible disease at the moment. Right now there were 23 bird flu cases (grand total, starting from 2005) 3 of them died. In the rainy season we have at the moment, the bird flu virus will circulate for three more months. The health service asked the whole society to watch out and be very carefull, especially the bird breeders.

"Then the "sub head" of the health service and a someone from the Riau Food Authority say this: ' There were extremely many bird flu cases in Riau, not only the 23. We will not know how much, because the cases were in the interior, dying from high fever is regarded as normal by the public'.

" We reported 23 cases, our take is there could be as many identical cases in the districts that were not reported". "Because of this we ask the whole community to watch out for this virus.

"People should go to a clinic or to the Health Service if they display symptoms especially sudden high fever, and get medication. The dedicated bird flu hospitals are: RSUD Arafin Ahmad, RSUD Dumai and RSUD Tembilahan."

So something is going on in Riau, where my count shows five confirmed cases of H5N1 have occurred this year, with four deaths, and five times that many suspected cases have been reported and treated as the Real Thing.  Not a good sign at all. Now we have ill nurses and a deepening mystery.

The close physical proximity of Riau to Singapore, Malaysia, should also be a cause for concern.  Singapore's luck won't hold out forever.  Neither will the Philippines'.

The noted infectious disease rock star Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison is back in the news today, this time in a much better light.  He and his team of researchers have confirmed that the H5N1 "Qinghai" substrain (Clade 2.2)has mutated into a form that is much easier for humans to catch.

The key is the ability of the virus to infect the upper respiratory tract.  H5N1 normally has a tremendous affinity for the lower respiratory tract -- deep in the bottom of the lungs.  This makes it extremely difficult for humans to catch the virus.  But it also dooms most of the flu's human victims to death.  The mutation noted by Kawaoka and his team adapts the virus to the comparatively colder regions of the human throat and nose.

As quoted in today's New York Times: http://www.nytimes.com/reuters/world/international-birdflu-mutations.html?_r=3&oref=slogin&oref=slogin&oref=slogin

NEW YORK (Reuters) - The H5N1 bird flu virus has mutated to infect people more easily, although it still has not transformed into a pandemic strain, researchers said on Thursday.

The changes are worrying, said Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison.

"We have identified a specific change that could make bird flu grow in the upper respiratory tract of humans," said Kawaoka, who led the study.

"The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus," Kawaoka said.

Recent samples of virus taken from birds in Africa and Europe all carry the mutation, Kawaoka and colleagues report in the Public Library of Science journal PLoS Pathogens.

The above image is from an early 2007 Powerpoint pandemic presentation I have given too many times to count.  It is a graphical representation of Dr. Henry Niman's discoveries regarding changes in H5N1.  All the mapped changes have been found in Qinghai H5N1.  Dr. Henry Niman has a superb explanation for this.  The link to his latest commentary is here:

http://www.recombinomics.com/News/10050702/H5N1_E627K_Temp.html

Dr. Niman was, as I recall, the first scientist to comment publicly on the presence of the mutation(s) in question.  Dr. Niman observed this change in the virus last year.  Here is a portion of today's commentary:

The detection of E627K in dead wild birds at Qinghai Lake in May, 2005 signaled a major change in the global spread of H5N1.  At the time “Asian” H5N1 had not been reported in any country west of China.  The massive die-off at Qinghai Lake signaled the movement of H5N1 in long range migratory birds and the strain of a major geographical expansion.

The data on the temperature dependence of E627K also explains why many surveillance programs fail to detect Qinghai H5N1 in live wild birds, including locations where H5N1 is readily detected in dead or dying wild birds.  The body temperature of live wild birds keeps the levels of the virus low, below the detection levels of these assays.  Dead and dying birds have a lower body temperature, allowing levels of the virus to rise.

Although the effect of E627K on viral replication has been know (sic) since 2001, this fact has been ignored in the surveillance programs that focus on live birds.  Instead of measuring H5N1 antibody levels, which are more stable and reliable, these groups test thousands of birds and then use the false negatives to issue assurances and denials of the transport and transmission of H5N1 by wild birds.

Consequently, the alarming expansion of Qinghai H5N1 has largely happened below the radar of these (sic) surveillance, which remains a cause for concern, as have changes in the receptor binding domain in Qinghai isolates from fatal human cases, including V223I, S227N, and M230I.

What this all means, in short:

1.  As we have speculated for almost a year, Qinghai H5N1 has developed at least one, and probably several changes to its  composition, the result of which is the ability of the virus to survive in the colder temperatures of the human throat and nose.

2.  Surveillance programs are unable to detect the presence of Qinghai in live wildfowl, because we're not testing the birds correctly.  This is why dead and dying birds (with lower temperatures) are filled with H5N1, but live birds (with higher temperatures) appear not to be affected -- at least, not until they begin dying of the virus.

Blessedly, this change in the receptor binding domain is not the only precondition for H5N1 to "go pandemic." As stated by Drs. Robert Webster and Elena Govorkova stated in the New England Journal of Medicine last November,

Moreover, receptor specificity is only one of the requirements for human infection; the virus must also find compatible enzyme systems in the infected human cells if the viral polymerase complex is to function. Currently, these conditions are apparently met in only a few persons. But the virus is always changing, and mutations that make it more compatible with human transmission may occur at any time.  http://content.nejm.org/cgi/content/full/355/21/2174

Today's news reminds us that influenza smoulders.  It moves and evolves/mutates at its own speed, on its own timetable.  Today's news also officially moves us one tick closer to pandemic.

The Swedish have stirred up a mild flurry of press coverage with the disclosure that Tamiflu does not break down in conventional wastewater treatment systems.  The Bloomberg news story says:

Tamiflu in Urine, Water May Fan Resistant Flu Virus, Study Says

Oct. 3 (Bloomberg) -- Roche Holding AG's Tamiflu persists in waste water, which may make the drug a less effective weapon in an influenza pandemic, Swedish researchers said.

The medicine's active ingredient, oseltamivir carboxylate, is excreted in the urine and feces of those taking it. Scientists at Sweden's Umea University found the drug isn't removed or degraded in normal sewage treatment, and its presence in waterways may allow flu-carrying birds to ingest it and incubate resistant viruses.

``That this substance is so difficult to break down means that it goes right through sewage treatment and out into surrounding waters,'' said Jerker Fick, a chemist at Umea University and leader of the study, in a statement yesterday distributed by EurekAlert, a Web-based science news service.

The findings add to concern about the availability of effective medicines in the event of a pandemic sparked by bird flu. Strains either resistant or less sensitive to Tamiflu have been linked to the deaths of at least five people in Vietnam and Egypt. A separate study found Tamiflu may be becoming a weaker weapon against the H5N1 avian flu strain in Indonesia, where the virus has killed the most people.

The spread of H5N1 in late 2003 has put the world closer to a flu pandemic than at any time since 1968, when the last of the previous century's three major outbreaks occurred, according to the World Health Organization. The virus has killed 201 of the 329 people it's known to have infected, the Geneva-based agency said yesterday.

Use With Care

``Antiviral medicines such as Tamiflu must be used with care and only when the medical situation justifies it,'' said Bjorn Olsen, professor of infectious diseases at Uppsala University and the University of Kalmar, in the statement. ``Otherwise there is a risk that they will be ineffective when most needed.''

Scientists say waterfowl, including ducks, are the natural hosts of avian flu. These birds often forage for food in water near sewage outlets. It's possible they might encounter oseltamivir in concentrations high enough to develop resistance in the viruses they carry, the Swedish scientists said in their study, which is to be published in the journal PLoS ONE.

``The biggest threat is that resistance will become common among low pathogenic influenza viruses carried by wild ducks,'' Olsen said. These viruses could then recombine with others that make humans sick to create new ones resistant to the drugs currently available, he said.

Excreted Tamiflu

Millions of doses of Tamiflu have been stockpiled by governments and WHO to treat and prevent flu infections caused by a pandemic. WHO recommends that people infected by avian flu who are older than 1 year receive a five-day course of 750 milligrams of the medicine. The same quantity would be needed for a 10-day course aimed at preventing infection, which could be extended for several weeks until there is no further risk.

As much as 80 percent of the Tamiflu taken in each dose is excreted in its active form in urine and feces and the drug could potentially be ``maintained in rivers receiving treated wastewater,'' researchers from the U.K.'s Centre for Ecology and Hydrology said in a January study.

The potential for resistant strains to emerge this way is greatest in Southeast Asia, ``where humans and waterfowl frequently come into close direct or indirect contact, and where significant Tamiflu deployment is envisaged,'' the study's authors said.

They recommended developing methods to minimize the release of the active Tamiflu ingredient into the waste stream, ``such as biological and chemical pre-treatment in toilets, which could eliminate much of the `downstream' risk.''

Adding to the story, from Reuters:

"Use of Tamiflu is low in most countries, but there are some exceptions such as Japan where a third of all influenza patients are treated with Tamiflu," Jerker Fick, a researcher at Umea University who led the study, said in a statement.

From the AFP wire service story:

Scientists led by Jerker Fick, a chemist at Umea University, tested the survivability of the Tamiflu molecule in water drawn from three phases in a typical sewage system.

The first was raw sewage water; the second was water that had been filtered and treated with chemicals; the third was water from "activated sludge," in which microbes are used to digest waste material.

By the way, the photo at the top of this blog entry is from Konanchubu Wastewater Treatment Plant on Lake Biwa in Shiga Prefecture, Japan. According to http://www.sewerhistory.org/articles/whregion/japan_waj01/index.htm , advanced treatment is used to meet environmental standards for the water quality preservation of this and other designated lakes. The source is the best-selling report  Making Great Breakthroughs - All about the Sewage Works in Japan (Japan Sewage Works Association: Tokyo, ca. 2002), pp. 1-56.  I know, I know, you've read this cover-to-cover, but I had to include it anyway.

Okay, add Tamiflu to the list of medications you should never dump down the toilet.  As we know, environmentalists have been pleading with consumers for years not to dump expired medicine down the crapper, because many of these compounds simply do not break down in the treatment process.  Scientists hold the practice of flushing old medicine as being at least partially responsible for the rise in drug-resistant germs.  Now we know that Tamiflu, like other medications, takes a licking and keeps on ticking.

What this study also did, by proxy, is help confirm a suspicion that we can adapt an old World War II medical trick for use in a pandemic.  This is old news, but it bears repeating.  During WWII, medics and corpsmen learned that penicillin use could be extended with the addition of a simple drug -- probenecid.  Probenecid slows down the kidneys' natural desire to flush substances quickly.   The effect is to double the ability of a drug to perform its desired function.  The bottom line effect in wartime was to effectively double the available supply of penicillin.  What a clever innovation!

Roche itself has experimented with the concept, as outlined by Dr. Michael Greger in his excellent book Bird Flu: A Virus of Our Own Hatching.  Quoting from Dr. Greger's Website:

Roche found that probenicid doubled the time that Tamiflu spent circulating in the human bloodstream, effectively halving the dose necessary to treat someone with the flu. Since probenicid is relatively safe, cheap, and plentiful, joint administration could double the number of people treated by current global Tamiflu stores. “This is wonderful,” exclaimed David Fedson, former medical director of French vaccine giant Aventis Pasteur. “It is extremely important for global public health because it implies that the stockpiles now being ordered by more than 40 countries could be extended, perhaps in dramatic fashion.”2495

Of course, Roche probably does not like the idea of halving the necessary stockpile of Tamiflu!  That is quite understandable.  But by dispensing and co-administering probenecid at the same time as Tamiflu, you could actually double the number of courses of the antiviral overnight.  This has got to be communicated to state governments as a way to heavily leverage the available stockpile of Tamiflu in times of pandemic -- or even severe epidemics, such as we saw/are seeing in Australia.   

As we all know, the jury is still out on whether or not Tamiflu will be effective against the next pandemic strain of influenza.  We also know the only common denominator among H5N1 human survivors is the administration of Tamiflu.  So we can at least hope the antiviral will have some modicum of effectiveness, should H5N1 go pandemic.  It is the only pharmaceutical arrow we have in the quiver!

A portion of Roche's study of the use of probenecid in 2002 comes from the blogsite Smart Economy, and the story can be found at: http://smarteconomy.typepad.com/smart_economy/2005/11/smart_wartime_t.html . In part, it says:

Tamiflu, like penicillin, is actively secreted by the kidneys, and that the process is inhibited by probenecid.  "Giving the flu drug together with probenecid doubles the time that Tamiflu's active ingredient stays in the blood, doubles its maximum blood concentration, and multiplies 2.5-fold the patient's total exposure to the drug (see graph, and G. Hill et al.  Drug Metab.  Dispos.  30, 13-19; 2002)"

So the use of probenecid alongside Tamiflu will improve the effectiveness of the capsule by 2.5 times! 

Now let's address the issue of the effect of probenecid on the groundwater and wastewater.  This abstract is from the Website bionewsonline.com, specifically at: http://www.bionewsonline.com/f/1/bioremediation_a.htm :

Acta Microbiol Pol, 2003, 52(1), 5 - 13
Overuse of high stability antibiotics and its consequences in public and environmental health; Zdziarski P et al.; In this paper the ecological aspects of widespread antibiotic consumption are described . Many practitioners, veterinarians, breeders, farmers and analysts work on the assumption that a antibiotics undergo spontaneous degradation . It is well documented that the indiscriminate use of antibiotics has led to the water contamination, selection and dissemination of antibiotic-resistant organisms, alteration of fragile ecology of the microbial ecosystems . The damages caused by the overuse of antibiotics include hospital, waterborne and foodborne infections by resistant bacteria, enteropathy (irritable bowel syndrome, antibiotic-associated diarrhea etc.), drug hypersensitivity, biosphere alteration, human and animal growth promotion, destruction of fragile interspecific competition in microbial ecosystems etc . The consequences of heavy antibiotic use for public and environmental health are difficult to assess: utilization of antibiotics from the environment and reduction of irrational use is the highest priority issue . This purpose may be accomplished by bioremediation, use of probenecid for antibiotic dosage reduction and by adoption of hospital infections methodology for control resistance in natural ecosystems.

From Wikipedia:

Bioremediation can be defined as any process that uses microorganisms, fungi, green plants or their enzymes to return the environment altered by contaminants to its original condition. Bioremediation may be employed to attack specific soil contaminants, such as degradation of chlorinated hydrocarbons by bacteria. An example of a more general approach is the cleanup of oil spills by the addition of nitrate and/or sulfate fertilisers to facilitate the decomposition of crude oil by indigenous or exogenous bacteria.

But hey, Wikipedia also says bioremediation was invented by Al Gore, so what do they know?  Just kidding on that one.

So let's get jiggy and begin stockpiling probenecid.  The use of probenecid alongside Tamiflu, accompanied by a scientific study, would also tell us if the increased time in the human body before peeing it out would reduce the amount of Tamiflu to go into the groundwater, lakes and rivers.  It may also tell us if the effective increased dosage (2.5 times!) of each pill might beat back the rapid escalation of virus in human lung cells (remember that Tamiflu is a neuraminidase inhibitor).

While we are at it, let's look at Japan and see if, indeed, we can make a correlation between the (over)prescription of Tamiflu, the amount of active Tamiflu found in treated wastewater, and the Tamiflu resistance now seen in 3% of Japanese Influenza B strains.  Again, from the AFP story:

The study, published online on Wednesday by the open-access Public Library of Science (PLoS), pointed the finger at Japan.

It quoted figures from Swiss maker Roche, which estimated that in the 2004-5 influenza season, 16 million Japanese fell ill with flu, of whom six million received Tamiflu.

At such dosages, the amount of Tamiflu released into the Japanese environment is roughly equivalent to what is predicted in areas where the drug would be widely used in a pandemic.

Coincidentally, "Japan also has a high rate of emerging resistance to Tamiflu," the paper said. A 2004 study published in The Lancet found that among a small group of infected Japanese children, 18 percent had a mutated form of the virus that made these patients between 300 and 100,000 times more resistant to Tamiflu.

And throw old medicines away:  Don't flush!

AP story reminds us that disease can be self-inflicted.

An Associated Press story from today deals with the dozens and dozens of lab accidents and Series of Unfortunate Events since 2003 in American research labs.

AP IMPACT: More than 100 incidents reported at labs handling deadly germs

2007-10-02 06:36:25 -
WASHINGTON (AP) - American laboratories handling the world's deadliest germs and toxins have experienced more than 100 accidents and missing shipments since 2003, and the number is increasing steadily as more labs across the country are approved to do the work.
No one died, and regulators said the public was never at risk during these incidents. But the documented cases reflect poorly on procedures and oversight at high-security labs, some of which work with organisms and poisons so dangerous that illnesses they cause have no cure. In some cases, labs have failed to report accidents as required by law.
The mishaps include workers bitten or scratched by infected animals, skin cuts, needle sticks and more, according to a review by The Associated Press of confidential reports submitted to federal regulators. They describe accidents involving anthrax, bird flu virus , monkeypox and plague-causing bacteria at 44 labs in 24 states. More than two-dozen incidents were still under investigation.
The number of accidents has risen steadily. Through August, the most recent period covered in the reports obtained by the AP, labs reported 36 accidents and lost shipments during 2007 _ nearly double the number reported during all of 2004.
Research labs have worked for years to find cures and treatments for diseases. However, the expansion of the lab network has been dramatic since President George W. Bush announced an upgrade of the nation's bio-warfare defense program five years ago. The National Institute of Allergy and Infectious Diseases, which funds much of the lab research and construction, was spending spent about $41 million (¤28.81 million) on bio-defense labs in 2001. By last year, the spending had risen to $1.6 billion (¤1.12 billion).
The number of labs approved by the government to handle the deadliest substances has nearly doubled to 409 since 2004. Labs are routinely inspected by federal regulators just once every three years, but accidents trigger interim inspections.
«It may be only a matter of time before our nation has a public health incident with potentially catastrophic results,» said Rep. Bart Stupak, chairman of the House Energy and Commerce investigations subcommittee. Stupak's panel has been investigating the lab incidents and will conduct a hearing Thursday.
Lab accidents have affected the outside world: Britain's health and safety agency concluded there was a «strong probability» a leaking pipe at a British lab manufacturing vaccines for foot-and-mouth disease was the source of an outbreak of the illness in livestock earlier this year. Britain was forced to suspend exports of livestock, meat and milk products and destroy livestock. The disease does not infect humans.
Accidents are not the only concern. While medical experts consider it unlikely that a lab employee will become sick and infect others, these labs have strict rules to prevent anyone from stealing organisms or toxins and using them for bioterrorism.
The reports were so sensitive the Bush administration refused to release them under the Freedom of Information Act, citing an anti-bioterrorism law aimed at preventing terrorists from locating stockpiles of poisons and learning who handles them.
Among the previously undisclosed accidents
_In Rockville, Maryland, ferret No. 992, inoculated with bird flu virus, bit a technician at Bioqual Inc. on the right thumb in July. The worker was placed on home quarantine for five days and directed to wear a mask to protect others.
_An Oklahoma State University lab in Stillwater in December could not account for a dead mouse inoculated with bacteria that causes joint pain, weakness, lymph node swelling and pneumonia. The rodent _ one of 30 to be incinerated _ was never found, but the lab said an employee «must have forgotten to remove the dead mouse from the cage» before the cage was sterilized.
_In Albuquerque, New Mexico, an employee at the Lovelace Respiratory Research Institute was bitten on the left hand by an infected monkey in September 2006. The animal was ill from an infection of bacteria that causes plague. «When the gloves were removed, the skin appeared to be broken in 2 or 3 places,» the report said. The worker was referred to a doctor, but nothing more was disclosed.
_In Fort Collins , Colorado, a worker at a federal Centers for Disease Control and Prevention facility found, in January 2004, three broken vials of Russian spring-summer encephalitis virus. Wearing only a laboratory coat and gloves, he used tweezers to remove broken glass and moved the materials to a special container. The virus, a potential bio-warfare agent, could cause brain inflammation and is supposed to be handled in a lab requiring pressure suits that resemble space suits . The report did not say whether the worker became ill.
Other reports describe leaks of contaminated waste, dropped containers with cultures of bacteria and viruses, and defective seals on airtight containers. Some recount missing or lost shipments, including plague bacteria that was supposed to be delivered to the Armed Forces Institute of Pathology in 2003. The wayward shipment was discovered eventually in Belgium and incinerated safely.
The reports must be submitted to regulators whenever a lab suffers a theft, loss or release of any of 72 substances known as «select agents» _ a government list of germs and toxins that represent the horror stories of the world's worst medical tragedies for humans and animals.
A senior CDC official, Dr. Richard Besser, said his agency is committed to ensuring that U.S. labs are safe and that all such incidents are disclosed to the government. He said he was unaware of any risk to the public resulting from infections among workers at the high-security labs, but he acknowledged that regulators are worried about accidents that could go unreported.
«If you're asking if it's possible for someone to not report an infection, and have it missed, that clearly is a concern that we have,» Besser said.
Texas A&M's laboratory failed to report, until this year, one case of a lab worker's infection from Brucella bacteria last year and three others' previous infection with Q fever _ missteps documented in news reports earlier this year. The illnesses are characterized by high fevers and flu-like symptoms that sometimes cause more serious complications.
«The major problems at Texas A&M went undetected and unreported, and we don't think that it was an isolated event,» critic Edward Hammond said. He runs the Sunshine Project, which has tracked incidents at other labs for years and first revealed the Texas A&M illnesses that the school failed to report.
Rules for working in the labs are tough and are getting more restrictive as the bio-safety levels rise. The highest is Level 4, where labs study substances that pose a «high risk of life-threatening disease for which no vaccine or therapy is available.» Besides wearing wear full-body, air-supplied suits, workers undergo extensive background checks and carry special identification cards.
«The risk that a killer agent could be set loose in the general population is real,» Hammond said.
In other lab accidents recounted in the reports, the Public Health Research Institute in Newark, New Jersey, was investigated by the FBI in 2005 when it couldn't account for three of 24 mice infected with plague bacteria. The lab and the CDC concluded the mice were cannibalized by other plague-infested mice or buried under bedding when the cage was sterilized with high temperatures.
The lab's director, Dr. David Perlin, told the AP it would be impossible for mice to escape from the building and said a worker failed to record their deaths.
«I feel 99 percent comfortable that was the case,» Perlin said. «The animals become badly cannibalized. You only see bits and pieces. They're in cages with shredded newspaper. You really have to search hard with gloves and masks.
A worker at the Army's biological facility in Fort Detrick, Maryland, was grazed by a needle in February 2004 and exposed to the deadly Ebola virus after a mouse kicked a syringe. She was placed in an isolation ward called «The Slammer,» but the Army said she did not become ill.
In other previously undisclosed accidents
In Decatur, Georgia, a worker at the Georgia Public Health Laboratory handled a Brucella culture in April 2004 without high-level precautions. She became feverish months later and tested positive for exposure at a hospital emergency room in July. She eventually returned to work. The lab's confidential report defended her: «The technologist is a good laboratorian and has good technique.
In April this year at the Loveless facility in Albuquerque, an African green monkey infected intentionally with plague-causing bacteria reached with its free hand and scratched at a Velcro restraining strap , cutting into the gloved hand of a lab worker. The injured worker at the Lovelace Respiratory Research Institute received medical treatment , including an antibiotic.
The National Animal Disease Center in Ames, Iowa, reported leaks of contaminated waste three times in November and December 2006. While one worker was preparing a pipe for repairs, he cut his middle finger, possibly exposing him to Brucella, according to the confidential reports.
A researcher at the CDC's lab in Fort Collins, Colorado, dropped two containers on the floor last November, including one with plague bacteria.
A worker at Walter Reed Army Institute of Research-Naval Medical Research Center in Silver Spring, Maryland, sliced through two pair of gloves while handling a rat carcass infected with plague bacteria. The May 2005 report said she was sent to an emergency room, which released her and asked her to return for a follow-up visit.

This is so timely because of the recent University of Wisconsin revelation that their superstar researcher, Dr. Yoshi Kawaoka, committed a "DOH!"

Wisconsin: Ebola Research in Unsecured Lab

Research at the University of Wisconsin, Madison, on the deadly Ebola virus was conducted for a year in a less-secure laboratory than required, until the National Institutes of Health alerted the school to the problem. The virus itself was never present in the laboratory, said Jan Klein, a university biological safety officer. Instead, DNA copies of the virus were being studied to understand one of the world’s most dangerous pathogens.

From the Wisconsin State Journal:

RYAN J. FOLEY
Associated Press
September 19, 2007

UW-Madison allowed a star researcher to study material that could be used to produce the Ebola virus in a lab less secure than what's required under federal guidelines.

The study was stopped last fall after a National Institutes of Health official told the university the material must be contained at labs with the highest level of security, or Biosafety Level 4.

Researcher Yoshi Kawaoka, his colleagues and the public were never at risk because the deadly virus itself was never present in the lab, said UW-Madison biological safety officer Jan Klein.

"It's more of a technical violation than a safety violation. No one was at risk," she said. "It was a matter of how you read the guidelines. NIH took a broader read of the guidelines than we were aware of and we were using."

A NIH spokesman said he was looking into the matter and had no immediate comment.

Kawaoka, a professor of virology in the School of Veterinary Medicine, was at a meeting in Chicago on Wednesday and did not immediately return an e-mail message.

Kawaoka is a leading researcher on infectious diseases such as bird flu and Ebola. The university retained him last year by promising to build a $9 million research institute after he received a lucrative offer from the University of Pittsburgh.

The federally funded study aimed to better understand the Ebola virus, one of the most dangerous pathogens on Earth. To do so, researchers were studying DNA copies of the virus. Klein said scientists could produce an infectious virus if they combined the material with "additional components."

"But that was not part of any planned experiment and would not be done by accident," she said.

Still, a watchdog group said Wednesday the case illustrates lax university and federal oversight of research involving potentially dangerous agents.

"The UW looked federal guidance in the face and ignored it," said Edward Hammond, director of the Austin, Texas-based Sunshine Project. "If the federal government isn't keeping careful tabs on Ebola labs, I'm a bit scared. I think others should be as well."

The group, which works to limit access to biological weapons agents, on Wednesday released documents related to the study obtained through an open records request.

Hammond questioned whether the university allowed the research to go forward out of favoritism to Kawaoka.

"The University of Wisconsin is willing to go to great lengths to keep Kawaoka there," he said. "Maybe that influenced their review of his research."

Klein denied that was the case. She said a university committee approved Kawaoka's research for a Biosafety Level 3 lab after performing a required risk assessment.

She said the university has about a dozen Level 3 labs but none that are Level 4, which have the most stringent guidelines meant to ensure pathogens cannot escape.

Kawaoka was actually pressing to relax the safety guidelines further by asking whether the study could take place in a Level 2 lab, Klein said. That's when the university asked NIH for guidance and learned the material was restricted to a Level 4 lab. (bold mine)

UW-Madison spokesman Terry Devitt said the research was immediately stopped in Madison and relocated to a higher security Canadian lab.

Klein said the episode has had no other repercussions.

"He is a very compliant researcher. He understands that his credibility is in jeopardy for doing anything that might jeopardize the safety of his personnel and those of his colleagues in his community," she said. "He's always been extraordinarily responsive and a pleasure to work with."

All-righty then!  A rock star researcher wanted to lessen -- not strengthen -- the conditions under which a fax of a virus would be analyzed! Seems perfectly logical to me.

None other than the Pope of Influenza himself, Dr. Robert Webster, has stated publicly that the 1977 age-specific influenza pandemic that reintroduced H1N1 into society was the direct result of a Soviet lab accident. And we understand that since 9/11, the government has funded a ton of new research into emerging potential biological threats to Americans.  But that is no excuse for lax oversight by the recipients of the research dollars.  Nor does the government concede shortcuts to research, such as was the case at U. Wisconsin.  

Now you may say that this is no biggie, there is little chance that lab techs would ever pass disease to civilians.  I offer this in rebuttal:

Parents say lab technician bit their son

Wed Sep 26, 5:49 PM ET

A laboratory technician has been fired after the parents of a 3-year-old boy claimed she bit his shoulder while drawing blood from his arm, a hospital spokesman said.

Faith Buntin took her son Victor to St. Vincent Hospital on Friday for a blood test because of recent recalls of toys involving lead. She said she saw the worker put her mouth on Victor's shoulder.

"I looked at her like that was the craziest thing that I'd ever seen," Faith Buntin told television station WRTV. "She looked at me and smiled and said, 'Oh, it was just a play bite. He's not hurt.'"

After they returned home, the boy's mother said, she saw teeth marks on his left shoulder, and her husband drove the child back to the hospital, where he was prescribed antibiotics.

"Taking a bite out of him like he's an apple, this is heinous," said James Buntin, the boy's father.

St. Vincent fired the technician after the incident was reported and is "reviewing the capabilities" of the employees of the subcontractor that does blood work for the hospital, spokesman Johnny Smith said.

"We're tying to determine the best approach," he said. "It's just an unfortunate and sad situation and our thoughts and prayers go out to the family."

No charges have been filed.

And a final cautionary tale that labs can, indeed, spread disease, even if human interaction is not responsible.  We all know the recent British outbreak of foot and mouth disease.  But we may not have read the conclusion: 

Damaged pipe at lab caused foot-and-mouth outbreak, BBC reports

The Associated Press

Wednesday, September 5, 2007

LONDON: Investigators have determined a pipe at a research laboratory facility in southern England caused last month's outbreak of foot-and-mouth disease, the British Broadcasting Corp. reported Wednesday.

Britain's Health and Safety Executive found there were biosecurity lapses at the facility in Pirbright, Surrey, the BBC reported. The investigators' official report is due to be published Friday.

The Environment Department would not comment on the report Wednesday.

The lab complex houses vaccine-maker Merial Animal Health — the British arm of U.S.-French pharmaceutical firm Merial Ltd. — and the government's Institute of Animal Health.

Virus traces were found in a pipe running from Merial's lab to a treatment plant operated by the government-run lab, the BBC reported, adding the pipe may have been damaged by tree roots.

Investigators found contractors working at Pirbright traveled to and from the site using a country road next to the farm where the first outbreak occurred, the BBC said.

Foot-and-mouth disease affects cloven-hoofed animals including cows, sheep, pigs and goats. It does not typically infect humans, but its appearance among farm animals can have a far-reaching economic impact.

After the outbreak was detected on Aug. 3, Britain suspended exports of livestock, meat and milk products for nearly three weeks.

About 600 animals were slaughtered as a result of the outbreak. The National Farmers' Union said restrictions on meat exports cost the industry about 1.8 million pounds (US$3.5 million; €2.6 million) a day since the first case was confirmed.

Though several sites were tested, only two farms — both about 30 miles (50 kilometers) southwest of London — had cattle confirmed with the disease.

Add routine maintenance to the list of issues to be dealt with at labs across the world.  The pipe could have been fixed for an estimated fifty thousand pounds sterling (£50 million).  http://www.timesonline.co.uk/tol/news/uk/article2406565.ece

Pipe repair for £50,000 could have prevented foot-and-mouth disease

This summer’s outbreak of foot-and-mouth disease, which has cost the country almost £50 million, could have been avoided if £50,000 had been spent on repairs to a leaking pipe.

It has also emerged that officials at the Department for the Environment, Food and Rural Affairs knew about the poor state of the drains at the Pirbright research laboratory site in Surrey four years ago.

But wrangling between the government-funded Institute of Animal Health (IAH) and the pharmaceutical company Merial Animal Health, which share the site, over how much each should pay towards repairs reached a deadlock and the work was not carried out. The issue is expected to be decided in the High Court.

Such a lax approach at a scientific establishment handling live viruses that could devastate livestock farming was revealed yesterday, after the publication of two official inquiries into the cause of the outbreak.

A culture of complacency at the IAH and scant regard for biosecurity measures emerge from the reports. As well as the leaky drains there was no system for disinfecting vehicles that could have picked up viruses at the plant. Although terrorism and sabotage have been ruled out as a cause of this outbreak, the inquiries suggest that it would be easy for an intruder to get into the high-risk laboratories.

The failings are considered to be so serious that an urgent system of inspections will now take place at each of the 432 British laboratories that deal with deadly and highly infectious human and animal disease pathogens. Hilary Benn, the Rural Affairs Secretary, made clear however that no official would face disciplinary action.

Mr Benn made it clear that there were no excuses for the escape from the Pirbright facility. He said: “It should not be possible for a live virus to escape from a secure laboratory. It should not have happened even under these extraordinary circumstances and must not happen again.”

Although the precise cause of the outbreak may never be established precisely the inquiries point to a cracked effluent pipe, tree roots and unsealed manhole covers. It is thought that the escaped virus was most likely from Merial, although not because of a breach in biosecurity, which leaked and contaminated surrounding soil. The infected mud was picked up on the tyres of contractors’ lorries that were driven along a lane near to the Normandy farm where the disease was identified 35 days ago.

Brian Spratt, an expert in infectious diseases at Imperial College, London, who headed an independent inquiry, said: “It is very clear that the drainage system was defective, poorly maintained, rarely inspected and could leak.”

The last Defra inspection took place in March but the drainage problem was not regarded as a problem to the work on a foot-and-mouth vaccine.

Professor Spratt highlighted a conflict of interest in Defra’s role as regulator, licenser, inspector and leading funder for research at the IAH. His report said: “The poor state of the IAH laboratories and the effluent pipes indicates that adequate funding has not been available to ensure the highest standards of safety for the work on foot-and-mouth disease.”

Geoffrey Podger, chief executive of the Health and Safety Executive, which led the investigation into the cause, highlighted “long-term damage” of the drainage system, inadequate controls on movement of people and vehicles and poor record-keeping. He said: “It was absolutely essential that the pipework was fully contained. It was not.”

The foot-and-mouth outbreak was declared over yesterday and at noon today restrictions in the surveillance zone near the infected farms and on animal movements are to be lifted.

The earliest date for trade to resume with countries outside of the EU will be November 7.