Entries in influenza and infectious diseases (390)

It's not always influenza that kills

Posted on Thursday, October 11, 2007 at 02:13PM by Registered CommenterScott McPherson in | Comments1 Comment

big-adenovirus-v3.gifWhile influenza hogs the world viral stage, adenovirus steals the show. 

One thing I have learned after a twenty-one month immersion into the world of influenza research is that you'd better be ready to learn a whole lot more about other illnesses.  That lesson could not be made clearer than this week, when I began to learn about the adenovirus.

Last week ,reports began to filter out of Mexico and Panama of a "mystery illness" that was killing scores of children.

As reported in the Miami Herald, edited by me:

Mystery disease strikes remote area of Panama

Posted on Tue, Oct. 02, 2007
BY ERIC JACKSON
Special to The Miami Herald

PANAMA CITY, Panama --
Local officials are reporting that 42 people have died, almost all of them children, in an outbreak of a still unidentified disease in the remote Ñurum district of Panama's indigenous Ngobe-Bugle region.

The ailment begins with a runny nose, coughing and fever, and when it gets deadly the victims present symptoms that look like bronchial pneumonia, according to a statement by Panama's Health Ministry.

The Health Ministry and the semi-automomous Gorgas Memorial Laboratory say they don't know the cause of the illness.

''We're studying it, and the Gorgas Lab is working on it, but to say anything now would be speculation,'' said a ministry official who asked for anonymity because he lacked authorization to comment on the case.

Word of a problem first got out in mid-September when local officials contacted the Health Ministry and then, alarmed by what they considered a lackadaisical response, took their story to the news media.

On September 23 Gladys Guerrero, the ministry's director of epidemiology, denied to a reporter for the tabloid El Siglo that there was any viral or bacterial pathogen at work, attributing the problem to complications of rainy season colds that are common in the area, especially because of its poor sanitary conditions.

Guerrero also said that local claims at the time of 10 deaths since late August were exaggerated. Within five days, Ngobe officials were reporting 40 deaths and many more sick. The La Prensa newspaper has reported that more than 30 children from Ñurum are being treated in various hospitals around the country.

The Health Ministry said in a Sept. 29 press release that the problem appears to be ''a known acute viral respiratory situation like influenza,'' but on Monday a ministry spokesman said that no flu or other virus had yet been identified.

The U.S. government has offered help, but as of Tuesday Panama had not asked for international assistance.

After news of the illness broke, President Martín Torrijos cut short a trip to the United States and flew into Ñurum with a team of some 60 healthcare workers. (bold mine)

Government officials fanned out to visit thousands of families and advise them to cooperate with health officials and that nobody evacuated to a city hospital would be left stranded -- a concern that had led some of the poor parents to refuse to let their children be taken to a hospital.

http://www.miamiherald.com/news/brea...ry/258274.html

So the president of panama ended his Washington visit with President Bush so he could take command of the situation.  That is telling.  Now, we have confirmation that the virus is none other than -- adenovirus.  From today's FluTrackers forum (edits by me), and a huge hat-tip to poster Dutchy:

Minister confirms deaths of Panamanian natives by adenovirus

Panama, 10 oct (PL) the minister of Panamanian Health, Rosario Turner, today confirmed the death of 17 smaller indigenous children of five years, victims of curable respiratory diseases that proliferate in the isolated region Ngobe Buglé.

In an appearance before the Commission of Health and Social Security of the National Assembly, Turner said that 93 members of the community were hospitalized and of them 77 withdrew after receiving the corresponding treatments.

Turner declared that the respiratory deaths and serious pictures that appeared the last weeks in the community of Ñurum, in the referred region, must adenovirus and influenza, (bold Dutchy) in as much discarded all possibility of a mortal germ.

Communitarian leaders said days back that at least 40 minors and an adult passed away of the attacks of cough, fevers and diarreas, but as many were buried near their houses, far from health facilities.

The holder of Health expressed that the problem must to a virus that affects to children and adults with nutricionales problems and of anemia, but that the fast action of the unfolded medical personnel in the region avoided new deaths.

Turner said that the arisen respiratory diseases in the indigenous community are own of the rainy station in the country reason why it reiterated to maintain the measures of personal hygiene.

http://www.prensa-latina.cu/article....7d&language=ES

By itself, this article would not amount to too much.  But let's seek context, and rewind two weeks ago to this report from Mexico, courtesy of WorldNetDaily:

Dozens in Mexican city ill with suspected avian flu
Raises concerns over international implications of epidemic

September 28, 2007


 

© 2007 WorldNetDaily.com

Dozens of people in a Mexican city are gravely ill with what is being treated as a possible outbreak of avian flu, according to a new report from a Spanish-language website.

According to El Universal, authorities in a neighborhood in Guanajuato say 45 patients have been given medical attention at the area's hospital after they reported symptoms including extreme headaches, stomachaches, vomiting and diarrhea.

The cases have developed over the last two weeks and "feel [like] death," according to Silvia Villalobos, one of the victims who spoke to El Universal correspondent Xochitl Alvarez in Spanish.

A spokesman for the regional general hospital, Ernesto Castle, said he does not know the cause of the problems, but officials are looking at an avian flu virus, which is transmitted by birds and is similar to botulism, as a source.

He reported at least 45 patients have been given emergency room medical attention, while others went to their private physicians for help.

One man reported his wife was hospitalized after the symptoms hit, waking her with fever and chills, before she fainted.

Guadalupe Gomez, a resident of the area, said her concern was that the epidemic was being carried by flies attracted by leather processed in the tanning industry, which includes leathers from other nations.

City spokesman Jose Eusebio Olague said officials have directed that barricades be set up so the sick do not spread the infections even further.

Traditional causes for fever and chills essentially have been ruled out by various tests, officials said. Sources in the air, water and other industries have been eliminated as a cause, officials said.

I will bet a dollar the Mexican virus is adenovirus.

Coincidentally, or perhaps serendipituously, a report was just issued this week on adenovirus 14 (oh, THAT adenovirus!). 

IDSA: Outbreak of Severe Pneumonia Traced to Adenovirus 14

SAN DIEGO, Oct. 9 -- A potentially deadly form of community-acquired pneumonia linked to adenovirus type 14 has emerged in the Pacific northwest, according to a report presented here.

 

First encountered in 2005 in Oregon, the viral pneumonia frequently leads to hospitalization and has a 20% fatality rate, (bold mine) Paul Lewis, M.D., of the Oregon State Public Health Department, said at the Infectious Diseases Society of America meeting.

 

"We recommend obtaining a viral culture in pneumonia patients who lack a specific etiology, especially those with severe disease," said Dr. Lewis. "If adenovirus 14 is detected, anticipate a stormy course. We encourage an infectious disease consultation to discuss the risks and benefits of any specific therapy that might be contemplated."

 

Recognition of the adenoviral pneumonia began with four patients hospitalized simultaneously at a Portland hospital. Upon comparing notes with physicians at area hospitals, Dr. Lewis and colleagues "almost fell out of our chairs because every hospital we called had recent severe and fatal cases of adenovirus disease."

 

(ditto)

Investigators followed up the informal communication with a systematic review of all cases of adenovirus disease identified by Oregon clinical laboratories from November 2006 to April 2007. Six months of active surveillance revealed what appeared to be a winter-spring predominant adenovirus disease, as the number of reported cases increased from January through April.

 

Isolates from the sickest patients were sent to the CDC, which found that almost all the cases involved adenovirus 14, a serotype identified more than 50 years ago but rarely detected since then and never in association with outbreaks.

 

Dr. Lewis and colleagues at the state health department reviewed analyzed specimens dating back to 1993 and found a few cases of adenoviral disease almost every year. Beginning in 2005 adenovirus 14 was the predominant serotype identified.

 

Comparison of 31 patients with adenovirus 14 disease and 14 patients with other adenovirus serotypes showed that adenovirus 14 tended to infect older men (median age 52.9), and almost half the cases involved smokers. Most strikingly, adenovirus 14 was associated with a hospitalization odds ratio of 15.9 compared with other adenovirus serotypes.

 

The most common clinical features leading to diagnosis of adenovirus 14 disease were fever (~80%), tachypnea (75% to 80%), hypoxia (~50%), and hypotension (40% to 45%). Chest x-rays were abnormal in 23 of 24 cases. Radiographic progression was common, including single-lobe disease to multilobe in 55% of cases and lobar disease to adult respiratory distress syndrome in 45%.

 

All patients received broad-spectrum antibiotics. Dr. Lewis said 22 of the 31 patients with adenovirus 14 disease were hospitalized, and 16 required ICU care. Median hospital and ICU length of stay was seven days. Of the patients treated in the ICU, 13 required ventilatory support and eight had severe hypotension requiring pressor drugs. Seven patients (22%) died.

 

Risk factors for death or ICU care were a creatinine level greater than 1.2 mg/dL, lymphocyte count less than 100 µL, and coinfection with another pathogen. None of those factors remained statistically significant in multivariate analysis.

 

"This came out of nowhere in 2005 in Oregon," said Dr. Lewis. Acknowledging that almost all of the cases have involved severe illness, he agreed that the scope of the problem could be much larger and involve a broader spectrum of illness severity.

 

I don't know about where you live, but here in Tallahassee, we have been hit with what appears to be an epidemic of pneumonia.  I personally know several people who were diagnosed with "viral pneumonia."  I had a terrible cold with severe chest congestion last month that nearly sent me to the hospital and recently floored my wife as well.  I am betting that where you live, you too had an experience similar to mine.

SARS was/is/will be again, a coronavirus that normally is associated with the common cold.  Only in 2003, in China, this cold virus jumped species and mutated into a respiratory illness with a 10% case fatality rate.  So what is to stop a mutant strain of adenovirus from growing in the jungles and rain forests of Central America and emerge on the world scene, as SARS emerged from the jungles of Southeast Asia?

Nothing. And, of course, there is no vaccine for adenovirus.

The CDC definition of adenovirus can be found at this link: http://www.cdc.gov/Ncidod/dvrd/revb/respiratory/eadfeat.htm . It says, in part:

Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other illnesses, such as gastroenteritis, conjunctivitis, cystitis, and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis. Patients with compromised immune systems are especially susceptible to severe complications of adenovirus infection. Acute respiratory disease (ARD), first recognized among military recruits during World War II, can be caused by adenovirus infections during conditions of crowding and stress. (bold mine).

Did Riau bird flu victim shed virus in Jakarta?

Posted on Tuesday, October 9, 2007 at 02:15PM by Registered CommenterScott McPherson in | CommentsPost a Comment

2007%20june%20medan%20indonesia%20human%20h5n1%20check.jpgFirst, 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

All eyes upon Riau, Indonesia

Posted on Monday, October 8, 2007 at 03:40PM by Registered CommenterScott McPherson in | Comments11 Comments | References18 References

riau%20map%20better%20resolution.gifAs 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 clock ticks one tock closer....

Posted on Friday, October 5, 2007 at 09:13AM by Registered CommenterScott McPherson in | Comments6 Comments | References1 Reference

H5N1%20E627K%20mutation%20et%20al%202007.jpgThe 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.

Also from the Reuters story, posted by MSNBC.com:

All flu viruses evolve constantly and scientists have some ideas about what mutations are needed to change a virus from one that infects birds easily to one more comfortable in humans.

Birds usually have a body temperature of 106 degrees F, and humans are 98.6 degrees F usually. The human nose and throat, where flu viruses usually enter, is usually around 91.4 degrees F. (bold mine)

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.

Killing two birds with one stone

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

japan%20wastewater%20lake.jpgOct. 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:

probenecid%20tamiflu%20extender.jpgTamiflu, 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!