A Journey Through The World of Pandemic Influenza

Pandemic Mitigation II

Last night I addressed pandemic mitigation from a general, community level (here), tonight I would like to discuss the issue on an individual level.

There are 300 million +/- people in the US and according to the 2000 US Census 69% percent of us live in areas that have a population of 50,000 or more, in 3,629 urban areas. For a breakdown of percentage by state see here. I was quite surprised to learn that my state (SC) is the least urban density in the nation—a good thing in a moderate to severe pandemic.

 

Using official estimates of what could be anticipated for a severe pandemic a 30% CAR (clinical attack rate) and 2% CFR (case fatality ratio) we can glimpse into our crystal balls and see what might be in store for our states and our cities.

For my area, the city, (Charleston), has 425,000+/- residents. That would mean that my city would see roughly 127,500 PanFlu illnesses and 2,550 illnesses directly attributed to those illnesses. Were I to figure it for the entire area, known locally as The Tri-County the figures are as follows: 603,500 residents, 181,050 PanFlu illnesses, and 3,621 PanFlu deaths.

Of course, we have no way of knowing what the CAR/CFR of the next pandemic will be, should one occur, but currently H5N1 has a cumulative CFR of just over 60%. Assuming a pandemic of H5N1 for my purposes here, a drop of 90% in the current CFR would still leave us dealing with a CFR of 6%, and that would translate to 7,650 deaths for my city and 10,863 for my entire area. When I type "deaths" and you read "deaths", it is important to remember that those numbers represent people: men, women and children. In the case of the figures I quoted those are my neighbors, co-workers, friends and family members.

 

I went through all the effort to type all of the above out because I feel it is important to be crystal clear about what I am addressing in this entry, what we, as individuals, can do to reduce our chances of being included in our community's statistics.

 

So, what can we reasonably do to protect ourselves? Until we have a vaccine released to our demographic/cohort, (for a draft guidance of vaccine priority sees here), we will have to rely on Non-pharmaceutical Interventions—NPI's.

• Keep your children out of school no matter what your school's official policy is. Not only are children the most efficient spreaders of influenza, schools are over crowed and perfect amplification points for any infectious disease.
• Maintaining social distancing: 3 feet or more.
• Frequent hand washing
• Avoiding touching our faces
• Avoiding touching common surfaces: anything someone else may have touched. Both influenza A and B viruses survived for 24-48 hr on hard, nonporous surfaces such as stainless steel and plastic but survived for less than 8-12 hr on cloth, paper, and tissues. Measurable quantities of influenza A virus were transferred from stainless steel surfaces to hands for 24 hr and from tissues to hands for up to 15 min. Virus survived on hands for up to 5 min after transfer from the environmental surfaces. J Infect Dis. 1982 Jul;146(1):47-51
• Use alcohol based hand sanitizer liquid or gel any time you touch a common surface
• Work from home if at all possible
• Stay home if possible (known as SIP or Shelter in Place by Flubies)
• Minimize physical contact
• Wear a mask: N95, surgical, homemade (in order of effectiveness and difficulty of obtaining during a pandemic) My blog entry for the CDC's offering on a homemade mask here, and a discussion thread about masks, as well as tossing around ideas on mask workarounds in general on P4P here.
• Stay home if you become ill with any illness; you will not know if it is PanFlu or not for a day or three and you do not want to be out spreading germs.

   

 

Will doing these things guarantee you will not get PanFlu should we suffer a pandemic? I cannot give you a definitive yes to that question, but they will reduce your chances of becoming infected, and short of an effective vaccine, that is probably the best we will be able to manage—reduce our chances of becoming infected. An aside: For the latest release on the steps and timeline involved in producing a PanFlu vaccine see the WHO's PDF here; the pandemic is likely to be over before we have an effective vaccine.

 

 

Here's hoping none of us end up as a PanFlu statistic.

 

SZ

Vitamin D and Pandemic Influenza

 

First things first:

 

I am not a medical professional. What I have chosen to arm myself and my family with is based on my own readings and my own evaluations of an item's efficacy. I do not recommend anyone blindly believe that what I post here has merit in the prevention or treatment of Pandemic Influenza. Instead, I hope you will be motivated to do further reading and independent evaluations to decide if the options are applicable to your situation.

 

Second things second:

 

When it comes to supplements there is a bewildering array of information available on the internet, some of it good, much of it bad. There are often conflicting findings; one study will find a supplement to be of benefit and another will debunk it. When deciding to utilize a substance that we intend to ingest into our bodies, or give to those we love, we should first strive to "do no harm". Secondly we must decide if the sought after benefit outweighs any of the possible/potential harm. Thirdly, we must understand the proper storage and usage of the supplement. Even the best, most efficacious vitamin or herb will do little or no good if we don't take it properly.

 

 

Vitamin D

 

One of the major items I have in my arsenal is plain old Vitamin D. If, and when, an Influenza Pandemic presents itself I will put my family on a daily maintenance regime of 2,000 IUs in divided doses. When PanFlu hits the shores of my country I will up the daily dosage to 4,000 IUs.

 

There are a few caveats associated with Vitamin D and influenza prevention/modulation that should be stated upfront. All points are taken from Wikipedia's entry on Vitamin D.

• The recommended daily allowance seems to be far too low to derive the sought after benefit.
  • The U.S. Dietary Reference Intake for Adequate Intake (AI) of vitamin D for infants, children and men and women aged 19–50 is 5 micrograms/day (200 units/day).^[11] Adequate intake increases to 10 micrograms/day (400 units/day) for men and women aged 51–70 and to 15 micrograms/day (600 units/day) past the age of 70.^[1]
• There are skin pigmentation absorption issues. The darker your skin the less Vitamin D you will make from sunlight, thus your risk of being Vitamin D deficient increase. The strong anecdotal evidence linking vitamin D deficiency and influenza would suggest that non-whites will suffer a far greater infection and mortality rate than fair skinned people, and therefore should have greater motivation to look after their levels of intake.
• At latitudes above or below 30° the decreased angle of the sun during the winter months, shorter days, colder weather, and heavier clothing will all contribute to an inability of the body producing the desired amount naturally, thus greatly increasing the risk of Vitamin D deficiency.
• In order to gain the benefit a daily allowance of at least 2,000 IUs are probably required.

   

 

From Wikipedia's entry on Vitamin D

Vitamin D is a group of fat-soluble prohormones, the two major forms of which are vitamin D₂ (or ergocalciferol) and vitamin D₃ (or cholecalciferol).^[1] The term vitamin D also refers to metabolites and other analogues of these substances. Vitamin D₃ is produced in skin exposed to sunlight, specifically ultraviolet B radiation.

    …..

Vitamin D plays an important role in the maintenance of several organ systems.^[2]

Vitamin D₂: ergocalciferol or calciferol (made from ergosterol)

Vitamin D₃: cholecalciferol (made from 7-dehydrocholesterol in the skin).

Vitamin D₂ is derived from fungal and plant sources, and is not produced by the human body. Vitamin D₃ is derived from animal sources and is made in the skin when 7-dehydrocholesterol reacts with UVB ultraviolet light at wavelengths between 270–290 nm.^[4] These wavelengths are present in sunlight at sea level when the sun is more than 45° above the horizon, or when the UV index is greater than 3.^[5] Adequate amounts of vitamin D₃ can be made in the skin only after ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen. With longer exposure to UVB rays, an equilibrium is achieved in the skin, and the vitamin simply degrades as fast as it is generated.^[1]

 

 

The Vitamin D story as it relates to Influenza infection in humans is not extensive, however what is available is promising. I can not do the concept justice in this blog entry, but what I can do is point you to where you need to go for support of Vitamin D's usage.

 

The ABCs of D

Almost everyone needs more of the sunshine vitamin

By Deborah Kotz

Posted 12/10/06

A single nutrient that keeps bones strong, wards off diabetes, and protects against tuberculosis, cancer, colds, and the flu. Sound too good to be true? There's more: It's free. But you're almost certainly not getting enough.

    [snip]

Prior to the industrial revolution, humans had no trouble getting an abundance of the sunshine vitamin; a mere 10 to 15 minutes outdoors at midday gives the average fair-skinned person 10,000 international units. That's far above the government's dietary recommendations of 200 IUs a day up to age 50, 400 IUs to age 70, and 600 IUs over 70. But most people nowadays spend little time outdoors, and food sources such as milk and salmon contain relatively modest amounts. What's more, the rash of new findings suggests to the experts that the guidelines are way too low. "There's no one working in the field who thinks these levels still make sense," says Walter Willett, a professor of epidemiology and nutrition at Harvard University whose recent studies have focused on the connection between vitamin D and cancer.

[snip]

An immune system link might explain why the flu seems to strike only during the winter. A review of more than 100 studies on vitamin D and respiratory diseases, published in the current Epidemiology and Infection, found that low levels probably allow the viruses to penetrate the immune system. "It's the first comprehensive theory set forth to explain the seasonality of influenza," says vitamin D expert and lead author John Cannell, president of the Vitamin D Council and staff psychiatrist at Atascadero State Hospital in California. What's now needed, he says, is a trial to see if those exposed to flu viruses are less likely to come down with an infection if they take supplements.

The possibility intrigues researchers bracing for an outbreak of avian flu, which quickly kills by triggering an excessive immune response. Victims often suffocate when an onslaught of disease-fighting cells, known as a cytokine storm, results in a rapid buildup of fluid in the lungs. Experts think vitamin D might rev up the part of the immune system that prevents the germs from gaining entry to cells in the first place. "This puts a damper on the part of the immune system that releases the cytokine storm," says Michael Zasloff, an immunologist and vitamin D researcher at Georgetown University in Washington, D.C. Research shows that the mechanism also seems to protect against multiple sclerosis and rheumatoid arthritis, in which the immune system attacks the body's own healthy tissue.

[snip]

How much to take? The government last year suggested that African-Americans and the elderly might want more than the guidelines suggest, but it has set 2,000 IUs as its ceiling for safety. Most experts think the limit is too conservative, noting that there's no evidence of toxicity at much higher doses and that 2,000 IUs is a worthy goal for everybody. Consuming 3 ounces of tuna, two glasses of milk, and a glass of fortified orange juice will get you to 500 IUs, and a supplement or two will get you the rest.

 

Further reading:

 

Pandemic Flu Information Discussion Forum thread: Vitamin D

 

Epidemic Influenza And Vitamin D 15 Sep 2006   

[snip]

Hope-Simpson had no way of knowing that vitamin D has profound effects on human immunity, no way of knowing that it increases production of broad-spectrum antimicrobial peptides, peptides that quickly destroy the influenza virus. We have only recently learned how vitamin D increases production of antimicrobial peptides while simultaneously preventing the immune system from releasing too many inflammatory cells, called chemokines and cytokines, into infected lung tissue.

 

Vitamin D and genomic stability

[snip]

Vitamin D is also effective in stimulating DNA synthesis in adult alveolar II cells and provides a novel mechanism of modulation of epithelial cell proliferation in the context of lung development and repair against injury.

 

Wikipedia's Vitamin D page

[snip]

Active vitamin D hormone also increases the production of cathelicidin, an antimicrobial peptide that is produced in macrophages triggered by bacteria, viruses, and fungi.[29] Vitamin D deficiency tends to increase the risk of infections, such as influenza and tuberculosis.

 

As I tell myself everyday: We are not helpless, even in the face of something as daunting as a severe Influenza Pandemic.

 

SZ

 

 

More on Statins and Pandemic Influenza

 

Reuters ran a story today about a new study on the apparent benefits of statin usage in providing a measurable protection against death from pneumonia and seasonal influenza. For an earlier post on Statin use during an Influenza Pandemic see here.

 

(Reuters) -- People who use statin drugs are less likely to die of influenza and chronic bronchitis, according to a study that shows yet another unexpected benefit of the cholesterol-lowering medications. Their study of more than 76,000 people showed that those who had taken statins for at least 90 days had a much lower risk of dying from chronic obstructive pulmonary disease or COPD, the technical name for emphysema and chronic bronchitis.

 

    [snip]

 

"This study found a dramatically reduced risk of death from COPD among statin users and a significantly reduced risk of death from influenza/pneumonia," the researchers wrote in their report, published in the journal Chest. "These findings suggest that moderate-dose statin use reduces the risk of influenza/pneumonia death and strongly suggest that statins reduce the risk of COPD death."

 

In 2006, researchers in Canada reported that statins act against sepsis, a dangerous blood infection, and a 2005 study found the death rate was 64 percent lower in pneumonia patients who had been taking statins.

 

As I stated in the first post on this concept: No one knows if the benefits found with seasonal influenza and statin usage would have any translatable benefit to an Avian Influenza Pandemic. But given the potential benefit weighed against the potential risks it seems a worth wild avenue of exploration.

Also in the previous post, and as stated above, it isn't something that you can begin taking the day you think you may have been infected. At minimum, it is assumed that taking it for thirty days would be needed to confer benefit, and this paper looked at ninety days as the measure. Either way, it will require preplanning and advance supplying. You should bring in your supply prior to a pandemic because it is believed that there will be no medication resupply during a severe pandemic.

 

See my previous entry to read about the natural alternative to prescription statins, Red Yeast Rice.

 

SZ

Fla_Medic's Lesson... to us all.

My dear friend, Cyber Twin, Compatriot, and All-Around-Wonderful Guy, Fla_Medic took ill suddenly.  I have cross-posted his blog entry from Avian Flu Diary because what he recounts is a very important lesson.  Not only for everyday, but most especially for PanFlu.

Many Flubies, myself included, are planning to make up PanFlu medical "kits" that we will use should we become infected with no one around to minister to us.  The severity of FM's illness from an "average" and "mundane" virus exposes the weakness and, perhaps, utter foolishness of self-treatment, for PanFlu.

It was especially sobering for me because I know how knowledgeable and capable FM is.  The fact that he was rendered "senseless" enough to neglect his critical hydration needs is a message in and of itself.

I think I will have to make a "cyber date" with FM after he fully recovers to go over a more specific plan of attack for our "flu kits".  Suddenly, my plans don't appear to be too sound... at all.

Lessons Learned

# 639

Thirty-six hours ago I was hit, and hit hard, by what I suspect was a norovirus.   In the space of an hour I went from feeling fine, to having a severe headache, fever, nausea, vomiting, dizziness,  and diarrhea.  

Being a sensible type, I figured if I laid down for a couple of hours, I'd feel better.  So around 6 pm Thursday night I took to my bed.   I didn't bother putting any medicines, or a water bottle by my bed, after all, the kitchen was only 30 feet away.

The next 24 hours are a feverish blur.  For the first 12 hours, I was afraid I was going to die, for the following twelve, I feared I wouldn't.

I managed to make more than a dozen semi-conscious runs to the bathroom, but the kitchen, 30 feet away, was too far to manage.   I knew I should be drinking fluids, and desperately wished I could reach my phenergan and loperamide to control the nausea and diarrhea, but it was simply beyond my means to get to them.

I'm pleased to report that after 24 hours of delirium, I managed to finally get to my meds, and to start taking fluids.  And twelve hours later, I'm in better shape.  Not well, by any sense of the definition, but getting better.

There is a lesson here, for me, and everyone one else. 

If you live alone, or with someone who isn't likely to be a good caregiver, put a `flu box' under your bed, an arm's reach away.   I desperately wished I had some basic meds and some sports drinks at hand. I could have saved myself considerable misery over the past 36 hours had I done that.

As a paramedic, I should have known better. I should have been better prepared.   But honestly, I never considered that a simple virus would knock me flat like this one did. 

The good news is, I've learned my lesson. I'll be better prepared the next time.

posted by FLA_MEDIC @ 4:26 AM

Stretching Our Supply of Tamiflu

Tamiflu is our first line of defense in preventing and treating H5N1 human infections.  It is utilized as a prophylactic, HCWs and poultry flock cullers often take it to prevent infection in a known high risk environment, it has also been used on occasion to give close contacts of confirmed or highly suspected cases.  When a Tamiflu Blanket is mentioned, this is what they are referring to.

Of course, it is also the primary treatment for human infection, and while not perfect, it is, currently, the best available treatment, affording the highest chance of survival.  Its success is the reason that governments around the world have or are building a Pre-Pandemic supply. 

Private businesses, of all sizes have either stocked, or are trying to stock Tamiflu for their critical personnel.  This would theoretically entice those workers to report to the job, keep them alive to perform it should they become infected, thus ensuring, theoretically, the continuity of the business.

While Tamiflu is currently our best defense, until we get a functional vaccine in place, ready to deploy, it is expensive, difficult to manufacture, under a patent held by one company, Roche Pharmaceuticals, and demand is far outstripping supply.

The final stressor on the limited supply is the suspected need of doubling the dosage over a longer period of time, a study spearheaded by WHO of this theory is currently getting under way.  So, anything that would effectively stretch the on hand stocks, both public and private would be a monumentally good thing, or you would think so anyway. 

Probenecid burst onto the Cyber Flu scene the end of October 2005 with Declan Butler's piece in Nature Wartime tactic doubles power of scarce bird-flu drug: Use of common drug could stretch world stocks of Tamiflu.

Doctors think they have hit on a way to effectively double supplies of a drug that fights bird flu. Administering Tamiflu alongside a second drug that stops it being excreted in urine means that only half doses of the treatment would be needed.

Tamiflu (oseltamivir phosphate) is the main antiflu medicine recommended by the World Health Organization (WHO). The WHO suggests that, in anticipation of a flu pandemic, countries should stockpile enough for at least a quarter of their population. But although Swiss drugmaker Roche, the sole supplier, has quadrupled its production capacity over the past two years, the current supply is thought to cover just 2% of the world population.

Last week, Joe Howton, medical director at the Adventist Medical Center in Portland, Oregon, suggested a way to double supplies, after browsing basic safety data from Roche for a talk on avian flu.

The technique was invented during the Second World War to extend precious penicillin supplies. Scientists found that a simple benzoic acid derivative called probenecid stops many drugs, including antibiotics, being removed from the blood by the kidneys. Probenecid is readily available and is still widely used alongside antibiotics to treat gonorrhoea and syphilis, and in emergency rooms, where doctors need their patients to have high, sustained levels of antibiotics in their blood.

. . . [And the article closes:]
Like many scientists, Fedson is stumped by the apparent lack of interest from Roche, and the relevant authorities. "It's stupefying," he says.

This information broke 17 months ago, beyond its repeated mention amongst the Flubies it gets no play or mention.  Several physicians who are active in Flublogia (the cyber pandemic flu community) have endorsed the idea of using Probenecid in combination with Tamiflu, although it would be an "off-label" usage.  Dr Grattan Woodson, perhaps one of the most well known Physician Flubies posted his comments about the concept at the original Fluwiki, the entire piece by him on Tamiflu found at the link is worth a read but I will just include the Probenecid portion here.

Using oseltamivir in combination with probenecid

While preparing a presentation on Bird Flu for his colleagues at Portland Adventist Medical Center in Oregon, Joe Howton, MD, Medical Director, Emergency Services at the hospital, ran across an obscure comment in the product information on the antiviral drug Tamiflu® used for treatment of influenza. The comment was in the section on safety and drug interactions and referred to the results of safety studies that were completed before the drug was approved for use. The finding was that when Tamiflu was given at the same time as another commonly used drug, probenecid which is used to treat gout, the blood level of Tamiflu doubled and the time it remained at effective levels in the body increased from about 8 hours to more than 20 hours.

This finding astounded Joe. He immediately realized its importance given our concerns about Bird Flu and the present severe shortage of Tamiflu. He understood that this means that if it were safe to give Tamiflu in combination with probenecid, it would increase the clinical effects of each Tamiflu tablet significantly and this would starch the available supply.

When Joe called me about this to see what I thought, at first I was a bit skeptical. Why hadn’t someone else figured this out before now? Besides gout, probenecid has been indicated for increasing penicillin blood levels and the length of time it stays in the body for years. So, it was not much of a stretch to think of it for use with Tamiflu especially since we are facing such a shortfall of this drug. So, I spent the night and much of the next on the National Library of Medicine’s web site and reading my trusty Goodman and Gilman Pharmacology Text and sure enough, Joe was right. Tamiflu levels could be increased as can the length of time it stays in the body fighting the virus by combining it with probenecid. I had used probenecid for as long as I had practiced, over 25 years now, and regarded it as a reliable old standby in my pharmaceutical armamentarium. What made this discovery all the sweeter, it is generic and relatively inexpensive at a cost of about $20 for a 10-day treatment course.

During my investigations, I discovered that infectious disease doctors worldwide were already using probenecid to increase the levels of drugs used to fight tuberculosis and HIV-AIDS, but did not find any references to using it intentionally with Tamiflu for this purpose. The way probenecid increased the effects of these drugs, including Tamiflu, is exactly the same way it increases the level and effective blood levels of penicillin. This was very reassuring. I was not too concerned that the combination of probenecid with Tamiflu was not formally approved by the any regulatory agency like the US FDA since every day, as a doctor who takes care of people, I find myself using approved drugs for “off label” indications. This is a perfectly acceptable and established practice as long as the doctor has good reason to believe that it will be of benefit to his or her patient.

In my opinion this is an important finding. We all owe Dr. Howton a debt of gratitude. While this novel combination does not solve our Bird Flu problem by any stretch of the imagination, it does mean that suddenly the world has the equivalent of two-and-a-half times more Tamiflu in the world’s stockpile now than we thought. What’s more, the Tamiflu produced from this point forward will also go two-and-a-half times further than we originally thought. Of course, this all depends on our ability to ramp up probenecid manufacture, which I believe can be accomplished rather quickly and inexpensively. On the whole, this is one of the few pieces of really good news concerning the Bird Flu pandemic that I have heard since becoming concerned about it in 2004.

 

Since this information hit 17 months ago it is hard for me to understand why it hasn't been "officially" looked at, but more importantly, why it isn't being loudly trumpeted.  In fairness, perhaps it is being whispered about in the official circles that need the information but where does that leave the individual that is trying to prepare for themselves and their family?  It leaves them out in the cold unless they just happen to stumble upon the information.

 

As always, I am not recommending Probenecid to anyone, I am providing a simple summary of what information is available on a promising option.  What I have personally planned I did so only after researching the issues.  Nothing is risk free and that includes using Probenecid.  Should you decide that Probenecid holds potential benefit to your personal pandemic preparations I strongly suggest you research the issue on your own, weigh it against your individual needs and potential risk vs. benefit scale, as it does have potentially dangerous side effects.  A listing of advisements and cautions can be found here.

 

We, as average citizens, are not helpless, even in the face of something as difficult and horrific as a severe pandemic.  There are things that we can and should do for ourselves to strengthen our possibility of survival, ours and those we love and care about.  But in order to take those actions we need information, good information, or what I like to term Best Available Information.  This post is dedicated to the practice of that concept.

 

SZ

Statins and H5N1 Infection Mitigation

My husband takes prescription cholesterol lowering medication and when the news started circulating around the Cyber Flu Community back in the fall of 2005 I sat up and took note.  Statins are ubiquitous in the US since doctors seem to like to prescribe them at the first hint of cholesterol elevation.

As this piece from one of the Reveres at EffectMeasure states, the research is intriguing and logically indicates that statins may be beneficial should those taking them become infected.  Please be aware that it is presumed that you must be on them for at least (guess) a month prior to infection to see the positive (if any) effects, but the benefits may mean the difference between living and dying.

From EffectMeasure (old site) [They have since moved: New Site]

Thursday, September 29, 2005

Bird flu and statins 

In an extremely interesting article in the Clinicians Biosecurity Network Weekly Bulletin (issue of 9/27/05) Borio and Bartlett review a suggestion of David Fedson, an expert on vaccines (and former Director of Medical Affairs at Aventis Pasteur), that statins (tradenames Zocor or Lipitor) might be helpful in preventing serious complications of influenza, perhaps by dampening the cytokine response.

The statins are widely used and available drugs used to lower cholesterol. They also have anti-inflammatory activities, perhaps by preventing activation of the transcription factor NF-kappaB. One mechanism thought to underlie the virulence of the H5N1 virus is production of a "cytokine storm," an unregulated systemic inflammatory response that results in a rapidly developing generalized clotting disorder, hemorrhage, kidney failure and fluid-filled lungs. The phenomenon is similar to or the same as what is called gram-negative sepsis or septic shock, a serious complication of bacterial infections that claims 400,000 to 500,000 lives each year in the US and has 50% to 70% mortality. Treatment for sepsis is a high priority independently of any role for the same or similar mechanism in influenza.

The idea that statins might be helpful for sepsis or influenza is based on more than speculation about mechanism. In 2004 Almog et al. (Circulation, Aug 17 2004;110(7):880-885) reported that patients admitted to the hospital with acute bacterial infections and who were on statins for more than a month for other reasons had a dramatically reduced incidence of severe sepsis (19% versus 2.2%) and reduced admission to the Intensive Care Unit (12.2% vs. 3.7%). An interesting point is that patients on statins might be expected to be at greater risk because they are taking a medication for a pre-existing medical condition.

Another study (.pdf available free on line here) looked back at the experience of over 700 patients that were admitted to a hospital for pneumonia. About 100 of them were also taking statins. Using 30-day mortality as a measure of outcome, the statin group had about two thirds fewer deaths than the non-statin group (odds ratio .36, 95% confidence interval .14 - .92).

Borio and Bartlett also report on an article from The Netherlands by Enserink to appear shortly in Science (hence not available to me other than through their summary). Enserink examined influenza seasons between 1996 to 2003, and using a database of 60,000 primary care patients compared those with at least two statin prescriptions in the previous year to those without. There was a 26% lower risk of pneumonia in the statin group. Because of the imprecision of the measure of statin use, I would expect the statin effect to be even greater than reported here.

Borio and Bartlett conclude:

These studies suggest that statin therapy may ameliorate the course and/or prevent complications of influenza. In these studies, it appears that all of the people were already receiving statins when they got infected. Whether statins would be beneficial after the onset of symptoms is still unknown. However, further investigation is merited. This is particularly important given the likelihood that vaccines and antiviral agents will be in short supply during an influenza pandemic, and statins are widely available and may be produced relatively inexpensively.

This is extremely interesting work. It is too early to say that prophylactic statin use in a pandemic is a reasonable strategy, but it is worth considering.

There is also an OTC product, Red Yeast Rice (the base ingredient in many statins) that is cheap and easily obtained.

The entry on Red Yeast Rice from the Mayo Clinic's site:

[snip]

Red yeast rice is the product of yeast ( Monascus purpureus ) grown on rice, and is served as a dietary staple in some Asian countries. It contains several compounds collectively known as Monacolins, substances known to inhibit cholesterol synthesis. One of these, "Monacolin K" is a potent inhibitor of HMG-CoA reductase, and is also known as Mevinolin or Lovastatin (Mevacor®, a drug produced by Merck & Co., Inc).

Red yeast rice extract has been sold as a natural cholesterol-lowering agent in over the counter supplements, such as Cholestin ^TM (Pharmanex, Inc). However, there has been legal and industrial dispute as to whether red yeast rice is a drug or dietary supplement, involving this manufacturer, the U.S. Food and Drug Administration (FDA) and the pharmaceutical industry (particularly producers of HMG-CoA reductase inhibitor prescription drugs or "statins").

[snip]

Uses based on scientific evidence

High cholesterol

Since the 1970s, human studies have reported that red yeast lowers blood levels of total cholesterol, low-density lipoprotein/LDL ("bad cholesterol"), and triglyceride levels. Other products containing red yeast rice extract can still be purchased, mostly over the Internet. However, these products may not be standardized, and effects are not predictable. For lowering cholesterol, there is better evidence for using prescription drugs such as lovastatin.

[snip]

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older):

1,200 milligrams of concentrated red yeast powder capsules have been taken two times per day by mouth with food.

The average consumption of naturally occurring red yeast rice in Asia has been reported as 14-55 grams per day.

Children (younger than 18 years):

There is not enough scientific evidence to recommend red yeast for children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

There is one report of anaphylaxis (a severe allergic reaction) in a butcher who touched meat containing red yeast.

Side Effects and Warnings

There is limited evidence about the side effects of red yeast. Mild headache and abdominal discomfort can occur. Side effects may be similar to those for the prescription drug lovastatin (Mevacor®). Heartburn, gas, bloating, muscle pain or damage, dizziness, asthma, and kidney problems are possible. People with liver disease should not use red yeast products.

In theory, red yeast may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. A metabolite of Monascus called mycotoxin citrinin (CTN) in fermentation may be harmful.

While no one knows if Statins or Red Yeast Rice will have any beneficial effects on an infection of H5N1 I will be utilizing them as prophylactic countermeasures for my family, but most especially for my son who is smack in the middle of the most-at-risk age group for dying from it.  I am fully cognizant of the risks and downsides.  I have done my homework and read all of the available information (scant though it is) and made a conscious and informed decision that the potential benefits outweigh any of the potential risks.  Should you consider these as options for yourself I suggest you do the same.  Nothing in life is entirely risk free, and everything generally comes at some price, the key is knowing enough to make informed and intelligent decisions.

My plan of attack is to utilize the supplement Red Yeast Rice once a Pandemic Influenza strain manifests and switch to the prescription Statin once the virus is in my area.  As can be appreciated, I have a lot more of the OTC supplement than I have of the prescription medication.  Timing will be all important.  My thanks to Bannor at PlanForPandemic for the idea of best use of the resources.

SZ

Tweaking Tamiflu Dosage

Today it was announced that a new human trial of Tamiflu dosage was going to be conducted.  The participants in the test will be human victims of H5N1 as well as severe seasonal flu.

Doctors test double Tamiflu dose to cut H5N1 deaths

Wed Mar 28, 2007 1:52PM BST

HONG KONG (Reuters) - Doctors in Asia and the United States will give double doses of Tamiflu to patients suffering bird flu and severe seasonal human flu from May in a trial aimed at cutting high death rates from avian flu.

People infected with the H5N1 bird flu virus are now prescribed the standard dose of Tamiflu, which is one capsule twice daily for five days.

But less than half the patients survive.

"In animal studies, higher doses of Tamiflu have resulted in higher cure rates for H5N1. The death rate from H5N1 is 60 percent, we want to see if we can solve this problem," said Tawee Chotpitayasunondh, senior medical officer at Thailand's Ministry of Public Health.

The Cyber Flu Community has been discussing the Tamiflu dosage regimen since the middle of 2005 when information on a mouse study came to our attention.  The published findings of this study may be found here, and a more "user friendly explanation of the study's findings may be found here, from the National Institute of Allergy and Infectious Diseases.

While we are not privy to treatment protocols, I do wonder if there are primary treatment doctors in areas experiencing human H5N1 infection that have already "tweaked" the Tamiflu dosage and that may be why we are seeing a reduction in CFR (Case Fatality Ratio).  Helen Branswell did an excellent piece on the recent meeting in Turkey of over 100 physicians with experience treating human H5N1 infections.

Doctors who have treated bird flu cases meet to share treatment info

HELEN BRANSWELL

Doctors who have treated H5N1 avian flu patients are meeting in a Turkish seaside town to try to find answers to the myriad mysteries that remain about what the brutal virus does to its human victims and how dismal survival rates might be improved.

The World Health Organization hopes that by pooling patient data, the meeting will answer critical questions such as whether all lineages of the H5N1 virus cause the same severity of disease and how best to treat pregnant women who become infected.

Based on what it learns at this meeting, the WHO will update H5N1 treatment guidelines, so that doctors who face cases in the future can benefit from the successes - and missteps - of those who have treated patients in the past.

"There's a real deficit there," says Dr. Frederick Hayden, a WHO influenza expert and a key organizer of the meeting.

"We don't have basic information at hand to try to give the best advice. We're going to address that gap."

The meeting will also seek buy-in from doctors for a new patient data collection system the WHO hopes to get up and running.

Doctors treating H5N1 patients - past, present and future - would be asked to submit a couple of pages of standardized clinical and treatment information so that the global health body can track patterns of disease and treatment efficacy on an ongoing basis.

"This will give us, I think, the best available opportunity under the current circumstances to make sense out of what's happening," Hayden said.

The 100 or so doctors and other experts are meeting in Antalya, in southern Turkey. The meeting, which is being held Monday through Wednesday, is being hosted by the Turkish government.

It is a follow-up to a conference that was held in Hanoi in May 2005. At that point three countries - Thailand, Vietnam and Cambodia - had reported human cases of H5N1; there were 89 confirmed cases and 52 deaths.

Since then nine more countries - Azerbaijan, Iraq, Indonesia, Laos, Egypt, Nigeria, Djibouti, Turkey and China - have reported human cases. As of Sunday, the WHO had confirmed 279 cases since November 2003; 169 of those people died.

In the intervening months, small collections of case data have been published in medical journals. An account of the treatment of eight patients in Turkey. A paper describing a similar number in Indonesia. A report that revealed how patients responded - or didn't - to treatment with the antiviral drug oseltamivir (Tamiflu) in southern Vietnam.

But in the main, the details of the symptoms and disease progression of the vast majority of H5N1 patients, the steps their doctors took to try to save them and the outcome of those treatment choices remain locked up in the files of doctors who cared for them.

"There is a huge number of unanswered questions about human infections with highly pathogenic H5N1 viruses," says Dr. Tim Uyeki, an influenza expert from the U.S. Centers for Disease Control in Atlanta, who is attending the meeting.

"I think it's so important to share information so others can benefit from the experiences of those who have dealt with this."

Pooling data should allow patterns to come into focus in a way that is impossible when two or three doctors are looking at a handful of cases.

The meeting is taking place behind closed doors to encourage doctors who may be working on scientific articles to share their findings before publication. Hayden says he's been told some large, unpublished sets of patient data will be presented in Antalya.

This bit is continually railed against in the Cyber Flu Community.  Instead of the free exchange of information that can be used to save people's lives it is being hoarded all in the name of being able to publish a paper.  Selfish and ego driven concerns outweigh the potential life saving addition to the general knowledge base.

"They'll tell us what's been done and what's happened. That may allow one to say: 'This does not work and we shouldn't be doing this.' That's sometimes just as important as saying: 'This does work,"' Hayden notes.

In addition to learning about past cases, gathering together the physicians who have treated H5N1 cases in 12 countries should enhance research collaborations - including planned clinical trials of intravenous forms of two antiviral drugs - zanamivir (sold as Relenza) and peramivir, a drug still in development.

(GlaxoSmithKline, which makes Relenza, has shelved plans to test an intravenous form of the drug in the United States, but is in discussions with a WHO-organized treatment network in Southeast Asia to test the new formulation there.)

Dr. Menno de Jong believes opportunities for additional research are inevitable when some many clinicians from so many countries are brought together.

"If we can make a list - What are the questions of highest priority and what needs to be done to answers those questions? - I think that already will be a big gain for a meeting like this," says de Jong, a virologist at the Tropical Medicine Hospital in Ho Chi Minh City, Vietnam, where some of the first H5N1 patients were treated.

Still, some mysteries won't be solved until more autopsies are done on H5N1 cases, de Jong insists.

It's believed there have only been about a handful of autopsies on people who succumbed to the assault of this vicious virus. To date cases have occurred in countries where, for cultural or religious reasons, autopsies are not done.

De Jong says pleas for more autopsies are made at every scientific meeting on H5N1, but they haven't produced results. He suggests a way around the autopsy barrier would be to encourage hospitals treating H5N1 cases to do post-mortem biopsies - using special biopsy needles to take bits of key organs for study.

Since the Cyber Flu Community has been aware of higher dose Tamiflu treatment for almost two years now, and many plan to utilize the increased dosage levels, why is it only now that the experts are getting their heads together and planning to put this protocol to the test?

It is widely believed that an H5N1 infection treated with Tamiflu runs the risk of creating Tamiflu resistant strain(s), and we have already seen a few instances of this.  If the current recommendations of 2 capsules a day for 5 days is inadequate to kill the virus, but only to blunt it, the danger of resistance is magnitudes greater.  This doesn't address the issue of life saving dosage, a separate issue, and one of no less importance. 

As Tamiflu is in such limited supply it would be much more efficacious if the supplies we did have were used to the maximum benefit, even though that means treating 2/3 fewer.  Whether that is for treatment of the ill or as a prophylactic for HCWs and other Essential Service persons can be argued separately, but if it is used as treatment we owe it to all those that will not receive any, to use what we have to gain the best possible outcome.  Of course, that means reducing our "courses of treatment" stockpile by two-thirds, assuming 32 capsules vs 10 for an effective course.

But this points out how far ahead of the curve the knowledgeable and dedicated Flubies are.... we had this information twenty-one months ago.  It also points out how important information is, if we have it, we can act upon it, if not, it could have dire consequences.

H5N1 and Prophylactic Elderberry

First things first:

I am not a doctor, nor affiliated in anyway with the medical profession.  I am not recommending that anyone do what I have planned for myself and my family should a moderate to severe pandemic come to pass.  I am simply sharing what I, as a layman, have reasonably deduced to be prudent and *hopefully* effective to some measure.

I will be posting various and sundry items of potential medical mitigation strategies that any average person can stock and utilize.  These are items that I have decided on after two years of watching, reading, researching, and analyzing.  Many of the items I have decided on were thoroughly "vetted" on the various flu forums, most specifically and thoroughly on CurEvents.com's Flu Clinic.  A lot of work and untold hours were put in by Flubies far more knowledgeable and medically astute than myself.  After reading their finding and weighing them against my own understanding I made my decisions.  I did not blindly accept anyone's recommendations, even if I knew the person to be knowledgeable and trustworthy, I did independent follow-on research and *studied* the issues.  I ask that if you are interested in non-pharmaceutical influenza interventions you do the exact same thing.  Our lives, and the lives of our loved ones are worth the effort.

 

Second things second:

This entry deals with Black Elderberry, Sambucus Nigra, and its use in regard to treatment of H5N1 is not without controversy.  The controversy swirls around Elderberry's increase of cytokines as part of its effectiveness in treating influenza, this entry deals with the prophylactic usage of Elderberry extract, and although the increase in cytokines is still an issue should infection occur, it is not as great an issue, in my layman's estimation, and therefor the benefits, again in my estimation, outweigh the (potential) risks.

Should you decide that you are interested in utilizing elderberry extract I stridently encourage you to do your own research into the pros and cons as they are too extensive and randomly flung around the Cyber Flu Community for me to address in this entry.

 

My personal plan for my family, and more importantly, for my son who is a patrol officer for a small city police department and will be at high risk for infection, is to take Elderberry extract prophylactically in hopes of preventing infection with H5N1 should the pandemic manifest. Secondarily, should infection occur, Elderberry may slow viral replication down at the beginning of the disease to (hopefully) prevent the cytokine storm so often mentioned with H5N1 human infection.  Since my son is in his mid-twenties he is smack in the middle of the cohort most at risk for the deadly immune response.

I have been using Elderberry extract as a preventive for the last two flu seasons, as has my husband.  We have both found it to be very effective at preventing seasonal flu, now whether that will translate as effectively to H5N1 is anyone's guess at this time.  My hope is that at minimum it will not hurt, and at best, it may help, and may help a great deal.

 

Here is a major piece I used for making my decision on Elderberry as a prophylactic during a pandemic influenza outbreak. 

 

J Int Med Res 2004;32(2):132-140

Randomized Study of the Efficacy and Safety of Oral Elderberry Extract in the Treatment of Influenza A and B Virus Infections

Z Zakay-Rones¹, E Thom², T Wollan³, J Wadstein^4
1Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel; ²Parexel Norway AS, PO Box 210, N-2001 Lillestrøm, Norway; ³Jernbanealléen 30, N-3210 Sandefjord, Norway; ⁴Østra Rønneholmsv 6B, 21147 Malmö, Sweden

 

Elderberry has been used in folk medicine for centuries to treat influenza, colds and sinusitis, and has been reported to have antiviral activity against influenza and herpes simplex. We investigated the efficacy and safety of oral elderberry syrup for treating influenza A and B infections. Sixty patients (aged 18 – 54 years) suffering from influenza-like symptoms for 48 h or less were enrolled in this randomized, double-blind, placebo-controlled study during the influenza season of 1999 – 2000 in Norway. Patients received 15 ml of elderberry or placebo syrup four times a day for 5 days, and recorded their symptoms using a visual analogue scale. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. Elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza. These findings need to be confirmed in a larger study.

KEY WORDS: BLACK ELDERBERRY; SAMBUCOL®; INFLUENZA A AND B; CLINICAL EFFICACY; TOLERABILITY; CONTROLLED STUDY

The black elder (Sambucus nigra L.) has been used in folk medicine for centuries to treat influenza, colds and sinusitis.³ Antiviral activity of three plants, including the elder, has been reported against influenza and herpes.⁴ The berries of black elder contain high levels of flavonoids,⁵ which are naturally occurring plant substances. Several plant extracts containing flavonoids or purified flavonoids have been shown to have antiviral activity against herpes simplex virus type 1, respiratory syncytial virus, and the parainfluenza and influenza viruses.^{6 – 9} The main flavonoids found in elderberries are the anthocyanins cyanidin 3-glucoside and cyanidin 3-sambubioside.^10,11 It has recently been shown that these substances are detectable in plasma after oral intake of elderberry extract.¹²

Elderberry extracts are commercially available as nutritional supplements for humans, and are used extensively in many countries. Standardized elderberry extract has been shown to reduce haemagglutination and inhibit replication of influenza A and B viruses in vitro,¹³ and be effective in treating influenza B/Panama.¹³ The prophylactic and symptom-dependent treatment of influenza-like symptoms using a commercial elderberry extract was also demonstrated in a colony of chimpanzees in the Jerusalem Zoo, Israel.¹⁴

We aimed to investigate the efficacy and tolerability of a standardized elderberry extract for treating influenza A and B infections in humans.

[snip]

Discussion

The efficacy of elderberry syrup has previously been investigated in a placebo-controlled, double-blind clinical study during an outbreak of influenza B/Panama.¹³ A complete cure was achieved within 2 – 3 days in nearly 90% of the elderberry-treated group compared with at least 6 days in the placebo group (P < 0.001). The results of our study show that elderberry syrup is also effective against influenza A virus infections. Both studies show that the duration of the illness can be reduced by 3 – 4 days with elderberry syrup compared with placebo. The prophylactic and curative effects of this syrup have been demonstrated in a study performed in a chimpanzee colony,¹⁴ in which the appearance of symptoms was reduced by two-thirds. To our knowledge, no placebo-controlled, double-blind studies have been done with other natural remedies against the influenza viruses.

The main flavonoids present in elderberries are the anthocyanins cyanidin 3-glucoside and cyanidin 3-sambubioside,^10,11 and are detectable in plasma after oral intake of elderberry extract.¹² A possible mechanism of action of elderberry extract in the treatment of influenza is that the flavonoids stimulate the immune system by enhancing production of cytokines by monocytes.¹⁸ In addition, elderberry has been shown to inhibit the haemagglutination of the influenza virus and thus prevent the adhesion of the virus to the cell receptors.¹³ Anthocyanins also have an anti-inflammatory effect comparable to that of acetylsalicylic acid;¹⁹ this could explain the pronounced effect on aches, pain and fever seen in the group treated with elderberry syrup.

Vaccination is effective for prophylaxis and in reducing the impact of influenza, but only about 60% of people aged 65 years and above, and less than 30% of people aged less than 65 years, are vaccinated annually (worldwide figures). Some elderly individuals and immunocompromised people do not respond optimally to the vaccine, and the vaccine may not always include the strain of virus circulating within a given community.¹

It is not known whether amantadine and rimantadine prevent the complications of type A influenza infections among people at high risk. Use of these drugs is limited due to their side-effects and the frequent incidence (approximately 30%) of drug resistance. No data are available to determine the efficacy of rimantadine among children, so it is currently approved for prophylaxis but not treatment of influenza in children.

Zanamivir has been shown to reduce the duration of influenza A and B infections by 1 – 2.5 days. The route of administration is by inhalation via a Diskhaler^® (GlaxoSmithKline, Middlesex, UK) and the drug is designed for patients aged 12 years and above.^20,21 Oseltamivir may reduce the duration of illness by 1.5 days.²²

In contrast to these antiviral drugs, elderberries can be administered to the whole population, including infants and children. It should, however, be stressed that a wide number of elderberry preparations are available on the market, in the form of both syrups and capsules. The extract tested in this study was standardized with respect to the content of flavonoids and was produced in accordance with good manufacturing practice. A number of the other preparations available lack or have a very low flavonoid content. We believe that adequate amounts, as well as the composition, of flavonoids present in the extract are essential for the therapeutic effect of elderberry syrup as reported in our study.

In view of its in vitro and in vivo efficacy on influenza A and B viruses, elderberry extract offers an efficient, safe and cost-effective supplement to the present armamentarium of medications for the prophylaxis and treatment of influenza. It should be stressed that our study involved only adult influenza patients who were otherwise healthy, and did not include any high-risk patients. Further studies are required to confirm these results in larger numbers of patients and to investigate the effect of elderberry syrup in other patient groups.

Acknowledgement

The study was sponsored by Razei Bar, Jerusalem, Israel.

• Received for publication 12 September 2003 • Accepted subject to revision 23 September 2003

• Revised accepted 3 November 2003

A Homemade Mask that May Actually Work

This is one of my favorite do-it-yourself pandemic mitigation items.  Should a moderate to severe pandemic occur I plan on making up as many of these as I can and handing them out to Police and EMS in Son's area.  I also plan on printing up the plans and passing them out as well.  This is so simple that anyone can make up one or three and the beauty of them is that they can be washed and reused.  While not as good as a NIOSH approved N95 mask, it will be better than nothing and nothing is about what the Police and EMS crews will have about a week or two into a PanFlu, after all on-hand stock is depleted.

Please visit the link to see the photo in a larger format, the blog is limits the size of photos that will display, unfortunately, it is too small to fully appreciate, but it is large enough to show the concept and its wonderful simplicity.

I ask everyone to realize and remember, we are not helpless in the face of a pandemic, even a severe one.  There are things we can do for ourselves, and should be prepared to do for ourselves, because it doesn't look like anyone will be doing them for us.

http://www.cdc.gov/ncidod/EID/vol12no06/05-1468.htm
Simple Respiratory Mask
Virginia M. Dato,* David Hostler,* and Michael E. Hahn*
*University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Suggested citation for this article
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To the Editor: The US Department of Labor recommends air-purifying respirators (e.g., N95, N99, or N100) as part of a comprehensive respiratory protection program for workers directly involved with avian influenza–infected birds or patients (1). N95 respirators have 2 advantages over simple cloth or surgical masks; they are >95% efficient at filtering 0.3-μm particles (smaller than the 5-μm size of large droplets—created during talking, coughing, and sneezing—which usually transmit influenza) and are fit tested to ensure that infectious droplets and particles do not leak around the mask (2–4). Even if N95 filtration is unnecessary for avian influenza, N95 fit offers advantages over a loose-fitting surgical mask by eliminating leakage around the mask.

The World Health Organization recommends protective equipment including masks (if they not available, a cloth to cover the mouth is recommended) for persons who must handle dead or ill chickens in regions affected by H5N1 (5). Quality commercial masks are not always accessible., but anecdotal evidence has showed that handmade masks of cotton gauze were protective in military barracks and in healthcare workers during the Manchurian epidemic (6,7). A simple, locally made, washable mask may be a solution if commercial masks are not available. We describe the test results of 1 handmade, reusable, cotton mask.

Figure. Prototype mask. A) Side view. B) Face side. This mask consisted of 1 outer layer (37 cm × 72 cm) rolled and cut as in panel B ...

For material, we choose heavyweight T-shirts similar to the 2-ply battle dress uniform T-shirts used for protective masks against ricin and saxitoxin in mouse experiments (. Designs and T-shirts were initially screened with a short version of a qualitative Bitrex fit test (9) (Allegro Industries, Garden Grove, CA, USA). The best were tested by using a standard quantitative fit test, the Portacount Plus Respirator Fit Tester with N95-Companion (TSI, Shoreview, MN, USA) (10). Poor results from the initial quantitative fit testing on early prototypes resulted in the addition of 4 layers of material to the simplest mask design. This mask is referred to as the prototype mask (Figure).

A Hanes Heavyweight 100% preshrunk cotton T-shirt (made in Honduras) (http://www.hanesprintables.com/Globals/Faq.aspx) was boiled for 10 minutes and air-dried to maximize shrinkage and sterilize the material in a manner available in developing countries. A scissor, marker, and ruler were used to cut out 1 outer layer (≈37 × 72 cm) and 8 inner layers (<18 cm2). The mask was assembled and fitted as shown in the Figure.

A fit factor is the number generated during quantitative fit testing by simulating workplace activities (a series of exercises, each 1 minute in duration). The Portacount Plus Respirator Fit Tester with N95-Companion used for the test is an ambient aerosol instrument that measures aerosol concentration outside and inside the prototype mask. The challenge agent used is the ambient microscopic dust and other aerosols that are present in the air.

A commercially available N95 respirator requires a fit factor of 100 to be considered adequate in the workplace. The prototype mask achieved a fit factor of 67 for 1 author with a Los Alamos National Laboratory (LANL) panel face size of 4, a common size. Although insufficient for the workplace, this mask offered substantial protection from the challenge aerosol and showed good fit with minimal leakage. The other 2 authors with LANL panel face size 10, the largest size, achieved fit factors of 13 and 17 by making the prototype mask inner layers slightly larger (22 cm2).

We do not advocate use of this respirator in place of a properly fitted commercial respirator. Although subjectively we did not find the work of breathing required with the prototype mask to be different from that required with a standard N95 filtering facepiece, persons with respiratory compromise of any type should not use this mask. While testers wore the mask for an hour without difficulty, we cannot comment on its utility during strenuous work or adverse environmental conditions.

We showed that a hand-fashioned mask can provide a good fit and a measurable level of protection from a challenge aerosol. Problems remain. When made by naive users, this mask may be less effective because of variations in material, assembly, facial structure, cultural practices, and handling. No easy, definitive, and affordable test can demonstrate effectiveness before each use. Wearers may find the mask uncomfortable.

We encourage innovation to improve respiratory protection options. Future studies must be conducted to determine levels of protection achieved when naive users, following instructions, produce a similar mask from identical or similar raw materials. Research is needed to determine the minimal level of protection needed when resources are not available for N95 air-purifying respirators since the pandemic threat from H5N1 and other possible influenza strains will exist for the foreseeable future.