Pandemic Flu!

Turtle · November 22, 2006

Jay made a comment in an earlier post about the people in the 1300's not having any idea where the plague might have come from, and Turtle said in the previous post that disease could be spread intentionally.

Seems in ages gone by it was common practice to load infested corpses and festering carcasses in catapults, to be hurled over a besieged city's walls! :) The idea behind this was to spread disease in the city...

Biological warfare is clearly not a new thing...

Roger that! Europeans gave North and South American indigenous people smallpox both accidently and on purpose. What I found unique in Cedars post is that it isn't like the organized groups that have done it intentionally, or like a terrorist act in the way we talk of it, but rather a random bad mood. More or less I think I mean to say no one is planning for that. Perhaps the more people become isolated, sick, and hungry, the more they tend to intentionally spread plague in random acts of digruntletude. :eek:

That said, some viruses can go airborn and others not so the poison apple may or may not work depending on which virus is involved. For all the genetic science and whatnot, the best defense is to wash everything you eat and wash your hands frequently. (Unless your PO'ed, then not.:) )

Michaelangelica · November 22, 2006

Just to cheer you all up?

The "cure"(?) could kill you

FDA Scrutinizes Deaths Of Japanese Kids Taking Tamiflu
NBC 4 ^ | 11/17/06 | online

Posted on 11/17/2005 11:08:59 PM PST by BurbankKarl

Federal health advisers are looking into the deaths of 12 Japanese children who took Tamiflu, part of their annual safety review of the anti-flu medication and seven other drugs.

http://www.freerepublic.com/focus/f-news/1524365/posts

Roche, estimates it has been given to about 20,000,000 people world-wide, although post-market surveillance is not well-developed. Roche claims that only one of every 10,000 patients has had one or more adverse reactions. During one review period, about 1000 of the 4000 adverse events were considered "serious." Most of the reports come from Japan.
My interpretation: adverse reactions are very uncommon, but when they occur may be more serious than with other drugs.

. . .
They cite its use during pregnancy in 61 cases, among which there were 10 reports of abortion"
. . .

Bottom line: this is a medicine, not a candy. Do not use without good reason

Do you like the understated "although post-market surveillance is not well-developed.Everone has a stake in seeing that this vaccine looks like it works.

http://www.pkblogs.com/effectmeasure/2005/03/tamiflu-storage-and-adverse-reactions.html

Interesting site

http://www.abc.net.au/science/expert/realexpert/birdflu/03.htm

Q:-Has Tamiflu gone through clinical trials for its efficacy on humans? Will it offer protection from bird flu?
A: Yes, it has been extensively tested in humans but only for seasonal influenza. We hope it has a high rate of efficacy for the H5N1 bird flu virus. In mice it requires a higher dose and longer treatment for bird flu than for seasonal flu. It also needs to be taken within six to 12 hours of catching the virus.

The current H5N1 strain prevalent without mutation is sensitive to both Tamiflu and Relenza. The question is will the mutated pandemic human flu be sensitive? We don't know that yet. In some cases overseas we have seen resistance of H5N1 to Tamiflu

The first documented case of human infection with the avian influenza A (H5N1) virus occurred in Hong Kong in 1997.1 As of July 26, 2006, a total of 232 H5N1 virus infections in humans had been documented, with a mortality rate of 58% among hospitalized patients

http://content.nejm.org/cgi/content/full/355/21/2179?query=TOC

gribbon · March 2, 2007

I also read about the black death the other day, man that plauge was crazy! A bacterial infection (from the bactirium Yersinia pestis) that was spread via flees! back in the 1300's they never would of had a clue where it was coming from, some blamed the jews and a lot where burnt at the stake, while others called it retribution from god....25 million died in the first 5 years as it swept across europe, and it hung around for almost 300 years!

Us Europeans know...which is why the sensible ones amongst us are far less concerned about Nuclear arms proliferation and far more concerned about Avian flu drugs proliferation. Anyone who actually fetches out a pen and paper and calculates how many people nuclear arms can kill and how many people disease pandemics can kill will soon realise where I (and a number of other people) are coming from.

Thus far, Bird flu hasn’t been entirely predictable and there have been a number of blunders by the WHO and regulatory authorities which seem quite intimidating. We seem to be mixing up all the places where all the treatments are needed, and in parallel, not making enough progress on determining which drugs we will use.

The fourth wave of outbreaks in 2006 involved chickens and encompassed 2 distinct areas, these being Phichit Province, (identified on July 23, 2006), and Nakhon Phanom Province, (July 28, 2006). All 8 gene segments of the 2 viruses isolated from Phichit and single virus isolated from Nakhon Phanom were then submitted to labs, where genome scrutiny illustrated that all samples had undergone minor mutations, and furthermore, this outbreak was connected with the strains of virus disseminated in Thailand during 2004 and 2005. Phylogenetic analysis also showed that the viruses isolated from Phichit belonged to genotype Z, and also that The phylogenetic tree of this sample proved that the hemagglutinin was similar to the cluster of samples isolated during 2004/2005 in Thailand and Vietnam, whereas virus isolated from Nakhon Phanom was clustered into the same group with viruses isolated from southeast People’s Republic of China, and belonged to genotype V, which differs from genotype Z in the PA gene. Other differences found included how the N-link glycosylation sites of the Pichit isolates were NST residues, whereas in the Nakhon Phanom isolate, NNT residues were observed. (I think the receptor-binding sites of HA were unchanged, though.)

In the neuraminidase gene, (the gene needed to make the neuraminidase protein which Influenza always needs) the new isolates contain 20 amino acid deletions within the stalk region, and were quite virulent but sensitive to treatment with interferon and tumour necrosis factor-α , and these isolates contain Glu627 of PB2, indistinguishable from the previous samples from Thailand and Indonesia, which could indicate that the new isolates were not so capable of replicating in mammalian hosts, which is quite good news. Drug resistance or sensitivity relies on sequences of M2 and NA. Substitution within residues including L26I, V27A/I, A30S, and S31N of the M2 ion channel protein was used to predict amantadine-resistant mutants, and H274Y of the NA was used to predict for oseltamivir resistance. The virus observed in 2006 isolates from Phichit was resistant to amantadine (not good news) but sensitive to oseltamivir, whereas the isolate from Nakhon Phanom was sensitive to amantadine and oseltamivir, which implies that infected patients received different antiviral drugs, showing us that we do need to keep track of its progression through Asia.

This finding is creditable of concern as the WHO had believed that most influenza (H5N1) viruses had 2 separate phylogenetic clades: Clade 1 viruses in Cambodia, Thailand, and Vietnam were responsible for human infections in those countries during 2004 and 2005, and Clade 2 viruses that in China and Indonesia spread westward to the Middle East, Europe, and Africa. The way in which the virus mutates when spread in this way should have been taken into account when developing a vaccine...

This map shows its spread throughout the Easter Hemisphere…it astonishes me that it hasn’t progressed further, but it’s powerful enough nevertheless…

http://upload.wikimedia.org/wikipedia/commons/9/99/Avian_influenza_spread_map.jpg

Another thing which concerns me is how little progress seems to be being made on finding and distributing mass produced vaccines. We should be looking at alternatives to Tamiflu, as the manufacturing problems that come with this cure are too great. Due to its likeness zanamivir, oseltamivir is a neuraminidase inhibitor, which forms a transition-state inhibitor of influenza neuraminidase, preventing new viruses (which requires the enzyme neuraminidase to bind to cells) from emerging from infected cells. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed. Amantadine (also called Symmetrel) and Rimantadine (also called Flumadine) which are better, but they have to be used in conjunction with each other because one is designed to cure influenza A infection, but not influenza B. Apart from this, they are both excellent. I used to know someone working in the Chinese Pharmaceutical industry, and the price figures I heard from him claimed that they are both significantly cheaper than Zanamivir or Tamiflu.We really do need to make sure they don’t become invalid due to mutations, and keep a proper track of were we administer treatments, but otherwise we can rely on these drugs fine.

The problem with Tamiflu is that it needs shikimic acid, which is extracted from star anise, and 30kg of star anise only produces 1kg of shikimic acid. There are ten steps, (taking a total of 6-8 months to complete) required in the synthesis of Tamiflu, and there are many fiddly parts to it, including one stage where explosive azide must be handled. The authorities should either pick the other two alternative drugs, or subsidise the institutions that are researching into new ways to extract this drug. The best idea I know of that can mass produce this drug is using a strain of E.Coli bacteria which you over feed with Glucose and so produce shikimic acid as waste.

Acrylate and Butadiene, (petrochemicals which I think are pretty cheap), along with an enzyme derived from the amino acid proline, can synthesise the Tamiflu drugs’ active ingredient, and this is a lot less fiddly, as all but one stage can be done at room temperature.

In conclusion:

.Time to keep track of the spreading od the virus and adminitration of treatments.

.Time to use Amantadine and Rimantadine.

.Time to use alternative methods for extracting Tamiflu.

:naughty:

Michaelangelica · March 3, 2007

gribbon,

How many weeks does Tamiflu give us, after the outbreak of a pandemic, before we need another anti-viral?

Should we be stocking up on star anise?

gribbon · March 5, 2007

gribbon,

How many weeks does Tamiflu give us, after the outbreak of a pandemic, before we need another anti-viral?

Should we be stocking up on star anise?

Your asking about how long it will take for the virus to mutate and develop a resistance to Tamiflu, right? Okay…I don't know anything about that, but here's an an anwser to your second question:

The reasons against Tamiflu:

Two people, despite being treated within the first 24 hours of incubation dies despite being given Tamiflu in Vietnam, and it is also my understanding that subsequent analysis’ in Vietnam found evidence the H5N1 avian influenza virus can quickly mutate into a form that resists the effects of the frontline drug. Not exactly a susrprise, but dissappointing nevertheless.

Although many people do wish to stock-pile this drug, Canada's chief public health officer, Dr. David Butler-Jones, advises against stockpiling the drug for personal use when it becomes available, and furthermore, the latest studies on Tamiflu show it won't be a magic bullet for treatment, and probably works better at preventing infection.

There are mainly four approved drugs used to treat or prevent influenza – amantadine, oseltamivir, rimantadine and zanamivir. Rimantadine and amantadine are effective only against type A influenza. Zanamivir and oseltamivir inhibit both influenza A and B viruses.

Adamantane Derivatives (Amantadine and Rimantadine)

These two will crush influenza A viruses, but not do anything against influenza B viruses, as they work by inhibiting the activity of the influenza virus M2 protein, (not found on Influenza :crying: which forms a channel in the virus membrane, disabling the virus from entering its target cell.

Side Effects

As far as I know, both these drugs are relatively safe, and have side effects that go away after they have been used. However, there are some more serious things being reported than just CNS side effects like anxiety, insomnia, and difficulty in concentrating, lightheadedness and nervousness. Anorexia, marked behavioral changes, delirium, hallucinations, seizures and Nausea has been seen in a small percentage of cases, and more often this is what comes with amantadine than with rimantadine. This could be due to the fact that rimantadine has been marketed for a shorter period, and thus has not been evaluated and tested as many times. As for the overdose danger ratings, they are pretty high. I don’t know about dependency ratings, but these are not painkillers, so I can’t imagine they’ll be too addictive.

Neuraminidase Inhibitors (Oseltamivir/Zanamivir)

How they work:

These work by blocking the neuraminidase glycoproteins that dot the surface of Influenza viruses. The enzyme Neuraminidase is needed for the viruses to break free from an infected cell after replication, setting free new viruses that can infect other cells and spread infection. Zanamivir (commonly known as Relenza) is administered via an inhaler, whereas Tamiflu is taken as a tablet The evolutionary path the virus seems to be taking is very much against Tamiflu (Oseltamivir), but Zanamivir seems to be going okay. Although the Adamantane and Rimantadine derivatives do seem to become outpaced by the virus more quickly, for the parts of Asia such as Nakhom and Indonesia, (plus Thailand) they will be much better. (It is also the breed of Virus being found in these two parts which has spread all over Africa and the Middle East). They are easier to acquire and are much cheaper.

Side Effects

As far as I know there have been very few cases of adverse CNS effects reported for the neuraminidase inhibitor drugs, but Nausea and vomiting have been observed in patients after Oseltamivir had been administered to them. A pretty low price to pay for having your life saved if you ask me, but still, Tamiflu doesn’t compare to Zanamivir, which has no side effects apart form irritation caused by inhalation. If you’re gonna use a Neuraminidase inhibitor, make it Zanamivir.

Although Tamiflu has many advantages, it is just far too slow to extract, too expensive, and although most experts have recommended it, the Virus, in Vietnam and in Nakhom province China, has already developed resistance. In Phichit province, the virus is resistant to Amantadine, but as I said earlier this is a problem with who gets treated with what, not the actual drug. Being as the outbreak in Nakhom involved viruses with a similar genetic make-up to those we see in Thailand, it is only a matter of time before Thailand has a Tamiflu resistant virus as well.

Michaelangelica · March 6, 2007

I also read about the black death the other day, man that plauge was crazy! A bacterial infection (from the bactirium Yersinia pestis) that was spread via flees! back in the 1300's they never would of had a clue where it was coming from, some blamed the jews and a lot where burnt at the stake, while others called it retribution from god.

25 million died in the first 5 years as it swept across europe, and it hung around for almost 300 years!

It is still around and still deadly.

From memory 1 in 4 who get it die.

About 100 Americans (USA) die from it every year.

(Check WHO site)

The connection with the rat & fleas was made by doctors in the Colony of New South Wales (What we know as most of Eastern Australia) in 1900.

It surprised me that it took so long to figure out-700+ years. There is no plague in Australia now.

The interesting thing is that the plague has left varying degrees of genetic "immunity" to the HIV virus in most European Countries. The further you go north the greater the resistance to HIV. The further you go south less resistance, till you get no resistance in Africa.

It may be our most recent evolutionary-"natural selection" genetic change in HS (?) Strange is it not?

Michaelangelica · March 21, 2007

10 million doses of flu shot to be wasted - Cold & Flu - MSNBC.com

Who makes the money from fear?

10 million doses of flu shot to be thrown away
Annual expiration date ensures up-to-date vaccine, but at a huge cost
Image: Ira Katz
John Amis / AP file
Updated: 10:48 p.m. ET March 20, 2007

Millions of doses of flu vaccine will expire at midnight June 30, unsold during this year’s mild flu season and written off as trash. Still perfectly good, and possibly useful for a few more years, the vaccine will wind up being destroyed.

This annual ritual is supposed to ensure that Americans get the most up-to-date vaccine, but the leftovers — more than 10 million of a record 110 million produced — will be destroyed before a new supply is guaranteed.

Buffy · March 21, 2007

Who makes the money from fear?

Are you suggesting that we want to always bet *against* a pandemic just because this year was a light year for flu? The drug companies are *not* for this, they actually have no incentive either way no matter what the policy is. If you think they'd like to always have to get paid to create new vaccines, sure, but the fact of the matter is no one will buy last year's vaccine anyway because its the wrong formula for this years most populous flu strains.

I think you're missing the important point of this story which is that a combination of government regulation and care provider practice forces the shots to be thrown away *even if there is demand* AND *even if there's money to be made*. The policy *ensures* that there are 3-5 months out of the year when *you cannot get a shot no matter what*. That's stupid.

Its good this is getting publicized, and hopefully something will happen.

Get your shot, its good for everyone,

Buffy

Zythryn · March 21, 2007

It is human nature. Preperation for a disaster that does not happen is always seen as a waste.

It is a shame this is so. However it seems to be deeply ingrained in human psyche.

Buffy · March 21, 2007

Just to reiterate because its a really important point:

I think you're missing the important point of this story which is that a combination of government regulation and care provider practice forces the shots to be thrown away *even if there is demand* AND *even if there's money to be made*. The policy *ensures* that there are 3-5 months out of the year when *you cannot get a shot no matter what*. That's stupid.

That's not a "waste", that's a crime!

No condoms allowed between June and September,

Buffy

Michaelangelica · March 25, 2007

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