Influenza Pandemic 'Could Be Avoided'

A global influenza outbreak with the potential to kill millions could be stopped in its tracks with concerted action and enough antiviral drugs for three million people.

Britain would be "overwhelmed" if a deadly strain was allowed to reach its shores, said an author of one of two international studies published today in the journals Nature and Science.

The World Health Organisation has given warning that the current outbreak of bird flu in the Far East could seed a human pandemic.

However, for the first time it appears to be feasible to stop a pandemic, after the two computer models of an outbreak revealed that early antiviral treatment - the drug Tamiflu (oseltamivir phosphate) - is critical.

The H5N1 avian flu virus, found in birds throughout south-east Asia, has already infected a number of species, including domestic poultry, pigs and people. There is a danger that the virus might mutate or infect a human already infected with flu, and then mix with the human influenza virus.

"If we wait until it gets to the UK we have no chance of stopping it. We would be overwhelmed," said Prof Neil Ferguson, of Imperial College in London, the lead author of the Nature paper.

Prof Ferguson said if nothing was done, half the world could be infected within a year. But a stockpile of Tamiflu, along with a policy of closing schools and workplaces, could have more than a 90 per cent chance of stopping a pandemic virus.

The Science study, led by Prof Ira Longini of Emory University, Atlanta, revealed that giving a prototype low-efficacy vaccine to half the population before the start would greatly enhance containment.

Dr Elizabeth Halloran, co-author, said: "Early intervention could at least slow the pandemic."

This PREDATES the recombination with Ebola SZ-277!!!

Commentary
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In Vivo Data and Tamiflu Pandemic Containment Myth

Recombinomics Commentary
July 18, 2005

Of 80 mice infected with H5N1 virus, 20 received a placebo, 30 were given oseltamivir at one of three dosage levels for five days, and 30 received the drug at one of three dosage levels for eight days. None of the mice receiving a placebo survived. Only five of 10 mice given the highest daily dose of oseltamivir for five days survived. Although oseltamivir suppressed the virus in the mice, the virus continued to grow if the drug was stopped after five days.

Mice given the drug for eight days fared better. Survivors included one of 10 mice given the lowest daily dose, six of 10 given the middle-range daily dose, and eight of 10 given the highest daily dose. The eight-day dose of oseltamivir allowed more time for virus levels to fall and less chance for avian flu to rebound after the drug was stopped.

The above description of the in vivo test of oseltamivir (Tamiflu) is consistent with prior in vitro studies which strongly suggest that use of Tamiflu at the recommended dosage will produce little benefit. Many countries have stockpiled Tamiflu and more have placed orders. However, the amount of Tamiflu ordered was based on the assumption that a course of 10 pills would be effective for 10 days of prevention or 5 days of treatment. However, this assumption was not supported by in vitro data and now is also not supported by in vivo data.

Tamflu targets the NA gene product neuraminidase. Influenza A codes for nine NA serotypes and Tamiflu had been previously tested against all nine, using two representative viruses for each. Although Tamiflu could inhibit spread of the virus, it was far more effective against N2 (as in human H3N2) than N1 (as in human H1N1 or avian H5N1). All of the human H5N1 isolates since 2004 have had a 20 amino acid deletion in N. Recent studies using the more recent isolates which have the deletion again showed that Tamiflu worked, but was even less effective than N1 without the deletion.

The latest in vivo results again show that Tamiflu works against H5N1 but when used at the recommended dose (2 pills a day for 5 days). Its benefit was marginal (50% of the treated mice died). However, in the latest test the Tamiflu was not administer after symptoms appeared, which in humans is 2-4 after infection), but instead was initially administered 4 hours before infection. Since 50% of the mice died when treated for 5 days, beginning before infection, treatments that begun after symptoms would probably produce little, if any benefit, even in the absence of Tamiflu resistance

The resposnse was dose dependent and suggests improvement may be obtained if a higher dose is used or if treatment is for a longer period of time, but the FDA approved treatment regime would probably not be effective.

These marginal results under ideal experimental conditions do not suggest Tamiflu would be effective under pandemic conditions if used at the recommended dose for the recommended time. Indeed, Tamiflu was used on tigers exposed to H5N1 at the Sri Rahka zoo in Thailand last year. Control of the outbreak with culling and aggressive Tamiflu use failed to save many, if any, of the exposed tigers, which may have been limited to the 147 that died or were euthanized.

The H5N1 isolate, A/Vietnam/1203/2004, used in the mouse experiments is a more aggressive version of the 2004 isolates and it is neurotropic, causing hind leg paralysis in infect ferrets. It has the G1906A polymorphism that produces the E627K change in the PB2 protein, which was also found in most of the tiger isolates as well as all isolates from Qinghai Lake. Thus, it might be useful to determine the effects of Tamiflu treatment on the ability of the H5N1 to reach the brain of infected mice if they survive the bird flu infections.

Clearly more work is required to determine the effective dose of Tamiflu. The boxun reports indicate that there are at least 10 distinct strains of H5N1 in China, and 8 can infect humans. Therefore information the effect of Tamiflu on a range of H5N1 variants might be useful.

However, at this time it seems that usefulness of Tamiflu at FDA recommended doses remains questionable for control of an H5N1 flu pandemic.

The leading edge of this expanding range is currently at the Urals, heading west. Some reports have it already on the West side of the Urals.

Qinghai Lake is the site of China's original nuclear weapons production, as well as a gulag, and one of the world's largest bird sanctuaries. Do a FR search on Qinghai and read the article I posted last night.

As for Tamiflu, it appears that the pure H5N1 strain that is in or near Europe is Amantidine and Rimantidine sensitive - for now. But the Qinghai Lake strains crossed with Ebola are NOT.

Here's why:

Ebola Recombinant Linked to Mystery Illness in Sichuan China?

Recombinomics Commentary
July 30, 2005

D: "It's alright. We ran tests on those samples and isolated the SZ77++A3231 virus."

I: "What is this SZ77++A3231 virus?"

D: "This is a strain of the Ebola virus."

I: "Would you like to comment about it?"

D: "It's rather impossible to totally explain it."

I: "I can understand so, but why is the term "less-infectious" always affixed to our version of the Ebola virus?"

D: "There are 2 reasons for doing so. First, to reduce panic among the people should it ever leak. And second, the Ebola virus has evolved in China. Re-combination has been detected. Most prominently at the portion which determines its effect on humans (very technical description, I can't describe it. sorry.). Also, abrupt breaks in the sequencing were detected, leading to changes in the incubation period. (Or possibly "changes in the incubation period were detected")

I: "How were these viruses classified then? / Could you elaborate more about the various strains?"

D: "Previously, strains of Ebola in China always had the EBO prefix. Subsequently following information leaks, the classification method was changed. We stopped using the EBO prefix. Instead, coupled with the discovery that the virus had become more virulent and lethal, we re-named the strains according to the placed where they were first discovered. For example, the strain in June became the SZ77++A3231. Sometimes, we don't even use their place of discovery, instead directly naming it the ++A3231."

I: "In that way, the Ebola virus wouldn't even be brought into the picture."

D: "Precisely, viruses such as the Ebola are national secrets."

The above comments by a physician involved in testng samples from patients in the mysterious swine outbreak in Sichuan indicate that one of the agents isolated is a recombinant Ebola virus originally isolated from Shenzen. Prior reports had listed the names and characteristics of various Ebola isolates and EB-SZ-277 was capable of infecting birds. SZ277++A3231 is a recombinant version of SZ-277 isolated from a patient. The discussion indicates China has an active Ebola project and the virus is rapidly evolving via recombination. It was not clear from earlier reports if the agent was isolated and sequenced, but this interview leaves little doubt that both isolation and sequencing of Ebola is quite active. It is unclear if the recombination is related to the region of identity between Ebola and H5N1. Ebola is considered a state secret, so there are no reports of the virus or availability of virus or sequences.

The interview also indicates that the streptococcus suis is not the cause of the illness. It is present in pigs and is merely activated by infectious agents, which include Ebola, plague, and an un-named virus which is considered "dangerous". The emphasis is on the bacteria because it can produce similar symptoms. The symptoms of the patients match pandemic flu of 1918, and H5N1 can produce such symptoms.

The interview, if accurate, would support the role of agents other than the bacteria, in the spread or progression of the illness. Streptococcus Suis does not produce the high case fatality rate, and can be treated with antibiotics, as can plague. The high case fatality rate also supports the involvement of a virus. The proximity to Qinghai Lake keeps H5N1bird flu and migratory birds on the short list of explanations for the rapid spread of the fatal disease that is resistant to antibiotic treatment.

Note that this form of Ebola is capable of INFECTING BIRDS. Additional vectors are blow flies and reports also show mosquitos as carrying the disease.

It doesn't look like it. Even the first step of stockpiling antivirural drugs isn't occurring. I think the US has 3 million doses or treatments (I don't remember which).

But even if it's treatments, that's hopelessly inadequate to protect a population of nearly 300 million.

And just consider how much more vulnerable today's society is to a highly-contagious fatal virus than we were in 1918. Back then, travel between cities was fairly limited. Many people were self-sufficient on their own land. Today, most people make multiple stops to the grocery store every week, the roads and airports are crowded and the population density is far higher.

We're certainly not more immune to viruses today. The only thing protecting us is luck. Hope it holds.

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