More Avian Flu Updates

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Avian Flu Updates—10/14/05

 

This update is provided to help provide context for interpreting the recent increase in news coverage on the H5N1 Avian Influenza currently endemic in Southeast Asia.

 

1. Viral traits

There appear to be two ‘clades’ of highly pathogenic avian influenza virus H5N1 with slightly different behaviors:

A. Qinghai Lake strain, from China. This strain carries genetic markers suggestive that it should be sensitive to Amantidine, Rimantidine, Tamiflu, and Relenza. This strain and its descendents are the ones found in the migrating birds heading toward Europe. This clade in laboratory testing is more lethal in mammals than the other, but has not yet been confirmed to have infected a human.

B. Thailand/Vietnam strains. These strains are resistant to Amantidine and Rimantidine, and appear to be limited to non-migrating birds in Vietnam, Thailand, and Cambodia. By inference they are also in Laos and very likely in southern China, where it has long been the illegal practice to feed Amantidine to poultry at sub-therapeutic levels in the mistaken belief this will protect poultry from flu. This clade is responsible for the known human infections in those countries.

C. One source reports that the strain in Indonesia is more closely related to the Qinghai strain than the Vietnamese ones, but I have not found confirmatory information on this. Notably Indonesia is not using Amantidine or Rimantidine to treat its human cases.

 

2. Geography

A. HPAI H5N1 has been found IN BIRDS in the following countries: China, Thailand, Vietnam, Cambodia, Indonesia, Mongolia, Romania, Turkey.

B. Suspicious die-offs of birds that are not yet confirmed as H5N1: Iran (3000+ ducks), Bulgaria (#?), Serbia (80 ‘poultry’), Greece (#? chickens), Italy (30? chickens)

C. Illegal trade in potentially infected poultry continues; a truckload of 2 day old ducklings was seized and destroyed leaving an infected province in Vietnam 2 days ago.

D. HPAI H5N1 IN HUMANS has been confirmed in the following countries: Thailand, Vietnam, Cambodia, Indonesia. Of these, only Indonesia continues to report new human cases in the past month.

E. HPAI H5N1 in humans is suspected in: China—in June, rebel newspaper Boxun reported human cases near Qinghai Lake, military suppression of an uprising there, and razed villages. None confirmed. By geography, Myanmar is also likely to have had human cases. Turkey currently has 9 asymptomatic people in quarantine who were exposed to infected birds.

 

3. Conflicting estimates of possible deaths.

There have been 3 flu pandemics in the past century—the H1N1 flu in 1918, the H2N1 flu in 1957 and the H3N2 flu in 1968. Of these, the 1918 flu was the most lethal at 2 – 5% of the general population.

A. The ‘low’ end of 7 million people worldwide is derived by applying the death rate for the 1968 flu to modern populations. This number is preferred by WHO spokesman Thompson

B. The ‘high’ end of 180 million people worldwide is derived by applying the death rate for the 1918 flu to modern populations. This number is preferred by the UN flu czar, Nabarro.

C. Neither of these estimates uses the current estimated death rate for H5N1 based on known cases. The current death rate for H5N1 in humans is around 52%. This number may be over-estimated because mild cases not resulting in death may not be seeking medical care and thus are not counted in the denominator. However if this death rate were to hold true, with a typical pandemic spread to 30% of the population, the result would be approximately 1 billion deaths. (1 in 6 people). While unlikely, this figure cannot be ruled out.

D. Regardless of death rate (for which only medical research has influence), the past pandemics have resulted in significant workplace absenteeism ranging from 30-60% (the latter in some regions in 1918) in affected regions. Effects of absenteeism must be managed.

 

4. Reporting issues/lack of “transparency”

A. The avian flu outbreak in Thailand was part of a change from growth of 8% for its agricultural sector in 2003 to a recession of 4 % in that sector in 2004. Peasant farmers rely upon their flocks for personal food production as well as for sale. Other birds such as fighting cocks, and in Indonesia, caged songbirds, have values greater than $1000US. Some birds in Indonesia enjoy the same status as household pets as cats and dogs do in the US. Government agencies in the affected regions lack the resources to compensate the owners of these birds at fair market value for their flocks. All of these reasons contribute to an economic and emotional disincentive for individuals and countries to report potential H5N1 in birds.

B. The CDC has likewise been non-transparent in reporting the flu sequences that it has obtained, citing issues of ‘intellectual property’ for those sequences which were given to them by private companies. CDC’s failure to share has contributed to resistance of foreign nations to share sequences, which are critical to vaccine development.

C. The SARS outbreak in Toronto is estimated to have cost that city more than $1.5 billion dollars in lost revenue from business and tourism. For these reasons, no nation wishes to be identified to be the first to have human-human transmissible H5N1, as this could result in quarantine or export embargos that would cut into trade and tourism.

D. Many governments seem to fear that transparency on this issue, in the event of an outbreak, could cause panic or lawlessness.

 

5. Errors in case identification

There are several issues of in the determination of what constitutes and ‘official’ case of H5N1 which may be resulting in an under-reporting of cases out of Indonesia:

A. WHO guidelines require two separate titers of rising H5N1 antibodies to confirm infection. In some cases, samples have not been gathered at appropriate times to make this determination, and so the case remains ‘unconfirmed’ although clinically appearing to be H5N1 and with H5N1 antibodies detected without proof of rising titer.

B. Because viral load is variable through the course of illness, failure to detect actual virus cannot rule out presence of H5N1, although detection of the virus certainly rules it in.

C. Influenza Rapid Tests of nasal swabs are accurate in detecting the presence of an influenza virus in cases of H5N1 only 40% of the time. Throat swabs have marginally better detection. This has delayed diagnoses as ‘flu’ at some early screenings.. The rapid test can detect presence of types A or B flu, but not subtype (H5N1, H3N2, etc.)

D. There is a Dengue outbreak in Indonesia at this time; early symptoms of flu and Dengue are similar and misdiagnosis is possible, especially in light of the rapid-test false-negatives. There is also a human flu outbreak; even Indonesia’s President Susilo has flu this week.

E. Patients reporting to the hospital with symptoms consistent with influenza are assessed for exposure to poultry. Those without poultry exposure are excluded from further testing for H5N1. This sampling error fundamentally prevents the early detection of any cases of human-to-human transmission.

 

6. Threat assessment issues

A. The WHO has asserted that for H5N1 to become dangerous to humans—for it to acquire the ability to transmit easily between humans—that it must re-assort with an existing human-capable flu virus. Given the simultaneous outbreak of human and avian flu in Indonesia, it may have that opportunity. However, this week's publication of the analysis of reconstituted H1N1 from 1918 shows that this virus, like H5N1, was of completely avian origin (although some argue that there was a porcine component) and did not reassort with a human virus prior to becoming a pandemic strain. This discovery invalidates the WHO’s assessments of strains thus far, which has relied on evidence of re-assortment as the criteria for danger to humans.

B. The clinical behavior of the virus in Indonesia, wherein 60 suspect cases were traced to an outbreak in birds in a Jakarta zoo, suggests that the virus has changed in a way that facilitates bird to human transmission.

C. In Vietnam, in a group of 10 patients with known poultry exposures, exposure to onset of symptoms averaged 3 days, range 2 to 4. In Indonesia, some cases where family members became ill in sequence at roughly 4 day intervals have been interpreted as a common source exposure with incubation up to 17 days—unusually long for a flu.

 

7. Medical defenses

A. Vaccines—Media reports of a stockpile of 2 million doses of vaccine assume a 15 micrograms protein requirement per dose. The human safety trial of this vaccine showed that the required dose to generate adequate immune response is 90 to 120 micrograms. Studies to see whether an adjuvant can reduce this requirement are beginning in Europe. Otherwise, this reduces the effective vaccine availability by a factor of 6 to 9. Because this vaccine is not an exact match to whatever pandemic strain emerges, it is likely to yield only partial protection—perhaps reducing death rate without preventing illness.

B. A single researcher in a single study generated a strain of H5N1 resistant to Tamiflu. Partial resistance was observed to develop in one Vietnamese patient receiving Tamiflu treatment. Reports of H5N1 resistance to Tamiflu are overstated.

C. Amantidine and Rimantidine may be effective against some strains.

D. Ordinary flu shots will not protect you from H5N1 but may reduce the chance of it re-assorting with a human virus.

E. Handwashing or alcohol hand cleaners and general hygiene remain important in infection control.

__________________

 

And another update:

 

Bird flu's tendency to mistakes makes it dangerous

14 Oct 2005 21:27:44 GMT

 

Source: Reuters

 

http://www.alertnet.org/thenews/newsdesk/N14521929.htm

 

 

 

Oct 14 (Reuters) - A feared strain of avian influenza known as H5N1 has spread to birds in Turkey and is likely to continue moving, experts say.

 

The World Health Organization believes it is only a matter of time before the virus develops the ability to pass easily from human to human, possibly causing a catastrophic pandemic.

 

It is the virus's tendency to make mistakes when replicating itself that makes it so dangerous and unpredictable. Here are some facts about H5N1 avian influenza:

 

-- The H5N1 strain first emerged in Hong Kong in 1997, causing the death or destruction of 1.5 million birds and sickening 18 people, killing six.

 

-- It re-emerged in 2003 in South Korea, and has now spread to China, Vietnam, Thailand, possibly Laos, Indonesia, Turkey and perhaps Romania. Japan, Malaysia and South Korea are considered free of H5N1 avian flu after having outbreaks. H5N1 has also been seen in wild birds in Mongolia, Kazakhstan and Russia's Siberia.

 

-- The outbreaks have led to the death or destruction of an estimated 150 million birds.

 

-- H5N1 has infected 117 people in four countries and killed 60, according to the World Health Organization. Experts say more people may have been infected but were not ill enough to seek medical attention, so it is not known what the fatality rate is.

 

-- Avian flu exists almost everywhere. There are 15 subtypes of influenza virus known to infect birds, but the so-called highly pathogenic forms tend to be caused by influenza A viruses of subtypes H5 and H7.

 

-- Influenza type A viruses are named according to two proteins they carry call hemagglutinin (H) and neuraminidase (N). There are 16 possible "H" variations and nine "N."

 

-- Influenza viruses are RNA viruses, meaning they lack mechanisms for proofreading and repairing genetic errors. This makes them especially prone to mutation. This is why there is a new strain of seasonal flu almost every year and why the annual vaccine must be reformulated every year.

 

-- Some years this means the flu is not especially deadly but it usually kills 250,000 people at a minimum globally, in an average season. About every 20 years or so the virus changes enough to cause a pandemic that infects and kills many more people than usual.

 

-- Three pandemics occurred in the 20th century -- the 1918 pandemic that killed anywhere between 20 million and 100 million people globally, the 1957 "Spanish influenza" which killed an estimated 2 million people globally and the 1968 "swine flu" which killed 1 million. Experts agree another pandemic could occur at any time.

 

-- The seasonal flu vaccine provides no protection against H5N1 avian flu. There is an experimental H5N1 avian flu vaccine but there are only a few thousand doses and it is unlikely to provide perfect protection.

 

-- H5N1 mutates rapidly and is beginning to show some of the changes that made the 1918 H1N1 flu pandemic so deadly.

 

-- Four drugs work against influenza. But two older drugs, amantadine and rimantadine, already have minimal activity against H5N1. Two newer drugs work better. Tamiflu, known generically as oseltamivir, was invented by Gilead Sciences and is made and marketed by Swiss drug giant Roche Holdings . Relenza, known generically as zanamivir, was developed by Australia's Biota Holdings and is marketed by GlaxoSmithKline .

 

Relenza is a powder given via the nose and is considered less desirable than a pill like Tamiflu.

 

-- Just as bacteria develop resistance to antibiotics, viruses develop resistance to antivirals and H5N1 has become resistant to amantadine. It has also begun to show signs of mutating into a form resistant to Tamiflu.

 

-- Tamiflu and Relenza, in a class known as neuraminidase inhibitors, do not cure influenza infection but can reduce the severity of illness if given within 48 hours after symptoms begin. They may also help prevent infection if given early.

 

-- WHO has urged countries to develop preparedness plans, but only around 40 have done so. WHO predicts that most developing countries will have no access to vaccines or antiviral drugs throughout the duration of a pandemic, and experts say developed nations will not have enough to cope well.

 

 

AlertNet news is provided by Reuters

[gardnmom]

There are ongoing discussions here.

http://effectmeasure.blogspot.com/2005/09/...-for-hills.html

Revere is several Drs who which to be unnamed.

Site was obtained from Geri Guidetti of the Ark Institute.