Indonesia - Pandemic 'dry run' is cause for concern [Nature]

[Theresa42]

Anybody have access?:

http://www.nature.com/news/2006/060529/full/441554a.html

[HenryN]

Re: Pandemic 'dry run' is cause for concern [Nature]

US edition not available yet. Can't access Asian edition which has

Pandemic 'dry run' is cause for concern
Indonesian bird-flu cluster rings alarm bells.
31 May 2006

[HenryN]

Re: Pandemic 'dry run' is cause for concern [Nature]

Nature 441, 554-555 (1 June 2006) | doi:10.1038/441554a; Published online 31 May 2006
Pandemic 'dry run' is cause for concern
Declan Butler
Top of page
Abstract
Indonesian bird-flu cluster rings alarm bells.
A cluster of avian flu cases in Indonesia last month is being seen by many experts as a dry run for the handling of an emerging pandemic virus. But although the World Health Organization (WHO) says that all went well, some critics allege that the response to the virus ? thought to have been moving between humans ? shows how ill-prepared the international community and affected nations still are.
"Any chance of containment was absolutely hopeless," says Andrew Jeremijenko, who until March was head of influenza surveillance at the US Naval Medical Research Unit 2 in Jakarta. "If this was a test to see whether Indonesia could contain a virus, then they just failed miserably."
If this was a test to see whether Indonesia could contain a virus, they failed miserably.
The difficulties encountered also raise questions as to the practicality of a plan to try to stop an emerging pandemic in its tracks by rapid intervention. Modelling studies predict that if a pandemic virus emerges, the WHO would have at most three weeks to help the affected country to quarantine all carriers and treat those infected with antivirals (N. M. Ferguson et al. Nature 436, 614?615; 2005).
The first case in the cluster fell ill on 24 April and died on 4 May. Samples were not taken, however, and alarm bells only rang when her relatives started going to hospitals in the days that followed. In total, eight members of an extended family in the village of Kubu Sembelang in north Sumatra became infected with H5N1. Six more of them have since died.
Jeremijenko says the response was slow and disorganized. The first WHO official and a team of local officials didn't reach the village until 12 May. Other international experts did not reach the village until the following week, at least in one case because of difficulties getting an invitation from Indonesia's ministry of health, according to Jeremijenko. Villagers also refused to cooperate with the team initially. Several of the H5N1 patients fled hospitals, returning coughing to the community.
Spreading the news
The WHO made the outbreak public on 18May. Health officials ? and stock markets ? worldwide trembled five days later when the WHO budged from its previous standard line that "the most plausible source" of the cluster was infected poultry, and acknowledged for the first time since the emergence of H5N1 that an extended chain of human transmission was the most likely explanation.
Steven Bjorge, a WHO official in Jakarta, disputes the allegation of unnecessary delays and bungling, arguing that the WHO and the Indonesian government reacted promptly. "The team was in the field early, and the Indonesians are doing a good job," he says. The abscondments from hospital were "an unusual experience", he adds.

AP PHOTO/BINSAR BAKKARA
Johannes Ginting is thought to have caught bird flu from a relative. Seven members of his family have died.
Concerns over the cluster itself have eased as no new cases have since been reported nearby, and the WHO says the virus's sequence shows "no evidence of significant mutations". The sequences have not been made public yet. The all-clear will not be given for another two weeks or so, however, and the pharmaceutical company Roche has been put on standby to send antiviral drugs to the region.
Teams on the ground are trying to monitor fresh cases. But thousands of Indonesians die every day from tuberculosis, dengue and other infectious diseases, and almost all go untested for H5N1. On 29 May, the WHO announced six more cases in other areas of Indonesia, two of which were also a family cluster.
"There have been a number of family clusters where only one person was tested," says Jeremijenko, adding that there is "only limited testing, in large cities such as Surabaya, Medan, Bandung and Jakarta. We know we are missing cases, especially in rural areas."
What caused the suspected human-to-human transmission at Kubu Sembelang is still a mystery. Nature has learned that the cases differed from past Indonesia cases, in that they had much higher viral loads in the throat and nose. Human-to-human transmission is more likely through droplets coughed from the nose and throat than from infections further down the respiratory tract.
Mutations in cases in Turkey earlier this year showed a substitution of glutamic acid with lycine at position 627 in the PB2 component of the polymerase gene. The mutation is thought to allow the virus to survive in the cooler nasal regions. This mutation has not been publicly reported in Indonesia previously, but Nature has learned that it occurred in at least one case in August 2005.
Another explanation is that the first case in last month's cluster had a particular genetic susceptibility to the virus, making her a 'superspreader'. But it is too soon and the data are too sparse to know for sure, says Bjorge.
Malik Peiris, a virologist at the University of Hong Kong who sequenced the virus, declined to comment on any mutations, saying that making sequences public is not his call. "Our job as a WHO reference lab is to report back to the originating country and the WHO," he says. The WHO also declined to give any details. "We will leave that to the government of Indonesia, the owner of the data," says Bjorge.
Related links
RELATED STORIES
Despite doubts, containment plans for pandemic take shape
Dreams of flu data
Disease surveillance needs a revolution
Alarms ring over bird flu mutations
Indonesia struggles to control bird flu outbreak
RELATED LINKS
Avian Flu mashup (requires Google Earth)
Avian flu web focus
Bird Flu in focus
EXTERNAL LINKS
Google Earth
WHO avian flu site
WHO updates on Indonesia
Indonesian ministry of health
Namru-2
Connotea web resources on avian flu

Dr Declan Butler, Senior reporter, Nature
Paris, France
Tel: (33) 1 43 36 59 90 or Skype: declan6016
d.butler@nature-france.com or d.butler@nature.com
* For science, read Nature?
* To see H5N1?s global spread in Google Earth visit my blog.
* Organize and share your references using the open-source social bookmarking service for science: Connotea.

[Theresa42]

Re: Pandemic 'dry run' is cause for concern [Nature]

Thanks, Dr. N.

[HenryN]

Re: Pandemic 'dry run' is cause for concern [Nature]

Commentray at

http://www.recombinomics.com/News/05...questered.html

[HenryN]

Re: Pandemic 'dry run' is cause for concern [Nature]

More commentary at

http://www.recombinomics.com/News/05310603/H5N1_Sumatra_E627K.html

[LMonty]

Re: Pandemic 'dry run' is cause for concern [Nature]

Nature has learned that the cases differed from past Indonesia cases, in that they had much higher viral loads in the throat and nose. Human-to-human transmission is more likely through droplets coughed from the nose and throat than from infections further down the respiratory tract.

This finding is ominous. Has anyone seen any further info on this?

[Theresa42]

More from Declan Butler [from his blog]

Declan Butler...another bf hero. Not to mention Andrew Jeremijenko..!

Breaking the silence: ?If this was a test to see whether Indonesia could contain a virus, they failed miserably?

Published May 31st, 2006 in avian influenza.

The latter quote is from a front-page article I?ve published in Nature tonight on what the experience of the large human cluster of avian flu cases in Indonesia says about the realities of attempting to slow the spread of, much less extinguishing at source, an emerging pandemic in the context of a developing country, with poor health infrastructure.

Plans by the World Health Organization (WHO) to try to slow or contain a pandemic show that to have any hope of success these would require rapid and decisive action within at most a three-week window from the emergence of a pandemic virus. But the handling of the cluster in Indonesia, as described in the article, is one of delays and confusion. Brief recap; this involved 8 members of an extended family in Kubu Sembelang, 7 of whom died, a patient fatality rate seen nowhere else.

WHO will no doubt argue that it reacted fast; it got samples on 10 May, results of viral testing on the 11th, and had one man, alongside local health teams, at the scene of the outbreak on the 12th. But that was already 19 days after the initial case fell ill, 16 days after she went to hospital, and more than a week after she died.

Meanwhile, villagers concerned that their animals would be killed became hostile to outsiders, resulting in international experts and local teams being subsequently barred from the village for a whole five days. Victims refused to take Tamiflu, fled the government hospital, while families refused protective gear when caring for their sick? the list of unanticipated confusion goes on.

The initial quote came from Andrew Jeremijenko, who until March was head of influenza surveillance at the US Naval Medical Research Unit 2 in Jakarta (NAMRU-2), and I?d like to thank him for having the courage to speak out in my article.

Andrew, who spent last weekend treating wounded at the scene of the Indonesian earthquake ? he was also involved in the tsunami response (see article here) ? explained his reasons to me in an email: ?I think it is our duty to point out that containment has serious limitations, and in an unusual event like this people need to be more aggressive then usual. Political deference though acceptable in some circumstances in others is not. I think this is important information to get out there.?

Working at NAMRU-2, Andrew witnessed the enormous gap between the official rhetoric and the reality on the ground. Take the recent declaration by Michael Leavitt, US Secretary of Health and Human Services? statement to the World Health Assembly: ?In closing, I ask this Assembly today to pledge with me to abide by four principles of pandemic preparedness:

* Transparency,
* Rapid reporting,
* Data sharing and,
* Scientific cooperation.

In reality of course, for many political and cultural reasons ? including those of the scientific community itself ? although some progress is being made, lip service is often paid to these on the ground, and that includes the US?s own CDC ? see Flu researchers slam US agency for hoarding data. The problem, as we pointed out over a year ago in Nature ? see ?On a wing and a prayer? ? is this:

?Each human case that occurs in Asia is potentially a global threat. The international virology community needs to be permanently there, on the ground. We need to diagnose cases swiftly, and treat the patients and all their contacts immediately with antiviral drugs to try to kill the pandemic at source.

To understand the genetics, and link this to the epidemiology and pathology of the virus, we need immediate sharing of all virus samples and data. None of this is happening adequately. National governments? performance is half-hearted, incomplete and far too slow. International organizations are working with their hands tied behind their backs, for bureaucratic and diplomatic reasons. In short, the level of current efforts is not commensurate with the threat we face.?

That remains the elephant in the room. The WHO, like FAO and OIE, answers to its member states ? not the other way round, as many seem to think ? and therefore it is almost taboo for its officials to criticize the actions of a member state, if they want to enjoy any cooperation on the ground. They deserve to have their hands strengthened, as noted in the recent Nature editorial, Dreams of flu data.

?Not before time, the WHO will have broader powers in 2007, when international health regulations, agreed by its members in May last year, come into force. These impose obligations on states to respond to any infectious disease of international concern. Cat-and-mouse games will no doubt continue, but the WHO will at least have a ?health policing? role, something that it currently lacks.?

But with the exception of a few reporters, notably Helen Branswell at Canadian Press, Maggie Fox at Reuters, and Nick Zamiska at the Wall Street Journal, many journalists simply regurgitate the parsimonious information from the PR departments of such agencies as if it were gospel.

The critical tone of my article tonight, should in no way be interpreted as disparaging of the valiant efforts of the many committed staff and doctors in Indonesia and within the WHO battling the problem on the ground. But we also must be aware, as journalists, and citizens, that politics complicated matters.

And last, let?s touch on the interesting question of sharing sequence data ? see again Dreams of flu data. The sequences of virus from the victims of the Indonesia cluster have not been made public. Why not? In the article, there is much buck passing among the three actors involved.

1.?Malik Peiris, a virologist, doing a great honest job at the University of Hong Kong who sequenced the virus, declined to comment on any mutations, saying that making sequences public is not his call. ?Our job as a WHO reference lab is to report back to the originating country and the WHO,? he says.?

2.?The WHO also declined to give any details. ?We will leave that to the government of Indonesia, the owner of the data,? says Bjorge.?

3. In an email received from the Indonesian government after my deadline, it states with respect to making data public: ?We are fully aware of the threat of the next influenza pandemic. And Indonesia is fully supporting whatever measures are considered necessary to prevent, control and contain a potential pandemic. ;?

So apparently, noone is opposed to depositing the sequences in Genbank immediately, but noone is taking the decision to do so. In the Nature editorial, ?Dreams of flu data? we argued: ?Genetic data are also lacking. When samples are sequenced, the results are usually either restricted by governments or kept private to an old-boy network of researchers linked to the WHO, the US Centers for Disease Control and Prevention, and the FAO. This is a far cry from the Human Genome Project, in which all the data were placed in the public domain 24 hours after sequencing. Many scientists and organizations are also hoarding sequence data, often for years, so they can be the first to publish in academic journals. With the world facing a possible pandemic, such practices are wholly unacceptable. Nature and its associated journals are not alone in supporting the rapid prior exposure of data when there are acute public-health necessities.?

Three cheers, then, to Ilaria Capua of the Tri-Veneto Region Experimental Animal Health Care Institute in Italy, who last month threw down the gauntlet to her colleagues by refusing to put her latest data on Nigeria and Italy in these private networks. Instead she uploaded them to GenBank and called on her colleagues worldwide to do likewise. Only in this way can researchers establish and track the global pattern of the evolution of the bird-flu virus.?

Is it perhaps time for the Human Genome Project?s ?Bermuda Agreement? on sequence deposition to be applied to all H5N1 sequences?

Below are a few excerpts from my article tonight.

?The WHO made the outbreak public on 18May. Health officials ? and stock markets ? worldwide trembled five days later when the WHO budged from its previous standard line that ?the most plausible source? of the cluster was infected poultry, and acknowledged for the first time since the emergence of H5N1 that an extended chain of human transmission was the most likely explanation.

Steven Bjorge, a WHO official in Jakarta, disputes the allegation of unnecessary delays and bungling, arguing that the WHO and the Indonesian government reacted promptly. ?The team was in the field early, and the Indonesians are doing a good job,? he says. The abscondments from hospital were ?an unusual experience?, he adds.?

And some discussion of possible explanations for the cluster:

?What caused the suspected human-to-human transmission at Kubu Sembelang is still a mystery. Nature has learned that the cases differed from past Indonesia cases, in that they had much higher viral loads in the throat and nose. Human-to-human transmission is more likely through droplets coughed from the nose and throat than from infections further down the respiratory tract.

Mutations in cases in Turkey earlier this year showed a substitution of glutamic acid with lycine at position 627 in the PB2 component of the polymerase gene. The mutation is thought to allow the virus to survive in the cooler nasal regions. This mutation has not been publicly reported in Indonesia previously, but Nature has learned that it occurred in at least one case in August 2005.?

http://declanbutler.info/blog/?p=41

[Shannon Bennett]

Re: Pandemic 'dry run' is cause for concern [Nature]

It is ominous however it also clearly indicates a method of treatment. If you can eliminate or substantially decrease the amount of virions in nose and throat, you might be able to lessen the chances of a cytokine storm. Possible treatments would include; fresh garlic juice, honey, thyme oil, and possibly tea tree or neem. All of which are viricides.

edited to add:
Fredness and I are waiting on some information from a specialist on what and how to apply alternative therapies. One of which is a method of spraying or flushing some of the above mentioned viricides through the nose and into the throat. We are making progress.

This finding is ominous. Has anyone seen any further info on this?

[Theresa42]

Re: Pandemic 'dry run' is cause for concern [Nature]

It is ominous however it also clearly indicates a method of treatment. If you can eliminate or substantially decrease the amount of virions in nose and throat, you might be able to lessen the chances of a cytokine storm. Possible treatments would include; fresh garlic juice, honey, thyme oil, and possibly tea tree or neem. All of which are viricides.

edited to add:
Fredness and I are waiting on some information from a specialist on what and how to apply alternative therapies. One of which is a method of spraying or flushing some of the above mentioned viricides through the nose and into the throat. We are making progress.

I luuuuuv garlic -- but I really hope I don't have to spray garlic juice up my nose! :p

[Snowy Owl]

Re: Pandemic 'dry run' is cause for concern [Nature]

Sannon, as I have said lately, we are working too on a nasal spray, we decided to take maple syrup instead of honey, and the Maple Sirup grade D, that is the last seva, darker, stronger and it needs more boiling because it has more bacterias.

The sugar we where looking for for this nasal spray was mannose to reinforce the cell membrane, then we add Melaleuca Alternifolia with less than 5 % of Cineole in it and more tesquerpenes for their antimicrobian activity and Glyco Thumoline for its alkanality apport.

Thymol is now the infgredients we evaluate.

[Shannon Bennett]

Re: Pandemic 'dry run' is cause for concern [Nature]

Snowy, I suspect thyme oil is going to come out a winner for you. The honey not only adds "sticking" power it also is a viricide. Not as much work done on its viricidal properties as I would have liked, but there are a few out there. I also thought it would overcome some of the more objectionable problems the other herbs would contribute. See Thereses post above for one of them. LOL If we can snort a product like Afrin (registered trademark) for our nose problems I think we can handle garlic and thyme. At least I didn't suggest capsaicin. (red pepper extract)

Yes, I wondered if the tea tree wasn't going to be an important ingredient. Thanks Snowy! You are a worth your weight in gold.

[LMonty]

Re: Pandemic 'dry run' is cause for concern [Nature]

a couple of thoughts- what about oil of oregano? and use a tea of scutellaria baicalensis or elder flower water as the base fluid, instead of plain water??

I'm thinking the baikal skulllcap has interesting possibilities becaue of the following article- if it inhibits the ability of the virus to sequester plasminogen, its not just antiviral as a contact, but like elder may prevent it from enetering the cells- so you have a dual approach with: the "contact antivirals" kills virions on contact, such as the essential oils mentioned, and the "inhibitors" that make it difficult for surviving virions to enter the cells to reproduce.

Biological properties of baicalein in cardiovascular system.

Huang Y, Tsang SY, Yao X, Chen ZY.

Department of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. yu-huang@cuhk.edu.hk

The dried roots of Scutellaria baicalensis (S. baicalensis) Georgi (common name: Huangqin in China) have been widely employed for many centuries in traditional Chinese herbal medicine as popular antibacterial and antiviral agents. They are effective against staphylococci, cholera, dysentery, pneumococci and influenza virus. Baicalein, one of the major flavonoids contained in the dried roots, possesses a multitude of pharmacological activities. The glycoside of baicalein, baicalin is a potent anti-inflammatory and anti-tumor agent. This review describes the biological properties of baicalein (Table 1), which are associated with the prevention and treatment of cardiovascular diseases. Baicalein is a potent free radical scavenger and xanthine oxidase inhibitor, thus improving endothelial function and conferring cardiovascular protective actions against oxidative stress-induced cell injury. Baicalein lowers blood pressure in renin-dependent hypertension and the in vivo hypotensive effect may be partly attributed to its inhibition of lipoxygenase, resulting in reduced biosynthesis and release of arachidonic acid-derived vasoconstrictor products. On the other hand, baicalein enhances vasoconstricting sensitivity to receptor-dependent agonists such as noradrenaline, phenylephrine, serotonin, U46619 and vasopressin in isolated rat arteries. The in vitro effect is likely caused by inhibition of an endothelial nitric oxide-dependent mechanism. The anti-thrombotic, anti-proliferative and anti-mitogenic effects of the roots of S. baicalensis and baicalein are also reported. Baicalein inhibits thrombin-induced production of plasminogen activator inhibitor-1, and interleukin-1beta- and tumor necrosis factor-alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. The pharmacological findings have highlighted the therapeutic potentials of using plant-derived baicalein and its analogs for the treatment of arteriosclerosis and hypertension.

Publication Types:
Review

PMID: 15853750 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum