Pandemic News/Awareness - Thread 3

Face up to socioeconomic toll of H5N1, experts urge

Although avian flu is not a human pandemic yet it is, however a pandemic in

birds and, it is already causing a hugh economic hit to communities in the

developing world.

Beating this disease will take money, lots of money, and an understanding of

how it impacts the way the local people live and raise animals for food.

http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/mar1808social.html

..."for every human being infected, there is at least 1 million animals infected--and that is probably an underestimate," Dr. Ilaria Capua, the head of virology at Italy's Istituto Zooprofilattico Sperimentale delle Venezie, said Tuesday morning. "The veterinary community . . . have never before faced a challenge this big."

Most of those animals are in the developing world, and the majority are owned by small farmers and households. So the basic outbreak-control measures of culling infected birds and closing live-bird markets pose immediate threats to the income and nutrition of individual families.

US Sets Up Strategic Flu Depot In Thailand

http://afludiary.blogspot.com/2008/03/us-sets-up-strategic-flu-depot-in.html

While the odds of actually stopping a pandemic outbreak anywhere in the world are slim, the attempt will still be made...

...the United States has created the first of three planned emergency influenza supply depots, this one located near the Bangkok (Suvarnabhumi) Airport.

The Duck-Rice Paddy Connection

http://afludiary.blogspot.com/2008/03/duck-rice-paddy-connection.html

Ducks, people and rice paddies - rather than chickens - are the major factors behind outbreaks of H5N1 highly pathogenic avian influenza in Thailand and Viet Nam, and are probably behind outbreak persistence in other countries of the region such as Cambodia and Lao PDR.

Vietnam

http://afludiary.blogspot.com/2008/03/vietnam-vaccine-concerns-and-suspicious.html

...birds known to have been vaccinated have died of bird flu, and so inspectors are investigating. Since vaccinations don't convey immediate immunity, it is possible the birds contracted the disease before the vaccine could take effect.

Meanwhile, doctors are testing samples from a 20-year-old man who died in a local hospital, suspected of bird flu.

Switzerland?

http://afludiary.blogspot.com/2008/03/switzerland-duck-tests-positive-for.html

Yes, Switzerland has bird flu, and not for the first time either. It isn't just in Asia

and Africa anymore.

Another duck...

With the permission of Effect Measure:

The Editors of Effect Measure are senior public health scientists and practitioners. Paul Revere was a member of the first local Board of Health in the United States (Boston, 1799). The Editors sign their posts "Revere" to recognize the public service of a professional forerunner better known for other things.

Dead ducks, live ducks and bird flu [updated]

Hard on the heels of my semi-facetious prediction that bird flu would return to Germany because Germany had declared itself bird flu free, the Swiss announced an infected wild duck on the shores of Lake Sempach. Since this duck didn't have a passport on him I am sure he never strayed over the nearby border with Germany. We don't know what kind of duck this was [see update, below], a question that is of surprising interest in light of a new paper.

Bird flu is avian influenza, i.e., an infection of birds by the influenza virus. The role of wild migratory birds versus human caused movement of poultry in the spread of bird flu is a hotly debated and controversial topic. If a bird is infected with highly pathogenic avian influenza virus, subtype H5N1, is it well enough to fly long distances? This is a potentially testable proposition, but there are a lot of different kinds of birds and it turns out even closely related bird species may act very differently. Wild waterbirds, such as ducks, have been prominently mentioned as a possible vector for bird flu spread but information about how severely they are debilitated by infection with H5N1 is confusing and sometimes contradictory. A team in The Netherlands recently undertook to infect six different common species of ducks to find some preliminary answers. They chose duck species that were abundant, favored freshwater habitats and had migration patterns spanning Asia, Europe and Africa.

Ducks are part of a large family of birds and come in two main varieties, diving ducks and dabbling ducks. Diving ducks forage for food underwater. They are good swimmers but not such good flyers, slower and heavier than the dabbling ducks. Dabblers feed on the surface or near surface or on land. The Dutch team infected 2 species of diving ducks (tufted and pochard) and 4 dabbling ducks (mallard, common teal, Eurasian wigeon and the gadwall) with highly pathogenic avian influenza virus (A/turkey/Turkey/1/2005 (H5N1)). The idea was to see which ducks would be infected, would excrete sufficient virus and be healthy enough to fly long distances. Here are the results:

By experimentally infecting wild ducks, we found that tufted ducks, Eurasian pochards, and mallards excreted significantly more virus than common teals, Eurasian wigeons, and gadwalls; yet only tufted ducks and, to a lesser degree, pochards became ill or died. These findings suggest that some wild duck species, particularly mallards, can potentially be long-distance vectors of highly pathogenic avian influenza virus (H5N1) and that others, particularly tufted ducks, are more likely to act as sentinels. (Keawcharoen et al., Emerging Infectious Diseases)

Even though low doses were used, all the species were readily infected. Both species of dabbling ducks (tufted and pochard) became clinically sick, while the dabbling ducks remained apparently well (NB: Redheads, a North American duck has been shown to be readily infected, not susceptible to illness and is a diving duck.) Ducks either excreted a lot of virus through their mouth or not. The high excreters were tufted ducks, pochards and mallards, although even within a species there was considerable variation in excretion. Not all ducks shed virus to the same degree. Cloacal ("rectal") excretion was low, suggesting that the common practice of sampling wild birds for virus with cloacal swabs might not be efficient. This also contrasts with low pathogenicity avian flu viruses which are mainly shed through the intestines. Chickens and other poultry have multisystem failure associated with active viral infection of the lining of the blood vessels and heart. This apparently doesn't occur in ducks.

The mallard and possibly some pochard are thus the birds most likely to spread the virus over distance, while the pochard and tufted duck are more likely to be found dead, sentinels of local infection. This means that active surveillance of live birds, as the Swiss were doing at Lake Sempach, should concentrate on mallards, while passive surveillance, analyzing dead birds, should look for tufted ducks and pochards. In either case, the virus should be looked for in pharyngeal swabs and "internal organs such as brain, trachea, lung, pancreas, kindey , and spleen."

The mallard emerges from this as a potential vector to be reckoned with. It is estimated that in Western Eurasia there are some 9 million mallard ducks flying around. Time, perhaps, to check their cargo manifests.

Update, 0830 EDST: We learn via CIDRAP News that the duck was a European pochard. This is consistent with the findings of the Dutch paper, although the diving pochards did become ill to varying degrees. This duck was alive and said to be asymptomatic when virus was obtained (it would be interesting to know the nature of the specimen) and any necropsy findings if they are available. The pochard sheds H5N1 through its pharynx (nose and throat) in good quantity so the discovery of this infected animal has to be of concern.

I read this with some sadness as I look out my window at the lake below, and see

our mallards visiting us for the winter from the north. These same three visit here

every year, my neighbor tells me. They are very fond of the bird seed that falls

under the feeders that she puts out for the land birds. I imagine that they

will be winging their way north soon, and I wonder where their final destination lies.

The Demise of Random Mutations

Recombination, a new way of thinking about how influenza viruses change,

reproduced here with permission from Recombinomics.

The older way of thinking is that random mutation is responsible for flu viruses acquiring new traits or SNPs (single nucleotide polymorphisms). That would require that two different viruses make the very same mistake in copying so that both sequences would have the same identical deletion. But, the changes that are

occurring just do not seem "random" enough. When we are seeing long stretches

of identity between from one parent virus and again long stretches of identity

with another parent virus within the same gene segment with absolute fideltiy for

decades, it is very difficult to explain this by random mutation.

Recombination is more like LEGO blocks of genetic material that can fit together

in a variety of ways to help the virus make changes to avoid the immune system

of the host. These pieces are made to come apart or combine, some more easily

than others depending on many factors. The virus can choose from an assortment

of combinations. This is a more efficient way to make adaptive changes for such

a rapidly evolving virus as H5N1.

http://www.recombinomics.com/News/03280802/Random_Mutations.html

The upcoming paper, with the unlikely title, "Homologous Recombination is Very Rare or Absent in Human Influenza A Virus" signals the beginning of the end of one of the basic tenets of influenza genetics, Genetic Drift via selection of random mutations. This basic tenet has guided research and vaccine development in influenza genetics and is an underlying principle of evolution in general.

For influenza and other single stranded RNA virus, evolution is thought to be driven by a series of random mutations generate during the copying of the virus' genetic information. The errors which provide a selection advantage would then be incorporated into the viral genome, and these changes would lead to a drift of genetic information. These changes would allow the virus to escape from immunological attack, and lead to frequent changes in vaccine targets.

Since changes by random mutation are thought to be unpredictable, new vaccine targets are selected after the virus has evolved. Of course this leads to vaccines that are already somewhat out of date by the time they are available for use.

The concept that the changes were due to recycling of prior selected mutations through recombination represented a paradigm shift that was thoroughly discounted by influenza geneticists, including the authors of the above paper. They had previously argued that changes in the 1918 pandemic virus were due to differential evolution of the HA gene, and that homologous recombination in negative sense RNA viruses was rare and played little or no role in viral evolution in general and influenza evolution in particular.

The above paper represents the results from an analysis of human influenza sequences. The search was in a limited database of complete human sequences, which eliminated the detection of recombination in partial sequences, or recombination that involved donor sequences influenza isolates from birds or swine. Thus, the number of examples would be significantly lower than the true instance. Although only two examples of recombination involving long stretches of recombined sequences were found, there were over 300 examples of small stretches of homolgous recombination which were statistically significant. The significance for the 240 examples in the NA gene had a p value of >1.2 X10 to the minus 10. Thus, the likelihood that the result was not due to chance was more than a billion to one.

Since the evidence for small regions of recombination was strong, the authors have focused on lab error to explain the examples. They cite amplification of contamination or mixed sequences to create lab generated recombination. However, they provide no evidence that any of the more than 300 short examples are due to such contamination. Moreover, examples of recombination in shorter human influenza sequences, which were excluded from this paper, as well as examples in swine and avian influenza, contain examples of recombination which are present in multiple isolates in multiple locations.

The statistically significant examples are the beginning of the end of the use of random mutations to explain influenza evolution. As additional sequences are generated, the random mutation explanation for rapid evolution becomes less tenable. For sequences from H5N1 genes, the number has risen markedly in recent years. Most newly acquired polymorphisms are readily detected in the database, and most are in other H5N1 sequences. Moreover, as the number of sequences rise, more shuffling of individual polymorphisms is found, especially when individual polymorphisms are traced. These tracings through the sequence database generate clear patterns, which can be used to predict new combination. Moreover, the same polymorphisms can jump from one genetic background to another.

Recombination is frequently between closely related sequences, which result in the stable transfer in a limited number of changes per recombination event. These changes are typically mistaken for single nucleotide polymorphisms linked to copy errors. However, the statistically significant patterns described in this paper will lead to more extensive analysis of these polymorphisms, which will lead to the understanding of the true nature of these genetic changes, which are driven almost exclusively by homologous recombination.

Protection of cats against lethal influenza H5N1 challenge infection

http://vir.sgmjournals.org/cgi/content/abstract/89/4/968

(hat tip flutrackers/florida1)

They used a different virus, H5N6 to protect the felines from H5N1. Feral

cats in Indonesia have been known to be infected with bird flu. It is

unknown as to whether or not they are involved in infecting humans.

As diseased cats can transmit the infection to naïve contact animals, the epidemiological role of H5N1-infected cats in endemically infected areas as a link between wild birds, poultry and humans needs close inspection, and vaccination of cats should be considered to reduce possible human exposure.

Comments from an Indonesian Virologist

An Indonesian scientist discusses using Indonesian strains of H5N1 to develop vaccine

for Asia. He is also distancing himself from Health Minister Supari's claims about

viruses being used as biological weapons.

The section on mammals as carriers of silent infection was interesting. No one

knows for sure if there are some unknown reservoirs in other animals but

apparently it is suspected that this may be so.

http://www.thejakartapost.com/news/2008/03/29/ri-bird-flu-virus-let039s-keep-scientific-loop.html

(hat tip PFI/Pixie)

In the case of silent infection, a human being and other animals such as dogs and cats can be infected and carry the bug in a tiny number before it will find a genetically susceptible human host. The level of infection is so low that it can not produce disease, nor an antibody response, in the carrying person or animal.

An environment of that kind is a paradise for the emergence of pandemic strain. The bug can reproduce and replicate continuously, which gives it the chance to mutate into what it will.

Bangladesh: Warmer Temperatures Slowing Bird Flu Spread

http://afludiary.blogspot.com/2008/03/bangladesh-warmer-temperatures-slowing.html

I am remembering the very real human cases that have occurred in the hot

months of summer in Egypt, but it is still good to hear that there are fewer

cases in poultry in the warmer months if this report is correct. Time will tell.

With so many outbreaks in an economically disadvantaged country, it is

unlikely that they will eradicate it completely. That takes money, and the

cooperation of the people that live there.

An official at the Bird Flu Control Room told Xinhua that some 1,536,542 chickens, ducks and pigeons have been culled so far till Saturday since the virus broke out in March last year.

The official said the disease affected 486 commercial farms and42 private farms in 47 districts out of 64 districts in the country.

Indonesia

It's too much, more kids either positive or dead from bird flu with the

strong possiblity of clusters of cases (govt hates to admit clusters

of cases are occurring):

http://afludiary.blogspot.com/2008/03/indonesia-confirms-two-bird-flu-deaths.html