Posts Tagged ‘pandemic’

From monkeys to humans, or…?

15 July, 2011

Adenovirus

A new Nature News item makes for interesting reading: it details how a new adenovirus, which had devastated a captive colony of titi monkeys, also jumped into a researcher working with them – and then into a family member who had had no other contact with the monkeys.

I put this comment up there:

While it may be unusual for adenoviruses to do this, there are a number of viruses which jump from monkeys to people – not the least of which are the HIVs.

This article, however, also raises to possibility that the virus may have gone the other way – that is, from humans to monkeys. This is also not that unusual; in fact, measles is a major risk factor in certain primate facilities, as certain monkeys can contract it easily, and often die.

The other possibility – that it came from a rodent or other animal – is potentially worrying, given that the virus was hitherto uncharacterised, and rodents tend to be ubiquitous.

Just goes to show: we really, really do need a Global Virome project, to pick up on all the little nasties out there.

Should remaining stockpiles of smallpox virus be destroyed?

19 April, 2011

Our Department has a journal club every Friday, when research folk (staff and students) get together to hear a postgrad student present an interesting new paper.  Last Friday Alta Hattingh from my lab gave a thought-provoking and insightful presentation on whether or not smallpox virus should be destroyed – so I asked her to turn it into a blog post.

Should remaining stockpiles of smallpox virus (Variola) be destroyed? 

Raymond S. Weinstein

Emerging Infectious Diseases (2011), Vol 17(4): 681 – 683

Smallpox virus replication cycle.  Russell Kightley Media

Smallpox virus replication cycle. Russell Kightley Media

Smallpox is believed to have emerged in the Middle East approximately 6000 to 10 000 years ago and is one of the greatest killers in all of human history, causing the death of up to 500 million people in the 20th century alone.  Smallpox is the first virus to ever be studied in detail and it is also the first virus for which a vaccine was developed.  Smallpox was beaten by the Jenner vaccine (first proposed in 1796) and the disease was declared eradicated in 1980 in one of the greatest public health achievements in human history.

The last officially acknowledged stocks of variola are held by the United States at the Centres for Disease Control and Prevention (consisting of 450 isolates) and in Russia at the State Research Centre of Virology and Biotechnology (various sources place the number of specimens at ~150 samples, consisting of 120 strains).  This includes strains that were collected during the Cold War as potential for biological weapons due to their increased virulence. Then, there is also the added possibility that stolen smallpox cultures are in the hands of terrorists organizations.

In 2011 the World Health Organisation (WHO) plans to announce its recommendation for the destruction of all known remaining stockpiles of smallpox virus.  They have wanted to destroy the virus ever since 1980 when the Secretary of Health and Human Services, Louis Sullivan, promised destruction of US stockpiles within 3 years. This never happened in the US or Russia and no official recommendation for destruction have been recommended by the World Health Assembly.  In 2007 the final deadline for a decision was postponed until 2011 as no consensus could be reached among the executive board of the WHO.

The only real benefit that could be gained from destroying all known remaining stockpiles of smallpox virus in the world would be the prevention of causing a lethal epidemic due to theft or accidental release of the virus.  However, according to Weinstein destruction would only provide an illusion of safety and that the drawbacks of eliminating variola from existence are many.

In this paper Weinstein mentions the possible reasons behind the hesitance to destroy smallpox.  The prolonged existence of smallpox along with the important clinical implications of its high infectivity and mortality rates suggests that the human immune system evolved under the disease’s evolutionary influence.  In the last decade research has been done which suggests that variola (and vaccinia) have the ability to alter the host immune response by targeting various components of the immune system.  We are only beginning to understand the complex pathophysiology and virulence mechanisms of the smallpox virus.  An example of the importance of smallpox in human evolution is the CC-chemokine receptor null mutation (CCR5Δ32), which first appeared in Europe ~3500 years ago one person and today it can be found in ~10% of all those from northern European decent.  The mutation prevents expression of the CCR5 receptor on the surface of many immune cells and provides resistance to smallpox.  This same mutation also confers nearly complete immunity to HIV. In a recent study done by Weinstein and co-workers (2010) it was postulated that exposure to vaccinia and variola may have previously inhibited successful spread of HIV, suggesting that we swopped out one major disease for another. By eliminating the variola stockpiles from existence on-going research in this direction might be hampered and the possibility future studies employing intact virus will be rendered impossible.

Finally, we are capable of creating a highly virulent smallpox-like virus from scratch or a closely related poxvirus through genetic manipulation.  This renders moot any argument for the destruction of remaining stockpiles of smallpox in the belief that it would be for the benefit of protecting mankind.

In an editorial of the Vaccine journal, the editors make a compelling case in favour for the destruction of remaining stockpiles of smallpox virus.    To follow is their take on the situation:

Why not destroy the remaining smallpox virus stocks?

Editorial (by J. Michael Lane and Gregory A. Poland)

Vaccine (2011), Vol 29:  2823 – 2824

The Advisory Committee on Variola Virus Research (created in 1998 as part of the WHO) concluded that live variola is no longer necessary except to continue attempts to create an animal model which might mimic human smallpox and assist in the licensure of new generation vaccines and antivirals.

The editors feel that scientific recommendation for keeping smallpox stocks need to be scrutinized and that a number of political and ethical issues need to be addressed.  Below are comments by editors on these issues:

Scientific issues:

The smallpox virus is no longer needed to elucidate its genome, 49 strains have been sequenced and published, the editors feel that there is no need to sequence additional strains.  The smallpox virus can be destroyed as it is possible to reconstruct it from published sequences or to insert the genes of interest into readily available strains of vaccinia or monkeypox.  Refinements regarding diagnostics can be made by using other orthopoxviruses or parts of the smallpox strains already sequenced; vaccines have been produced that are far less reactogenic than the first and second generation of vaccinia vaccines and they are very effective against other orthopoxviruses.  Finally, the development of an animal model is difficult to perfect as variola is host-specific, thus there are no guarantees that a model will be found that mimics the pathophysiology of smallpox in humans.

Political/ethical issues:

The US is a supporter of the WHO and the UN and failure to comply with the request of the World Health Assembly jeopardizes the US’s potential to work with the UN to further their foreign policy and population health goals.  Biological weapons have been banned from the US military arsenal and there is no way they would use a biological weapons such as smallpox whether it be in offense or defence.  The editors reckon that the risk of a biological warfare attack using smallpox is highly unlikely as terrorists who have the knowledge and sophistication to grow and prepare smallpox for dispersal would realize that they could cause harm to their own countries.  Apart from that, Western nations have the facilities to isolate and vaccinate against smallpox in a timely manner.

According to the editors there is no ethical way to justify maintaining an eradicated virus.  Even though the possibility of accidental release is very small, it is an unacceptable risk.  Maintenance of the smallpox virus stocks is expensive and time consuming, it also burdens the CDC without scientific merit and their resources are better used to protect the public from infectious diseases.

In conclusion the editors maintain that the remaining smallpox stocks should be destroyed and the world should make possession of the virus an “international crime against humanity”.

We are presented with two very different views with regards to whether or not smallpox virus stocks should be destroyed forever.  The WHO meets again this year to decide the final fate of smallpox. Will the board reach consensus or will the smallpox virus yet again receive a stay of execution? 

Note added 1 Oct 2015

Interestingly, I found the following text written by me in my archive of articles – published as a Letter in the now sadly defunct HMS Beagle, in 1999:

HMS Beagle

( Updated May 28, 1999 · Issue 55) http://news.bmn.com/hmsbeagle/55/viewpts/letters

Use logic, not fear

The destruction of all (known) stocks of smallpox virus (Reprieve for a Killer: Saving Smallpox by Joel Shurkin) seems to be a very emotive issue. Perhaps, if people looked at it less in terms of a threat, and more in terms of a resource, most of the problem would go away. For example, although the original article made mention of monkey pox, and how it was almost as dangerous as smallpox, and appeared to be adapting to human-to-human spread, nothing has been said about investigating why smallpox was so much more effective at spreading within human populations than monkey pox is. It is all very well having the smallpox genome sequence; however, without the actual DNA, it is difficult to recreate genome fragments of the size that may be needed to make recombinant viruses to investigate the phenomenon of host/transmission adaptation. Additionally, without the actual virus, it will be impossible to compare the effects of a doctored vaccine strain with the real thing. Destroying known stocks of the virus will not affect the stocks that are most likely to be used for bioterrorism. It will, however, handicap research into ways of combating the virus/understanding how it worked in the first place.

And so it’s over – is it??

26 August, 2010

The WHO recently declared the H1N1 “swine flu” pandemic to be over – on August 10th, 2010.   From the AFP article:

“The world is no longer in phase six of the pandemic alert. We are now moving into the post-pandemic period,” WHO Director General Margaret Chan said

….

Swine flu has killed more than 18,449 people and affected some 214 countries and territories since it was uncovered in Mexico and the United States in April 2009, according to WHO data.

The new virus spread swiftly worldwide despite drastic measures including a week long shutdown in Mexico, prompting the UN health agency to scale up its alerts and declare a pandemic on June 11, 2009, banishing kisses and frowning on handshakes.

Fears about the impact of swine flu on unprotected populations and a harmful mutation sparked a rush for hundreds of millions of dollars worth of specially-developed vaccines and a flurry of public health precautions.

However, those concerns dwindled in late 2009 to be replaced by recriminations in Western nations about the cost of unused vaccines and what some European critics regarded as an unjustified scare.

Amazing, that: the world authorities get it right, help mitigate what could have been a nasty pandemic – then get it in the neck for being alarmist, and helping drug companies make a profit.

Further from the article:

After petering out in Europe and the United States before their winter flu season was over, in recent months swine flu has affected parts of South Asia and “limited areas” of tropical South and Central America, as well as Africa for their second season.

But unlike 2009, when A(H1N1) ousted most other types of flu viruses around the world, known seasonal viruses now are prevalent and even dominant in countries such as South Africa.

Yeeessssss…and that’s all very well, because do you know what happened in South Africa?  They’ve only just released H1N1 vaccine stockpiled for health workers for the duration of the Soccer World Cup, is what – late in the flu season, and almost too late to do any good.  Meaning exactly what was predicted at the beginning of the pandemic, came to pass: there was not enough vaccine for developing countries, and even a year after its emergence, it was still not being distributed evenly.

Not a very good practice run for the Big One, if you ask me: still not enough vaccine being made quickly enough; vaccine not being distributed to at-risk countries; too much fussing over the welcome news that it was not as bad as it could have been.

I’m going to put my faith in plants….

So it wasn’t so bad…THIS time.

13 January, 2010

Influenza A viruses mixing in susceptible hosts

 

I have been waiting with great interest to see what would happen in the wrong northern hemisphere 2009-2010 winter season with the Mexican – sorry; politically incorrect, aka pandemic H1N1 – flu – and it has pretty much happened, and it wasn’t nearly as bad as it could have been.

From ProMED:

 

INFLUENZA PANDEMIC (H1N1) (05): VACCINE UPDATE

**********************************************

A ProMED-mail post
Date: Mon 11 Jan 2010
Source: Reuters News [edited]

Countries re-think swine flu vaccine orders

– ——————————————-

The United States said on Monday [11 Jan 2010] it had cut in half its order for influenza pandemic (H1N1) 2009 virus vaccine from Australia’s CSL Ltd, but said it is not certain how far orders from other suppliers will be trimmed. While U.S. officials are still calculating how much swine flu vaccine they will need, it is becoming increasingly clear that the United States will not need all 251 million doses it ordered from 5 companies. …

Several other governments have started to cut orders for [pandemic] H1N1 vaccines because the pandemic has not turned out to be as deadly as originally feared and most people need only one dose, not 2, to be fully protected.

…Germany’s Bild newspaper reported that the German government had agreed to cut its vaccine order with GlaxoSmithKline Plc by one-3rd. The newspaper said the agreement would save states about 133 million euros (USD 193 million). On Friday [8 Jan 2010], Britain said it was in talks with Glaxo about reducing supplies. ….

…While the pandemic is slowing down in North America, the World Health Organization said on Monday [11 Jan 2010] the virus was still active in parts of central, eastern and southeastern Europe, North Africa and South Asia. Governments are torn between trying to encourage companies to make influenza vaccine and wasting money on doses that are never given. But bulk antigen — the vaccine before it is put into a syringe – — can be stored and might be used in next year’s seasonal vaccine.

The U.S. government was still promoting vaccination, reminding people that influenza is unpredictable and that [pandemic] H1N1 could come back in a 3rd wave. One potentially large market for the vaccine is children. Children under 10 need 2 doses of vaccine to be fully protected and some U.S. school districts were planning more vaccination clinics this week to get children a 2nd dose. …
[Byline: Maggie Fox]

– —

Communicated by:
ProMED-mail Rapporteur Mary Marshall

Communicated by:
ProMED-mail

 

Influenza virus A H1N1 2009: gets to parts the other flu doesn’t reach

14 September, 2009

Flu virus life cycle. Copyright Russell Kightley Media

The September 2009 issue of Nature Biotechnology has a letter concerning the receptor specificity of AH1N1 2009 pandemic influenza virus – which accounts pretty well for why it CAN be pretty nasty, and for why it may get nastier yet.

Childs et al., in a letter entitled “Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray“, describe what amounts to a tour de force analysis of the receptor binding of a number of influenza viruses, which concludes with the statement that:

“The differences in receptor binding between the 2009 pandemic and seasonal H1N1 viruses may therefore account, at least in part, for the higher virus replication and greater pathology reported in the lungs of ferrets, mice and nonhuman primates infected with pandemic viruses, than observed with contemporary seasonal viruses.”

Which would help explain why some otherwise healthy young people are dying of the virus, while others are getting only mildly ill.  But we get ahead of ourselves: in January last year I wrote in MicrobiologyBytes about recpetor specificities of A-type influenza viruses, in the context of how H5N1 was less likely to mutate to easy human-to-human transmissibility than had origianlly been thought.

I wrote at the time:

According to a letter in the January 2008 issue of Nature Biotechnology, it is a characteristic structural topology, and not just the α2,6 linkage, that enables specific binding of HA to α2,6 sialylated glycans. The authors state:

…recognition of this topology may be critical for adaptation of HA to bind glycans in the upper respiratory tract of humans. An integrated biochemical, analytical and data mining approach demonstrates that HAs from the human-adapted H1N1 and H3N2 viruses, but not H5N1 (bird flu) viruses, specifically bind to long α2-6 sialylated glycans with this topology. This could explain why H5N1 viruses have not yet gained a foothold in the human population.

Apparently the critical shape in humans is umbrella-like, whereas the avian receptor is characteristically cone-like. Again from the paper:

The topology of α2-3 and α2-6 is governed by the glycosidic torsion angles of the trisaccharide motifs-Neu5Aca2-3Galb1-3/4GlcNAc and Neu5Aca2-6Galb1-4GlcNAc, respectively (Supplementary Fig. 3 online).

Ram Sasisekharan and colleagues showed that human-adapted viruses with mixed α2,3/α2,6 binding ability that bound the umbrella-type receptor were efficiently transmitted, whereas viruses with the same basic specificity that did not have HA binding specificity to “long” α2,6, were not.

The present paper reports the following investigation:

“We have compared directly, by carbohydrate microarray analysis, the receptor-binding characteristics of two isolates of the novel pandemic H1N1 virus, Cal/09 and A/Hamburg/5/2009 (Ham/09), with those of a seasonal human H1N1 virus, A/Memphis/14/96-M (Mem/96), as representative of a virus well adapted to humans [and a reassortant human H3N2 virus A/Aichi/2/68 x PR8 (X31)]. As the HA of the novel H1N1 pandemic virus originated from a virus similar to triple reassortant swine H1N1 viruses, we compared one such example, A/Iowa/1/2006 (Iowa/06), isolated from a human infection, and an older close relative of classical swine H1N1 viruses, A/New Jersey/76 (NJ/76), the human isolate that initiated the concern of a pandemic threat in 1976.”

This is a really comprehensive analysis – for such a short communication – which throws up a number of interesting points.  First, I was not aware it was possible to do “carbohydrate microarrays”!  Second, the paper shows quite conclusively that the swine-derived AH1N1 viruses have a significantly wider range of receptor specificities than a standard seasonal AH1N1 virus, and – but to a lesser extent – than the reassortant H3N2 virus X31.

Carbohydrate microarray analyses of the six viruses investigated.
From the following article (with permission from NBT):
Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray.
Robert A Childs, Angelina S Palma, Steve Wharton, Tatyana Matrosovich, Yan Liu, Wengang Chai, Maria A Campanero-Rhodes, Yibing Zhang, Markus Eickmann, Makoto Kiso, Alan Hay, Mikhail Matrosovich & Ten Feizi.
Nature Biotechnology 27, 797 – 799 (2009).
doi:10.1038/nbt0909-797

flu_receptor

Legend:
Numerical scores for the binding signals are shown as means of duplicate spots at 5 fmol per spot (with error bars). The microarrays consisted of eighty sialylated and six neutral lipid-linked oligosaccharide probes, printed on nitrocellulose-coated glass slides. These are listed in Supplementary Table 1 and arranged according to sialic acid linkage, oligosaccharide backbone chain length and sequence. The various types of terminal sialic acid linkage are indicated by the colored panels as defined at the bottom of the figure.

And what does all this mean, exactly?  The authors sum it up well:

These results indicate that no major change in receptor-binding specificity of the HA was required for the emergent pandemic virus to acquire human-like characteristics and become established in the human population. …

The broader specificity, namely, the ability to bind to 2-3- in addition to 2-6-linked receptors is also pertinent to the greater virulence of the pandemic virus than seasonal influenza viruses observed in animal models, and its capacity to cause severe and fatal disease in humans, despite the generally mild nature of most infections. Binding to 2-3-linked receptors is thought to be associated with the ability of influenza viruses to infect the lower respiratory tract where there is a greater proportion of 2-3- relative to 2-6-linked sialyl glycans, although long chain 2-3-linked sialyl (poly-N-acetyllactosamine) sequences are present in ciliated bronchial epithelial cells in humans where they are the receptors for another human pathogen, Mycoplasma pneumoniae.

So there you have it: the viruses can get deeper in to your lungs than the standard flu – which, if it happens, can make you seriously ill.

So what happens if it gets better at binding the 2,3-type receptors in humans?  Well, we’re only in the middle of the pandemic.  We may yet find out the hard way.

H1N1 – view on a pandemic

26 August, 2009

Well, “The Big One” that we have all been waiting for since 1968 – or 1977, if you count the accidental re-release of the original humanised H1N1 as a pandemic – is well and truly here.  A nice little animated graphic for depicting how it arose, while a bit simplistic, is available here.

And what have we learned?  Has civilisation fallen; have populations been decimated?

Well, quite a lot; no, and no, in answer.  Explanations for some of this are contained in a survey just released.  Here from the News24 report published today, sourced from SAPA:

Paris – More than half the fatalities from H1N1 swine flu have been among young adults, according to one of the first surveys to gather mortality data from across the globe for the new A(H1N1) virus.

The analysis of 574 pandemic deaths from 28 countries through mid-July, released this week, also found that being diabetic or obese significantly boosted the risk of dying.

Neither children nor the elderly are as vulnerable as initial reports indicated, found the study, published by Eurosurveillance, the monitoring arm of the European Centre for Disease Prevention and Control.

“Most deaths (51%) occurred in the age group of 20-to-49 year-olds, but there is considerable variation depending on country or continent,” the researchers reported.

Only 12% of those who died were 60 or older.

All of these features – high mortality among young adults and the obese, but not the very young or elderly – are sharply different than for the seasonal flu.

More than 90% of deaths from seasonal flu – which claims 250 000 to 500 000 lives annually according to the WHO – are in people over 65.

By contrast, with the pandemic H1N1, “the elderly seem to be protected from infection to some extent, perhaps due to previous exposure to similar strains”, the study conjectured.

Persons born before 1957, other studies have suggested, were almost certainly exposed to the milder seasonal A(H1N1) viruses that evolved from the terrible pandemic of 1918, which left some 40 million dead.

With the 2009 strain, “when infection does occur, however, the percentage of deaths in elderly cases seems to be higher that in others”.

One common target across both pandemic and season strains is pregnant women, according to the study, led by Philippe Barboza of the French Institute for Public Health Surveillance….

And that’s the sinister part…here in South Africa, of 18 fatalities known to have been associated with pandemic AH1N1 infection, NINE were pregnant women, mostly in the third trimester of pregnancy.  In a report published yesterday, SA’s Minister of Health Dr Aaron Motsoaledi said the following:

“We find it very worrying that there is an increasing number of pregnant women who are succumbing to this pandemic,” Motsoaledi said.

“The directive to all health care workers… is to put pregnant women with flu-like symptoms (even if they are mild) on Tamiflu treatment.

“Doctors should not wait for any tests before such treatment is administered.”

Further on in the same report:

On Monday, the National Institute for Communicable Diseases [NICD] also said pregnancy had been identified as a particular risk factor for severe H1N1 flu.

It said that in the second and especially the third trimester, urgent treatment with antiviral drugs should be considered even before any laboratory results were received.

The institute added however that most H1N1 flu cases in South Africa remained mild and “self-limiting”.

Routine H1N1 testing for everyone with flu-like illness was still not recommended.

Nationwide, there had been 5 118 laboratory-confirmed cases of H1N1 flu, it said.

The figure is essentially meaningless, given that most suspected flu cases are not laboratory-diagnosed (it costs R700, or ~US$70, for a single test) and the pandemic flu is pretty much indistinguishable from seasonal, and may in fact have supplanted the normal flu.  It certainly has in Australia and Argentina, which remain the two worst-hit southern hemisphere countries, and probably has in South Africa too: the CDC has a very useful map illustrating this, accessible here.

International news, via the CDC site, is the following:

As of August 13, the World Health Organization (WHO) regions have reported over 182,166 laboratory-confirmed cases of 2009 H1N1 influenza virus (2009 H1N1) with 1,799 deaths. The laboratory-confirmed cases represent an underestimation of total cases in the world as many countries now focus surveillance and laboratory testing only in persons with severe illness. The 2009 H1N1 influenza virus continues to be the dominant influenza virus in circulation in the world.

One very important piece of information further down this report is the following:

There have been no significant changes detected in the 2009 H1N1 influenza virus isolated from persons in the Southern Hemisphere as compared to viruses isolated from persons in the Northern Hemisphere.

This is important because the frantic rush to make vaccines to combat the expected northern hemisphere upsurge in infections in their autumn season – October or so – depends upon the virus not having changed much from the seed material which was derived from virus isolated earlier this year.  This could negate some of theh fears that the much-anticipated “second wave” of virus infections could be a lot worse than the first.

Good news on the vaccine front – for Australians at least – is that an Australian company, CSL Ltd, has the world’s first data from human trials of a pandemic strain vaccine, and looks set to be able to provide Australia with 21 million doses of vaccine – and 2 million doses of the vaccine at the end of the month.

Other vaccine news is also fairly encouraging, notwithstanding a rather alarming report in New Scientist recently about the new strain growing only half as well in eggs as seasonal flu types: while this remains a worry, newer, faster-growing variants have been derived and distributed – though possibly not in time for a northern hemisphere autumn roll-out.

Mind you, all of this production relies on the well-proven-but-seriously-archaic 1930s technology of growing live virus in hen’s eggs: we are still trapped, in the 21st century, into having to use early 20th century methods to produce vaccines for fast-adapting pathogens.  Things ARE changing: various pharma companies are diversifying into mammalian and insect cell culture; people (including us!) are investigating making recombinant subunit vaccines in plants (see here) – and there is at least the tantalising possibility that “universal vaccines” may become available in the not-too-distant future.  These will exploit all or part of the highly conserved M2 “ion channel” protein of influenza viruses as recombinant subunit vaccines.

However, all of this is at least six months in the future for conventional vaccines, and many years hence for newer offerings.  Meantime – there is disturbing news concerning trans-species transmissions of pandemic AH1N1 viruses.

ProMED Mail (ProMED Digest V2009 #394) reports that “Chile finds H1N1 swine flu in turkeys“:

Chilean health authorities announced on Thursday night [20 Aug 2009] that they had detected and controlled an outbreak of swine flu in 2 turkey farms, according to a communication from the Agricultural and Livestock Service (SAG).

“The presence of an influenza type A virus was detected in 2 farms in the Valparaiso Region, and immediate precautionary measures were adopted to prevent the dissemination of the disease and to protect the population’s health,” said the text.

And again from ProMED on 20th August, quoting The Straits Times and AFP:

A 2nd Australian piggery was placed in quarantine due to swine flu on Wednesday [19 Aug 2009] as the number of human deaths from the virus reached 121.

Authorities ordered a biosecurity lockdown at the piggery in Victoria state amid concerns the virus could mutate and return to humans in a more deadly form.

Another piggery in New South Wales state has been quarantined since late July [2009], although the state government said most of the animals had recovered from the disease.

Victoria Agriculture Minister Joe Helper said tests confirmed the presence of influenza at the piggery after its owners reported earlier this week that the animals were not eating.

‘It is important to stress that this is not a human health issue and that national and international food authorities continue to advise that pork and pork products are safe to eat,’ he said.

Media reports said the pigs were believed to have contracted the virus from workers at the property who were suffering the human form of the disease.

Health experts fear swine flu in humans, which is easily spread but has a relatively low fatality rate, could mutate in other animals and emerge in a more virulent form. [my emphasis]

So: two independent incidents, on different continents, of pandemic AH1N1 viruses getting into different species of farmed livestock – and luckily controlled.

What would have happened if domestic fowl and/or pigs had been infected in places like Vietnam, Thailand, Indonesia, Turkey and Egypt – where highly pathogenic avian H5N1 influenza viruses appear to be endemic, and not well controlled?  Given the complex origins of the current pandemic virus – from several swine, avian and human viruses – it could be a recipe for disaster, on a scale even greater than the 1918 pandemic.

The REAL Big One.  Let’s all help get a vaccine, people!!

While you have the flu….

7 August, 2009

…as I think I do…

KEEP_CALM_AND_DON'T_SNEEZE

Thanks Michael Rolfe!

Where the new H1N1 came from

29 June, 2009

Mixing of flu viruses to produce a new strain. copyright Russell Kightley Media

In Nature 459, 1122-1125 (25 June 2009): Smith et al. on “Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic“.

In March and early April 2009, a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States1. During the first few weeks of surveillance, the virus spread worldwide to 30 countries (as of May 11) by human-to-human transmission, causing the World Health Organization to raise its pandemic alert to level 5 of 6. This virus has the potential to develop into the first influenza pandemic of the twenty-first century. [I thought a pandemic alert level of 6 meant it had already?? – Ed] Here we use evolutionary analysis to estimate the timescale of the origins and the early development of the S-OIV epidemic. We show that it was derived from several viruses circulating in swine, and that the initial transmission to humans occurred several months before recognition of the outbreak. A phylogenetic estimate of the gaps in genetic surveillance indicates a long period of unsampled ancestry before the S-OIV outbreak, suggesting that the reassortment of swine lineages may have occurred years before emergence in humans, and that the multiple genetic ancestry of S-OIV is not indicative of an artificial origin. Furthermore, the unsampled history of the epidemic means that the nature and location of the genetically closest swine viruses reveal little about the immediate origin of the epidemic, despite the fact that we included a panel of closely related and previously unpublished swine influenza isolates. Our results highlight the need for systematic surveillance of influenza in swine, and provide evidence that the mixing of new genetic elements in swine can result in the emergence of viruses with pandemic potential in humans.
[my bolded sections – Ed]

An important paper for a number of reasons – not the least of which is pigs have

Depiction of virus mixing in a pig

been pushed to the fore as a potential source of new and dangerous human flu viruses.

Through no fault of their own, I might add: the only pigs proven to have had the new virus were probably infected by a handler who had been to Mexico!

The most important observation to emerge from this is that pigs should be surveilled systematically and worldwide – to stop yet another possible avenue for zoonotic infection for us vulnerable humans.

H5N1 flu: The End is still in sight

15 July, 2008

While the much-dreaded Big One – a major flu pandemic – still seems to be holding off, I am pleased to see that the latest edition of Nature has devoted an editorial and other commentary space to pandemic flu in general, and H5N1 flu in particular.

The Nature issue of 10th July 2008 – which has Ebola virus glycoprotein on the cover, about which, more later – has as its lead editorial title, “The long war against flu“.  The header goes on:

“That the H5N1 strain of bird flu has not yet caused a pandemic is no cause for complacency. Preparations for the inevitable must be redoubled to mitigate the potential devastation.”

My feelings entirely, and especially for the developing world – shared with you here and here, in MicrobiologyBytes, and here, in your own ViroBlogy.  It is all too easy to easy to fall into a state of complacency, or even H5N1 pandemic fatigue: however, this is really dangerous, especially for planners.  The editorial goes on:

“Five years after the deadly H5N1 avian influenza virus exploded into a global epidemic in birds, it has infected more than 300 people. Happily, it has not yet evolved into a strain that can transmit easily between humans — an event that would trigger a pandemic that could kill tens of millions. But as long as H5N1 continues to be present in animals, that risk persists. And with so many other flu strains out in the world, all constantly evolving, a flu pandemic is inevitable.”

 And:

“…improved control measures, especially for H5N1 itself, and public-health infrastructure are our frontline defences against a pandemic. Unfortunately, the overall control picture is bleak. Thailand, Vietnam and China have notched up successes in curbing outbreaks in birds, which is key to minimizing the chance that the virus can pass to humans. But South Korea had its worst outbreak ever in April, and the disease has become endemic in Indonesia, Bangladesh, Vietnam and Egypt. Eradication now seems impossible, and the task of containing the virus has become chronic and costly.”

Which sets the stage for Commentaries in the same issue: in “Ready for Avian Flu“, Tadataka Yamada et al. offer up “…a roadmap for heading off a global avian influenza catastrophe“.  They discuss how the WHO has made plans for stockpiling H5N1 vaccines, and that major vaccine manufacturers have offered to contribute – but also that the necessary allocation plan and ethics framework still need to be worked out.  They discuss how adjuvanting flu vaccines can reduce the dose by up to to four times, and how this together with dedicating the existing manufacturing framework – capable of some 500 million doses of trivalent vaccine a year  – to single-valency production, could allow some 6 billion doses a year to be produced.

Which, of course, would neatly cover the world’s population.  This sounds wonderful – but ignores the fact that H5N1 viruses are notoriously difficult to produce via conventional egg-based methods, which is what provides the bulk of the present manufacturing capacity….  Still, they also point out that adjuvanted, non-matched vaccines can still cross-protect against strains that have undergone seven or so years of genetic drift, meaning that stockpiled H5N1 vaccines could still be relevant in several years time.

They state the following:

“In the next 18 months we [Bill & Melinda Gates Foundation, the Pasteur Institute and the Wellcome Trust] will develop, maintain and disseminate a central inventory of funded research activities that are relevant to human influenza to ensure that stakeholders are well-informed. We will also coordinate roadmapping exercises to identify knowledge gaps. These will assist funders and researchers in establishing research-funding priorities, with specific focus on vaccines, drug therapies and epidemiology/population science (for example, diagnostics, surveillance, transmission and modelling). The Bill & Melinda Gates Foundation and the Wellcome Trust will collaborate to fund these activities.”

And how much developing country input will there be into this?  Distressingly little, probably, given the propensity of these funds to at best give money to developed country groups to work with developing country folk, but at least the roadmap addresses issues that are relevant to the whole world community.  Like intellectual property concerns, coordination of stockpiling and distribution, fair distribution, funding…and surveillance, the forgotten and possibly most important factor in determining if a flu outbreak is getting out of hand.  

Apropos of which, another commentary in the same issue – “The contents of the syringe“, by Steven Salzberg – notes that the influenza vaccine failed this northern hemisphere winter, and that future success relies on sharing data more widely and making the virus strain selection process more transparent.  Salzburg says:

 
“The WHO met on 11–13 February this year to decide on the strains to be included in the vaccine for the 2008–09 season. As usual, the meeting was closed to all but invited participants, who this year included members of the WHO influenza surveillance network, representatives of national drug regulatory agencies, and influenza vaccine manufacturers. The experts involved chose to replace the H3N2 strain with a more recent isolate, from 2007, which should be a better match to the circulating viruses next season. Neither the WHO nor the CDC publishes the evidence used to support their decision [my emphasis]. That evidence includes hemagglutinin inhibition tests of hundreds of isolates, genome sequences of some isolates and data on the ease with which the isolates can be grown in eggs.”

“The process of choosing flu-vaccine strains needs to be much more open. Other scientists, such as those in evolutionary biology with expertise in sequence analysis, could meaningfully contribute to the selection. At present, external scientists cannot review the data that went into the decision, nor can they suggest other types of data that might improve it.”

Whoops…so those who would safeguard us, feel no need to tell us what is going on??  Salzburg has some suggestions:

“The leaders of the influenza community, especially the WHO and the CDC, should create policies — for sharing data and isolates — that are more open, and should insist that their own scientists follow those policies. When these leading organizations set an example, the rest of the community will follow.”

“Of course, preparing vaccine in cell culture could reduce some of the pressures put on that dark room of vaccine predictors. The current system, in which most of the world’s vaccine supply is grown in chicken eggs, is an antiquated, inefficient method requiring six months or more to ramp up production, which in turn means that the vaccine strains must be chosen far in advance of each flu season. More crucially it sometimes prevents the use of the optimal strain, as it did in 2007. And, if the next pandemic is an avian-influenza strain such as H5N1, then it could easily sweep through the chicken farms that we rely on to produce eggs for vaccines. [me again]”

 He goes on to extol the benefits of sharing sequence information in particular, so as to enable rational, evidence-based choice of flu strains for vaccines – and the use of non-egg-based cell culture methods for vaccine production, and how these should allow far quicker development of flu vaccines.

All of this is very cogent and timeous.  However, it begs the question, previously raised in ViroBlogy, as to how production will be increased to take care of everyone who may be affected.

I still think plants are the answer…!  I note the plant-based flu vaccine group paper that I blogged on previously in this forum has a sequel: this is a better paper all around, and points up the need to explore this sort of production system for this kind of virus.

But I digress – so let me do so thoroughly.  The Nature issue also has a news item on the Eppendorf Song, a new piece of viral advertising with a boy band extolling the virtues of a multipettor.  Not a patch on the Biorad PCR Song, guys – but nice to see some popular culture making its way into science equipment advertising!

Bird Flu Vaccine Launched – But For Whom?

22 May, 2008

The online 20 May issue of Nature News trumpets the release and marketing of a new H5N1 bird flu vaccine: GlaxoSmithKline’s Prepandrix has just been approved by the European Commission. 

Published online 20 May 2008 | Nature | doi:10.1038/news.2008.844

Bird flu vaccine to hit the shelves

Europe approves pandemic vaccine; countries must decide own strategies.

Tony Scully

The European Commission has approved a new vaccine against the H5N1 bird flu virus — the first vaccine designed to ward off a future pandemic. But how the drug, called Prepandrix, will be deployed by national governments remains unclear.The vaccine, produced by the UK drug giant GlaxoSmithKline, is aimed at the H5N1 strain currently circulating in birds as epidemiologists think that this is the most likely strain to cause a human pandemic. H5N1, which originated in south-east Asia and is carried by migrating birds and domestic poultry, has caused 382 human cases and 241 deaths worldwide since 2003.

Prepandrix targets an antigen from an H5N1 strain called A/Vietnam/1194/04, which has been detected in birds in Asia, Europe and Africa. Clinical tests have shown that the vaccine is also effective against other closely related variants of H5N1, such as H5N2. The release of the vaccine is seen as a gamble that any future pandemic strain will closely resemble the Vietnamese version used to derive the vaccine.

The article goes on to describe how “The first orders for Prepandrix were placed last year by Finland and Switzerland, before it had been approved by the European Commission. In 2007, sales for Prepandrix totalled US$284 million worldwide….”

Yes.  Well.  Um.  Where is the pandemic going to hit first?  Finland?  Switzerland?  I doubt it.  How about Indonesia, Thailand, Vietnam, Turkey, Egypt…or, horror of horrors, India or China?  All the places which will need a LOT of doses, cheap.

Do they stand any chance of getting them?  Not unless they have preordered.  And not – in the case a pandemic strikes – unless they are willing to take military action to prise their stocks out of the hands of the governments in the developed countries where the vaccines are made.

A senior WHO official stated the case very succinctly, at the Virus Africa virology conference in Cape Town in November 2005: “You people in the developing countries will be on your own if the pandemic comes.  You need to make your own vaccine…”.

We wait in hope.