Posts Tagged ‘Influenza’

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!!

H1N1: coming to a South African home near you, soon

14 July, 2009

And after a very pleasant holiday, I come back to work to find…85 cases of confirmed pandemic H1N1 in South Africa!

Yes, it is true – at least, as far as the National Institute for Communicable Diseases (NICD) Director, Prof Barry Schoub, is concerned: he was featured yesterday on eTV News explaining how it was all going.  And it is “mild” according to him: it looks the same as standard flu, although most cases so far are due to people bringing it into the country, without much community spread…yet

In an article just published by the Independent Online (IOL), Kanina Foss says:

Swine flu cases will probably spike when schools reopen next week. Health officials will monitor schools, but are still advising that mild cases should be treated no differently from seasonal flu.

Only patients with serious symptoms – such as high fever, persistent vomiting, pain in the chest, or shortness of breath – should seek medical assistance. These are symptoms that people would seek medical assistance for anyway, says National Institute for Communicable Diseases (NICD) deputy director Lucille Blumberg.

The number of confirmed swine flu cases in South Africa is 75 [since modified, see above]. Once this number reaches 100, the NICD will stop counting. It will focus instead on severe cases and those at high risk because of compromised immune systems, such as HIV-positive people.  The institute will also monitor schools.  Counting cases was resource intensive, said the NICD on Monday, and served no more purpose than counting cases of seasonal flu. The overwhelming majority of cases worldwide had been mild, and had required no special treatment.

The World Health Organisation (WHO) has said the spread of the H1N1 virus is inevitable, and the NICD is expecting many more South Africans will be infected. It is unsure how the country’s high HIV prevalence will affect the severity of infections.

“It’s something we need to monitor very carefully,” said Blumberg.

The highest number of confirmed cases are in Gauteng (39), followed by the Eastern Cape (nine), and Western Cape (five).

Oh, and in my other persona, a post on AIDS denialism….

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.

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.

Influenza vaccines from plants??

22 April, 2008

I should have known Alan Cann would find this one; it’s just too good to miss – so I am going to add to what he said, as a way of further exploring what they could/should have done, as a result of discussions in our Journal Club this morning.

Alan wrote:

Influenza vaccines from plants

Posted by ajcann on April 16, 2008

 Our major defense against infection with influenza viruses is immunization of individuals with an annually updated vaccine that is currently produced in chicken eggs, with a global annual capacity of about 400 million doses, a scale of production insufficient to combat a pandemic. Furthermore, at least six months is required between the identification of new virus strains to be included in the vaccine formulation and the manufacture of bulk quantities. Uncertainties over the robustness of egg-based vaccine production are intensified even further by the emergence of H5N1 strains that are highly virulent to both chickens and eggs. There is a need to develop alternative vaccine production systems capable of rapid turnaround and high capacity. Recombinant subunit vaccines should circumvent some of the concerns regarding our current dependence on egg-based production.This paper reports on the production and evaluation of domains of influenza haemagglutinin (HA) and neuraminidase (NA) fused to the thermostable enzyme lichenase. All vaccine targets were produced using a plant-based transient expression system (Nicotiana). When tested in ferrets, vaccine candidates containing these engineered plant-produced influenza HA and NA antigens were highly immunogenic, and were protective against infection following challenge with homologous influenza virus. This plant-based production system offers safety and capacity advantages, which taken together with the protective efficacy data reported, demonstrates the promise of this approach for subunit influenza vaccine development.

A plant-produced influenza subunit vaccine protects ferrets against virus challenge
Influenza and Other Respiratory Viruses 2008 2: 33–40

There are a couple of interesting features of this paper, chief among them being the complete obscurity of the reasons why they use lichenase fusions, and what exactly their “launch vector” – which is what they use to express their proteins transiently – is.  Because the reference they give is incorrect – it is to a journal they erroneously call “Influenza”, which is not listed by PubMed, and turns out to be Influenza and Other Respiratory Viruses in fact – and is unavailable at our institution.  I am assuming, given the system uses a CaMV 35S promoter to drive RNA production, and they talk of “viral replication and target sequence expression from the [TMV] CP subgenomic mRNA promoter”, that the vector is a TMV-based replicon.  I was alerted by colleagues at the Journal Club to the fact that the same group used the same system – pBID4 “launch vector”, fusions to lichenase – for production of a HPV E7 vaccine in plants.  And referred to the same paper as this one does, for the vector and constructs.   Aargh!  I still don’t know why lichenase fusions are such a good idea!! 

A hint is given in the E7 paper: they say that “…these LicKM fusion proteins alone are able to activate both innate and adaptive antigen-specific immune responses”.  But they found in the paper under discussion here that alum was needed to get the best response…and they got the best yield AND immunogenicity out of their NA protein, which was expressed as a (presumably) soluble truncated native protein.  So the reason is still obscure.

The purification section of this paper is also woefully inadequate: saying “…recombinant antigens were enriched by ammonium sulphate precipitation followed by immobilised metal affinity chromatography and anion exchange chromatography, with dialysis after each step, to at least 80% purity” is NOT a method!  It is an anecdote, fit for a 1-minute talk maybe, but NOT for the Methods section of a paper.  Naughty, naughty!

Another interesting thing is the complexity of the vaccine constructs – again, exactly the same type of constructs as made for HPV E7; assembly-line vaccine producers, these guys!  These consist of the Gene of Choice (GoC) with a poly-His tag AND a KDEL (ER retention) tag at the C-terminus, AND the signal sequence of Nicotiana tabacum PR1a protein at their N-terminus.  This means (a) proteins get into the ER lumen, (b) get retained in the ER, (c) can be purified by Ni or other metal affinity column.  In addition to being fused to LickM.  Granted, the PR1 signal sequence is lost and the His tags can be removed – but the proteins still have significant “other” constituents – which is rather frowned on in a vaccine intended for humans.

I am also interested that they did not do the standard thing with their plant-produced HA GD protein and test for haemagglutination / RBC binding: this was in any case superseded by the fact that the vaccines were protective and antisera elicited by them worked in HI [haemagglutination-inhibition] assays, but it has long been regarded as a necessary first step.  I like these guys’ approach: forget the biochemistry; let’s see if it works!

All in all, a good paper despite our criticisms, which points up the very distinct possibility of being able to use plant production of influenza virus antigens for the rapid production of effective vaccines.

But I wish they’d included some more details….

MicrobiologyBytes Archive

14 December, 2007

Before I established this site, I posted a number of guest blogs to do with viruses on Alan Cann’s very wonderful MicrobiologyBytes site. Here are links to all the virus-related ones.

Maybe Not Quite The End

Posted on January 15, 2008
Review of a paper describing the receptor for the H5N1 HA protein

Given the current scare over H5N1 influenza virus in swans in the UK, it is possibly timely to recall that I wrote a little while ago in MicrobiologyBytes about how easy it appeared to be for […]

Bandicoot Blues

Posted on November 30, 2007
Description of a unique newly-described virus that looks like a chimaera of a papillomavirus and a polyomavirus

Now that the dust has begun to settle after the launch of Merck’s much-hyped Gardasil genital papillomavirus vaccine – discussed in MicrobiologyBytes here and here – people are turning again to looking at the natural history […]

Hurting rather than helping?

Posted on November 21, 2007
Some news on the failure of the Merck Adenovirus 5-vectored HIV vaccine

It should not have escaped the eye of the interested bystander that there has been a most unfortunate and premature end to a HIV vaccine trial recently – and that something that had been tested as […]

A Deeper Meaning

Posted on November 10, 2007
Some microbiology-related poetry….

I inadvertently became a published literary critic a little while ago. A long-time English Department colleague asked me for some help interpreting the collected works of possibly the most important modern poet from South Africa, and […]

Don’t look now, they’re in your genes

Posted on September 14, 2007
Description of natural insertions of virus gene fragments into a variety of organisms and how they elicit pathogen-derived resistance

And they’re protecting you! If you’re an insect, that is. Or possibly a plant.
In a remarkable convergence of news, an Israeli group led by Ilan Sela described how Israeli acute paralysis virus, which is implicated in […]

To bee or not to bee

Posted on September 11, 2007
News of how a single virus is suspected in the causation of “colony collapse disorder” of bee hives in the USA

A major recent mystery in US agriculture has been the phenomenon of “colony collapse disorder” (CCD) in honey bees. […]

This is the End

Posted on August 29, 2007
H5N1 highly pathogenic avian influenza virus mutates…

This is the End. Or the beginning of the end. Or possibly, the end of the beginning?
To misquote the immortal Bill Shankly: “It’s not a matter of life and death: it’s much more important than that”.
Having […]

Rolling down the road

Posted on August 27, 2007
Musings on rolling circle replication in viruses

In my idle moments (alas, too few these days!) I often try to think up lists of rock songs with a virus theme: you know, like “Cucumo” by the Beech Boys… “I got them ol’ burnin’, […]

Rooting the tree

Posted on August 3, 2007
News on inferring “ancestor sequences” for HIV to help make broadly effective vaccines

While fossilized viruses have never been found, we can often infer probable lines of evolutionary descent by analysis of extant genomic sequences. This sort of molecular phylogenetic approach has thrown up all sorts of interesting […]

It’s Life, Jim, but not as we know it…

Posted on July 24, 2007
Exploring what it means to be “alive”

Which could well apply to viruses, my very own favourite organisms – after all, they don’t respire, grow, excrete or any of those other good things […]

A feeling for the molechism*

Posted on June 26, 2007
Musings on what viruses are.

I think it’s permissible, after working on your favourite virus for over 20 years, to develop some sort of feeling for it: you know, the kind of insight that isn’t […]

Plus ça change, plus c’est … le same Web, only better?

Posted on June 8, 2007
A personal history of teaching Virology via the Web.

My, how things do change… I found myself reflecting, while I was looking over the detritus on our Web server of some 13 years of posting pages on the Web. “Orphan” pages, unconnected […]