Archive for June, 2009

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about the immediate origin of the epidemic, despite the fact that we included a panel of closely related and previously unpublished swine influenza isolates.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.

And now it’s here

24 June, 2009

Yes, H1N1 “Mexico” flu is in South Africa: from the Mail & Guardian of 18th June.

H1N1 flu virus in the country, the Department of Health said on Thursday.

Spokesperson Fidel Hadebe said the results of laboratory tests confirmed the case in the early hours of Thursday. [after apparently having shown signs of fever in Atlanta! - Ed R]

Hadebe said the patient, a 12-year-old child, arrived in South Africa from the United States on Sunday.

The child had flu-like symptoms and was admitted to a private hospital on Monday morning.

“The patient was kept in isolation and discharged after a few days in hospital. He is well and recovering in isolation at home,” he said.

“All contacts have been followed up and given necessary advice and treatment.”

The case was dealt with in accordance with the World Health Organisation and the health department guidelines, Hadebe said.

More details were not immediately available.

Last week, the World Health Organisation declared the outbreak a pandemic. – Sapa 

 Latest news on the global front from ProMED:

As of 07:00 GMT+2 today [22 Jun 2009], there have been a total of 52 160 cases with 231 deaths attributable to influenza A(H1N1) infection confirmed to WHO from 92 countries. New countries that have confirmed cases and reported to WHO since the last update (19 Jun 2009) include: Algeria, Bangladesh, Brunei Darussalam, Fiji and Slovenia.

In addition, according to newswires, new countries reporting cases since the release of the daily WHO summary include Antigua and Iran.

There are still newswires mentioning confirmation of 2 cases of H1N1 in Ethiopia, but official confirmation to WHO is still pending. In addition, there are newswires mentioning suspected cases in Cote d’Ivoire and the Democratic Republic of the Congo (Kinshasa), but until there is mention of laboratory confirmation, these should be viewed as suspected cases and not confirmed cases. – Mod.MPP

So it’s in Africa for sure, and probably quite widespread.  In the Nature issue of the 11th June, Erika Check Hayden had this to say concerning the southern hemisphere flu season which is presently upon us:

People in poor nations already suffer from a higher incidence of conditions, such as malnutrition and HIV, that make them more vulnerable to the new virus. In addition, they are likely to be left out of the global scramble for a vaccine, which has already started as nations such as the United States and Britain rush to tie up vaccine contracts.

But perhaps the biggest global challenge is arriving now, as the Southern Hemisphere enters its flu season and swine flu threatens many of the least-ready countries. “In general, the developing countries are not prepared,” Oshitani says. The World Bank has released billions of dollars for preparedness in these regions, but many developing nations still do not have plans for dealing with a pandemic — and some that do have simply cut and pasted versions of plans from developed countries, which do not apply to poorer nations unable to afford vaccines and antivirals. 

Which is nothing new to readers of this blog…but alarming all over again.

Good news – potentially – comes from the realms of vaccine pharming: at the Plant-Based Vaccines and Antibodies meeting in Verona recently, Marc-Andre D’Aoust of Medicago Inc and Vidadi Yusibov of Fraunhofer USA detailed how they had managed to produce pilot batches of several grams of purified pandemic H1N1 HA protein from plants, in less than a month from obtaining the sequence.

I know I’d eat the plant directly, if it’d keep the flu away – but that’s just me.  Don’t try this at home…!

…In Fact, It’s Coming Here

10 June, 2009

From ProMED this morning:

INFLUENZA A (H1N1) – WORLDWIDE (60): EGYPT (CAIRO)

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

A ProMED-mail post

Date: Tue 9 Jun 2009
Source: Angola Press Agency (Angop) [in French, trans. Mod.FE, edited]

The influenza A (H1N1) virus has been detected in 2 foreign students of the American University of Cairo while [another 140 students] have been placed in quarantine, as we learnt from the medical services and the establishment.

Police officers wearing masks were stationed in front of their university dormitory in the Zamaleck area between the 2 arms of the Nile. Nobody was allowed either to go in or to come out.

“Two students were confirmed positive for the H1N1 virus.  Consequently, the residence was placed under quarantine for 24 hours,” a representative of the university declared, adding that a 3rd student who had fever, had been hospitalized for precautionary motives. All the students shall be subjected to a screening test.

The 1st Egyptian case of influenza A was detected last Tuesday [2 Jun 2009]. It is a 12-year-old American girl who arrived on holiday in Cairo. It is equally the 1st case detected in Africa.

Communicated by: ProMED-mail

[This is an update providing some details of the 1st case of influenza A (H1N1) in Egypt and Africa as a whole. Despite all the awareness of this novel virus raised in the last month in most countries in the world, it seems the disease is spreading steadily across the globe.

This new outbreak is particularly concerning as there is concurrent circulation of H5N1 virus in both human and poultry populations, increasing the pathways by which a highly transmissible and high mortality virus could evolve. [EPR: my bold]

ProMED-mail will be interested in the sequence of events following the detection of cases of influenza A (H1N1) in Egypt. – Mods.FE/PC]

And so it begins….  While a lot of people are eagerly watching the unfolding, essentially in real time, of what MUST be termed a pandemic whether the WHO wants to call it that or not, there is a very real human element to this unfolding phenomenon.

That is, a LOT of people in Africa and elsewhere in the developing world will get sick – and many may die, whether or not this is a “mild” flu.  Declan Butler, writing in the 27th May online version of Nature, says this:

“With the influenza season over in the temperate Northern Hemisphere, and just getting under way on the other side of the world, scientists are watching the A(H1N1) swine flu virus to see where it goes next and whether it will reassort with other flu viruses, or mutate, to cause more severe disease or acquire resistance to antiviral drugs.

Some researchers are warning, however, that such changes might be more likely to occur not in the northern or southern temperate zones where flu is seasonal, but in the narrow, often-overlooked belt of tropical countries where flu circulates all year round.”

And later:

“Surveillance is not just academic; it is key to getting early warnings of events that call for swift adaptations of control strategies. Swine flu is currently sensitive to the antiviral drug oseltamivir (Tamiflu), for example, but seasonal H1N1 is resistant. Were the new virus to acquire resistance, that would render redundant the Tamiflu stockpiled by many nations as part of their pandemic plans.

Tropical countries may be pivotal in such changes. “Tropical zones are the black box of influenza,” says Antoine Flahault, dean of the French School of Public Health in Rennes and Paris. Tropical southeast Asian countries in particular are a hotbed of flu viruses, ranging from H9N2 in children in Hong Kong and China, to H6N1 in birds and, by far the most prevalent, H4N6 in ducks and other waterbirds. The threat of reassortments occurring in poor tropical countries is compounded by the fact that humans tend to live in close proximity with livestock. “If it reassorts, who knows what could result,” says Shortridge.”

What a pleasant prospect…!  As for the sociopolitical side, the WHO is holding off declaring this to be Stage 6 of a pandemic – for who knows what reason, given that human-to-human sustained chains of transmission have been amply demonstrated outside of the place of origin.

Debora MacKenzie, writing in the 22nd May issue of New Scientist, says the following:

“The WHO rules for declaring different degrees of flu pandemic threat are based on epidemiology (how the virus is spreading) for good reasons. This is because any new flu virus to which most of the world has little immunity, and which spreads well enough person-to-person to escape its continent of origin, is very likely to go global, and to cause more sickness and death than flu usually does. That is the definition of a flu pandemic.

The virus’s ability to spread is what matters. H5N1 bird flu has travelled across Eurasia, mainly in birds, but it hasn’t spread readily in people, so it isn’t a pandemic.

The Mexican swine flu H1N1, however, has. When it spread across the Americas, the WHO followed its rules and declared it a level 5 situation; one down from a pandemic. When it starts spreading outside the Americas, through “community transmission” – meaning it crops up generally, not just in people who have visited Mexico or New York recently or their contacts – that means it’s got a foothold globally.

A flu that can do that is very unlikely to stop there. The WHO rules make that a full-blown level 6 pandemic.

And frankly, that is starting to happen. As I write, the number of confirmed cases in Japan (and that’s just people sick enough to see a doctor and get tested) has jumped by 35 in the past 24 hours, to nearly 300, mostly due to that perennial vector of flu, the gregarious teenager. The main cluster started without any known links to the Americas.

Meanwhile in Europe, countries are deliberately not testing cases that could be community acquired – almost as if someone doesn’t want to trigger level 6.”

I wonder why….  Global economic meltdown, possibly?  We watch and wait.  Meantime, the last word from New Scientist again – from an editorial in the June 6th issue:

Just do the swine flu tests
06 June 2009

GREEK doctors and flu scientists are saying what New Scientist revealed two weeks ago: swine flu could be spreading round Europe undetected because people without known links to flu aren’t being tested (see “Europe should test more broadly for swine flu”).

Maybe countries worry that if they test, they’ll be forced to use precious antiviral medicines on a mild strain. Maybe they just want this virus to spread quietly, so people will become immune to its successors. Maybe a basic understanding of epidemiology is lacking, though that seems unlikely.

But we know one thing: the only item of faith you need in science is that it’s better to know than not to know. If Europe’s leaders want everyone’s trust – trust they will need if this virus really does go global – it should emulate Australia, and do the tests.”

Amen.

Down, Lujo!

4 June, 2009

I am indebted to Ms Ngimezi Phiri – muli bwanji! – in the MCB2016F class, to whom I have just lectured Virology, for pointing this out – from Yahoo! News:

Scientists identify new lethal virus in Africa

By MIKE STOBBE, AP Medical Writer  Thu May 28, 9:15 pm ET

ATLANTA – Scientists have identified a lethal new virus in Africa that causes bleeding like the dreaded Ebola virus. The so-called “Lujo” virus infected five people in Zambia and South Africa last fall. Four of them died, but a fifth survived, perhaps helped by a medicine recommended by the scientists.

It’s not clear how the first person became infected, but the bug comes from a family of viruses found in rodents, said Dr. Ian Lipkin, a Columbia University epidemiologist involved in the discovery.

“This one is really, really aggressive” he said of the virus.

A paper on the virus by Lipkin and his collaborators was published online Thursday on in PLoS Pathogens.”

Of course, regular readers of this blog will be familiar with the Zambian arenavirus discovered under tragic circumstances last October, and covered here as follows:

Now the agent has a name – albeit an unfortunate victim of political compromise; they are calling it “Lujo” after Lusaka (where it came from, sort of) and Johannesburg, where nearly everyone who got it was treated.

The (relatively) rapid characterisation of the virus owes a lot to modern technology: in the words of the authors (MCB3019F take note – this is serious viromics…):

“RNA extracts from two post-mortem liver biopsies (cases 2 and 3) and one serum sample (case 2) were independently submitted for unbiased high-throughput pyrosequencing. The libraries yielded between 87,500 and 106,500 sequence reads. Alignment of unique singleton and assembled contiguous sequences to the GenBank database … using the Basic Local Alignment Search Tool (blastn and blastx; …) indicated coverage of approximately 5.6 kilobases (kb) of sequence distributed along arenavirus genome scaffolds: 2 kb of S segment sequence in two fragments, and 3.6 kb of L segment sequence in 7 fragments (Figure 2) [see here for depiction of arenavirus genome]. The majority of arenavirus sequences were obtained from serum rather than tissue, potentially reflecting lower levels of competing cellular RNA in random amplification reactions.”

Sequence data was used to allow primer synthesis for cDNA PCR to fill in gaps, and the whole genome is now available.  It is a novel arenavirus, with all genome segments giving the same sort of phylogenetic tree topology, which shows the virus to be near the root of Old World arenaviruses.

The authors conclude:

“To our knowledge is LUJV the first hemorrhagic fever-associated arenavirus from Africa identified in the past 3 decades. It is also the first such virus originating south of the equator (Figure 1). The International Committee on the Taxonomy of Viruses (ICTV) defines species within the Arenavirus genus based on association with a specific host, geographic distribution, potential to cause human disease, antigenic cross reactivity, and protein sequence similarity to other species. By these criteria, given the novelty of its presence in southern Africa, capacity to cause hemorrhagic fever, and its genetic distinction, LUJV appears to be a new species.”

Ex Africa, semper aliquid novi(rus)…B-)


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