What we know about swine flu, and what we don’t (LRB)

[Guest guest]

What we know about swine flu, and what we don't

May 8th 2009 Hugh Pennington, LRB Ltd., 2009.

Influenza virus has only eight genes. The molecular structure of the most

important proteins they code for is known in intimate detail. The coming and

going of its epidemics have been studied by statisticians continually since the

1840s. But predicting pandemics remains a fools' game. It falls into the

category of Alvin Weinberg's `trans-science' – a question of fact that can be

stated in the language of science but is unanswerable by it. Weinberg's examples

focused on the impossibility of predicting the probability of extremely

improbable events. There have only been three influenza pandemics in the last

century: in 1918, 1957 and 1964. The uncertainty is massively amplified by

evolution – the random and frequent genetic mutations and the swapping of genes

between bird, pig and human viruses.

For public health planners, trying to predict when a pandemic will occur is not

the only problem. Foreseeing what will happen when one starts is nearly as

difficult, because the working assumption that a brand new virus will behave in

the same way as its predecessors has a good chance of being wrong. One of the

big issues right now is whether there will be a second wave of cases next

winter, after the current epidemic in North America has run its course, and

whether their mortality rate will be higher than at present. This happened in

1918. A popular current explanation is that the virus evolved during the

pandemic to become more lethal. But there is no scientific evidence to support

this. Only three cases from the 1918 pandemic have been confirmed in the

laboratory; all died in the second wave.

Gene sequencing of viruses isolated since the beginning of the current epidemic

hasn't shown any changes, so far. The only major one has been to its name,

altered by the US Centers for Disease Control and Prevention (CDC) from 'swine

flu' to `novel H1N1 influenza' (although the CDC flu specialists have coined the

useful shorthand title S-OIV – swine-origin influenza virus). The change

signifies its most important property, which gives it pandemic potential: it is

different enough from its predecessors to make it unlikely that anyone has good

protective immunity against it. The other certainty about the virus is its

ancestry. Six of its genes are related to those found in North American pig

influenza viruses (which themselves have a mixed ancestry from bird, human and

pig viruses) and two have come from pig viruses from Europe/Asia.

This porcine origin has been a big surprise. The UK Pandemic Plan mentions pigs,

but only in passing, because its working assumption is that the next pandemic

will be caused by a bird virus. Indeed, the plan was prepared in response to the

occurrence and spread of the highly pathogenic avian H5N1 virus in poultry in

South East Asia since 2003 and the rare but lethal human infections caused by

it. `A potentially pandemic or pandemic strain . . . is most likely to emerge in

China or the Far East,' the plan says. So Mexico was another surprise. According

to the plan, `it seems reasonable to assume that, if the disease starts in Asia,

taking about a month to build up to about a thousand cases and a further two to

four weeks to spread to the UK, estimates of the mortality rate will be

available by the time it reaches the UK.' This is optimistic. More than a month

after the first laboratory-confirmed cases occurred outside Mexico, it is still

far from certain what the mortality rate will be across all age groups.

And under the heading `What We Know', the Plan says: `A pandemic flu outbreak

cannot be contained in the UK because of the large numbers of seed cases (i.e.

people bringing in the disease in from abroad) that would be expected. The

disease would be expected to spread to all major UK centres of population within

one to two weeks.' Wrong again, but pessimistic this time. After more than two

weeks, the UK is still in containment mode, aggressively searching for cases and

identifying their contacts, quarantining them, and closing schools.

That so many assumptions in the Pandemic Plan must now be questioned does not

mean that it is bad. But just as J.K.Galbraith's The Great Crash, 1929 is

enjoying a boost in sales, I guess that Neustadt and Harvey Fineberg's

The Epidemic That Never Was: Policy-Making And The Swine Flu Affair (1983) will

be reread. It describes the events that followed the first recorded death of a

healthy individual from swine influenza. was an 18-year old army

recruit at Fort Dix, New Jersey. He died on the night of 4 February 1976 after a

forced march done against medical advice; he had developed a respiratory

infection earlier in the day. The virological consensus then was that the 1918

pandemic virus came from pigs (the work of Jeffery Taubenberger at the Armed

Forces Institute of Pathology in Washington, DC has shown since that it came

from birds).

There was intense lobbying. On 24 March a `Blue Ribbon Panel' of experts met

with President Ford in the Oval Office. The decision was taken to vaccinate the

whole population. The programme started in October. But its complication rate

was higher than expected, and the virus never got out of Fort Dix. The

vaccination programme was suspended on 16 December, and never restarted. In

February 1977 Neustadt and Fineberg were commissioned by the incoming

administration to review the programme and look for lessons to be learned. Their

report was called `The Swine Flu Affair: Decision-Making on a Slippery Disease'.

Slipperiness comes not only from the changing character of the virus, but from

ignorance about it. In 1976 experts were `overconfident in theories validated

through but two or three pandemics . . . it is not that conclusions were

inconsistent with evidence, but that the paucity of evidence belied the force

with which conclusions were advanced.'

A lot of research has been done since then. But the work done on influenza in

pigs and its relevance to the evolution of new human pandemic viruses has been

almost completely overshadowed by worries about the potential threat from H5N1

bird flu. Pigs are susceptible to infection with human and bird flu strains. The

evidence that they act as `mixing vessels' in which human, bird and swine

viruses evolve by swapping their genes is sound and strong, as is the evidence

that people can be infected from pigs, and vice versa. Many papers have been

published on the subject, including one in 2005 from Yucatan in Mexico showing

that Mayans living very close to their pigs, turkeys, ducks and chickens showed

evidence of infection with swine viruses. It concluded by saying that the

human/animal encounters in Yucatan could lead to the generation of novel

reassortant viruses. But the minute of the Department of Health Joint Committee

on Vaccination and Immunisation meeting on 21 June 2006 speaks for itself:

The Advisory Committee on Dangerous Pathogens (ACDP) had noted at an earlier

meeting that the hypothesis that pigs act as the mixing vessel for influenza

viruses from which the new pandemic human strain arises is no longer widely held

to be correct as there is little evidence that a flu strain dangerous to human

health has been produced in this way.

The ACDP meeting had been convened urgently in October 2005 to consider the

public health measures that would be needed if bird flu occurred in the UK.

Most of the evidence about S-OIV comes from CDC. As of yesterday there have been

896 laboratory-confirmed cases in the US, in 43 states, with two deaths. The

average age of the cases is 15. So far the virus is behaving like seasonal flu

because it is targeting the young, and because there are many outbreaks

happening at different stages of progression. Maybe more cases than would be

expected are being hospitalised. It is too early to be certain. But so far the

elderly have been spared. It is not known whether this is because previous

influenza has given them some immunity, because the young are more susceptible,

because differences in social networks favour transmission to them, or because

there is a bias in case detection thanks to the vigorous investigation of

outbreaks in schools. It is still too early to judge the current hypothesis that

the deaths in Mexico can be explained as the tip of the iceberg of a big S-OIV

outbreak.

Whether Tamiflu, Relenza and the internet (CDC is using Widgets, Buttons,

Podcasts, eCards, Twitter/Microblogs, Online Videos, Facebook, MySpace and

DailyStrength to get its messages across) will help to bring the epidemic in

North America – at six o'clock this morning GMT, 1112 laboratory-confirmed cases

had been reported from Mexico and 214 from Canada – to a close remains to be

seen. So far the rest of the world has had very few cases, and there has been no

sustained transmission of the virus. As Sam Goldwyn said, however, `making

predictions is difficult, particularly about the future.'

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