Tag: Flu

Another day in bed as Greg’s Spanish Flu, aka Merville Fever, continued.  Still no flying for him.  But what was the origin of Spanish Flu?  

Diary

Saturday June 22nd. Stayed in bed all day. 

Origin of Spanish Flu

After yesterday’s excursion into epidemiology, here’s a bit of a voyage into virology. (We’ll return to aviation soon enough.)

Let’s get one thing out of the way first: the origin of Spanish flu is probably not Spain.  It is generally thought that the name came about because Spain’s neutrality in the First World War merely permitted more extensive reporting of the pandemic.  See Trilla et al. Clinical Infectious Diseases 47(5) 668–673 (2008) (https://doi.org/10.1086/590567) for more.

We now know – but in 1918 they didn’t – that the causative agent of flu is a virus.  At the time, it was thought to be caused by a bacterium, Haemophilus influenzae, which is now known to be the cause of various other conditions, including some cases of bacterial meningitis.

Viruses

Like all viruses, influenza virus isn’t really a living entity.  It’s a package of genetic material (in this case RNA rather than DNA) wrapped up in a protein-studded lipid (fatty) coat.  It can’t reproduce on its own.  It can only replicate by infecting a host cell and hijacking the cell’s replication machinery.  The infected host then churns out vast quantities of progeny virus, and the cycle begins again.

Today we know what the virus looks like.  Here is an electron micrograph of a recreated form of the 1918 Spanish Flu virus: 

Surface Proteins and Subtypes

Among the proteins studding the lipid coat of the virus particles (which are in the order of 100 nm in diameter), two that are important for the way that the virus infects its host cells are haemagglutinin (abbreviated HA or H) and neuraminidase (NA or N).  Haemagglutinin is involved in the virus binding to the host cell, and neuraminidase assists in viral trafficking.  Here’s a schematic  picture of a flu virus particle:

Although there are three kinds of influenza virus, A, B and C, it is only influenza A that poses a serious threat to public health.  The 1918 so-called Spanish Flu was an example of influenza A.  We now know (see below) that it was a subtype known as H1N1, so called because it contains haemagglutinin of subtype 1 (of 16 known subtypes) and neuraminidase of subtype 1 (of 9). Formally, the Spanish Flu virus is therefore known as 1918 A(H1N1) influenza.

Reassortment

When a flu pandemic arises, it is often because of genetic reassortment of the virus. This arises when two different viruses infect the same individual (human or another susceptible species such as pigs or birds).  Because the RNA in the nucleus is in different segments, these segments can reassort to give a new genetic combination.  In this way, an H1N1 virus might reassort with an H5N3 virus to give an H5N1 virus, say (not a random example, but that is another story). And the human immune system might not have ‘seen’ this reassortment before – at least in the recent past – and therefore have no effective immunity against it.

And the Origin of Spanish Flu is…

…actually not clear.  It seems that the reassortment mechanism just discussed did not give rise to the  Spanish Flu virus in 1918. Taubenberger and colleagues, working in the mid-1990s with archival influenza autopsy materials collected in the autumn of 1918, sequenced the RNA of the virus and determined it to be an H1N1 subtype and similar to a bird flu virus from an unknown source.  (For a review, see Taubenberger & Morens “1918 Influenza: the Mother of All Pandemics” Emerg Infect Dis. 2006;12(1):15-22 (https://dx.doi.org/10.3201/eid1201.050979)). Similar to a bird flu virus, that is, but not exactly the same:  it had a mutation, or mutations, that enabled it to infect humans – and pigs.  So this proposed bird flu-like virus seems to have been new – immunologically speaking – both to us and to pigs. 

It has to be said that not everyone goes along with the Taubenberger bird virus origin theory.   A lively debate in the pages of Nature testifies to that.  And even Taubenberger says that it is not just a question of a single mutation arising in a pre-existing H1N1 bird flu.  That theory is discounted by the large number of mutations found between the 1918 virus and known bird flu viruses.  For the moment, the answer to the question “what is the origin of Spanish Flu?” is the unsatisfactory “we don’t really know”.  But the bird flu theory is still a contender. 

A Live Issue

Intriguingly, this is not merely a question of historical interest.  The legacy of the 1918 Spanish Flu is still with us today. The reason that Taubenberger & Morens called the Spanish Flu pandemic in 1918 “the mother of all pandemics” in the title of their 2006 review article is that, in their words :

All influenza A pandemics since that time, and indeed almost all cases of influenza A worldwide…, have been caused by descendants of the 1918 virus.

Yet another long shadow cast from the years of the Great War.

Greg’s flu – ‘Merville Fever’ as he called it yesterday – continued.   Today he said it was Spanish Flu.  Unsurprisingly, he did not fly.

Diary

Friday June 21st. Stayed in bed all day.  (Known in England as ‘Spanish Flu’.)

Spanish Flu

Greg equates what was evidently known within 42 Squadron as ‘Merville Fever’ with Spanish Flu.  Possibly the words in brackets in his diary entry were added at a later date.  But in any event, can he really have been talking about the same ‘Spanish Influenza’ that killed so many in 1918 and 1919? Especially  if, as he said yesterday, it was merely “a sort of ‘flu lasting three or four days”?

Perhaps surprisingly, the answer was quite probably ‘yes’ – for a couple of reasons.  (Nice bit of epidemiology coming up.)  

The W-Curve

First, he was the right age not to be too badly affected.  At 19 and in good health he would have had a fairly robust constitution.  Furthermore, the 1918-19 influenza pandemic did not affect all age groups equally.  Mortality was greatest among children under four and among the elderly – two immunocompromised groups –  as one might expect. Also, there was also a curious minor peak of mortality among those aged 25-34, but Greg’s age put him only on the lower slopes of that peak. 

Because of the minor peak among 25-34 year olds, a plot of mortality rate against age for the 1918-19 pandemic became known as the W-curve. This contrasts with the more expected U-curve that was seen in earlier years between pandemics:

The Three Waves

Secondly, as shown by the following plot of mortality rate against time (not age of patient, as in the above figure) there were three waves of the 1918-19 influenza pandemic, of unequal lethality. They were:

• A first, mild wave in June/July 1918;
• The second, most severe wave in Autumn 1918; and
• A third, moderately severe wave in Spring 1919.

We see this three-wave pattern even more clearly from the UK data shown in Figure 1 of Taubenberger & Morens (2006), cited above:

Greg’s illness was in the first wave, which had the least rate of mortality of the three waves. 

Not a Great Threat

So all in all, Spanish Flu – or Merville Fever – was by this stage not the great threat that it became, particularly for a young man of his age.  At the time, it was quite plausibly regarded as “a sort of ‘flu lasting three or four days”.  This is entirely in line with the observation by Taubenberger & Morens (2006) that:

Despite the extraordinary number of global deaths, most influenza cases in 1918 (>95% in most locales in industrialized nations) were mild and essentially indistinguishable from influenza cases today.