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Archive Number 20090618.2251
Published Date 18-JUN-2009
Subject PRO/AH> Influenza A (H1N1) - worldwide (67): comments on 1918 virus
INFLUENZA A (H1N1) - WORLDWIDE (67): COMMENTS ON THE 1918 INFLUENZA VIRUS
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Date: Wed 17 Jun 2009
From: Neil Rau <NRAU@haltonhealthcare.on.ca>


A question
----------
Could one of the readers or moderators please provide the virologic 
basis, if any, to support the often touted statement that the 1918 
pandemic was worse in the Fall of that year due to a mutational 
change? I don't recall exhumed bodies from the Arctic having provided 
this level of detail. This claim accompanied the recent statement 
regarding the mutations observed in Brazil [see part [1] of 
ProMED-mail Influenza A (H1N1) - worldwide (66): new strain, sequence 
analysis 20090617.2235].

--
Neil V Rau
Infectious Diseases Specialist / Medical Microbiologist
Medical Director, Infection Prevention and Control
Halton Healthcare Services,
Oakville Ontario Canada
<NRAU@haltonhealthcare.on.ca>

[An interesting question, but not one that can be answered directly. 
Some comments from ProMED-mail Moderators.

"I think the statement comes from mortality data. In a recently 
posted paper (N Engl J Med. 2009 May 7: The Signature Features of 
Influenza Pandemics -- Implications for Policy. Miller MA, Viboud C, 
Balinska M, Simonsen L)
<http://content.nejm.org/cgi/content/short/360/25/2595>
there are graphs over the estimated flu mortality in percent of total 
mortality and for the 1918 epidemic data are shown from Copenhagen 
and the total mortality due to flu was approximately 5 percent in 
July and 60 percent in November. This is interpreted as a more 
virulent virus appearing in the 2nd wave, which I think is a 
reasonable hypothesis." - Mod.EP

"The mortality data have been well known right along. I think that 
there are many different ways of interpreting these differences other 
than more virulent virus. Some of these are differences in 
populations affected, more circulation of pneumococci and 
staphylococci during cold weather, more circulation of other viral 
pathogens, more virulence and larger inocula with the crowding and 
cold air inhaled." - Mod.DK

"Since a series of isolates taken over time during the 1918-19 
pandemic is not available for genetic analysis, that opportunity to 
assess drift or mutation is not possible. That leaves change in the 
severity of the clinical picture and case fatality rates as perhaps 
the only indicators of possible changes in virulence over time. I do 
not know if those data are available and reliable, and parse out 
secondary pulmonary bacterial infection." - Mod.TY

"Given what I believe is an 'n' of 1 for the number of Frankenstein 
(reanimated) 1918 viruses that have been studied, there are no data 
on phenotypic or genotypic changes from spring to fall virus." - 
Mod.LL

With the availability of the complete 1918 influenza virus coding 
sequence, derived from fixed and frozen lung tissue of 1918 influenza 
victims, it was possible using reverse genetics to generate an 
influenza virus bearing all 8 gene segments of the pandemic virus, 
allowing study of the properties associated with its extreme 
virulence. In contrast to contemporary human influenza H1N1 viruses, 
the 1918 pandemic virus had the ability to replicate in the absence 
of trypsin, caused death in mice and embryonated chicken eggs, and 
displayed a high-growth phenotype in human bronchial epithelial cells 
(see Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne 
DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A: 
Characterization of the Reconstructed 1918 Spanish Influenza Pandemic 
Virus. Science. 2005, Oct 7; 310(5745): 77-80; abstract available at 
<http://www.sciencemag.org/cgi/content/abstract/310/5745/77>).

The sequence of the 1918 virus is presumably derived from aggregated 
material and not from biologically cloned isolates. As far as I am 
aware there are no sequences derived from material isolated 
sequentially during the course of the pandemic, indeed the 1st 
isolates of human influenza virus date only from the 1930s. That 
apart due to the inherent high mutability of viruses with RNA genomes 
it is a difficult task in any situation to unequivocally attribute 
specific genetic changes conferring altered virulence during the 
course of a single epidemic. - Mod.CP]

[If others have substantive data (serology?), we would be interested 
in learning more. - Mod.LM]

[see also:
Influenza A (H1N1) - worldwide (66): new strain, sequence analysis 
20090617.2235]
...................................cp/mj/lm

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