INTERESTING from WHO

plan for 2006- 2008

http://www.searo.who.int/LinkFiles/Avian_Flu_SEA-CD-148_A4.pdf

Quick summary

excerpt...

There are three theories for the emergence of pandemic viruses:

• genetic reassortment occurring in humans or between human and
animal viruses
• direct transfer of viruses between animals and humans
• re-emergence of viruses from unrecognized or unsuspected
reservoirs

The first theory is based on the fact that both the type A(H2N2) pandemic strain
from 1957 and the type A(H3N2) pandemic strain from 1968 contained genes
derived from avian influenza viruses and human viruses (Webster, 1992). Indeed,
the main difference between these two viruses is the substitution of the gene coding
for the haemagglutinin in 1968, changing it from H2 to H3.

Due to the segmented nature of the influenza viral genome, genetic reassortment readily occurs during mixed infections. It is thought that reassortment between avian and human viruses could take place in pigs, which appear susceptible to infections with some influenza
viruses of human and avian origin (Scholtissek, 1987).
Historical records suggest that pandemic strains first appeared in China in the 1957,
1968 and 1977 pandemics. China has a large population and many communities
practice both pig and duck farming.

Also, there is wide climatic variation from North
China to South China, so that influenza infections of humans occur normally every
month of the year somewhere in this single country. This combination of factors
could be the key to the origin of influenza pandemics. Thus, it is possible that the
agricultural practices and ecological circumstances in this area provide continual
opportunities for the co-infection of animals to occur with human, avian and swine
influenza viruses.

Such co-infections would enable reassortants to arise, from which
those with human epidemic properties could then be selected through a series of
transmissions between animals or humans over an extended period of time. However,
locations other than China exist where close contact between species, including
humans, enables reassortant influenza viruses to arise that can infect humans, as
suggested by the isolation of avian-human influenza A(H3N2) reassortant viruses from
children in the Netherlands (Claas, 1994).

The second theory is best supported by genetic evidence that nucleic acid found in
tissues preserved from victims of the 1918 pandemic are closely related to genes of
early swine H1N1 viruses (Taubenberger, 1997). Swine influenza viruses themselves
appear quite closely related to avian influenza viruses (Webster, 1992). If this were so,
then the combination of evidence again would suggest an importance for avian
species as a reservoir of influenza virus genes capable of contributing to human
pandemic strains.

The possibility for direct transfer of avian viruses to humans, without
reassortment, was confirmed when pathogenic avian influenza A(H5N1) virus caused
a limited number of infections, but some with serious illness and death, in residents
of Hong Kong SAR in 1997 (WHO, 1998). Other examples of apparent direct
transmission of influenza virus from bird to human are the isolation of avian influenza
A(H7N7) from an adult in England (Kurtz, 1996) and influenza A (H9N2) in 2 cases in
Hong Kong SAR (1999). Person-to-person transmission was not found.

Superimposed on both the above theories is the possibility that only certain HA subtypes
(i.e., H1, H2, H3) have epidemic potential in humans, and that these will recycle
in humans in some manner. Such a theory is based on studies of antibodies in sera
from people alive during earlier pandemic periods. This serologic data suggests that
the pandemic virus in 1889 had an H2 haemagglutinin, related to that found in the
1957 pandemic virus, and that the pandemic virus in about 1900 had an H3
haemagglutinin related to that found in the 1968 pandemic virus. Similarly, the type
A(H1N1) virus, which reappeared in 1977, had both haemagglutinin and
neuraminidase genes (as well as all other genes) essentially the same as found in

H1N1 virus from 1950. If this theory of limitation on the sub-types capable of infecting
and transmitting in humans is true, it is not known whether these sub-types can be
maintained for 20-80 years between pandemics only in the form of animal influenza
viruses, or in some other way. It is certainly difficult to explain the close overall similarity
between the 1977 and 1950 type A(H1N1) viruses without invoking “dormancy”, which
therefore should be considered, in theory, as a third possible mechanism for
emergence of pandemic influenza viruses, despite the lack of knowledge of how
influenza virus could remain hidden for many years.