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Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

L

Laidback Al

Well-known member
Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza
A(H5N1)?
<o:p> </o:p>
As of today, the case counts of S-OIV infections still seem to be climbing. Accurate mortality and morbidity data are not yet available, but this novel virus, although capable of human to human transmission, does not appear to be exceptionally virulent. Influenza A (H1N1) has been found in 24 countries and has infected at least 2371 individuals, but to date only 44 deaths have attributed to this novel virus.
<o:p> </o:p>
In contrast, Influenza A (H5N1) is exceptionally lethal, killing 6 of every 10 infected individuals (based on WHO case counts). Since WHO began tracking Influenza A (H5N1) cases in 2003, there have been 423 cases identified in 15 countries. Of those, fully 61% or 258 have died, the most recent death occurred in <st1:country-region w:st="on"><st1:place w:st="on">Viet Nam</st1:place></st1:country-region> on April 22. So far, Influenza A (H5N1) has been lacking the capabilities to easily transmit between humans.
<o:p> </o:p>
Confirmed Influenza A (H1N1) cases are now starting to be reported in countries that have had previously confirmed human cases of Influenza A (H5N1). The possibility exists that some where in the world there could be a human coinfection of Influenza A (H1N1) with Influenza A (H5N1) and that the highly virulent Influenza A (H5N1) could pick the transmissibility characteristics of Influenza A (H1N1) or alternatively that Influenza A (H1N1) could pick up the virulence of Influenza A (H5N1).
<o:p> </o:p>
So, it is time to speculate on where that coinfection might be most likely to occur. But first we need to consider the demographics of the Influenza A (H1N1) outbreak as we understand them today.
<o:p> </o:p>
Over the past few days the CDC has been revising the median age infection downward, it is now at 15 years for Influenza A (H1N1) with a dozen cases of children under 1 year old. A newly published article on 11 human cases of swine flu infections between 2005 and early 2009 indicates that the median age of the infected individuals was 10 years old. This indicates to me that the Influenza A (H1N1), and possibly earlier recent swine flu infections, represent a children?s disease, rather than a disease that attacks young healthy adults as is expected with a pandemic virus.
<o:p> </o:p>
But is this even a pandemic virus? Twenty-first century technology and world wide surveillance and monitoring have identified this novel virus and numerous infections. But would a novel virus of this nature have even been detected 90 years ago by public health officials who had to rely on epidemiological data? At that time, influenza viruses were only recognized by their effects on the population through epidemiological analysis, more people getting sick, more healthy adults getting sick and dying, etc. While we don?t have all of the numbers yet for this outbreak of Influenza A (H1N1), it may only represent a late season bump on the world wide influenza patterns for the 2008-2009 season.
<o:p> </o:p>
One question that is often posed about the 1918 pandemic is how could the virus spread so quickly around the world. There are conflicting reports that it started in various locations around the world just about the same time, yet this was the era of horse and buggy transportation. Perhaps this current outbreak of Influenza A (H1N1) suggests a potential answer. It may be that the world-wide seeding mechanism for a pandemic virus is spread of a novel, but minimally lethal, virus through children and young adult populations first, and only later infecting healthy adults and older individuals perhaps in later waves with higher virulence.
<o:p> </o:p>
Given this argument about world seeding of a novel virus, one might ask where in the world would this novel swine-based strain reassort or recombine with an existing strain of Influenza A (H5N1) to produce an easily transmissible, potentially highly virulent pandemic strain of either Influenza A (H1N1) or Influenza A (H5N1).
<o:p> </o:p>
I assume for a particular location to be the geographical candidate for the mixing vessel, it would have to take place in country where there have been many cases of human Influenza A(H5N1) infection over the years. For no particular reason, I set the initial cut off at 25 or more cases. If a country has 24 or less confirmed human cases I removed it from consideration. Of the 15 countries with human Influenza A (H5N1), There are only five that have had 25 or more cases, <st1:country-region w:st="on">China</st1:country-region>, <st1:country-region w:st="on">Egypt</st1:country-region>, <st1:country-region w:st="on">Indonesia</st1:country-region>, <st1:country-region w:st="on">Thailand</st1:country-region>, and <st1:country-region w:st="on"><st1:place w:st="on">Viet Nam</st1:place></st1:country-region>.
<o:p> </o:p>
Considering that <st1:country-region w:st="on">Thailand</st1:country-region> has only had 25 human cases and the last one was in 2006, I don?t consider <st1:country-region w:st="on"><st1:place w:st="on">Thailand</st1:place></st1:country-region> as a likely location for a genetic interaction between Influenza A (H1N1) and Influenza A (H5N1). Likewise, I don?t think <st1:place w:st="on"><st1:country-region w:st="on">Viet Nam</st1:country-region></st1:place> is a likely candidate. Although <st1:country-region w:st="on"><st1:place w:st="on">Viet Nam</st1:place></st1:country-region> initially had many cases in 2003 and 2004, the number of cases has fallen over the last two years (although they may be increasing in 2009).
<o:p> </o:p>
That leaves three high potential countries, <st1:country-region w:st="on">China</st1:country-region>, <st1:country-region w:st="on">Indonesia</st1:country-region>, and <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region>. I believe that <st1:country-region w:st="on"><st1:place w:st="on">China</st1:place></st1:country-region> learned some lessons from the SARS episode several years ago. I think that <st1:country-region w:st="on">China</st1:country-region> has specific contingency plans to restrict and control any outbreak of either Influenza A (H1N1) and Influenza A (H5N1) as demonstrated by the recent quarantine measures in <st1:place w:st="on">Hong Kong</st1:place>. A strong central government with tight political and economic control, such as <st1:country-region w:st="on"><st1:place w:st="on">China</st1:place></st1:country-region>, may be able to contain an outbreak of a virulent pandemic virus, regardless of its origin. I don?t think that a lethal pandemic virus will escape immediately from <st1:country-region w:st="on"><st1:place w:st="on">China</st1:place></st1:country-region>.
<o:p> </o:p>
<st1:country-region w:st="on"><st1:place w:st="on">Indonesia</st1:place></st1:country-region> is the next potential candidate country. Influenza A (H5N1) is known to be endemic in the poultry throughout the country. Indonesia has the highest number of confirmed human Influenza A (H5N1) cases in the world, many of those human cases have been concentrated in the greater Metropolitan Jakarta area where the population density is very high. <st1:place w:st="on"><st1:country-region w:st="on">Indonesia</st1:country-region></st1:place> has the highest case fatality rate (CFR) of the five countries with more than 25 human Influenza A (H5N1) cases. Based on current WHO data, the Indonesia CFR is about 82%; more than 8 out of every 10 confirmed cases in <st1:place w:st="on"><st1:country-region w:st="on">Indonesia</st1:country-region></st1:place> dies directly or indirectly from Influenza A (H5N1) infection.
<o:p> </o:p>
Recently, <st1:country-region w:st="on"><st1:place w:st="on">Indonesia</st1:place></st1:country-region> has officially declined to report human Influenza A (H5N1) cases in a timely manner. Besides the 141 officially reported cases by WHO, locals news reports have identified perhaps another half dozen individuals who were locally confirmed with Influenza A (H5N1), but who have not yet been reported to WHO. The artificially high CFR from Indonesia probably results from the fact that local news media can and do follow up on deaths attributed to bird flu, in some cases forcing the Health Ministry to report these deaths from Influenza A (H5N1) infection.
<o:p> </o:p>
However, in the short run, I don?t think that <st1:country-region w:st="on"><st1:place w:st="on">Indonesia</st1:place></st1:country-region> will be where Influenza A (H1N1) and Influenza A (H5N1) comingle and escape. It is clear that <st1:country-region w:st="on"><st1:place w:st="on">Indonesia</st1:place></st1:country-region> is assaulting any potential cluster of Influenza A (H5N1) with a Tamiflu ?blanket?. Any potentially infected individual is immediately treated with Tamiflu. Family members, friends, neighbors, or anyone else who had contact with the individual including health care workers are routinely given Tamiflu as a prophylaxis to minimize infectious spread. Given this breadth of experience of coping with the largest number of human Influenza A (H5N1) infections in the world coupled with indiscriminate distribution of Tamiflu, I think Indonesia will be able to contain a reassortment of Influenza A (H1N1) for a while, but only until either Influenza A (H1N1) or Influenza A (H5N1) loses its sensitivity to Tamiflu.
<o:p> </o:p>
Finally we are left with <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region>. In my estimation, <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region> is the most likely country for the origin of a novel pandemic virus with high virulence coupled with ease of transmission through reassortment or recombination of the Influenza A (H1N1) and Influenza A (H5N1).
<o:p> </o:p>
Like <st1:country-region w:st="on">Indonesia</st1:country-region>, Influenza A (H5N1) is known to be endemic in the poultry throughout the country and <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region> has not been able to eradicate it. Unlike <st1:country-region w:st="on">Indonesia</st1:country-region>, <st1:country-region w:st="on">Egypt</st1:country-region> does not have much experience suppressing clusters with Tamiflu because the strain(s) circulating in <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region> have not yet produced long H2H2H chains. Also, the strain(s) in <st1:country-region w:st="on">Egypt</st1:country-region> seem to be less virulent than those circulating in <st1:country-region w:st="on">China</st1:country-region> and <st1:country-region w:st="on"><st1:place w:st="on">Indonesia</st1:place></st1:country-region>. Less virulence means a greater likelihood of H2H transmission before it is detected and contained.
<o:p> </o:p>
Containment of a reassorted virus in <st1:place w:st="on"><st1:country-region w:st="on">Egypt</st1:country-region></st1:place> will be difficult. Population densities in lower Egypt in the Nile Delta region are among the highest in the world. This is the area of <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region> where most of the Influenza A (H5N1) cases have occurred. Once a virulent and highly transmissible virus originates in this area, the reproductive number could be very high.
<o:p> </o:p>
Finally, the demographics of Influenza A (H5N1) infections in <st1:country-region w:st="on">Egypt</st1:country-region> suggest that <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region> is a suitable breeding ground for a new, lethal pandemic reassortment of Influenza A (H5N1) and Influenza A (H1N1). Ten of the last 13 human cases of Influenza A (H5N1) infections in <st1:country-region w:st="on"><st1:place w:st="on">Egypt</st1:place></st1:country-region> were toddlers under 3 years of age. While most of them have recovered, almost all required hospitalization. Half of all of the confirmed cases of Influenza A (H1N1) in <st1:country-region w:st="on">USA</st1:country-region> and <st1:country-region w:st="on"><st1:place w:st="on">Mexico</st1:place></st1:country-region> are under 19 years of age. This suggest to me, that toddlers, young children, and teenagers in Egypt provide the perfect mixing vessel for a dual infection of Influenza A (H1N1) and Influenza A (H5N1) and the development of a novel strain of influenza with much increased virulence. It seems that me that the most likely location for a reassortment of Influenza A (H1N1) and Influenza A (H5N1) will take place in toddlers or young children in the Nile Delta region of Egypt and could result in a second and more lethal wave of Influenza A (H1N1) in the next several months when the next influenza season start in the northern hemisphere in August or September.
<o:p> </o:p>
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

Good post, Al. I cannot argue with what you are saying.

I wonder what WHO and CDC would make of it. We never hear them talk about H1N1 meeting up with H5N1, but surely they must think about it. It was the first thing I thought about when learning how transmissible the new H1N1 was.
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

why should this be a problem ?
H5N1 had reassorted a lot already with other (avian) strains.

seasonal H1N1,H3N2 should be the bigger danger ---wait,
in a pandemic swine flu may kill those ...
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

Despite the immense opportunity H5N1 has had to reassort with other type and subtypes (and in facts, it really reassorted with H9N2), it is not happen it became quickly transmissible among humans.

Conversely, a unique novel H1N1 strain emerged in North America, where the surveillance is considered excellent.

The reassortment event(s) is not well understood at this moment.

The animal reservoir remains to be established.

And thus I continue to repeat my question:

Why should this novel H1N1 virus have to reassort or recombine with H5N1 and not with H9N2 (as this latest is already well established in swine population)?

Why does people need to seek the worst of the worst when a pandemic is ongoing and the most urgent quest is to reach a consensus on vaccine manufacturing and treatment regimen for the most wide portion of world population?

Recombinations theories failed to predict this evolution of swine influenza.

People should start to be more cautious when drawing future scenarios when data is scarce and model not so perfect.

Our main quest is to protect ourselves and those in need, not to design The End of The World Virus Perfect Model.

I am very disconcerted.
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

IOH:

YOur concerns are why I left H5N1 out of the discussion of the "genetics menu" thread I started. I think we need to concentrate on the most likely. It may not make for such an "exciting" discussion", but I find it a far more productive use of my time.

I'm also concerned that this low-mortality(so far) epidemic is displacing discussions and siphoning resources away from other preventible disease that is causing far more deaths.

.
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

I absolutely agree with you.

The derelict conditions of hundreds of millions of people is the most important contribute to the emerging infectious diseases spreading around the world.

But people in need continue to remain at the bottom of the discussion these days (in the mainstream media), as happened before.

Thank you for the interest in these crucial issues.
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

Excellent post Laidback al.

Just my 2 cents.

China has the largest population in the world, by FAR the largest pig production in the world and the second largest poultry production in the world (after the US)

http://www.xist.org/default1.aspx

http://indexmundi.com/agriculture/?commodity=swine-meat&graph=production

http://indexmundi.com/agriculture/?commodity=broiler-meat&graph=production

Also they tend to be very secretive about reporting things like cases of bird flu.

Statistically isn't China likely to be the first place this will happen?

Mind you, after reading this post this morning by Dutchy this morning, Indonesia might be a good candidate too.

http://www.flutrackers.com/forum/showthread.php?p=230833#post230833

Tamiflu blankets don't inspire much confidence in me for some reason.:(
 
Re: Discussion: Where in the World will S-OI A (H1N1) meet up with Influenza A(H5N1)?

Finally, people must start to recognize that a pandemic cannot be stopped when it is so widespread.

The reality of the facts is that this novel H1N1 virus cannot be contained and its path toward full blown outbreaks in Asia and elsewhere is unavoidable.

Any other discussion appears to me futile.

We are in the same situation world was decades ago: even when health authorities states that ''the world is well prepared to flu pandemic'' the only thing clear is that we are seeing the greatest fiasco in the history of WHO influenza surveillance.

No words about surveillance in nothern America...

Pandemic is in the facts, now, here and no denial is further acceptable.
 
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