Scott McPherson's Web Presence

A reader of this Blogsite, Jonathan Singleton, asked me to comment on the recent proMED report regarding Na Tao, Vietnam.  As you may know, Na Tao is at the heart of a possible cluster of human cases of bird flu.  My previous two blogs have covered this developing situation.

The proMED report in question is below.

Influenza A (H5N1) is not transmitted from human to human

---------------------------------------------------------------------------

Yesterday afternoon [14 Apr 2010], at a meeting of the National Steering Committee for pandemic influenza control and prevention, Dr Tran Nhu Duong, Deputy Director of the National Institute of Hygiene and Epidemiology confirmed that influenza A (H5N1) has not been transmitted from human to human.

The investigation of the Institute on 2 cases of influenza A (H5N1) in Na Tao village, Nhu Co commune, Cho Moi District, Bac Kan province did not detect human to human virus transmission.

Reports of two investigation teams of the Institute in Bac Kan showed that the two patients were living about 100 meters apart, and they had never been in direct contact with each other.

All 33 people who had contact with the patients, including relatives, visitors, neighbors, nurses, and physicians, were tested and monitored for 16 days. There has been no case with symptoms of the disease. All the test results were negative.

Communicated by:

PRO/MBDS

<promed-mbds@promedmail.org>

As we now know, there are three suspected human cases, not two.  But that is not material to our discussion.  What is material is that two persons, living about a little more than a football field's distance apart, contracted H5N1 bird flu. 

The report seems to conclude that distance alone, coupled with a lack of direct contact of one with another, eliminates the possibility of human-to-human (H2H) transmission.  That sounds logical enough.

But the larger issue -- the proverbial elephant in the room -- is this:  Has the virus itself changed enough in Na Tao, Vietnam, to allow for an easier method of transmission from avian to human respiratory cells?   If so, that disclosure would prove to be almost as big (and ultimately more potentially troublesome) than another H2H cluster.

That is a question that the Vietnamese report does not answer.

Let's consider the facts.  Three persons in one district contract bird flu.  Apparently they all contracted it via contact with diseased poultry.  That tells me that either the virus in that area of Vietnam is more potent, and/or the ability of the virus to favor human epithelial cells as much as it favors chicken epithelial cells.

We all know from reading the research papers that this proclivity toward one species or another is primarily driven by temperature.  The fact that both diseased poultry and diseased villagers have been detected in a cluster bears investigating by the WHO.  For a cluster is a cluster whenever you get multiple persons in a close area, H2H or no H2H.  Three B2H bird flu cases in one hamlet should be significant enough to want to gather many samples and look at them very, very carefully.

The world press is beginning to focus on the province of Bak Kan (or Bac Can), Vietnam.  Bak Kan is in the extreme north of Vietnam, near the Chinese border.  Last week, I blogged on the potential H5N1 bird flu cluster that was threatening to emerge within that province. Just scroll down to read my previous blog.

Following my blog, a second story appeared regarding a second human infection.  It was dated at 6:01 PM, 04/09/2010.  It appears below, and the link to the VOV story is in the headline:

Another A/H5N1 infection case reported in Bac Kan

Yesterday, Vietnam confirmed yet another human bird flu case.  This time, however, this case bears watching, because it could signal something far more disconcerting than just a single human case.

From the proMED report:

The Director of the Bac Kan provincial Health Department, Nong Quoc Chi, confirmed an A (H5N1)-infected case on [5 Apr 2010]. The patient, [male], 22, from Na Tao hamlet, Nhu Co commune, Cho Moi district, is currently in critical condition. He is being treated at the [National Institute of Tropical and Infectious Diseases]. The patient got sick on [30 Mar 2010] with symptoms of high fever and cough. He was admitted to Bac Kan provincial hospital, and then sent to the [National Institute of Tropical and Infectious Diseases] on [3 Apr 2010] where he tested positive for the lethal strain of A (H5N1) virus.

At present, 4 other people in Nhu Co commune show similar symptoms of high fever and cough. They are under quarantine and being treated at Bac Kan provincial hospital.

The patient in question was taken ill on the 30th of March, and then sent to Hanoi when his condition worsened. The four suspected human bird flu cases are currently in quarantine at the provincial hospital in the provincial capital of Bak Kan. (Or Bac Can, as shown on map at left).

There are many unanswered questions.  The most obvious of these is whether these four suspected cases are bird flu, or swine flu?

If these cases are indeed bird flu, has there been human-to-human chain transmission, or were these people all infected during the same timeframe by a single vector?  Were they all infected by sick poultry, or were they sickened by a human infection?

OK, let's assume these four people were all H1N1/swine flu infections.  That is not good news!  That would mean that, once again, bird flu and swine flu had "rubbed elbows" in rural Vietnam.  Search my Blogsite for the earlier known case, back in 2009. 

According to the Vietnamese Department of Preventive Medicine and the Environment, there are no outbreaks of H1N1 anywhere in Vietnam.  From VOA News:

No more A/H1N1 outbreaks in Vietnam

As you know, I have been kvetching recently about the potential for a hybrid (or maybe "hybird," as I originally typed, in error but perhaps a Freudian slip?), avian/human flu virus to emerge from somewhere other than here.

Today, respected researcher Dr. Yoshihiro Kawaoka of the University of Wisconsin-Madison (left) has issued a paper where he postulates that such an occurrence is not only possible -- he has done it. 

Let's read the release and then talk.  From the University of Wisconsin-Madison press release:

VIRUS HYBRIDIZATION COULD CREATE PANDEMIC BIRD FLU

MADISON - Genetic interactions between avian H5N1 influenza and human seasonal influenza viruses have the potential to create hybrid strains combining the virulence of bird flu with the pandemic ability of H1N1, according to a new study.

In laboratory experiments in mice, a single gene segment from a human seasonal flu virus, H3N2, was able to convert the avian H5N1 virus into a highly pathogenic form. The findings are reported the week of Feb. 22 in the online early edition of the Proceedings of the National Academy of Sciences.

"Some hybrids between H5N1 virus and seasonal influenza viruses were more pathogenic than the original H5N1 viruses. That is worrisome," says Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison and senior author of the new study.

The H5N1 bird flu virus has spread worldwide through bird populations and has caused 442 confirmed human cases and 262 deaths, according to the World Health Organization. To date, however, bird flu has not been able to spread effectively between people.

"H5N1 virus has never acquired the ability to transmit among humans, which is why we haven't had a pandemic. The worry is that the pandemic H1N1 virus may provide that nature in the background of this highly pathogenic H5N1 virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine.

Two viruses infecting a single host cell can swap genetic material, or reassort, creating hybrid strains with characteristics of each parent virus.

Before the current study, hybrid viruses generated in lab studies had always been less virulent than parent strains. However, the new findings raise concerns that H5N1 and pandemic H1N1 viruses could reassort in individuals exposed to both viruses and generate an influenza strain that is both highly virulent and contagious.

The increased virulence seen in the new study seems to arise from one of the eight genes in the viral genome, called PB2, which is known to affect how well the bird flu virus grows in mammalian hosts, including humans. When tested in mice, the human virus version of PB2 swapped into H5N1 converted the avian virus to a highly pathogenic form.

The researchers say surveillance of viral populations is critical to monitor the potential emergence of highly pathogenic viral variants due to reassortment of avian and human influenza viruses. Their results, including identification of the PB2 segment as a key to enhanced virulence, offer information likely to be useful in the event of a pandemic caused by a hybrid avian-human influenza strain.

"With the new pandemic H1N1 virus, people sort of forgot about H5N1 avian influenza. But the reality is that H5N1 avian virus is still out there," Kawaoka says. "Our data suggests that it is possible there may be reassortment between H5 and pandemic H1N1 that can create a more pathogenic H5N1 virus."

The work was funded by the U.S. National Institutes of Health, the Japan Society for the Promotion of Science, the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Japan Science and Technology Agency. (bold mine)

Dr. Kawaoka's research is getting a lot of attention, including a recent grant from the Bill and Melinda Gates Foundation.  What is so interesting about Dr. Kawaoka's recent experiments is that he targeted PB2, the segment which few know enough about to be decisive.  Dr. Kawaoka and his research team have taken a human PB2 gene segment and spliced it to H5N1 bird flu.  The result is a more lethal and even more virulent virus than the parent H5N1 strain!

Dr. Kawaoka and his staff have now, and pretty conclusively, named PB2 as the gene segment responsible for lethality in humans.  In prepping for this blog, I stumbled across a blogsite by the name of Monotreme's Blog, and how I never saw it before now is a mystery to me.  Anyway, this blog has an interesting confirmation of Kawaoka's discovery.  But it turns things in a different direction than an avian/swine hybrid doomsday virus.  From Monotreme's Blog entry of December 2, 2009:

The PB2 gene is reported to be key in the adaptation of a virus that infects birds to one that infects humans. In particular, it has been reported that the amino acid at position 627 is critical for this adaptation (Van Hoeven et al. 2009). Viruses that infect birds typically have a glutamic acid (E) in this position. Flu A viruses that are fully adapted to humans usually have a lysine (K) at this position. This same position in PB2 appears to be key in determining the lethality of flu viruses (Hatta et al. 2001). In the 1918 pandemic and H5N1 viruses, a lysine in this position is associated with a higher level of lethality. The presence of a lysine at position 627 appears to permit flu viruses to replicate in both the lungs and nose and thus spread more easily from person to person.

It is possible, perhaps likely, that as pandemic H1N1 adapts to humans, a mutation will occur that will create a lysine in position 627 in this virus. If so, will the virus become more virulent? At this point, it is difficult to say. On the one hand, “seasonal” flu viruses that are not considered particularly lethal have a lysine at position 627. On the other hand, a change from glutamic acid, when the virus is infecting birds, to a lysine, when the virus is starts to infect humans, is associated with much greater virulence. How to reconcile these apparently contradictory facts? It may be that the change to a lysine is initially associated much greater virulence due to interactions with other proteins. As the virus moves through the human population immune responses are triggered. Thus, a year or two after a pandemic begins, the virus comes under selection to escape immune system detection. This selection may result in the preferential propagation of new versions of other proteins which no longer interact with PB2 to create a more lethal virus. In this scenario, a mutation at position 627 from gluatamic acid to lysine will initially create a more lethal virus, but, as the virus is “tamed” by the immune system selection, this mutation will utlimately be insufficient to sustain a high degree of lethality.

Given that human-adapted flu A viruses tend to have a lysine at position 627, it seems likely that the new pandemic H1N1 will eventually lose its “avian” glutamic acid and acquire a lysine at this position. There have already been sporadic instances of this. If/when this occurs in a strain that spreads widely, it would not be surprising if it becomes more lethal.

Kawaoka's research has taken Monotreme's (and others') speculation and turned it into fact.  

Monotreme offers a theory that immune responses in humans will ultimately steer this lysine-altered virus toward a less lethal path in order for it to evade antibody detection and eradication.  But how long will that process take, and how many lives would be impacted by the virus in the meantime, are only known to God.

In the meantime, bird flu continues to buck the tradition of flu viruses during a pandemic.  this virus refuses to go away.  Just today, comes word of two more Egyptians struck down with H5N1 bird flu.

Now I am going to make a statement, and I want you to read it and absorb it.

There have been more Egyptians hit by H5N1 bird flu thus far in 2010 than there are Americans who have tested positive for H1N1 or H3N2 seasonal influenza.

Bird flu continues to spread again, in defiance of tradition and in defiance of all governments' attempts to eradicate it.  As the H1N1v pandemic continues to strike and spread in Asia, the potential for dual infection with H5 and H1 simultaneously increases.  How many cross-infections does it take to achieve some sort of viral critical mass?

Only one. 

My last blog focused on the return of H5N1 avian influenza in humans in 2009.  Just scroll down to read it... I'll wait.

OK, welcome back.  What is happening is a veritable explosion of bird flu across Asia and the Middle East in 2010.  We have over 400 residents of West Bengal (India) under Tamiflu blankets; human cases seemingly every third day in Egypt, and at one point we had three confirmed cases in one day; and a quite sudden acceleration of H5N1 in poultry and wild birds across most of southeast Asia. 

Now Indonesia, a nation which has thankfully turned away from insanity with the appointment of a new health minister. is back in the timely reporting category.  Hey, anything was better than the last two years under Supari!  They could have had a zombie epidemic and the rest of the world could have been blissfully unaware -- until the undead came down Broadway.  And speaking of zombies -- where the Sam Hill is that World War Z movie?  Brad Pitt and Plan B, don't make me come down there and read you the Zombie Riot Act.  Why do you think Zombieland was such a financial success?   And a bit of movie trivia -- Zombieland's central character (right) was named Tallahassee, by the way.

But I digress.  Anyway, Indonesia has now reported two confirmed human H5N1 cases.  One case is in West Java, and one is in Jakarta.  Regrettably, the West Java case -- a 25-year old of unknown gender -- died.  I am sure that if you go to www.flutrackers.com, you will find plenty of stories about the deaths. 

And just this morning, news of a third Indonesian bird flu patient arrives via proMED.  This patient, a woman in Lampung, accompanies a huge die-off of birds in the province.

While this is taking place, the Western press is reporting about the roasting of public health officials over regarding what some misguided souls proclaim to be a "false pandemic" of H1N1v.  As the public health officers of the civilized world circle the wagons in the West, swine flu continues to insinuate itself throughout Asia.  Ans as it does what the flu does, it will absolutely have multiple opportunities to rub elbows with bird flu in towns and villages.  It has already had multiple opportunities with each and every confirmed human H5N1 case since April of 2009. 

Everyone is asking him/herself, "What virus was shed by those who are testing positive for bird flu?  Who might have walked into a cloud of H5N1 particles expunged by someone?  And what if that person, in turn, also acquires H1N1v swine flu?  Deep in the lungs of those dual-flu victims, what terrible reassortment experiments might be churning?  And what is the form and substance of that mutation, if it survives?"

Wait, you ask.  Why should swine flu mix with bird flu?  Recall that swine flu is only one-third swine.  It is also one-third human, and one-third avian.  Look at the number of flocks of turkeys all over the world that have acquired swine flu.  (interesting that I can only recall turkey flocks having acquired H1N1v).

For these flocks to have acquired a human strain of flu surely must tell us that H1N1v retains enough of an avian genetic footprint that direct infection from humans to birds is not just possible -- it has happened.  Numerous times.

Follow my logic here.  If birds can catch swine flu from humans, then it means swine flu retains enough of its bird ancestry that reassortment with bird flu is absolutely possible.  All it takes is enough exposure, in enough hosts, all over the world, to cook a strain that can both infect humans and kill in greater numbers than swine flu.

Sure, the swine flu pandemic was not what we were fearing.  But let's finish the sentence.

The swine flu pandemic was not what we were fearing -- yet.  We have a long, long way to go.