Effect Measure

Highly pathogenic variant of avian influenza A of the subtype H5N1 is here to stay, at least in the world’s poultry population. While it’s around it continues to cause sporadic but deadly human infections, some 369 of them of whom 234 have died (official WHO figures as of 28 February 2008). So this virus can infect humans and make them seriously or fatally ill. There is truly massive exposure because people live in close contact with infected domestic poultry in many countries. And the human population has not seen this subtype of virus before so there is little natural immunity. All that’s necessary for a really catastrophic pandemic is for this virulent virus to move easily from poultry to humans and then from human to human. These may require different changes in the virus but since it can already move into humans on rare occasions, the human to human feature is the crucial one.

However if it does acquire the ability to move into humans more easily from birds, we could have a lot of bird to human cases, given the exposure, and each of those cases presents the opportunity for the emergence of a human to human transmissible agent because the virus mutates quickly, even in the short span of time it infects a single person. After some days of infection the virus the patient has often changed genetically. So the question of bird to human transmission is of real importance. Lots of poultry workers and cullers of infected poultry flocks are in close contact with diseased birds. Maybe they do get infected only mildly so transmission from birds to humans has been overlooked. As we have noted often here, this would mean the observed case fatality ratio (CFR) is lower than the current dismal 60% plus. Now a new study has been published looking for evidence of infection in poultry farmers in five provinces in Thailand that had large H5N1 outbreaks in late 2003 and 2004. The news is good and bad.

First the good news:

During late 2003 and 2004, highly pathogenic avian influenza virus (H5N1) caused extensive outbreaks and die-offs in poultry flocks in Thailand and several other countries in Southeast Asia. From January through March 2004, 12 cases, 8 fatal, in humans resulted from infection with influenza virus (H5N1) in Thailand. In response, the Thailand Department of Livestock Development enlisted government employees to conduct a large-scale cull of poultry in the affected provinces (www.dld.go.th/home/bird_flu/emergency.html). This effort began on January 23, 2004, and resulted in the slaughter of >21 million birds (www.fao.org/ag/againfo/subjects/en/health/diseases-cards/avian_bg.html). Poultry farmers and persons involved in culling are at increased risk for infection. In May 2004, we conducted a seroepidemiologic investigation of Thai poultry farmers to determine the frequency of avian influenza (H5N1) transmission to humans. (Soawapak Hinjoy et al., Emerging Infectious Diseases [cites omitted])

The study involved taking blood from 322 farmers and cullers (92% response rate) and testing to see if there was evidence of past infection with H5N1. The test was to look for specific antibodies to the H5N1 virus. This was definitely an exposed and at risk population (age 5 to 50 years old). 58% of the subjects reported handling sick or dying birds, 33% worked in culling of well birds in outbreak areas while 9% had contact with apparently well birds during routine farming. The level of antibody titer for presumptive infection is set at 80 and no subject had anti-H5N1 antibody levels that high. Seven had antibody levels that were detectable but much lower. They could have been the result of cross-reactivity with other flu viruses, the failure of mild infection to produce high enough levels, the disappearance of antibody levels soon after infection, or an insufficiently sensitive antibody test. In any event, the good news seems to be that there was no evidence of bird to human transmission in a clearly at risk occupationally exposed population.

That’s also the bad news. It means that the hope against hope that there is a lot of mild and inapparent infection with this virus that would mitigate the extraordinary case fatality ratio once again does not seem to have panned out, similar to studies in Cambodia and Nigeria.

As far as we can tell, infection with this virus is unusually virulent. Unlike many infectious diseases, really serious cases are not the tip of the iceberg. They are the whole iceberg. So far it is a small one. If it gets really big, spaceship Earth is going to look more like Titanic Earth.


  1. #1 Jonathon Singleton
    March 3, 2008

    Revere: “In any event, the good news seems to be that there was no evidence of bird to human transmission in a clearly at risk occupationally exposed population. That’s also the bad news…”

    Hey! As many EM folk (eg. Victoria and Attack Rate) are aware it’s a public holiday in OZ and wouldn’t be at all surprised to hear I’ve downed a few bevvies.

    I feel… I feel so bloody over it all, actually — it’s like us lot know the effing script and are just waiting around for the inevitable (that pisses me off to the max cos I wanna do somethang concrete to alter the outcome)!

    When I sobbed back in 1997 ’bout the Love Theme from Titanic, my then boyfriend (a medico) just patted me on the head like a dumb dawg — back then, my darling ex-hubby wouldn’t say boo till a politician told him to…

    Why are politicians determined to publicly act as if science is a load of wank compared to religion — and why do ordinary folk put up with this crap when they instinctively know it’ll end up killing everybody!?!

    Celine Dion — My Heart Will Go On (1997) Near, far, wherever you are I believe that the heart does go on
    Once more you open the door And you’re here in my heart And my heart will go on and on…

  2. #2 M. Randolph Kruger
    March 3, 2008

    Jonny-Good Day to you ole son. It might be that with all of the gizzies that all these guys have in every field we are just now getting where its starting to accelerate knowledge in God Awful amounts. Doctors/Masters of all fields are just beginning to get a handle on the intricacies of a human. Bush signed the Human Genome bill and all things we “know” started to change. Biology, Chemistry etc. All things just got turned upside down.

    Its almost funny but all these things they “know” in ten years will be upset by what will be the facts of twenty years. I just hope that they get their shit together enough to stop this one. Else one helluva lot of people are very likely going to die. Preventable? Not really. Its a human cull machine…Just make damned sure you do what is necessary to stay alive. This is where God/Nature come in and do a little housecleaning. It might even be me and all or part of my family. But it wont be from the lack of trying to survive here.

    Titanic is a good example. Brash, bold, beautiful and sleek it was the techno-monster of its time. But it had huge flaws and thats what we have here. We are cruising full steam into ice laden waters and brother, it would hurt me to see your seriously gay ass gone. Everyone has something to contribute as far as I am concerned, mostly for the better. But its survival of the fittest. Look at who got onto the boats. Those with money, power, position all got onto the boats and steerage…Well you know the rest of the story. Just make sure that you are one of the ones writing about it rather than one of the ones that are found floating two weeks later.

  3. #3 victoria
    March 3, 2008

    Jonathon, Randy,

    One thing is for sure, I won’t be listening to Celine or standing on the prow of the ship shouting I am King of the world.

    Randy, great analogy.

    The waiting part is the killer. Maybe it isn’t………

  4. #4 Goliath
    March 4, 2008

    Seven of 322 had antibody titers, but at a level less than 80. I don’t understand this science, and Revere provides a few possible explanations for the low number, but does this level of detection not warrant further investigation? Is there sufficiently settled consensus about antibody titer levels that low levels can be confidently written off as background noise? Thanks for any who can shed light on this for me.

  5. #5 revere
    March 4, 2008

    Goliath: No consensus on this. The conventional cutoff is 80 but sometimes 40 hs been used. There is not extremely robust evidence for any particular value IMO. I did lay out some possibilities here (they were also in the paper). Science is seldom tidy when you look at the details.