A tantalizing Reuters story yesterday called attention to the uptick in human bird flu cases in Egypt, the African country with more cases than any other (although far behind Asian countries like Indonesia). The observation prompting renewed expressions of concern are that new cases seem to be in the very young (toddlers) but adult cases have almost disappeared. So where are these toddlers picking up the virus? A possibility that is consistent with the observations is that adults are giving it to the toddlers but are themselves symptomless carriers. It's not impossible, because we know that flu affects different age groups differently (most existing cases of bird flu are under the age of 40, with new among the elderly, unlike seasonal influenza); and a large proportion (possibly as many as half) of human seasonal influenza infections are asymptomatic. So it could be that the virus has changed dramatically to hit infants and children hard but not affect adults as much. Could be. But I doubt it.
First, I think that a change in the virus that suddenly becomes almost avirulent for one age group but retains virulence for toddlers isn't very likely. There's a lot we don't understand about the flu virus, so maybe this is just what is happening. But I'd like to see some evidence, not just speculation. Second, we have seen surprisingly little evidence of elsewhere of subclinical or asymptomatic infection. I was among those who was pretty certain there was a lot of it and if we looked we'd find it. But every time we look, for example by surveying contacts of cases or even whole villages where there is a case and infected poultry for evidence of antibodies against H5N1 in blood, we don't find it. The absence of detected adult cases in Egypt is something to ponder and worth keeping an eye on. One way to keep an eye on it is to do another seroprevalence survey in Egypt ASAP. It sounds like something like that is in the works. Egypt has competent public health scientists, so they can do this. I hope we hear something relatively soon.
Suppose it is true that the virus has changed so that there are now asymptomatic adults walking around, possibly infecting toddlers? Is that good or bad? The Reuters article is all about the downside of that development, primarily, that it could enable the virus to mutate to a more easily transmissible form because the number of human hosts infected is now larger and survives to allow the virus to mutate. That's the glass half empty version. The glass half full version is that this could be evidence of a dramatic change in virulence. The current case fatality ratio of 62% is horrific, and if a virus with that kind of CFR became easily transmissible from person to person it would be beyond catastrophic -- apocalyptic might be a better description. It's not impossible. It isn't mandatory that infectious agents moderate their virulence to become more transmissible, although it frequently happens. But both smallpox and HIV are examples where it didn't happen, and it doesn't have to on theoretical grounds. So if this is one that does, so much the better.
We will mention again that there are a number of unexplained patterns in the H5N1 story. In China cases have been appearing for years in areas where there are no reports of infected poultry. Is that because vaccination has allowed birds to survive but still be infective? Could be. Maybe there are also asymptomatic adults there. Could be.
Lots of possibilities and too early to settle on one. We need some data.
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Revere, what do you think are the other likely causes of the pattern of cases in Egypt, other than asymptomatic adults?
Mathematician: The most obvious are reporting bias (toddlers more likely to be detected/diagnosed than adults) or exposure differences (toddlers exposed but not adults) or a combination. There might be others, too, although it is too early in the morning to run through the possibilities (maybe after my i.v. coffee).
Assuming that the virus has not changed at all, we should probably examine why it then infected only young children, and why they survived. I believe the answer is a lot less complicated than what we may think. First, if the virus has not changed, then perhaps itâs just a simple coincidence that they were all young this time. Sometimes we might see 3 â 4 women in a row get infected, but that doesnât mean the virus has changed. This group of children being infected was merely a matter of âChanceâ. As we know, in a lot of these cultures, the young kids have been known to frequently play with âdead chickensâ, such as previous reports in which kids would actually play a game entailing kicking around dismembered chicken heads. So there could be some obvious reasons why we might see a group of kids being infected from time to time. Young children have no clue about h5n1, so you would think that accidental exposure would be a lot more common in small kids than in the older folk. In this particular culture, itâs also the role of young children to handle and clean the food, which again would explain why children might be infected in different regions. Also -- case # 59 was a 38-year old female.
As for their survival rate, that too could be a simple coincidence, or even more explainable. People in general always watch their young children very closely for any signs of illness, so itâs natural to take a baby to the doctor in you notice your child getting sick. This is the same for all cultures. An adult may try waiting out the symptoms, which would be fatal with an h5n1 infection, but if your baby is sick, you will most likely take them to the doctor on DAY ONE. Therefore, the survival rate is also explainable.
Simply, if the virus has not changed, then look for the obvious. There wonât be antibodies in Egyptian adults because again the virus never changed.
Now, there are some claims and rumors that the virus has mutated and is now silently spreading around the world, and all because of these last few cases in Egypt. Itâs amazing how something like that can happen. Itâs almost beyond a case of disinformation.
Albert: All good points. You have added to my short list the important one that this is just random variation. Quite possible, although how likely we don't know because we don't know the underlying probabilities. But a very valid point.
Thanks revere. Unfortunately watching avian flu developments has been my curse for the last few years⦠lol.
Of this group of toddlers, most are almost or around 2 years old. This is too young to be playing kick the chicken or cleaning chicken. However, they could be crawling around while mom cleans the chicken. I know many times I cared for my son when he was sick and I didn't catch whatever he had. Maybe that is why the moms don't have it.
If this is the strain that makes it around the world (assuming it stays this mild) that would be fine with me. But Indo has a much higher fatality rate, as do the other places that have reported deaths. What keeps this strain mild?
Also, since their goverment doesn't reimberse farmers for their sick chickens, are they not killing off whole flocks? Maybe, the resistent ones are living and reproducing?
"Maybe, the resistent ones are living and reproducing?"
The possibility is very high.
Revere,
Could these cases of mild H5N1 possibly be the herald wave for the pandemic?
victoria: I have no way of knowing for sure, but I rather doubt it. We need more evidence about what is going on (or not going on). It doesn't seem like pre-pandemic to me. Just my 2 cents.
DebP: There's not enough information to make any determination or even reasonable hunches here. The info is compatible with wildly different scenarios. So I'm not even speculating, other than citing some possibilities.
If the virus hasn't changed, then that means they could not have been infected with a mild strain. Make sense? Again, you can probably attribute the high survival rate to the parents seeking early treatment at the first sign of symptoms. In fact, if you research all of the past surviving cases, you will probably find that they were all very young infants that received early treatment. If the virus hasnât changed, then we âhave toâ rule out there is a new strain.
Hmm. The trouble with all these other explanations, except for "random variation", is that they don't explain why we have this pattern only in Egypt now, not also in Egypt in years past or elsewhere in the world now. No Albert, it's by no means the case that all surviving H5N1 patients have been very young. I suppose it could be a change in the virus *plus* one of those other explanations: e.g., maybe if the virus gets a bit milder, then exposed adults don't get ill enough to seek treatment, so we no longer see them, but toddlers do: i.e. still B2H transmission, but different virulence characteristics.
albert, mathematician: We don't know if the virus has changed or not. Statements by the Egyptians that it hasn't I take with a grain of salt, because there are always differences in viral isolates, most of which are small and unimportant for the biology. People have ideas about what is important (e.g., changes in the binding site of HA) and when HA doesn't change in any way we think is relevant there is a tendency to say the virus hasn't changed. But changes in the internal genes (e.g., PB1 or PB2 or NS) might be important and we wouldn't know it. It's likely they haven't even looked, but since we don't know all the things to look for that isn't the key point.
As far as I'm concerned, the key point is this about the Egypt situation (and others like it): at the moment we don't have the evidence to differentiate between several plausible but starkly different possibilities. Given this, we are engaged in rank speculation that often betrays our predilections more than anything else. We need more data, like seroprevalence studies, to begin to narrow down the possibilities and lead us in new directions. Until we get some more, I am reluctant to draw any conclusions.
revere,
That just about sums it up. "several plausible but starkly different possibilities." Just cos we wish we know the truth, really doesn't make any one answer more likely than the other.
A US company is about to publicly describe a method of creating a personalized therapeutic vaccine for H5N1 from an infected subjects own strain of virus. It has already been proven to be effective in treating mice infected with H1N1. The research has been conducted at two major US medical schools. Athough it is currently a 20-30 minute process, they belief they can reduce it to 5-10 minutes and design it to be administered in an office or lab setting.
medtrader: Highly unlikely. If you have a cite, give it to me. Sounds like bullshit.
I'm not a doctor, just a mom, but the first question I had about this story was: "Were these toddlers weaned?" and "How long had they been weaned?"
I wonder if breastfeeding had given them immunities that kept them safe until they were weaned, thus the victims were all "toddlers". Or perhaps breastfeeding protected them in a different way, much like it protects CF kids, in whom the disease often goes undiagnosed until weaning.
Susan: Good question. Don't know. Probably they were.