We have two contradictory impressions. One is that the pandemic has continued to develop in a very robust fashion. So it’s a dynamic picture of change. The second is that it looks like a normal pandemic, just going about its business. We have been very struck by how , in general, we are accustomed to the experience of constant change, not just for influenza but for modern life in general and we are gestating a post on influenza as the disease of modernism par excellance. That’s another of the benefits of stepping away from the daily view. It allows for some reflection. But that’s for another day (soon, we hope). When it comes to the current status, WHO issued quite a nice one the day we were starting to pack up (August 28). Crof noted it at the H5N1 blog and Mike Coston over at Avian Flu Diary seems to have pretty much reproduced the whole thing. Both Crof’s blog and Avian Flu Diary are superior single voice flu sites and there are other group efforts and forums like Flu Wikihttp://www.newfluwiki2.com/frontPage.do with a ton of information, more than you will ever get here. But we want to say some more about the WHO analysis, “Preparing for the second wave: lessons from current outbreaks.”

The first thing we want to say about it is we think it’s pretty good. We have a lot of readers who really have it in for WHO and I doubt they’d approve of anything it does. But as an epidemiologist who follows flu closely, I think this is an admirable, measured and wise assessment based on experience of its member nations around the world, north and south. What does it say?

1. WHO is advising northern hemisphere countries to prepare for a second wave of pandemic spread. That’s good advice but neither WHO nor anyone else can say with certainty what’s going to happen. This is a recommendation, not a prediction, and while I have said I think the fall will see an early and bad swine flu season up north, I could well be wrong about that. But getting ready for it seems to be the only sensible thing to do. As we have commented and a recent story by Helen Branswell of Canadian Press emphasizes, a bad flu season will make itself felt in specific vulnerabilities, of which critical care facilities is one of the most obvious (along with demand for emergency room and walk-in care). WHO reports that among the fatal and severe cases is a severe form of respiratory failure (likely a primary viral pneumonia) not usually seen in seasonal flu deaths (which are mainly among the elderly). This has stressed critical care facilities and this needs attention for the upcoming flu season in the north.

But they also point out that in tropical countries the timing may be different or anomalous. Our gloss on this is two fold. It shows we still don’t understand the influence of environment very well (“seasonality” is one way to express this); the other is flu is notoriously patchy and inhomogeneous in its spatial and temporal distribution. There are lots of ways flu is unpredictable and that’s one of them.

2. The current pandemic strain is not changing much and it is tending to crowd out the seasonal strains. In our view the relative stability of the virus may be related to the fact that it is quite transmissible. The ability to make new copies is the trait that is being selected for. That’s a combination of the ability to infect a host cell (infectivity) and once that has been accomplished and lots of copies of itself made, the ability to find a new host cell to do it all over again. If changing its virulence (the ability to cause severe disease) affects transmissibility, then we might expect to see an increase in virulence. But by the looks of it, this virus has found a nice recipe and it’s sticking to it, more or less. That’s the picture at the moment. We’ll have to be watchful because flu virus never seems to do what you expect it to. For example, we’ve all been waiting for the Tamiflu resistance shoe to drop. But so far it hasn’t. It would be very surprising if this virus, like its H1N1 seasonal counterpart didn’t become completely resistant to Tamiflu. But “very surprising” seems to be what to expect.

The question of crowding out seasonal virus is interesting, and as far as I know, the mechanism isn’t completely understood. It certainly implies that co-infection is not an independent event (if it were, then we wouldn’t expect to see this kind of competitive exclusion, or so it seems to us; we’re open to alternate arguments). Until 1977 we essentially only had one subtype circulating at a time, each pandemic replacing the subtype of the previous one. Then in 1977 H1N1 and H3N2 started circulating simultaneously. We plan to discuss this, too, at a later time. In the meantime, there is a good chance next flu season will be a swine H1N1 season, not a “seasonal” H1N1 or H3N2 season. We’ll see, but that’s what WHO is reporting it is seeing in the southern hemisphere which is now well into its usual flu season.

3. In the north, particularly, there is a large reservoir of susceptibles to this novel flu virus. The under 60 crowd seems to be largely naive to the virus. The large pool of residual susceptibles is one of the main reasons we predict a bad flu season. The reason for the comparative sparing of the oldest age group is a puzzle and underscores another of WHO’s points. This isn’t seasonal flu.

4. The difference between seasonal flu and swine flu is primarily one of epidemiology, that is, the pattern and distribution of the disease in the population. Younger age groups are affected (and older ones not affected), and the increased infections in the young are producing increased severe and fatal infections. By most accounts we’ve seen, the virus doesn’t seem more virulent than seasonal flu virus. Seasonal flu always kills a certain proportion of its victims, usually in the oldest age groups. But it also does it in the younger age groups, and with so many more susceptibles in this age category we are seeing many more severe and fatal cases in previously young, health adults, adolescents and children. Usually that number is relatively small, so if you greatly increase the number of cases, the extra number and nature of fatal or severe outcomes in healthy young people has quite a psychological impact. We don’t yet have a good understanding of how or why the distribution of cases has shifted to the young in pandemics, but it could also be asked differently. Why are we not seeing a huge increase in death among the elderly? The age distribution of mortality of flu during pandemics is poorly understood. One of the most prominent features of the 1918 pandemic was its “W-shape.” In seasonal flu it is “U-shaped”, high among infants and high among the elderly but low between them. In 1918 there was a huge hump in the middle, the young adults. There have been many attempted explanations for this, but none that are conclusive or even convincing. In swine flu, the impact is in the under 50 age group with little above it, yet another pattern.

5. The attention being paid to swine flu has revealed that pregnancy is a special risk factor. This has been known but the larger number of young people being infected by this virus makes it a special problem. All societies place a special premium on the next generation and fear for the safety of babies is almost universal. It’s probably hard wired into our brains. If we didn’t have it we wouldn’t have survived as a species. But it makes the added risk in pregnant women take on added public policy significance. It also seems true that children and adolescence with well controlled underlying medical conditions like diabetes and asthma are also at risk. And a new finding, people with Body Mass Index (BMI) over 40 are also at special risk. Add to this certain populations, like indigenous peoples in various parts of the world, and we have a lot of people who may be very vulnerable to this highly transmissible virus.

6. One of the strange (and happy) early impressions, however, is that HIV positive people do not seem to be at special risk as long as they are receiving antiretroviral therapy. These people seem to have roughly the same spectrum of clinical outcomes as the non-HIV infected population. Since we are talking about 33 million people in this category, that’s good news. The bad news is that only about 15% are receiving life saving antiretrovirals.

That’s our quick once over of where we think we are as we resume active flu blogging. Not everyone will agree with our (or WHO’s) assessment. There’s lots of room for disagreement, in the large or in the small. Probably the best comment about what the fall flu season will bring came from Helen Branswell, she she said somewhere she expected it to be “complex.” Can’t argue with that.