Influenza: Yet another surprise

It has been noted on several occasions that influenza is always full of surprises; now we have another to discuss to try to gain some perspective on what is happening. Last month, Donald Kaye, MD, discussed the current status of avian (H5N1) influenza, especially as it involved human disease, and outlined the reasons for his doubt that H5N1 strains would emerge to cause the next pandemic. The timing of his editorial comments proved to be an extraordinary segue into what happened next.

We had read about severe influenza-like illnesses in Mexico earlier in the year, but since no definitive information was presented to elucidate what was going on, little attention was paid to these reports in the United States. When cases of swine (H1N1) influenza began to be confirmed and reported by CDC in the United States, starting on April 17, 2009, suddenly the Mexico outbreak got a lot of attention.

Theodore C. Eickhoff

The H1N1 influenza virus causing the outbreak has evidently never been seen before and has been described as having components of human, avian and swine sources in its genome. If true, this would strongly suggest multiple reassortant events in the past. A recent Pro-Med Mail posting, dated April 28, however disputes that, and claims that a Columbia University laboratory analysis revealed only components of swine origin. The actual origin of this virus is but one of the unknowns that await clarification.

Spread of disease

It seems futile to engage in a case count, death count (the CDC recently confirmed the first U.S. death), state count or country count; for by the time these comments are read, the situation will likely be vastly different. The virus is widely seeded all over the world by this time, but at this writing we know of sustained transmission within communities only in Mexico and the United States. Much of this global seeding was apparently done by travelers returning from Mexico. Whether sustained transmission will result in these countries remains to be seen. Of note, WHO has raised its "pandemic alert level." Does this mean that a pandemic is inevitable? Not at all, but it certainly makes it more likely.

Reporting of this new virus began less than two weeks ago and, as always in such circumstances, we must deal with very incomplete information. Among the most needed missing information is detailed information on the Mexican outbreak. Why is the disease in Mexico so relatively severe, while the cases in the United States are so apparently mild? How many of the approximately 2,000 cases reported are actually swine influenza? Is there another infection that is co-circulating with influenza? How many of the reported deaths are actually confirmed as due to swine influenza? Are some of the deaths due to other causes (eg, pneumococcal pneumonia)? What is the age distribution of cases that are have been reported/confirmed? And on and an. The missing data was well described by Larry Altman, MD, (himself an ex-EIS officer) in The New York Times on April 28, in an editorial that could just as well have been entitled “Influenza Epidemiology 101,” instead of the actual title, “Sound the alarm: A swine flu bind.”

As could have been predicted, irrational behavior is occurring both among individuals and among countries. The most glaring example is concern about eating pork. Although the science should easily put that one to rest, there will be people who will not be convinced and will avoid pig products altogether. At the country level, the several Eurasian countries that have banned importation of pork from North America seem equally irrational.

Current attempts to eliminate the name “swine” when referring to this virus have some basis in history, but nonetheless are somewhat amusing. We have, of course had the Spanish flu (1918), Asian flu (1957, Hong Kong flu (1968) and Russian flu (1977). Perhaps today the current swine influenza virus should be known as Mexican flu or, alternatively, North American flu. The swine industry would be wholly in favor of that, but much of the push seems to be coming from the United States government — for reasons that I don’t fully appreciate.

Extent of the outbreak

So is this finally “the big one,” the long predicted influenza pandemic? It certainly could be; time will tell. There seem to be three possible scenarios. In the first scenario, the outbreak stabilizes and fizzles out over the next several weeks and that’s the last we hear of it. That seems to me to be the least likely scenario. In the second scenario, the outbreak progresses to a full-blown pandemic, of a severity unknown at this time, and involving most of the entire world over the next four to six months. Possible, but I think also unlikely; summertime pandemics are virtually unknown. The third scenario, and by exclusion the one I consider most likely, is that the outbreak stabilizes and subsides over the next several weeks, since it’s so late in the influenza season, reemerging again in the late summer and fall, possibly with even more vigor, to cause a pandemic at least in the northern hemisphere. This would actually be close to a replay of both the 1918 and 1957 scenarios. Do not interpret this as a prediction on my part, but rather simply an opinion about what might evolve as we move forward.

CDC is already developing seed strains for vaccine manufacturers and the FDA is developing the necessary reagents for vaccine production. Both manufacturers and government agree that new technologies are needed for influenza vaccine production, but the most immediately promising technology, cell-based vaccine production, is still several years away; hence we are still reliant on egg-based vaccine production. The manufacturers are now fully engaged in preparing the 2009-2010 seasonal influenza vaccine and probably could not begin to make a pandemic swine flu vaccine until sometime this summer. That would likely put vaccine release into a November-December time frame, probably too late for any pre-pandemic use except perhaps for a limited number of people at highest need or highest risk. The current seasonal influenza H1N1 component in the vaccine is said to provide little or no protection against the swine virus, but no data is yet available to support that statement. Many decisions about vaccine production, recommendations, and use remain for the future.

Meanwhile the 2008-2009 seasonal influenza outbreak has all but ended. It consisted of mostly H1N1 and B infection, with very little H3N2. Hence there was no excess pneumonia and influenza mortality and the other parameters of surveillance were quite mild compared to previous years. Will it be payback time next year?

Addendum

Since these comments were written, WHO has moved the pandemic threat level from 4 to 5 (meaning a pandemic is imminent) and this could easily go to 6 (meaning a pandemic is upon us) anytime. The virus is now widespread around the globe. Note, however, that the WHO terminology refers only to epidemiologic activity and not to clinical severity. It has been reported that this H1N1 virus lacks the genes that were responsible for the clinical severity of the 1918 H1N1 pandemic, and the relative mildness (Mexico aside) of cases thus far appears to bear that out. The third scenario, discussed above, looks more and more likely; the virus will disseminate widely, probably result in localized outbreaks during the months ahead, possibly even subside, only to emerge again in the fall, likely with renewed epidemiologic vigor. Look to the experience in the Southern Hemisphere in the next four to five months for major clues to what is likely to happen here in the 2009-2010 season.

Theodore C. Eickhoff, MD is an Infectious Diseases in Children Editorial Board member.