Tuesday, September 1, 2009

Does swine flu need to become more lethal?

A news story,discussing the possibility of the pandemic H1N1 becoming more virulent or transmissible via reassortment with circulating human influenzaviruses is spreading around the internet and flublogia now.

I think they may be looking in the wrong direction. The "common knowledge" of 1918 is that there was a relatively mild form of the virus that broke out in the late spring of 1918 and spent the next several months spreading around the globe, to be replaced, essentially, with a more lethal strain for the second and third waves of fall and winter 1918-1919. Unfortunately there are really no solid samples of the 1918 virus, and little to nothing to indicate how it evolved after introduction (see Wikipedia So is there any evidence the 1918 virus reassorted in the late summer of 1918 to produce the more lethal strain? It would seem that any such evidence would be tenuous at best.

So what of the mild spring/summer wave in 1918 and what might it tell us about 2009, which also had a "mild" summer wave? From Wikipedia:

Deadly second wave

The second wave of the 1918 pandemic was much deadlier than the first. During the first wave, which began in early March, the epidemic resembled typical flu epidemics. Those at the most risk were the sick and elderly, and younger, healthier people recovered easily. But in August, when the second wave began in France, Sierra Leone and the United States,[39] the virus had mutated to a much more deadly form. This has been attributed to the circumstances of the First World War.[40] In civilian life evolutionary pressures favour a mild strain: those who get really sick stay home, but those mildly ill continue with their lives, go to work and go shopping, preferentially spreading the mild strain. In the trenches the evolutionary pressures were reversed: soldiers with a mild strain remained where they were, while the severely ill were sent on crowded trains to crowded field hospitals, spreading the deadlier virus. So the second wave began and flu quickly spread around the world again.[41] It was the same flu, in that most of those who recovered from first-wave infections were immune, but it was now far more deadly and the most vulnerable people were those who were like the soldiers in the trenches - young, otherwise healthy, adults.[42] Consequently, during modern pandemics, health officials pay attention when the virus reaches places with social upheaval, looking for deadlier strains of the virus.[41]


The first thing of note is that it is already established that the 2009 virus has a predilection for the young and healthy. But beyond that, we have two pandemic viruses that started as relatively mild spring/summer outbreaks, which many would not be able to distinguish from a seasonal human influenzavirus. Furthermore, we now have the WHO reporting as follows: New York Times

WASHINGTON (Reuters) - Doctors are reporting a severe form of swine flu that goes straight to the lungs, causing severe illness in otherwise healthy young people and requiring expensive hospital treatment, the World Health Organisation said on Friday.

Some countries are reporting that as many as 15 percent of patients infected with the new H1N1 pandemic virus need hospital care, further straining already overburdened healthcare systems, WHO said in an update on the pandemic.


Now, I would submit that there is nothing new here, this virus has always had the ability to hospitalize those numbers and kill a significant portion of them. So what would make this virus worse? Perhaps no added lethality is necessary. Perhaps it needs to transmit just a little better:

US News

Their conclusions: The 2009 H1N1 virus is spreading at a rate comparable to the 1957 and 1968 flu pandemics -- the most recent pandemics prior to this year's swine flu -- and to the SARS (Sudden Acute Respiratory Syndrome) outbreak, which surprised the world in 2003.
"Even if flu has a reproduction only a little bit above 1 [in this case 1.5], it has its effect because, in a susceptible population, it can start jumping from person to person within one to two days," said study co-author Dr. Nathaniel Hupert, co-director of Cornell University and Weill Cornell Medical College's joint Institute for Disease and Disaster Preparedness. He is also director of the Centers for Disease Control and Prevention's Preparedness Modeling Unit.
"What that means is, three days later, you've got an additional half a person infected. In three days, each of those new people have infected an additional half person, and it's like compound interest. It's the same calculation that lets you grow $1,000 into a $1 million 20 years later."


Suppose the first wave of 1918 was of such a mild nature, not because of the lethality of the virus, but because it couldn't transmit at a high rate?

Study on Transmission Rates for 1918

Recurrent outbreaks of the avian H5N1 influenza virus in Asia represent a constant global pandemic threat. We characterize and evaluate hypothetical public health measures during the 1918 influenza pandemic in the Canton of Geneva, Switzerland. The transmission rate, the recovery rate, the diagnostic rate, the relative infectiousness of asymptomatic cases, and the proportion of clinical cases are estimated through least-squares fitting of the model to epidemic curve data of the cumulative number of hospital notifications. The latent period and the case fatality proportion are taken from published literature. We determine the variance and identifiability of model parameters via a simulation study. Our epidemic model agrees well with the observed epidemic data. We estimate the basic reproductive number for the spring wave R1;=1.49 (95% CI: 1.45-1.53) and the reproductive number for the fall wave R2;=3.75 (95% CI: 3.57-3.93). In addition, we estimate the clinical reporting for these two waves to be 59.7% (95% CI: 55.7-63.7) and 83% (95% CI: 79-87). We surmise that the lower reporting in the first wave can be explained by a lack of initial awareness of the epidemic and the relative higher severity of the symptoms experienced during the fall wave. We found that effective isolation measures in hospital clinics at best would only ensure control with probability 0.87 while reducing the transmission rate by >76.5% guarantees stopping an epidemic.


This study has the transmission rate for the spring of 1919 at ~1.5, the same as for the 2009 pandemic. With the tremendous increase in transmissibility in the second wave, did the virus really need to be that much more lethal, or would it simply have become obvious?