Norovirus (from J Virol. 82:2079-2088 (2008))

Noroviruses cause an unpleasant, but rarely serious, diarrhea and vomiting-type disease — “cruise ship flu”1 is one term for it.  As well as cruise ships, nursing homes and hospitals and other more or less closed systems also see outbreaks of norovirus disease fairly regularly, and as you’d expect the elderly and immune-compromised are more at risk from the disease.

Noroviruses have been around for a long time (they were first identified in the early 1970s, as “Norwalk Viruses”), but it’s in the last ten years or less that they really exploded; in 2002 there was an abrupt, worldwide upsurge of norovirus outbreaks, and more epidemics have followed almost every winter. Those outbreaks were all different mutant variants of norovirus; I talked about this earlier.2 Each outbreak3 was associated with a new variant of norovirus, that is no longer controlled by the immunity that controlled the previous outbreak.

A couple of recent papers look at norovirus epidemics more closely. One4 analyzed the different strains involved in global outbreaks. They found that there were eight distinct variants of the GII.4 noroviruses, three of which caused global epidemics. Other strains did become epidemic, but on a more local scale (countries or continents, rather than everywhere).

My first thought was that that’s essentially the strategy that influenza viruses have used, also very effectively; each new flu season sees new variants of influenza virus, and each season’s most abundant viruses are the ones that are less well controlled by the immunity among their target population. This is the notorious “antigenic shift” that beginning virologists learn to parrot in their first class. The parallel to influenza epidemics was also noted by the authors, and they pointed out another parallel: Most of the global norovirus epidemics seem to have originated in Asia, as with influenza A.

What surprised me originally about the norovirus equivalent of antigenic shift was that at the time, conventional wisdom had it that immunity doesn’t play a big part in controlling seasonal norovirus outbreaks; immunity to noroviruses is weak and short-lived, and I had not thought that immunity from the previous winter would be a factor in controlling outbreaks this winter. The previous paper I talked about showed evidence, though, that immunity is a major factor in determining norovirus epidemics, and the other paper I have here5 looks at this in much more detail. I won’t go into their work in any detail6 but what they’re doing is building predictive models for norovirus epidemics. Very briefly, their overall conclusion is:

These results point to a complex interplay between host, viral and climatic factors driving norovirus epidemic patterns. Increases in norovirus are associated with cold, dry temperature, low population immunity and the emergence of novel genogroup 2 type 4 antigenic variants.5

The “new variant” part matches the first paper’s description of epidemics — mostly, but not always, they’re driven by a new version of the virus, but new variants don’t necessarily explode globally. It seems that a new variant may often be necessary for an outbreak, but isn’t sufficient; and in some cases, other factors may mean new variants aren’t absolutely necessary. Cool, dry weather supports an epidemic (and this is probably a big part of the highly seasonal pattern of norovirus infections, as well; it’s charmingly called “Winter vomiting disease” by some). And epidemics are possible when population immunity to a particular strain of norovirus drops under a certain level.

Norovirus outbreak prediction
“Daily norovirus laboratory reports (grey circles) and
predicted values (red line) from full model including
temperature, relative humidity, immunity, new variants
and autoregressive terms and other confounders.

The authors point out that new variants are selected by population immunity, so two of these factors are not strictly independent. However, “Despite this, these two factors had significant effects after controlling for the other”;5 perhaps there’s some immunity even to variant strains of norovirus. Since immunity to norovirus does drop very quickly,7 perhaps a year is enough to open a window for new strains, but not for the same one; particularly if the weather cooperates. Or perhaps the arrow is going the other way — population immunity at the end of one season chokes out the prevalent strain, and only new strains that are relatively resistant survive to cause the next epidemic once the weather cooperates.

At any rate, from these parameters the authors derived a predictive model. Applied retrospectively, it looks pretty impressive (see the figure to the right; click for a larger version). 8  It will be interesting to see how well it actually predicts new outbreaks.

By the way, regular readers may have noticed that this is two weeks in a row with only one new post — I usually aim for two or three per week, but what with my kids starting their school this week, and my teaching schedule9 kicking in, I’m scrambling some to keep up.  Hopefully I’ll be in more control soon, but I make no promises.

  1. It’s not flu![]
  2. Referring to this paper: Lindesmith, L.C., Donaldson, E.F., LoBue, A.D., Cannon, J.L., Zheng, D., Vinje, J., Baric, R.S. (2008). Mechanisms of GII.4 Norovirus Persistence in Human Populations . PLoS Medicine, 5(2), e31. DOI: 10.1371/journal.pmed.0050031[]
  3. Except for the 2007/08 outbreak, which was mainly the same strain as the previous year’s[]
  4. Siebenga, J., Vennema, H., Zheng, D., Vinjé, J., Lee, B., Pang, X., Ho, E., Lim, W., Choudekar, A., Broor, S., Halperin, T., Rasool, N., Hewitt, J., Greening, G., Jin, M., Duan, Z., Lucero, Y., O’Ryan, M., Hoehne, M., Schreier, E., Ratcliff, R., White, P., Iritani, N., Reuter, G., & Koopmans, M. (2009). Norovirus Illness Is a Global Problem: Emergence and Spread of Norovirus GII.4 Variants, 2001–2007 The Journal of Infectious Diseases, 200 (5), 802-812 DOI: 10.1086/605127[]
  5. Lopman, B., Armstrong, B., Atchison, C., & Gray, J. (2009). Host, Weather and Virological Factors Drive Norovirus Epidemiology: Time-Series Analysis of Laboratory Surveillance Data in England and Wales PLoS ONE, 4 (8) DOI: 10.1371/journal.pone.0006671[][][]
  6. There are intimidating equations and everything[]
  7. Though it’s not known exactly how quickly[]
  8. By the way, while looking around for images to illustrate this norovirus post, I came across a lot of images of people hurling, and worse.  I decided to stick with obscure graphs instead.  No need to thank me.[]
  9. A half-dozen classes in graduate immunology, a half dozen veterinary virology, and a dozen in veterinary immunology this year; plus a couple of guest lectures, where I’ll talk about immunity to viruses, probably focusing on swine-origin influenza virus as a particularly topical example[]