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Friday, January 24, 2014

Norovirus - It's a game of Cat and Mouse

The truth of efficacy testing for disinfectants is that it's not as easy as just "growing" the bug you want to test and seeing if a product can kill it.  Certainly there is a plethora of scientific literature to show how long bugs can survive on surfaces and this often leads us to incorrectly conclude, that if a bug is hardy enough to live on a surface for a significant period of time then it must be hardy enough to be grown in a lab.

Unfortunately, the organisms of interest cannot always be reliably cultured ("grown")  and as a result surrogate organisms are used.

What the heck are surrogates?  Well they are bugs that show genetic and stability similarities to the bug we're interested in.  Perhaps not the best analogy, but one that I certainly know very well from experience is cooking and baking your favorite recipes when your husband is allergic to dairy.  Milk or cream gets substituted with Soya Milk, Almond Milk or Goat's Milk.  Butter is substituted for margarine - but beware, depending on the recipe you also need to consider whether you should use soft or hard margarine and for the record....don't bother trying to make short bread cookies.  With margarine they are NEVER EVER going to taste as good as your Grandma's.

Getting back to surrogates and Norovirus, at present there is no recognized cell culture infectivity model for testing efficacy against Human Norovirus. Efficacy testing relies on the use of viral surrogate models for which a number of factors are considered in selecting a surrogate microorganism such as (a) safety for lab workers, (b) ease of culture and quantitation in the lab, (c) relative resistance to physical and chemical agents, (d) stability in the ambient environment and (e) a reasonable fast turn‐around of test results.

Feline Calicivirus (FCV) is currently accepted around the world as the representative surrogate. FCV is primarily a respiratory pathogen in cats and is found mainly in respiratory secretions. It is also found in cat feces, which can play a role in FCV spread. FCV is also known to infect dogs where it can cause
acute diarrhea, thereby making FCV a very suitable surrogate for Human Norovirus for use in efficacy testing of disinfectants.  FCV is the surrogate recognized and approved by the EPA for making claims against Norovirus on EPA registered disinfectants.

In recent years, we have seen Murine (Mouse) Norovirus (MNV) suggested as a suitable surrogate as it shows greater genetic similarities, pathological and environmental stability to Human Norovirus. MNV can be cultured in the lab. While there are greater genetic similarities between Murine Norovirus and Human Norovirus, Murine Norovirus appears to be less stable and less resistant to microbicides than FCV.  The CDC has made recommendations in their Norovirus Prevention Guideline to perhaps consider products that have been tested against both FCV and MNV.  That certainly can be done, but the long and the short is the EPA ONLY recognizes FCV and when it comes to disinfectant claims in the US - the EPA is the king of the castle!

Certainly, there are a number of researchers who have presented data showing efficacy of different disinfectants to Human Norovirus. However, after conducting a quick literature review, I was unable to find any studies on human Norovirus with an animal end point.  There are a number of studies with Human Norovirus that are based on non-kill parameters (e.g. DNA, RNA, protein analysis).  These types of studies are not accepted by EPA to date as they do not confirm that the virus has been inactivated.  The EPA only accepts efficacy studies that shows that all cells, eggs, or living animals survive after the virus has been treated with a disinfectant. 

In the end, the debate on which virus is a better surrogate for the Human Noroviruses is likely to continue for some time to come. The reality, however, is that the moment you grow a virus in the lab you alter its surroundings and characteristics, including its susceptibility and its resistance to physical and chemical agents. I expect science will find a way some day to effectively grow Human Norovirus so that it can be used to determine disinfectant efficacy, but  for now it's a cat and mouse game where FCV reigns supreme (at least in the eyes ofthe EPA).


Bugging Off!



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