Disinfectant testing against human norovirus surrogates—What infection preventionists need to know

To the Editor—Human norovirus is the leading cause of acute viral gastroenteritis worldwide, and it is the greatest contributor to foodborne illness. The illness affects millions of people every year, as well as many restaurants, schools, and healthcare establishments, among others.^{1, 2} Symptoms include nausea, vomiting, and diarrhea and usually last 2–3 days. The virus is transmitted by direct routes (person-to-person most commonly), or indirectly (via contaminated surfaces or contaminated food and water).³ Viruses are typically studied and quantified using cell-culture–based infectivity assays, a model in which viruses are propagated in the laboratory in vitro. However, until very recently, such a system did not exist for human norovirus.⁴ In its absence, molecular-based techniques such as real-time polymerase chain reaction (RT-PCR) have been used to quantify reductions in norovirus. However, these techniques cannot differentiate between infectious and noninfectious virus, so they have limited utility in disinfection studies.⁵ Due to the issues with culturing and quantifying human norovirus, the US Environmental Protection Agency (EPA) has turned to the use of culturable norovirus surrogates for petitioning label claims.

The EPA currently only allows virucidal claims against human norovirus to be made from data that demonstrate a disinfectant’s efficacy against feline calicivirus (FCV)⁶. Despite this, there are EPA-registered products that cite efficacy against murine norovirus (MNV) as the basis for their antinoroviral claims. The problem with these surrogates is that their response to sanitizers and disinfectants may not reflect the true behavior of human norovirus, a problem that the CDC recognizes for feline calicivirus.⁷ For example, it is well documented that FCV is readily inactivated at low and high pH. However, human norovirus must survive the highly acidic gastrointestinal tract to infect its host, so it is much more resistant to low pH (ie, acid environment) than is FCV.⁸ As FCV is the only EPA-accepted surrogate,⁶ manufacturers of disinfectants have no choice but to use it as the basis for claims of antinoroviral activity. Even replacing FCV with MNV is not advisable because data have shown MNV to be more susceptible to alcohols than FCV,^{8, 9} and based on PCR assays, many human norovirus strains appear to be more resistant to alcohols than MNV.^{8, 9} In short, whether the surrogate is FCV or MNV, there are documented instances in which inactivation of norovirus surrogates with a sanitizer or disinfectant does not translate to equal efficacy against human norovirus. When this occurs, human norovirus is almost always the more resistant.

A third surrogate has recently begun appearing in the literature that shows less susceptibility to alcohols and/or pH extremes. Tulane virus is another member of the Caliciviridae family, to which human norovirus belongs, and shares many important features with its norovirus cousins.¹⁰ For example, Tulane virus is the only human norovirus surrogate that binds histo-blood group antigens, which are believed to be the norovirus host cell receptor. The ability of Tulane virus to bind these antigens is likely due to the similarity between its capsid and that of human norovirus.¹⁰ Similarities in the capsid protein are important because disruption of this protein is usually a critical aspect of inactivation by disinfectants.¹⁰ Because evidence is mounting regarding the behavior of Tulane virus in disinfection studies, it should be considered by regulatory agencies as a justifiable surrogate for human norovirus.

As the new human norovirus culture technique improves and is used more widely, it should become feasible to test disinfectants against the real virus of concern. This would prevent the confusion associated with interpreting results from surrogates. Until that time, it is best to follow the guideline of the Centers for Disease Control and Prevention (CDC) to use a chlorine-bleach solution, ⁷ which based on current data, is the most effective disinfectant against human norovirus.⁸ As the regulatory landscape continues to evolve, it is important for health practitioners to be cognizant of potential limitations of surrogates, specifically their differential behavior compared to one another and to human norovirus, even those recognized by the EPA. Public health, not regulatory compliance, should form the cornerstone of infection control. As practitioners, let us be cognizant of the scientific limitations in our current regulatory system and always choose what is right for health.