Photo Credit – CDC
#16,554
Since fomite transmission is assumed to play a significant role in the spread of many diseases, over the years we've looked at the stability, and viability, of a variety of viruses on surfaces (see EID Journal: Prolonged Infectivity of SARS-CoV-2 in Fomites).
Environmental factors (ambient temperature, humidity, UV exposure) and the type of surface (steel, plastic, skin, etc.) all impact viability outside of a host organism, but the type of virus also appears to play a role.
We also know that some viruses (e.g. Norovirus) are harder to kill with alcohol hand sanitizer or disinfectants (see CMAJ: Hand Sanitizers May Be `Suboptimal’ For Preventing Norovirus).
In 2014's ICAAC Video: How Quickly A Virus Can Spread In A Building, we looked at an experiment on fomite transmission, which they described as:
Using tracer viruses, researchers found that contamination of just a single doorknob or table top results in the spread of viruses throughout office buildings, hotels, and health care facilities. Within 2 to 4 hours, the virus could be detected on 40 to 60 percent of workers and visitors in the facilities and commonly touched objects. Simple use of common disinfectant wipes reduced virus spread by 80 to 99 percent.We've even seen evidence that viruses may be aerosolized via a more circuitous route (see NIOSH Video: Adventures In Toilet Plume Research). So understanding how long different viruses persist on various environmental surfaces (including human skin), and what it takes to deactivate them, are important topics for infection control.
Normally influenza viruses are expected to remain viable - under optimal conditions - for only a few hours outside of a living host (see Influenza Virus Survival At Opposite Ends Of The Humidity Spectrum).
But we've also seen reports of much longer persistence in the wild, particularly of HPAI H5N1.
A 2010 study conducted by researchers at the National Institute of Animal Health, Tsukuba, Ibaraki, Japan determined that the H5N1 virus may also on the dropped feathers from infected ducks and may therefore spread to the environment.
Persistence of Avian Influenza Virus (H5N1) in Feathers Detached from Bodies of Infected Domestic Ducks
Yu Yamamoto, Kikuyasu Nakamura, Manabu Yamada, and Masaji Mase
At 4°C (39F) the the H5N1 virus was detectable in feathers for 160 days, while at the higher temperature 20°C (68F), the virus was detected for 15 days.
Detectable doesn't necessarily mean viable, however. RT-PCR tests can often pick up remnants of inactivated viruses.
In 2012's EID Journal: Persistence Of H5N1 In Soil, we looked at several studies that found H5N1 could remain viable on various surfaces, and in different types of soil, for up to 13 days (depending upon temperature, relative humidity, and UV exposure).
And in 2017, researchers showed that - when refrigerated - H5N1 infected poultry could remain infectious for months (see Appl Environ Microbiol: Survival of HPAI H5N1 In Infected Poultry Tissues).
During the 2015 HPAI H5 Epizootic in North America, we saw serious discussion of the airborne spread of avian flu - over miles - via contaminated dust (see Nature: Airborne Transmission May Have Played A Role In Spread Of U.S. 2015 HPAI Epizootic).
With the Eurasian H5N1 virus recently determined to have some zoonotic potential (see ECDC/EFSA Raise Zoonotic Risk Potential Of Avian H5Nx), and its continued spread around the globe - including now into North America - there is an increased need to better understand how it persists in the environment.
All of which bring us to a new research article in the CDC's EID Journal that finds that H5N1 demonstrates an enhanced ability to survive on some surfaces, and is less affected by low concentrations of ethanol than than other common influenza subtypes.
Volume 28, Number 3—March 2022
Research
Higher Viral Stability and Ethanol Resistance of Avian Influenza A(H5N1) Virus on Human Skin
Risa Bandou, Ryohei Hirose, Takaaki Nakaya, Hajime Miyazaki, Naoto Watanabe, Takuma Yoshida, Tomo Daidoji, Yoshito Itoh, and Hiroshi Ikegaya
Abstract
Evaluating the stability of highly pathogenic avian influenza viruses on human skin and measuring the effectiveness of disinfectants are crucial for preventing contact disease transmission. We constructed an evaluation model using autopsy skin samples and evaluated factors that affect the stability and disinfectant effectiveness for various subtypes.The survival time of the avian influenza A(H5N1) virus on plastic surfaces was ≈26 hours and on skin surfaces ≈4.5 hours, >2.5-fold longer than other subtypes. The effectiveness of a relatively low ethanol concentration (32%–36% wt/wt) against the H5N1 subtype was substantially reduced compared with other subtypes. Moreover, recombinant viruses with the neuraminidase gene of H5N1 survived longer on plastic and skin surfaces than other recombinant viruses and were resistant to ethanol.Our results imply that the H5N1 subtype poses a higher contact transmission risk because of its higher stability and ethanol resistance, which might depend on the neuraminidase protein.(SNIP)
Discussion
Although previous studies have suggested that the stability of AIVs might vary among subtypes, the details remain unknown (20–22,25). In this study, we first evaluated the stability (survival time and half-life) of several influenza subtypes on plastic and human skin surfaces and clarified the differences in their stability. No significant differences were observed in the survival times and half-lives of most subtypes. However, the survival times and half-lives of 2 different H5N1 strains (H5N1-Ky and H5N1-Eg) on plastic and skin surfaces were approximately twice as long as those of the other subtypes tested, indicating that the H5N1 subtype had significantly higher stability.
These findings suggest that the H5N1 subtype poses a higher risk for contact transmission than other subtypes. Specifically, the higher stability of the H5N1 subtype might be a reason that among AIVs, the H5N1 subtype is often transmitted from birds to humans. In addition, because the 4-hour survival time of the H5N1 subtype on human skin increases the risk for viral invasion into the body or for transmission from the skin to other surfaces, appropriate hand hygiene practices are especially vital (compared with other subtypes) for preventing contact transmission of this subtype. Furthermore, the survival times revealed in this study will help determine the interval during which contact transmission could occur and how contact transmission might be established.
Next, we evaluated the effectiveness of disinfectants against influenza viruses on the skin surface by using our ex vivo evaluation model that reproduced actual hand hygiene condition and elucidated the differences in disinfectant efficacy against different subtypes (26–28). All viruses on the skin surface were completely inactivated by exposure to alcohol-based disinfectants (high concentrations of EA or IPA) for 15 seconds. In addition, most viruses on the skin surface were completely inactivated by exposure to 36% EA for 15 seconds, but the H5N1 subtype was not. These findings reveal that the H5N1 subtype was more resistant to EA than other subtypes and that the effectiveness of relatively low EA concentrations (36% wt/wt or 43% vol/vol) against the H5N1 subtype was lower. Therefore, to control contact transmission of the H5N1 subtype, disinfectants with appropriate EA concentrations, as proposed by the World Health Organization (>52% wt/wt or >60% vol/vol), should be used (41). Although low-level disinfectants such as BAC and CHG were much less effective than alcohol-based disinfectants, high concentrations of low-level disinfectants (i.e., 0.2% BAC or 1.0% CHG) were relatively effective against all influenza viruses on the skin surface. These results suggest that high concentrations of BAC-based and CHG-based disinfectants might be applicable for hand hygiene targeting influenza viruses as an alternative to alcohol-based disinfectants, although additional studies are needed to validate this possibility.
Finally, we tried to elucidate the genetic mechanisms responsible for differences in stability and disinfectant effectiveness among subtypes by using different recombinant viruses. The stability of all recombinant viruses tested (except rH5N3-H5N1-NA) on plastic and human skin surfaces was similar to that of all influenza viruses studied (except H5N1). Moreover, the survival time and half-life of rH5N3-H5N1-NA (a recombinant H5N3 virus with the NA gene of an H5N1 virus) on the plastic and human skin surfaces were approximately twice as long as other recombinant viruses, and it had the same stability as the H5N1 subtype (H5N1-Ky and H5N1-Eg). While evaluating the effectiveness of disinfectants, we found that although all recombinant viruses tested (except rH5N3-H5N1-NA) were completely inactivated by exposure to 36% EA for 15 seconds, only rH5N3-H5N1-NA was not significantly inactivated by exposure to 36% EA, and it had the same EA resistance as the H5N1 subtype. These results strongly suggest that the higher stability and EA resistance of the H5N1 subtype might depend on NA, a spike protein. Although several studies have focused on the relationship between the NA segment and virulence (42,43), to the best of our knowledge, no study has focused on the relationship between the NA segment and stability. Future studies focusing on the NA segment are expected to elucidate factors that determine the stability and help identify subtypes with high stability and a high risk for contact transmission.
The first limitation of our study is that we used an ex vivo evaluation model in this study using human skin samples collected during forensic autopsies, because the application of highly pathogenic viruses (such as the H5N1 subtype) on the skin of humans is dangerous. At this stage, we tentatively conclude that virus survival time would not substantially differ between autopsy skin specimens and live human skin or between the different autopsy specimens. However, improving measurement accuracy, increasing the number of cumulative measurement samples, and more thorough evaluation of skin properties might elucidate the properties of skin samples and donor factors that affect virus survival. Second, we analyzed virus stability by mixing virus and PBS in this study. The use of solvents other than PBS (e.g., cell culture medium or human upper respiratory tract–derived mucus) might affect the residual virus titer on the surface and the analysis results. Furthermore, the evaluation was performed in a controlled environment (25°C and 45%–55% relative humidity); however, changes in temperature and humidity might have an effect on virus stability. Finally, this study revealed that the NA proteins in the influenza virus might contribute to the high stability of the H5N1 subtype, but the properties of the NA proteins that affect virus stability were not elucidated. In the future, preparing recombinant viruses with various NA proteins and clarifying the properties of NA that affect virus stability will be necessary.
In conclusion, we found that the H5N1 subtype had a higher risk for contact transmission because of its higher stability on plastic and skin surfaces and higher resistance to EA than other subtypes. Therefore, the optimal infection control methods may differ for each subtype. Our findings also suggest that these characteristics might depend on the NA protein.
Dr. Bandou is a project researcher in the Department of Forensics Medicine at Kyoto Prefectural University of Medicine, Kyoto, Japan.
