Friday, May 31, 2024

Viruses: Assessment of Survival Kinetics for Emergent Highly Pathogenic Clade 2.3.4.4 H5Nx Avian Influenza Viruses


Photo Credit – FAO

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One of the things that makes H5Nx avian flu so difficult to contain is that it continues to evolve at a rapid pace, and it has diversified into literally scores of different subtypes and genotypes, many of which circulate simultaneously around the world. 

This diversity means something we might say about the H5N1 virus infecting mammals in Peru may not apply to the H5N1 virus infecting cows in the American Midwest, or to the H5N1 virus spreading in birds in Canada. 

Until about a decade ago, H5N1 was almost exclusively a cold weather threat, even in Asia where the virus has been endemic for more than 2 decades.  

Outbreaks would typically begin in November and end by early spring. Only rarely would we see reports over the summer.

When HPAI H5 arrived in North America for the very first time in December of 2014, it faded away by early summer, and did not return the following fall (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl). 

But something happened to the the HPAI H5 virus that invaded Europe in the fall of 2016. During its summer travels China and Russia it reinvented itself by reassorting with other viruses (see EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016), sparking Europe's largest avian epizootic on record.

In addition to being far more virulent in wild and migratory birds (see Europe: Unusual Mortality Among WIld Birds From H5N8), it also displayed the ability to infect a much wider range of birds (see ESA list of 78 species).

Over the next few years we'd see different subtypes (and new genotypes) emerge, sparking epizootics of varying sizes and intensities across Europe, Russia, the Middle East, Asia, and Northern Africa.  In 2017, HPAI H5N8 crossed the equator in Africa and found its way to South Africa.

Again, in 2020-2021, the HPAI H5 virus changed, switching back to a dominant H5N1 subtype, one which unexpectedly crossed the Atlantic, and rapidly spread across North and then South America. Unlike in the past, it was now able to maintain itself (albeit at lower levels) over the summer. 

While much of this success has been attributed to its ability to infect, and persist, in wild birds there is also evidence to suggest that it may persist longer in the environment as well

 A few studies we've looked at over the years include:

  • 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 lest we forget, in 2022, we saw a cautionary report in the EID Journal: Higher Viral Stability and Ethanol Resistance of Avian Influenza A(H5N1) Virus on Human Skin, that found 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.

Today we have a report from the UK looking at the survivability of 5 different HPAI H5 clade 2.3.4.4b viruses collected between 2014 and 2021, in a laboratory environment at 3 different temperatures

Since far more goes into the survival of a virus in the real world than just temperature (e.g. humidity, UV exposure, surface and/or medium, pH, etc.), their results may not tell much much about the survival of H5N1 in the wild, but it does allow us to compare their relative stability at different temperatures.

And from this we learn that not all clade 2.3.4.4b H5 viruses are created equal.  First, the list of viruses used in this study:

Next some excerpts from a much longer study.  Follow the link to read it in its entirety.  I'll have a postscript after the break.  

Assessment of Survival Kinetics for Emergent Highly Pathogenic Clade 2.3.4.4 H5Nx Avian Influenza Viruses

Caroline J. Warren 1,*,Sharon M. Brookes 1, Mark E. Arnold 2, Richard M. Irvine 1,3, Rowena D. E. Hansen 1,4, Ian H. Brown 1,5, Ashley C. Banyard 1,5 and Marek J. Slomka 1,*
Abstract

High pathogenicity avian influenza viruses (HPAIVs) cause high morbidity and mortality in poultry species. HPAIV prevalence means high numbers of infected wild birds could lead to spill over events for farmed poultry. How these pathogens survive in the environment is important for disease maintenance and potential dissemination.

We evaluated the temperature-associated survival kinetics for five clade 2.3.4.4 H5Nx HPAIVs (UK field strains between 2014 and 2021) incubated at up to three temperatures for up to ten weeks. The selected temperatures represented northern European winter (4 °C) and summer (20 °C); and a southern European summer temperature (30 °C).

For each clade 2.3.4.4 HPAIV, the time in days to reduce the viral infectivity by 90% at temperature T was established (DT), showing that a lower incubation temperature prolonged virus survival (stability), where DT ranged from days to weeks. The fastest loss of viral infectivity was observed at 30 °C. Extrapolation of the graphical DT plots to the x-axis intercept provided the corresponding time to extinction for viral decay.

Statistical tests of the difference between the DT values and extinction times of each clade 2.3.4.4 strain at each temperature indicated that the majority displayed different survival kinetics from the other strains at 4 °C and 20 °C.

          (SNIP)

(SNIP)

Overall, for a given H5Nx clade 2.3.4.4 isolate, these data showed the reduction in survival time at 20 °C was at least 2.5-fold faster than the DT values observed at the low incubation temperature (4 °C).

Wild waterfowl cases, during the clade 2.3.4.4 epizootic waves, peaked in the European winter months when these heightened infection pressures would result in accompanying incursions in farmed poultry [12,16]. The two least stable viruses, at least when ranked by their extinction times, were H5N8-2014 and H5N6-2017 (Table 2), and their corresponding significance tests at 20 °C (Table 4) showed this virus pair was significantly different from the other viruses. 

Interestingly, the European winter incursions of H5N8-2014 and H5N6-2017 were the smallest of the five H5Nx clade 2.3.4.4 epizootics, which in the case of H5N6-2017 were essentially limited to wild birds with no accompanying commercial poultry outbreaks during winter 2017–2018 [12,40]. The relative instability of H5N8-2014 and H5N6-2017, reflected in low DT and extinction values, may have contributed to the limited scale of these incursions.

(SNIP)

Conclusions

These quantified virus survival data provide evidence to refine disease prevention strategies for poultry units and inform future veterinary risk assessments for outbreak management, particularly in view of the continuing H5N1 clade 2.3.4.4 HPAIV global epizootic [50,51]. Importantly, these virus survival outcomes contribute to the understanding of AIV persistence in the environment, thereby informing protection of poultry health and commercial production systems. 

These data highlight HPAIV persistence at low temperatures, so presenting a greater infection risk to avian species during the cooler months in temperate latitudes, especially in the case of clade 2.3.4.4 H5Nx HPAIVs to waterfowl with subsequent incursion risks for farmed poultry. Our statistical data, using pairwise comparisons of virus DT values and extrapolated extinction times at 4 °C and 20 °C, (p < 0.05; Table 3 and Table 4), revealed that, in many instances, the virus survival (stability) of each isolate was significantly different from the others. 

The relevance of these experimental findings has been underlined by the detection of H5N1 HPAIV in the immediate farm environment during UK clade 2.3.4.4 outbreaks in 2023 [38], affirming observations during earlier H5N1 GsGd HPAIV outbreaks [37].
These experimental and field-based studies are now identifying the consequences of environmental contamination, which have arisen from AIV incursions (either wild birds or poultry) and may influence onward spread. The temperature stability of isolates can also inform the likelihood of continuing infectivity, particularly during the vulnerable period prior to statutory cleansing and on-farm disinfection interventions [52,53]. Interestingly, heat treatment may provide an alternative to chemical disinfection, thereby giving additional importance to the outcomes of viral temperature stability investigations [54,55].
         (Continue . . . )


Interestingly, while the 2021 H5N1 virus came in 3rd in the 4 °C and 20 °C stability tests, it tied for 2nd at 30 °C.  But by any of their measures, the H5 virus of today is far hardier than the virus that emerged in 2014. 

While it would have been nice to see a 2023/2024 H5N1 isolate tested, with multiple genotypes currently circulating in the UK - and more expected - those results might not tell us very much. 

H5Nx remains very much a moving target. 

We have a long history of underestimating viruses, but they have evolved over ten of millions of years with only one purpose; to survive. And they've gotten exceedingly good at that.

Studies like today's remind us just how well adapted, and formidable, H5N1 has become. And it is only through a better understanding of how it functions that we can hope to contain it.