Friday, March 31, 2023

NOAA SPC: Large Swath Of Central US Under Moderate Risk Of Severe Storms

 


#17,381

Later today portions of 7 states (Iowa, Illinois, Missouri, Kentucky, Tennessee, Arkansas, and Mississippi) will find themselves under a moderate risk of severe storms, including tornadoes, less than a week after an F4 tornado tore through northern Mississippi claiming 25 lives. 

The latest forecast advisory from the NWS SPC reads:

   

There have already been more than 310 confirmed tornadoes across the United States in the first 3 months of 2023, and April and May - often the most active months - still lie ahead. 


I you haven't already, you should activate weather alerts on your cell phone, and have a NSWS weather radio as a backup.  If you are in a warned area, take it seriously, and seek shelter immediately. 


For most Americans, a severe weather event is their biggest regional disaster threat; hurricanes, tornado outbreaks, blizzards, Derechos, and ice storms affect millions of people every year. Having a good (and well rehearsed) family emergency plan is essential for any disaster.


It is important for your plan to include emergency meeting places, out-of-state contacts, and individual wallet information cards - before you need it (see #NatlPrep : Create A Family Communications Plan).

Together with adequate emergency supplies, a solid first aid kit, and an emergency battery operated NWS Weather Radio, these steps will go a long ways to protecting you, and your family, from a wide variety of potential disasters.
As a Floridian I am more than aware that we are only 2 months from the start of the Atlantic Hurricane season - and while the worst storms aren't expected until later in the summer - I'll review my hurricane preps in May.  

Before I need them. 

For some recent preparedness blogs to help get you prepared for whatever may come, you may wish to revisit:

Because it's not a matter of `if' another disaster will strike . .  . 

It's only a matter of wherewhen, and how bad. 

 

Nature: Within-host Genetic Diversity of SARS-CoV-2 Lineages in Unvaccinated and Vaccinated Individuals

Credit ACIP/CDC 

#17,380

Although COVID vaccines have undoubtedly saved millions of lives, and spared countless more from severe illness, one of the theoretical concerns over the deployment of any pandemic vaccine is that they might help drive viral evolution, leading to the generation of vaccine-escape variants

There is some evidence to suggest that the use of (often substandard, or poorly matched) poultry vaccines has led to the rise of new new, potentially more dangerous, avian flu strains. 

The following comes from a 2014 EID Journal dispatch titled  Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China: 

HPAI mass vaccination played a crucial role in HPAI control in China. However, this study demonstrated multiple disadvantages of HPAI mass vaccination, which had been suspected (13,14). For example, this study showed that H5N1 subtype HPAI virus has evolved into multiple H5N2 genotypes, which are all likely vaccine-escape variants, suggesting that this virus can easily evolve into vaccine-escape variants.

This observation suggests that HPAI mass vaccination, which is highly effective in the beginning of an outbreak, may lose its effectiveness with time unless the vaccine strains are updated. Moreover, this study showed that vaccinated chicken flocks can be infected with vaccine-escape variants without signs of illness.

We know that vaccines don’t always prevent infection. Sometimes they only mask or minimize the symptoms, and in that environment vaccine resistant mutations may emerge and potentially be transmitted onward. 

This is a concern we explored in the summer of 2021 (see UK Sage: International Vaccination: Potential impact on Viral Evolution and UK), in a report that looked at the potential impact of vaccine-induced viral evolution of SARS-CoV-2. 

While the authors argued that increased international vaccine coverage was more likely to help prevent the emergence of new variants, they acknowledged there were unknowns.

At roughly the same time, in  UK SAGE: Can We Predict the Limits of SARS-CoV-2 Variants and their Phenotypic Consequences?), that expert group called additional genetic and antigenic drift of the virus almost inevitable. As predicted, since then we've seen a remarkable expansion in the diversity of SARS-CoV-2 viruses, including the emergence of the (now dominant) Omicron lineage. 

But the question remains: Did the COVID vaccine contribute to this abrupt evolutionary shift in the virus?

Last fall, in Viruses: Evolutionary Pattern Comparisons of the SARS-CoV-2 Delta Variant in Countries/Regions with High and Low Vaccine Coverage, we looked at a study - based on limited, country-level data - that found little evidence that high vaccine uptake was driving the evolution of the SARS-CoV-2 virus. 

Today we've another look at the issue from some well-known names in virology from the University of Hong Kong.  

Instead of comparing the emergence of variants from high and low vaccine uptake countries, they actually looked at the diversity of COVID strains detected within thousands of vaccinated and unvaccinated individuals. 

This is, as you might imagine, a lengthy, detailed, and highly technical report.  I've only reproduced the Abstract, and some excerpts from the Introduction and Discussion. 

Those without a high tolerance for statistics and a basic understanding of virology will find it tough sledding (I know I did), but the whole report is very much worth reading. 

While this may not be the final word on the subject, reassuringly these researchers did not find any evidence suggesting vaccinated individuals are more likely to produce, and spread, viral variants. 

Article
Open Access
Published: 31 March 2023

Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals

Haogao GuAhmed Abdul QuadeerPavithra KrishnanDaisy Y. M. NgLydia D. J. ChangGigi Y. Z. LiuSamuel M. S. ChengTommy T. Y. LamMalik PeirisMatthew R. McKayLeo L. M. Poon

Nature Communications volume 14, Article number: 1793 (2023) Cite this article


Abstract

Viral and host factors can shape SARS-CoV-2 evolution. However, little is known about lineage-specific and vaccination-specific mutations that occur within individuals. Here, we analysed deep sequencing data from 2,820 SARS-CoV-2 respiratory samples with different viral lineages to describe the patterns of within-host diversity under different conditions, including vaccine-breakthrough infections.

In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity and were under neutral to purifying selection at the full genome level compared to non-VOC SARS-CoV-2. Breakthrough infections in 2-dose or 3-dose Comirnaty and CoronaVac vaccinated individuals did not increase levels of non-synonymous mutations and did not change the direction of selection pressure. Vaccine-induced antibody or T cell responses did not appear to have significant impact on within-host SARS-CoV-2 sequence diversification.

Our findings suggest that vaccination does not increase exploration of SARS-CoV-2 protein sequence space and may not facilitate emergence of viral variants.

Introduction

The SARS-CoV-2 pandemic continues to spread globally. Despite the vaccination of over 69% of the world population1, the risk of SARS-CoV-2 reinfections and breakthrough infections is increasing due to the emergence of new viral variants2,3. Multiple variants of concern (VOC) have demonstrated the ability to evade naturally-acquired or vaccine-induced immunity4,5,6. Therefore, it is crucial to investigate the impact of vaccination on the mutational and evolutionary processes of SARS-CoV-2.

Genomic surveillance has been used to trace the transmission and evolution of SARS-CoV-2 mutations at local, regional, and global scales throughout the pandemic7,8,9. However, there is still limited knowledge of how these mutations originate and accumulate within hosts. Within-host mutations can arise through replication errors or RNA damage/editing10 and they may be subject to fixation by stochastic (genetic drift) and deterministic (natural selection) processes. We and others have previously found that the SARS-CoV-2 transmission bottleneck between hosts is narrow8,11,12,13,14, suggesting that only few virions are transferred from the host during transmission. Most of the low-frequency mutations are not transmitted between patients, which constrains the use of intrahost single nucleotide variants (iSNVs) for effective contact tracing12,15,16. However, it remains important to investigate the within-host diversity of SARS-CoV-2 to understand host-level evolutionary forces.

Studying SARS-CoV-2 within-host diversity under different conditions may reveal factors that control virus evolution. Host and viral factors can both contribute to within-host diversity. Host factors such as species (animals/humans)17, viral shedding time18, and immune status19 were previously reported to have effects on intrahost SARS-CoV-2 diversity. It was hypothesized that prolonged infections in hosts with distinct immunological backgrounds (e.g., animals or immunocompromised patients) may hasten viral evolution and lead to the emergence of novel variants17,20. However, there is limited knowledge about post-vaccination characteristics of within-host selection pressures, which consistently act on the virus during the entire course of breakthrough infection. Besides, viral factors such as different virus lineages may also affect SARS-CoV-2 replication properties. SARS-CoV-2 VOCs have exhibited varying capacities to evade immunity4,6 and acquire higher transmissibility21,22. However, it is not clear whether different SARS-CoV-2 variants differ in within-host selection pressures.

Here, we analysed 2,820 deep-sequenced SARS-CoV-2 samples collected in Hong Kong (HK) between mid-2020 and 2022. The within-host diversity in SARS-CoV-2 infections from different lineages (VOCs and non-VOCs) and in breakthrough (Delta or Omicron) infections after Comirnaty or CoronaVac vaccination (two or three doses) were studied. Our results provide insights into the variation of within-host diversity, and the mutational patterns and selection pressures acting on viruses.
(SNIP)

Discussion

(Excerpt)
Vaccination is another factor which may affect the within-host virus evolution. We studied samples from Comirnaty and CoronaVac vaccine breakthrough infections and found that vaccination may be associated with changed mutation rates but might not change selection pressure. We found 2-dose Comirnaty vaccination was associated with increased synonymous nucleotide diversity and marginally significant purifying selection pressure at the full genome level, while similar effects of 2-dose CoronaVac vaccination was not as significant. Notably, the increased nucleotide diversity in specimens of Delta breakthrough infection in 2-dose Comirnaty vaccinated individuals is mostly synonymous rather than non-synonymous (Supplementary Table 4). Comirnaty vaccine is known to be more immunogenic than CoronaVac vaccine43 and this may contribute to our observation. It is also relevant to note that Comirnaty vaccine only has the spike protein as an immunogen but appears to impact on purifying selection elsewhere in the genome.
Crucially, vaccination does not increase exploration of the protein sequence space as non-synonymous nucleotide diversity does not seem to be increasing. For Omicron virus samples, we did not observe significant changes in incidence of iSNVs, nucleotide diversity or selection pressure in samples with 2-dose Comirnaty/CoronaVac vaccination. However, 3-dose Comirnaty vaccination virus samples seemed to have significantly lower incidence of iSNVs and nucleotide diversity than 2-dose or unvaccinated Omicron virus samples. The viral loads of 3-dose samples are similar to viral loads of other samples (Supplementary Fig. 13), suggesting that vaccination did not directly suppress viral replication, but might have limited exploration of sequence space. The low diversity observed in 3-dose Comirnaty Omicron samples was not as significant in 3-dose CoronaVac Omicron samples (there was no significant difference between collection lags or time since last dose between the two vaccines), possibly due to immunogenic difference between the two vaccines. We, however, do not exclude alternative hypotheses to explain this observation. Furt
As HK used an elimination strategy to control COVID-19, the individuals investigated in our study can be reliably categorised as immunologically naïve or vaccinated individuals, which is a significant advantage of our study. Nonetheless, our study has several limitations. Most of the studied cases have only single-timepoint samples, making it hard to study the temporal changes of within-host selection pressures. Although we made an effort to account for biases from sampling and different viral loads, false positive variant calls can still be an issue in analysing next-generation sequencing data, particularly from clinical samples that are of limited availability. A well-planned cohort, which can control major potential confounding factors, e.g., different demographic backgrounds, vaccination time lags, sample collection time points, and sequencing conditions, would provide a more robust estimation on iSNVs profiles in SARS-CoV-2 infections. Besides, in studying the effect of T cell pressure on within-host viral evolution, we could not perform an individual-based analysis since HLA typing of the patients was not possible in our study. In addition, since most of the individuals in our study were either infection naïve or vaccinated prior to infection, the effect of hybrid immunity on SARS-CoV-2 within-host evolution could not be addressed and requires further investigation.
In conclusion, our work suggests that SARS-CoV-2 within-host evolution may exhibit different patterns in different virus lineages and in vaccinated individuals. We found that 2-dose or 3-dose Comirnaty and CoronaVac COVID-19 vaccination does not seem to increase non-synonymous mutations in VOCs, suggesting that vaccination may limit the exploration of protein sequence space and the emergence of more viral variants.

         (Continue . . . )

Gu, H., Quadeer, A.A., Krishnan, P. et al. Within-host genetic diversity of SARS-CoV-2 lineages in unvaccinated and vaccinated individuals. Nat Commun 14, 1793 (2023). https://doi.org/10.1038/s41467-023-37468-y

Thursday, March 30, 2023

USDA Adds More H5N1 Mammalian Detections To List



#17,379

Today the USDA has updated their list of H5N1 detections in mammalian wildlife, adding 6 new cases (3 of which we've seen previously reported here and here), since their last update on March 17th.  To date, 154 mammals have been identified in the United States, although this is almost certainly a significant undercount. 

Peridomestic mammals, like red foxes and skunks, are the most commonly reported terrestrial mammals infected, although we are seeing an increasing number of big cats and bears being infected in recent months.

Earlier this month, in ECDC/EFSA Avian Influenza Overview December 2022 – March 2023, researchers described recent changes to the virus that may make it more of a threat to mammalian hosts.

Mutations identified in A(H5N1) viruses from mammals 

About half of the characterized viruses contain at least one of the adaptive markers associated with an increased virulence and replication in mammals in the PB2 protein (E627K, D701N or T271A) (Suttie et al., 2019). These mutations have never (T271A) or rarely (E627K, D701N) been identified in the HPAI A(H5) viruses of clade 2.3.4.4b collected in birds in Europe since October 2020 (<0.5% of viral sequences from birds). 

This observation suggests that these mutations with potential public health implications have likely emerged upon transmission to mammals. Moreover, the viruses collected in October 2022 from a HPAI A(H5N1) outbreak in intensively farmed minks in northwest Spain (Aguero et al., 2023) shows mutations in the NA protein which cause disruption of the second sialic acid binding site (2SBS). This feature is typical of human-adapted influenza A viruses, which may favour the emergence of mutations in the receptor binding site of the HA protein (de Vries and de Haan, 2023). These same mutations were detected also in seven A(H5N1) viruses from birds. 

All of which means, that while often repetitive, reports of additional spillovers into mammals are of great importance.   

The new additions to the list include:







Although surveillance and testing of wild birds is limited, H5N1 has now been reported in Alaska and all 48 of the lower states.


So far, unlike with SARS-CoV-2 in deer, we haven't seen signs of H5N1 transmitting efficiently in mammalian wildlife (possible, but unproven exceptions are in marine mammals). But once again, surveillance is extremely limited. 

For more on the risks from avian flu spilling over into wildlife, you may wish to revisit:


UK Novel Flu Surveillance: Quantifying TTD


Credit CDC


#17,378

Although it is only Thursday, this week we've already seen two novel flu detections announced in humans; an H3N8 case in Guangdong Province, China and an H5N1 case reported last night in Northern Chile

While these cases appear to be sporadic and likely due to bird-to-human transmission - and there are no indications of community spread - the reality is our ability to detect a community outbreak in its early stages is limited.

We've discussed this often over the years, but it requires more than a little luck to detect sporadic cases, like the ones reported this week, even in countries with well-equipped and functioning public health systems.

First, an infected person must become sick enough to seek medical care, which - depending on the flu strain - may exclude > 90% of infections. They then must have access to modern medical care, an option not available to > 40% of the world's population, and then be lucky enough to be properly tested for novel influenza. 

We've seen numerous studies (see here, here, and here) suggesting that only a small fraction of novel flu (or MERS-CoV) cases are ever detected, and reported, by surveillance.  Perhaps as few as 1% or 2%. 

While there have been only a handful of clade 2.3.4.4b H5N1 infections reported in humans over the past 18 months, the real number of spillover events is unknown. The good news, however, is we've seen no signs of sustained of efficient community spread. 

But the obvious question is, how long would it take for us to recognize community spread if it were occurring? 

That obviously depends on where an outbreak occurs, its severity, and how fast it is spreading (R-Value). It would presumably be easier to detect in places London, or Tokyo, or New York City than in Outer Mongolia, or Ethiopia.  

But according to yesterday's UKHSA Technical Briefing #3 on H5N1, even in a developed  country like the UK, it might take weeks

Yesterday we looked at the UK's three working `pandemic scenarios', but today we'll look at an analysis of the UK's ability to detect community transmission of a novel flu virus.  As you'll see, the Expected time to detection (TTD) and the cumulative number of infections (CI) before we'd know there was community spread are sobering. 

Investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing 3

Updated 29 March 2023
(EXCERPT)

3.3 Time to detection


The above scenarios are used to derive estimates of time to detection (TTD) of avian influenza under various testing scenarios. This is based on the assumption of sustained person to person transmission, and no cross-immunity from previous influenza vaccination or infection.

Disease growth in such a situation can be simply modelled as daily growth equals R to the power of 1 over the serial interval (SI). To account for variation in the SI, it is sampled from a Weibull distribution, with mean and median of 3 days, and growth simulation run 100,000 times to yield an expected growth curve and confidence intervals.

The TTD is determined for a number of testing scenarios
, estimating the point at which the outbreak will have grown large enough we expect to detect a case. This depends both on the growth rate and the severity (for hospital-based testing). Testing scenarios modelled are:
  • sampling of asymptomatic individuals in the community with coverage of 1 in 1,000 people tested daily
  • sampling of asymptomatic individuals in the community with coverage of 1 in 200 people tested daily
  • testing of all hospital admissions (with influenza-like illness (ILI) symptoms)
  • testing of admissions to intensive care units (ICU) only (with ILI symptoms).
Figure 7 shows the expected TTD in each scenario with an R of 1.2, with Figure 8 showing the equivalent when R equals 2. Day 0 is the day the first case becomes infected. The TTD includes delays for: testing (2 days); admission to hospital (9 days); and admission to ICU (a further 2 days) as appropriate. For simplicity the community testing is assumed to take place in the mild severity scenario.

With a lower R (and hence longer doubling time) it may take twice as long to detect an avian influenza case using lower coverage community testing, as it does to detect when testing hospital admissions. Therefore, there may be substantial numbers of infections in the community by the time the first case is detected.

Tables 3a and 3b show the expected number of infections by the time each testing scenario detects the first case. Being able to test in multiple settings improves the speed of detection across a range of plausible R values.







 (Continue . . . )


The UK now estimates it would likely take between 3 and 10 weeks before community spread would become apparent to authorities, after anywhere between a few dozen to a few thousand community infections.  

And this is for the UK. The TTD in many less-developed regions would presumably take longer.

A reminder than anything we say about the current threat from H5N1, H3N8, MERS-CoV, or any other pandemic threat must carry an implied asterisk.  

A disclaimer that says, ` * based on available, and likely incomplete, information. . .  '


Wednesday, March 29, 2023

Chile: MOH Reports Their 1st Human H5N1 Infection


#17,377


Although details are scant at this hour, Chile's Ministry of Health tweeted late this afternoon on their first confirmed H5N1 infection, in a 53-year old male in the northern part of the country.  A hat tip to Sharon Sanders at FluTrackers for the head's up. 

The brief announcement from the Ministry's website follows:

March 29, 2023
MINSAL reports first human case of bird flu in Chile

The Ministry of Health reports the first case of bird flu in humans in Chile, reported in northern Chile.

The sick person corresponds to a 53-year-old man affected by a severe influenza case. The patient is stable within his gravity.

The health protocols established for the management of this disease were activated and the corresponding tests were taken for analysis by the Institute of Public Health (ISP), which confirmed that it is avian influenza.

The source of contact is investigated and whether there is a history of others affecte in the patient's environment.

The H5N1 virus or “bird flu” is a virus that can be transmitted from birds or marine mammals to humans, but there are no known cases of human-to-human transmission.

The Ministry of Health calls on citizens not to handle sick or dead birds or mammals and urges poultry workers to follow the corresponding safety protocols and to get vaccinated against seasonal influenza.


This case is the 2nd reported in South America (see Ecuador's case report), and the 8th overall from clade 2.3.4.4b H5N1 (note: some doubt has been cast on the infection status 2 cases from Spain).   

Given that mild or moderate influenza infections are rarely hospitalized and then tested for novel viruses, it is possible - perhaps even likely -  that some cases have escaped detection. 

So far, however, we've not seen any evidence of efficient or sustained human-to-human transmission. 

UK Technical Briefing (#3) On Risk To Human Health From HPAI H5N1

 

#17,376

Although it still isn't clear whether avian H5N1 has the `right stuff' to spark a human pandemic, over the past 18 months we've seen it spread across two new continents (North & South America), spillover into dozens of mammalian species (including a few humans), and reinvent itself into more than 5 dozen new genotypes. 

Regardless of whether it will be successful, it is certainly sending out warning signs. 

Along the way we've seen - with increasing frequency - a number of detailed risk assessments, and technical documents, released by major public health entities like the WHO, CDC, ECDC, and the UK's HSA.   

A few in recent months include:

CDC Technical Report: Highly Pathogenic Avian Influenza A(H5N1) Viruses
New information on outbreaks in poultry, spillovers into mammals, new emerging genotypes, and sporadic human infections emerges practically every day, necessitating frequent updates. Today, for the third time in as many months, the UK's Health Security Agency has updated and published their risk assessment. 

This is a lengthy, and quite detailed report, and while much of it is a rehash of what we've seen in previous reports, in today's briefing they include 3 potential pandemic scenarios of differing severity. 

They had briefly mentioned the first two scenarios (a mild and a severe 1918-style pandemic) in their last report, but have fleshed it out to include a 3rd, even more severe scenario. 

You'll note, however, that the `tabloid-favored' 50% fatality rate is not considered, as that is based only on a very limited sample of hospitalized H5N1 cases reported over the past 20 years (mostly from places with limited healthcare delivery). 

For a more detailed look at why a 50% fatality rate is highly unlikely, you may with to revisit The H5N1 CFR (Case Fatality Rate) Debate.

I've only posted a few excerpts from the UK report, so follow the link to read it in its entirety.

Research and analysis
Investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing 3
Updated 29 March 2023
Applies to England
Contents

The UK Health Security Agency (UKHSA) is working with the Animal and Plant Health Agency (APHA), the Department for Environment, Food and Rural Affairs (DEFRA) and the public health agencies of the 4 nations to investigate the risk to human health of avian influenza (influenza A H5N1) in England. This briefing is produced to share data useful to other public health investigators and academic partners undertaking related work. It includes early evidence and preliminary analyses which may be subject to change.

Data reported in the technical briefing is as of 15 March 2023 (or as specified in the text) to allow time for analysis.

Code associated with technical briefings can be found on GitHub.
Levels of human health risk related to the outbreak of avian influenza in England

Since the previous technical briefings, risk levels have been updated by the Technical Group. These adjusted levels synthesise epidemiological, virological and genomic indicators at every stage.

The following indicators are used for assessment of the risk level:
The avian influenza outbreak can be considered to fall into one of 7 potential levels of transmission:
  • detections in wild and farmed birds, avian host range and seasonal pattern
  • the frequency, nature and host range of mammalian spillover infections
  • exposures of confirmed human cases
  • the size of any clusters of mammalian or human infections, the implied mode of transmission (for example, evidence of long-range aerosol transmission), and estimated transmissibility where possible
  • genomic and phenotypic evidence of changes in receptor binding or other changes that may impact transmissibility (haemagglutinin)
  • genomic and phenotypic evidence of other adaptation for mammalian infection (non-haemagglutinin)
Level 0  Avian influenza circulating in birds, with normal epidemiology.
Level 1  Avian influenza circulating in birds, with abnormal epidemiology.
Level 2  Evidence of propensity to infect humans or other mammalian species. 
Level 3  Limited mammalian transmission (excluding human).
Level 4  Limited human-to-human transmission.
Level 5  Sustained transmission in mammals.
Level 6  Sustained human-to-human transmission.

Emerging influenza viruses may jump levels in this scheme (for example, from level 3 to 6), either because they emerge directly and successfully into humans, or because intermediate stages are not detected through surveillance.
Assessment

The UK risk is assessed as level 3 (limited mammalian transmission, low confidence).

Influenza A(H5N1) clade 2.3.4.4b can successfully infect mammals and humans with high levels of direct exposure (for example, scavenger mammalian species, humans working closely with birds).

Polymerase basic protein (PB2) mutations associated with mammalian adaptation, including E627K, are seen in mammalian infections. There is evidence of transmission in farmed mink and possible, though unconfirmed, transmission in populations of seals and sea lions.

There is limited mammalian surveillance.

The confidence level is assessed through the synthesis of epidemiology, genomic and virology data. 
(SNIP) 

Part 3. Planning scenarios
3.1 Scenario development: summary of assumptions

UKHSA has developed scenarios of early human transmission of influenza A(H5N1). It is not possible to know key parameters in advance, so these scenarios are not predictive. They are useful to explore the very early period of circulation of a new influenza virus in the UK, up to the time human-to-human transmission is detected, and the potential impact of pharmaceutical and non-pharmaceutical interventions.

The Technical Group reviewed and agreed the following parameters to be used in preliminary scenarios:

Transmission

These scenarios assume that sustained human-to-human transmission has begun – by definition a reproduction number (R) above one. Past avian influenza outbreaks which have not led to sustained human-to-human transmission cannot be used as a guide to transmission parameters. Based on pandemic influenza data, we judge that looking at scenarios where R is between 1.2 and 2 (or where doubling times are roughly between 3 days and 11 days) is a useful initial assumption. 
Severity

Three scenarios have been developed, each assuming a different level of clinical severity associated with the disease. All 3 scenarios should be considered severe compared to the most recent influenza pandemic in 2009.

In scenario 1, the infection-fatality rate (IFR) is around 0.25%, similar to that of coronavirus (COVID-19) in autumn 2021, though considerably higher than the overall severity of the 2009 H1N1 outbreak (0.01% IFR) (Riley and colleagues, 2011; Wong and colleagues, 2013). There are very few studies with estimates of an infection-hospitalisation rate (IHR), and for this scenario it has been set at 1%.

Scenario 2 is more severe. We base our parameters on the 1918 influenza pandemic, which had an IFR of around 2.5% (Murray and colleagues, 2006). We also assume in this scenario an IHR of 5%. Although various H5N1 outbreaks have much higher fatality estimates, these are not examples of sustained human-to-human transmission and are therefore not directly comparable (for example see Li and colleagues, 2008; Poovorawan and colleagues, 2013).

In scenario 3, we choose a higher IHR of 10%, with IFR 5%.
This approximates the type of outbreak seen with SARS-CoV-1 in 2002 (9% reported case fatality rate). We note significant variation in reported CFR rates for SARS-CoV-1, suggesting the underlying IFR may have been even higher than the crude average of reported deaths as a fraction of reported cases.
          (Continue . . . )

California: CDFW Reports Avian H5N1 In Two Deceased Mountain Lions

Credit USDA (as of 3/16/23)

#17,375

As the USDA map above (updated 3/16/23) shows, there have been nearly 150 documented spillovers of HPAI to mammalian wildlife in the United States, but it is expected that many more mammalian deaths have occurred due to the virus. 

Mammals often die in remote and difficult to access places where their carcasses are quickly scavenged by other animals, meaning they are never discovered or tested. 

Why nearly all of the reports to date have come from northern states isn't clear, although it may come down to differences in climate and terrain (swamps vs. forests vs. deserts), and the fact that some states may be looking harder than others.

Until now, California has only reported one mammalian infection with H5N1; a bobcat which died last December (see USDA listing below).


Late yesterday, the California Department of Fish and Wildlife (CDFW) released the following information on the detection of HPAI H5N1 in two deceased (and related) mountain lions.  

As we've seen with so many other mammalian infection (see here, here, here, and here), necropsy uncovered signs of neurological involvement (encephalitis). 

These two animals were discovered largely because both were tagged with GPS monitoring collars by wildlife biologists, allowing researchers to retrieve their remains.  Otherwise, it is likely they'd have gone uncounted. 

First the press release detailing their findings, after which I'll return with more.  

Avian Influenza Detected In Deceased Mountain Lions
March 28, 2023

The Eurasian strain of highly pathogenic avian influenza (HPAI H5N1) was detected in two mountain lions in Mono County in December 2022 and January 2023, according to wildlife health experts with the California Department of Fish and Wildlife (CDFW). While additional disease testing is being conducted to rule out the possibility of co-infections, HPAI H5N1 is suspected to be the cause of the death for both mountain lions.

This is the second species of wild mammal known to have contracted HPAI H5N1 in California since the virus was reported in wild birds in July 2022. In January, the virus was detected in a bobcat found in Butte County.

The new findings also mark the first detection of HPAI H5N1 in Mono County. To date, the virus has been found in 45 counties statewide.

“The Eurasian lineage of avian influenza is primarily a disease impacting birds but is occasionally being detected in wild mammals. We don’t expect this to have a population-level impact for California’s mountain lions or other mammalian carnivores, but it is a disease we will continue to monitor,” said Dr. Jaime Rudd, a pesticide and disease investigations specialist in CDFW’s Wildlife Health Lab.

“The main route of disease transmission for carnivores seems to be through ingestion of infected birds – typically waterfowl such as geese. Biologists following the movements of these mountain lions noted that they had preyed upon wild Canada geese in the past,” Rudd said.

Remains of the two mountain lions, who were related (mother and daughter), were collected from Mono Lake in Mono County on December 23 and January 14. Samples were submitted to the California Animal Health and Food Safety Laboratory in Davis for preliminary testing. Last week, the U.S. Department of Agriculture’s National Veterinary Services Laboratories confirmed the detection of HPAI H5N1.

“The main pathological finding for these two mountain lions was encephalitis, which is inflammation of the brain. Additionally, there were lesions in the lungs causing pulmonary edema. Much of the lesions in the brain and lungs were associated with the virus, but additional disease testing is being performed to rule out the possibility of co-infection,” said Rudd.

Of note is that both mountain lions were wearing GPS collars as part of a CDFW population study. The mortality notification sent from the collar helped biologists track the deceased animals and allowed for their remains to be collected in a timely manner to perform necropsies and determine cause of death.

“HPAI H5N1 is still considered a low-risk zoonotic pathogen,” said CDFW Senior Wildlife Veterinarian Dr. Deana Clifford. “It’s significant that the detections occurred far from the bobcat detection, and in an area where the disease had not yet been detected in wild birds. This means it’s possible that the mountain lions may represent detections of a new foci of infections for wild birds.”

Notwithstanding the mountain lion and bobcat detections, infection of wild mammals with avian influenza viruses appears to be relatively rare. Elsewhere in the U.S. and Canada, periodic detections of HPAI H5N1 have been made in mammalian carnivores including foxes, bobcats, raccoons, skunks and bears. Detections in mountain lions have occurred in five other states. The virus has also been detected in a small number of marine mammals.

The strain of HPAI H5N1 currently circulating in the U.S. and Canada has caused illness and death in a higher diversity of wild bird species than during previous avian influenza outbreaks, affecting raptors and avian scavengers such as turkey vultures and ravens. Mammalian and avian predators and scavengers may be exposed to avian influenza viruses when feeding on infected birds.

An informational flyer addressing frequently asked questions about avian influenza is available on CDFW’s website. Currently, the Centers for Disease Control(opens in new tab) considers the transmission risk of avian influenza to people to be low, but recommends taking basic protective measures (i.e., wearing gloves and face masks and handwashing) if contact with wildlife cannot be avoided. CDFW does not recommend people handle or house sick wildlife.

Practicing biosecurity is the most effective way to keep people, domestic poultry and pets healthy. Please visit the CDFA(opens in new tab) and USDA(opens in new tab) websites for biosecurity information. Please report sick or dead poultry and pet birds to the CDFA hotline at (866) 922-2473.

CDFW’s Wildlife Health Laboratory, in coordination with partners, continues to monitor wildlife for signs of illness and investigate mortality events. The public is encouraged to report dead wildlife using CDFW’s mortality reporting form. For non-urgent questions concerning wildlife, please contact your local CDFW Regional Office or your local animal control service.

Media contact:
Ken Paglia, CDFW Communications, (916) 825-7120


While the CDFW reassures that `. . .  infection of wild mammals with avian influenza viruses appears to be relatively rare . . . ', each spillover into a non-avian species is another opportunity for the virus to better adapt to a mammalian host. 

Also of concern, H5N1 appears to be becoming increasingly neurotropic in mammals. 

This month alone, we've looked at several studies that have documented profound neurological manifestations in infected mammals, including:

UK Reports 2 Dolphins With HPAI H5N1 & EID Report On Infected Harbor Porpoise in Sweden

PLoS Pathogens: Evolution of Highly Pathogenic H5N1 Influenza A Virus in the Central Nervous System of Ferrets

While we've seen reports in the past suggesting that H5N1 (and even seasonal influenza) could produce severe neurological manifestations, it was always thought to be more the exception than the rule. 

Tthere were anecdotal reports from Vietnam and Indonesia, but it wasn't until 2015 that we got our first detailed look (with MRI imaging and extensive histological analysis) of a fatal Neurotropic H5N1 Infection in a Nurse in Canada who recently returned from a visit to China.

The authors of that study warned:

These reports suggest the H5N1 virus is becoming more neurologically virulent and adapting to mammals. Despite the trend in virulence, the mode of influenza virus transmission remains elusive to date. It is unclear how our patient acquired the H5N1 influenza virus because she did not have any known contact with animals or poultry.

While the future course and impact of H5N1 in humans is still very much up in the air,  we've seen ample evidence that cats and dogs are susceptible to HPAI H5 (see 2015's HPAI H5: Catch As Cats Can and 2010's Study: Dogs And H5N1). 

Since the majority of wildlife detections of H5N1 have come from peridomestic animals in urban or suburban settings, it makes sense to protect your cat and dog when they are outside.

While the risks are still probably low, they are not zero.  The CDC has some advice on keeping your pets, and yourself, safe from the virus.  With the spring return migration now underway, and millions of birds headed north, a little extra caution is probably wise. 

Pet Owners

If your domestic animals (e.g., cats or dogs) go outside and could potentially eat or be exposed to sick or dead birds infected with bird flu viruses, or an environment contaminated with bird flu virus, they could become infected with bird flu. While it’s unlikely that you would get sick with bird flu through direct contact with your infected pet, it is possible. For example, in 2016, the spread of bird flu from a cat to a person was reported in NYC. The person who was infected [2.29 MB, 4 pages] was a veterinarian who had mild flu symptoms after prolonged exposure to sick cats without using personal protective equipment.

If your pet is showing signs of illness compatible with bird flu virus infection and has been exposed to infected (sick or dead) wild birds/poultry, you should monitor your health for signs of fever or infection.

Take precautions to prevent the spread of bird flu.

As a general precaution, people should avoid direct contact with wild birds and observe wild birds only from a distance, whenever possible. People should also avoid contact between their pets (e.g., pet birds, dogs and cats) with wild birds. Don’t touch sick or dead birds, their feces or litter, or any surface or water source (e.g., ponds, waterers, buckets, pans, troughs) that might be contaminated with their saliva, feces, or any other bodily fluids without wearing personal protective equipment (PPE). More information about specific precautions to take for preventing the spread of bird flu viruses between animals and people is available at Prevention and Antiviral Treatment of Bird Flu Viruses in People. Additional information about the appropriate PPE to wear is available at Backyard Flock Owners: Take Steps to Protect Yourself from Avian Influenza.

Tuesday, March 28, 2023

FEMA National Risk Index For Natural Disasters



#17,374


Although there is no place you can go where you can be completely safe from natural disasters, some places are more prone to disasters than others.   The interactive FEMA map above clearly shows that Southern California, and much of the state of Florida, are at the highest risk. 

We looked at FEMA's National Risk Index (NRI) map two years ago, but since then it has undergone a major revision (and new data has been added), which has changed some of its rankings. 
 
A side-by-side comparison of the state of Florida (then vs now) illustrate these changes.

Recent hurricanes have obviously changed the risk profile, particularly where I live, on Florida's west coast.  Add in the continual influx of new residents, many of whom are unfamiliar with hurricanes, and you have the ingredients for a disaster. 

But if you want to talk about the most people living in the highest risk region, then it would be hard to top Southern California (see map below). Los Angeles County ranks as the most disaster-prone county in the nation. 


These indexes refer to the relative frequency of disasters, which is why even a low risk area like Sharkey County, Mississippi - which saw an F4 tornado last week - can still be devastated.

While I promote an `all hazards' approach to preparedness, knowing the the type of risks where you live is an important first step to getting better prepared. Living in Florida, earthquakes aren't something I have to worry about, but hurricanes, tornadoes, wildfires are genuine concerns. 

By clicking on any county, this interactive map provides a pop-up scrollable list of disaster risks and demographic information for that region. You can also elect to create and download a full and highly detailed report.

Whether you want to look up your own risks, or find someplace a bit less risky or more resilient to move to, this interactive website will give you plenty to consider. 

Even though every year brings dozens of local and even regional disasters (see 2022 map below of $1 billion dollar disasters), most Americans remain woefully unprepared to deal with a prolonged disruption of essential services. 


According to FEMA's 2021 Household Survey on Preparedness, only 59% of households took 3 or more (of 12 recommended) preparedness steps in 2021.

Although that is up 2% from the 2019 survey, it is far from ideal. 

So, no matter where you live . . .  if a disaster struck your region today, and the power went outstores closed their doors, and water stopped flowing from your kitchen tap for the next 7 to 14 days . . . you are you prepared with:

  • A battery operated NWS Emergency Radio to find out what was going on, and to get vital instructions from emergency officials
  • A decent first-aid kit, so that you can treat injuries
  • Enough non-perishable food and water on hand to feed and hydrate your family (including pets) for the duration
  • A way to provide light when the grid is down.
  • A way to cook safely without electricity
  • A way to purify or filter water
  • A way to handle basic sanitation and waste disposal. 
  • A way to stay cool (fans) or warm when the power is out.
  • A small supply of cash to use in case credit/debit machines are not working
  • An emergency plan, including meeting places, emergency out-of-state contact numbers, a disaster buddy, and in case you must evacuate, a bug-out bag
  • Spare supply of essential prescription medicines that you or your family may need
  • A way to entertain yourself, or your kids, during a prolonged blackout
If not, you've got some important work to do. A good place to get started is by visiting Ready.gov.

Some of my practical preparedness blogs from the past year you may wish to revisit include:

The Gift of Preparedness

#NatlPrep: When Evacuation Is The Better Part of Valor

Sweltering In Place (2022 Edition)

Hurricane Preparedness: Some Simple Off-The-Shelf Solar Solutions For Power Outages