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Unexplained severe liver inflammation among young children

Uncahareistsed and so far rare cases of liver inflammation (hepatitis) have been appearing in low numbers among young children worldwide since January…

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Uncahareistsed and so far rare cases of liver inflammation (hepatitis) have been appearing in low numbers among young children worldwide since January 2022. The most often-detected pathogen is an adenovirus but work continues to ensure that isn’t just a coincidental finding as cases are identified in more countries.

What is hepatitis?

Hepatitis (Greek hêpar, “liver”) is inflammation of the liver which can result in a range of outcomes. If rapid onset (acute) and viral, signs and symptoms can range from mild to severe. Asymptomatic acute viral hepatitis is more common than symptomatic versions (detectable upon liver enzyme testing). And hepatitis also comes in a chronic form that can build from acute illness.

Symptoms can be indistinguishable among the viral causes of hepatitis and can include fever, jaundice, malaise, fatigue, light stools, abdominal pain and diarrhoea.

Diagnosis can include the detection of specific genetic material, viral proteins (antigens) or detection of anti-virus IgM antibodies. The detection of elevated levels of alanine aminotransferase (ALT; found mostly in the liver) and aspartate aminotransferase (AST; found in several tissues) can flag some degree of liver cell damage, which has resulted in the release of these enzymes into the bloodstream where they are not normally elevated.

Viral causes of acute hepatitis

The most common causes are hepatitis viruses and they come in a range of colours and flavours. [4,5]

Hepatitis A virus (HAV)

A positive-sense RNA virus of the family Picornviridae, genus Hepatovirus, species Hepatovirus A, exists as multiple genotypes and is transmitted via a faecal-oral route. The virus replicates in the epithelial cells of the small intestine and in the liver cells of primates. They are not associated with chronic hepatitis

This is typically an acute self-limited illness in adults. The disease can be more severe if on top of chronic HBV or HCV. Vaccines and treatments are available.

Hepatitis B virus (HBV)

A double-stranded DNA virus of the family Hepadnaviridae, genus Orthohepadnavirus, species Hepatitis B virus, exists as multiple genotypes and is transmitted via entry of infected blood or body fluids into the bloodstream or open wounds, sexual contact, perinatal transmission from an infected mother and possible via “inapparent horizontal” transmission, particularly between children in low socio-economic settings.

 Schematic representation of a particle of hepatitis delta virus.
Image from Figure 1, Deltavirus page, ICTV.[6]

They are associated with chronic hepatitis which can lead to liver cirrhosis and hepatocellular carcinoma complications which can, in turn, lead to death. Chronic infection can follow perinatal infection. In adults, infection usually resolves in healthy people. Infant vaccines and treatments are available.

Hepatitis C virus (HCV)

A positive-sense RNA virus of the family Flaviviridae, genus Hepacivirus, species Hepacovirus C, exists as multiple genotypes and is transmitted via entry of infected blood, blood products and blood-contaminated objects into the bloodstream. The virus replicates in the liver cells and possible lymphocytes.

Hepacivirus genome organization (not to scale) and polyprotein processing.
Image from Figure 1, Hepacivirus page, ICTV.[7]

infection is often associated with chronic hepatitis following acute infection and without treatment can result in liver cirrhosis. Therapies are available.

Hepatitis D virus (HDV)

A negative-sense RNA satellite virus of the family Flaviviridae, genus Deltavirus, species Hepacovirus C, which requires envelope proteins from a helper virus, HBV (so cellular coinfection is required), to create more infectious particles.

The transmission, replication and outcome of infection of HDV are similar to that of HBV and they exist as multiple genotypes.

Hepatitis E virus (HEV)

A positive-sense RNA virus of the family Hepeviridae, genus Orthohepevirus, species Orthohepevirus A, exists as multiple genotypes and is transmitted via the faecal-oral route, and via contaminated water, raw/undercooked meats and rarely through blood transfusions. The virus replicates in the liver cells.


Negative contrast electron micrograph of hepatitis E virus virions from a case stool collected in Nepal. (A) virion and (B) empty capsid. The bar represents 100nm (photo from M. Purdy).
mage from Figure 1, Hepeviridae page, ICTV.[8]

Infection is usually self-limited in the healthy individual similar to that for HAV but can become a significant problem for the immunocompromised. Vaccines and treatments exist.

Disease in this new outbreak

In approximately 10% of the recent cases, which are generally being noticed in younger children, inflammation was so severe that a liver transplant was required. Symptoms included jaundice, diarrhoea, vomiting and abdominal pain. All of th original 10 cases were hospitalized.

Where has this undiagnosed round of hepatitis been noted so far?

Scotland, England, Ireland, The United States, Spain, Israel, Belgium, Denmark, France, Italy, the Netherlands, Norway and Romania have reported cases.[11] If these are all cases with the same cause, this supports an infectious agent’s role – in some way – rather than a more localised foodborne or chemical contamination event.

Working case definitions to find cases

The WHO initially described the following:[9]

  • Confirmed: A person presenting with acute hepatitis (non-hepatitis viruses A, B, C, D, E) with aspartate transaminase (AST) or Alanine transaminase (ALT) over 500 U/L, who is 10 years old and under, since 1 January 2022.
  • Possible: A person presenting with acute hepatitis (non-hepatitis viruses A-E) with AST or ALT over 500 U/L, who is 11-16 years old, since 1 January 2022.
  • Epi-linked: A person presenting with acute hepatitis (non-hepatitis viruses A-E) of any age who is a close contact of a confirmed case since 1 January 2022.

What might be the cause?

The most commonly detected agent so far has been an adenovirus, particularly adenovirus 41 (HAdV-41). This is on a background of increased levels of HAdV detection in the community.[12]

There are seven species of adenovirus that include human-infecting enveloped DNA viruses that are more often thought of as “common cold” viruses. Transmission occurs from the throat, faeces, eye or urine, depending on the HAdV type.[12]

Most infections are mild or asymptomatic but some HAdVs have been associated with specific outcomes like adenoidal–pharyngeal conjunctivitis (types 3, 4, 7, 14), acute respiratory outbreaks (types 4, 7, 14, 21), epidemic keratoconjunctivitis (types 8, 19, 37, 53, 54) or venereal disease (HAdV-37). HAdV-40 and HAdV-41 can be isolated from the faeces of young children with acute gastroenteritis and are a major cause of infantile viral diarrhoea.[12]

The Scottish cases were recently written up and included the first documented instances from March 2022.[2] But the US now reports cases from November 2021.[11]

It may not be that any single virus is the cause though. Concurrent infection with another virus may create disease or an immune-mediated process due to prior infection by something could be at play. So of course SARS-CoV-2 is being considered in this space. Not as high a proportion of children have tested positive for the virus that causes COVID-19,[2] but that doesn’t rule it out. Nor have we yet ruled out anything entirely new, or specific evolution o HAdV-41 into something that has a direct liver-damaging outcome.

Some have of course jumped on the anti-virus bandwagon and blamed childhood COVID-19 vaccination. But in many instances, the children here have been too young to be vaccinated yet, so this is an easy piece of potential misinformation to debunk.

Ways to stop the spread of adenoviruses

HAdVs do have a history of surviving in a manufactured aerosolized state.[3] In one study from 1964, ultraviolet light was found to dramatically reduce a very high load of AdV-2 in an aerosolized suspension.[3] This suggests measures to reduce viral loads in aerosols – the same that would work to reduce influenza virus, enterovirus and SARS-CoV-2 virus infections for example – should be hugely useful here as well. We should have already begun investing in this technology. Perhaps this serves as yet another reminder of why we should if we haven’t?

Handwashing also rates here as a lot of viruses and bacteria spread by contact with contaminated surfaces.

I’ve run out of time to write this so will circle back later and re-tweet future versions..

References

  1. Spike in child hepatitis cases linked to common virus
    https://www.bbc.com/news/health-61177329
  2. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022
    https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.15.2200318
  3. INACTIVATION OF AIRBORNE VIRUSES BY ULTRAVIOLET IRRADIATION
    https://pubmed.ncbi.nlm.nih.gov/14215971/
  4. International Committee on Taxonomy of Viruses (ICTV)
    https://talk.ictvonline.org/
  5. Principles and Practice of Infectious Diseases, 8th edition. Eds Bennet, Dolin, Blaser
  6. Deltavirus
    https://talk.ictvonline.org/ictv-reports/ictv_online_report/negative-sense-rna-viruses/w/deltavirus
  7. Hepacivirus
    https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/flaviviridae/362/genus-hepacivirus
  8. Hepeviridae
    https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/hepeviridae
  9. Acute hepatitis of unknown aetiology – the United Kingdom of Great Britain and Northern Ireland
    https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatitis-of-unknown-aetiology—the-united-kingdom-of-great-britain-and-northern-ireland
  10. Increase in acute hepatitis cases of unknown aetiology in children
    https://www.gov.uk/government/publications/hepatitis-increase-in-acute-cases-of-unknown-aetiology-in-children/increase-in-acute-hepatitis-cases-of-unknown-aetiology-in-children
  11. WHO says 12 countries have reported unusual cases of hepatitis in kids
    https://www.statnews.com/2022/04/23/who-says-12-countries-have-reported-unusual-cases-of-hepatitis-in-kids/
  12. Adenoviridae
    https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/93/adenoviridae

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The post Unexplained severe liver inflammation among young children appeared first on Virology Down Under.

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Cruise Line Drops Pre-Cruise Covid Testing Rule

The major cruise lines walk a delicate line. They need to take the actual steps required to keep their passengers safe and they also need to be aware of…

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The major cruise lines walk a delicate line. They need to take the actual steps required to keep their passengers safe and they also need to be aware of how things look to the outside public. It's a mix of practical covid policy balanced with covid theater.

You have to do the right thing -- and Royal Caribbean International (RCL) - Get Royal Caribbean Group Report, Carnival Cruise Lines (CCL) - Get Carnival Corporation Report, and Norwegian Cruise Lines (NCLH) - Get Norwegian Cruise Line Holdings Ltd. Report have been doing that with very meticulous protocols-- but you also have to show the general public you're taking the pandemic seriously. The cruise industry has been under the microscope of both public perception and the Centers for Disease Control (CDC) since covid first appeared.

That's not because you're likely to get infected on a cruise ship than at a concert, sporting event, theme park, restaurant, or any other crowded space. It's because when you get sick at one of those locations nobody can pinpoint the source of your infection

Cruises last from 3 days to 7 days or even longer and that means that some people will get covid onboard and that will be blamed on the cruise industry. To mitigate that Carnival, Royal Caribbean, and Norwegian have rigid protocols in place that require passengers 12 and over to be vaccinated as well as pre-cruise covid tests taken no more than two days before your cruise leaves.

Once cruise line has dropped that testing requirement (at least on a few sailings) and that could lead Royal Caribbean, Carnival, and Norwegian to follow. 

Sina Schuldt/picture alliance via Getty

Holland America Drops Some Covid Testing

As the largest cruise lines sailing from the U.S., Royal Caribbean, Carnival, and Norwegian don't want to be the first to make major covid policy changes. They acted more or less in tandem when it came to loosening, then dropping mask rules and have generally followed the lead of the CDC, even when that agency's rules became optional.

Now, Holland America cruise line has dropped pre-cruise covid testing on a handful of cruises. It's a minor move, but it does provide cover and precedent for Royal Caribbean, Carnival, and Norwegian to eventually do the same.

"Holland America Line becomes the first US-based cruise line to remove testing for select cruises. Unfortunately for those taking a cruise from the United States, the new protocols are only in place for certain cruises onboard the company’s latest ship, the Rotterdam, in Europe," Cruisehive reported.

The current CDC guidelines do recommend pre-cruise testing, but the cruise lines into following those rules. By picking cruises sailing out of Europe, Holland America avoids picking a fight with the federal agency just yet, but it will be able to gather data as to whether the pre-cruise testing actually helps.

Holland America has not changed its vaccination requirements for those cruises which mirror the 12-and-up rule used by Royal Caribbean, Carnival, and Norwegian.

Some guests have called for the end of the testing requirement because they believe it's more theater than precaution because people can test and then contract covid while traveling to their cruise.

The Current Cruise Protocols Work

Royal Caribbean President Michael Bayley does expect changes to come in his cruise line's covid protocols, and he talked about them during Royal Caribbean's recent President's Cruise, the Royal Caribbean Blog reported.

"I think pre cruise testing is going to be around for another couple of months," Bayley told passengers during a question and answer session. "We obviously want it to go back to normal, but we're incredibly cognizant of our responsibilities to keep our crew, the communities and our guests safe."

People do still get covid onboard despite the crew being 100% vaccinated and all passengers 12 and over being vaccinated, but the protocols have worked well when it comes to preventing serious illness.

Bayley said that the CDC shared some information with him in a call.

"The cruise industry sailing out of the US ports over the past 12 months and how many people have been hospitalized with Covid and how many deaths occurred from Covid from people who'd sailed on the industry's ships, which is in the millions," he said, "And the number of people who died from COVID who'd sailed on ships over the past year was two."

That success may be why the major cruise lines are reluctant to make changes. The current rules, even if they're partially for show, have been incredibly effective.

"Two is terrible. But but but against the context of everything we've seen, that's it's truly been a remarkable success." he added.

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Visualizing A Decade Of Population Growth And Decline In US Counties

Visualizing A Decade Of Population Growth And Decline In US Counties

There are a number of factors that determine how much a region’s population…

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Visualizing A Decade Of Population Growth And Decline In US Counties

There are a number of factors that determine how much a region’s population changes.

If an area sees a high number of migrants, along with a strong birth rate and low death rate, then its population is bound to increase over time. On the flip side, as Visual Capitalists Nick Routley details below, if more people are leaving the area than coming in, and the region’s birth rate is low, then its population will likely decline.

Which areas in the United States are seeing the most growth, and which places are seeing their populations dwindle?

This map, using data from the U.S. Census Bureau, shows a decade of population movement across U.S. counties, painting a detailed picture of U.S. population growth between 2010 and 2020.

Counties With The Biggest Population Growth from 2010-2020

To calculate population estimates for each county, the U.S. Census Bureau does the following calculations:

      A county’s base population → plus births → minus deaths → plus migration = new population estimate

From 2010 to 2020, Maricopa County in Arizona saw the highest increase in its population estimate. Over a decade, the county gained 753,898 residents. Below are the counties that saw the biggest increases in population:

Phoenix and surrounding areas grew faster than any other major city in the country. The region’s sunny climate and amenities are popular with retirees, but another draw is housing affordability. Families from more expensive markets—California in particular—are moving to the city in droves. This is a trend that spilled over into the pandemic era as more people moved into remote and hybrid work situations.

Texas counties saw a lot of growth as well, with five of the top 10 gainers located in the state of Texas. A big draw for Texas is its relatively affordable housing market. In 2021, average home prices in the state stood at $172,500$53,310 below the national average.

Counties With The Biggest Population Drops from 2010-2020

On the opposite end of the spectrum, here’s a look at the top 10 counties that saw the biggest declines in their populations over the decade:

The largest drops happened in counties along the Great Lakes, including Cook County (which includes the city of Chicago) and Wayne County (which includes the city of Detroit).

For many of these counties, particularly those in America’s “Rust Belt”, population drops over this period were a continuation of decades-long trends. Wayne County is an extreme example of this trend. From 1970 to 2020, the area lost one-third of its population.

U.S. Population Growth in Percentage Terms (2010-2020)

While the map above is great at showing where the greatest number of Americans migrated, it downplays big changes in counties with smaller populations.

For example, McKenzie County in North Dakota, with a 2020 population of just 15,242, was the fastest-growing U.S. county over the past decade. The county’s 138% increase was driven primarily by the Bakken oil boom in the area. High-growth counties in Texas also grew as new sources of energy were extracted in rural areas.

The nation’s counties are evenly divided between population increase and decline, and clear patterns emerge.

Pandemic Population Changes

More recent population changes reflect longer-term trends. During the COVID-19 pandemic, many of the counties that saw the strongest population increases were located in high-growth states like Florida and Texas.

Below are the 20 counties that grew the most from 2020 to 2021.

Many of these counties are located next to large cities, reflecting a shift to the suburbs and larger living spaces. However, as COVID-19 restrictions ease, and the pandemic housing boom tapers off due to rising interest rates, it remains to be seen whether the suburban shift will continue, or if people begin to migrate back to city centers.

Tyler Durden Sat, 07/02/2022 - 21:00

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Tesla EV deliveries fall nearly 18% in second quarter following China factory shutdown

Tesla delivered 254,695 electric vehicles globally in the second quarter, a nearly 18% drop from the previous period as supply chain constraints, China’s…

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Tesla delivered 254,695 electric vehicles globally in the second quarter, a nearly 18% drop from the previous period as supply chain constraints, China’s extended COVID-19 lockdown and challenges around opening factories in Berlin and Austin took their toll on the company.

This is the first time in two years that Tesla deliveries, which were 310,048 in the first period this year, have fallen quarter over quarter. Tesla deliveries were up 26.5% from the second quarter last year.

The quarter-over-quarter reduction is in line with a broader supply chain problem in the industry. It also illustrates the importance of Tesla’s Shanghai factory to its business. Tesla shuttered its Shanghai factory multiple times in March due to rising COVID-19 cases that prompted a government shutdown.

Image Credits: Tesla/screenshot

The company said Saturday it produced 258,580 EVs, a 15% reduction from the previous quarter when it made 305,407 vehicles.

Like in other quarters over the past two years, most of the produced and delivered vehicles were Model 3 and Model Ys. Only 16,411 of the produced vehicles were the older Model S and Model X vehicles.

Tesla said in its released that June 2022 was the highest vehicle production month in Tesla’s history. Despite that milestone, the EV maker as well as other companies in the industry, have struggled to keep apace with demand as supply chain problems persist.

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