Is the bird flu virus inching closer to humans?

New Delhi, April 29 (IANS) While there is no record to date of sustained human-to-human bird flu transmission, the recent virus mutations show it may be inching closer to humans, according to health experts on Monday.

The bird flu or avian influenza A (H5N1) virus outbreak in poultry farms is not a new occurrence. It has periodically been reported all around the world, including poultry farms in parts of India.

Migrating wild birds bring the virus to poultry farms. However, in recent years, this bird flu virus H5N1 has jumped to mammals.

In 2023, the H5N1 virus killed a record number of birds and also spread to otters, sea lions, foxes, dolphins, and seals, among others. More recently it also affected numerous cattle farms across the US. Health officials in the US found fragments of bird virus in pasteurised milk sold in stores, including in about 20 per cent of samples in initial testing across the country.

"This shows that the H5N1 bird flu virus has now adapted for circulating among mammals. It is now able to easily spread from mammal to mammal, rather than having to jump each time from bird to mammal. This shows the virus has made suitable adaptations already. And bird flu virus has moved one step closer to humans," Dr Rajeev Jayadevan, co-chairman of the Indian Medical Association’s National Covid-19 Task Force, told IANS.

Importantly, "there is no record to date of sustained human-to-human transmission. This can only occur if the virus makes more adaptations by mutating. The concern now is the virus has found a new host among cattle, which is always in contact with man," he added.

Can bird flu infect humans?

Bird flu -- a common phenomenon seen in India -- raised infection concerns among humans in Jharkhand’s Ranchi last week. Two doctors and six staff members of the Regional Poultry Farm in Hotwar were quarantined for two days. However, their throat swab samples sent for tests on April 27, were found to be negative.

According to data from the World Health Organisation, from 2003 to 2023, a total of 873 human cases of infection with influenza A (H5N1) and 458 deaths have been reported globally from 21 countries. However, to date, no sustained human-to-human transmission has been detected.

"Human infection due to avian influenza happens only with close contact with infected animals. Although the risk for human infection is rare, such occurrences come with a high mortality rate," biologist Vinod Scaria, told IANS.

The high mortality rate is because "humans have no prior immune memory for this particular type of influenza virus", said Dr Jayadevan.

The WHO believes that available epidemiological and virological evidence does not indicate that current bird flu viruses have acquired the ability of sustained transmission among humans. However, the recent episode of transmission to cattle, where it has reportedly affected one human, has raised fresh concerns.

Genomic analysis suggests that it has silently been spreading among the cattle for months - since December or January.

"Scientists are worried whether the virus will now make further adaptations where it can not only easily infect man, but also spread from man to man, in which case it could become a major catastrophic event. We hope it will not happen," Dr Jayadevan told IANS.

The WHO advises people in close contact with cattle and poultry to regularly wash hands and employ good food safety and food hygiene practices, pasteurise milk, as well as to get vaccinated against seasonal human flu, to reduce the risk that H5N1 could recombine with a human avian virus."Appropriate personal protection while handling infected birds/dead birds or excreta is very important and awareness of this among the public is important," Scaria told IANS.Is the bird flu virus inching closer to humans? | MorungExpress | morungexpress.com
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The first pig kidney has been transplanted into a living person. But we’re still a long way from solving organ shortages

In a world first, we heard last week that US surgeons had transplanted a kidney from a gene-edited pig into a living human. News reports said the procedure was a breakthrough in xenotransplantation – when an organ, cells or tissues are transplanted from one species to another.

The world’s first transplant of a gene-edited pig kidney into a live human was announced last week.

Champions of xenotransplantation regard it as the solution to organ shortages across the world. In December 2023, 1,445 people in Australia were on the waiting list for donor kidneys. In the United States, more than 89,000 are waiting for kidneys.

One biotech CEO says gene-edited pigs promise “an unlimited supply of transplantable organs”.

Not, everyone, though, is convinced transplanting animal organs into humans is really the answer to organ shortages, or even if it’s right to use organs from other animals this way.

There are two critical barriers to the procedure’s success: organ rejection and the transmission of animal viruses to recipients.

But in the past decade, a new platform and technique known as CRISPR/Cas9 – often shortened to CRISPR – has promised to mitigate these issues.

What is CRISPR?

CRISPR gene editing takes advantage of a system already found in nature. CRISPR’s “genetic scissors” evolved in bacteria and other microbes to help them fend off viruses. Their cellular machinery allows them to integrate and ultimately destroy viral DNA by cutting it.

In 2012, two teams of scientists discovered how to harness this bacterial immune system. This is made up of repeating arrays of DNA and associated proteins, known as “Cas” (CRISPR-associated) proteins.

When they used a particular Cas protein (Cas9) with a “guide RNA” made up of a singular molecule, they found they could program the CRISPR/Cas9 complex to break and repair DNA at precise locations as they desired. The system could even “knock in” new genes at the repair site.

In 2020, the two scientists leading these teams were awarded a Nobel prize for their work.

In the case of the latest xenotransplantation, CRISPR technology was used to edit 69 genes in the donor pig to inactivate viral genes, “humanise” the pig with human genes, and knock out harmful pig genes.

How does CRISPR work?

A busy time for gene-edited xenotransplantation

While CRISPR editing has brought new hope to the possibility of xenotransplantation, even recent trials show great caution is still warranted.

In 2022 and 2023, two patients with terminal heart diseases, who were ineligible for traditional heart transplants, were granted regulatory permission to receive a gene-edited pig heart. These pig hearts had ten genome edits to make them more suitable for transplanting into humans. However, both patients died within several weeks of the procedures.

Earlier this month, we heard a team of surgeons in China transplanted a gene-edited pig liver into a clinically dead man (with family consent). The liver functioned well up until the ten-day limit of the trial.

How is this latest example different?

The gene-edited pig kidney was transplanted into a relatively young, living, legally competent and consenting adult.

The total number of gene edits edits made to the donor pig is very high. The researchers report making 69 edits to inactivate viral genes, “humanise” the pig with human genes, and to knockout harmful pig genes.

Clearly, the race to transform these organs into viable products for transplantation is ramping up.

From biotech dream to clinical reality

Only a few months ago, CRISPR gene editing made its debut in mainstream medicine.

In November, drug regulators in the United Kingdom and US approved the world’s first CRISPR-based genome-editing therapy for human use – a treatment for life-threatening forms of sickle-cell disease.

The treatment, known as Casgevy, uses CRISPR/Cas-9 to edit the patient’s own blood (bone-marrow) stem cells. By disrupting the unhealthy gene that gives red blood cells their “sickle” shape, the aim is to produce red blood cells with a healthy spherical shape.

Although the treatment uses the patient’s own cells, the same underlying principle applies to recent clinical xenotransplants: unsuitable cellular materials may be edited to make them therapeutically beneficial in the patient.

CRISPR technology is aiming to restore diseased red blood cells to their healthy round shape. Sebastian Kaulitzki/Shutterstock

We’ll be talking more about gene-editing

Medicine and gene technology regulators are increasingly asked to approve new experimental trials using gene editing and CRISPR.

However, neither xenotransplantation nor the therapeutic applications of this technology lead to changes to the genome that can be inherited.

For this to occur, CRISPR edits would need to be applied to the cells at the earliest stages of their life, such as to early-stage embryonic cells in vitro (in the lab).

In Australia, intentionally creating heritable alterations to the human genome is a criminal offence carrying 15 years’ imprisonment.

No jurisdiction in the world has laws that expressly permits heritable human genome editing. However, some countries lack specific regulations about the procedure.

Is this the future?

Even without creating inheritable gene changes, however, xenotransplantation using CRISPR is in its infancy.

For all the promise of the headlines, there is not yet one example of a stable xenotransplantation in a living human lasting beyond seven months.

While authorisation for this recent US transplant has been granted under the so-called “compassionate use” exemption, conventional clinical trials of pig-human xenotransplantation have yet to commence.

But the prospect of such trials would likely require significant improvements in current outcomes to gain regulatory approval in the US or elsewhere.

By the same token, regulatory approval of any “off-the-shelf” xenotransplantation organs, including gene-edited kidneys, would seem some way off.The Conversation

Christopher Rudge, Law lecturer, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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