The Cambodian girl who died of H5N1 this month did not have the worrying 2.3.4.4b virus.Credit: Cambodian Ministry of Health/AP/Shutterstock
An 11-year-old girl in southern Cambodia who died last week after being infected with avian influenza A (H5N1) had a different strain than the one causing mass deaths of wild and domestic birds around the world, said the scientist who led the sequencing effort. viral samples from the girl. Scientists initially feared the girl had been infected with the widely-spread virus which is now spreading in some species of mammals and has infected a handful of people since 2020.
Erik Karlsson, virologist at the Institut Pasteur du Cambodge in Phnom Penh, spoke with Nature on how he and his colleagues sequenced the full genome of the girl’s virus sample in less than a day before sharing the data on the public repository GISAID. He says the sequenced virus belongs to a group that has been found in chickens and ducks in the region for at least a decade, although the girl is the first person to be detected with H5N1 in the country in nine years. .
Cambodia’s health ministry took 12 of his close contacts, and only his 49-year-old father tested positive. H5N1 infections usually occur in people who have had close contact with poultry, and so far there is no evidence that this strain has spread between people. Investigations into how the girl was exposed to the virus are ongoing.
When did you receive the virus sample from the girl?
The sample was first tested at the National Institute of Public Health in Phnom Penh and then transferred to us. We received the sample around 5 p.m. on February 22, and it was sequenced within 24 hours. This really illustrates how the COVID-19 pandemic has increased our ability to sequence and share data very quickly.
The viral load in the sample was high enough that we could amplify the entire flu genome at once. If the viral load had been low, which it often is, we would have had to wait about three days to grow it in cells or eggs to get enough virus to sequence. Our goal has been to get the virus sequenced and into the public domain as quickly as possible.
What did you learn from the sequence?
The virus belongs to clade 2.3.2.1c, which is an endemic strain in the region. It’s the same strain that caused a number of human infections in 2013 and 2014 in Cambodia, and has been detected intermittently in poultry since then, including chickens at bird markets. living.
Everyone was worried that the girl might have had the 2.3.4.4b strain, which is circulating all over the world and is currently causing big problems in Europe, North America and South America. 2.3.4.4b is a new virus clade, and we don’t know much about it.
Researchers have been monitoring 2.3.2.1c for some time and have information about it to make reasonable judgments about its transmissibility and pathogenicity. But whenever there is a zoonotic spillover, we have to treat it with the utmost importance.
What’s worrying about zoonotic fallout?
Viruses, especially RNA viruses such as influenza, are extremely promiscuous and will quickly adapt to a new host. We have seen it with the virus that causes COVID-19. An overflow indicates that the virus now has a chance to adapt to a new host. This is concerning because this adaptation could result in a virus that could potentially be transmitted between people. Getting ahead and blocking any potential for transmission, as well as understanding what the virus is doing in its new host, is critically important and can inform outbreak response.
Do you also sequence samples from the father?
We’re trying to sequence samples from the father, but he seems to have had a lower viral load, which makes it a bit more difficult to get a sequence quickly. We will try more targeted approaches, as well as virus isolation. But often there is not enough viral load to get more than partial sequences.
What do we know about how the girl was infected?
I don’t know why the virus spread from poultry to humans in this case, after about ten years without being detected. Many factors still need to be investigated, but there have been many global changes in farming practices due to the COVID-19 pandemic that could have created the conditions for a spillover.
We know that in Cambodia, the pandemic has increased the number of backyard poultry farms. Many people, for example tour guides, could not work and had to supplement their income and food sources for their families. People around the world are still struggling, which has led to changes in farming practices that can increase the risk of contagion. And changes in people’s health, such as malnutrition or overweight, can make people more susceptible to infection.
Hopefully this is an isolated incident, but it could be a sign of a larger problem.
What additional analysis does your team perform?
Hopefully we will have more information about the poultry samples surrounding the case soon. We can then compare these virus sequences with historical virus data, for example from live bird market monitoring, from those parts of Cambodia, to see if anything major has changed, or if anything is happening in the population of poultry that forces the virus into, for example, riskier phenotypes, or pose a higher risk to people.
We will also isolate and grow this virus in our biosafety level 3 facility, which will help us develop tools to better understand the epidemiology of this case and the virus in the region. For example, we could develop blood tests for the presence of antibodies – a marker of past infection – in samples taken from the father, others living in the girl’s home, and the wider community. The isolates will also be essential for laboratories around the world to study the transmissibility and pathogenicity of the virus, including in animal models, such as ferrets.
This interview has been edited for length and clarity.