The death of an 11-year-old Cambodian girl in February from an influenza strain known as H5N1 has sparked new concern about a virus that many public health experts say could someday cause a pandemic. H5N1, which has been spreading among birds since the late 1990s, has caused fewer than 1,000 confirmed cases in humans over that time, and incidents of human-to-human transmission appear extremely rare. But more than half of the people who were infected have died, a lethal potency that has many health officials concerned about what the virus could do if it adapts to spread more easily among humans.
Gavin Smith, Ph.D., a global health professor at Duke and director of the Emerging Infectious Diseases Programme at Duke-NUS Medical School in Singapore, has spent the past two decades studying how flu viruses mutate and move between species. His lab helped analyze the genetics of the strain responsible for the girl’s death in Cambodia, which also infected her father, who did not become ill. We asked Smith about the recent cases and whether H5N1 appears any closer to becoming an imminent pandemic threat.
H5N1 has been circulating for more than 20 years and there have been relatively few cases in humans. Why are public health officials concerned about this virus?
Smith:: H5N1 has a very high fatality rate in humans, so it has consistently been considered a top pandemic threat. Since 1996, H5N1 has been commonly found in poultry across Asia. Because of live-bird markets – where people can buy a chicken or duck and have it freshly slaughtered – there is a huge exposure of people, both shoppers and workers, to the virus. This has resulted in sporadic infections, and some limited human to human transmission in the past. So there is concern that given enough chances the virus could adapt to efficient spread in humans.
The World Health Organization has said the risk to humans of this virus is low, but they are now reassessing. What’s changed?
Smith: In the last few years, H5 viruses (not just H5N1 but other N subtypes) had become more widely spread in wild birds and poultry across the world. The virus was initially restricted to Asia, then found its way to Europe and Africa before finally crossing to North America, first in 2014[GJS1] , which quickly died out by 2015, and then again in 2022[GJS2] . Subsequently H5N1 viruses have been detected in South America.
This wider geographic spread has increased the exposure of humans and other mammal species, such as seals, to H5N1 infection. This naturally increases the chances that the virus could adapt to mammals and potentially humans. While there is no evidence for this at the moment it is important that the situation is closely monitored.
What do we know about the recent cases in Cambodia? Is there any evidence that the virus is passing between people?
Smith: There were only two confirmed cases in Cambodia, the daughter and father. There is no evidence that there was transmission between the pair, it could also have been from two independent infections from poultry.
Are you concerned that the virus may be evolving to spread more easily among humans?
Smith: At this stage, no. There is no evidence for adaptation to efficient human transmission. But repeated infection of mammal species, including humans, always increases that risk.
I’ve seen some experts say that the strains that have been spreading since 2020 may be causing less lethal illnesses in people. Is that true, and if so, what would that mean in terms of assessing the pandemic risk of this virus?
Smith: This is very hard to assess, and I am personally not convinced either way. We are not even sure of the extent of human infection in many countries because surveillance is either not done or is insufficient. Regardless, even if the virus was less deadly than in the past, it would still cause a pandemic similar in severity to SARS-CoV-2.
The WHO has called for wider production of H5N1 flu vaccines. What other steps should countries be taking to prevent a possible outbreak?
Smith: We need to develop smarter ways of controlling the virus in animals, primarily through vaccination. Vaccination in poultry won’t prevent infection by H5N1 but it does reduce the overall amount of virus in the poultry population, which leads to less spillover into humans. This approach has been successfully used in many countries to prevent human infection. Because people mainly get infected from poultry, we should concentrate on reducing the amount of virus in live-bird markets and farms.
Obviously, in a world still coming out of the COVID-19 pandemic, people are going to be very anxious about what might be next. Overall, how worried do you think people should be about this virus?
Smith: We have been studying these viruses for more than 25 years, and we have vaccines for birds available and human vaccines have been tested. There is also a good track record of influenza vaccines being used in people and we also have influenza specific anti-viral medicines. So overall we are in a better position than when SARS-CoV-2 emerged. COVID-19 has also left us better prepared. We are more vigilant and already taking steps to prepare for a possible pandemic.