The girl, from the southeastern province of Prey Veng, reportedly became ill Feb. 16, suffering from a 102-degree fever, cough, and throat pain, according to a tweet from the Cambodian government. She died shortly after arriving at a hospital in the capital, Phnom Penh, the Associated Press reported, citing the country’s health ministry.

11-year-old Girl in #PreyVeng Died of H5N1 Bird Flu https://t.co/LOxLD6t0L1

— Office of Cambodian PM 🇰🇭 (@PeacePalaceKH) February 22, 2023

The Khmer Times, a Cambodian news outlet, reported Thursday that 12 additional people from Prey Veng had been infected, also citing the health ministry. Four of the 12 have begun to show symptoms, and results of lab testing should be released tomorrow, according to the Times, making it unclear if any have been officially diagnosed so far.

The World Health Organization is “aware of the media reports,” the agency told Fortune in a statement Thursday. “We are following up and are in close touch with Cambodian authorities. We will update as we have more information.”

Recent days have brought increased reports of H5N1 bird flu spreading among mammals throughout the world—a situation that must be “monitored closely” owing to their physiological similarities with humans, WHO Director General Tedros Adhanom Ghebreyesus said at a Feb. 8 news conference.

H5N1 avian flu, rare in humans, is almost always transmitted by direct contact with sick birds. Only rarely have human cases occurred over the quarter century it’s been known to exist, with no sustained transmission reported among humans.

But “we cannot assume that will remain the case,” Ghebreyesus said Feb. 8. If birds have transmitted the virus to small mammals and it’s spreading among them—as seems to be the case, given recent mass mortality events among minks—it could signal that the virus has evolved and could spread more easily among humans, experts caution.

While the risk to people remains low, public health officials must prepare “to face outbreaks in humans, and be ready also to control them as soon as possible,” Dr. Sylvie Briand, director of global infectious hazard preparedness and emergency preparedness at the WHO, told Fortune on Feb. 8.

The mortality rate currently sits between 50% and 60%, according to the WHO and other sources.

A new sustained mode of transmission?

Reports of the Cambodian girl’s death and sickened locals “does raise the concern that we are transitioning from what has been a bird-to-human status quo to more of a human-to-human transmission scenario,” Rajiv Chowdhury, senior epidemiologist and professor of global health at Florida International University, told Fortune on Thursday.

It has not yet been determined how the girl was infected, though 22 chickens and three ducks at her home recently died, and there has been an unusual number of deaths among wild birds in the area as of late, BNO News reported Wednesday, citing Cambodian government officials. It’s also unclear if the individuals experiencing symptoms who live near the girl had contact with birds.

“I recommend that people do not touch dead or sick birds,” Chowdhury said, adding that children especially should be prevented from collecting eggs and/or playing with domestic poultry.

Pathogen surveillance systems must be “strengthened worldwide to prepare and act for any further outbreak,” he added.

Dr. Amesh Adalja, an infectious-disease specialist and senior scholar at the Johns Hopkins Center for Health Security, told Fortune that it’s too early to draw definitive conclusions from the relatively little information available.

The strain of H5N1 spreading in millions of birds throughout the world, clade 2.3.4.4b, “has not been causing severe human disease in the manner of other clades of the virus,” but “it has the ability to do so,” he said. “It will be important to see if the other ill individuals actually have H5N1 influenza and what their risk factor was. Did they have exposure to poultry species?”

Dr. Georges Benjamin, executive director of the American Public Health Association, told Fortune that the report, not yet confirmed by the WHO, is “very concerning.”

Even if sustained human-to-human transmission is not taking place in Cambodia, Chowdhury is concerned about a recent pattern of spillovers from birds to humans “in entirely different parts of the world.”

A previously healthy Ecuadorian girl was hospitalized with the virus in January, and was under sedation and on a ventilator, the WHO recently reported. The girl, who was recovering as of earlier this month, contracted the virus from poultry her family had recently purchased that died without apparent cause, WHO officials told Fortune on Feb. 8, adding that no additional human cases were reported in her area.

Her case was the seventh of H5N1 clade 2.3.4.4b reported to the WHO since 2020, and the 868th case since 2003, according to a Feb. 17 avian influenza weekly report from the organization.

Similarities with the Spanish flu

The likelihood of sustained human-to-human transmission of H5N1 is “very low,” Chowdhury recently told Fortune. But if it were to occur, it could rock the globe in a way not seen since the 1918 Spanish flu.

“The potential impact could be significant,” he said, signifying the start of a “new global influenza pandemic.” It’s thought that human population immunity against H5N1 clade 2.3.4.4b is “minimal,” according to a Dec. 21 report from the WHO.

Like the H5N1 flu, the Spanish flu is thought to have avian origins. Both viruses contain genes that allow them to replicate efficiently in human bronchial cells, according to a 2006 report from the Washington, D.C.-based Population Reference Bureau.

When H5N1 infects humans, the inflammation it causes can lead to lung cells becoming “intensely inflamed,” to an extent not seen in a usual flu. A similar effect was noted in Spanish flu victims, autopsies of which revealed “lungs choked with debris from the excessive inflammation,” resulting in drowning, the report noted.

While seasonal flu symptoms include fever, cough, sore throat, runny nose, aches, and fatigue, according to the CDC, symptoms of H5N1 in humans are typically much more severe. They include an often high fever, weakness, cough, sore throat, muscle aches, abdominal pain, chest pain, and diarrhea, according to the WHO. These symptoms can quickly give way to difficulty breathing, pneumonia, and/or acute respiratory distress syndrome, which is often deadly, as well as neurologic effects like seizures.

Because the virus hasn’t crossed over to humans in a sustained manner, it’s uncertain what an easily transmissible human version of H5N1 might look like, Dr. Jay Varma, chief medical adviser at New York–based think tank Kroll Institute, recently told Fortune. “But we can guess, based on prior flu epidemics, that it would be very deadly to humans.”

COVID has been “somewhat manageable” because younger individuals are typically less likely to suffer severe disease, he said. The same was not true of the Spanish flu, which killed more young than old. If human-to-human transmission of H5N1 begins to occur, “we shouldn’t automatically assume that young people or even children will be better protected,” he said. “They may very well be at higher risk.”