The WHO “urges heightened vigilance from all countries,” Dr. Sylvie Briand, director of global infectious hazard preparedness and emergency preparedness for the organization, said at a news conference. WHO officials were conferencing with Cambodian health officials, performing a risk assessment as she spoke.

Cambodian Health Ministry Detects Second Case of H5N1 https://t.co/UZ1f8JO1q0

— Office of Cambodian PM 🇰🇭 (@PeacePalaceKH) February 24, 2023

“When you see that there are a number of potential cases surrounding an initial case, you always wonder what happened,” she said. “Is it because maybe the initial case has transmitted the disease to other humans? We are really concerned about the potential human-to-human transmission coming from this initial spillover from animals.”

A December WHO risk assessment of circulating H5N1 clade 2.3.4.4b viruses classified the risk to humans as “low.” Briand said the WHO believes that level “has not changed,” given the Cambodian cases, “but we are really looking at this new information to see if we need to change the way we see things or not.” The clade of the Cambodian cases’ virus is currently unknown.

H5N1 is “worrying, given the wide spread of the virus in birds around the world and increasing reports of cases in mammals, including humans,” she said. She characterized the virus as a “severe respiratory disease with a range of symptoms, from mild to fatal.”

The mortality rate is over 50%, she added.

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.

The Khmer Times, a Cambodian news outlet, reported Thursday that 12 additional people from Prey Veng were being tested for H5N1, also citing the health ministry. Four of the 12 had begun to show symptoms, and results of lab testing should be released Friday, according to the Times.

It has not yet been determined how the girl or her dad were infected. But 22 chickens and three ducks at her home recently died, and there have 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 girl’s contacts who are experiencing symptoms had contact with birds.

If human-to-human transmission of H5N1 is confirmed in Cambodia, interventions like isolating cases, contact identification, and the use of antivirals after exposure can be used to prevent further spread among humans, Briand said.

Disease surveillance can also be increased in areas that see such transmission, and in surrounding communities. And an attempt can be made to “control the source of the virus in the animal population, reducing the risk of spillover from animals to humans,” she added.

“We are not there yet,” she said, referencing the need for such actions. But stakeholders at regional, national, and global levels are “starting to exchange information so everybody is aware of the risk and can very quickly react.”

Increased spread among mammals, including humans

Rajiv Chowdhury, senior epidemiologist and professor of global health at Florida International University, told Fortune on Friday that the additional confirmed case is “alarming.”

The illnesses in Cambodia “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,” Chowdhury told Fortune on Thursday.

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 has infected millions of birds around the world this season. But it’s rare in humans and is almost always transmitted by direct contact with sick birds. Roughly 900 human cases have been reported 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, sea lions, seals, and the like—it could signal that the virus has evolved and could spread more easily among humans.

“Clusters” of human H5N1 cases have occurred since 1997, “so the question is whether this cluster is due to common exposure to chicken or birds, or sustained human-to-human transmission,” Dr. Jay Varma, chief medical adviser at New York–based think tank Kroll Institute, told Fortune.

“The latter would be worrisome.”

A previously healthy Ecuadoran girl was hospitalized with the virus in January, and was under sedation and on a ventilator, the WHO recently reported. The girl contracted the virus from poultry her family had recently purchased that died without apparent cause. She is now out of the hospital, and no additional human cases were reported in connection with her illness, WHO officials told Fortune on Friday.

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.

Candidate vaccines, antiviral treatments exist

Nearly 20 candidate vaccines for H5 flu strains exist and are licensed for pandemic use, health officials said at the WHO’s Friday press conference.

Serum collected from those who received H5 flu vaccines in the past “reacts quite well” with some of the recently circulating strains of H5 flu—an “encouraging” sign that existing vaccines might be effective against new strains, Dr. Kanta Subbarao, director of the WHO Collaborating Centre for Reference and Research on Influenza at the Victorian Infectious Diseases Reference Laboratory in Australia, said.

What’s more, some countries developed H5N1 vaccines in 2003, when it was feared the virus would become a pandemic, Dr. Wenqing Zhang, head of the WHO Global Influenza Programme, added.

While stockpiled vaccine might not be a perfect match to a concerning circulated strain, it could likely be used to protect from severe disease while a more tailored vaccine is being created, said Richard Webby, director of the WHO Collaborating Centre for Studies on the Ecology of Influenza in Animals and Birds at the St. Jude Children’s Research Hospital’s Department of Infectious Diseases.

It would likely take five or six months to develop an updated vaccine using traditional approaches, he added—excluding an mRNA vaccine, the production of which could be faster.

H5N1 clade 2.3.4.4b candidate vaccines currently exist, according to the WHO. Scientists’ ability to choose a closely matching vaccine for customization, if such an effort is needed, will shave six to eight weeks off the production timeline, said David Wentworth, director of the WHO Collaborating Centre for Surveillance, Epidemiology, and Control of Influenza at the U.S. Centers for Disease Control and Prevention.

It took about 100 days to develop a vaccine during the 2009 H1N1 pandemic, he added.

Oseltamivir, an antiviral also known as Tamiflu, has been used to treat H5N1 cases since 2003, and multiple new antibody treatments have since been made available, Briand said.

The WHO is “working very closely” with the manufacturers of those antivirals to see “how fast they can scale up production in case we need more of these drugs,” she said.