Bird flu case of unknown origin increases fears about human transmission

The threat of a global H5N1 bird flu epidemic is increasing. The United States has identified the first infected patient whose route of infection is unknown. Apparently, the patient had not had contact with farm animals, nor had he consumed raw cow’s milk, the most likely ways to get infected. On Friday, the Centers for Disease Control (CDC) disclosed that a household contact of this individual also developed symptoms on the same day; although this second person was not tested for bird flu, it raises the possibility of person-to-person infection. U.S. authorities said there was no evidence of human transmission, but the lack of data does not allow this possibility to be ruled out.

The world is experiencing the worst avian influenza epidemic known to date. It originates from a subtype of the H5N1 virus known as 2.3.4.4b, which has already killed hundreds of millions of wild and domestic birds. The virus should in theory only be able to infect birds, but multiple jumps to mammals have been recorded, from seals and sea lions in South America to minks on a farm in Spain.

One of the main hotspots of infection is dairy farms in the United States, with 207 herds affected in 14 states. The pathogen has gained the ability to infect birds and mammals alike, it accumulates in the cows’ udders and in their milk, and spreads without clear transmission pathways. Last July, a team of American scientists who analyzed viruses detected in cows warned that the “pandemic potential” of the pathogen was increasing. H5N1 has jumped from birds to humans on at least 889 occasions since 2003, and killed 463 people (52% of cases). Even so, both the United Nations and the U.S. authorities consider that the risk to human health remains “low.”

So far, 13 people have been infected with the highly pathogenic variant in the United States. All the patients were associated with farms and had only mild symptoms. But last week the CDC confirmed the case of a patient from Missouri who had been hospitalized with chest pain, vomiting and diarrhea, and was found, after extensive testing, to have developed bird flu. The virus had the same genetic profile as the variants detected in farm cattle, which this patient had not been exposed to.

The CDC has also reported two other suspected cases. The first is a close contact of the Missouri patient who experienced symptoms on the same day, but was not tested to confirm infection. A health care worker who treated the patient also experienced symptoms, but tested negative. According to the federal authority, there is no indication that the virus was transmitted, but rather that the patient and his contact were probably infected at the same time. After 10 days, no further cases have been reported. It is not yet possible to explain how the patient from Missouri, a state with no farm infections for months, could have become infected.

The new case has also exposed the lack of coordination and transparency by authorities. The Missouri patient was identified in mid-August, but the state only reported the case on September 5 and assured that no one else had become ill. A day later, the CDC admitted the existence of the second patient, the household contact. The initial data only indicated that it was H5 influenza, one of the two external proteins that characterize influenza viruses. Confirmation that the other key protein was N1 and the publication of the complete genetic sequence of the virus in an international database took another week, partly due to the low viral load of the first patient.

Maria Van Kherkove, acting director of epidemic and pandemic preparedness and prevention at the World Health Organization (WHO), has expressed her concern about the U.S. case. “More work needs to be done by the agricultural sector to get to the bottom of — and put a stop to — transmission of H5N1 bird flu in dairy cattle in the United States,” she said in statements reported by STAT. She also called for greater collaboration and transparency between veterinary and health authorities in order to have “the complete picture” of what is happening.

“One close contact of H5N1 case without animal link was also ill but not tested. Can anyone here from Missouri please work on the state government and bring CDC in!! We cannot sit and wait in the rest of the world to watch a potential pandemic evolve,” tweeted the Dutch virologist Marion Koopmans, who worked for the WHO to investigate the origins of the coronavirus pandemic.

The virus isolated from the Missouri patient has two new mutations. One of the mutations has been shown in animal studies to reduce the virus-neutralizing ability by 10- to 100-fold, said computational virologist Jesse Bloom, a researcher at the Howard Hughes Medical Institute, in a preliminary analysis published in X. “The importance of these mutations is that they help prepare vaccine candidates if H5N1 begins to spread among humans, although by themselves they do not allow us to say whether this is more likely than before,” the researcher explained in an email.

Elisa Pérez, a veterinary virologist at the CSIC Animal Health Research Center in Spain, considers the situation to be “very worrying.” The scientist sees parallels with what happened in April 2009, when two children in California were infected with an H1N1 flu virus of swine origin without having had any contact with these animals. It was not possible to determine how they became infected. Two months later, the WHO declared a global swine flu pandemic in which there were more than 60 million infections and 12,000 deaths, although the number of deaths not confirmed by testing may have exceeded half a million, according to the CDC.

Pérez focuses on the epidemiological surveillance in the United States, which she considers “disappointing” and suffering from “a lack of transparency.” “It could be the first evidence that there is human-to-human transmission of H5N1. It is incredible that no samples were taken from the close contact. I understand that the general risk remains low, but it is one more step on the risk scale. We still lack information on this case in Missouri. I do not know if we will ever know how the person was infected, but at least the epidemiological investigation must be as complete as possible and the data must be shared quickly,” she explains. There is still the possibility of confirming the infections by doing a blood test in search of antibodies against H5N1.

With the new flu season just around the corner, the veterinarian stresses the importance of vaccinating all people who work on animal farms or have contact with livestock. Otherwise, she explains, a terrifying scenario could occur: human viruses infecting animals already infected with H5N1 and recombining, which could give rise to even more transmissible pathogens.

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