A New Bird Flu Death Is Making Experts Uneasy

The threat of bird flu to humans appears to be growing. As outbreaks of H5N1—a dangerous strain of avian influenza—continue to affect cows in the U.S., Canada, South America, Europe, and Asia, the World Health Organization (WHO) reported on June 5 the first-ever case of a human infection with H5N2, a different strain of avian influenza. The infection was fatal.

The case was first reported to the WHO on May 23 by health officials in Mexico City, where a 59-year-old man with several other health conditions was hospitalized. Before reporting shortness of breath, diarrhea, and nausea, the man had been bedridden for three weeks. Testing by the national lab showed that the man had H5N2, and further genetic sequencing confirmed the strain.

Unlike the recent U.S. cases of H5N1 in people, the patient did not have any known exposure to infected animals. (However, outbreaks of H5N2 have recently been reported in poultry in Mexico.) The good news is that none of the patient’s close contacts or those caring for him in the hospital tested positive for the virus.

What this means for people

Avian influenza generally does not cause serious disease in people, and in previous cases of rare human infections, the virus did not spread easily from person to person. The first report of human infection with H5N2 “doesn’t really change anything in my mind,” says Dr. Shira Doron, chief infection control officer at Tufts Medicine Health System. “We’ve been seeing sporadic avian flu infection in humans for a long time, and it very rarely transmits to other humans. But like any avian flu, it bears watching to make sure it does not herald a new phenomenon.”

Questions that urgently need answering

Genetic sequencing of the virus from the Mexican patient will be important, as it could reveal from which animal it likely arose, or whether there are any concerning changes signaling that the virus is evolving to spread more easily among people.

Sequencing will also be critical to potentially answering some questions about how the bird flu virus is jumping into more mammalian species. “There is likely a role here for different kinds of receptors in different species and in different tissues in those species,” says Doron, since the virus seems to preferentially infect respiratory tissues in birds, mammary tissues in cows, and the conjunctiva, or eyes, in people.

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“What is not clear is that in any new mammal infected, how the virus is introduced and how it is passing between them,” she says. “We still don’t definitely have an understanding of how the virus is transmitting from cow to cow, because there are especially high concentrations in the mammary glands but not in the respiratory tract. That throws a wrench into our entire spectrum of understanding.”

The virus is inching closer to humans

The U.S. Department of Agriculture reported that H5N1 has been found in 11 house mice in New Mexico. Farms in the state have reported H5N1 outbreaks in cows, so it’s possible that the mice consumed unpasteurized milk from infected cows and became infected themselves. But that means the virus is inching closer to contact with people, since most people are more likely to encounter house mice than dairy cattle. “Any house, any home, any lodging or campground could bring humans in close contact with mice,” says Doron.

In the U.S., health officials are monitoring for H5N1 in wastewater, which can provide an early signal for rises cases. Scientists with WastewaterSCAN—a collaboration between academic researchers and the health data company Verily that contributes data to the U.S. Centers for Disease Control and Prevention—retested old samples from municipal sewage treatment plants and found H5N1 in the samples about a week before there were reports of a unknown illness in cows in Texas, where some of the first outbreaks occurred. “Had we had testing in real time then, it definitely would have provided a leading edge [on the outbreak],” says Marlene Wolfe, co-program director for WastewaterSCAN and an assistant professor of environmental health at the Rollins School of Public Health at Emory University.

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The group continues to monitor for H5N1 and will still do so into the fall and winter, when other influenza strains start to spread among people. That way, we'll be better able to determine if bird flu is having any impact on humans.

Determining how big a threat avian influenza could be for people is a growing priority for health officials, and learning more about how the virus is moving from species to species is critical for making that assessment. For example, it’s not clear which tissue samples from the mice were positive, so it’s unknown whether the mice are transmitting the virus through urine or feces (which could pose a risk to people who might come into contact with them) or via other means. Cows, on the other hand, don’t seem to excrete much virus in their urine or feces, so even though the virus is circulating in mammals, “it’s not necessarily highly transmissible,” says Doron. “We could get lucky here.”

Nonetheless, some farmers have been culling sick cows to avoid widespread cases and the potential of infected, unsellable milk. And “scientists should worry, since there is always potentially a first time that a genetic shift could mean more transmissibility in humans,” says Doron.

A wake-up call

The H5N1 outbreaks and the first case of human H5N2 highlight the need for health officials to rethink how they monitor for flu. “We didn’t realize avian flu was circulating in cows for probably three months,” says Doron. “By the same token, there may be more H5N2 in Mexico in more species than birds—and we need to be doing more surveillance. We need to broaden our minds going forward to look for flu even in places where we don’t think we’ll find it.”

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