Enlarge / Holstein dairy cows in a freestall barn. (credit: Getty | )

The US Department of Agriculture this week posted an unpublished version of its genetic analysis into the spillover and spread of bird flu into US dairy cattle , offering the most complete look yet at the data state and federal investigators have amassed in the unexpected and worrisome outbreak—and what it might mean.

The preprint analysis provides several significant insights into the outbreak—from when it may have actually started, just how much transmission we're missing, stunning unknowns about the only human infection linked to the outbreak, and how much the virus continues to evolve in cows. The information is critical as flu experts fear the outbreak is heightening the ever-present risk that this wily flu virus will evolve to spread among humans and spark a pandemic.

But, the information hasn't been easy to come by. Since March 25—when the USDA confirmed for the first time that a herd of US dairy cows had contracted the highly pathogenic avian influenza H5N1 virus—the agency has garnered international criticism for not sharing data quickly or completely. On April 21, the agency dumped over 200 genetic sequences into public databases amid pressure from outside experts. However, many of those sequences lack descriptive metadata, which normally contains basic and key bits of information, like when and where the viral sample was taken. Outside experts don't have that crucial information, making independent analyses frustratingly limited. Thus, the new USDA analysis—which presumably includes that data—offers the best yet glimpse of the complete information on the outbreak.

Enlarge / Farm cats drinking from a trough of milk from cows that were just milked. (credit: Getty | )

On March 16, cows on a Texas dairy farm began showing symptoms of a mysterious illness now known to be H5N1 bird flu. Their symptoms were nondescript, but their milk production dramatically dropped and turned thick and creamy yellow. The next day, cats on the farm that had consumed some of the raw milk from the sick cows also became ill. While the cows would go on to largely recover, the cats weren't so lucky. They developed depressed mental states, stiff body movements, loss of coordination, circling, copious discharge from their eyes and noses, and blindness. By March 20, over half of the farm's 24 or so cats died from the flu.

In a study published today in the journal Emerging Infectious Diseases , researchers in Iowa, Texas, and Kansas found that the cats had H5N1 not just in their lungs but also in their brains, hearts, and eyes. The findings are similar to those seen in cats that were experimentally infected with H5N1 , aka highly pathogenic avian influenza virus (HPAI). But, on the Texas dairy farm, they present an ominous warning of the potential for transmission of this dangerous and evolving virus.

The contaminated milk was the most likely source of the cat's fatal infections, the study authors concluded. Although it can't be entirely ruled out that the cats got sick from eating infected wild birds, the milk they drank from the sick cows was brimming with virus particles, and genetic data shows almost exact matches between the cows, their milk, and the cats. "Therefore, our findings suggest cross-species mammal-to-mammal transmission of HPAI H5N1 virus and raise new concerns regarding the potential for virus spread within mammal populations," wrote the authors, who are veterinary researchers from Iowa, Texas, and Kansas.

Enlarge (credit: Getty | Jeffrey Greenberg )

The Food and Drug Administration reported late Thursday that about 20 percent of retail milk samples from around the country tested positive for genetic fragments of the bird flu , aka highly pathogenic avian influenza (HPAI) virus H5N1. While retail milk is still considered to be safe, the finding suggests that the spread of the virus in cows is more extensive than is currently known.

The FDA used a test called quantitative polymerase chain reaction (qPCR), which can only detect the presence of genetic fragments. In pasteurized retail milk, it is highly likely that those genetic snippets are merely remnants of virus particles destroyed during pasteurization. The FDA is currently conducting additional testing using egg inoculation tests, a gold-standard for detecting a live virus, to confirm the effectiveness of pasteurization. Meanwhile, the director of the National Institute of Allergy and Infectious Diseases, Jeanne Marrazzo, told reporters Wednesday that tests at the agency's federal labs so far did not identify live virus from any of its sampling. Additionally, several previous studies have found that pasteurization of eggs—which is done at a lower temperature than it is for milk—was effective at destroying H5N1.

While experts are largely unconcerned with the safety of commercial milk, the potential for wide, unrecognized spread of bird flu in dairy herds is alarming. To date, the US Department of Agriculture has only confirmed infections in 33 herds in eight states . The FDA acknowledged that of its positive samples, "a greater proportion of positive results [are] coming from milk in areas with infected herds." But with tens of thousands of dairy herds in the US, the finding suggests that infections are being missed. It does not necessarily suggest that 20 percent of all cows are affected, since milk is pooled for commercial distribution. But 33 herds alone are unlikely to explain the high prevalence.

Enlarge / Cows being milked (credit: Getty | Edwin Remsberg )

The Food and Drug Administration on Tuesday announced that genetic fragments from the highly-pathogenic avian influenza virus H5N1 have been detected in the pasteurized, commercial milk supply. However, the testing completed so far—using quantitative polymerase chain reaction (qPCR)—only detects the presence of viral genetic material and cannot tell whether the genetic material is from live and infectious viral particles or merely remnants of dead ones killed by the pasteurization process.

Testing is now ongoing to see if viable, infectious H5N1 can be identified in milk samples.

So far, the FDA still believes that the milk supply is safe. "To date, we have seen nothing that would change our assessment that the commercial milk supply is safe," the agency said in a lengthy explanation of the finding and ongoing testing .

Enlarge / Greylag geese sit on a field and rest while a cow passes by in the background. (credit: Getty | Daniel Bockwoldt )

Researchers around the world are growing more uneasy with the spread of highly pathogenic avian influenza (H5N1) in US dairy cows as the virus continues to make its way into new herds and states. Several experts say the US is not sharing enough information from the federal investigation into the unexpected and growing outbreak, including genetic information from isolated viruses.

To date, the US Department of Agriculture has tallied 32 affected herds in eight states : Idaho, Kansas, Michigan, New Mexico, North Carolina, Ohio, South Dakota, and Texas. In some cases, the movement of cattle between herds can explain the spread of the virus. But the USDA has not publicly clarified if all the herds are linked in a single outbreak chain or if there is evidence that the virus has spilled over to cows multiple times. Early infections in Texas were linked to dead wild birds (pigeons, blackbirds, and grackles) found on dairy farms. But the USDA reportedly indicated to Stat News that the infections do not appear to be all linked to the Texas cases .

Spread of the virus via cattle movements indicates that there is cow-to-cow transmission occurring, the USDA said. But it's unclear how the virus is spreading between cows. Given that even the most symptomatic cows show few respiratory symptoms, the USDA speculates that the most likely way it is spreading is via contaminated milking equipment.