USDA genome study sheds light on H5N1 avian flu spillover to cows, but data gaps remain

dairy cows in barn

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The H5N1 virus infecting dairy cattle in multiple states was probably circulating in the animals for 4 months before scientists confirmed it in late March, and missing data and surveillance gaps raise the possibility of undetected transmission chains, a research team led by the US Department of Agriculture (USDA) National Veterinary Services Laboratory (NVSL) reported in a new preprint study.

In the first published report that interlaces genetic sequencing findings with what's known from the epidemiological investigation, the group said asymptomatic cattle movement to other states is likely driving transmission and that they are already seeing a few variants with mutations that could lead to interspecies transmission. The group published their findings yesterday on the preprint server bioRxiv.

In other H5N1 developments, the USDA last night announced that its tests on retail ground beef from affected states were negative, and two affected states—Michigan and Colorado—announced new emergency measures.

Data gaps and timeline questions

Phylogenetic analysis using genome sequencing suggests that there was a reassortment event in late 2023 between the current highly pathogenic 2.3.4.4b clade in wild birds and a low-pathogenic wild bird strain, which produced the B3.13 genotype now circulating in dairy cows.

The NP gene acquired during reassortment may have played a role in the emergence in cattle, they wrote, noting that the NP gene seems to allow influenza viruses to spread more easily in pigs.

Their analysis suggests there were as many as five B3.13 introductions from cattle to poultry, one to a raccoon, two to domestic cats, and three to wild birds. Though the findings track with epidemiological findings of spread through movement of herds to other states, they emphasized that there are still gaps.  "We cannot exclude the possibility that this genotype is circulating in unsampled locations and hosts as the existing analysis suggests that data are missing and under surveillance may obscure transmission inferred using phylogenetic methods," they wrote. 

For example, they said the B3.13 virus from the human infection doesn't nest within cattle sequences, which could suggest that viruses from unsampled cows were the source of the infection or that evolution within the host was enough to result in a different phylogenetic grouping. "It is most likely, however, that asymptomatic transmission and undersurveillance in epidemiologically important populations drove this pattern."

They conclude that the potential for B3.13 to become endemic in cattle will influence the zoonotic risk from the virus and warned that if the low level of mammalian adaptations they're seeing become dominant, the risk of interspecies transmission will be higher.

Scientists welcome new data

After the group published its report, Angela Rasmussen, PhD, a virologist with the University of Saskatchewan's Vaccine and Infectious Disease Organization, on X (formerly known as Twitter), praised the group for sharing the critical data.

However, she said more information is needed, such as the tissue and or sample type each genome came from, which is essential for understanding how cows are transmitting the virus and planning experiments to test transmission hypotheses. "This is an all-hands situation and transparency & data access are required for an effective response," Rasmussen wrote.

Michael Osterholm, PhD, MPH, who directs the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, publisher of CIDRAP News, also credited the USDA group for sharing their findings and said the science community has been anxiously waiting for the critical information.

"This will help people better understand how the spillover unfolded," he said.

Ground beef tests negative for H5N1 traces

In its update, the USDA said it tested 30 samples of retail ground beef from states where dairy herds tested positive for H5N1. The samples underwent polymerase chain reaction (PCR) testing, which can identify traces of the virus but not live virus, at the NVSL. All were negative.

"These results reaffirm that the meat supply is safe," the agency said.

The USDA added that PCR testing is under way on muscle samples from culled dairy cows at selected USDA Food Safety and Inspection Service (FSIS) slaughter facilities and that its Agricultural Research Service is conducting a cooking study using a virus surrogate in ground beef to examine the impact of different cooking temperatures on virus levels.

Michigan and Colorado announce emergency measures

Two states affected by H5N1 outbreaks in dairy herds yesterday announced emergency measures aimed at controlling the spread of the virus.

In Michigan, where recent outbreaks in dairy cows and massive outbreaks in poultry were reported across seven counties, the Department of Agriculture and Rural Development (MDARD) announced an extraordinary emergency measure that requires dairy farms and commercial poultry farms to implement biosecurity steps such as designating a biosecurity manager, establish cleaning procedures, and keeping a log book of vehicles and people who have crossed farm-access points.

The order also bars all lactating cattle from being displayed until the state has passed 60 days with no new dairy farm detections. Officials also announced a similar restriction for poultry, but for 30 days with no new detections.

Elsewhere, Colorado's agricultural commission approved, and the state's agriculture commissioner yesterday adopted, an emergency rule designed to limit the spread of H5N1. Colorado is the most recently affected state in the outbreak involving dairy cattle, and so far, it's not clear how the cows were exposed to the virus. 

In its announcement, the Colorado Department of Agriculture said the emergency rule requires mandatory testing of lactating cattle moving interstate, which they said allows implementation of the recent federal order, which took effect on April 29.

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