Avian Flu Diary: Preprint: A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms

#18,217

While the total number of dairy farms reporting HPAI hovers just above 170, and only 4 dairy workers (and 9 poultry workers) have been diagnosed with the new bovine strain (B3.13) of the virus, there are reasons to believe the scope of this outbreak is larger than those numbers would suggest.

First, cattle were reportedly falling ill in Texas (and other states) for months before the first diagnosis - last March - of HPAI H5N1.

Second, we're repeatedly heard that farm owners - and farm workers - have been less-than-receptive to testing of cattle, or personnel. Testing of cattle (except prior to interstate transport) remains largely optional.

Third, we've seen numerous anecdotal reports of sick cattle workers who were never tested, including in last month's EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA.

Testing of exposed farm workers, when it is done, is generally limited to symptomatic individuals only. The CDC justifies this decision by citing a recent (small) seroprevalence study in Michigan, which tested 35 farm workers and found no neutralizing or HI antibodies specific to avian influenza A(H5N1) virus.

That said, we've seen a number of seroprevalence studies on (various) HPAI H5N1 strains over the years that have found limited evidence of asymptomatic (or very mild) infection with H5 avian influenza.

Of course getting people to voluntarily submit to a serological study (which may involve multiple blood draws over time), can be difficult. Language barriers, the migratory aspects of farm work, and a general distrust of the government are additional hurdles.

All of which brings us to a preprint - published on the MedRxiv website yesterday - which among other things, reports finding a small number (n=2) of H5 seropositive farm workers among a small cohort (n=14) that were tested across two farms in Texas.

They also report several mutations associated with increased spillover potential in cattle.

It is worth noting these researchers used Microneutralisation (MN) assay rather than Haemagglutination Inhibition (HAI) testing. Both are viewed as the gold standard for antibody testing, but the MN assay's superior sensitivity can be more prone to detecting cross-reacting antibodies from previous influenza A virus infections or vaccinations.

First, the link an abstract to the 43-page preprint, followed by some excerpts from an interview with lead author Gregory Grey on KFF Health News, a nonprofit health policy research, polling, and news organization.

The entire KFF Health News report is worth reading. I'll have a brief postscript after the break.

A One Health Investigation into H5N1 Avian Influenza Virus Epizootics on Two Dairy Farms
Ismaila Shittu, Diego Silva, Judith U. Oguzie, Lyudmyla V. Marushchak, Gene G. Olinger, John A. Lednicky, Claudia M. Trujillo-Vargas, Nicholas E. Schneider, Haiping Hao, Gregory C. Gray
doi: https://doi.org/10.1101/2024.07.27.24310982

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Abstract

Background: In early April 2024 we studied two Texas dairy farms which had suffered incursions of H5N1 highly pathogenic avian influenza virus (HPAIV) the previous month.

Methods: We employed molecular assays, cell and egg culture, Sanger and next generation sequencing to isolate and characterize viruses from multiple farm specimens (cow nasal swab, milk specimens, fecal slurry, and a dead bird).

Results: We detected H5N1 HPAIV in 64% (9/14) of milk specimens, 2.6% (1/39) of cattle nasal swab specimens, and none of 17 cattle worker nasopharyngeal swab specimens. We cultured and characterized virus from eight H5N1-positive specimens. Sanger and next-generation sequencing revealed the viruses were closely related into other recent Texas epizootic H5N1 strains of clade 2.3.4.4b. Our isolates had multiple mutations associated with increased spillover potential. Surprisingly, we detected SARS-CoV-2 in a nasal swab from a sick cow.

Additionally, 14.3% (2/14) of the farm workers who donated sera were recently symptomatic and had elevated neutralizing antibodies against a related H5N1 strain.

Conclusions: While our sampling was limited, these data offer additional insight into the large H5N1 HPAIV epizootic which thus far has impacted at least 96 cattle farms in twelve US states. Due to fears that research might damage dairy businesses, studies like this one have been few. We need to find ways to work with dairy farms in collecting more comprehensive epidemiological data that are necessary for the design of future interventions against H5N1 HPAIV on cattle farms.

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From KFF Health News:

Bird Flu Cases Are Going Undetected, New Study Suggests. It’s a Problem for All of Us.

By Amy Maxmen JULY 31, 2024

A new study lends weight to fears that more livestock workers have gotten the bird flu than has been reported.

“I am very confident there are more people being infected than we know about,” said Gregory Gray, the infectious disease researcher at the University of Texas Medical Branch who led the study, posted online Wednesday and under review to be published in a leading infectious disease journal. “Largely, that’s because our surveillance has been so poor.”

As bird flu cases go underreported, health officials risk being slow to notice if the virus were to become more contagious. A large surge of infections outside of farmworker communities would trigger the government’s flu surveillance system, but by then it might be too late to contain.

“We need to figure out what we can do to stop this thing,” Gray said. “It is not just going away.”

The Centers for Disease Control and Prevention bases decisions on its surveillance. For example, the agency has bird flu vaccines on hand but has decided against offering them to farmworkers, citing a low number of cases.

But testing for bird flu among farmworkers remains rare, which is why Gray’s research stands out as the first to look for signs of prior, undiagnosed infections in people who had been exposed to sick dairy cattle — and who had become ill and recovered.

Gray’s team detected signs of prior bird flu infections in workers from two dairy farms that had outbreaks in Texas earlier this year. They analyzed blood samples from 14 farmworkers who had not been tested for the virus and found antibodies against it in two. This is a nearly 15% hit rate from only two dairy farms out of more than 170 with bird flu outbreaks in 13 states this year.

One of the workers with antibodies had been taking medicine for a lingering cough when he agreed to allow researchers to analyze his blood in April. The other had recently recovered from a respiratory illness. She didn’t know what had caused it but told researchers that untested farmworkers around her had been sick too.

Richard Webby, director of the World Health Organization Collaborating Center for Influenza at St. Jude Children’s Research Hospital in Memphis, Tennessee, said the results confirmed his suspicions that the 13 human bird flu cases reported this year by the CDC were an undercount.

“Maybe what we see isn’t exactly the tip of the iceberg, but it’s certainly not the whole story,” Webby said.

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I can't say that I'm particularly surprised by these findings, but they should serve as a wake-up call.

It has been more than 4 months since the first (belated) detection of HPAI H5 in cattle, and sad to say, we continue to treat HPAI H5 as more of an agricultural economic problem than as a potential public health threat.