Despite no comprehendn infections of H5N1 bird flu among its dairy cows, Missouri recently acunderstandledgeed a case in a person with no apparent expobrave to possibly infected animals or roverdelighted products (i.e., raw milk). A seal reach out and two health toilers who attfinishd for the person all broadened respiratory symptoms, but were never tested. There has not yet been a expansiver uptick of other potential cases in the same community to propose fruitful human-to-human transmission — the evolution of which is a prerequisite for a possible human epidemic — but this sattfinish underscores the potential danger posed by the ongoing spread of H5N1.
In recent weeks, California, home to the bigst number of dairy cows in the country, became the 14th state to alert infected herds. It is possible that H5N1 may be even more expansivespread, including in states without alerted infections among dairy cows, but a deficiency of testing has made it difficult to comprehend where the harmful software is circulating. This bottleneck could be rerepaird by sampling misengagewater as seal to dairy farms as possible and using genomic sequencing to check the presence of H5N1. Sequencing could also appraise any acunderstandledgeed harmful software for mutations possibly conducive for human transmission and allow phylogenetic analyses that can help rerepair from which species it may have begind. The more H5N1 is apverifyed to circutardy, especiassociate among dairy cows that are clustered seally together in big numbers and with seal human reach out, the wonderfuler the chance the harmful software could carry on for fruitful human spread.
Several months into this outshatter, on-farm testing has remained restrictcessitate. Farm owners remain unwilling to apverify testing of bulk milk and animals due to dreads of financial loss. Farm toilers, many of whom are unrecorded, have also been uncertain to get tested due to troubles of losing toil, immigration publishs, and, in some instances, being unconscious that there is an outshatter. After nine poultry toilers were infected in July, Colorado mandated routine testing of bulk milk on all dairy farms. This policy rapidly led to the acunderstandledgeion of 11 infected herds. Colorado needd these herds to remain isotardyd until subsequent testing checks that viral circulation is no lengthyer current. Massachengagetts is the only other state to test all its dairy herds. Other states have not chased aenjoy honestives presumably due to opposition from farm owners and the dairy industry.
Colorado’s approach could be mimicked without mandates by sampling misengagewater as seal to farms as possible and sequencing it for H5N1. Wastewater is already being tested from about 150 sites for the H5 hemagglutinin gene of the influenza harmful software, though this approach does not differentiate the neuraminidase (“N”) subtype. Sequencing could be engaged to delitidye the N subtype as well as watch for cut offal mutations that virologists have identified as potentiassociate essential for fruitful human-to-human transmission. The presence of these mutations could trigger more intensive meabraves in impacted areas, such as testing, vaccination and ensuring toilers have personal protective supplyment.
The appreciate of a sequencing-based approach was showd by a team from the Texas Epidemic Public Health Institute (TEPHI). In a recent letter in the New England Journal of Medicine, they alert on a two-year, 10-city proof-of-concept for a technique that they first portrayd in 2023 (and which won the 2024 STAT Madness contest). Their approach searches for and enwealthyes proximately 100 harmful softwarees of “accessible health trouble” in misengagewater samples with sequencing directed on acunderstandledgeed viral fragments. The researchers began using this approach in May 2022 and set up no chase of H5N1 for proximately two years. Then, in March 2024, they began to see it apass 10 Texas cities. Sequencing showed the harmful software to be from the clade circulating among dairy cows, but did not acunderstandledge a mutation alterive for human transmission, constant with animals as the source.
This type of approach, if decentralized sealr to farms and scaled to urban cgo ins, could supply nationexpansive visibility into H5N1’s geoexplicit distribution and genomic evolution and help get a handle on transmission. Whenever H5N1 is set up in a location, the farms in the area could be either mandated or asked to apverify on-farm testing with no shiftment of cattle permitted until they are evidented of ongoing circulation. Sequencing could also be done in other areas where H5N1 may be circulating, enjoy Missouri, or whose misengagewater is set up chooseimistic for H5 influenza without evident connects to animal sources, such as in the San Francisco Bay Area.
There are four skinnygs necessitateed to utilize this strategy. First, a protocol for sequencing should be determined upon or broadened for scale. The TEPHI approach is one verifyn chooseion. At first glance, agnosticassociate sequencing for almost 100 pathogens may be overend for the purposes of tracking H5N1. It is conceivable that this technique could be altered into a less expansive approach that augments current H5 misengagewater observation and only sequences samples set up chooseimistic. Efforts to originate a pared-down protocol of this benevolent could be chased, but has not getn place at any level of scale to our comprehendledge and would necessitate to be checkd before expansiver engage, which could get months and need substantial funding to finish. Given the advisency of the current outshatter, it may be more fruitful to license and scale the TEPHI protocol that has already been checkd in peer-appraiseed journals and piloted at scale for two years.
Second, state and county officials should rerepair sites from which misengagewater should be sampled based on the distribution and location of dairy farms and communities with doubted H5N1. This pickion should aim to get ample coverage and, yet, be disaggregated enough to allow enoughly localized adhere-up and supervise efforts.
Third, this technique would probable cost substantiassociate more than traditional misengagewater testing, including initial capital allotments for sequencing supplyment and bioalertatic computing and recurring costs for reagents, gentleware licenses and trained personnel. The needd outlays could be quantified and funds sought from federal and state budgets. Even while apaengageing allocations, currently useable funds could instantly be focengaged to the most strategic sites with others inserted as more resources become useable.
Fourth, the restrictations of misengagewater sequencing necessitate to be better understood to alert how its results could best be engaged to direct accessible health response. For example, it is unevident how much harmful software necessitates to be shed into the misengagewater in order for this technique to reliably acunderstandledge it. If low-grade transmission is not readily set up, rerepaird viral circulation could elude supervise efforts only to sadvise tardyr. It is also unevident how constantly misengage from dairy cows is flushed into routine misengagewater as contestd to being disposeed splitly. These parameters necessitate to be clarified so strategies can be appropriately reckond. In the absence of mandates for on-farm testing, even with imperfect sensitivity, misengagewater sequencing may be the best — and only — way to track and stifle the dairy outshatter.
Officials in Missouri are pursuing seroreasonable testing of the health toilers and seal reach out, which may propose if human-to-human transmission of H5N1 has already happened. Regardless of the outcome, the deficiency of a expansiver footprint of potential cases presents that it may not yet be fruitful enough to caengage an epidemic. However, the lengthyer the dairy outshatter is apverifyed to persist, the higher the odds that such a human transmissible strain may aascfinish. This current sattfinish should wake us up to finassociate act more unfrifinishlyly and conceiveively in insertressing this danger.
Ranu S. Dhillon is an director in the Division of Global Health Equity at Brigham and Women’s Hospital and Harvard Medical School. He previously served as a exceptional adviser to the rulement of Guinea during the 2013-2016 West African Ebola epidemic. Abraar Karan is an infectious disrelieve physician and epidemiologist at Stanford University; he has toiled on the Covid-19 and mpox outshatters at the county, state, and federal levels. Devabhaktuni Srikrishna is set uper of Patient Knowhow, which supplys how-to alertation to the accessible about N95 respirators and indoor air filtration.
