New reports clarify the clinical picture of recent human illnesses caused by the H5N1 virus in the United States and Canada

Two groups of researchers today deepened their clinical understanding of North American patients recently infected with H5N1 avian influenza, one describing a Canadian teenager who had a severe infection and the other examining the disease characteristics of 46 patients Americans, most of whom had mild infections. following exposure to sick dairy cows or poultry.

The teams published their reports today in the New England Journal of Medicine.

In the final months of 2024, U.S. health authorities continue to battle outbreaks in dairy cattle with the B3.13 genotype, with sporadic human impacts and fallout from raw milk contamination. The United States and Canada are now facing a sharp increase in outbreaks of poultry of a different genotype carried by wild birds migrating south, which have been linked to two serious human infections, one on each side of the border , and a wave of deaths of American cats.

Canadian teenager had high viral load, lower respiratory sample showed mutations

In one of the reports, Canadian researchers described the clinical findings of a Canadian teenager who contracted a serious infection from an undetermined source. The 13-year-old girl has mild asthma and a high body mass index. She was first seen in the emergency room after 2 days of conjunctivitis in both eyes and 1 day of fever, and was then sent home without treatment.

Her condition worsened and 3 days later, she returned to the emergency room in respiratory distress and hemodynamic instability and was admitted to the intensive care unit. The initial nasopharyngeal swab was positive for influenza A, but not for the seasonal subtype. Further testing suggested a high viral load with a new infection with the influenza A virus, which turned out to be H5 avian influenza. The next day, she started taking oseltamivir.

After her respiratory function deteriorated further, she was intubated and placed on extracorporeal membrane oxygenation (ECMO). Doctors also added a combination antiviral treatment, including baloxavir and amantadine.

Over the next few days, serial PCR tests showed a drop in viral load. However, lower respiratory tract samples showed higher viral loads than upper respiratory tract samples. Sequencing of a lower respiratory tract isolate obtained 8 days after symptom onset identified three mutations potentially linked to increased virulence and human adaptation: E627K in the polymerase basic 2 gene, as well as E186D and Q222H in the H5 hemagglutinin gene. Further analysis revealed that the virus belonged to the D1.1 genotype which was closely related to the virus then circulating in wild birds in British Columbia.

When the patient's respiratory condition improved, her medical team discontinued ECMO on November 22 and extubated her on November 28.

Mild, self-limiting US farm worker cases

In the other report, a team from the U.S. Centers for Disease Control and Prevention (CDC) and collaborators from six states analyzed data from a standardized case report form linked to H5 subtyping kits of CDC. Although the CDC has recorded 66 confirmed human cases this year, today's report covers illnesses reported from March through October.

Of the 46 patients, all but one hospitalized Missouri resident were exposed to dairy cattle or poultry. Twenty-five of them had been exposed to infected or probably infected dairy cattle and 20 to diseased poultry.

All people exposed to the animals had mild illnesses and none were hospitalized. All but three (93%) had conjunctivitis, about half (49%) had a fever, and just over a third (36%) had respiratory symptoms. For 15 (33%) of the patients, conjunctivitis was the only symptom. Most patients received oseltamivir, which was started on average 2 days after symptom onset.

No related cases were found among the 97 contacts of patients with animal exposure.

When researchers looked at the type of personal protective equipment (PPE) used by animal workers, they found that only 71% used gloves, 60% used protective eyewear, and 47% wore face masks. PPE use among occupationally exposed individuals was suboptimal, suggesting that additional strategies are needed to reduce exposure risk, the authors wrote.

Lingering Questions and Deep Concerns About Preparedness

In an editorial in the same issue of NEJM, two experts from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) offered their opinions on the two reports. The authors are Michael Ison, MD, of the Respiratory Diseases Branch of the Division of Microbiology and Infectious Diseases, and Jeanne Marrazzo, MD, MPH, group director.

Regarding the Canadian patient, they said it was unclear whether the mutations were present in the virus that infected the girl or whether they arose during the course of her illness.

They said both reports highlight critical features of the human health threat and response options. They said the U.S. report illustrates collaboration between human and animal health providers, public health leaders and occupational health authorities. The standard surveillance approach is geared toward detecting new cases, they noted. This approach involves cultivating trust not only among many entities, but also with people seeking care for symptoms of concern, including conjunctivitis, they wrote.

Meanwhile, the Canadian case highlights the urgent need to monitor mutations, Ison and Marrazzo said. However, they pointed out that genomic sequencing of animals often lacks metadata, making it difficult to track phylogenetic connections and how the virus is spreading.

They also noted that the prolonged virus shedding seen by the Canadian team highlights the need for longer antiviral treatment, which was recently reflected in updated CDC recommendations.

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