Mutations? Not good.
The teams published their reports in the New
England Journal of Medicine (NEJM).
In the final months of 2024, US health officials continue to
battle outbreaks in dairy cattle from the B3.13 genotype, with sporadic
spillovers to people and fallout from contamination in raw milk. The United
States and Canada are now juggling a steep rise in poultry outbreaks from a
different genotype carried by wild birds migrating south, which have been
linked two severe human infections—one on each side of the border—and a spate
of deaths in US cats.
Canadian teen had high viral loads, lower airway sample showed mutations
In one of the reports, Canadian researchers described clinical
findings from a Canadian teen who contracted a severe infection from an
undetermined source. The 13-year-old girl has mild asthma and elevated body
mass index. She was first seen at an emergency department (ED) after a 2-day
history of conjunctivitis in both eyes and a 1-day history of fever, then was
sent home without treatment.
Her condition worsened, and 3 days later she returned to the
ED 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 the seasonal subtype. Further testing suggested a high viral load
with a novel influenza A infection, which was found to be H5 avian influenza.
The following day she was started on oseltamivir.
After her respiratory function deteriorated further, she was
intubated and placed on extracorporeal membrane oxygenation (ECMO). Doctors
also added combination antiviral treatment, which included baloxavir and
amantadine.
Over the next few days, serial PCR testing showed declining
viral loads. However, lower respiratory samples showed higher viral loads than
those from upper-airway samples. Sequencing from a lower-airway isolate
obtained 8 days after symptom onset identified three mutations potentially
linked to enhanced virulence and human adaptation: E627K in the polymerase
basic 2 gene, along with E186D and Q222H in the H5 hemagglutinin gene. Further
analysis found that the virus belonged to the D1.1 genotype that was closely
related to the virus circulating in British Columbia’s wild birds at the time.
When the patient’s respiratory status improved, her medical
team discontinued ECMO on November 22 and extubated her on November 28.
US farm worker cases mild and self-limiting
In the other report,
a team from the US Centers for Disease Control and Prevention (CDC) and
collaborators in six states analyzed data from a standardized case-report form
that was linked to the CDC’s H5 subtyping kits. Though 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—a resident of Missouri who
was hospitalized—was exposed to dairy cattle or poultry. Twenty-five had been
exposed to infected or likely infected dairy cattle and 20 were exposed to sick
poultry.
All of the people with animal exposure had mild illnesses,
and none were hospitalized. All but three (93%) had conjunctivitis, about half
(49%) had 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 a median of 2 days after symptoms
began.
No related cases were found among 97 contacts of patients
who had animal exposures.
When researchers looked at the type of personal protective
equipment (PPE) animal workers used, they found only 71% used gloves, 60% used
eye protection, and 47% wore face masks. “PPE use among occupationally exposed
persons was suboptimal, which suggests that additional strategies are needed to
reduce exposure risk,” the authors wrote.
Lingering questions, deep concerns about preparedness
In an editorial in
the same NEJM issue, two experts from the National Institutes
of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID)
weighed in on both reports. The authors are Michael Ison, MD, with the
respiratory diseases branch of the division of microbiology and infectious
diseases, and Jeanne Marrazzo, MD, MPH, the group’s director.
Regarding the Canadian patient, they said it’s not clear if
the mutations were present in the virus that infected the girl or emerged
during her illness course.
They said both reports shine a light on critical features of
the threat to human health and response options. They said the US report
exemplifies collaboration between human and animal health providers, public
health leadership, and occupational health authorities. The standard
surveillance approach is geared toward detecting novel cases, they noted. “This
approach involves cultivating trust not only among numerous entities but with
people seeking care for symptoms of concern, including conjunctivitis,” they
wrote.
Meanwhile, the Canadian case underscores the urgent need to
monitor for mutations, Ison and Marrazzo said. However, they pointed out that
genomic sequencing from animals often lacks the metadata, making it difficult
to track phylogenetic linkages and how the virus is spreading.
They also noted that the prolonged virus shedding that the
Canadian team found highlights the need for longer antiviral therapy, which was
recently reflected in updated CDC recommendations.
