Canadian Teen Recovers From Severe H5N1 Bird Flu Infection

A 13-year-old Canadian girl recovered after being hospitalized in critical condition with H5N1 avian influenza, researchers reported.

The girl was hospitalized on Nov. 7 and transferred to BC Children’s Hospital the next day, where she was intubated and put on extracorporeal membrane oxygenation (ECMO) and treated with three different antivirals, David Goldfarb, MD, of BC Children’s Hospital in Vancouver, and colleagues reported in the New England Journal of Medicine (NEJM).

The girl had a history of asthma and a body mass index greater than 35. She first presented to an emergency department in British Columbia on Nov. 4 with a 2-day history of conjunctivitis in both eyes and a 1-day history of fever. She was discharged without treatment, but then she developed a cough, vomiting, and diarrhea.

She went back to the ED on Nov. 7 with respiratory distress with hemodynamic instability, Goldfarb’s group reported. The next day, she was transferred to the pediatric ICU at BC Children’s while on bilevel positive airway pressure. She had respiratory failure, pneumonia in the left lower lobe, acute kidney injury, thrombocytopenia, and leukopenia.

Her doctors started oseltamivir (Tamiflu) on Nov. 8, but with signs of respiratory deterioration and chest radiographs consistent with progression to acute respiratory distress syndrome, she was intubated and started on ECMO on Nov. 9, with continuous renal replacement starting the day after that.

Physicians added amantadine (Gocovri) on Nov. 9, and baloxavir (Xofluza) on Nov. 11. She received daily plasma exchange for 3 days starting Nov. 14.

Over the next days, her respiratory status improved, and she was able to discontinue ECMO on Nov. 22, with extubation on Nov. 28. The authors didn’t provide additional details on her discharge or recovery.

As for testing, the girl’s first swab at BC Children’s was positive for influenza A but negative for H1 or H3 disease. Further polymerase chain reaction testing for flu, COVID, and respiratory syncytial virus showed a cycle threshold (Ct) value of 27.1, suggesting a relatively high viral load, which prompted further subtyping, revealing H5 disease.

The researchers added that lower respiratory specimens consistently yielded lower Ct values than upper respiratory specimens, suggesting higher viral loads in the lower respiratory tract.

Researchers also sequenced the viral genome from a sample collected on Nov. 9, which was 8 days after the onset of symptoms. It was clade 2.3.4.4b, genotype D1.1, which was most closely related to wild birds in British Columbia from around the same time. This is the same genotype reported in a patient from Louisiana who had been hospitalized with severe illness after being exposed to sick birds in a backyard poultry flock.

Goldfarb and colleagues noted that sequencing also found markers of adaptation to humans in three locations: E627K in the polymerase basic 2 (PB2) gene, and in E186D and Q222H in the hemagglutinin gene, which has previously been shown to give the virus an advantage in entering cells in the human respiratory tract and enable replication.

The researchers called these changes, particularly the ones in the hemagglutinin gene, “worrisome.”

In an accompanying editorial, Michael Ison, MD, and Jeanne Marrazzo, MD, MPH, both of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, wrote that these mutations “highlight the urgent need for vigilant surveillance of emerging mutations and assessment of the threat of human-to-human transmission.”

They cautioned that “genomic sequencing data collected from animals frequently lack critical metadata. Without information pertaining to where and when isolates were collected, the data cannot be linked phylogenetically to other reported sequences, which limits insight into how the virus is spreading.”

Having the metadata would also help with early detection of mutations that might show adaptations to humans, they noted.

NEJM also published a report on the 46 human cases of H5N1 identified from March through October in the U.S., most of whom had been exposed to poultry (n=20) or dairy cattle (n=25). Only one patient, who was hospitalized with non-respiratory symptoms, had no exposure identified.

Of these patients with known animal exposures, none were hospitalized, and there were no deaths, according to Shikha Garg, MD, of the CDC, and colleagues.

The vast majority (93%) had conjunctivitis, about half (49%) had fever, and 36% had respiratory symptoms. One in three had conjunctivitis only. Among the 16 patients with available data, the mean duration of illness was 4 days.

No cases were identified among 97 household contacts of case patients with animal exposures, the researchers added.

They also found that use of personal protective equipment in these patients had been suboptimal, as only 71% wore gloves, 60% wore eye protection, and 47% wore face masks.

It’s not clear why U.S. cases have thus far been mild, even though the case fatality rate reported globally has been around 50%. Aside from under-reporting of cases, other factors could include early detection and initiation of antiviral treatment, route of exposure, virologic characteristics, and preexisting immunologic profiles of infected hosts, the researchers wrote.

Ison and Marrazzo called for a “balance between enhanced vigilance and ‘business as usual.'”

“The past weeks have seen more cases detected in more states as well as more persons with respiratory illness acquired through exposure to poultry or from an unknown source,” they noted. “Without a clearer understanding of the extent of exposure, infection, viral evolution, and transmission, we will be unable to properly protect our communities from a pathogen that has proven to be a formidable challenge to human and animal health.”