British Columbia - Credit Wikipedia
#18,518
On November 9th the B.C. Govt Announced a Presumptive Positive H5 Case In a Teenager, who was hospitalized at B.C. Children's Hospital. Initial details provided were scant, but 3 days later BC's health officer Dr. Bonnie Henry revealed in a press conference that the patient was in critical condition.While H5N1 has a history of producing severe illness, all of the recent human infections (n=44 up until that time) in the United States had been mild.
On November 14th we learned that this patient's infection was from the newly emerging D.1.1 genotype, recently reported in wild birds and poultry in the Pacific Northwest and which have infected ≈ 12 poultry workers in Washington State.
On November 26th the B.C. Govt announced that after extensive investigation - including contract tracing and testing of HCWs, monitoring friends and family members, and testing more than 2 dozen animals - they had been unable to find the source of the virus, or any indication of onward transmission.Since then, we've seen another severe case reported from Louisiana (see CDC Statement On First Severe Case Of H5N1 In The United States), again from the D1.1 genotype.
The patient was reported still be in critical - but stable - condition, and no further updates would be provided.
Of considerable interest, todays report discusses the detection of several significant amino acid substitutions, which are believed to increase mammalian adaptations.
Just over a month ago, in Referral: MedCram On Avian Flu Mutations That Favor Human Transmission, we looked at early reports of ambiguous mutations at several key sites (Q226 and E190 (H3 numbering)) in the HA gene.
These mutations have previously been linked to increased binding to `mammalian' α2-6–linked sialic acid receptor cells, which are commonly found in the human upper airway.
Today's report adds that the PB2-E627K mutation was also detected (52% allele frequency). This mutation is known to increase IAV replication in mammalian cells, and is considered a particularly important finding.
Curiously, we've seen more than twice as many human infections with the bovine B3.13 genotype, and so far, none have been severe. Both genotypes continue to evolve and adapt, however.While we've only seen a small number (≈ 20) of human infections with this D1.1 genotype, at least two have proved serious enough to require hospitalization. Both shared at least one HA mutation; E186E/D (aka E190E/D H3 numbering).
These two cases (B.C. & Louisiana) demonstrate that North American H5N1 viruses are capable of producing severe illness, and both have shown genetic changes to their HA that may increase binding to human airway receptors.
Events that the authors of this report call `worrisome'.
I've provided the link below. Follow it to read the report in its entirety. After which you'll you'll find an NIH Press release and a link to an accompanying editorial.
Critical Illness in an Adolescent with Influenza A(H5N1)Virus Infection
A.N. Jassem and Others
NIH Officials Assess Threat of H5N1
Balancing Enhanced Vigilance and “Business as Usual”
December 31, 2024
Highly pathogenic H5N1 avian influenza A virus (HPAI H5N1) remains a low risk to the general public, and public health experts in the United States believe that available treatments and vaccines, as well as those in development, are sufficient to prevent severe disease. However, the National Institutes of Health (NIH) and its federal partners remain focused on monitoring the virus and evaluating changes, according to leading officials at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH.
In a commentary published in the New England Journal of Medicine, NIAID Director Jeanne M. Marrazzo, M.D., M.P.H., and Michael G. Ison, M.D., M.S., chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases, say people should find a balance between enhanced vigilance and “business as usual” with respect to HPAI H5N1.
Since 1996, HPAI H5N1 influenza viruses have circulated in at least 23 countries. In late 2021, HPAI H5N1 spread from Europe to North America causing sporadic infections among wild birds and poultry farms. In 2022, the virus spread to South America where it devastated birds and marine mammals. In March 2024, USDA scientists identified HPAI H5N1 in U.S. dairy cows, and it subsequently reached herds in 16 states. The virus has been detected in dairy herds in three states over the past 30 days, according to USDA/APHIS. In 2024, the virus has caused 66 confirmed and 7 probable cases of influenza in people in the U.S. and one case in Canada. These human cases have been caused by either the H5N1 type circulating in birds (D1.1) or the type circulating in dairy cows (B3.13).
Against this backdrop, Drs. Marrazzo and Ison say there are four keys to controlling the current outbreak. The first imperative is timely, effective collaborations among investigators in human and veterinary medicine, public health, health care, and occupational workers, such as dairy and poultry workers.
This involves cultivating trust not only between numerous entities, but with people seeking care for symptoms of concern, including conjunctivitis, the authors write. Fortunately, so far most U.S. cases of HPAI H5N1 have been mild and resolved on their own without the need for treatment.
Their second key is a focus on the Canadian HPAI H5N1 patient, who developed respiratory failure and required life-saving medical intervention and treatment before recovering. The authors write that mutations found in the virus in this patient highlight an urgent need for vigilant disease surveillance to identify and assess viral changes to evaluate the risk for person-to-person transmission. Effective surveillance, they say, requires that complete genomic sequencing data from animals and people are made rapidly and readily available.
Without information pertaining to where and when isolates were collected, the data cannot be linked phylogenetically to other reported sequences, limiting insight into how the virus is spreading, they write. These data would also provide opportunity for early detection of mutations that might portend avidity for human respiratory epithelium, which may require as little as one mutation in the virus.
Third, researchers must continue to develop and test medical countermeasures—such as vaccines and therapies that eliminate or alleviate disease—against H5N1 and other influenza viruses. Fortunately, current vaccine candidates neutralize the circulating strains, which so far are susceptible to antivirals that could mitigate transmission and severity of illness, they write.
Lastly, Drs. Marrazzo and Ison encourage people to take precautions to prevent exposure to the virus and minimize the risk of infection. For example, people who work with poultry and cows should use personal protective equipment and educate themselves about occupational risks when working with birds and mammals, as CDC and USDA have repeatedly recommended.
Ideally, following these four steps will help scientists and public health officials investigating HPAI H5N1 to answer the many remaining questions more quickly about how the virus is spreading, evolving, and affecting people, other mammals, and birds.
ARTICLE:
M Ison and J Marrazzo. The Emerging Threat of H5N1 to Human Health. NEJM DOI: 10.1056/NEJMe2416323 (2024).
WHO:
NIAID Director Jeanne M. Marrazzo, M.D., M.P.H., and Michael G. Ison, M.D., M.S., chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases, are available for comment.
The Emerging Threat of H5N1 to Human Health
Michael G. Ison, M.D., and Jeanne Marrazzo, M.D., M.P.H.
