The Centers for Disease Control and Prevention (CDC) on September 13 shared new information from Missouri officials on recently reported human H5 avian flu case, including that a household contact got sick with similar symptoms the same day and that a healthcare worker had mild symptoms.
In another key development, the CDC detailed findings from genetic sequencing of the virus in the patient’s clinical specimen, including confirmation that the neuraminidase is N1. Though not all genes could be sequenced owing to low amounts of genetic material in the patient's sample, the lab work found more evidence that the H5N1 virus that infected that patient is closely related to the US dairy cow virus.
Household illness timing hints at common exposure
News of symptomatic contacts came as a surprise, after a CDC official said a day earlier that the evidence so far pointed to a "one-off" case. The CDC had said Missouri health officials are leading the investigation, but that it was in close, almost daily contact with the state's health department about the case. So far, no links to animals or raw milk have been found.
In a September 13 situation update, the CDC said the state has subsequently shared information about two symptomatic contacts. One is the patient's household contact, who had similar symptoms on the same day. The patient wasn't tested and has since recovered.
The index patient was hospitalized for a significant underlying medical condition and reported to the hospital with chest pain, nausea, vomiting, diarrhea and weakness. However, the person wasn’t severely ill and wasn't transferred to the intensive care unit. The CDC had said earlier that a respiratory panel was done during hospitalization, which turned up a positive flu result that was batched with other samples and sent to the state lab for subtyping.
The patient received antiviral treatment, was discharged from the hospital, and has recovered. "The simultaneous development of symptoms does not support person-to-person spread but suggests a common exposure," the CDC said.
Missouri officials also told the CDC that a health worker developed mild symptoms but tested negative for flu.
At last week's briefing, a CDC official said serology testing for H5 infection has been discussed for the index patient's contacts, but it's probably too soon for detectable antibody levels to be found.
Sequencing finds 2 HA mutations, confirms N1
In its update, the CDC also shared findings from sequencing, which was limited by low amounts of genetic material in the flu virus from the patient's sample. CDC scientists were able to fully sequence the matrix (M) and nonstructural (NS) genes, but were only able to partially sequence the hemagglutinin (HA) and neuraminidase (NA) genes.
The HA sequence analysis confirms that the patient's virus belongs to the 2.3.4.4b clade and the NA analysis confirms N1. The CDC said there were two amino acid substitutions in the HA sequence that haven't been seen in other human cases, and though they aren't thought to affect infectivity or spread, they are located on an area of the virus that might affect cross-reactivity of 2.3.4.4b candidate vaccine viruses. One of the HA differences (HA A156T) has been seen in less than 1% of dairy cow samples, and the other (HA P136S) has turned up in only one dairy cow sequence.
In other tests on the sample, the CDC said it found no markers of reduced susceptibility to neuraminidase inhibitor antiviral drugs and no mutations linked to an increased potential for human-to-human spread. Despite multiple tries, scientists weren't able to grow the virus from the patient's sample.
Virologist weighs in on mutation implications
After the CDC submitted the sequences to two databases, other labs began analyzing the findings. Jesse Bloom, PhD, MPhil, who leads the Bloom Lab that studies virus evolution at Fred Hutchinson Cancer Center in Seattle, said on X that earlier work by a scientist from the team found that the A160T mutation (which corresponds with A156T in H5 numbering) causes a 10- to 100-fold drop in neutralization by sera from ferrets exposed to the current candidate vaccine virus. He added that, so far, the mutation has been seen in only a handful of infected dairy cattle.
He noted that the mutation underscores the challenges of the candidate vaccine virus approach, adding that the CDC'’s update acknowledges the potential implication.
Bloom said though the second mutation is on the antigenic region of the HA head, it doesn't seem to have much impact on neutralization. He said, however, that it could slightly affect receptor binding. He said the mutation, referenced as P136S in the CDC update, deserves further study because of an estimated modest improvement in receptor binding and the fact that it was found in the Missouri human case, even though it had been found in only one of many known dairy cow sequences.
