What you should know

This is a technical summary of an analysis of genome sequence data for an influenza A(H5N1) virus from a pediatric case in California This was confirmed by the CDC on November 22nd. This analysis supports the conclusion that the overall risk to the general public associated with the ongoing HPAI A(H5N1) outbreak in dairy cattle and poultry in the United States has not changed and currently remains low.

CDC update

December 10, 2024 – As previously reported, on November 22, 2024, the CDC, in collaboration with the California Department of Public Health (CDPH), confirmed a human infection with avian influenza virus A(H5N1) (H5N1 avian influenza) in a child in California. The patient was initially identified as a suspected case of A(H5N1) through influenza testing and reported to CDPH as part of influenza surveillance, with initial subtyping performed by Stanford Medicine Clinical Virology Laboratory results reported by CDPH on November 19, 2024 and presumptive positive test results.

Based on real-time RT-PCR cycle thresholds (Ct) obtained during diagnostic testing, the patient’s nasopharyngeal sample was found to have very low levels of influenza virus RNA. Initial attempts to sequence the viral RNA from both Stanford Medicine and CDC using standard next-generation sequencing methods resulted in weak amplicons resulting from the PCR process and their sequencing using both Nanopore and CDC methods Illumina sequencing methods were difficult. Additionally, attempts to isolate the virus from the sample were unsuccessful. Using nucleic acid enrichment techniques, CDC and Stanford Medicine were able to generate the following viral RNA sequence data: full-length neuraminidase (NA) and nucleoprotein (NP) genes, as well as partial hemagglutinin (HA), polymerase basic 2 (PB2), and polymerase basic 1 ( PB1) genes. CDC and Stanford Medicine submitted these data for A/California/192/2024 to both the GISAID and GenBank databases with accession numbers EPI_ISL_19597300 and PQ724471-PQ724473, respectively.

Initial sequence analysis, based on short fragments of the HA and NA genes, showed that the virus was a class 2.3.4.4b A(H5N1), similar to viruses found in the United States Cause outbreaks in dairy cattle and poultry. After obtaining full-length NA and NP genes, the CDC was able to conduct a comprehensive phylogenetic analysis that showed the virus was similar to viruses detected in dairy cattle and poultry as well as A(H5N1) viruses from previous infections People were very similar to dairy workers in California. Although the genetic data generated was not sufficient to classify the virus as a specific genotype, the NA and NP sequences had close nucleotide identity and phylogenetic clustering with NA and NP genes from B3 recently discovered in California in humans, dairy cattle, and poultry .13 viruses. Epidemiological and environmental studies have not clearly identified a possible source of exposure. Because no additional sequence data could be generated from the case, it is unlikely that the source of the child’s exposure to the A(H5N1) virus will be identified and thus the genotype and exposure investigation will be completed.

In addition to the phylogenetic analysis of the NA and NP genes, the CDC conducted an assessment of the virus sample’s sequences for molecular changes that could affect infectivity or transmissibility in humans or reduce susceptibility to antiviral drugs such as oseltamivir. The partial HA sequence, despite missing parts of the 5′ end of the gene, had no additional changes in the predicted antigenic sites compared to the available vaccine candidate viruses (CVVs) of class 2.3.4.4b. No changes were also detected in the receptor binding domain of the virus, suggesting that the virus retained avian receptor binding properties and no mutations occurred that would impact changes in infectivity or transmissibility in humans. The PB2 and PB1 genes did not exhibit genetic changes associated with mammalian adaptation, nor were any genetic changes associated with reduced susceptibility to neuraminidase inhibitors such as oseltamivir identified in the NA sequence data. Finally, sequence data confirmed that the virus from this case is not closely related to the virus that caused severe illness in a human in British Columbia, Canada. Overall, these data suggest that the virus detected in this pediatric case is very similar to most other influenza A(H5N1) viruses detected in the United States and does not show evidence of worrisome mutations.

Although the sequence data obtained does not allow for definitive determination of viral genotype and no specific animal exposure source has been identified, these results provide important contextual information and aid in CDC’s overall risk assessment. They also highlight the value of a collaborative approach to this response, including virological risk assessments based on genetic data.

Follow-up actions

Sporadic human infections with a novel influenza virus where animal exposure has not been detected are not uncommon and have occurred during the current H5N1 avian influenza outbreak in dairy cattle and poultry in the United States, as well as in previous outbreaks around the world. This case does not change the CDC’s assessment of the immediate risk to the public, which currently remains low.

There is no evidence of person-to-person transmission of the H5N1 virus in California or elsewhere in the United States. However, there is a risk for people who are occupationally exposed to infected animals, such as: Some people, such as poultry farmers, poultry workers and dairy farm workers, are at higher risk of infection with the influenza A(H5N1) virus. Public health surveillance and investigations of all identified cases will continue at the local, state and federal levels to monitor for any concerning changes in the epidemiology of human cases or changes in influenza A(H5N1) viruses that may indicate an increased threat to public health could include more serious consequences for those currently at risk of exposure and infection, or increased risk for the general public.