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Peer reviewedOpen accessInfluenza

Whole Genome Sequencing of Influenza Virus Transmission Pairs Confirms the Efficacy of Baloxavir in Reducing Household Transmission

Clinical Infectious Diseases·

Adam S Lauring, Leigh Papalambros, William J Fitzsimmons, Emily E Bendall, Aeron C Hurt, Klaus Kuhlbusch, Eriola Berisha, Steffen Wildum

DOI
10.1093/cid/ciag489
PMID
42592831
PMCID
OpenAlex
W7202387353
Study type
Genomic study
Publisher
Oxford University Press (OUP)
Article type
journal-article
Integrity
current

Why this research matters now

The findings provide evidence that genomic sequencing can be used to refine classification of suspected household influenza transmission events. Within the supplied article, the results are relevant to evaluating household transmission and treatment effects, but they do not establish a broader population-level surveillance signal.

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Structured evidence summary

Research question

The study examined whether whole-genome sequencing could distinguish true within-household influenza transmission pairs from possible coincident community infections and whether this changed the estimated effect of baloxavir on household transmission.

Study design

This was a sequence-based genomic reanalysis of specimens from CENTERSTONE households containing at least two influenza-positive individuals. The investigators compared consensus genomes and intrahost variants, constructed phylogenetic trees, and used sequence distances to define transmission-pair thresholds.

Population and setting

The analysis involved influenza-positive individuals from CENTERSTONE households across study-site countries. Complete high-quality genomes were available for 376 of 393 influenza A specimens and 39 of 64 influenza B specimens; reliable sequence data from both individuals were available for 145 of 259 putative transmission pairs.

Main findings

Using the most stringent sequence-distance cutoff, the adjusted household transmission incidence was 9.2% in the baloxavir group and 12.9% in the placebo group, with an adjusted odds ratio of 0.69 and a 95.38% confidence interval of 0.50 to 0.95. The authors report that this sequence-based approach supported the primary CENTERSTONE endpoint and the reported reduction in household influenza transmission after baloxavir treatment.

Public-health relevance

The findings provide evidence that genomic sequencing can be used to refine classification of suspected household influenza transmission events. Within the supplied article, the results are relevant to evaluating household transmission and treatment effects, but they do not establish a broader population-level surveillance signal.

Important limitations

The analysis was limited to putative pairs with reliable sequence data from both individuals, leaving 114 of 259 pairs without such paired data. Influenza B genome completeness was lower than influenza A genome completeness, and this summary is limited to the supplied single-article abstract and metadata; the original paper is required for decision-grade interpretation of additional study limitations.

GIDS interpretation

The article is discoverable under influenza, genomic epidemiology, transmission dynamics, and treatment. Its supplied content provides context on sequence-based assessment of household transmission, but it should not be interpreted as confirmation of a live surveillance signal.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 9 auditable classifier relationships to diseases, places, topics, and study design.

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