Genomic investigation of an Influenza A(H3N2) subclade K outbreak in a secondary school in Burundi, 2026

Abstract

Severe acute respiratory infections (SARI) are an important public health concern, particularly in settings where identification of the causative pathogen can be challenging. Testing of patients with unexplained SARI (SARI surveillance) and characterization of causative pathogens also is seen as an important pillar of emerging disease preparedness. Therefore, we applied targeted viral enrichment sequencing as a tool for understanding a broad range of disease etiologies. In January 2026, an increase in respiratory illness cases was reported in a secondary school in Bujumbura, Burundi, raising concerns about a possible resurgence of coronavirus disease 2019 (COVID-19). However, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of symptomatic individuals was negative, suggesting the involvement of another respiratory pathogen. To identify the causative agent, nasopharyngeal samples collected from symptomatic students were investigated using targeted viral enrichment sequencing. Eight SARS-CoV-2-negative samples were sequenced using the Illumina Viral Surveillance Panel v2 on the iSeq 100 platform. Sequencing reads were quality-checked and analysed for viral identification, followed by genome reconstruction, clade assignment, and phylogenetic analysis of the identified viruses. Influenza A virus (IAV) was detected in seven of the eight analyzed samples. Four samples yielded near-complete IAV genomes, allowing detailed genomic characterization. All characterized genomes were identified as Influenza A(H3N2) subclade K, representing the first genomic detection and characterization of this subclade in Burundi. Phylogenetic analysis showed that Burundian sequences clustered into two distinct groups, suggesting the circulation of at least two viral lineages during the outbreak. No neuraminidase inhibitor resistance-associated markers were detected. Influenza sequences were shared through GISAID to support global influenza surveillance. This study shows the usefulness of targeted viral-enrichment sequencing for investigating acute respiratory outbreaks when the cause is not known, particularly when initial testing is negative and routine testing for other respiratory viruses is limited. We provide the first genomic characterization of Influenza A(H3N2) subclade K in Burundi. The identification of different viral lineages highlights the value of genomic approaches to complement routine laboratory testing and support outbreak investigation and respiratory pathogen surveillance in Burundi.