Haemagglutinin and neuraminidase sequencing delineate nosocomial influenza outbreaks with accuracy equivalent to whole genome sequencing

Abstract

We describe haemagglutinin (HA) and neuraminidase (NA) sequencing in an apparent cross-site influenza A(H1N1) outbreak in renal transplant and haemodialysis patients, confirmed with whole genome sequencing (WGS). Isolates were sequenced from influenza positive individuals. Phylogenetic trees were constructed using HA and NA sequencing and subsequently WGS. Sequence data was analysed to determine genetic relatedness of viruses obtained from inpatient and outpatient cohorts and compared with epidemiological outbreak information. There were 6 patient cases of influenza in the inpatient renal ward cohort (associated with 3 deaths) and 9 patient cases in the outpatient haemodialysis unit cohort (no deaths). WGS confirmed clustered transmission of two genetically different influenza A(H1N1)pdm09 strains initially identified by analysis of HA and NA genes. WGS took longer, and in this case was not required to determine whether or not the two seemingly linked outbreaks were related. Rapid sequencing of HA and NA genes may be sufficient to aid early influenza outbreak investigation making it appealing for future outbreak investigation. However, as next generation sequencing becomes cheaper and more widely available and bioinformatics software is now freely accessible next generation whole genome analysis may increasingly become a valuable tool for real-time Influenza outbreak investigation.