OP6 -Antiviral susceptibility of seasonal influenza A and B strains to neuraminidase inhibitors (oseltamivir, zanamivir, peramivir and laninamivir) from 2013– 2024 in Sri Lanka

Abstract

Introduction

Neuraminidase inhibitors (NAIs) are the main antiviral medications for influenza worldwide. Antiviral susceptibility monitoring has become an integral part of influenza surveillance conducted by laboratories participating in the Global Influenza Surveillance Response System. Phenotypic assays for determining 50% inhibitory concentrations (IC₅₀) for NAIs are commonly fluorescence-based.

Objectives

To report antiviral susceptibility to NAIs (oseltamivir, zanamivir, peramivir and laninamivir) among seasonal influenza A and B viruses circulating from 2013–2024 in Sri Lanka.

Design, setting and methods

Representative samples from patients on antiviral from routine surveillance (geographically), clinical samples (ward, ICU), post-mortem samples, different age groups, and tissue culture isolates were sent to the WHO Collaborating Centre (WHO CC), Australia, for NAI susceptibility testing from 2013–2024. Samples were subjected to Sanger/whole-genome sequencing, and where virus isolates were available, these were tested for susceptibility to NAIs using the 2′-(4-Methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) substrate phenotypic assay. IC₅₀ values for viruses were compared to the median IC₅₀ of viruses of the respective type/subtype/lineage known to be susceptible to the NAIs. Three categories of inhibition were determined: normal inhibition, reduced inhibition, and highly reduced inhibition.

Results

Of 1402 samples, 217 strains were cultured and tested in phenotypic assays. From the years 2013 to 2024, 20, 13, 19, 20, 39, 17, 20, 08, 30, 13, 0, and 18 strains that were isolated were tested, respectively. All influenza A, pandemic H1N1 2009 (n=78), H3N2 (n=88) strains and influenza B (n=51) strains showed normal inhibition to oseltamivir, zanamivir, peramivir and laninamivir, and no genetic markers associated with reduced/highly reduced inhibition were identified.

Conclusions

All isolated strains of seasonal influenza virus showed normal inhibition to oseltamivir, zanamivir peramivir and laninamivir. Due to cost and logistic constraints, a limited number of samples were sent for testing. National Influenza Centres and WHO CCs should monitor as many samples as possible for genetic markers for antiviral resistance, with a subset being selected for phenotypic testing. This is the first report of antiviral susceptibility of peramivir and laninamivir in Sri Lanka.