Molecular characterization of Influenza A pandemic H1N1 viruses circulating in eastern India during 2017-19: Antigenic diversity in comparison to the vaccine strains.

In the endemic settings of India, high CFR (3.6-7.02%) was observed in the consecutive 2009, 2015 and 2017 A/H1N1pdm09 outbreaks, though in eastern India CFR varied between 0 and 5.5% during same period. Recurrent outbreaks of pandemic Influenza A/H1N1pdm09, fragmented nationwide incidence data, lack of national policy for Influenza vaccination in India underscores the necessity for generating regional level data. Thus, during 2017-19, 4106 referred samples from patients hospitalized with severe acute respiratory illness (SARI) in eastern India were tested for A/H1N1pdm09 infection. Among which 16.5% (n = 677/4106) were found A/H1N1pdm09 positive. Individuals <20 years and middle-aged persons (40-60 years) were most susceptible to A/H1N1pdm09 infection. The vaccine strain (A/human/California/07/2009) which was globally used before 2017, clustered in a different lineage away from the representative eastern Indian strains in the phylogenetic dendrogram. The vaccine strain (A/human/Michigan/45/2015) used in India during the study period and the WHO recommended strain (A/human/Brisbane/02/2018) for 2019-20 flu season for the northern hemisphere, clustered with the circulating isolates in the same lineage-6b. Dissimilarities in the amino acids encompassing the antigenic epitopes were seen to be highest with the vaccine strain- A/human/California/07/2009. The significant amino acid variations in the circulating strains with the current WHO recommended vaccine strain, implies the exigency of continuous pandemic A/H1N1pdm09 surveillance studies in this epidemiological setting. The absence of any Oseltamivir resistant mutation (H275Y) in the neuraminidase gene of the current isolates suggests continuing use of Tamiflu® as an antiviral therapy in suspected subjects in this region.