Phylodynamics of Influenza A/H1N1pdm09 in India Reveals Circulation Patterns and Increased Selection for Clade 6b Residues and Other High Mortality Mutants

The clinical severity and observed case fatality ratio of influenza A/H1N1pdm09 in India, particularly in 2015 and 2017 far exceeds current global estimates. Reasons for these frequent and severe epidemic waves remain unclear. We used Bayesian phylodynamic methods to uncover possible genetic explanations for this, while also identifying the transmission dynamics of A/H1N1pdm09 between 2009 and 2017 to inform future public health interventions. We reveal a disproportionate selection at haemagglutinin residue positions associated with increased morbidity and mortality in India such as position 222 and clade 6B characteristic residues, relative to equivalent isolates circulating globally. We also identify for the first time, increased selection at position 186 as potentially explaining the severity of recent A/H1N1pdm09 epidemics in India. We reveal national routes of A/H1N1pdm09 transmission, identifying Maharashtra as the most important state for the spread throughout India, while quantifying climactic, ecological, and transport factors as drivers of within-country transmission. Together these results have important implications for future A/H1N1pdm09 surveillance and control within India, but also for epidemic and pandemic risk prediction around the world.