Characterizing the Countrywide Epidemic Spread of Influenza A(H1N1)pdm09 Virus in Kenya between 2009 and 2018

Abstract

The spatiotemporal patterns of spread of influenza A(H1N1)pdm09 viruses on a countrywide scale are unclear in many tropical/subtropical regions mainly because spatiotemporally representative sequence data are lacking. We isolated, sequenced, and analyzed 383 A(H1N1)pdm09 viral genomes from hospitalized patients between 2009 and 2018 from seven locations across Kenya. Using these genomes and contemporaneously sampled global sequences, we characterized the spread of the virus in Kenya over several seasons using phylodynamic methods. The transmission dynamics of A(H1N1)pdm09 virus in Kenya were characterized by (i) multiple virus introductions into Kenya over the study period, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters, (ii) persistence of transmission clusters over several epidemic seasons across the country, (iii) seasonal fluctuations in effective reproduction number (Re) associated with lower number of infections and seasonal fluctuations in relative genetic diversity after an initial rapid increase during the early pandemic phase, which broadly corresponded to epidemic peaks in the northern and southern hemispheres, (iv) high virus genetic diversity with greater frequency of seasonal fluctuations in 2009–2011 and 2018 and low virus genetic diversity with relatively weaker seasonal fluctuations in 2012–2017, and (v) virus spread across Kenya. Considerable influenza virus diversity circulated within Kenya, including persistent viral lineages that were unique to the country, which may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied low-to-middle-income tropical and subtropical regions is required to understand the full diversity and global ecology of influenza viruses in humans and to inform vaccination strategies within these regions.

Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons

“…The genetic diversity of A(H1N1)pdm09 viruses in specific regions arising from multiple virus introductions and subsequent establishment of local transmission clusters [13] composed of viruses harboring considerable amino acid substitutions in antigenic epitopes and RBS could lead to predominance of circulating viruses that are not closely matched to previously selected vaccine strains as shown in our study. In countries like Kenya, where influenza virus spread is year-round [9], there also exists unpredictability of which genetic virus strain may predominate and when.…”

“…Analysis of virus sequence data from Kenya during the pandemic in 2009 identified the introduction of clades 2 and 7 viruses into Kenya [21]. We recently confirmed these findings and showed that clades 6 and 7 viruses were introduced into Kenya, disseminated countrywide, and persisted across multiple epidemics as local transmission clusters [13]. A recent study from Kenya reported the circulation of clade 6B, subclade 6B.1, and subclade 6B.2 viruses in the 2015-18 influenza seasons [22].…”

“…We identified considerable amino acid substitutions in antigenic epitopes and RBS among the circulating viruses, which confirms the continued evolution of circulating influenza viruses in Kenya. We recently reported that the evolutionary dynamics of A(H1N1)pdm09 virus in Kenya was associated with multiple virus introductions into the country between 2009 and 2018, although only a few of those introductions instigated local seasonal epidemics that then established local transmission clusters across the country [13]. We also observed substitutions in NA protein, which have been associated with reduced susceptibility to neuraminidase inhibitors in vitro [19], substitutions in M2 protein associated with adamantine-resistance, and substitutions in NS1 protein that possibly result in increased virulence [20].…”

“…Influenza vaccines with broad coverage (“universal” vaccines) could be key to managing the influenza disease burden in such settings. Currently, Kenya does not have a national influenza vaccination policy [28], but it would be important to consider deployment of quadrivalent influenza vaccines with representative A(H1N1)pdm09 virus, A(H3N2) virus, and both influenza B virus lineages (B/Victoria and B/Yamagata) for optimal vaccine effectiveness [13, 29, 30]. It will also be important to investigate further whether the use of SH or NH formulated vaccines could have a place in tropical regions like in Kenya, where virus importations from both hemispheres are common.…”

“…The rapid ability of the virus to spread globally upon its emergence highlights the public health threat posed by emergent viruses [3, 10, 11]. The countrywide surveillance for influenza viruses among medically-attended patients in Kenya since the emergence of the A(H1N1)pdm09 virus strain allows for exploring the phenotypic characteristics of the virus [7, 12, 13].…”