Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy

Abstract

BackgroundIn-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data.ResultsOur results showed that both immigration and local circulation fuel the current Italian HCV1a epidemic. The United States and European continental lineages dominate import into Italy, with the latter taking the lead from the 1970s onwards. Since similar migration patterns were found for Q80K and other lineages, no clear differentiation of the risk for failing simeprevir can be made between patients based on their migration and travel history. Importantly, since HCV only occasionally recombines, these results are readily transferable to the genetic sequencing policy concerning NS5A RAVs.ConclusionsThe patient migration and travel history cannot be used to target only part of the HCV1a infected population for drug resistance testing before start of antiviral therapy. Consequently, it may be cost-effective to expand genotyping efforts to all HCV1a infected patients eligible for simeprevir-based therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-017-0913-3) contains supplementary material, which is available to authorized users.

In Search of Covariates of HIV-1 Subtype B Spread in the United States—A Cautionary Tale of Large-Scale Bayesian Phylogeography

“…Most notably, we introduce novel subsampling strategies to reduce the number of taxa to more manageable numbers. Prior studies have independently used phylogenetic diversity and geographic clusters with the purpose of accounting for sampling biases and reducing the number of sequences [15][16][17], but have not applied these methods to phylogeographic analyses of this magnitude. Our phylogenetically informed subsampling procedure offers a systematic and objective way to significantly reduce the initial number of sequences while preserving as much information on the underlying spatial diffusion process as possible.…”

“…The different trait diffusion models come with different assumptions and their application may also depend on the spatial resolution of the location data. The discrete model makes abstractions of precise geographic data-sometimes made necessary by the absence of fine-scale geographic information-but may still provide a powerful approach to infer epidemiological dynamics, as illustrated in applications like investigating the relevance of migration on public health planning [13][14][15][16][17], identifying the determinants of the spread of dog rabies virus in North Africa [18], or determining the role of swine movements in the dynamics of influenza in the United States [19]. More specifically to HIV, phylogeographic analyses have been used to reconstruct the early continental expansion of HIV-1 group M in Africa [20] and the spread of subtype B across the globe [21] and to North America [22].…”

Cross-country migration linked to people who inject drugs challenges the long-term impact of national HCV elimination programmes

“…As the chronic nature of most HCV infections hampers reliably reconstructing contact networks from patient interviews, virus genetic data can be a valuable alternative source of information for elucidating the geographic history of virus lineages (e.g. 5,6). Using such data, we have recently shown that for the most prevalent subtype among PWID in Spain (40%, 7 ), HCV1a, infections often link to infections abroad -in recent years >50% link to Western European countries, mostly European Union (EU) member states -as opposed to other infections within Spain.…”

“…These sequences were complemented with a background dataset of publicly available data from GenBank (totalling 2752 taxa), and analysed as previously described. 5,8 The Ethics Committee of the San Cecilio Hospital, Granada, approved the study, and no informed consent was required as patient information was anonymised and de-identified prior to analysis.…”

Accurate quantification of within- and between-host HBV evolutionary rates requires explicit transmission chain modelling

“…Reliable estimates of evolutionary rates are critical for testing hypotheses in molecular epidemiology, involving, for example, the timing of viral emergence ( Faria et al 2016 ) or associating past demographic changes with ecological factors ( Bryant et al 2007 ; Markov et al 2012 ; Trovão et al 2015 ; Gill et al 2016 ; Al-Qahtani et al 2017 ; Cuypers et al 2017 ). Various statistical descriptions of sequence divergence through time, collectively referred to as ‘clock models’, have been proposed to estimate the rate of nucleotide substitution (see Ho and Duchêne 2014 for a comprehensive overview).…”