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Abstract

Background

Reducing the burden of the hepatitis C virus (HCV) requires large-scale deployment of intervention programmes, which can be informed by the dynamic pattern of HCV spread. In Spain, ongoing transmission of HCV is mostly fuelled by people who inject drugs (PWID) infected with subtype 1a (HCV1a).

Aim

Our aim was to map how infections spread within and between populations, which could help formulate more effective intervention programmes to halt the HCV1a epidemic in Spain.

Methods

Epidemiological links between HCV1a viruses from a convenience sample of 283 patients in Spain, mostly PWID, collected between 2014 and 2016, and 1,317, 1,291 and 1,009 samples collected abroad between 1989 and 2016 were reconstructed using sequences covering the NS3, NS5A and NS5B genes. To efficiently do so, fast maximum likelihood-based tree estimation was coupled to a flexible Bayesian discrete phylogeographic inference method.

Results

The transmission network structure of the Spanish HCV1a epidemic was shaped by continuous seeding of HCV1a into Spain, almost exclusively from North America and European countries. The latter became increasingly relevant and have dominated in recent times. Export from Spain to other countries in Europe was also strongly supported, although Spain was a net sink for European HCV1a lineages. Spatial reconstructions showed that the epidemic in Spain is diffuse, without large, dominant within-country networks.

Conclusion

To boost the effectiveness of local intervention efforts, concerted supra-national strategies to control HCV1a transmission are needed, with a strong focus on the most important drivers of ongoing transmission, i.e. PWID and other high-risk populations.

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/content/10.2807/1560-7917.ES.2019.24.9.1800227
2019-02-28
2019-03-18
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2019.24.9.1800227
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References

  1. Chung RT, Ghany MG, Kim AY, Marks KM, Naggie S, Vargas HE, et al. Hepatitis C guidance 2018 update: AASLD-IDSA recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis. 2018;67(10):1477-92.  https://doi.org/10.1093/cid/ciy585  PMID: 30215672 
  2. Centers for Disease Control and Prevention (CDC). New hepatitis C infections nearly tripled over five years. Atlanta: CDC; 2017. Available from: https://www.cdc.gov/media/releases/2017/p-hepatitis-c-infections-tripled.html
  3. Al-Qahtani AA, Baele G, Khalaf N, Suchard MA, Al-Anazi MR, Abdo AA, et al. The epidemic dynamics of hepatitis C virus subtypes 4a and 4d in Saudi Arabia. Sci Rep. 2017;7(1):44947.  https://doi.org/10.1038/srep44947  PMID: 28322313 
  4. Cuypers L, Vrancken B, Fabeni L, Marascio N, Cento V, Di Maio VC, et al. Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy. BMC Evol Biol. 2017;17(1):70.  https://doi.org/10.1186/s12862-017-0913-3  PMID: 28270091 
  5. Jacka B, Applegate T, Poon AF, Raghwani J, Harrigan PR, DeBeck K, et al. Transmission of hepatitis C virus infection among younger and older people who inject drugs in Vancouver, Canada. J Hepatol. 2016;64(6):1247-55.  https://doi.org/10.1016/j.jhep.2016.02.031  PMID: 26924451 
  6. Baele G, Dellicour S, Suchard MA, Lemey P, Vrancken B. Recent advances in computational phylodynamics. Curr Opin Virol. 2018;31:24-32.  https://doi.org/10.1016/j.coviro.2018.08.009  PMID: 30248578 
  7. Dennis AM, Herbeck JT, Brown AL, Kellam P, de Oliveira T, Pillay D, et al. Phylogenetic studies of transmission dynamics in generalized HIV epidemics: an essential tool where the burden is greatest? J Acquir Immune Defic Syndr. 2014;67(2):181-95.  https://doi.org/10.1097/QAI.0000000000000271  PMID: 24977473 
  8. Pérez AB, Chueca N, García F. Resistance testing for the treatment of chronic hepatitis C with direct acting antivirals: when and for how long? Germs. 2017;7(1):40-4.  https://doi.org/10.18683/germs.2017.1107  PMID: 28331841 
  9. Lavin AC, Perello C, Llerena S, Gomez M, Escudero MD, Rodriguez L, et al. Prevalence of hepatitis C in the Spanish population. The prevhep study (ethon cohort). J Hepatol. 2017;66(1):S272.  https://doi.org/10.1016/S0168-8278(17)30857-7 
  10. Aguilera A, Navarro D, Rodríguez-Frias F, Viciana I, Martínez-Sapiña AM, Rodríguez MJ, et al. Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000-2015 period (the GEHEP 005 study). J Viral Hepat. 2017;24(9):725-32.  https://doi.org/10.1111/jvh.12700  PMID: 28248445 
  11. Kartashev V, Döring M, Nieto L, Coletta E, Kaiser R, Sierra S, et al. New findings in HCV genotype distribution in selected West European, Russian and Israeli regions. J Clin Virol. 2016;81:82-9.  https://doi.org/10.1016/j.jcv.2016.05.010  PMID: 27367545 
  12. Berenguer J, Rivero A, Jarrín I, Núñez MJ, Vivancos MJ, Crespo M, et al. Human immunodeficiency virus/hepatitis C virus coinfection in Spain: prevalence and patient characteristics. Open Forum Infect Dis. 2016;3(2):ofw059.  https://doi.org/10.1093/ofid/ofw059  PMID: 27186584 
  13. Plan estratégico para el abordaje de la hepatitis C en el sistema nacional de salud. [Strategic plan for tackling hepatitis C in the Spanish national health system]. Madrid: Ministry of Health, Social Services and Equality; 2015. Available from: http://www.emcdda.europa.eu/system/files/attachments/9473/14%20ES%20plan_estrategico_hepatitis_C.pdf
  14. Gifford RJ, de Oliveira T, Rambaut A, Pybus OG, Dunn D, Vandamme AM, et al. Phylogenetic surveillance of viral genetic diversity and the evolving molecular epidemiology of human immunodeficiency virus type 1. J Virol. 2007;81(23):13050-6.  https://doi.org/10.1128/JVI.00889-07  PMID: 17898057 
  15. Libin P, Deforche K, Abecasis AB, Theys K. VIRULIGN: fast codon-correct alignment and annotation of viral genomes. Bioinformatics. 2018.  https://doi.org/10.1093/bioinformatics/bty851  PMID: 30295730 
  16. Vaughan TG, Kühnert D, Popinga A, Welch D, Drummond AJ. Efficient Bayesian inference under the structured coalescent. Bioinformatics. 2014;30(16):2272-9.  https://doi.org/10.1093/bioinformatics/btu201  PMID: 24753484 
  17. De Maio N, Wu CH, O’Reilly KM, Wilson D. New routes to phylogeography: a Bayesian structured coalescent approximation. PLoS Genet. 2015;11(8):e1005421.  https://doi.org/10.1371/journal.pgen.1005421  PMID: 26267488 
  18. Faria NR, Hodges-Mameletzis I, Silva JC, Rodés B, Erasmus S, Paolucci S, et al. Phylogeographical footprint of colonial history in the global dispersal of human immunodeficiency virus type 2 group A. J Gen Virol. 2012;93(Pt 4):889-99.  https://doi.org/10.1099/vir.0.038638-0  PMID: 22190015 
  19. Magiorkinis G, Magiorkinis E, Paraskevis D, Ho SY, Shapiro B, Pybus OG, et al. The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis. PLoS Med. 2009;6(12):e1000198.  https://doi.org/10.1371/journal.pmed.1000198  PMID: 20041120 
  20. Pybus OG, Tatem AJ, Lemey P. Virus evolution and transmission in an ever more connected world. Proc Biol Sci. 2015;282(1821):20142878.  https://doi.org/10.1098/rspb.2014.2878  PMID: 26702033 
  21. Bover O, Pilar V. Migration in Spain: Historical background and current trends. In: Zimmermann KF, editor. European migration: what do we know? 1999. 31 p.
  22. Robaeys G, Bielen R, Azar DG, Razavi H, Nevens F. Global genotype distribution of hepatitis C viral infection among people who inject drugs. J Hepatol. 2016;65(6):1094-103.  https://doi.org/10.1016/j.jhep.2016.07.042  PMID: 27520879 
  23. Beyrer C, Razak MH, Lisam K, Chen J, Lui W, Yu XF. Overland heroin trafficking routes and HIV-1 spread in south and south-east Asia. AIDS. 2000;14(1):75-83.  https://doi.org/10.1097/00002030-200001070-00009  PMID: 10714570 
  24. Bielejec F, Baele G, Vrancken B, Suchard MA, Rambaut A, Lemey P. SpreaD3: interactive visualization of spatiotemporal history and trait evolutionary processes. Mol Biol Evol. 2016;33(8):2167-9.  https://doi.org/10.1093/molbev/msw082  PMID: 27189542 
  25. Minin VN, Suchard MA. Fast, accurate and simulation-free stochastic mapping. Philos Trans R Soc Lond B Biol Sci. 2008;363(1512):3985-95.  https://doi.org/10.1098/rstb.2008.0176  PMID: 18852111 
  26. Rodrigo C, Eltahla AA, Bull RA, Grebely J, Dore GJ, Applegate T, et al. Historical trends in the hepatitis C virus epidemics in North America and Australia. J Infect Dis. 2016;214(9):1383-9.  https://doi.org/10.1093/infdis/jiw389  PMID: 27571901 
  27. van Asten L, Verhaest I, Lamzira S, Hernandez-Aguado I, Zangerle R, Boufassa F, et al. Spread of hepatitis C virus among European injection drug users infected with HIV: a phylogenetic analysis. J Infect Dis. 2004;189(2):292-302.  https://doi.org/10.1086/380821  PMID: 14722895 
  28. Culasso AC, Farías A, Di Lello FA, Golemba MD, V, Barbini L, et al. Spreading of hepatitis C virus subtypes 1a and 1b through the central region of Argentina. Infect Genet Evol. 2014;26:32-40.  https://doi.org/10.1016/j.meegid.2014.05.008  PMID: 24820342 
  29. Kreienbrink A. Focus Migration: Country profile 6; Spain. Hamburg: Institute of International Economics; 2008. Available from: http://focus-migration.hwwi.de/uploads/tx_wilpubdb/CP_06_Spain-08.pdf
  30. European Union. About the EU. Spain. Trade and economy. Brussels: European Commission. [Accessed: 20 Feb 2019]. Available from: https://europa.eu/european-union/about-eu/countries/member-countries/spain_en#trade-and-economy
  31. Cochrane A, Searle B, Hardie A, Robertson R, Delahooke T, Cameron S, et al. A genetic analysis of hepatitis C virus transmission between injection drug users. J Infect Dis. 2002;186(9):1212-21.  https://doi.org/10.1086/344314  PMID: 12402190 
  32. Vrancken B, Adachi D, Benedet M, Singh A, Read R, Shafran S, et al. The multi-faceted dynamics of HIV-1 transmission in Northern Alberta: A combined analysis of virus genetic and public health data. Infect Genet Evol. 2017;52:100-5.  https://doi.org/10.1016/j.meegid.2017.04.005  PMID: 28427935 
  33. Parczewski M, Cielniak I, Kordek J, Aksak-Wąs B, Urbańska A, Leszczyszyn-Pynka M, et al. Transmission networks of HCV genotpye 1a enriched with pre-existing polymorphism Q80K among HIV-infected patients with acute hepatitis C in Poland. J Acquir Immune Defic Syndr. 2018;77(5):514-22.  https://doi.org/10.1097/QAI.0000000000001628  PMID: 29337848 
  34. Cuypers L, Pérez AB, Chueca N, Aldamiz-Echevarría T, Alados JC, Martínez-Sapiña AM, et al. Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis. PLoS One. 2018;13(7):e0201268.  https://doi.org/10.1371/journal.pone.0201268  PMID: 30044871 
  35. Gräf T, Vrancken B, Maletich Junqueira D, de Medeiros RM, Suchard MA, Lemey P, et al. Contribution of epidemiological predictors in unravelling the phylogeographic history of HIV-1 subtype C in Brazil. J Virol. 2015;89(24):12341-8.  https://doi.org/10.1128/JVI.01681-15  PMID: 26423943 
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