Colonial history and contemporary transmission shape the genetic diversity of hepatitis C virus genotype 2 in Amsterdam

Abstract

Evolutionary analysis of hepatitis C virus (HCV) genome sequences has provided insights into the epidemic history and transmission of this widespread human pathogen. Here we report an exceptionally diverse set of 178 HCV genotype 2 (HCV-2) isolates from 189 patients in Amsterdam, comprising 8 distinct HCV subtypes and 10 previously not recognized, unclassified lineages. By combining study subjects' demographic information with phylogeographic and molecular clock analyses, we demonstrate for the first time that the trans-Atlantic slave trade and colonial history were the driving forces behind the global dissemination of HCV-2. We detect multiple HCV-2 movements from present-day Ghana/Benin to the Caribbean during the peak years of the slave trade (1700 to 1850) and extensive transfer of HCV-2 among the Netherlands and its former colonies Indonesia and Surinam over the last 150 years. The latter coincides with the bidirectional migration of Javanese workers between Indonesia and Surinam and subsequent immigration to the Netherlands. In addition, our study sheds light on contemporary trends in HCV transmission within the Netherlands. We observe multiple lineages of the epidemic subtypes 2a, 2b, and 2c (together 67% of HCV-2 infections in Amsterdam), which cluster according to their suspected routes of transmission, specifically, injecting drug use (IDU) and contaminated blood/blood products. Understanding the epidemiological processes that generated the global pattern of HCV diversity seen today is critical for exposing associations between populations, risk factors, and specific HCV subtypes and might help HCV screening and prevention campaigns to minimize the future burden of HCV-related liver disease.

Fig 1

Maximum likelihood phylogeny including the 167 sequences originating from our study spanning both fragments 1 and 2. Taxon labels are colored by individual's risk factor: red, IDU; blue, blood transfusion/nosocomial; green, sexual/MSM; brown, birth in a non-Western country and also include the individual's country of birth using International Organization for Standardisation (ISO) codes. Blue dots indicate well-supported clades (bootstrap value ≥ 70).

Fig 2

Maximum likelihood phylogeny of subtype 2a sequences from our study and all available homologous reference sequences in the HCV sequence database. Dots next to taxon names indicate sequences originating from our study. Taxon labels are color coded by risk factor: red, IDU; blue, blood transfusion. Tip labels denote the country of birth for sequences originating from our study and the country of isolation for sequences obtained from the HCV sequence database using International Organization for Standardization (ISO) codes.

Fig 3

Molecular clock phylogeny of endemic HCV genotype 2 strains. Black dots next to phylogeny tips indicate sequences resulting from our study. Tree branches are colored according to inferred lineage locations: green, West Africa (Senegal, Gambia, Guinea Bissau, and Guinea); blue, Benin-Ghana area (Benin, Burkina Faso, and Ghana); red, (Cameroon, Central African Republic); pink, Madagascar; brown, Caribbean; orange, Asia; light blue, North Africa; black, Western countries. Orange dots on nodes indicate well-supported clades (posterior probability ≥ 80); red dots on nodes indicate clades with excellent support (posterior probability ≥ 90). The capital letters with arrows label the root nodes of the major migrant clades.

Fig 4

Estimated time periods of HCV genotype 2 global lineage migrations and the numbers of individuals transported as part of the trans-Atlantic slave trade over time. (a) Molecular clock-based intervals for lineage migration dates and their credible intervals: lower box, trans-Atlantic migration events; upper box, migration events to other areas. Gray circles in the middle of the intervals indicate our best estimate of time of migration. In some estimates a vertical bar is shown, representing an ancestral node with weak support. In these cases, the left end of the interval represents a conservative estimate of the upper date of migration (see Materials and Methods). Whiskers represent 95% highest posterior density (HPD) credible regions of the most conservative estimates on both sides. Color coding as in Fig. 3. Capital letters in brackets next to arrival destinations correspond to the clade labels in Fig. 3. CAR, Central African Republic. (b) Number of individuals transported as part of the trans-Atlantic slave trade over time: black line, numbers of individuals disembarked in Dutch Guianas; gray line, total numbers of individuals disembarked in the New World (in quarter-century periods). Brown marks indicate the best estimates for times of movement of the trans-Atlantic infection lineages.