Phylogeography and epidemic history of hepatitis C virus genotype 4 in Africa

Abstract

HCV genotype 4 is prevalent in many African countries, yet little is known about the genotype׳s epidemic history on the continent. We present a comprehensive study of the molecular epidemiology of genotype 4. To address the deficit of data from the Democratic Republic of the Congo (DRC) we PCR amplified 60 new HCV isolates from the DRC, resulting in 33 core- and 48 NS5B-region sequences. Our data, together with genotype 4 database sequences, were analysed using Bayesian phylogenetic approaches. We find three well-supported intra-genotypic lineages and estimate that the genotype 4 common ancestor existed around 1733 (1650–1805). We show that genotype 4 originated in central Africa and that multiple lineages have been exported to north Africa since ~1850, including subtype 4a which dominates the epidemic in Egypt. We speculate on the causes of the historical intra-continental spread of genotype 4, including population movements during World War 2.

Historical Trends in the Hepatitis C Virus Epidemics in North America and Australia

“…For example, the origins of subtype 6 in East Asia have been traced back to approximately 1000 CE by evolutionary analysis of sequence data [32]. Similarly, the origin of the genotype 4 epidemic in Africa has been traced back to the 17th century [33]. However, evolutionary analysis of the more common subtypes with a global distribution (1a, 1b, and 3a), which are frequently referred to as "epidemic" subtypes, have consistently traced the ancestor to within the last century in many locations around the world [34,35].…”

Hepatitis C Virus Genotype 7, a New Genotype Originating from Central Africa

“…This considerable level of genetic diversity suggests that genotype 7 has been propagated and maintained for a long time in the DRC. Interestingly, in a recent survey of HCV genotypes in the DRC, Iles et al (17) did not detect isolates belonging to genotype 7. However, genotype 7 may have remained undetected as the NS5B sequence data used for accessing the genotypes were not obtained for 20% of the sam- Mean distances between genotypes were calculated using the sequences described in Fig.…”

“…ples that had detectable HCV RNA in the 5= UTR (17). This indicates that although genotype 7 may well have its origin in the DRC, it is not highly prevalent in this country or is delimited to certain regions.…”

Estimating infectious disease transmission distances using the overall distribution of cases

“…Phylogeographic methods have been developed to estimate rates of viral movement across countries or continents under these conditions (Faye et al, 2015; Rabaa et al, 2013). However, these approaches have not yet been able to reliably capture micro-scale dynamics except in isolated settings such as hospital-based outbreaks (Cotten et al, 2013; Iles et al, 2014; Pybus et al, 2012; Rabaa et al, 2010), and may be impossible where genome mutation rates are particularly low or high relative to the generation time. Even where phylogenetic approaches can be used, it is likely to require potentially prohibitive labor-intensive sequencing of large numbers of pathogens throughout the course of an outbreak (Stack et al, 2010).…”