Bayesian Phylogeography of Crimean-Congo Hemorrhagic Fever Virus in Europe

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a zoonosis mainly transmitted by ticks that causes severe hemorrhagic fever and has a mortality rate of 5-60%. The first outbreak of CCHF occurred in the Crimean peninsula in 1944-45 and it has recently emerged in the Balkans and eastern Mediterranean. In order to reconstruct the origin and pathway of the worldwide dispersion of the virus at global and regional (eastern European) level, we investigated the phylogeography of the infection by analysing 121 publicly available CCHFV S gene sequences including two recently characterised Albanian isolates. The spatial and temporal phylogeny was reconstructed using a Bayesian Markov chain Monte Carlo approach, which estimated a mean evolutionary rate of 2.96 x 10-4 (95%HPD=1.6 and 4.7 x 10-4) substitutions/site/year for the analysed fragment. All of the isolates segregated into seven highly significant clades that correspond to the known geographical clades: in particular the two new isolates from northern Albania clustered significantly within the Europe 1 clade. Our phylogeographical reconstruction suggests that the global CCHFV clades originated about one thousand years ago from a common ancestor probably located in Africa. The virus then spread to Asia in the XV century and entered Europe on at least two occasions: the first in the early 1800s, when a still circulating but less or non-pathogenic virus emerged in Greece and Turkey, and the second in the early 1900s, when a pathogenic CCHFV strain began to spread in eastern Europe. The most probable location for the origin of this European clade 1 was Russia, but Turkey played a central role in spreading the virus throughout Europe. Given the close proximity of the infected areas, our data suggest that the movement of wild and domestic ungulates from endemic areas was probably the main cause of the dissemination of the virus in eastern Europe.

Crimean-Congo Hemorrhagic Fever Virus Clades V and VI (Europe 1 and 2) in Ticks in Kosovo, 2012

“…The phylogeographic reconstruction revealed two distinct successive introductions of CCHFV in Kosovo: the most probable location of the MRCA of the Kosovo I lineage (clade VI) was in Greece in 1949, and for lineage IIa and IIb in Turkey in 1977. Our results support previous studies, which reported a complex web of viral introductions/transmissions from Turkey to Kosovo [39]. Furthermore, our data also support the thesis that Europe experienced at least two distinct introductions of two highly divergent CCHFV strains, the first from Africa in the 1800s (low or apathogenic virus present in vector and animal host populations from Greece and Turkey), and the second in the first decades of the 1900s, when a more pathogenic strain spread, a strain that to this day is responsible for human outbreaks in eastern European countries [39].…”

“…Our results support previous studies, which reported a complex web of viral introductions/transmissions from Turkey to Kosovo [39]. Furthermore, our data also support the thesis that Europe experienced at least two distinct introductions of two highly divergent CCHFV strains, the first from Africa in the 1800s (low or apathogenic virus present in vector and animal host populations from Greece and Turkey), and the second in the first decades of the 1900s, when a more pathogenic strain spread, a strain that to this day is responsible for human outbreaks in eastern European countries [39]. In order to calculate the tMRCAs for the root and internal nodes of the clades V and VI, we estimated a mean evolutionary rate of 5.71×10 −4 for all of the sampled CCHFV variant clades, 1.71×10 −4 for clade V and 2.45×10 −3 for clade VI.…”

Meeting report: First International Conference on Crimean-Congo hemorrhagic fever

“…A study on the Bayesian phylogeography of CCHFV in Europe showed that the virus originated from Africa, spread to Asia, and entered Europe at least twice: in the early 1800s, with a less or non-pathogenic strain, and in the early 1900s, with a pathogenic strain (Zehender et al, 2013). Country-wide studies have shown that the seroprevalence in humans is 3.7%, but the rate is >10% in some mountainous regions.…”

Phylogeography of Crimean Congo Hemorrhagic Fever Virus

“…The most ancient lineages (branching close to the tree root in phylogenetic reconstructions) are generally found in Africa, with the exception of strain Ap92, which was isolated in Greece. Most of the European isolates belong to GtV and are much more conserved than CCHFV circulating elsewhere [3, 7, 8]. Strains related to Ap92 (GtVI) are also occasionally found in Europe [7].…”

“…The sample coverage for Europe is better than for Asia and much better than for Africa. Discrete phylogeography may be more robust in this case, and indeed such study based on a partial S segment sequence was published recently [8]. On the other hand, discrete phylogeography relies on arbitrary assignment of location categories, which may be subjective.…”