Abstract
BackgroundRabies is an important but underestimated threat to public health, with most cases reported in Asia. Since 2000, a new epidemic wave of rabies has emerged in Yunnan Province, southwestern China, which borders three countries in Southeast Asia.MethodWe estimated gene-specific evolutionary rates for rabies virus using available data in GenBank, then used this information to calibrate the timescale of rabies virus (RABV) spread in Asia. We used 452 publicly available geo-referenced complete nucleoprotein (N) gene sequences, including 52 RABV sequences that were recently generated from samples collected in Yunnan between 2008 and 2012.ResultsThe RABV N gene evolutionary rate was estimated to be 1.88 × 10−4 (1.37–2.41 × 10−4, 95% Bayesian credible interval, BCI) substitutions per site per year. Phylogenetic reconstructions show that the currently circulating RABV lineages in Yunnan result from at least seven independent introductions (95% BCI: 6–9 introductions) and represent each of the three main Asian RABV lineages, SEA-1, -2 and -3. We find that Yunnan is a sink location for the domestic spread of RABV and connects RABV epidemics in North China, South China, and Southeast Asia. Cross-border spread from southeast Asia (SEA) into South China, and intermixing of the North and South China epidemics is also well supported. The influx of RABV into Yunnan from SEA was not well-supported, likely due to the poor sampling of SEA RABV diversity. We found evidence for a lineage displacement of the Yunnan SEA-2 and -3 lineages by Yunnan SEA-1 strains, and considered whether this could be attributed to fitness differences.ConclusionOverall, our study contributes to a better understanding of the spread of RABV that could facilitate future rabies virus control and prevention efforts.
Highlights
Rabies is an important but underestimated threat to public health, with most cases reported in Asia
Overall, our study contributes to a better understanding of the spread of RABV that could facilitate future rabies virus control and prevention efforts
Lineages of the three main Asian clades circulate in Yunnan Consistent with previous analyses, a phylogenetic analysis of the N gene from nonflying mammals identified six distinct clusters in Asia, which exhibited clear spatial structure: the Indian subcontinent, cosmopolitan, Arctic-related, Southeast Asia-1 (SEA-1), southeast Asia (SEA)-2, and SEA-3 lineages (Fig. 1) [7, 8, 11, 13]
Summary
Rabies is an important but underestimated threat to public health, with most cases reported in Asia. Rabies has one of the highest mortality rates of infectious diseases in humans, and kills almost 60,000 persons each year [1] It is caused by the rabies virus (RABV), a virus that belongs to the genus Lyssavirus within the family Rhabdoviridae, and which is distributed almost worldwide, in particular in developing countries [2]. Zhang et al Virology Journal (2017) 14:102 the African, cosmopolitan, Arctic-related, Asian, and Indian subcontinent clades [7, 8] Viruses of the latter three clades circulate in Asia: (i) Indian subcontinent clade viruses are found in southern India and Sri Lanka; (ii) Arctic-related clade viruses have been reported across a large region, from Russia and central Asia to eastern Asia [9, 10]; (iii) Asian clade viruses are mainly distributed in Southeast Asia [8]. An increasing incidence of rabies cases has been reported in Yunnan, occurring in only one county in 2000 but in 77 counties in 2012 [12]
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