Ongoing spillover of Hantaan and Gou hantaviruses from rodents is associated with hemorrhagic fever with renal syndrome (HFRS) in China

Abstract

Background: Longquan City, Zhejiang province, China, has been seriously affected by hemorrhagic fever with renal syndrome (HFRS) since the first cases were registered in 1974. To understand the epidemiology and emergence of HFRS in Longquan, which may be indicative of large parts of rural China, we studied long-term incidence patterns and performed a molecular epidemiological investigation of the causative hantaviruses in human and rodent populations.

Method/principal findings: During 1974-2011, 1866 cases of HFRS were recorded in Longquan, including 20 deaths. In 2011, the incidence of HFRS remained high, with 19.61 cases/100,000 population, despite the onset of vaccination in 1997. During 1974-1998, HFRS cases in Longquan occurred mainly in winter, while in the past decade the peak of HFRS has shifted to the spring. Notably, the concurrent prevalence of rodent-borne hantaviruses in the region was also high. Phylogenetic analyses of viral sequences recovered from rodents in Longquan revealed the presence of novel genetic variants of Gou virus (GOUV) in Rattus sp. rats and Hantaan virus (HTNV) in the stripe field mice, respectively. Strikingly, viral sequences sampled from infected humans were very closely related to those from rodents.

Conclusions/significance: HFRS represents an important public health problem in Longquan even after years of preventive measures. Our data suggest that continual spillover of the novel genetic variant of GOUV and the new genetic lineage of HTNV are responsible for the high prevalence of HFRS in humans. In addition, this is the first report of GOUV associated with human HFRS cases, and our data suggest that GOUV is now the major cause of HFRS in this region.

Figure 1. Incidence of HFRS in Longquan.

Annual numbers and incidence (cases/100,000 population) of HFRS reported during 1974–2011 in Longquan city, Zhejiang Province, China.

Figure 2. The monthly distribution (seasonality) of HFRS cases in Longquan.

The seasonal distribution of HFRS cases during the period 1974–2011 in Longquan city.

Figure 3. Phylogenetic relationships of hantaviruses identified in Longquan based on partial M segment sequences.

Sequences obtained in this study are shown in blue (HTNV) and red (GOUV), with those viruses collected from humans shown in italics. Numbers (>0.7/>70%) at nodes indicate posterior probabilities and bootstrap support values. Puumala virus (PUUV) was used as an outgroup. All GenBank accession numbers are described in Table S2. The scale bar represents the number of nucleotide substitutions per site.

Figure 4. Phylogenetic relationships of hantaviruses identified in Longquan based on partial S segment sequences.

Sequences obtained in this study are shown in blue (HTNV) and red (GOUV), with those viruses collected from humans shown in italics. Numbers (>0.7/>70%) at nodes indicate posterior probabilities and bootstrap values. Puumala virus (PUUV) was used as an outgroup. All GenBank accession numbers are given in Table S2. The scale bar represents the number of nucleotide substitutions per site.