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

Wen Wang1 Miao-Ruo Wang Xian-Dan Lin Wen-Ping Guo Ming-Hui Li Sheng-Hua Mei Zhao-Mei Li Mei-Li Cong Rui-Lan Jiang Run-Hong Zhou Edward C Holmes Alexander Plyusnin Yong-Zhen Zhang
Affiliations 1 institutions
  1. State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Abstract

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. 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. 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.

Supporting text Virus Host Location
Animals 1948 China 229 Cluster Analysis 31 Hemorrhagic Fever with Renal Syndrome 5 Humans 1440 Incidence 17 Mice 253 Molecular Epidemiology 21 Molecular Sequence Data 160 Orthohantavirus 18 Phylogeny 805 Prevalence 62 Rats 73 RNA, Viral 193 Rodent Diseases 28 Seasons 47 Sequence Analysis, DNA 113 Zoonoses 397

Evidence records

7 total
Zoonotic Surveillance
2 records · 1 evidence types
Evidence type
2 records
OVE1609
Key finding

Gou virus (GOUV) genetic variants were detected in Rattus sp. rats captured in Longquan, Zhejiang province, China.

Virus
Host
Location
Supporting text

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.

Method
phylogenetic analysis | sequence recovery
Sample type
rodents
Geographic raw
Longquan | Zhejiang province | China
Country inferred
CHN
OVE1610
Key finding

Hantaan virus (HTNV) was detected in stripe field mice in Longquan, Zhejiang province, China.

Virus
Host
Location
Supporting text

Phylogenetic analyses of viral sequences recovered from rodents in Longquan revealed the presence of Hantaan virus (HTNV) in the stripe field mice.

Method
phylogenetic analysis | sequence recovery
Sample type
rodents
Geographic raw
Longquan | Zhejiang province | China
Country inferred
CHN
Transmission Evidence
3 records · 2 evidence types
Evidence type
2 records
OVE1611
Key finding

Continual spillover of Gou virus (GOUV) from rodents to humans causes human hemorrhagic fever with renal syndrome (HFRS) cases in Longquan, China.

Virus
Host
Location
Supporting text

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.

Method
phylogenetic analysis | molecular detection
Study design
molecular epidemiological investigation linking human and rodent viral sequences
Transmission direction
animal-to-human
Geographic raw
Longquan | Zhejiang province | China
Country inferred
CHN
OVE1612
Key finding

Ongoing spillover of Hantaan virus (HTNV) from rodents to humans contributes to human hemorrhagic fever with renal syndrome (HFRS) in Longquan, China.

Virus
Host
Location
Supporting text

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.

Method
phylogenetic analysis | molecular detection
Study design
molecular epidemiological investigation linking human and rodent viral sequences
Transmission direction
animal-to-human
Geographic raw
Longquan | Zhejiang province | China
Country inferred
CHN
Evidence type
1 records
OVE1613
Key finding

An outbreak investigation in Longquan, China recorded 1866 human HFRS cases and 20 deaths from 1974–2011, with phylogenetic evidence linking Hantaan virus (HTNV) and Gou virus (GOUV) from rodents to infected humans.

Virus
Host
Location
Supporting text

During 1974-2011, 1866 cases of HFRS were recorded in Longquan, including 20 deaths. 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.

Method
epidemiological surveillance data | case reporting | molecular epidemiological investigation
Transmission direction
animal-to-human
Geographic raw
Longquan, Zhejiang province, China
Outbreak setting
community in Longquan, Zhejiang province
Outbreak time
1974–2011
Outbreak scale
1866 cases and 20 deaths
Genomic Evolution
2 records · 1 evidence types
Evidence type
2 records
OVE1614
Key finding

Phylogenetic analysis revealed novel genetic variants of Gou virus (GOUV) in Rattus sp. rats that were closely related to GOUV sequences from infected humans in Longquan, China.

Virus
Host
Location
Not specified
Supporting text

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. Strikingly, viral sequences sampled from infected humans were very closely related to those from rodents.

Analysis methods
phylogenetic analysis
OVE1615
Key finding

Phylogenetic analysis identified a new genetic lineage of Hantaan virus (HTNV) in stripe field mice that was closely related to HTNV sequences from human infections in Longquan, China.

Virus
Host
Location
Not specified
Supporting text

Phylogenetic analyses of viral sequences recovered from rodents in Longquan revealed the presence of a new genetic lineage of Hantaan virus (HTNV) in the stripe field mice. Strikingly, viral sequences sampled from infected humans were very closely related to those from rodents.

Analysis methods
phylogenetic analysis