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Clin Infect Dis. 2019 Mar 20. pii: ciz234. doi: 10.1093/cid/ciz234. [Epub ahead of print]

Active Targeted Surveillance to Identify Sites of Emergence of Hantavirus.

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Department of Microbiology, College of Medicine, Korea University, Seoul, Republic of Korea.
5th R&D Institute, Agency for Defense Development, Daejeon, Republic of Korea.
The Armed Forces Medical Center, Seongnam, Republic of Korea.
65th Medical Brigade/MEDDAC-Korea, Unit, APO AP, USA.
The Center for Genome Science, U.S. Army Medical Research Institute of Infectious Disease at Fort Detrick, MD, USA.
Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM, USA.



Endemic outbreaks of hantaviruses pose a critical public health threat worldwide. Hantaan orthohantavirus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS) in humans. Using comparative genomic analyses of partial and nearly complete sequences of HTNV from humans and rodents, we are able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequence; finer granularity of rodent sampling reflects more precisely the circulation of strains.


A total of five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during the hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex PCR-based NGS (Next-Generation Sequencing) to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated by the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents.


The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens with the HTNV circulating in rodents at suspected sites of patient infections.


This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing to the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will enable identification of infectious sources, disease risk assessment and preparedness against vector-borne viruses.


Active targeted surveillance; Epidemiology; Hantavirus; Hemorrhagic fever with renal syndrome; Next-generation sequencing


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