Active Targeted Surveillance to Identify Sites of Emergence of Hantavirus

Abstract

Background 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 were able to localize, with limitations, the putative infection locations for HFRS patients. Partial sequences might not reflect precise phylogenetic positions over the whole-genome sequences; finer granularity of rodent sampling reflects more precisely the circulation of strains. Methods Five HFRS specimens were collected. Epidemiological surveys were conducted with the patients during hospitalization. We conducted active surveillance at suspected HFRS outbreak areas. We performed multiplex polymerase chain reaction–based next-generation sequencing to obtain the genomic sequence of HTNV from patients and rodents. The phylogeny of human- and rodent-derived HTNV was generated using the maximum likelihood method. For phylogeographic analyses, the tracing of HTNV genomes from HFRS patients was defined on the bases of epidemiological interviews, phylogenetic patterns of the viruses, and geographic locations of HTNV-positive rodents. Results The phylogeographic analyses demonstrated genetic clusters of HTNV strains from clinical specimens, with HTNV circulating in rodents at suspected sites of patient infections. Conclusions This study demonstrates a major shift in molecular epidemiological surveillance of HTNV. Active targeted surveillance was performed at sites of suspected infections, allowing the high-resolution phylogeographic analysis to reveal the site of emergence of HTNV. We posit that this novel approach will make it possible to identify infectious sources, perform disease risk assessment, and implement preparedness against vector-borne viruses.

Genetic diversity and evolution of Hantaan virus in China and its neighbors

“…But the transmission sources to Heilongjiang and Shaanxi are still unclear. The samples collected from South Korea have been studied before [ 55 – 57 ], so we do not discuss them too much here. But the migration of HTNV from South Korea to Jiangsu indicates the possibility of HTNV import from other countries.…”

The Needs for Developing Experiments on Reservoirs in Hantavirus Research: Accomplishments, Challenges and Promises for the Future

“…These technologies are still scarcely used in the case of hantaviruses. Moreover, the rare studies that used HTS to analyze hantavirus diversity were often performed on patient, cell culture-based or wild reservoir samples [106,107,108,109]. To our knowledge, HTS has never been combined with experiments to assess hantavirus diversity and its evolution throughout the course of reservoir infection.…”

Amplicon-Based, Next-Generation Sequencing Approaches to Characterize Single Nucleotide Polymorphisms of Orthohantavirus Species

“…Four distinct approaches have been reported for WGS of Old World hantavirus species Hantaan virus (HTNV) and Seoul virus from patient and rodent specimens (Kim et al, 2016 , 2018 , 2019 ; Song et al, 2017 ). These include sequence-independent, single primer amplification (SISPA), rapid amplification of cDNA ends (RACE), target-capture using virus-specific probes, and amplicon-based approaches.…”