scholarly journals Genomic Epidemiology and Active Surveillance to Investigate Outbreaks of Hantaviruses

Author(s):  
Won-Keun Kim ◽  
Seungchan Cho ◽  
Seung-Ho Lee ◽  
Jin Sun No ◽  
Geum-Young Lee ◽  
...  

Emerging and re-emerging RNA viruses pose significant public health, economic, and societal burdens. Hantaviruses (genus Orthohantavirus, family Hantaviridae, order Bunyavirales) are enveloped, negative-sense, single-stranded, tripartite RNA viruses that are emerging zoonotic pathogens harbored by small mammals such as rodents, bats, moles, and shrews. Orthohantavirus infections cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome in humans (HCPS). Active targeted surveillance has elucidated high-resolution phylogeographic relationships between patient- and rodent-derived orthohantavirus genome sequences and identified the infection source by temporally and spatially tracking viral genomes. Active surveillance of patients with HFRS entails 1) recovering whole-genome sequences of Hantaan virus (HTNV) using amplicon (multiplex PCR-based) next-generation sequencing, 2) tracing the putative infection site of a patient by administering an epidemiological questionnaire, and 3) collecting HTNV-positive rodents using targeted rodent trapping. Moreover, viral genome tracking has been recently performed to rapidly and precisely characterize an outbreak from the emerging virus. Here, we reviewed genomic epidemiological and active surveillance data for determining the emergence of zoonotic RNA viruses based on viral genomic sequences obtained from patients and natural reservoirs. This review highlights the recent studies on tracking viral genomes for identifying and characterizing emerging viral outbreaks worldwide. We believe that active surveillance is an effective method for identifying rodent-borne orthohantavirus infection sites, and this report provides insights into disease mitigation and preparedness for managing emerging viral outbreaks.

2021 ◽  
Author(s):  
Phillip Davis ◽  
Joseph A Russell

Leveraging prior viral genome sequencing data to make predictions on whether an unknown, emergent virus harbors a phenotype-of-concern has been a long-sought goal of genomic epidemiology. A predictive phenotype model built from nucleotide-level information alone has previously been considered un-tenable with respect to RNA viruses due to the ultra-high intra-sequence variance of their genomes, even within closely related clades. Building from our prior work developing a degenerate k-mer method to accommodate this high intra-sequence variation of RNA virus genomes for modeling frameworks, and leveraging a taxonomic group-shuffle-split paradigm on complete coronavirus assemblies from prior to October 2018, we trained multiple regularized logistic regression classifiers at the nucleotide k-mer level capable of accurately predicting withheld SARS-CoV-2 genome sequences as human pathogens and accurately predicting withheld Swine Acute Diarrhea Syndrome coronavirus (SADS-CoV) genome sequences as non-human pathogens. LASSO feature selection identified several degenerate nucleotide predictor motifs with high model coefficients for the human pathogen class that were present across widely disparate classes of coronaviruses. However, these motifs differed in which genes they were present in, what specific codons were used to encode them, and what the translated amino acid motif was. This emphasizes the importance of a phenetic view of emerging pathogenic RNA viruses, as opposed to the canonical phylogenetic interpretations most-commonly used to track and manage viral zoonoses. Applying our model to more recent Orthocoronavirinae genomes deposited since October 2018 yields a novel contextual view of pathogen-potential across bat-related, canine-related, porcine-related, and rodent-related coronaviruses and critical adaptations which may have contributed to the emergence of the pandemic SARS-CoV-2 virus. Finally, we discuss the utility of these predictive models (and their associated predictor motifs) to novel biosurveillance protocols that substantially increase the pound-for-pound information content of field-collected sequencing data and make a strong argument for the necessity of routine collection and sequencing of zoonotic viruses.


2021 ◽  
Vol 15 (9) ◽  
pp. e0009707
Author(s):  
Seungchan Cho ◽  
Won-Keun Kim ◽  
Jin Sun No ◽  
Seung-Ho Lee ◽  
Jaehun Jung ◽  
...  

Background Hantavirus infection occurs through the inhalation of aerosolized excreta, including urine, feces, and saliva of infected rodents. The presence of Hantaan virus (HTNV) RNA or infectious particles in urine specimens of patient with hemorrhagic fever with renal syndrome (HFRS) remains to be investigated. Methodology/Principal findings We collected four urine and serum specimens of Republic of Korea Army (ROKA) patients with HFRS. We performed multiplex PCR-based next-generation sequencing (NGS) to obtain the genome sequences of clinical HTNV in urine specimens containing ultra-low amounts of viral genomes. The epidemiological and phylogenetic analyses of HTNV demonstrated geographically homogenous clustering with those in Apodemus agrarius captured in highly endemic areas, indicating that phylogeographic tracing of HTNV genomes reveals the potential infection sites of patients with HFRS. Genetic exchange analyses showed a genetic configuration compatible with HTNV L segment exchange in nature. Conclusion/Significance Our results suggest that whole or partial genome sequences of HTNV from the urine enabled to track the putative infection sites of patients with HFRS by phylogeographically linking to the zoonotic HTNV from the reservoir host captured at endemic regions. This report raises awareness among physicians for the presence of HTNV in the urine of patients with HFRS.


2021 ◽  
Vol 9 (6) ◽  
pp. 1306
Author(s):  
Jennifer Mayor ◽  
Olivier Engler ◽  
Sylvia Rothenberger

Ecological changes, population movements and increasing urbanization promote the expansion of hantaviruses, placing humans at high risk of virus transmission and consequent diseases. The currently limited therapeutic options make the development of antiviral strategies an urgent need. Ribavirin is the only antiviral used currently to treat hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV), even though severe side effects are associated with this drug. We therefore investigated the antiviral activity of favipiravir, a new antiviral agent against RNA viruses. Both ribavirin and favipiravir demonstrated similar potent antiviral activity on HTNV infection. When combined, the efficacy of ribavirin is enhanced through the addition of low dose favipiravir, highlighting the possibility to provide better treatment than is currently available.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Myat Htut Nyunt ◽  
Hnin Ohnmar Soe ◽  
Kay Thi Aye ◽  
Wah Wah Aung ◽  
Yi Yi Kyaw ◽  
...  

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major health concern globally. Genomic epidemiology is an important tool to assess the pandemic of coronavirus disease 2019 (COVID-19). Several mutations have been reported by genome analysis of the SARS-CoV-2. In the present study, we investigated the mutational and phylogenetic analysis of 30 whole-genome sequences for the virus's genomic characteristics in the specimens collected in the early phase of the pandemic (March–June, 2020) and the sudden surge of local transmission (August–September, 2020). The four samples in the early phase of infection were B.6 lineage and located within a clade of the samples collected at the same time in Singapore and Malaysia, while five returnees by rescue flights showed the lineage B. 1.36.1 (three from India), B.1.1 (one from India) and B.1.80 (one from China). However, there was no evidence of local spread from these returnees. Further, all 19 whole-genome sequences collected in the sudden surge of local transmission showed lineage B.1.36. The surge of the second wave on SARS-CoV-2 infection was linked to the single-introduction of a variant (B.1.36) that may result from the strict restriction of international travel and containment efforts. These genomic data provides the useful information to disease control and prevention strategy.


2010 ◽  
Vol 29 (12) ◽  
pp. 1507-1511 ◽  
Author(s):  
Qunying Han ◽  
Lei Zhang ◽  
Zhengwen Liu ◽  
Wen Kang ◽  
Sai Lou ◽  
...  

2021 ◽  
Vol 9 (2) ◽  
pp. 454
Author(s):  
Esther Viedma ◽  
Elias Dahdouh ◽  
José González-Alba ◽  
Sara González-Bodi ◽  
Laura Martínez-García ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Madrid, Spain, on 25 February 2020. It increased in frequency very fast and by the end of May more than 70,000 cases had been confirmed by reverse transcription-polymerase chain reaction (RT-PCR). To study the lineages and the diversity of the viral population during this first epidemic wave in Madrid we sequenced 224 SARS-CoV-2 viral genomes collected from three hospitals from February to May 2020. All the known major lineages were found in this set of samples, though B.1 and B.1.5 were the most frequent ones, accounting for more than 60% of the sequences. In parallel with the B lineages and sublineages, the D614G mutation in the Spike protein sequence was detected soon after the detection of the first coronavirus disease 19 (COVID-19) case in Madrid and in two weeks became dominant, being found in 80% of the samples and remaining at this level during all the study periods. The lineage composition of the viral population found in Madrid was more similar to the European population than to the publicly available Spanish data, underlining the role of Madrid as a national and international transport hub. In agreement with this, phylodynamic analysis suggested multiple independent entries before the national lockdown and air transportation restrictions.


Vaccine ◽  
2012 ◽  
Vol 30 (11) ◽  
pp. 1951-1958 ◽  
Author(s):  
Ellen F. Boudreau ◽  
Matthew Josleyn ◽  
Diane Ullman ◽  
Diana Fisher ◽  
Lonnie Dalrymple ◽  
...  

2019 ◽  
Author(s):  
Stephen C. Watts ◽  
Kathryn E. Holt

AbstractHaemophilus influenzaeexclusively colonises the human nasopharynx and can cause a variety of respiratory infections as well as invasive diseases including meningitis and sepsis. A key virulence determinant ofH. influenzaeis the polysaccharide capsule of which six serotypes are known, each encoded by a distinct variation of the capsule biosynthesis locus (cap-a tocap-f).H. influenzaetype b (Hib) was historically responsible for the majority of invasiveH. influenzaedisease and prevalence has been markedly reduced in countries that have implemented vaccination programs targeting this serotype. In the postvaccine era, non-typeableH. influenzaeemerged as the most dominant group causing disease but in recent years a resurgence of encapsulatedH. influenzaestrains has also been observed, most notably serotype a. Given the increasing incidence of encapsulated strains and the high frequency of Hib in countries without vaccination programs, there is growing interest in genomic epidemiology ofH. influenzae. Here we present hicap, a software tool for rapid in silico serotype prediction fromH. influenzaegenome sequences. hicap is written using Python3 and is freely available at github.com/scwatts/hicap under a GPLv3 license. To demonstrate the utility of hicap, we used it to investigate the cap locus diversity and distribution in 691 high-qualityH. influenzaegenomes from GenBank. These analyses identifiedcaploci in 95 genomes and confirmed the general association of each serotype with a unique clonal lineage and also identified occasional recombination between lineages giving rise to hybridcaploci (2% of encapsulated strains).


2021 ◽  
Vol 15 (5) ◽  
pp. e0009400
Author(s):  
Kyungmin Park ◽  
Won-Keun Kim ◽  
Seung-Ho Lee ◽  
Jongwoo Kim ◽  
Jingyeong Lee ◽  
...  

Background Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics or vaccines for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK). Methodology/Principal findings We collected small mammals on Jeju Island during 2018–2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mice harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analyses identified a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence. Conclusions/Significance Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.


Sign in / Sign up

Export Citation Format

Share Document