Accurate Genetic Detection of Hepatitis C Virus Transmissions in Outbreak Settings

Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections are associated with unsafe injection practices, drug diversion, and other exposures to blood and are difficult to detect and investigate. Here, we developed and validated...

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Veröffentlicht in:The Journal of infectious diseases 2016-03, Vol.213 (6), p.957-965
Hauptverfasser: Campo, David S., Xia, Guo-Liang, Dimitrova, Zoya, Lin, Yulin, Forbi, Joseph C., Ganova-Raeva, Lilia, Punkova, Lili, Ramachandran, Sumathi, Thai, Hong, Skums, Pavel, Sims, Seth, Rytsareva, Inna, Vaughan, Gilberto, Roh, Ha-Jung, Purdy, Michael A., Sue, Amanda, Khudyakov, Yury
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container_end_page 965
container_issue 6
container_start_page 957
container_title The Journal of infectious diseases
container_volume 213
creator Campo, David S.
Xia, Guo-Liang
Dimitrova, Zoya
Lin, Yulin
Forbi, Joseph C.
Ganova-Raeva, Lilia
Punkova, Lili
Ramachandran, Sumathi
Thai, Hong
Skums, Pavel
Sims, Seth
Rytsareva, Inna
Vaughan, Gilberto
Roh, Ha-Jung
Purdy, Michael A.
Sue, Amanda
Khudyakov, Yury
description Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections are associated with unsafe injection practices, drug diversion, and other exposures to blood and are difficult to detect and investigate. Here, we developed and validated a simple approach for molecular detection of HCV transmissions in outbreak settings. We obtained sequences from the HCV hypervariable region 1 (HVR1), using end-point limiting-dilution (EPLD) technique, from 127 cases involved in 32 epidemiologically defined HCV outbreaks and 193 individuals with unrelated HCV strains. We compared several types of genetic distances and calculated a threshold, using minimal Hamming distances, that identifies transmission clusters in all tested outbreaks with 100% accuracy. The approach was also validated on sequences obtained using next-generation sequencing from HCV strains recovered from 239 individuals, and findings showed the same accuracy as that for EPLD. On average, the nucleotide diversity of the intrahost population was 6.2 times greater in the source case than in any incident case, allowing the correct detection of transmission direction in 8 outbreaks for which source cases were known. A simple and accurate distance-based approach developed here for detecting HCV transmissions streamlines molecular investigation of outbreaks, thus improving the public health capacity for rapid and effective control of hepatitis C.
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Outbreaks of hepatitis C virus (HCV) infections are associated with unsafe injection practices, drug diversion, and other exposures to blood and are difficult to detect and investigate. Here, we developed and validated a simple approach for molecular detection of HCV transmissions in outbreak settings. We obtained sequences from the HCV hypervariable region 1 (HVR1), using end-point limiting-dilution (EPLD) technique, from 127 cases involved in 32 epidemiologically defined HCV outbreaks and 193 individuals with unrelated HCV strains. We compared several types of genetic distances and calculated a threshold, using minimal Hamming distances, that identifies transmission clusters in all tested outbreaks with 100% accuracy. The approach was also validated on sequences obtained using next-generation sequencing from HCV strains recovered from 239 individuals, and findings showed the same accuracy as that for EPLD. On average, the nucleotide diversity of the intrahost population was 6.2 times greater in the source case than in any incident case, allowing the correct detection of transmission direction in 8 outbreaks for which source cases were known. 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subjects Cluster Analysis
Disease Outbreaks
Genetic Linkage
Genetic Variation
Genotype
Hepacivirus - genetics
Hepacivirus - isolation & purification
Hepatitis C - epidemiology
Hepatitis C - transmission
Hepatitis C - virology
Hepatitis C virus
Humans
Reproducibility of Results
VIRUSES
title Accurate Genetic Detection of Hepatitis C Virus Transmissions in Outbreak Settings
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