Accurate Genetic Detection of Hepatitis C Virus Transmissions in Outbreak Settings.

Accurate Genetic Detection of Hepatitis C Virus Transmissions in Outbreak Settings.
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DOI:
10.1093/infdis/jiv542
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发表时间:
2016-03-15
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Khudyakov Y
Khudyakov Y
中科院分区:
其他
文献类型:
--
作者:
Campo DS;Xia GL;Dimitrova Z;Lin Y;Forbi JC;Ganova-Raeva L;Punkova L;Ramachandran S;Thai H;Skums P;Sims S;Rytsareva I;Vaughan G;Roh HJ;Purdy MA;Sue A;Khudyakov Y

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丙型肝炎是美国和世界范围内的一个主要公共卫生问题。丙型肝炎病毒(HCV)感染的爆发与不安全的注射做法、药物转移和其他血液暴露有关,难以检测和调查。在这里,我们开发并验证了一种简单的方法,用于在暴发环境中检测HCV传播。我们获得的序列从HCV高变区1(HVR1)使用终点限制性稀释(EPLD)从127例涉及32流行病学定义的HCV爆发和193个人无关的HCV毒株。我们比较了几种类型的遗传距离,并使用最小汉明距离计算了一个阈值,该阈值可以100%准确地识别所有测试疫情中的传播簇。该方法也验证了使用下一代测序获得的239个个体的序列,显示出与EPLD相同的准确性。平均而言,宿主内人群的核苷酸多样性是6.2倍以上的源比在任何事件的情况下,允许正确检测的传播方向在8个爆发的源病例是已知的。这里开发的一种简单而准确的基于距离的检测HCV传播的方法简化了暴发的分子调查,从而提高了快速有效控制丙型肝炎的公共卫生能力。
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, being 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) 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 from 239 individuals obtained using next-generation sequencing, showing the same accuracy as EPLD. In average, nucleotide diversity of the intra-host population was 6.2-times greater in the source 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 for detecting HCV transmissions developed here streamlines molecular investigation of outbreaks, thus improving the public health capacity for rapid and effective control of hepatitis C.
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