Antuori Adrián, Montoya Vincent, Piñeyro David, Sumoy Lauro, Joy Jeffrey, Krajden Mel, González-Gómez Sara, Folch Cinta, Casabona Jordi, Matas Lurdes, Colom Joan, Saludes Verónica, Martró Elisa
Microbiology DepartmentLaboratori Clínic Metropolitana NordHospital Universitari Germans Trias i PujolInstitut d'Investigació en Ciències de la Salut Germans Trias i PujolBadalonaSpain.
Genetics and Microbiology DepartmentUniversitat Autònoma de BarcelonaBellaterraSpain.
Hepatology. 2021 Aug;74(2):591-606. doi: 10.1002/hep.31757. Epub 2021 Aug 25.
Accurate identification of recent HCV infections is critical for tracing the extent and mechanisms of ongoing transmission. We aimed to validate dried blood spot (DBS) samples for the assessment of Hepatitis C virus (HCV) genetic diversity and to determine epidemiological parameters including incidence, determinants of acute infection, and phylogenetic clustering in people who inject drugs (PWID).
HCV nonstructural protein 5B next-generation sequencing was performed from plasma and/or DBS in 220 viremic PWID from the HepCdetect II study. No significant differences were found in consensus sequences or Shannon entropy (SE) intrahost diversity estimate between paired plasma/DBS specimens. SE values were used to identify acute infections with 93.3% sensitivity (95% CI, 0.81-1.06) and 95.0% specificity (95% CI, 0.88-1.02) in a set of well-defined controls. An acute HCV infection (either primary infection or reinfection) was detected in 13.5% of viremic participants and was associated with age ≤30 years (OR, 8.09), injecting less than daily (OR, 4.35), ≤5 years of injected drug use (OR, 3.43), sharing cocaine snorting straws (OR, 2.89), and being unaware of their HCV status (OR, 3.62). Annualized HCV incidence was estimated between 31 and 59/100 person-years. On phylogenetic analysis, 46.8% of viremic cases were part of a transmission pair or cluster; age ≤30 years (OR, 6.16), acute infection (OR, 5.73), and infection with subtype 1a (OR, 4.78) were independently associated with this condition.
The results obtained from plasma and DBS characterize PWID with acute infection and those involved in ongoing HCV transmission and allow estimating incidence from cross-sectional data. This information is critical for the design and assessment of targeted harm reduction programs and test-and-treat interventions and to facilitate monitoring of HCV elimination in this key population.
准确识别近期丙型肝炎病毒（HCV）感染对于追踪正在进行的传播范围和机制至关重要。我们旨在验证干血斑（DBS）样本用于评估丙型肝炎病毒（HCV）基因多样性，并确定包括发病率、急性感染的决定因素以及注射吸毒者（PWID）中的系统发育聚类等流行病学参数。
对来自HepCdetect II研究的220例病毒血症PWID的血浆和/或DBS进行HCV非结构蛋白5B下一代测序。配对的血浆/DBS标本之间在共有序列或宿主内多样性估计的香农熵（SE）方面未发现显著差异。在一组明确界定的对照中，SE值用于识别急性感染，敏感性为93.3%（95%CI，0.81 - 1.06），特异性为95.0%（95%CI，0.88 - 1.02）。在13.5%的病毒血症参与者中检测到急性HCV感染（原发性感染或再感染），并且与年龄≤30岁（OR，8.09）、非每日注射（OR，4.35）、注射吸毒≤5年（OR，3.43）、共用可卡因吸管（OR，2.89）以及不知道自己的HCV感染状态（OR，3.62）相关。年化HCV发病率估计在31至59/100人年之间。在系统发育分析中，46.8%的病毒血症病例属于传播对或聚类；年龄≤30岁（OR，6.16）、急性感染（OR，5.73）和1a亚型感染（OR，4.78）与这种情况独立相关。
从血浆和DBS获得的结果表征了急性感染的PWID以及参与正在进行的HCV传播的人群，并允许从横断面数据估计发病率。这些信息对于设计和评估有针对性的减少伤害计划以及检测和治疗干预措施以及促进对这一关键人群中HCV消除的监测至关重要。
