Hepatitis C Virus (HCV) RNA screening and sequencing using dry plasma spots

J Clin Virol. 2017 Dec:97:18-21. doi: 10.1016/j.jcv.2017.10.012. Epub 2017 Oct 23.

Abstract

Background: HCV RNA screening of large sample repositories provides data on HCV epidemic patterns that may help guide control policies. In resource-limited settings, shipment of frozen samples to molecular laboratory facilities and testing of individual samples may be prohibitively expensive.

Objective: Our aim was to detect and sequence HCV RNA in a large HIV-positive cohort from Kumasi, Ghana, using pooled and individual dried plasma spots (DPS) produced from samples stored at -80°C.

Study design: In the validation phase, replicate DPS were prepared with six dilutions (500-10,000 IU/ml) of the 4th International Standard for HCV and tested in three independent experiments. In the testing phase, DPS prepared with plasma samples from 875 HIV-positive subjects were pooled for screening, followed by testing of individual DPS of positive pools. Input from individual DPS was two 6mm punches; pools comprised two punches from each of five DPS. Genotypes were determined by Sanger sequencing of HCV core and NS5B.

Results: With the dilution series, sensitivity of HCV RNA detection was ≥2500 IU/ml. Replicate DPS gave intra-assay and inter-assay coefficients of variation ≤1.4%. With the stored samples, HCV RNA was detected in 5/175 DPS pools and in one DPS from each positive pool, yielding a HCV RNA prevalence of 5/875 (0.57%; 95% confidence interval 0.07-1.07%). The five samples were sequenced as HCV genotypes 2l and 2r.

Discussion: DPS allowed reproducible HCV RNA detection, and pooling effectively contained the cost and labour of screening a previously untested, low-prevalence cohort. DPS were also suitable for HCV sequencing.

Keywords: Dried plasma spots; Epidemiology; HCV RNA; Sequencing; Sub-Saharan Africa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genotype
  • Ghana / epidemiology
  • HIV Infections / complications
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • Hepacivirus / genetics*
  • Hepatitis C / diagnosis*
  • Hepatitis C / epidemiology
  • Hepatitis C / virology
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Mass Screening / methods
  • Plasma / virology*
  • RNA, Viral / genetics
  • RNA, Viral / isolation & purification*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Specimen Handling
  • Viral Load / instrumentation
  • Viral Load / methods*

Substances

  • RNA, Viral