Development and validation of a multiplexed-tandem qPCR tool for diagnostics of human soil-transmitted helminth infections

PLoS Negl Trop Dis. 2019 Jun 17;13(6):e0007363. doi: 10.1371/journal.pntd.0007363. eCollection 2019 Jun.

Abstract

Soil-transmitted helminths (STH) are a major cause of morbidity in tropical developing countries with a global infection prevalence of more than one billion people and disease burden of around 3.4 million disability adjusted life years. Infection prevalence directly correlates to inadequate sanitation, impoverished conditions and limited access to public health systems. Underestimation of infection prevalence using traditional microscopy-based diagnostic techniques is common, specifically in populations with access to benzimidazole mass treatment programs and a predominance of low intensity infections. In this study, we developed a multiplexed-tandem qPCR (MT-PCR) tool to identify and quantify STH eggs in stool samples. We have assessed this assay by measuring infection prevalence and intensity in field samples of two cohorts of participants from Timor-Leste and Cambodia, which were collected as part of earlier epidemiological studies. MT-PCR diagnostic parameters were compared to a previously published multiplexed qPCR for STH detection. The MT-PCR assay agreed strongly with qPCR data and showed a diagnostic specificity of 99.60-100.00% (sensitivity of 83.33-100.00%) compared to qPCR and kappa agreement exceeding 0.85 in all tests. In addition, the MT-PCR has the added advantage of distinguishing Ancylostoma spp. species, namely Ancylostoma duodenale and Ancylostoma ceylanicum. This semi-automated platform uses a standardized, manufactured reagent kit, shows excellent run-to-run consistency/repeatability and supports high-throughput detection and quantitation at a moderate cost.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cambodia
  • Child
  • Child, Preschool
  • Feces / parasitology*
  • Female
  • Helminthiasis / diagnosis*
  • Helminths / classification
  • Helminths / genetics
  • Helminths / isolation & purification*
  • Humans
  • Infant
  • Infant, Newborn
  • Intestinal Diseases, Parasitic / diagnosis*
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques / methods*
  • Multiplex Polymerase Chain Reaction / methods*
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction / methods*
  • Sensitivity and Specificity
  • Timor-Leste
  • Young Adult

Supplementary concepts

  • Intestinal helminthiasis

Grants and funding

This work, including the efforts of ARJ, was funded by a NHMRC Career Development Fellowship (APP1126395). KS, CVA, RJT and ARJ are supported by the Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme. KS is supported by a Melbourne Research Scholarship (Australian Government) and the Riady Scholarship (Victoria, Australia). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.