Diagnostic reliability of nested PCR depends on the primer design and threshold abundance of Helicobacter pylori in biopsy, stool, and saliva samples

Helicobacter. 2020 Apr;25(2):e12680. doi: 10.1111/hel.12680. Epub 2020 Feb 14.

Abstract

Background: The aim of this work was to find a reliable nested PCR for the detection of Helicobacter pylori in biopsy, stool, and saliva specimens.

Materials and methods: Novel nested PCR was elaborated and validated on 81 clinical biopsy, stool, and saliva samples from the same individual and compared to available H pylori assays: histology, rapid urease test (RUT), stool antigen test (SAT), 13 C-urea breath test (UBT).

Results: The efficiency and selectivity of 17 published nested polymerase chain reactions (PCR) available for Helicobacter pylori detection were re-evaluated. Most of them had serious limitations and mistakes in primer design. Hence, we elaborated a nested PCR for the unambiguous identification of H pylori in biopsy, stool, and saliva, using primers targeted to variable regions of the 16S ribosomal RNA (rRNA) gene. Moreover, we determined the detection limit by adding a known number of cells. This number was as low as 0.5 cells in a PCR vial, but due to the DNA isolation procedures, it required 1-5 × 103 cells/g or ml of specimen. The sensitivity for nested PCR from stomach biopsies was on the same scale as 13 C-UBT (93.8%), but it was much lower in amplifications from stool (31.3%). Sequencing of all obtained PCR products exclusively confirmed H pylori-specific DNA sequences.

Conclusions: Elaborated nested PCR assay can serve as an auxiliary method for controversial samples (patients with bleeding or taking proton-pump inhibitor) in laboratories with basic equipment. The sensitivity and specificity for the amplification from gastric biopsies was almost like 13 C-UBT. Despite the good sensitivity, the threshold occurrence and the ability to survive in the oral cavity aside from and independent of the stomach is the reason why H pylori DNA cannot be reliably detected in saliva, stool, and some biopsy samples.

Keywords: H pylori; detection limit; diagnostic reliability; nested PCR.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bacterial Load
  • Biopsy
  • Feces / microbiology
  • Female
  • Gastroscopy
  • Helicobacter Infections / diagnosis*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / isolation & purification*
  • Humans
  • Limit of Detection
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • RNA, Ribosomal, 16S
  • Saliva / microbiology
  • Sensitivity and Specificity
  • Young Adult

Substances

  • RNA, Ribosomal, 16S