Molecular detection and typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing: diagnostic and epidemiologic implications

Am J Trop Med Hyg. 2012 Feb;86(2):335-40. doi: 10.4269/ajtmh.2012.11-0346.

Abstract

Diagnosis of dengue virus (DENV) infection in fatal cases is challenging because of the frequent unavailability of blood or fresh tissues. For formalin-fixed, paraffin-embedded (FFPE) tissues immunohistochemistry (IHC) can be used; however, it may not be as sensitive and serotyping is not possible. The application of reverse transcription-polymerase chain reaction (RT-PCR) for the detection of DENV in FFPE tissues has been very limited. We evaluated FFPE autopsy tissues of 122 patients with suspected DENV infection by flavivirus and DENV RT-PCR, sequencing, and DENV IHC. The DENV was detected in 61 (50%) cases by RT-PCR or IHC. The RT-PCR and sequencing detected DENV in 60 (49%) cases (DENV-1 in 16, DENV-2 in 27, DENV-3 in 8, and DENV-4 in 6 cases). No serotype could be identified in three cases. The IHC detected DENV antigens in 50 (40%) cases. The RT-PCR using FFPE tissue improves detection of DENV in fatal cases and provides sequence information useful for typing and epidemiologic studies.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Dengue / diagnosis*
  • Dengue / epidemiology*
  • Dengue / virology
  • Dengue Virus / classification*
  • Dengue Virus / isolation & purification*
  • Dengue Virus / pathogenicity
  • Female
  • Fixatives / chemistry
  • Formaldehyde / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Infant
  • Male
  • Middle Aged
  • Paraffin Embedding / methods
  • Prevalence
  • RNA, Viral / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods*
  • Sequence Analysis, RNA
  • Serotyping
  • Specimen Handling
  • Tissue Fixation
  • Young Adult

Substances

  • Fixatives
  • RNA, Viral
  • Formaldehyde