Still Searching for a Suitable Molecular Test to Detect Hidden Plasmodium Infection: A Proposal for Blood Donor Screening in Brazil

PLoS One. 2016 Mar 9;11(3):e0150391. doi: 10.1371/journal.pone.0150391. eCollection 2016.

Abstract

Background: Efforts have been made to establish sensitive diagnostic tools for malaria screening in blood banks in order to detect malaria asymptomatic carriers. Microscopy, the malaria reference test in Brazil, is time consuming and its sensitivity depends on microscopist experience. Although molecular tools are available, some aspects need to be considered for large-scale screening: accuracy and robustness for detecting low parasitemia, affordability for application to large number of samples and flexibility to perform on individual or pooled samples.

Methodology: In this retrospective study, we evaluated four molecular assays for detection of malaria parasites in a set of 56 samples previously evaluated by expert microscopy. In addition, we evaluated the effect of pooling samples on the sensitivity and specificity of the molecular assays. A well-characterized cultured sample with 1 parasite/μL was included in all the tests evaluated. DNA was extracted with QIAamp DNA Blood Mini Kit and eluted in 50 μL to concentrate the DNA. Pools were assembled with 10 samples each. Molecular protocols targeting 18S rRNA, included one qPCR genus specific (Lima-genus), one duplex qPCR genus/Pf (PET-genus, PET-Pf) and one duplex qPCR specie-specific (Rougemont: Roug-Pf/Pv and Roug-Pm/Po). Additionally a nested PCR protocol specie-specific was used (Snou-Pf, Snou-Pv, Snou-Pm and Snou-Po).

Results: The limit of detection was 3.5 p/μL and 0.35p/μl for the PET-genus and Lima-genus assays, respectively. Considering the positive (n = 13) and negative (n = 39) unpooled individual samples according to microscopy, the sensitivity of the two genus qPCR assays was 76.9% (Lima-genus) and 72.7% (PET-genus). The Lima-genus and PET-genus showed both sensitivity of 86.7% in the pooled samples. The genus protocols yielded similar results (Kappa value of 1.000) in both individual and pooled samples.

Conclusions: Efforts should be made to improve performance of molecular tests to enable the detection of low-density parasitemia if these tests are to be utilized for blood transfusion screening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brazil
  • DNA, Protozoan / genetics
  • Diagnostic Tests, Routine / trends*
  • Donor Selection
  • Humans
  • Malaria / diagnosis*
  • Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Sensitivity and Specificity

Substances

  • DNA, Protozoan

Grants and funding

Funding was provided by the U.S. Agency for International Development (USAID) through the Amazon Malaria Initiative (AMI). Author who received the funding AMO; São Paulo Research Foundation (FAPESP) by grant #2012/18014-5. Author who received the funding SMDS; Superintendência de Controle de Endemias (SUCEN). Author who received the funding SMDS; and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Author who received the funding GFMCL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.