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Plasmodium 18S rRNA of intravenously administered sporozoites does not persist in peripheral blood

Authors
  • Murphy, Sean C.1, 2
  • Ishizuka, Andrew S.3
  • Billman, Zachary P.1
  • Olsen, Tayla M.1
  • Seilie, Annette M.1
  • Chang, Ming1
  • Smith, Nahum1
  • Chuenchob, Vorada4
  • Chakravarty, Sumana5
  • Sim, B. Kim Lee5
  • Kappe, Stefan H. I.4
  • Hoffman, Stephen L.5
  • Seder, Robert A.3
  • 1 University of Washington, Departments of Laboratory Medicine and Microbiology, 750 Republican St., E630, Seattle, WA, 98109, USA , Seattle (United States)
  • 2 Center for Emerging and Re-emerging Infectious Diseases, University of Washington, 750 Republican St., Seattle, WA, 98109, USA , Seattle (United States)
  • 3 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 40, Room 3512, 40 Convent Drive, Bethesda, MD, 20814, USA , Bethesda (United States)
  • 4 Center for Infectious Disease Research, 307 Westlake Ave N #500, Seattle, WA, 98109, USA , Seattle (United States)
  • 5 Sanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA , Rockville (United States)
Type
Published Article
Journal
Malaria Journal
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jul 27, 2018
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12936-018-2422-2
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundPlasmodium 18S rRNA is a biomarker used to monitor blood-stage infections in malaria clinical trials. Plasmodium sporozoites also express this biomarker, and there is conflicting evidence about how long sporozoite-derived 18S rRNA persists in peripheral blood. If present in blood for an extended timeframe, sporozoite-derived 18S rRNA could complicate use as a blood-stage biomarker.MethodsBlood samples from Plasmodium yoelii infected mice were tested for Plasmodium 18S rRNA and their coding genes (rDNA) using sensitive quantitative reverse transcription PCR and quantitative PCR assays, respectively. Blood and tissues from Plasmodium falciparum sporozoite (PfSPZ)-infected rhesus macaques were similarly tested.ResultsIn mice, when P. yoelii sporozoite inoculation and blood collection were performed at the same site (tail vein), low level rDNA positivity persisted for 2 days post-infection. Compared to intact parasites with high rRNA-to-rDNA ratios, this low level positivity was accompanied by no increase in rRNA-to-rDNA, indicating detection of residual, non-viable parasite rDNA. When P. yoelii sporozoites were administered via the retro-orbital vein and blood sampled by cardiac puncture, neither P. yoelii 18S rRNA nor rDNA were detected 24 h post-infection. Similarly, there was no P. falciparum 18S rRNA detected in blood of rhesus macaques 3 days after intravenous injection with extremely high doses of PfSPZ. Plasmodium 18S rRNA in the rhesus livers increased by approximately 101-fold from 3 to 6 days post infection, indicating liver-stage proliferation.ConclusionsBeyond the first few hours after injection, sporozoite-derived Plasmodium 18S rRNA was not detected in peripheral blood. Diagnostics based on 18S rRNA are unlikely to be confounded by sporozoite inocula in human clinical trials.

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