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Plasmodium 18S rRNA of intravenously administered sporozoites does not persist in peripheral blood.
Murphy, Sean C; Ishizuka, Andrew S; Billman, Zachary P; Olsen, Tayla M; Seilie, Annette M; Chang, Ming; Smith, Nahum; Chuenchob, Vorada; Chakravarty, Sumana; Sim, B Kim Lee; Kappe, Stefan H I; Hoffman, Stephen L; Seder, Robert A.
Afiliación
  • Murphy SC; Departments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA. murphysc@uw.edu.
  • Ishizuka AS; Center for Emerging and Re-emerging Infectious Diseases, University of Washington, 750 Republican St., Seattle, WA, 98109, USA. murphysc@uw.edu.
  • Billman ZP; 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.
  • Olsen TM; Departments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
  • Seilie AM; Departments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
  • Chang M; Departments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
  • Smith N; Departments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
  • Chuenchob V; Departments of Laboratory Medicine and Microbiology, University of Washington, 750 Republican St., E630, Seattle, WA, 98109, USA.
  • Chakravarty S; Center for Infectious Disease Research, 307 Westlake Ave N #500, Seattle, WA, 98109, USA.
  • Sim BKL; Sanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
  • Kappe SHI; Sanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
  • Hoffman SL; Center for Infectious Disease Research, 307 Westlake Ave N #500, Seattle, WA, 98109, USA.
  • Seder RA; Sanaria, Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Malar J ; 17(1): 275, 2018 Jul 27.
Article en En | MEDLINE | ID: mdl-30053881
BACKGROUND: Plasmodium 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. METHODS: Blood 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. RESULTS: In 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. CONCLUSIONS: Beyond 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium yoelii / ARN Ribosómico 18S / ARN Protozoario Límite: Animals Idioma: En Revista: Malar J Asunto de la revista: MEDICINA TROPICAL Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plasmodium yoelii / ARN Ribosómico 18S / ARN Protozoario Límite: Animals Idioma: En Revista: Malar J Asunto de la revista: MEDICINA TROPICAL Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido