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Seilie, Annette M.; Chang, Ming; Hanron, Amelia E.; Billman, Zachary P.; Stone, Brad C.; Zhou, Kevin; Olsen, Tayla M.; Daza, Glenda; Ortega, Jose; Cruz, Kurtis R.; Smith, Nahum; Healy, Sara A.; Neal, Jillian; Wallis, Carolyn K.; Shelton, Lisa; Mankowski, Tracie (VonGoedert); Wong-Madden, Sharon; Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Kappe, Stefan H. I.; Fishbaugher, Matt; Betz, Will; Kennedy, Mark; Hume, Jen C. C.; [...]

Beyond Blood Smears: Qualification of Plasmodium 18S rRNA as a Biomarker for Controlled Human Malaria Infections

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  • Medientyp: E-Artikel
  • Titel: Beyond Blood Smears: Qualification of Plasmodium 18S rRNA as a Biomarker for Controlled Human Malaria Infections
  • Beteiligte: Seilie, Annette M.; Chang, Ming; Hanron, Amelia E.; Billman, Zachary P.; Stone, Brad C.; Zhou, Kevin; Olsen, Tayla M.; Daza, Glenda; Ortega, Jose; Cruz, Kurtis R.; Smith, Nahum; Healy, Sara A.; Neal, Jillian; Wallis, Carolyn K.; Shelton, Lisa; Mankowski, Tracie (VonGoedert); Wong-Madden, Sharon; Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Kappe, Stefan H. I.; Fishbaugher, Matt; Betz, Will; Kennedy, Mark; Hume, Jen C. C.; [...]
  • Erschienen: American Society of Tropical Medicine and Hygiene, 2019
  • Erschienen in: The American Journal of Tropical Medicine and Hygiene
  • Sprache: Nicht zu entscheiden
  • DOI: 10.4269/ajtmh.19-0094
  • ISSN: 0002-9637; 1476-1645
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>18S rRNA is a biomarker that provides an alternative to thick blood smears in controlled human malaria infection (CHMI) trials. We reviewed data from CHMI trials at non-endemic sites that used blood smears and <jats:italic>Plasmodium</jats:italic> 18S rRNA/rDNA biomarker nucleic acid tests (NATs) for time to positivity. We validated a multiplex quantitative reverse transcription–polymerase chain reaction (qRT-PCR) for <jats:italic>Plasmodium</jats:italic> 18S rRNA, prospectively compared blood smears and qRT-PCR for three trials, and modeled treatment effects at different biomarker-defined parasite densities to assess the impact on infection detection, symptom reduction, and measured intervention efficacy. Literature review demonstrated accelerated NAT-based infection detection compared with blood smears (mean acceleration: 3.2–3.6 days). For prospectively tested trials, the validated <jats:italic>Plasmodium</jats:italic> 18S rRNA qRT-PCR positivity was earlier (7.6 days; 95% CI: 7.1–8.1 days) than blood smears (11.0 days; 95% CI: 10.3–11.8 days) and significantly preceded the onset of grade 2 malaria-related symptoms (12.2 days; 95% CI: 10.6–13.3 days). Discrepant analysis showed that the risk of a blood smear–positive, biomarker-negative result was negligible. Data modeling predicted that treatment triggered by specific biomarker-defined thresholds can differentiate complete, partial, and non-protective outcomes and eliminate many grade 2 and most grade 3 malaria-related symptoms post-CHMI. <jats:italic>Plasmodium</jats:italic> 18S rRNA is a sensitive and specific biomarker that can justifiably replace blood smears for infection detection in CHMI trials in non-endemic settings. This study led to biomarker qualification through the U.S. Food and Drug Administration for use in CHMI studies at non-endemic sites, which will facilitate biomarker use for the qualified context of use in drug and vaccine trials.</jats:p>
  • Zugangsstatus: Freier Zugang