Open forum infectious diseases · 2023
Plasmodium 18S Ribosomal RNA Biomarker Clearance After Food and Drug Administration-Approved Antimalarial Treatment in Controlled Human Malaria Infection Trials.
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Chavtur Chris, Staubus Weston J, Ho Mabel, Hergott Dianna E B, Seilie Annette M, Healy Sara, Duffy Patrick, Jackson Lisa, Talley Angela, Kappe Stefan H I, Hoffman Stephen L, Richie Thomas L, Kublin James G, Chang Ming, Murphy Sean C
Аннотация
BACKGROUND: Sensitive molecular assays, such as quantitative reverse-transcription polymerase chain reaction (qRT-PCR) of Plasmodium 18S ribosomal RNA (rRNA), are increasingly the primary method of detecting infections in controlled human malaria infection (CHMI) trials. However, thick blood smears (TBSs) remain the main method for confirming clearance of parasites after curative treatment, in part owing to uncertainty regarding biomarker clearance rates.
METHODS: For this analysis, 18S rRNA qRT-PCR data were compiled from 127 Plasmodium falciparum-infected participants treated with chloroquine or atovaquone-proguanil in 6 CHMI studies conducted in Seattle, Washington, over the past decade. A survival analysis approach was used to compare biomarker and TBS clearance times among studies. The effect of the parasite density at which treatment was initiated on clearance time was estimated using linear regression.
RESULTS: The median time to biomarker clearance was 3 days (interquartile range, 3-5 days), while the median time to TBS clearance was 1 day (1-2 days). Time to biomarker clearance increased with the parasite density at which treatment was initiated. Parasite density did not have a significant effect on TBS clearance.
CONCLUSIONS: The Plasmodium 18S rRNA biomarker clears quickly and can be relied on to confirm the adequacy of Food and Drug Administration-approved treatments in CHMI studies at nonendemic sites.
METHODS: For this analysis, 18S rRNA qRT-PCR data were compiled from 127 Plasmodium falciparum-infected participants treated with chloroquine or atovaquone-proguanil in 6 CHMI studies conducted in Seattle, Washington, over the past decade. A survival analysis approach was used to compare biomarker and TBS clearance times among studies. The effect of the parasite density at which treatment was initiated on clearance time was estimated using linear regression.
RESULTS: The median time to biomarker clearance was 3 days (interquartile range, 3-5 days), while the median time to TBS clearance was 1 day (1-2 days). Time to biomarker clearance increased with the parasite density at which treatment was initiated. Parasite density did not have a significant effect on TBS clearance.
CONCLUSIONS: The Plasmodium 18S rRNA biomarker clears quickly and can be relied on to confirm the adequacy of Food and Drug Administration-approved treatments in CHMI studies at nonendemic sites.