ACREME Webinar: 26 October 2022
Join the Australian Centre of Research Excellence in Malaria Elimination (ACREME) at the fortnightly webinars.
A phase 1b study to characterise the PK/PD relationship of pyronaridine in healthy volunteers experimentally infected with blood-stage P. falciparum with Associate Professor Bridget Barber
The antimalarial pyronaridine has potent activity against P. falciparum and P. vivax, including multidrug resistant isolates, and is currently available in fixed-dose combination with artesunate as Pyramax®. However, the antimalarial activity of pyronaridine alone has not been completely characterized. We conducted a Phase 1b study to characterize the PK/PD profile of pyronaridine in healthy volunteers infected with P. falciparum. Ten participants were enrolled and inoculated with blood-stage P. falciparum, and treated on day 8 with a single oral dose of 360 mg (n=4), 540 mg (n=4) or 720 mg (n=1) of pyronaridine; one participant tested positive for COVID-19 and was treated with artemether-lumefantrine. Rapid parasite clearance occurred in all participants, with a median parasite clearance half-life of 5.6, 5.7 and 5.1 hrs following treatment with 360 mg, 540 mg and 720 mg pyronaridine, respectively. Parasite recrudescence occurred in all participants administered 360 mg, 2/4 participants administered 540 mg, and not in the single participant administered 720 mg. Gametocytes occurred following treatment with pyronaridine in 8/9 participants. PK/PD parameters were identified with reasonable precision and will inform selection of an appropriate partner drug for pyronaridine for new antimalarial combination therapy.
Understanding patterns of antigen diversity and immune selection pressure amongst leading Plasmodium vivax vaccine candidates and serosurveillance markers with Paolo Bareng.
Paolo completed a comprehensive meta-population genetic analysis of the diversity and immune selection hotspots of the leading Plasmodium vivax antigen candidate genes and sero-surveillance markers. He measured patterns of genetic diversity and selection pressure using traditional population genetics, Tajima’s D, haplotype network analysis, and structural bioinformatics. Information gathered from his study will guide researchers on the rational selection of antigen gene constructs to be included in designing a widely effective vaccine against Plasmodium vivax
Genomic diversity of Plasmodium Vivax in the Solomon Islands with Caitlin Bourke
Plasmodium vivax is a historically understudied parasite population in the Solomon Islands with little known about its genomic diversity and the impact of changes in transmission intensity. Here, we describe the genetic diversity of this parasite population, where samples have been obtained from a clinical trial (ACT-Radical) conducted in the Solomon Islands during 2017-2019. We provide an insight into the broad genetic background of the population with respect to parasite populations from other countries in the region and explore signatures of selection. Finally, we leverage the clinical trial design to explore within-host parasite relatedness using samples from individuals with recurrent infections.
Recordings will be available on the ACREME website.