Absence of Plasmodium falciparum resistance to pyronaridine in vitro over 2009-2023 in French Guiana - 13/12/24
Résumé |
Introduction |
A Guiana Shield free of P. falciparum by 2029 – a long-term objective challenged by the regular emergence of drug resistant parasites. In 2022, artesunate-pyronaridine (AS-PY) was recommended by the WHO as an artemisinin-based combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum and P. vivax malaria. To date clinical studies have shown high efficacy and safety profile of pyronaridine even against chloroquine (CQ), amodiaquine and piperaquine-resistant strains. Little data is available on pyronaridine resistance. Few molecular markers have been associated with reduced susceptibility to pyronaridine, pfcrt, pfcarl and pfmdr1. To date, AS-PY is not deployed in the Amazonian region, but this study aimed to characterize the in vitro susceptibility to pyronaridine of P. falciparum isolates over the past 15 years in French Guiana. Regarding the constant increase of imported cases from Africa, isolates from this continent have also been evaluated.
Methods |
Between 2009 and 2023, more than 600 P. falciparum isolates were collected and analyzed in the frame of antimalaria drug surveillance. Susceptibility to PY was evaluated using the in vitro isotopic test to determine the 50% and 90% inhibitory concentrations (IC50, IC90). GraphPad Prism v.8.1.2 (GraphPad Software, USA) was used for data analysis. One-way ANOVA test was performed through years. Data were previously validated based on positive controls obtained on reference strains. The cutoff value for PY resistance was set up to 60 nM (IC50>60nM) according to the literature, based on statistical analysis of published data.
Results |
Over 2009-2023, pyronaridine IC50 values ranged between 0.11nM to 38.62nM with a mean of 6.13 ± 6.38 nM. A 4.5-fold increase was observed between 2009 and 2023 (one-way ANOVA (F (11, 641) = 25,22, p<0.0001)), although values remaining below the 60 nM resistance threshold.
Discussion |
Despite an increase in IC50 values over 2009-2023, no evidence of pyronaridine in vitro resistance has been observed in P. falciparum isolates, suggesting a fully sensitive parasite population. To determine this natural susceptibility level prior to the deployment of this drug is fundamental to follow the susceptibility evolution trends from this reference value. These results support the use of AS-PY as a potential efficacious artemisinin combination therapy in French Guiana and probably extensively in the Guiana Shield. While P. falciparum developed a resistance to almost all artemisinin parent drugs except lumefantrine, this information is crucial to achieve malaria elimination.
Le texte complet de cet article est disponible en PDF.Vol 3 - N° 4S
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