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Partner resistance accelerates resistance to first-line malaria drug

Partner-drug resistance accelerates resistance of first-line malaria drug
A girl from Côte d’Ivoire is tested for malaria. According to the World Health Organization, in 2020, malaria caused an estimated 241 million clinical episodes and 627,000 deaths. Credit: Dan Lesher, Penn State University

The drug artemisinin is the world’s most important first-line treatment for malaria, a mosquito-borne disease that killed 627,000 people globally in 2020. Prevention of malaria parasites (Plasmodium) Due to the evolving resistance of Plasmodium falciparum to artemisinin, the World Health Organization has recommended co-administration of partner drugs with artemisinin since 2005. However, parasites have developed resistance to many of these drugs. A new research collaboration between Penn State University, Oxford University and Imperial College London shows that resistance to partnered drugs drives the evolution of resistance to artemisinin.

“Resistance surveillance efforts have recently focused on understanding the emergence and spread of artemisinin resistance in Plasmodium falciparum, said Maciej Boni, associate professor of biology. “Our findings suggest that there is also a need to focus on monitoring partner resistance to slow the spread of artemisinin resistance.”

A team of modeling groups used multiple mathematical models to predict the evolution of artemisinin resistance across a range of epidemiological settings. Specifically, these models examine varying degrees of malaria prevalence and pre-existing partner resistance, as well as varying degrees of antimalarial combination therapy, including dihydroartemisinin-piperaquine, artesunate-amodie Quine and artemether-benzfluorenol.

The team found that the presence of higher frequencies of partner-resistant P. falciparum genotypes caused these parasites to develop earlier Artemisinin resistance was established. The frequency of partner-resistant P. falciparum increased on average 10-fold across all models, implying that artemisinin efficacy was lost 2-12 years earlier than the artemisinin efficacy at full effect of the partner drug. Among the three drug combinations, dihydroartemisinin-piperaquine was most susceptible to the chaperone resistance process, accelerating the evolution of artemisinin resistance. Notably, the team observed that even at lower partner resistance frequencies, the establishment time of artemisinin resistance was significantly reduced.

The results of the study were published on August 2 in the journal The Lancet Microbe.

“Our findings suggest that , early detection of partner resistance is necessary to prevent the spread of artemisinin resistance, as even low frequency partner resistance can promote the emergence of early artemisinin resistance,” Boni said. . “While public health concerns typically arise only after partner resistance is prevalent, our study suggests that early detection and preemptive action against partner resistance would be beneficial in delaying partner resistance, artemisinin resistance Medicinal properties and treatment failure, all at once.”

Further information: Oliver J Watson et al, Pre-existing partner -drug resistance to artemisinin combination therapy Emergence and spread of artemisinin resistance: a consensus model study, Lancet Microbes (2022). DOI: 10.1016/S2666-5247(22)00155-0

Citation : Partner drug resistance accelerates resistance to first-line malaria drugs (August 2022 September 29), Retrieved September 7, 2022 from

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