Dihydroartemisinin-piperaquine efficacy in Plasmodium falciparum treatment and prevalence of drug-resistant molecular markers along China-Myanmar border in 2014–2023

Abstract

ABSTRACT: Objectives: The study aims to monitor dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in Plasmodium falciparum and detect molecular markers associated with its resistance. Methods: The World Health Organization's standard protocol for therapeutic efficacy studies (TES) was performed from 2014 to 2018; integrated drug efficacy surveillance (iDES) was performed from from 2019 to July 2023. Molecular markers were detected by polymerase chain reaction. The association between gene mutations and delayed parasite clearance was analysed by multivariate logistic regression analysis. Results: A total of 226 P. falciparum patients were enrolled in the TES from 2014 to 2018, and 26 patients with P. falciparum from Africa were recruited in the iDES from 2019 to July 2023. The PCR-adjusted clinical and parasitological cure rate was 93.7% (95% CI: 92.6–99.5%) in the TES and 96.2% (95% CI: 80.4–99.9%) in the iDEs. Twelve mutants and an overall 55.0% prevalence of pfK13 mutations were detected. Of them, G533S, C447R, C447S, N458Y, C469Y, and A676D were first detected out along the China-Myanmar border. Referred to the wild strain, adjusted odds ratios of treatment failure for G533S, N458Y, and P574L by 42 days were 7.54 (95% CI: 1.605–45.86), 13.68 (95% CI: 1.95-130.72), and 89.00 (95% CI: 1.98–2482.1), respectively. Conclusion: The efficacy of DHA-PPQ from 2014 to 2018 declined in comparison with 2003 to 2013, but it is still effective for treatment of P. falciparum malaria. Results of the iDES indicate a risk of artemisinin resistance in Africa. G533S, N458Y, and P574L are associated with delayed parasite clearance and treatment failure.

Keywords

• Artemisinin resistance
• Plasmodium falciparum
• Therapeutic efficacy study
• Integrated drug efficacy surveillance
• Molecular markers
• China-Myanmar border