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

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.

Investigation and control of a Plasmodium falciparum malaria outbreak in Shan Special Region II of Myanmar along the China-Myanmar Border from June to December 2014.

BACKGROUND: From 2007 to 2013, intensive control measures reduced malaria burden by 90 % along the China-Myanmar border. However, despite these measures a P. falciparum malaria outbreak was reported in the Shan Special Region II of Myanmar in June of 2014. METHODS: Epidemiological, parasitological and entomological investigations were performed. Dihydroartemisinin piperaquine (DAPQ) was immediately administered to treat parasite positive individuals. Long lasting insecticidal nets (LLIN), indoor residual spraying (IRS) with insecticides and behavior change communication (BCC) were also provided for outbreak control. An embedded efficacy study was conducted evaluating DP. Molecular genotyping via polymerase chain reaction (PCR) was performed on the Kelch gene on chromosome 13. RESULTS: All infections were identified as Plasmodium falciparum by RDT and microscopy. Two fatalities resulted from the outbreak. The attack rate was 72.8 % (67/92) and the incidence density rate was 14.2 per 100 person-weeks. The positive rate of rapid diagnostic test (RDT) was 72.2 % (65/90) and microscopically-determine parasite rate 42.2 % (38/90). Adjusted odds ratio (OR) of multivariate logistic regression analysis for aged <15 years, 15-45 years, inappropriate treatment from a private healer and lack of bed nets were 13.51 (95 % confidence interval, 2.21-105.89), 7.75 (1.48-44.97), 3.78 (1.30-46.18) and 3.21(1.21-15.19) respectively. In the six surrounding communities of the outbreak site, positive RDT rate was 1.2 % (4/328) and microscopically-determine parasite rate 0.6 % (2/328). Two light traps collected a total of 110 anopheline mosquitoes including local vectors, An. minimus, An. sinensis and An. maculates. After intensive control, the detection of malaria attacks, parasites and antigen were reduced to zero between July 1 and December 1, 2014. The cure rate of P. falciparum patients at day 42 was 94.3 % (95 % CI, 80.8-99.3 %). The PCR did not detect K13-propeller mutations. CONCLUSION: Imported P. falciparum caused the outbreak. Age, seeking inappropriate treatment and lack of bed nets were risk factors for infection during the outbreak. P. falciparum was sensitive to treatment with DAPQ. The integrated measures controlled the outbreak and prevented the spread of P. falciparum effectively. The results of this study indicate that malaria control on the China-Myanmar border, especially among special populations, needs further collaboration between China, Myanmar and international societies.