Chloroquine (CQ) is the first-line treatment for Plasmodium vivax malaria in most endemic countries. Monitoring P.vivax CQ resistance (CQR) is critical but remains challenged by the difficulty to distinguish real treatment failure from reinfection or liver relapse. Therapeutic efficacy of CQ against uncomplicated P.vivax malaria was evaluated in Gia Lai province, Vietnam. Sixty-seven patients were enrolled and followed-up for 42 days using microscopy and (RT)qPCR. Adequate clinical and parasitological response (ACPR) was 100% (66/66) on Day 28, but 75.4% (49/65) on Day 42. Eighteen recurrences (27.7%) were detected with a median time-to-recurrence of 42 days (IQR 35, 42) and blood CQ concentration <100ng/ml. Primary infections leading to recurrence occurred in younger individuals (median age for ACPR=25 years [IQR 20, 28]; recurrences=18 [16, 21]; p=0.002), had a longer parasite clearance time (PCT for ACPR=47.5h [IQR 36.2, 59.8]; recurrences=54.2h [48.4, 62.0]; p=0.035) and higher pvcrt gene expression (median relative expression ratio for ACPR=0.09 [IQR 0.05, 0.22]; recurrences=0.20 [0.15, 0.56]; p=0.002), but showed no differences in ex vivo CQ sensitivity. Parasite genotyping by microsatellites, SNP-barcoding and whole-genome sequencing (WGS) identified a majority of homologous recurrences, with 80% (8/10) showing >98% identity-by-descent to paired Day 0 samples. This study shows that CQ remained largely efficacious to treat P.vivax in Gia Lai, i.e. recurrences occurred late (>Day 28) and in the presence of low blood CQ concentrations. However, the combination of both WGS and gene expression analysis (pvcrt) with clinical data (PCT) allowed to identify potential emergence of low-grade CQR that should be closely monitored.

Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test (SD Biosensor, Seoul, Republic of Korea) was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination.

Thử nghiệm in vivo 120 ngày để so sánh hiệu lực điều trị chống tái phát và tính an toàncủa thuốc Primaquin trong điều trị bệnh nhân P.vivax phác đồ 7 ngày liều 0,5mg/kg/ngàyvới phác đồ 14 ngày liều 0,25mg/kg/ngày đã được tiến hành tại Gia Lai và Bình Phước từnăm 2019 đến năm 2020. Số liệu thu thập được từ 38 bệnh nhân cho thấy: Tỷ lệ xuất hiệnlại P. vivax là 15% ở phác đồ 7 ngày (n=20 vào ngày D51, D65, D100), và 22% ở phác đồ14 ngày (n=18 vào ngày D42, D57, D60, D99). Hai phác đồ Primaquin liều 7 ngày và 14ngày không ghi nhận trường hợp nào đái huyết cầu tố cũng như các biến cố bất lợi liênquan đến thuốc. Nghiên cứu đã cho thấy không có sự khác biệt về hiệu quả chống tái phátcũng như tính an toàn giữa phác đồ 7 ngày Primaquin liều 0.5mg/kg/ngày và phác đồ 14ngày liều 0.25mg/kg.ngày.

From March to December 2021, this prospective, open-label, single-armobservational clinical trial, conducted in Binh Phuoc, Gia Lai and Phu Yen provinces,evaluated the safety and efficacy of oral Pyronaridine tetraphosphate-Artesunate oncedaily for three consecutive days in adults and children with microscopically confirmedP. falciparum malaria. Patients were treated as in-patients for Days 0–3, with followup visits on Days 7, 14, 21, 28, 35 and 42. The primary outcome was PCR-adjustedadequate clinical and parasitological response (ACPR) at Day 42. The results from 54P. falciparum patients has shown that: The efficacy of Pyronaridine tetraphosphate -Artesunate to P. falciparum has still high, with the rate of ACPR is 100%, the rate ofpositive parasitemia at day 3 is 50%, 54.5% and 54.8% in Binh Phuoc, Phu Yen andGia Lai, respectively. Pyronaridine-Artesunate is safety for the patients. None seriousadverd event are recorded.

Chloroquine (CQ) is the first-line treatment for Plasmodium vivax malaria in most endemic countries. Monitoring P.vivax CQ resistance (CQR) is critical but remains challenged by the difficulty to distinguish real treatment failure from reinfection or liver relapse. Therapeutic efficacy of CQ against uncomplicated P.vivax malaria was evaluated in Gia Lai province, Vietnam. Sixty-seven patients were enrolled and followed-up for 42 days using microscopy and (RT)qPCR. Adequate clinical and parasitological response (ACPR) was 100% (66/66) on Day 28, but 75.4% (49/65) on Day 42. Eighteen recurrences (27.7%) were detected with a median time-to-recurrence of 42 days (IQR 35, 42) and blood CQ concentration <100ng/ml. Parasite genotyping by microsatellites, SNP-barcoding and whole-genome sequencing (WGS) identified a majority of homologous recurrences, with 80% (8/10) showing >98% identity-by-descent to paired Day 0 samples. Primary infections leading to recurrence occurred in younger individuals (median age for ACPR=25 years [IQR 20, 28]; recurrences=18 [16, 21]; p=0.002), had a longer parasite clearance time (PCT for ACPR=47.5h [IQR 36.2, 59.8]; recurrences=54.2h [48.4, 62.0]; p=0.035) and higher pvcrt gene expression (median relative expression ratio for ACPR=0.09 [IQR 0.05, 0.22]; recurrences=0.20 [0.15, 0.56]; p=0.002), but there was no difference in ex vivo CQ sensitivity. This study shows that CQ remained largely efficacious to treat P.vivax in Gia Lai, i.e. recurrences occurred late (>Day 28) and in the presence of low blood CQ concentrations. However, the combination of WGS and gene expression analysis (pvcrt) with clinical data (PCT) allowed to identify potential emergence of low-grade CQR that should be closely monitored.