Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam

Abstract

BackgroundReduced artemisinin susceptibility and artemisinin-based combination therapy (ACT)-resistance against Plasmodium falciparum and chloroquine (CQ)-resistant P. vivax malaria has been reported in Vietnam. Two therapeutic efficacy studies were conducted in Thuan Bac District (Ninh Thuan Province, Vietnam) in 2015 and 2016 to determine the extent of reduced artemisinin susceptibility and ACT resistant falciparum malaria, and CQ-resistant vivax malaria were present.MethodsTwenty-seven patients with falciparum malaria were randomized to receive artesunate alone (AS ~ 4 mg/kg/day) for 4 days followed by dihydroartemisinin (DHA) (2.2 mg/kg)–piperaquine (PPQ) (18 mg/kg) daily for 3 days or artemether (AM) (1.7 mg/kg)–lumefantrine (LUM) (12 mg/kg) twice daily for 3 days. Sixteen subjects with vivax malaria received CQ (total 25 mg/kg over 3 days). The therapeutic efficacy study for treating falciparum malaria was complemented with molecular analysis for artemisinin and piperaquine resistance, and in vitro drug susceptibility testing. Patient’s drug exposure following both falciparum and vivax treatment studies was determined.ResultsTwenty-five of 27 patients treated with the artemisinin regimens completed the 42-day follow-up period. None had parasites present on day 3 after commencing treatment with no incidence of recrudescence (100% curative rate). One patient on AS + DHA–PPQ was lost to follow-up and one patient had Plasmodium falciparum and Plasmodium vivax infection on day 0 by PCR. Of the vivax patients, 15 of 16 completed CQ treatment and two had a recurrence of vivax malaria on day 28, a failure rate of 13.3% (2/15). No mutations in the Pfkelch-13 gene for artemisinin resistance or exo-E415G gene polymorphism and amplification in plasmepsins 2 and 3 for piperaquine resistance were observed. In vitro testing of patient’s falciparum parasites indicated susceptibility (low IC50 nM values) to dihydroartemisinin, lumefantrine, piperaquine and pyronaridine. Patient’s drug exposure to artesunate and lumefantrine was comparable to published data, however, blood CQ concentrations were lower.ConclusionsClinical findings, molecular analysis and in vitro testing revealed that the falciparum parasites at Phuoc Chien Commune were artemisinin susceptible. The clinical failure rate of the 15 vivax patients who completed CQ treatment was 13%. Further studies are required to determine whether CQ-resistant vivax malaria is present at the commune.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2640-2) contains supplementary material, which is available to authorized users.

Susceptibility of Plasmodium falciparum isolates to antimalarial drugs in a highly seasonal malaria endemic village in Mali

“…Our result was similar to 51nM by Phong, NC. et al in 2019 in Vietnam [22] and much lower than 143.94 nM by Kaddouri [21]. This increased sensitivity of the isolates could be related to the decreased or absent pressure on CQ.…”

“…and al. in 2019 in Vietnam [22]. In terms of sensitivity, 6.8 % (5/73) of isolates had reduced sensitivity to AQ (CI 50 > 61 nM).…”

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces

“…The fact that the use of indoor spraying and insecticide-treated mosquito nets (ITN) is equally to contribute to these changes in the malaria epidemiology. Studies of the therapeutic efficacy of first-line treatment with DHA-PPQ at national sentinel sites have shown delayed parasite clearance in Gia Lai Province (2010), Dak Nong Province (2011), Quang Nam Province (2012), Khanh Hoa Province (2014) and Ninh Thuan Province (2015), with over 10% of patients being microscopically positive on day 3 after treatment initiation [ 32 , 33 ].…”

Progress and challenges in the use of fluorescence‐based flow cytometric assays for anti‐malarial drug susceptibility tests

“…For biochemical assays, the microtechnique was modified to a semiautomatic tritiated hypoxanthine incorporation assay, measuring Plasmodium uptake of radiolabelled hypoxanthine, a nucleic acid precursor, to assess the growth inhibitory effect of anti-malarial drugs [ 19 ] or immune serum [ 20 ]. Given a rapid, more precise and quantitative method, many recent reports have been adopted for the assessment of Plasmodium growth inhibition in experiments [ 21 ] and in a clinical trial setting [ 22 ] and for surveillance of drug resistance in field isolates [ 23 ]. In addition to DNA synthesis-based assays, Plasmodium parasites in intraerythrocytic stages also actively synthesize cell membranes composed of phospholipids; thus, an assay based on incorporation of the radioisotope-labeled phospholipid precursor ethanolamine was developed [ 24 ], allowing an assessment of anti-malarial compounds targeting enzyme functioning in fatty acid biosynthesis [ 25 ].…”