scholarly journals A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

Nature ◽  
2015 ◽  
Vol 520 (7549) ◽  
pp. 683-687 ◽  
Author(s):  
Alassane Mbengue ◽  
Souvik Bhattacharjee ◽  
Trupti Pandharkar ◽  
Haining Liu ◽  
Guillermina Estiu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Mechanism ◽  
Falciparum Malaria ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria

scholarly journals Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Van Vinh Chau Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Control Strategies ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Public Health Burden

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

scholarly journals Efficacy of dihydroartemisinin/piperaquine and artesunate monotherapy for the treatment of uncomplicated Plasmodium falciparum malaria in Central Vietnam

2020 ◽  
Author(s):  
Eduard Rovira-Vallbona ◽  
Nguyen Van Hong ◽  
Johanna H Kattenberg ◽  
Ro Mah Huan ◽  
Nguyen Thi Thu Hien ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Ex Vivo ◽  
Survival Rates ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Parasite Clearance ◽  
Resistance Mutations ◽  
Malaria Burden ◽  
Central Vietnam

Abstract Background Artemisinin-based combination therapies (ACTs) have significantly contributed to reduce Plasmodium falciparum malaria burden in Vietnam, but their efficacy is challenged by treatment failure of dihydroartemisinin/piperaquine ACT in Southern provinces. Objectives To assess the efficacy of dihydroartemisinin/piperaquine for uncomplicated P. falciparum malaria in Gia Lai, Central Vietnam, and determine parasite resistance to artemisinin (ClinicalTrials.gov identifier NCT02604966). Methods Sixty patients received either dihydroartemisinin/piperaquine (4 mg/kg/day, 3 days; n = 33) or artesunate monotherapy (4 mg/kg/day, 3 days; n = 27) followed by dihydroartemisinin/piperaquine (AS + DHA/PPQ). Clinical phenotypes were determined during a 42 day follow-up and analysed together with ex vivo susceptibility to antimalarials and molecular markers of drug resistance. Results Day 3 positivity rate was significantly higher in the AS + DHA/PPQ arm compared with dihydroartemisinin/piperaquine (70.4% versus 39.4%, P = 0.016). Parasite clearance time was 95.2 h (AS + DHA/PPQ) versus 71.9 h (dihydroartemisinin/piperaquine, P = 0.063) and parasite clearance half-life was 7.4 h (AS + DHA/PPQ) versus 7.0 h (dihydroartemisinin/piperaquine, P = 0.140). Adequate clinical and parasitological response at Day 42 was 100% in both arms. By RT–qPCR, 36% (19/53) patients remained positive until Day 7. No recurrences were detected. kelch13 artemisinin resistance mutations were found in 87% (39/45) of isolates and 50% (20/40) were KEL1/C580Y. The piperaquine resistance marker plasmepsin-2 was duplicated in 10.4% (5/48). Isolates from Day 3-positive patients (n = 18) had higher ex vivo survival rates to artemisinin compounds (P &lt; 0.048) and prevalence of kelch13 mutations (P = 0.005) than Day 3-negative patients (n = 5). The WHO definition of artemisinin resistance was fulfilled in 60% (24/40) of cases. Conclusions Although dihydroartemisinin/piperaquine remained effective to treat P. falciparum, the high Day 3 positivity rate and prevalence of KEL1 strains calls for continuous monitoring of dihydroartemisinin/piperaquine efficacy in Central Vietnam.

scholarly journals Spread of Artemisinin Resistance in Plasmodium falciparum Malaria

2014 ◽  
Vol 371 (5) ◽  
pp. 411-423 ◽  
Author(s):  
Elizabeth A. Ashley ◽  
Mehul Dhorda ◽  
Rick M. Fairhurst ◽  
Chanaki Amaratunga ◽  
Parath Lim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria

scholarly journals Quantitative and rapid Plasmodium falciparum malaria diagnosis and artemisinin-resistance detection using a CMOS Lab-on-Chip platform

2019 ◽  
Vol 145 ◽  
pp. 111678 ◽  
Author(s):  
Kenny Malpartida-Cardenas ◽  
Nicholas Miscourides ◽  
Jesus Rodriguez-Manzano ◽  
Ling-Shan Yu ◽  
Nicolas Moser ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Artemisinin Resistance ◽  
Malaria Diagnosis ◽  
Plasmodium Falciparum Malaria ◽  
Lab On Chip ◽  
On Chip ◽  
Resistance Detection

scholarly journals Clinical and in vitro resistance of Plasmodium falciparum to artesunate-amodiaquine in Cambodia

2020 ◽  
Author(s):  
Melissa Mairet-Khedim ◽  
Rithea Leang ◽  
Camille Marmai ◽  
Nimol Khim ◽  
Saorin Kim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Falciparum Malaria ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Open Label ◽  
Parasite Survival ◽  
Adults And Children

Abstract Background Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia. Methods Between September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat and Siem Reap Provinces, Cambodia. Adults and children with microscopically-confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for three days plus single-dose primaquine, with follow-up on Days 7, 14, 21 and 28. The primary outcome was Day-28 PCR-adjusted adequate clinical and parasitological response (ACPR). An amodiaquine parasite survival assay (AQSA) was developed and applied to whole genome sequencing results to evaluate potential amodiaquine resistance molecular markers. Results In 63 patients, Day-28 PCR-adjusted ACPR was 81.0% (95% confidence interval [CI], 68.9–88.7). Day 3 parasite positivity rate was 44.4% (28/63; 95%CI, 31.9–57.5). All 63 isolates had the K13(C580Y) marker for artemisinin resistance; 79.4% (50/63) had Pfpm2 amplification. The AQSA resistance phenotype (≥45% parasite survival) was expressed in 36.5% (23/63) of isolates and was significantly associated with treatment failure (P = 0.0020). Pfmdr1 mutant haplotypes were N86/184F/D1246 and Pfcrt was CVIET or CVIDT at positions 72–76. Additional Pfcrt mutations were not associated with amodiaquine resistance, but the G353V mutant allele was associated with ACPR compared to Pfmdr1 haplotypes harboring F1068L or S784L/R945P mutations (P = 0.030 and P = 0.0004, respectively). Conclusions For uncomplicated falciparum malaria in Cambodia, artesunate-amodiaquine had inadequate efficacy owing to amodiaquine-resistant P. falciparum. Amodiaquine resistance was not associated with previously identified molecular markers.

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