scholarly journals A review of the frequencies of indigenous Plasmodium falciparum Kelch 13 artemisinin resistance mutations in Africa

2021 ◽  
Author(s):  
Leonard Ndwiga ◽  
Kelvin M. Kimenyi ◽  
Kevin Wamae ◽  
Victor Osoti ◽  
Mercy Akinyi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Resistance Mutations ◽  
Kelch 13

scholarly journals Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016

2018 ◽  
Vol 62 (4) ◽  
Author(s):  
Theerayot Kobasa ◽  
Eldin Talundzic ◽  
Rungniran Sug-aram ◽  
Patcharida Boondat ◽  
Ira F. Goldman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Gene Mutations ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Resistance Mutations ◽  
Content Type ◽  
Artemisinin Derivatives ◽  
Reduced Ring ◽  
Control And Prevention ◽  
Greater Mekong Subregion

ABSTRACT Artemisinin-based combination therapy (ACT) is the most effective and widely used treatment for uncomplicated Plasmodium falciparum malaria and is a cornerstone for malaria control and prevention globally. Resistance to artemisinin derivatives has been confirmed in the Greater Mekong Subregion (GMS) and manifests as slow parasite clearance in patients and reduced ring stage susceptibility to artemisinins in survival assays. The P. falciparum kelch13 gene mutations associated with artemisinin-resistant parasites are now widespread in the GMS. We genotyped 277 samples collected during an observational study from 2012 to 2016 from eight provinces in Thailand to identify P. falciparum kelch13 mutations. The results were combined with previously reported genotyping results from Thailand to construct a map illustrating the evolution of P. falciparum kelch13 mutations from 2007 to 2016 in that country. Different mutant alleles were found in strains with different geographical origins. The artemisinin resistance-conferring Y493H and R539T mutations were detected mainly in eastern Thailand (bordering Cambodia), while P574L was found only in western Thailand and R561H only in northwestern Thailand. The C580Y mutation was found across the entire country and was nearing fixation along the Thai-Cambodia border. Overall, the prevalence of artemisinin resistance mutations increased over the last 10 years across Thailand, especially along the Thai-Cambodia border. Molecular surveillance and therapeutic efficacy monitoring should be intensified in the region to further assess the extent and spread of artemisinin resistance.

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 < 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 Molecular Profile of Malaria Drug Resistance Markers of Plasmodium falciparum in Suriname

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Stella M. Chenet ◽  
Sheila Akinyi Okoth ◽  
Julia Kelley ◽  
Naomi Lucchi ◽  
Curtis S. Huber ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Therapeutic Efficacy ◽  
Artemisinin Resistance ◽  
Molecular Profile ◽  
Resistance Mutations ◽  
Molecular Surveillance ◽  
Content Type ◽  
Resistance Markers ◽  
High Parasite

ABSTRACT In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum. We genotyped the PfK13 propeller domain of P. falciparum in 40 samples as well as other mutations proposed to be associated with artemisinin-resistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia, but we found fixed resistance mutations for chloroquine (CQ) and sulfadoxine-pyrimethamine. Additionally, the PfCRT C350R mutation, associated with reversal of CQ resistance and piperaquine-selective pressure, was present in 62% of the samples. Our results from neutral microsatellite data also confirmed a high parasite gene flow in the Guiana Shield. Although recruiting participants for therapeutic efficacy studies is challenging in areas where malaria endemicity is very low due to the low number of malaria cases reported, conducting these studies along with molecular surveillance remains essential for the monitoring of artemisinin-resistant alleles and for the characterization of the population structure of P. falciparum in areas targeted for malaria elimination.

scholarly journals Expansion of the Plasmodium falciparum Kelch 13 R622I mutation in Northwest Ethiopia

2021 ◽  
Author(s):  
Aberham A. Alemayehu ◽  
Daniel Castaneda-Mogollon ◽  
Habtie Tesfa ◽  
Sisay Getie ◽  
Abu Naser Mohon ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Northwest Ethiopia ◽  
Efficacy Trial ◽  
North West ◽  
North West Ethiopia ◽  
Parasitological Response ◽  
Kelch 13

Abstract According to the WHO, almost two thirds of the Ethiopian population are at risk of contracting malaria, where infection with Plasmodium falciparum accounts for approximately 60% of cases today. The risk of artemisinin resistance spreading from SE Asia to Africa is a major concern. We conducted a 28-day in vivo efficacy trial of Artemether-Lumefantrine (Co-Artem) for treatment of uncomplicated malaria (n = 97) in the Gondar Region, North West Ethiopia in 2017–2018. Our results confirmed 100% adequate clinical and parasitological response (ACPR) with no parasites observed at day 3 by microscopy. Further analysis of day 0 samples showed the expansion of a kelch13 mutation R622I to 9.5% from 2.4% of isolates reported three years earlier. Closer examination of the R622I mutation in vitro is warranted.

scholarly journals Polymorphisms in Plasmodium falciparum Kelch 13 and P. vivax Kelch 12 Genes in Parasites Collected from Three South Pacific Countries Prior to Extensive Exposure to Artemisinin Combination Therapies

2019 ◽  
Vol 63 (7) ◽  
Author(s):  
Karryn Gresty ◽  
Karen Anderson ◽  
Cielo Pasay ◽  
Norman C. Waters ◽  
Qin Cheng
Keyword(s):  
Plasmodium Falciparum ◽  
Papua New Guinea ◽  
Solomon Islands ◽  
Artemisinin Resistance ◽  
South Pacific ◽  
New Guinea ◽  
Combination Therapies ◽  
Baseline Information ◽  
Artemisinin Combination Therapies ◽  
Kelch 13

ABSTRACT The South Pacific countries Solomon Islands, Vanuatu, and Papua New Guinea (PNG) adopted artemisinin-based combination therapies (ACTs) in 2008. We examined Kelch 13 and Kelch 12 genes in parasites originating from these countries before or at ACT introduction. Four Kelch 13 and two Kelch 12 novel sequence polymorphisms, not associated with artemisinin resistance, were observed in parasites from Solomon Islands and Vanuatu. No polymorphisms were observed in PNG parasites. The findings provide useful baseline information.

scholarly journals Continued Sensitivity of Plasmodium falciparum to Artemisinin in Guyana, With Absence of Kelch Propeller Domain Mutant Alleles

2016 ◽  
Vol 3 (3) ◽  
Author(s):  
Reyaud Rahman ◽  
Maria Jesus Sanchez Martin ◽  
Shamdeo Persaud ◽  
Nicolas Ceron ◽  
Dwayne Kellman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Confidence Interval ◽  
Clearance Rate ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Wild Type ◽  
Resistance Monitoring ◽  
Mining Areas ◽  
Widespread Availability ◽  
Kelch 13

Abstract Because of concerns about possible emergence of artemisinin resistance strains of Plasmodium falciparum in mining areas of the interior of Guyana, a 7-day artesunate trial was conducted from March to December 2014. The day-3 parasite clearance rate, the efficacy of artesunate at day 28, and polymorphism of Kelch 13 (PfK13)—the marker of artemisinin resistance—were assessed. The study confirmed the continued sensitivity of P falciparum to artemisinin. A 7-day course of artesunate was 100% efficacious with only 2% (95% confidence interval, .1%–10.9%) of enrolled subjects positive at day 3. All day-0 parasite samples were wild type. Continued resistance monitoring is nevertheless recommended, given the widespread availability and uncontrolled use of artemisinin drugs in mining areas of Guyana.

scholarly journals No Plasmodium falciparum Chloroquine Resistance Transporter and Artemisinin Resistance Mutations, Haiti

2018 ◽  
Vol 24 (11) ◽  
pp. 2124-2126 ◽  
Author(s):  
Jeanne P. Vincent ◽  
Kanako Komaki-Yasuda ◽  
Alexandre V. Existe ◽  
Jacques Boncy ◽  
Shigeyuki Kano
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Chloroquine Resistance ◽  
Resistance Mutations ◽  
Chloroquine Resistance Transporter

scholarly journals Independent Emergence of Artemisinin Resistance Mutations Among Plasmodium falciparum in Southeast Asia

2014 ◽  
Vol 211 (5) ◽  
pp. 670-679 ◽  
Author(s):  
Shannon Takala-Harrison ◽  
Christopher G. Jacob ◽  
Cesar Arze ◽  
Michael P. Cummings ◽  
Joana C. Silva ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Artemisinin Resistance ◽  
Resistance Mutations

scholarly journals Genetic Architecture and Dynamics of PfKelch13’s Propeller Domain in Plasmodium Falciparum Clinical Isolates Collected in Senegal.

2021 ◽  
Author(s):  
Mariama Pouye ◽  
Gora Diop ◽  
celine Derbois ◽  
Babacar Mbengue ◽  
oumar Ka ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Artemisinin Resistance ◽  
Clinical Isolates ◽  
Health Concern ◽  
Gene Marker ◽  
Resistance Mutations ◽  
Malaria Epidemiology ◽  
Strategic Plans ◽  
Transmission Area

Abstract Plasmodium resistance to Artemisinin Combination-based Therapies (ACT) in Southeast Asia is a major public health concern that is sporadically appearing in Africa. Senegal has shifted from malaria control to elimination plans. Given notable progresses obtained through robust strategic plans, it is still crucial to assess genetic variability of the Plasmodium falciparum artemisinin resistance gene marker Kelch13 (PfKelch13) in circulating field isolates. We here report an analysis of PfKelch13-propeller polymorphism in clinical isolates collected nine years after ACT introduction in five Senegalese regions with different malaria transmission settings. Sequencing of PfKelch13-propeller domain from 280 clinical isolates reveals that 16% (45/280) of the parasite population harbored variants. Dynamics of PfKelch13 variants reveals emerging, persistent but also disappearing mutations over time. In addition to the malaria epidemiology, our survey also shows the dynamics of PfKelch13 variants in different malaria transmission settings in Senegal. Despite the absence of PfKelch13 associated artemisinin resistance mutations, a shift from 86% to 68% of PfKelch13WT was observed when comparing parasites collected prior vs. post ACT intensive usage in Dakar a low malaria transmission area. All together, our data confirms the need to closely monitor PfKelch13 polymorphism to anticipate and or prevent emergence of P. falciparum resistance in Senegal.

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