Monitoring artemisinin resistance in Plasmodium falciparum: comparison of parasite clearance time by microscopy and real-time PCR and evaluation of mutations in Pfatpase6 gene in Odisha state of India

2015 ◽  
Vol 114 (9) ◽  
pp. 3487-3496 ◽  
Author(s):  
Ruchi Gupta ◽  
Neelima Mishra ◽  
Ashwani Kumar ◽  
Roma Rana ◽  
Bina Srivastava ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Real Time ◽  
Real Time Pcr ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Parasite Clearance Time

scholarly journals Delayed Parasite Clearance after Treatment with Dihydroartemisinin-Piperaquine in Plasmodium falciparum Malaria Patients in Central Vietnam

2014 ◽  
Vol 58 (12) ◽  
pp. 7049-7055 ◽  
Author(s):  
Kamala Thriemer ◽  
Nguyen Van Hong ◽  
Anna Rosanas-Urgell ◽  
Bui Quang Phuc ◽  
Do Manh Ha ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clearance Rate ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Sensitivity Testing ◽  
Content Type ◽  
Parasite Clearance Time ◽  
Central Vietnam

ABSTRACTReduced susceptibility ofPlasmodium falciparumtoward artemisinin derivatives has been reported from the Thai-Cambodian and Thai-Myanmar borders. Following increasing reports from central Vietnam of delayed parasite clearance after treatment with dihydroartemisinin-piperaquine (DHA-PPQ), the current first-line treatment, we carried out a study on the efficacy of this treatment. Between September 2012 and February 2013, we conducted a 42-dayin vivoandin vitroefficacy study in Quang Nam Province. Treatment was directly observed, and blood samples were collected twice daily until parasite clearance. In addition, genotyping, quantitative PCR (qPCR), andin vitrosensitivity testing of isolates was performed. The primary endpoints were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates, qPCR clearance profiles,in vitrosensitivity results (for chloroquine, dihydroartemisinin, and piperaquine), and genotyping for mutations in the Kelch 13 propeller domain. Out of 672 screened patients, 95 were recruited and 89 available for primary endpoint analyses. The median parasite clearance time (PCT) was 61.7 h (interquartile range [IQR], 47.6 to 83.2 h), and the median parasite clearance rate had a slope half-life of 6.2 h (IQR, 4.4 to 7.5 h). The PCR-corrected efficacy rates were estimated at 100% at day 28 and 97.7% (95% confidence interval, 91.2% to 99.4%) at day 42. At day 3, theP. falciparumprevalence by qPCR was 2.5 times higher than that by microscopy. The 50% inhibitory concentrations (IC50s) of isolates with delayed clearance times (≥72 h) were significantly higher than those with normal clearance times for all three drugs. Delayed parasite clearance (PCT, ≥72 h) was significantly higher among day 0 samples carrying the 543 mutant allele (47.8%) than those carrying the wild-type allele (1.8%;P= 0.048). In central Vietnam, the efficacy of DHA-PPQ is still satisfactory, but the parasite clearance time and rate are indicative of emerging artemisinin resistance. (This study has been registered at ClinicalTrials.gov under registration no. NCT01775592.)

scholarly journals Plasmodium falciparum clearance time in Malawian children with cerebral malaria: a retrospective cohort study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Alexuse M. Saidi ◽  
Geoffrey Guenther ◽  
Rima Izem ◽  
Xiaojun Chen ◽  
Karl Seydel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cohort Study ◽  
Cerebral Malaria ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
First Year ◽  
Clearance Time ◽  
Parasite Clearance Time

Abstract Background Standard treatment for both uncomplicated and severe malaria is artemisinin derivatives. Delayed parasite clearance times preceded the appearance of artemisinin treatment failures in Southeast Asia. Most worldwide malaria cases are in sub-Saharan Africa (SSA), where clinically significant artemisinin resistance or treatment failure has not yet been detected. The recent emergence of a resistance-conferring genetic mutation in the Plasmodium falciparum parasite in Africa warrants continued monitoring throughout the continent. Methods An analysis was performed on data from a retrospective cohort study of Malawian children with cerebral malaria admitted between 2010 and 2019 to a public referral hospital, ascertaining parasite clearance times across years. Data were collected from patients treated for severe malaria with quinine or artesunate, an artemisinin derivative. Parasite density was determined at admission and every subsequent 6 h until parasitaemia was below 1000 parasites/µl.The mean parasite clearance time in all children admitted in any one year was compared to the parasite clearance time in 2014, the first year of artesunate use in Malawi. Results The median population parasite clearance time was slower from 2010 to 2013 (quinine-treated patients) compared to 2014, the first year of artesunate use in Malawi (30 h (95% CI: 30–30) vs 18 h (95% CI: 18–24)). After adjustment for admission parasite count, there was no statistically significant difference in the median population parasite clearance time when comparing 2014 with any subsequent year. Conclusion Malaria parasite clearance times in Malawian children with cerebral malaria remained constant between 2014 and 2019, arguing against evolving artemisinin resistance in parasites in this region.

EVALUATION THE RATE OF DELAYED PARASITE CLEARANCE IN UNCOMPLICATED PLASMODIUM FALCIPARUM PATIENT AFTER 3 DAYS TREATMENT WITH DIHYDROARTEMISININ PLUS PIPERAQUIN PHOSPHATE (DHA-PPQ) IN HUONG HOA DISTRICT, QUANG TRI PROVINCE

2016 ◽  
pp. 46-51
Author(s):  
Thi Hang Giang Phan ◽  
Dinh Chien Huynh
Keyword(s):  
Plasmodium Falciparum ◽  
Real Time ◽  
Falciparum Malaria ◽  
Real Time Pcr ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Positive Contribution ◽  
Cross Sectional ◽  
Initial Report ◽  
Study Results

Background: Malaria is still remains a public health disease with high circulating levels, each year causes the death of about 1.5 million people worldwide, and almost all deaths are caused by falciparum malaria. The emergence of multidrug-resistant P. falciparum parasites has made these drugs useless in many areas where malaria is endemic. As with earlier antimalarial drugs,parasite resistance to artemisinin and its derivatives has emerged in Southeast Asia. Evaluate the effectiveness of antimalarial drug is an essential activity for assessing sensitivity of drug resistance are taking a positive contribution to the prevention of malaria. Research objective: To evaluate the rate of delayed parasite clearance (DPC) in uncomplicated Plasmodium falciparum patient after 3 days treatment with DHA-PPQ in Huong Hoa district, Quang Tri province. Research methods: Cross-sectional studyandempirical research. The research samples included all patients with falciparum malaria uncomplicated in Huong Hoa district, Quang Tri province agreed to participate in our study. There are 84 patients were collected smears and whole blood samples before and after 3 days of treatment with DHA-PPQ for evaluating parasitemiae by microscopy method and Real time PCR. Results: In total 84 samples of malaria patients were collected to determine the rate of delayed parasite clearance (DPC) after 3 days of treatment with DHA-PPQ, there were 22 samples (26.2%) are parasites in blood after treatment 3days determined by microscopy; Real time PCR with 33 samples (39.3%) were parasites in the blood after treatment 3 days. Conclusion: The epidemiology of malaria in our study had a rate of delayed parasite clearance (DPC)after treatment with DHA-PPQ 3 days were 26.2% (22/84 samples) determined by microscopy and 39.3% (33/84 samples) by Real time PCR. As defined by WHO, the study results contribute to the initial report suspected artemisinin resistance occurs in endemic areas of our research. Key words: Plasmodium falciparum, Artemisinin.

Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria

The Lancet ◽  
1997 ◽  
Vol 350 (9093) ◽  
pp. 1776
Author(s):  
Peter G Kremsner ◽  
Christian H Brandts ◽  
Maryse Ndjave ◽  
Wolfgang Graninger
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Parasite Clearance Time

Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria

The Lancet ◽  
1997 ◽  
Vol 350 (9079) ◽  
pp. 704-709 ◽  
Author(s):  
Christian H Brandts ◽  
Maryse Ndjavé ◽  
Wolfgang Graninger ◽  
Peter G Kremsner
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Parasite Clearance Time

Pyronaridine-Artesunate (Pyramax®) for the Treatment of Artemisinin- and Piperaquine-Resistant Plasmodium falciparum in the Central Highlands of Vietnam

2021 ◽  
Author(s):  
Nguyen Duc Manh ◽  
Nguyen Van Thanh ◽  
Huynh Hong Quang ◽  
Nguyen Thi Thanh Van ◽  
Nguyen Ngoc San ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Clearance Time ◽  
Need To Evaluate ◽  
Multiple Copies ◽  
Adults And Children ◽  
Central Highlands ◽  
Parasitological Response ◽  
C580y Mutation

The rise in Plasmodium falciparum resistance to dihydroartemisinin-piperaquine in Vietnam justifies the need to evaluate alternative artemisinin-based combination therapies. Between July 2018 and October 2019, a single-arm trial of pyronaridine-artesunate (Pyramax, PA) was conducted in Dak Nong province, Vietnam. PA (3-day course) was administered to adults and children infected with P. falciparum . PA was well tolerated by the participants. The proportion of patients with Day 42 PCR-corrected adequate clinical and parasitological response was 95.2% (95% confidence interval [CI], 82.3 to 98.8, n  = 40/42) for treating falciparum malaria. The median parasite clearance half-life was 6.7 h (range, 2.6 to 11.9) and the median parasite clearance time was 72 h (range, 12 to 132) with 44.9% (22/49) of patients having positive blood films at 72 h. The two patients that recrudesced had comparable Day 7 blood pyronaridine concentrations (39.5 and 39.0 ng/ml) to the 40 patients who did not recrudesce (median 43.4 ng/ml, 95% CI, 35.1 to 54.9). Ring-stage and piperaquine survival assays revealed that of the 29 P. falciparum isolates collected from the patients before PA treatment, 22 (75.9%) had reduced susceptibility to artemisinins and 17 (58.6%) were resistant to piperaquine. Genotyping confirmed that 92.0% (46/50) of falciparum patients were infected with parasites bearing the Pfkelch13 C580Y mutation associated with artemisinin resistance. Of these, 56.0% (28/50) of the isolates also had multiple copies of the plasmepsin 2/3 genes responsible for piperaquine resistance. Overall, PA was effective in treating P. falciparum in the Central Highlands of Vietnam.

scholarly journals Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine and polymorphism in Plasmodium falciparum kelch13-propeller gene in Equatorial Guinea

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Matilde Riloha Rivas ◽  
Marian Warsame ◽  
Ramona Mbá Andeme ◽  
Salomón Nsue Esidang ◽  
Policarpo Ricardo Ncogo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
Equatorial Guinea ◽  
Inclusion Criteria ◽  
Treatment Groups ◽  
Three Samples ◽  
Cure Rates ◽  
Al Treatment ◽  
Parasitological Response

Abstract Background Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the currently recommended first- and second-line therapies for uncomplicated Plasmodium falciparum infections in Equatorial Guinea. This study was designed to evaluate the efficacy of these artemisinin-based combinations and detect mutations in P. falciparum kelch13-propeller domain gene (Pfkelch13). Methods A single-arm prospective study evaluating the efficacy of ASAQ and AL at three sites: Malabo, Bata and Ebebiyin was conducted between August 2017 and July 2018. Febrile children aged six months to 10 years with confirmed uncomplicated P. falciparum infection and other inclusion criteria were sequentially enrolled first in ASAQ and then in AL at each site, and followed up for 28 days. Clinical and parasitological parameters were assessed. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples on day-0 were analysed for mutations in Pfkelch13 gene. Results A total 264 and 226 patients were enrolled in the ASAQ and AL treatment groups, respectively. Based on per-protocol analysis, PCR-adjusted cure rates of 98.6% to 100% and 92.4% to 100% were observed in patients treated with ASAQ and AL, respectively. All study children in both treatment groups were free of parasitaemia by day-3. Of the 476 samples with interpretable results, only three samples carried non-synonymous Pfkelch13 mutations (E433D and A578S), and none of them is the known markers associated with artemisinin resistance. Conclusion The study confirmed high efficacy of ASAQ and AL for the treatment of uncomplicated falciparum infections as well as the absence of delayed parasite clearance and Pfkelch13 mutations associated with artemisinin resistance. Continued monitoring of the efficacy of these artemisinin-based combinations, at least every two years, along with molecular markers associated with artemisinin and partner drug resistance is imperative to inform national malaria treatment policy and detect resistant parasites early. Trial registration ACTRN12617000456358, Registered 28 March 2017; http://www.anzctr.org.au/trial/MyTrial.aspx

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.

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