scholarly journals Limited Polymorphism in Plasmodium falciparum Artemisinin Resistance Kelch13-Propeller Gene Among Clinical Isolates from Bushenyi District, Uganda

2021 ◽  
Vol Volume 14 ◽  
pp. 5153-5163
Author(s):  
Josephat Nyabayo Maniga ◽  
Saheed Adekunle Akinola ◽  
Martin Odoki ◽  
John Odda ◽  
Ismail Abiola Adebayo
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Clinical Isolates

scholarly journals Screening for antifolate and artemisinin resistance in Plasmodium falciparum clinical isolates from three hospitals of Eritrea

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 628
Author(s):  
Harriet Natabona Mukhongo ◽  
Johnson Kang'ethe Kinyua ◽  
Yishak Gebrekidan Weldemichael ◽  
Remmy Wekesa Kasili
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Point Mutations ◽  
Artemisinin Resistance ◽  
Pcr Amplification ◽  
Clinical Isolates ◽  
Genetic Mechanism ◽  
Dried Blood Spot ◽  
Nested Polymerase Chain Reaction ◽  
Blood Spot

Background: Antimalarial drug resistance is a major challenge hampering malaria control and elimination. Plasmodium falciparum, the leading causative parasite species, has developed resistance to basically all antimalarials. Continued surveillance of drug resistance using genetic markers provides important molecular data for treatment policies. This study sought to verify the genetic mechanism of resistance to sulfadoxine-pyrimethamine and assess the occurrence of point mutations associated with artemisinin resistance in P. falciparum clinical isolates from Eritrea. Methods: Nineteen dried blood spot samples were collected from patients visiting Adi Quala, Keren and Gash Barka Hospitals, Eritrea. The patients were followed up after receiving treatment with first line artesunate-amodiaquine. Nested polymerase chain reaction and Sanger sequencing techniques were employed to genotype point mutations in the P. falciparum bifunctional dihydrofolate reductase-thymidylate synthase (Pfdhfr, PF3D7_0417200), dihydropteorate synthase (Pfdhps, PF3D7_0810800) and kelch 13 (PfK13, PF3D7_1343700) genes. Results: Eight of nineteen (42%) of the dried blood spot samples were successful for PCR-amplification. Data analyses of the PCR-positive isolates revealed the following point mutations: Pfdhfr N51I in four isolates, C59R in one isolate, S108N in four isolates, a rare non-synonymous substitution V45A in four isolates and Pfdhps K540E in four isolates. No PfK13 point mutations were reported. Conclusions: Pfdhfr C59R and Pfdhps K540E point mutations are reliable markers for the sulfadoxine-pyrimethamine quintuple mutant haplotype combination. These findings highlight first reports in Eritrea, which verify the underlying genetic mechanism of antifolate resistance. Continuous monitoring of the PfK13 marker is recommended.

scholarly journals No Polymorphism inPlasmodium falciparum K13Propeller Gene in Clinical Isolates from Kolkata, India

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Moytrey Chatterjee ◽  
Swagata Ganguly ◽  
Pabitra Saha ◽  
Biswabandhu Bankura ◽  
Nandita Basu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Artemisinin Resistance ◽  
Drug Regimen ◽  
Clinical Isolates ◽  
Wild Genotype ◽  
Emergence Of Resistance ◽  
Sulphadoxine Pyrimethamine

Molecular markers associated with artemisinin resistance inPlasmodium falciparumare yet to be well defined. Recent studies showed that polymorphisms inK13gene are associated with artemisinin resistance. The present study was designed to know the pattern of polymorphisms in propeller region ofK13gene among the clinical isolates collected from urban Kolkata after five years of ACT implementation. We collected 59 clinical isolates from urban Kolkata and sequenced propeller region ofK13gene in 51 isolates successfully. We did not find any mutation in any isolate. All patients responded to the ACT, a combination of artesunate + sulphadoxine-pyrimethamine. The drug regimen is still effective in the study area and there is no sign of emergence of resistance against artemisinin as evidenced by wild genotype ofK13gene in all isolates studied.

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.

scholarly journals K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates

Science ◽  
2014 ◽  
Vol 347 (6220) ◽  
pp. 428-431 ◽  
Author(s):  
J. Straimer ◽  
N. F. Gnadig ◽  
B. Witkowski ◽  
C. Amaratunga ◽  
V. Duru ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Clinical Isolates

scholarly journals The Diversity of the Plasmodium falciparum K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Melissa D. Conrad ◽  
Sam L. Nsobya ◽  
Philip J. Rosenthal
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Artemisinin Resistance ◽  
Standard Of Care ◽  
Parasite Clearance ◽  
Sub Saharan Africa ◽  
Clinical Isolates ◽  
Nucleotide Polymorphisms ◽  
Content Type ◽  
Sub Saharan

ABSTRACT Artemisinin-based combination therapies (ACTs) are the standard of care to treat uncomplicated falciparum malaria. However, resistance to artemisinins, defined as delayed parasite clearance after therapy, has emerged in Southeast Asia, and the spread of resistance to sub-Saharan Africa could have devastating consequences. Artemisinin resistance has been associated in Southeast Asia with multiple nonsynonymous single nucleotide polymorphisms (NS-SNPs) in the propeller domain of the gene encoding the Plasmodium falciparum K13 protein (K13PD). Some K13PD NS-SNPs have been seen in Africa, but the relevance of these mutations is unclear. To assess whether ACT use has selected for specific K13PD mutations, we compared the K13PD genetic diversity in clinical isolates collected before and after the implementation of ACT use from seven sites across Uganda. We detected K13PD NS-SNPs in 16 of 683 (2.3%) clinical isolates collected between 1999 and 2004 and in 26 of 716 (3.6%) isolates collected between 2012 and 2016 (P = 0.16), representing a total of 29 different polymorphisms at 27 codons. Individual NS-SNPs were usually detected only once, and none were found in more than 0.7% of the isolates. Three SNPs (C469F, P574L, and A675V) associated with delayed clearance in Southeast Asia were seen in samples collected between 2012 and 2016, each in a single isolate. No differences in diversity following implementation of ACT use were found at any of the seven sites, nor was there evidence of selective pressures acting on the locus. Our results suggest that selection by ACTs is not impacting on K13PD diversity in Uganda.

scholarly journals Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Brandyce St. Laurent ◽  
Becky Miller ◽  
Timothy A. Burton ◽  
Chanaki Amaratunga ◽  
Sary Men ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Artemisinin Resistance ◽  
Rapid Expansion ◽  
Clinical Isolates ◽  
Anopheles Coluzzii ◽  
Mosquito Vectors ◽  
Anopheles Dirus ◽  
Global Spread

Abstract Artemisinin-resistant Plasmodium falciparum parasites are rapidly spreading in Southeast Asia, yet nothing is known about their transmission. This knowledge gap and the possibility that these parasites will spread to Africa endanger global efforts to eliminate malaria. Here we produce gametocytes from parasite clinical isolates that displayed artemisinin resistance in patients and in vitro, and use them to infect native and non-native mosquito vectors. We show that contemporary artemisinin-resistant isolates from Cambodia develop and produce sporozoites in two Southeast Asian vectors, Anopheles dirus and Anopheles minimus, and the major African vector, Anopheles coluzzii (formerly Anopheles gambiae M). The ability of artemisinin-resistant parasites to infect such highly diverse Anopheles species, combined with their higher gametocyte prevalence in patients, may explain the rapid expansion of these parasites in Cambodia and neighbouring countries, and further compromise efforts to prevent their global spread.

scholarly journals Plasmodium falciparum Malaria Parasites in Ghana Show Signatures of Balancing Selection at Artemisinin Resistance Predisposing Background Genes

2021 ◽  
Vol 17 ◽  
pp. 117693432199964
Author(s):  
Kwesi Z Tandoh ◽  
Lucas Amenga-Etego ◽  
Neils B Quashie ◽  
Gordon Awandare ◽  
Michael Wilson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Falciparum Malaria ◽  
Early Warning ◽  
Balancing Selection ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Clinical Isolates ◽  
Malaria Parasites ◽  
Molecular Surveillance

Sub-Saharan Africa is courting the risk of artemisinin resistance (ARTr) emerging in Plasmodium falciparum malaria parasites. Current molecular surveillance efforts for ARTr have been built on the utility of P. falciparum kelch13 ( pfk13) validated molecular markers. However, whether these molecular markers will serve the purpose of early detection of artemisinin-resistant parasites in Ghana is hinged on a pfk13 dependent evolution. Here, we tested the hypothesis that the background pfk13 genome may be present before the pfk13 ARTr-conferring variant(s) is selected and that signatures of balancing selection on these genomic loci may serve as an early warning signal of ARTr. We analyzed 12 198 single nucleotide polymorphisms (SNPs) in Ghanaian clinical isolates in the Pf3K MalariaGEN dataset that passed a stringent filtering regimen. We identified signatures of balancing selection in 2 genes (phosphatidylinositol 4-kinase and chloroquine resistance transporter) previously reported as background loci for ARTr. These genes showed statistically significant and high positive values for Tajima’s D, Fu and Li’s F, and Fu and Li’s D. This indicates that the biodiversity required to establish a pfk13 background genome may have been primed in clinical isolates of P. falciparum from Ghana as of 2010. Despite the absence of ARTr in Ghana to date, our finding supports the current use of pfk13 for molecular surveillance of ARTr in Ghana and highlights the potential utility of monitoring malaria parasite populations for balancing selection in ARTr precursor background genes as early warning molecular signatures for the emergence of ARTr.

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