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artemisinin resistance

Detection of mutations associated with artemisinin resistance at k13-propeller gene and a near complete return of chloroquine susceptible falciparum malaria in Southeast of Tanzania

March 3, 2020 - 12:39 -- Open Access
Author(s): 
Bwire GM, Ngasala B, Mikomangwa WP, Kilonzi M, Kamuhabwa AAR
Reference: 
Sci Rep. 2020 Feb 26;10(1):3500

In Tanzania, chloroquine was replaced by sulphadoxine- pyrimethamine (SP) as a first-line for treatment of uncomplicated malaria. Due to high resistance in malaria parasites, SP lasted for only 5 years and by the end of 2006 it was replaced with the current artemisinin combination therapy. We therefore, set a study to determine the current genotypic mutations associated with Plasmodium falciparum resistance to artemisinin, partner drugs and chloroquine.

Role of Plasmodium falciparum Kelch 13 Protein Mutations in P. falciparum Populations from Northeastern Myanmar in Mediating Artemisinin Resistance

March 2, 2020 - 15:34 -- Open Access
Author(s): 
Siddiqui FA, Boonhok R, Cui L, et al.
Reference: 
mBio. 2020 Feb 25; 11(1). pii: e01134-19

Mutations in the Plasmodium falciparum Kelch 13 (PfK13) protein are associated with artemisinin resistance. PfK13 is essential for asexual erythrocytic development, but its function is not known. We tagged the PfK13 protein with green fluorescent protein in P. falciparum to study its expression and localization in asexual and sexual stages. We used a new antibody against PfK13 to show that the PfK13 protein is expressed ubiquitously in both asexual erythrocytic stages and gametocytes and is localized in punctate structures, partially overlapping an endoplasmic reticulum marker.

A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites

January 14, 2020 - 16:49 -- Open Access
Author(s): 
Birnbaum J, Scharf S, Schmidt S, Jonscher E, Hoeijmakers WAM, Flemming S, Toenhake CG, Schmitt M, Sabitzki R, Bergmann B, Fröhlke U, Mesén-Ramírez P, Blancke Soares A, Herrmann H, Bártfai R, Spielmann T
Reference: 
Science, 03 Jan 2020: Vol. 367, Issue 6473, pp. 51-59

Artemisinin and its derivatives (ARTs) are the frontline drugs against malaria, but resistance is jeopardizing their effectiveness. ART resistance is mediated by mutations in the parasite’s Kelch13 protein, but Kelch13 function and its role in resistance remain unclear. In this study, we identified proteins located at a Kelch13-defined compartment. Inactivation of eight of these proteins, including Kelch13, rendered parasites resistant to ART, revealing a pathway critical for resistance.

NOT Open Access | Viability Screen of LOPAC1280 Reveals Tyrosine Kinase Inhibitor Tyrphostin A9 as a Novel Partner Drug for Artesunate Combinations To Target the Plasmodium falciparum Ring Stage

April 2, 2019 - 11:46 -- NOT Open Access
Author(s): 
Jie Xin Tong, Sarah E. L. Ang, Esther H. N. Tan and Kevin S. W. Tan
Reference: 
Antimicrob Agents Chemother 63:e02389-18

The emergence of artemisinin-resistant Plasmodium falciparum poses a major threat to current frontline artemisinin combination therapies.

How can interventions that target forest-goers be tailored to accelerate malaria elimination in the Greater Mekong Subregion? A systematic review of the qualitative literature

February 5, 2019 - 16:23 -- Open Access
Author(s): 
Stephanie D. Nofal, Thomas J. Peto, Bipin Adhikari, Rupam Tripura, James Callery, Thanh Mai Bui, Lorenz von Seidlein and Christopher Pell
Reference: 
Malaria Journal 2019 18:32, 1 February 2019

A more detailed characterization of forest activities is needed but research on this topic raises methodological challenges.

A single nucleotide polymorphism in the Plasmodium falciparum atg18 gene associates with artemisinin resistance and confers enhanced parasite survival under nutrient deprivation

October 30, 2018 - 15:46 -- Open Access
Author(s): 
Kimberly F. Breglio, Roberto Amato, Anna Katharina Simon, et al.
Reference: 
Malaria Journal 2018 17:391, 26 October 2018

These results suggest that the atg18 T38I polymorphism may provide additional resistance against artemisinin derivatives, but not partner drugs, even in the absence of kelch13 mutations, and may also be important in parasite survival during nutrient deprivation.

Effectiveness and safety of 3 and 5 day courses of artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar

July 15, 2018 - 16:52 -- Open Access
Author(s): 
Kyaw Myo Tun, Atthanee Jeeyapant, Frank Smithuis, et al.
Reference: 
Malaria Journal 2018 17:258, 11 July 2018

Despite a high prevalence of k13 mutations, the current first-line treatment, AL, was still highly effective in this area of South-East Myanmar.

Medical Treatment: 

A novel field-based molecular assay to detect validated artemisinin-resistant k13 mutants

April 25, 2018 - 15:18 -- Open Access
Author(s): 
Laurence Vachot-Ganée, Nimol Khim, Didier Ménard, et al.
Reference: 
Malaria Journal 2018 17:175, 24 April 2018

The K13 ready-to-use bMx prototype assay, considered by the end-users as a user-friendly assay to perform (in shorter time than the K13 reference assay) and easy to interpret, was found to require less budget planning and had fewer logistical constraints.

NOT Open Access | Remodeling of the malaria parasite and host human red cell by vesicle amplification that induces artemisinin resistance

March 20, 2018 - 14:32 -- NOT Open Access
Author(s): 
Souvik Bhattacharjee, Isabelle Coppens, Kasturi Haldar, et al.
Reference: 
Blood 2018 Volume: 131 Issue: 11 Pages: 1234-1247

Artemisinin resistance threatens worldwide malaria control and elimination.

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