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Genetic diversity of the Plasmodium falciparum GTP-cyclohydrolase 1, dihydrofolate reductase and dihydropteroate synthetase genes reveals new insights into sulfadoxine-pyrimethamine antimalarial drug resistance

January 6, 2021 - 13:10 -- Open Access
Turkiewicz A, Manko E, Sutherland CJ, Diez Benavente E, Campino S, Clark TG
PLoS Genet. 2020 Dec 31;16(12):e1009268

Plasmodium falciparum parasites resistant to antimalarial treatments have hindered malaria disease control. Sulfadoxine-pyrimethamine (SP) was used globally as a first-line treatment for malaria after wide-spread resistance to chloroquine emerged and, although replaced by artemisinin combinations, is currently used as intermittent preventive treatment of malaria in pregnancy and in young children as part of seasonal malaria chemoprophylaxis in sub-Saharan Africa. The emergence of SP-resistant parasites has been predominantly driven by cumulative build-up of mutations in the dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps) genes, but additional amplifications in the folate pathway rate-limiting pfgch1 gene and promoter, have recently been described.

NOT Open Access | Multiple SNPs detection for antimalarial pyrimethamine resistance via allele-specific PCR coupled with gold nanoparticles-based lateral flow biosensor

December 30, 2020 - 13:45 -- NOT Open Access
Jiang T, Huang Y, Cheng W, Sun Y, Wei W, Wu K, Shen C, Fu X, Dong H, Li J.
Antimicrob Agents Chemother. 2020 Dec 23:AAC.01063-20

Molecular genotyping holds tremendous potential to detect antimalarial drug resistance (ADR) related to single nucleotide polymorphisms (SNPs). However, it suffers from complicated procedures and expensive instruments. Thus, rapid point-of-care testing (POCT) molecular tools are urgently needed for field survey and clinical use. Herein, a POCT platform consisted of multiple allele-specific PCR (AS-PCR) and gold nanoparticles (AuNPs) based lateral flow biosensor was designed and developed for SNPs detection of Plasmodium falciparum dihydrofolate reductase (pfdhfr) gene related to pyrimethamine resistance.

NOT Open Access | Age reduces resistance and tolerance in malaria-infected mice

December 30, 2020 - 13:32 -- NOT Open Access
Sorci G, Léchenault-Bergerot C, Faivre B
Infect Genet Evol. 2020 Dec 25:104698

Once infected, hosts can rely on two strategies to cope with parasites: fight them (resist the infection) or minimize the damage they induce (tolerate the infection). While there is evidence that aging reduces resistance, how tolerance varies as hosts become old has been barely studied. Here, we used a rodent malaria parasite (Plasmodium yoelii) to investigate whether 2- and 12-month old house mice differ in their capacity to resist and tolerate the infection.

NOT Open Access | Recent advances in Quantitative Structure-Activity Relationship models of antimalarial drugs

December 29, 2020 - 15:15 -- NOT Open Access
Ojha PK, Kumar V, Roy J, Roy K
Expert Opin Drug Discov. 2020 Dec 26

Due to emerging resistance to the first-line artemisinin-based antimalarials and lack of efficient vaccines and limited chemotherapeutic alternatives, there is an urgent need to develop new antimalarial compounds. In this regard, quantitative structure-activity relationship (QSAR) modeling can provide essential information about required physicochemical properties and structural parameters of antimalarial drug candidates.

Is malaria parasite ex-vivo viability reduction really "superior" to observed parasite clearance rate

December 29, 2020 - 15:06 -- Open Access
White NJ, Watson JA
J Infect Dis. 2020 Dec 28:jiaa790

Ina study of 10 P. falciparum infected volunteers with submicroscopic parasitemias given a single 200mg dose of artesunate, Rebelo et al (1) report a substantial difference in the ex-vivo growth of sequentially sampled circulating ring stage(2) parasites comparing infections with artemisin insensitive (Pfkelch wild type) and artemisinin resistant(PfkelchR539T)parasites.

Investigation of DDT resistance mechanisms in Anopheles funestus populations from northern and southern Benin reveals a key role of the GSTe2 gene

December 23, 2020 - 09:53 -- Open Access
Genevieve M. Tchigossou, Seun M. Atoyebi, Romaric Akoton, Eric Tossou, Djegbe Innocent, Jacob Riveron, Helen Irving, Akadiri Yessoufou, Charles Wondji and Rousseau Djouaka
Malaria Journal 2020 19:456, 17 December 2020

Understanding the molecular basis of insecticide resistance in mosquito, such as Anopheles funestus, is an important step in developing strategies to mitigate the resistance problem. This study aims to assess the role of the GSTe2 gene in DDT resistance and determine the genetic diversity of this gene in An. funestus.

A Systematic Literature Review of Microscopy Methods Reported in Malaria Clinical Trials

December 23, 2020 - 08:50 -- Open Access
Das D, Dahal P, Dhorda M, Citarella BW, Kennon K, Stepniewska K, Felger I, Chappuis F, Guerin PJ
Am J Trop Med Hyg. 2020 Dec 21

Microscopy of stained blood films is essential for the diagnosis of malaria, differentiation of parasite species, and estimation of parasite density performed for assessments of antimalarial drug efficacy. The accuracy and comparability of these measures over time and space are vital to discern the emergence or spread of antimalarial drug resistance. Although evidence-based guidelines for malaria microscopy methods exist, the age-old microscopy techniques for parasitological assessments are subject to considerable methodological variations.

Increased prevalence of pfdhfr and pfdhps mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates from Jazan Region, Southwestern Saudi Arabia: important implications for malaria treatment policy

December 3, 2020 - 12:58 -- Open Access
Aymen M. Madkhali, Hesham M. Al-Mekhlafi, Wahib M. Atroosh, Ahmad Hassn Ghzwani, Khalid Ammash Zain, Ahmed A. Abdulhaq, Khalid Y. Ghailan, Alkhansa A. Anwar and Zaki M. Eisa
Malaria Journal 2020 19:446, 2 December 2020

Despite significant progress in eliminating malaria from the Kingdom of Saudi Arabia, the disease is still endemic in the southwestern region of the country. Artesunate plus sulfadoxine–pyrimethamine (AS + SP) has been used in Saudi Arabia since 2007 as a first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to artemisinin and sulfadoxine–pyrimethamine (SP) resistance in P. falciparum parasites circulating in Jazan region, southwestern Saudi Arabia.

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

November 18, 2020 - 12:07 -- Open Access
Mbaba M, Golding TM, Smith GS
Molecules. 2020 Nov 12;25(22):E5276

In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance.

Three signatures of adaptive polymorphism exemplified by malaria-associated genes

November 18, 2020 - 10:58 -- Open Access
Tennessen JA, Duraisingh MT
Mol Biol Evol. 2020 Nov 13:msaa294

Malaria has been one of the strongest selective pressures on our species. Many of the best-characterized cases of adaptive evolution in humans are in genes tied to malaria resistance. However, the complex evolutionary patterns at these genes are poorly captured by standard scans for non-neutral evolution. Here we present three new statistical tests for selection based on population genetic patterns that are observed more than once among key malaria resistance loci.


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