A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms.

BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

A systematic review on anti-malarial drug discovery and antiplasmodial potential of green synthesis mediated metal nanoparticles: overview, challenges and future perspectives.

BACKGROUND: The recent emergence in Southeast Asia of artemisinin resistance poses major threats to malaria control and elimination globally. Green nanotechnologies can constitute interesting tools for discovering anti-malarial medicines. This systematic review focused on the green synthesis of metal nanoparticles as potential source of new antiplasmodial drugs. METHODS: Seven electronic database were used following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 17 papers were included in the systematic review. 82.4% of the studies used plant leaves to produce nanoparticles (NPs) while three studies used microorganisms, including bacteria and fungi. Silver was the main metal precursor for the synthesis of NPs. The majority of studies obtained nanoparticles spherical in shape, with sizes ranging between 4 and 65 nm, and reported no or little cytotoxic effect of the NPs. Results based on 50% inhibitory concentration (IC50) varied between studies but, in general, could be divided into three NP categories; (i) those more effective than positive controls, (ii) those more effective than corresponding plant extracts and, (iii) those less effective than the positive controls or plant extracts. CONCLUSIONS: This study highlights the high antiplasmodial potential of green-synthesized metal nanoparticles thereby underscoring the possibility to find and develop new anti-malarial drugs based on green synthesis approaches. However, the review also highlights the need for extensive in vitro and in vivo studies to confirm their safety in humans and the elucidation of the mechanism of action.

Green-synthesized metal nanoparticles for mosquito control: A systematic review about their toxicity on non-target organisms.

Studies capturing the high efficiency of green-synthesized metal nanoparticles (NPs) in targeting mosquito vectors of the world's main infectious diseases suggest the NPs' possible utilization as bio-insecticides. However, it is necessary to confirm that these potential bio-insecticides are not harmful to non-target organisms that are often sympatric and natural enemies of the vectors of these diseases. In this systematic review, we comprehensively analyse the content of 56 publications focused on the potentially deleterious effects of NPs on these non-target organisms. Current research on biosynthesised NPs, characterization, and impact on mosquito vectors and non-target larvivorous organisms is reviewed and critically discussed. Finally, we pinpoint some major challenges that merit future investigation. Plants (87.5%) were mainly used for synthesizing NPs in the studies. NPs were found to be spherical or mainly spherical in shape with a large distribution size. In most of the included studies, NPs showed interesting mosquitocidal activity (LC50 < 50 ppm). Some plant families (e.g., Meliaceae, Poaceae, Lamiaceae) have produced NPs with a particularly high larvicidal and pupicidal activity (LC50 < 10 ppm). Regarding non-target organisms, most of the studies concluded that NPs were safe to them, with boosted predatory activity in NP-treated milieu. In contrast, some studies reported NP-elicited adverse effects (i.e., genotoxic, nuclear, and enzymatic effects) on these non-target organisms. This review outlines the promising mosquitocidal effects of biosynthesized NPs, recognizing that NPs' potential usage is currently limited by the harm NPs are thought pose to non-target organism. It is of utmost importance to investigate green NPs to determine whether laboratory findings have applications in the real world.