Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy

Abstract

Purpose of Review Five years have passed since the World Health Organization released its Global Technical Strategy for Malaria (GTS). In that time, progress against malaria has plateaued. This review focuses on the implications of antimalarial drug resistance for the GTS and how interim progress in parasite genomics and antimalarial pharmacology offer a bulwark against it. Recent Findings For the first time, drug resistance–conferring genes have been identified and validated before their global expansion in malaria parasite populations. More efficient methods for their detection and elaboration have been developed, although low-density infections and polyclonality remain a nuisance to be solved. Clinical trials of alternative regimens for multidrug-resistant malaria have delivered promising results. New agents continue down the development pipeline, while a nascent infrastructure in sub-Saharan Africa for conducting phase I trials and trials of transmission-blocking agents has come to fruition after years of preparation. Summary These and other developments can help inform the GTS as the world looks ahead to the next two decades of its implementation. To remain ahead of the threat that drug resistance poses, wider application of genomic-based surveillance and optimization of existing and forthcoming antimalarial drugs are essential.

Potential Opportunities and Challenges of Deploying Next Generation Sequencing and CRISPR-Cas Systems to Support Diagnostics and Surveillance Towards Malaria Control and Elimination in Africa

“…However, in 2020, malaria deaths increased from 2019 levels, with the majority of both cases and deaths involving children and pregnant women from sub-Saharan Africa (SSA) ( World Health Organization, 2021 ). The increase in malaria cases can be partially explained by the emergence and spread of insecticide resistance in Anopheles populations ( Kisinza et al., 2017 ⁠ and antimalarial resistance in parasites ( Dondorp et al., 2009 ; Haldar et al., 2018 ; Ippolito et al., 2021 ) both of which threaten the effectiveness of the major malaria interventions, long-lasting insecticide treated bed-nets (LLINs), indoor residual spraying (IRS) and antimalarial drugs ( Tawe et al., 2018 ; Apinjoh et al., 2019 ; Morgan et al., 2020 ). Increased malaria cases in 2020 were also attributed to the COVID-19 pandemic, which was believed to have disrupted malaria control activities ( World Health Organization, 2021 ).…”

The Artemiside-artemisox-artemisone-M1 Tetrad: Efficacies Against Blood Stage P.<em> falciparum</em> Parasites, DMPK Properties, and the Case for Artemiside

“…Overall these amino-artemisinins are pan-reactive against all blood stages of Pf. Activities against liver stage P. berghei sporozoites are IC50 81.3 nM for artemiside and 28.3 nM for artemisone; in comparison the activity of artemether 3 is >10 4 (Table S4c, Supplementary Material) [7].…”

“…Given the problems both of enhanced tolerance of the malaria parasite Plasmodium falciparum (Pf) to the current clinical artemisinins (Figure 1) and formal resistance to the antimalarial partner drug in artemisinin combination therapies (ACTs) [1,2,3,4,5], rational new triple artemisinin combination therapies (TACTs) based on discrete consideration of mechanism of action of the components are urgently required [6,7]. We thereby focus on newer artemisinin derivatives that are pan-reactive against blood stage parasites, a redox active second drug such as methylene blue, phenoxazine or naphthoquinone which displays synergism with the artemisinins [6,7] and a third drug type such as a quinolone that has a distinct target [8].…”

Molecular analysis of Bio-makers of Chloroquine resistance in Plasmodium falciparum Isolate from Gombe Local Government Area, Gombe State, Nigeria

“…Chloroquine resistance emanates from Southeast Asia [28] and South America [29] as early as the late fifties [30] and within two decades the resistant strain spread to the vast majority of malaria-endemic countries [31] including Sub Saharan Africa and particularly Nigeria [32]. This led to a decline in the efficacy of chloroquine, as a result, almost all countries changed their treatment policy from chloroquine to other alternative antimalarials drugs with high efficacy, such as antifolates, mefloquine and artemisinin derivatives [33].…”