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plasmodium falciparum

Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility

September 24, 2020 - 14:02 -- Open Access
Author(s): 
Harding CR, Sidik SM, Petrova B, Gnädig NF, Okombo J, Herneisen AL, Ward KE, Markus BM, Boydston EA, Fidock DA, Lourido S
Reference: 
Nat Commun. 2020 Sep 23;11(1):4813.

Artemisinins have revolutionized the treatment of Plasmodium falciparum malaria; however, resistance threatens to undermine global control efforts. To broadly explore artemisinin susceptibility in apicomplexan parasites, we employ genome-scale CRISPR screens recently developed for Toxoplasma gondii to discover sensitizing and desensitizing mutations.

Dispensable Role of Mitochondrial Fission Protein 1 (Fis1) in the Erythrocytic Development of Plasmodium falciparum

September 24, 2020 - 14:01 -- Open Access
Author(s): 
Maruthi M, Ling L, Zhou J, Ke H
Reference: 
mSphere. 2020 Sep 23;5(5):e00579-20

Malaria remains a huge global health burden, and control of this disease has run into a severe bottleneck. To defeat malaria and reach the goal of eradication, a deep understanding of the parasite biology is urgently needed. The mitochondrion of the malaria parasite is essential throughout the parasite's life cycle and has been validated as a clinical drug target. In the asexual development of Plasmodium spp., the single mitochondrion grows from a small tubular structure to a complex branched network.

NOT Open Access | Structural Basis for Inhibitor Potency and Selectivity of Plasmodium falciparum Phosphatidylinositol 4-kinase Inhibitors

September 24, 2020 - 08:11 -- NOT Open Access
Author(s): 
Fienberg S, Eyermann CJ, Arendse L, Basarab GS, McPhail J, Burke JE, Chibale K
Reference: 
ACS Infect Dis. 2020 Sep 23

Plasmodium falciparum phosphatidylinositol 4-kinase (PfPI4K) has emerged as a promising new drug target for novel antimalarial therapeutics. In the absence of a reliable high-resolution three-dimensional structure, a homology model of PfPI4K was built as a tool for structure-based drug design.

NOT Open Access | Methnaridine is an orally bioavailable, fast-killing and long-acting antimalarial agent that cures Plasmodium infections in mice

September 23, 2020 - 09:36 -- NOT Open Access
Author(s): 
Wang W, Yao J, Chen Z, Sun Y, Shi Y, Wei Y, Zhou H, Yu Y, Li S, Duan L
Reference: 
Br J Pharmacol. 2020 Sep 22

Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy.

Estimating Annual Fluctuations in Malaria Transmission Intensity and in the Use of Malaria Control Interventions in Five Sub-Saharan African Countries

September 23, 2020 - 09:34 -- Open Access
Author(s): 
Rts S Epidemiology Epi-Mal-Study Group, Adeniji E, Asante KP, Wéry S, et al.
Reference: 
Am J Trop Med Hyg. 2020 Sep 21

RTS,S/AS01E malaria vaccine safety, effectiveness, and impact will be assessed in pre- and post-vaccine introduction studies, comparing the occurrence of malaria cases and adverse events in vaccinated versus unvaccinated children. Because those comparisons may be confounded by potential year-to-year fluctuations in malaria transmission intensity and malaria control intervention usage, the latter should be carefully monitored to adequately adjust the analyses.

Will More of the Same Achieve Malaria Elimination? Results from an Integrated Macroeconomic Epidemiological Demographic Model

September 23, 2020 - 09:32 -- Open Access
Author(s): 
Smith RD, Keogh-Brown MR, Chico RM, Bretscher MT, Drakeley C, Jensen HT
Reference: 
Am J Trop Med Hyg. 2020 Sep 21

Historic levels of funding have reduced the global burden of malaria in recent years. Questions remain, however, as to whether scaling up interventions, in parallel with economic growth, has made malaria elimination more likely today than previously. The consequences of "trying but failing" to eliminate malaria are also uncertain. Reduced malaria exposure decreases the acquisition of semi-immunity during childhood, a necessary phase of the immunological transition that occurs on the pathway to malaria elimination.

Ultrasensitive CRISPR-based diagnostic for field-applicable detection of Plasmodium species in symptomatic and asymptomatic malaria

September 23, 2020 - 09:25 -- Open Access
Author(s): 
Lee RA, Puig H, Nguyen PQ, Angenent-Mari NM, Donghia NM, McGee JP, Dvorin JD, Klapperich CM, Pollock NR, Collins JJ
Reference: 
Proc Natl Acad Sci U S A. 2020 Sep 21:202010196

Asymptomatic carriers of Plasmodium parasites hamper malaria control and eradication. Achieving malaria eradication requires ultrasensitive diagnostics for low parasite density infections (<100 parasites per microliter blood) that work in resource-limited settings (RLS). Sensitive point-of-care diagnostics are also lacking for nonfalciparum malaria, which is characterized by lower density infections and may require additional therapy for radical cure.

NOT Open Access | Red blood cell tension protects against severe malaria in the Dantu blood group

September 23, 2020 - 09:23 -- NOT Open Access
Author(s): 
Kariuki SN, Marin-Menendez A, Rayner JC, et al.
Reference: 
Nature. 2020 Sep 16

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine.

Modelling and mapping the intra-urban spatial distribution of Plasmodium falciparum parasite rate using very-high-resolution satellite derived indicators

September 23, 2020 - 09:04 -- Open Access
Author(s): 
Georganos S, Brousse O, Lennert M, et al.
Reference: 
Int J Health Geogr. 2020 Sep 21;19(1):38

The rapid and often uncontrolled rural–urban migration in Sub-Saharan Africa is transforming urban landscapes expected to provide shelter for more than 50% of Africa’s population by 2030. Consequently, the burden of malaria is increasingly affecting the urban population, while socio-economic inequalities within the urban settings are intensified. Few studies, relying mostly on moderate to high resolution datasets and standard predictive variables such as building and vegetation density, have tackled the topic of modeling intra-urban malaria at the city extent. In this research, we investigate the contribution of very-high-resolution satellite-derived land-use, land-cover and population information for modeling the spatial distribution of urban malaria prevalence across large spatial extents. As case studies, we apply our methods to two Sub-Saharan African cities, Kampala and Dar es Salaam.

Purification and initial characterization of Plasmodium falciparum K(+) channels, PfKch1 and PfKch2 produced in Saccharomyces cerevisiae

September 23, 2020 - 09:02 -- Open Access
Author(s): 
Molbaek K, Tejada M, Ricke CH, Scharff-Poulsen P, Ellekvist P, Helix-Nielsen C, Kumar N, Klaerke DA, Pedersen PA
Reference: 
Microb Cell Fact. 2020 Sep 21;19(1):183

Resistance towards known antimalarial drugs poses a significant problem, urging for novel drugs that target vital proteins in the malaria parasite Plasmodium falciparum. However, recombinant production of malaria proteins is notoriously difficult. To address this, we have investigated two putative K+ channels, PfKch1 and PfKch2, identified in the P. falciparum genome.

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