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Using Plasmodium knowlesi as a model for screening Plasmodium vivax blood-stage malaria vaccine targets reveals new candidates

July 6, 2021 - 14:38 -- Open Access
Ndegwa DN, Kundu P, Hostetler JB, Marin-Menendez A, Sanderson T, Mwikali K, Verzier LH, Coyle R, Adjalley S, Rayner JC
PLoS Pathog. 2021 Jul 1;17(7):e1008864

Plasmodium vivax is responsible for the majority of malaria cases outside Africa. Unlike P. falciparum, the P. vivax life-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine against P. vivax blood stages would limit symptoms and pathology from such recurrent infections, and therefore could play a critical role in the control of this species. Vaccine development in P. vivax, however, lags considerably behind P. falciparum, which has many identified targets with several having transitioned to Phase II testing.

NOT Open Access | Structural analyses of the malaria parasite aminoacyl-tRNA synthetases provide new avenues for antimalarial drug discovery

June 30, 2021 - 11:28 -- NOT Open Access
Chhibber-Goel J, Yogavel M, Sharma A
Protein Sci. 2021 Jun 28

Malaria is a parasitic illness caused by the genus Plasmodium from the apicomplexan phylum. Five plasmodial species of P. falciparum, P. knowlesi, P. malariae, P. ovale and P. vivax are responsible for causing malaria in humans. According to the World Malaria Report 2019, there were 229 million cases and ~ 0.04 million deaths of which 67% were in children below five years of age.

Activity of Plasmodium vivax promoter elements in Plasmodium knowlesi, and a centromere-containing plasmid that expresses NanoLuc throughout the parasite life cycle

June 9, 2021 - 07:38 -- Open Access
Roberto R. Moraes Barros, Kittisak Thawnashom, Thomas E. Wellems, et al.
Malaria Journal 2021 20:247, 5 June 2021

Plasmodium knowlesi is now the major cause of human malaria in Malaysia, complicating malaria control efforts that must attend to the elimination of multiple Plasmodium species. Recent advances in the cultivation of P. knowlesi erythrocytic-stage parasites in vitro, transformation with exogenous DNA, and infection of mosquitoes with gametocytes from culture have opened up studies of this pathogen without the need for resource-intensive and costly non-human primate (NHP) models. For further understanding and development of methods for parasite transformation in malaria research, this study examined the activity of various trans-species transcriptional control sequences and the influence of Plasmodium vivax centromeric (pvcen) repeats in plasmid-transfected P. knowlesi parasites.

Endothelial glycocalyx degradation and disease severity in Plasmodium vivax and Plasmodium knowlesi malaria

May 12, 2021 - 09:43 -- Open Access
Barber BE, Grigg MJ, Piera KA, Chen Y, William T, Weinberg JB, Yeo TW, Anstey NM
Sci Rep. 2021 May 7;11(1):9741

Degradation of the endothelial glycocalyx is associated with mortality in adult falciparum malaria. However, its role in the pathogenesis of non-falciparum malaria is unknown. In Malaysian patients with knowlesi (n = 200) and vivax (n = 61) malaria, and in healthy controls (n = 50), we measured glycocalyx breakdown products plasma syndecan-1 and urinary glycosaminoglycans, and evaluated correlations with biomarkers of disease severity. Urinary glycosaminoglycans were increased in patients with knowlesi and vivax malaria compared to healthy controls, and in knowlesi malaria were highest in those with severe disease.

NOT Open Access | Exploring Heteroaromatic Rings as a Replacement for the Labile Amide of Antiplasmodial Pantothenamides

April 6, 2021 - 14:29 -- NOT Open Access
Guan J, Spry C, Auclair K, et al.
J Med Chem. 2021 Apr 1

Malaria-causing Plasmodium parasites are developing resistance to antimalarial drugs, providing the impetus for new antiplasmodials. Although pantothenamides show potent antiplasmodial activity, hydrolysis by pantetheinases/vanins present in blood rapidly inactivates them. We herein report the facile synthesis and biological activity of a small library of pantothenamide analogues in which the labile amide group is replaced with a heteroaromatic ring.

Reduced circulating dendritic cells in acute Plasmodium knowlesi and Plasmodium falciparum malaria despite elevated plasma Flt3 ligand levels

February 17, 2021 - 09:15 -- Open Access
Jessica R. Loughland, Tonia Woodberry, Gabriela Minigo, et al.
Malaria Journal 2021 20:97, 16 February 2021

Plasmodium falciparum malaria increases plasma levels of the cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic factor associated with dendritic cell (DC) expansion. It is unknown if the zoonotic parasite Plasmodium knowlesi impacts Flt3L or DC in human malaria. This study investigated circulating DC and Flt3L associations in adult malaria and in submicroscopic experimental infection.

Plasmodium-a brief introduction to the parasites causing human malaria and their basic biology

January 16, 2021 - 09:54 -- Open Access
Sato S
J Physiol Anthropol. 2021 Jan 7;40(1):1

Malaria is one of the most devastating infectious diseases of humans. It is problematic clinically and economically as it prevails in poorer countries and regions, strongly hindering socioeconomic development. The causative agents of malaria are unicellular protozoan parasites belonging to the genus Plasmodium. These parasites infect not only humans but also other vertebrates, from reptiles and birds to mammals. To date, over 200 species of Plasmodium have been formally described, and each species infects a certain range of hosts.

Malaria parasites in macaques in Thailand: stump-tailed macaques (Macaca arctoides) are new natural hosts for Plasmodium knowlesi, Plasmodium inui, Plasmodium coatneyi and Plasmodium fieldi

October 6, 2020 - 12:39 -- Open Access
Wirasak Fungfuang, Chanya Udom, Daraka Tongthainan, Khamisah Abdul Kadir and Balbir Singh
Malaria Journal 2020 19:350, 1 October 2020

Certain species of macaques are natural hosts of Plasmodium knowlesi and Plasmodium cynomolgi, which can both cause malaria in humans, and Plasmodium inui, which can be experimentally transmitted to humans. A significant number of zoonotic malaria cases have been reported in humans throughout Southeast Asia, including Thailand. There have been only two studies undertaken in Thailand to identify malaria parasites in non-human primates in 6 provinces. The objective of this study was to determine the prevalence of P. knowlesi, P. cynomolgi, P. inui, Plasmodium coatneyi and Plasmodium fieldi in non-human primates from 4 new locations in Thailand.

Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models

September 1, 2020 - 10:12 -- Open Access
Melanie J. Shears, Annette M. Seilie, B. Kim Lee Sim, Stephen L. Hoffman and Sean C. Murphy
Malaria Journal 2020 19:313, 31 August 2020

Rhesus macaques are valuable pre-clinical models for malaria vaccine development. The Plasmodium knowlesi/rhesus and Plasmodium falciparum/rhesus models are two established platforms for malaria vaccine testing, and both have previously been used to assess live-attenuated sporozoite vaccines. However, there is evidence that the susceptibility of the rhesus liver to P. knowlesi versus P. falciparum sporozoites likely differs, potentially complicating comparisons between these two platforms.

Comparative evaluation of two commercial real-time PCR kits (QuantiFast™ and abTES™) for the detection of Plasmodium knowlesi and other Plasmodium species in Sabah, Malaysia

September 1, 2020 - 09:48 -- Open Access
Nor Afizah Nuin, Angelica F. Tan, Matthew J. Grigg, et al.
Malaria Journal 2020 19:306, 27 August 2020

The monkey parasite Plasmodium knowlesi is an emerging public health issue in Southeast Asia. In Sabah, Malaysia, P. knowlesi is now the dominant cause of human malaria. Molecular detection methods for P. knowlesi are essential for accurate diagnosis and in monitoring progress towards malaria elimination of other Plasmodium species. However, recent commercially available PCR malaria kits have unpublished P. knowlesi gene targets or have not been evaluated against clinical samples.


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