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R. S. Katete
R. S. Katete
Alena Pance
Alena Pance
Nature Reviews
Nature Reviews
Microbiology (2019)
Microbiology (2019)
9 January 2019
9 January 2019
Pregnant women are highly susceptible to Plasmodium falciparum malaria, leading to substantial maternal, perinatal, and infant mortality. While malaria vaccine development has made significant progress in recent years, no trials of malaria vaccines have ever been conducted in pregnant women. In December 2016, an expert meeting was convened at NIAID, NIH, in Rockville, Maryland to deliberate on the rationale and design of malaria vaccine trials in pregnant women.
Pregnant women are highly susceptible to Plasmodium falciparum malaria, leading to substantial maternal, perinatal, and infant mortality. While malaria vaccine development has made significant progress in recent years, no trials of malaria vaccines have ever been conducted in pregnant women. In December 2016, an expert meeting was convened at NIAID, NIH, in Rockville, Maryland to deliberate on the rationale and design of malaria vaccine trials in pregnant women.
Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
Expert Rev Vaccines. 2017 Jul;16(7):1-13
Expert Rev Vaccines. 2017 Jul;16(7):1-13
Trends in Parasitology, Volume 34, Issue 10, October 2018.
Trends in Parasitology, Volume 34, Issue 10, October 2018.
Marc H.V.Van Regenmortel.
Marc H.V.Van Regenmortel.
EMBO Rep. 2004 November; 5(11): 1016–1020.
EMBO Rep. 2004 November; 5(11): 1016–1020.
The intracellular development and differentiation of the Plasmodium parasite in the host liver is a prerequisite for the actual onset of malaria disease pathology. Since liver-stage infection is clinically silent and can be completely eliminated by sterilizing immune responses, it is a promising target for urgently needed innovative antimalarial drugs and/or vaccines. Discovered more than 65 years ago, these stages remain poorly understood regarding their molecular repertoire and interaction with their host cells in comparison to the pathogenic erythrocytic stages.
The intracellular development and differentiation of the Plasmodium parasite in the host liver is a prerequisite for the actual onset of malaria disease pathology. Since liver-stage infection is clinically silent and can be completely eliminated by sterilizing immune responses, it is a promising target for urgently needed innovative antimalarial drugs and/or vaccines. Discovered more than 65 years ago, these stages remain poorly understood regarding their molecular repertoire and interaction with their host cells in comparison to the pathogenic erythrocytic stages.
How the 'cat parasite' could help find a treatment for malaria
The toxoplasma parasite is an important experimental model for this group, and it is often used to learn about the biology of other parasites, such as those that cause malaria. This is because the cells of toxoplasma and malaria-causing parasites contain the same unique structures..
The toxoplasma parasite is an important experimental model for this group, and it is often used to learn about the biology of other parasites, such as those that cause malaria. This is because the cells of toxoplasma and malaria-causing parasites contain the same unique structures..
Yvette van Kooyk
Yvette van Kooyk
A vaccine platform developed from a synthetic polymeric glyco-adjuvant and reversibly conjugated to an antigen was shown to target dendritic cells leading to cellular and humoral immune response against malaria.
A vaccine platform developed from a synthetic polymeric glyco-adjuvant and reversibly conjugated to an antigen was shown to target dendritic cells leading to cellular and humoral immune response against malaria.
Nature Materials volume 18, pages94–96 (2019)
Nature Materials volume 18, pages94–96 (2019)
Nature Reviews Drug Discovery volume14, pages424–442 (2015)
Nature Reviews Drug Discovery volume14, pages424–442 (2015)
Volume 24, Issue 1, 11 July 2018, Pages 43-56
Malaria Vaccine Candidates in Clinical Development
Date: March 27, 2017
Source: Centre for Research in Agricultural Genomics
Summary: Scientists have discovered a gene that allows to double the production of artemisinin in the Artemisia annua plant. The artemisinin-based combination therapy (ACT) is the standard treatment for malaria worldwide. The new article presents an important step towards reducing artemisinin production costs.
Artemisia annua leaf is seen under the scanning electron miscroscope. The glandular trichomes (with a more circular shape) which produce artemisinin are clearly visible.
Credit: CRAG Journal Reference:
- Luis Matías-Hernández, Weimin Jiang, Ke Yang, Kexuan Tang, Peter E. Brodelius, Soraya Pelaz. AaMYB1 and its orthologue AtMYB61 affect terpene metabolism and trichome development in Artemisia annua and Arabidopsis thaliana. The Plant Journal, 2017; DOI: 10.1111/tpj.13509
Date: April 11, 2016
Source: National University of Singapore
Summary: The World Health Organization recommends treating malaria with artemisinin combination therapy (ACT), consisting of artemisinin and another drug. However, malaria resistance to ACT has already started emerging in Southeast Asia. Scientists have now developed a novel hybrid drug that combines a killing factor with an agent that reverses drug resistance. The hybrid drug is very effective against chloroquine- and artemisinin-resistant malaria, presenting a new avenue for treating resistant malaria.
Journal Reference:
Aicha Boudhar, Xiao Wei Ng, Chiew Yee Loh, Wan Ni Chia, Zhi Ming Tan, Francois Nosten, Brian W. Dymock, Kevin S. W. Tan. Overcoming Chloroquine Resistance in Malaria: Design, Synthesis and Structure-Activity Relationships of Novel Hybrid Compounds. Antimicrobial Agents and Chemotherapy, 2016; AAC.02476-15 DOI: 10.1128/AAC.02476-15
'Anti-malarial for mosquitoes': The British scientist behind a major malaria breakthrough
Exclusive: Compounds identified that could prevent mosquitoes from spreading the disease
Shehab Khan@ShehabKhan Saturday 7 April 2018 18:08
Increasing antimalarial drug resistance once again threatens effective antimalarial drug treatment, malaria control, and elimination. Artemisinin combination therapies (ACTs) are first-line treatment for uncomplicated falciparum malaria in all endemic countries, yet partial resistance to artemisinins has emerged in the Greater Mekong Subregion. Concomitant emergence of partner drug resistance is now causing high ACT treatment failure rates in several areas. Genetic markers for artemisinin resistance and several of the partner drugs have been established, greatly facilitating surveillance. Single point mutations in the gene coding for the Kelch propeller domain of the K13 protein strongly correlate with artemisinin resistance. Novel regimens and strategies using existing antimalarial drugs will be needed until novel compounds can be deployed. Elimination of artemisinin resistance will imply elimination of all falciparum malaria from the same areas. In vivax malaria, chloroquine resistance is an increasing problem.
Published in Advance March 13, 2017, doi: 10.1101/cshperspect.a025619Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved
Souvik Bhattacharjee, Isabelle Coppens, Alassane Mbengue, Niraja Suresh, Mehdi Ghorbal, Zdenek Slouka, Innocent Safeukui, Hsin-Yao Tang, David W. Speicher, Robert V. Stahelin, Narla Mohandas and Kasturi Haldar
Blood 2018 131:1234-1247; doi: https://doi.org/10.1182/blood-2017-11-814665
Artemisinin resistance threatens worldwide malaria control and elimination. Elevation of phosphatidylinositol-3-phosphate (PI3P) can induce resistance in blood stages of Plasmodium falciparum. The parasite unfolded protein response (UPR) has also been implicated as a proteostatic mechanism that may diminish artemisinin-induced toxic proteopathy. How PI3P acts and its connection to the UPR remain unknown, although both are conferred by mutation in P falciparum Kelch13 (K13), the marker of artemisinin resistance. Here we used cryoimmunoelectron microscopy to show that K13 concentrates at PI3P tubules/vesicles of the parasite’s endoplasmic reticulum (ER) in infected red cells. K13 colocalizes and copurifies with the major virulence adhesin PfEMP1. The PfEMP1-K13 proteome is comprehensively enriched in multiple proteostasis systems of protein export, quality control, and folding in the ER and cytoplasm and UPR. Synthetic elevation of PI3P that induces resistance in absence of K13 mutation also yields signatures of proteostasis and clinical resistance. These findings imply a key role for PI3P-vesicle amplification as a mechanism of resistance of infected red cells. As validation, the major resistance mutation K13C580Y quantitatively increased PI3P tubules/vesicles, exporting them throughout the parasite and the red cell. Chemical inhibitors and fluorescence microscopy showed that alterations in PfEMP1 export to the red cell and cytoadherence of infected cells to a host endothelial receptor are features of multiple K13 mutants. Together these data suggest that amplified PI3P vesicles disseminate widespread proteostatic capacity that may neutralize artemisinins toxic proteopathy and implicate a role for the host red cell in artemisinin resistance. The mechanistic insights generated will have an impact on malaria drug development.
Paul Sondo, Karim Derra, Thierry Lefevre, Seydou Diallo-Nakanabo, Zekiba Tarnagda, Odile Zampa, Adama Kazienga, Innocent Valea, Hermann Sorgho, Jean-Bosco Ouedraogo, Tinga Robert Guiguemde & Halidou Tinto
Scientific Reports volume 9, Article number: 127 (2019)
This study provides evidence that P. falciparum genetic diversity influenced the severity of particular malaria symptoms and supports the existence of within-host competition in genetically diverse P. falciparum
15 January 2019
The life cycle of the human Plasmodium species.
(Adapted from White NJ. Antimalarial drug resistance. J Clin Invest 2004;113:1084–92.)
Davis TM, Moore BR, Salman S, Page-Sharp M, Batty KT, Manning L.
The use of pharmacokinetic (PK) and pharmacodynamic (PD) data to inform antimalarial treatment regimens has accelerated in the past few decades, due in no small part to the stimulus provided by progressive development of parasite resistance to most of the currently available drugs. An understanding of the disposition, interactions, efficacy and toxicity of the mainstay of contemporary antimalarial treatment, artemisinin combination therapy (ACT), has been facilitated by PK/PD studies which have been used to refine treatment regimens across the spectrum of disease, especially in special groups including young children and pregnant women. The present review highlights recent clinically-important examples of the ways in which these quantitative pharmacology tools have been applied to improve ACT, as well as 8-aminoquinoline use and the characterisation of novel antimalarial therapies such as the spiroindolones.
Expert Rev Clin Pharmacol. 2016;9(2):303-16. doi: 10.1586/17512433.2016.1129273. Epub 2015 Dec 25.
Adrian V. S. Hill
There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates
Philos Trans R Soc Lond B Biol Sci. 2011 Oct 12; 366(1579): 2806–2814.
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