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Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar

CiteULike malaria tags - 21 September 2017 - 10:53am
Wellcome Open Research, Vol. 2 (6 September 2017), 81, doi:10.12688/wellcomeopenres.12240.1
Jordi Landier, Ladda Kajeechiwa, May Thwin, Daniel Parker, Victor Chaumeau, Jacher Wiladphaingern, Mallika Imwong, Olivo Miotto, Krittaya Patumrat, Jureeporn Duanguppama, Dominique Cerqueira, Benoit Malleret, Laurent Rénia, Suphak Nosten, Lorenz von Seidlein, Clare Ling, Stéphane Proux, Vincent Corbel, Julie Simpson, Arjen Dondorp, Nicholas White, François Nosten
Categories: malaria news feeds

A genetic screen in rodent malaria parasites identifies five new apicoplast putative membrane transporters, one of which is essential in human malaria parasites

CiteULike malaria tags - 20 September 2017 - 9:23am
Cellular Microbiology (13 September 2017), e12789, doi:10.1111/cmi.12789
Claire Sayers, Vanessa Mollard, Hayley Buchanan, Geoffrey McFadden, Christopher Goodman
Categories: malaria news feeds

PhenoPlasm: a database of disruption phenotypes for malaria parasite genes

CiteULike malaria tags - 4 August 2017 - 8:08am
Wellcome Open Research, Vol. 2 (21 June 2017), 45, doi:10.12688/wellcomeopenres.11896.1
Theo Sanderson, Julian Rayner
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An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

CiteULike malaria tags - 3 August 2017 - 12:39pm
Wellcome Open Research, Vol. 2 (16 June 2017), 42, doi:10.12688/wellcomeopenres.11864.1
Erica Pasini, Ulrike Böhme, Gavin Rutledge, Annemarie Voorberg-Van der Wel, Mandy Sanders, Matt Berriman, Clemens Kocken, Thomas Otto
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Rapid evolution of female-biased genes among four species of Anopheles malaria mosquitoes

CiteULike malaria tags - 3 August 2017 - 12:22pm
Genome Research (26 July 2017), gr.217216.116, doi:10.1101/gr.217216.116

An international, peer-reviewed genome sciences journal featuring outstanding original research that offers novel insights into the biology of all organisms
Francesco Papa, Nikolai Windbichler, Robert Waterhouse, Alessia Cagnetti, Rocco D'Amato, Tania Persampieri, Mara Lawniczak, Tony Nolan, Philippos Papathanos
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The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites

CiteULike malaria tags - 27 July 2017 - 10:09am
PLOS ONE, Vol. 12, No. 7. (21 July 2017), e0181656, doi:10.1371/journal.pone.0181656

Malaria is caused by five different Plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. The two main causes of malaria, P. falciparum and P. vivax, differ in their ability to cause severe disease, mainly due to differences in the cytoadhesion of infected erythrocytes (IE) in the microvasculature. Cytoadhesion of P. falciparum in the brain leads to a large number of deaths each year and is a consequence of exported parasite proteins, some of which modify the erythrocyte cytoskeleton while others such as PfEMP1 project onto the erythrocyte surface where they bind to endothelial cells. Here we investigate the effects of knocking out an exported Hsp70-type chaperone termed Hsp70-x that is present in P. falciparum but not P. vivax. Although the growth of Δhsp70-x parasites was unaffected, the export of PfEMP1 cytoadherence proteins was delayed and Δhsp70-x IE had reduced adhesion. The Δhsp70-x IE were also more rigid than wild-type controls indicating changes in the way the parasites modified their host erythrocyte. To investigate the cause of this, transcriptional and translational changes in exported and chaperone proteins were monitored and some changes were observed. We propose that PfHsp70-x is not essential for survival in vitro, but may be required for the efficient export and functioning of some P. falciparum exported proteins.
Sarah Charnaud, Matthew Dixon, Catherine Nie, Lia Chappell, Paul Sanders, Thomas Nebl, Eric Hanssen, Matthew Berriman, Jo-Anne Chan, Adam Blanch, James Beeson, Julian Rayner, Jude Przyborski, Leann Tilley, Brendan Crabb, Paul Gilson
Categories: malaria news feeds

Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes

CiteULike malaria tags - 20 July 2017 - 12:15pm
Cell, Vol. 170, No. 2. (July 2017), pp. 260-272.e8, doi:10.1016/j.cell.2017.06.030
Ellen Bushell, Ana Gomes, Theo Sanderson, Burcu Anar, Gareth Girling, Colin Herd, Tom Metcalf, Katarzyna Modrzynska, Frank Schwach, Rowena Martin, Michael Mather, Geoffrey McFadden, Leopold Parts, Gavin Rutledge, Akhil Vaidya, Kai Wengelnik, Julian Rayner, Oliver Billker
Categories: malaria news feeds

Rapid identification of genes controlling virulence and immunity in malaria parasites

CiteULike malaria tags - 20 July 2017 - 11:54am
PLOS Pathogens, Vol. 13, No. 7. (12 July 2017), e1006447, doi:10.1371/journal.ppat.1006447

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites. Developing a greater understanding of malaria genetics is a key step in combating the threat posed by the disease. Here we use a novel approach to study two important properties of the parasite; the rate at which parasites grow within a single host, and the means by which parasites are affected by the host immune system. Two malaria strains with different biological properties were crossed in mosquitoes to produce a hybrid population, which was then grown in naïve and vaccinated mice. Parasites with genes conveying increased growth or immune evasion are favoured under natural selection, leaving a signature on the genetic composition of the cross population. We describe a novel mathematical approach to interpret this signature, identifying selected genes within the parasite population. We discover new genetic variants conveying increased within-host growth and resistance to host immunity in a mouse malaria strain. Experimental validation highlights the ability of this rapid experimental process for generating insights into malaria biology.
Hussein Abkallo, Axel Martinelli, Megumi Inoue, Abhinay Ramaprasad, Phonepadith Xangsayarath, Jesse Gitaka, Jianxia Tang, Kazuhide Yahata, Augustin Zoungrana, Hayato Mitaka, Arita Acharjee, Partha Datta, Paul Hunt, Richard Carter, Osamu Kaneko, Ville Mustonen, Christopher Illingworth, Arnab Pain, Richard Culleton
Categories: malaria news feeds

Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection

CiteULike malaria tags - 7 July 2017 - 10:00am
bioRxiv (06 July 2017), 159830, doi:10.1101/159830

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
Shang Ma, Stuart Cahalan, Rakhee Lohia, Gregory LaMonte, Weizheng Zeng, Swetha Murthy, Emma Paytas, Nathan Grubaugh, Ramya Gamini, Laurence Berry, Viktor Lukacs, Tess Whitwam, Meaghan Loud, Andrew Su, Kristian Andersen, Elizabeth Winzeler, Eric Honore, Kai Wengelnik, Ardem Patapoutian
Categories: malaria news feeds

Nutrient sensing modulates malaria parasite virulence

CiteULike malaria tags - 6 July 2017 - 10:50am
Nature, Vol. advance online publication (05 July 2017), doi:10.1038/nature23009
Liliana Mancio-Silva, Ksenija Slavic, Margarida Grilo Ruivo, Ana Grosso, Katarzyna Modrzynska, Iset Vera, Joana Sales-Dias, Ana Gomes, Cameron MacPherson, Pierre Crozet, Mattia Adamo, Elena Baena-Gonzalez, Rita Tewari, Manuel Llinás, Oliver Billker, Maria Mota
Categories: malaria news feeds

Nutrient sensing modulates malaria parasite virulence

CiteULike malaria tags - 6 July 2017 - 4:59am
Nature, Vol. advance online publication (05 July 2017), doi:10.1038/nature23009
Liliana Mancio-Silva, Ksenija Slavic, Margarida Grilo Ruivo, Ana Grosso, Katarzyna Modrzynska, Iset Vera, Joana Sales-Dias, Ana Gomes, Cameron MacPherson, Pierre Crozet, Mattia Adamo, Elena Baena-Gonzalez, Rita Tewari, Manuel Llinás, Oliver Billker, Maria Mota
Categories: malaria news feeds

Panoptes: web-based exploration of large scale genome variation data

CiteULike malaria tags - 30 June 2017 - 9:59am
Bioinformatics (23 June 2017), doi:10.1093/bioinformatics/btx410
Paul Vauterin, Ben Jeffery, Alistair Miles, Roberto Amato, Lee Hart, Ian Wright, Dominic Kwiatkowski
Categories: malaria news feeds

Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies

CiteULike malaria tags - 23 June 2017 - 10:48am
JCI Insight, Vol. 2, No. 12. (15 June 2017), doi:10.1172/jci.insight.93683
Ruth Payne, Sarah Silk, Sean Elias, Kathryn Milne, Thomas Rawlinson, David Llewellyn, Rushdi Shakri, Jing Jin, Geneviève Labbé, Nick Edwards, Ian Poulton, Rachel Roberts, Ryan Farid, Thomas Jørgensen, Daniel Alanine, Simone de Cassan, Matthew Higgins, Thomas Otto, James McCarthy, Willem de Jongh, Alfredo Nicosia, Sarah Moyle, Adrian Hill, Eleanor Berrie, Chetan Chitnis, Alison Lawrie, Simon Draper
Categories: malaria news feeds

Cracking Ali Baba?s code

CiteULike malaria tags - 22 June 2017 - 10:21am
eLife, Vol. 6 (14 June 2017), doi:10.7554/elife.28600
Oliver Billker
Categories: malaria news feeds

Targeting host factors to circumvent anti-malarial drug resistance.

CiteULike malaria tags - 19 June 2017 - 2:37pm
Current pharmaceutical design, Vol. 19, No. 2. (2013), pp. 290-299

The most common treatments for infectious diseases target the invading pathogen. The efficacy of such an approach may, however, be countered by the possibility of the development of resistance to a pharmacophore, through mutation(s) in pathogen molecules required for activity. Given the fact that pathogens exploit host factors in order to grow in an otherwise hostile environment, one possible way to circumvent the emergence of resistance is to develop drugs that target non-essential host factors hijacked by the pathogen, rather than the pathogen's own molecules. Such solutions are already being developed for various viral and bacterial pathogens, but much less has been achieved with infections caused by protozoan parasites, as is the case of Plasmodium. Here, we highlight recent progress in host target-based anti-viral and anti-bacterial approaches and discuss possible host targets that may be used for anti-malarial interventions. Host molecules that play a role during either the liver or the blood stage of Plasmodium infection are outlined and their potential merits as anti-malarial targets are discussed.
Miguel Prudêncio, Maria Mota
Categories: malaria news feeds

Proteomic profiling of the brain of mice with experimental cerebral malaria

CiteULike malaria tags - 14 June 2017 - 11:49am
Journal of Proteomics (June 2017), doi:10.1016/j.jprot.2017.06.002

Cerebral malaria (CM) is a severe neurological complication of malaria infection in both adults and children. In pursuit of effective treatment of CM, clinical studies, postmortem analysis and animal models have been employed to understand the pathology and identify effective interventions. In this study, a shotgun proteomics analysis was conducted to profile the proteomic signature of the brain tissue of mice with experimental cerebral malaria (ECM) in order to further understand the underlying pathology. To identify CM-associated response, proteomic signatures of the brains of C57/Bl6N mice infected with P. berghei ANKA that developed neurological syndrome were compared to those of mice infected with P. berghei NK65 that developed equally high parasite burdens without neurological signs, and to those of non-infected mice. The results show that the CM-associated response in mice that developed neurological signs comprise mainly acute-phase reaction and coagulation cascade activation, and indicate the leakage of plasma proteins into the brain parenchyma. Cerebral malaria (CM) remains a major cause of death in children. The majority of these deaths occur in sub-Saharan Africa. Even with adequate access to treatment, mortality remains high and neurological sequelae can be found in up to 20% of survivors. No adjuvant treatment to date has been shown to reduce mortality and the pathophysiology of CM is largely unknown. Experimental cerebral malaria (ECM) is a well-established model that may contribute to identify and test druggable targets. In this study we have identified the disruption of the blood-brain barrier following inflammatory and vascular injury as a mechanism of disease. In this study we report a number of proteins that could be validated as potential biomarkers of ECM. Further studies, will be required to validate the clinical relevance of these biomarkers in human CM.
Ehab Moussa, Honglei Huang, Malika Ahras, Amar Lall, Marie Thezenas, Roman Fischer, Benedikt Kessler, Arnab Pain, Oliver Billker, Climent Casals-Pascual
Categories: malaria news feeds

Human Migration And The Spread Of Malaria Parasites To The New World

CiteULike malaria tags - 8 June 2017 - 12:33pm
bioRxiv (29 May 2017), 141853, doi:10.1101/141853

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
Priscila Rodrigues, Hugo Valdivia, Thais Oliveira, Joao Marcelo, Ana Maria, Crispim Cerutti-Junior, Julyana Buery, Cristiana Brito, Julio Souza, Zelinda Maria Braga Hirano, Rosely Malafronte, Simone Ladeia-Andrade, Toshihiro Mita, Ana Santamaria, Jose Calzada, Fumihiko Kawamoto, Leonie Raijmakers, Ivo Mueller, Maria Pacheco, Ananias Escalante, Ingrid Felger, Marcelo Ferreira
Categories: malaria news feeds