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Quantifying the Impact of Human Mobility on Malaria

CiteULike malaria tags - 29 April 2016 - 12:15pm
Science, Vol. 338, No. 6104. (11 October 2012), pp. 267-270, doi:10.1126/science.1223467

Human movements contribute to the transmission of malaria on spatial scales that exceed the limits of mosquito dispersal. Identifying the sources and sinks of imported infections due to human travel and locating high-risk sites of parasite importation could greatly improve malaria control programs. Here, we use spatially explicit mobile phone data and malaria prevalence information from Kenya to identify the dynamics of human carriers that drive parasite importation between regions. Our analysis identifies importation routes that contribute to malaria epidemiology on regional spatial scales.
A Wesolowski, N Eagle, AJ Tatem, DL Smith, AM Noor, RW Snow, CO Buckee
Categories: malaria news feeds

Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines

CiteULike malaria tags - 28 April 2016 - 9:21am
Malaria Journal, Vol. 15, No. 1. (21 April 2016), doi:10.1186/s12936-016-1254-1
Susana Campino, Ernest Benavente, Samuel Assefa, Eloise Thompson, Laura Drought, Catherine Taylor, Zaria Gorvett, Celine Carret, Christian Flueck, Al Ivens, Dominic Kwiatkowski, Pietro Alano, David Baker, Taane Clark
Categories: malaria news feeds

Palmitoyl Transferases have Critical Roles in the Development of Mosquito and Liver Stages of Plasmodium

CiteULike malaria tags - 21 April 2016 - 11:50am
Cellular Microbiology (1 April 2016), pp. n/a-n/a, doi:10.1111/cmi.12601

As the Plasmodium parasite transitions between mammalian and mosquito host, it has to adjust quickly to new environments. Palmitoylation, a reversible and dynamic lipid posttranslational modification plays a central role in regulating this process and has been implicated with functions for parasite morphology, motility and host cell invasion. While proteins associated with the gliding motility machinery have been described to be palmitoylated, no palmitoyl transferase responsible for regulating gliding motility has previously been identified. Here, we characterize two palmityol transferases with gene tagging and gene deletion approaches. We identify DHHC3, a palmitoyl transferase as a mediator of ookinete development, with a crucial role for gliding motility in ookinetes and sporozoites and we co-localize the protein with a marker for the inner membrane complex in the ookinete stage. Ookinetes and sporozoites lacking DHHC3 are impaired in gliding motility and exhibit a strong phenotype in vivo; with ookinetes being significantly less infectious to their mosquito host and sporozoites being non-infectious to mice. Importantly, genetic complementation of the DHHC3-ko parasite completely restored virulence. We generated parasites lacking both DHHC3, as well as the palmitoyl transferase DHHC9, and found an enhanced phenotype for these double knockout parasites, allowing insights into the functional overlap and compensational nature of the large family of PbDHHCs. These findings contribute to our understanding of the organization and mechanism of the gliding motility machinery, which as is becoming increasingly clear, is mediated by palmitoylation. This article is protected by copyright. All rights reserved.
CS Hopp, AE Balaban, E Bushell, O Billker, JC Rayner, P Sinnis
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Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes

CiteULike malaria tags - 15 April 2016 - 8:59am
Science, Vol. 352, No. 6283. (14 April 2016), pp. 349-353, doi:10.1126/science.aad9279
CD Goodman, JE Siregar, V Mollard, J Vega-Rodriguez, D Syafruddin, H Matsuoka, M Matsuzaki, T Toyama, A Sturm, A Cozijnsen, M Jacobs-Lorena, K Kita, S Marzuki, GI McFadden
Categories: malaria news feeds

Study of Plasmodium falciparum DHHC palmitoyl-transferases identifies a role for PfDHHC9 in gametocytogenesis

CiteULike malaria tags - 13 April 2016 - 10:44am
Cellular Microbiology (1 April 2016), pp. n/a-n/a, doi:10.1111/cmi.12599

Palmitoylation is the post-translational reversible addition of the acyl moiety, palmitate, to cysteine residues of proteins, and is involved in regulating protein trafficking, localisation, stability and function. The DHHC protein family, named for their highly conserved Aspartate-Histidine-Histidine-Cysteine (DHHC) signature motif, is thought to be responsible for catalysing protein palmitoylation. Palmitoylation is widespread in all eukaryotes, including the malaria parasite, Plasmodium falciparum, where over 400 palmitoylated proteins are present in the asexual intraerythrocytic schizont stage parasites, including proteins involved in key aspects of parasite maturation and development. The P. falciparum genome includes 12 proteins containing the conserved DHHC motif. In this study, we adapted a palmitoyl-transferase activity assay for use with P. falciparum proteins and demonstrated for the first time that P. falciparum DHHC proteins are responsible for the palmitoylation of P. falciparum substrates. This assay also reveals that multiple DHHCs are capable of palmitoylating the same substrate, indicating functional redundancy at least in vitro. To test whether functional redundancy also exists in vivo, we investigated the endogenous localisation and essentiality of a subset of schizont-expressed PfDHHC proteins. Individual PfDHHC proteins localised to distinct organelles, including parasite-specific organelles such as the rhoptries and inner membrane complex. Knock-out studies identified individual DHHCs that may be essential for blood stage growth, and others that were functionally redundant in the blood stages but may have functions in other stages of parasite development. Supporting this hypothesis, disruption of PfDHHC9 had no effect on blood-stage growth, but reduced the formation of gametocytes, suggesting that this protein could be exploited as a transmission-blocking target. The localisation and stage-specific expression of the DHHC proteins may be important for regulating their substrate specificity and thus may provide a path for inhibitor development. This article is protected by copyright. All rights reserved.
Chwen Tay, Matthew Jones, Nicola Hodson, Michel Theron, Jyoti Choudhary, Julian Rayner
Categories: malaria news feeds

Genomic epidemiology of artemisinin resistant malaria

CiteULike malaria tags - 13 April 2016 - 9:58am
eLife, Vol. 5 (04 March 2016), e08714, doi:10.7554/elife.08714

Genomic epidemiology of artemisinin resistant malaria | Plasmodium falciparum kelch13 mutations that cause artemisinin resistant malaria in Southeast Asia show markedly different patterns of evolutionary selection in Africa.
MalariaGEN Plasmodium falciparum Community Project, Richard Neher, Roberto Amato, Olivo Miotto, Charles Woodrow, Jacob Almagro-Garcia, Ipsita Sinha, Susana Campino, Daniel Mead, Eleanor Drury, Mihir Kekre, Mandy Sanders, Alfred Amambua-Ngwa, Chanaki Amaratunga, Lucas Amenga-Etego, Voahangy Andrianaranjaka, Tobias Apinjoh, Elizabeth Ashley, Sarah Auburn, Gordon Awandare, Vito Baraka, Alyssa Barry, Maciej Boni, Steffen Borrmann, Teun Bousema, Oralee Branch, Peter Bull, Kesinee Chotivanich, David Conway, Alister Craig, Nicholas Day, Abdoulaye Djimdé, Christiane Dolecek, Arjen Dondorp, Chris Drakeley, Patrick Duffy, Diego Echeverry, Thomas Egwang, Rick Fairhurst, Md, Caterina Fanello, Tran Hien, Abraham Hodgson, Mallika Imwong, Deus Ishengoma, Pharath Lim, Chanthap Lon, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Pascal Michon, Victor Mobegi, Olugbenga Mokuolu, Jacqui Montgomery, Ivo Mueller, Myat Kyaw, Paul Newton, Francois Nosten, Rintis Noviyanti, Alexis Nzila, Harold Ocholla, Abraham Oduro, Marie Onyamboko, Jean-Bosco Ouedraogo, Aung Pyae, Christopher Plowe, Ric Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Pascal Ringwald, Lastenia Ruiz, David Saunders, Alex Shayo, Peter Siba, Shannon Takala-Harrison, Thuy-Nhien Thanh, Vandana Thathy, Federica Verra, Jason Wendler, Nicholas White, Htut Ye, Victoria Cornelius, Rachel Giacomantonio, Dawn Muddyman, Christa Henrichs, Cinzia Malangone, Dushyanth Jyothi, Richard Pearson, Julian Rayner, Gilean McVean, Kirk Rockett, Alistair Miles, Paul Vauterin, Ben Jeffery, Magnus Manske, Jim Stalker, Bronwyn MacInnis, Dominic Kwiatkowski
Categories: malaria news feeds

Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria

CiteULike malaria tags - 24 March 2016 - 11:55am
Nature Communications, Vol. 7 (22 March 2016), 11078, doi:10.1038/ncomms11078
Sesh Sundararaman, Lindsey Plenderleith, Weimin Liu, Dorothy Loy, Gerald Learn, Yingying Li, Katharina Shaw, Ahidjo Ayouba, Martine Peeters, Sheri Speede, George Shaw, Frederic Bushman, Dustin Brisson, Julian Rayner, Paul Sharp, Beatrice Hahn
Categories: malaria news feeds

Transmission model of endemic human malaria in a partially immune population

CiteULike malaria tags - 21 March 2016 - 8:10pm
In Math. Comput. Model., Vol. 46, No. 5–6. (2007), 806-822, doi:10.1016/j.mcm.2006.12.010

A new transmission model of human malaria in a partially immune population with three discrete delays is formulated for variable host and vector populations. These are latent period in the host population, latent period in the vector population and duration of partial immunity. The results of our mathematical analysis indicate that a threshold parameter R 0 exists. For R 0 > 1 , the expected number of mosquitoes infected from humans R h m should be greater than a certain critical value R h m ∗ or should be less than R h m ∗ when R h m ∗ > 1 , for a stable endemic equilibrium to exist. We deduce from model analysis that an increase in the period within which partial immunity is lost increases the spread of the disease. Numerically we deduce that treatment of the partially immune humans assists in reducing the severity of the disease and that transmission blocking vaccines would be effective in a partially immune population. Numerical simulations support our analytical conclusions and illustrate possible behaviour scenarios of the model.
C Chiyaka, W Garira, S Dube
Categories: malaria news feeds

Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum

CiteULike malaria tags - 21 March 2016 - 3:35pm
Proc. R. Soc. B, Vol. 283, No. 1826. (16 March 2016), 20153038, doi:10.1098/rspb.2015.3038
Mary Bushman, Lindsay Morton, Nancy Duah, Neils Quashie, Benjamin Abuaku, Kwadwo Koram, Pedro Dimbu, Mateusz Plucinski, Julie Gutman, Peter Lyaruu, Patrick Kachur, Jacobus de Roode, Venkatachalam Udhayakumar
Categories: malaria news feeds

Landscape and Dynamics of Transcription Initiation in the Malaria Parasite Plasmodium falciparum

CiteULike malaria tags - 17 March 2016 - 10:33am
Cell Reports, Vol. 14, No. 10. (March 2016), pp. 2463-2475, doi:10.1016/j.celrep.2016.02.025

A genome-wide map of transcription start sites (TSSs) for P. falciparum Sequence and chromatin features for core promoters of malaria parasites are defined Dynamic study of TSS usage identifies developmentally regulated transcript isoforms A comprehensive map of transcription start sites (TSSs) across the highly AT-rich genome of P. falciparum would aid progress toward deciphering the molecular mechanisms that underlie the timely regulation of gene expression in this malaria parasite. Using high-throughput sequencing technologies, we generated a comprehensive atlas of transcription initiation events at single-nucleotide resolution during the parasite intra-erythrocytic developmental cycle. This detailed analysis of TSS usage enabled us to define architectural features of plasmodial promoters. We demonstrate that TSS selection and strength are constrained by local nucleotide composition. Furthermore, we provide evidence for coordinate and stage-specific TSS usage from distinct sites within the same transcription unit, thereby producing transcript isoforms, a subset of which are developmentally regulated. This work offers a framework for further investigations into the interactions between genomic sequences and regulatory factors governing the complex transcriptional program of this major human pathogen.
Sophie Adjalley, Christophe Chabbert, Bernd Klaus, Vicent Pelechano, Lars Steinmetz
Categories: malaria news feeds

A global bionomic database for the dominant vectors of human malaria

CiteULike malaria tags - 14 March 2016 - 2:51pm
Scientific Data, Vol. 3 (01 March 2016), doi:10.1038/sdata.2016.14

mosquitoes were first recognised as the transmitters of human malaria in the late 19th Century and have been subject to a huge amount of research ever since. Yet there is still much that is unknown regarding the ecology, behaviour (collectively âbionomicsâ) and sometimes even the identity of many of the worldâs most prominent disease vectors, much less the within-species variation in their bionomics. Whilst malaria elimination remains an ambitious goal, it is becoming increasingly clear that knowledge of vector behaviour is needed to effectively target control measures. A database of bionomics data for the dominant vector species of malaria worldwide has been compiled from published peer-reviewed literature. The data identification and collation processes are described, together with the geo-positioning and quality control methods. This is the only such dataset in existence and provides a valuable resource to researchers and policy makers in this field.
Claire Massey, Gala Garrod, Antoinette Wiebe, Andrew Henry, Zhi Huang, Catherine Moyes, Marianne Sinka
Categories: malaria news feeds

Redox Polypharmacology as an Emerging Strategy to Combat Malarial Parasites

CiteULike malaria tags - 10 March 2016 - 4:31pm
ChemMedChem (1 March 2016), pp. n/a-n/a, doi:10.1002/cmdc.201600009

3-Benzylmenadiones are potent antimalarial agents that are thought to act through their 3-benzoylmenadione metabolites as redox cyclers of two essential targets: the NADPH-dependent glutathione reductases (GRs) of Plasmodium-parasitized erythrocytes and methemoglobin. Their physicochemical properties were characterized in a coupled assay using both targets and modeled with QSPR predictive tools built in house. The substitution pattern of the west/east aromatic parts that controls the oxidant character of the electrophore was highlighted and accurately predicted by QSPR models. The effects centered on the benz(o)yl chain, induced by drug bioactivation, markedly influenced the oxidant character of the reduced species through a large anodic shift of the redox potentials that correlated with the redox cycling of both targets in the coupled assay. Our approach demonstrates that the antimalarial activity of 3-benz(o)ylmenadiones results from a subtle interplay between bioactivation, fine-tuned redox properties, and interactions with crucial targets of P. falciparum. Plasmodione and its analogues give emphasis to redox polypharmacology, which constitutes an innovative approach to antimalarial therapy.
Pavel Sidorov, Israel Desta, Matthieu Chessé, Dragos Horvath, Gilles Marcou, Alexandre Varnek, Elisabeth Davioud-Charvet, Mourad Elhabiri
Categories: malaria news feeds

The Relationship Between Invasive Nontyphoidal Salmonella Disease, Other Bacterial Bloodstream Infections, and Malaria in Sub-Saharan Africa

CiteULike malaria tags - 10 March 2016 - 10:57am
Clinical Infectious Diseases, Vol. 62, No. suppl 1. (15 March 2016), pp. S23-S31, doi:10.1093/cid/civ893

Background. Country-specific studies in Africa have indicated that Plasmodium falciparum is associated with invasive nontyphoidal Salmonella (iNTS) disease. We conducted a multicenter study in 13 sites in Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania to investigate the relationship between the occurrence of iNTS disease, other systemic bacterial infections, and malaria.
Se Park, Gi Pak, Peter Aaby, Yaw Adu-Sarkodie, Mohammad Ali, Abraham Aseffa, Holly Biggs, Morten Bjerregaard-Andersen, Robert Breiman, John Crump, Ligia Maria Cruz Espinoza, Muna Eltayeb, Nagla Gasmelseed, Julian Hertz, Justin Im, Anna Jaeger, Leon Kabore, Vera von Kalckreuth, Karen Keddy, Frank Konings, Ralf Krumkamp, Calman MacLennan, Christian Meyer, Joel Montgomery, Aissatou Niang, Chelsea Nichols, Beatrice Olack, Ursula Panzner, Jin Park, Henintsoa Rabezanahary, Raphaël Rakotozandrindrainy, Emmanuel Sampo, Nimako Sarpong, Heidi Schütt-Gerowitt, Arvinda Sooka, Abdramane Soura, Amy Sow, Adama Tall, Mekonnen Teferi, Biruk Yeshitela, Jürgen May, Thomas Wierzba, John Clemens, Stephen Baker, Florian Marks
Categories: malaria news feeds

Genomic epidemiology of artemisinin resistant malaria

CiteULike malaria tags - 8 March 2016 - 10:16am
eLife, Vol. 5 (04 March 2016), e08714, doi:10.7554/elife.08714

Genomic epidemiology of artemisinin resistant malaria | Plasmodium falciparum kelch13 mutations that cause artemisinin resistant malaria in Southeast Asia show markedly different patterns of evolutionary selection in Africa.
MalariaGEN Plasmodium falciparum Community Project, Richard Neher, Roberto Amato, Olivo Miotto, Charles Woodrow, Jacob Almagro-Garcia, Ipsita Sinha, Susana Campino, Daniel Mead, Eleanor Drury, Mihir Kekre, Mandy Sanders, Alfred Amambua-Ngwa, Chanaki Amaratunga, Lucas Amenga-Etego, Voahangy Andrianaranjaka, Tobias Apinjoh, Elizabeth Ashley, Sarah Auburn, Gordon Awandare, Vito Baraka, Alyssa Barry, Maciej Boni, Steffen Borrmann, Teun Bousema, Oralee Branch, Peter Bull, Kesinee Chotivanich, David Conway, Alister Craig, Nicholas Day, Abdoulaye Djimdé, Christiane Dolecek, Arjen Dondorp, Chris Drakeley, Patrick Duffy, Diego Echeverry, Thomas Egwang, Rick Fairhurst, Md, Caterina Fanello, Tran Hien, Abraham Hodgson, Mallika Imwong, Deus Ishengoma, Pharath Lim, Chanthap Lon, Jutta Marfurt, Kevin Marsh, Mayfong Mayxay, Pascal Michon, Victor Mobegi, Olugbenga Mokuolu, Jacqui Montgomery, Ivo Mueller, Myat Kyaw, Paul Newton, Francois Nosten, Rintis Noviyanti, Alexis Nzila, Harold Ocholla, Abraham Oduro, Marie Onyamboko, Jean-Bosco Ouedraogo, Aung Pyae, Christopher Plowe, Ric Price, Sasithon Pukrittayakamee, Milijaona Randrianarivelojosia, Pascal Ringwald, Lastenia Ruiz, David Saunders, Alex Shayo, Peter Siba, Shannon Takala-Harrison, Thuy-Nhien Thanh, Vandana Thathy, Federica Verra, Jason Wendler, Nicholas White, Htut Ye, Victoria Cornelius, Rachel Giacomantonio, Dawn Muddyman, Christa Henrichs, Cinzia Malangone, Dushyanth Jyothi, Richard Pearson, Julian Rayner, Gilean McVean, Kirk Rockett, Alistair Miles, Paul Vauterin, Ben Jeffery, Magnus Manske, Jim Stalker, Bronwyn MacInnis, Dominic Kwiatkowski
Categories: malaria news feeds

Composition of the gut microbiota modulates the severity of malaria

CiteULike malaria tags - 29 February 2016 - 7:08pm
Proceedings of the National Academy of Sciences, Vol. 113, No. 8. (23 February 2016), pp. 2235-2240, doi:10.1073/pnas.1504887113

Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from “resistant” or “susceptible” mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.
Nicolas Villarino, Gary LeCleir, Joshua Denny, Stephen Dearth, Christopher Harding, Sarah Sloan, Jennifer Gribble, Shawn Campagna, Steven Wilhelm, Nathan Schmidt
Categories: malaria news feeds

Malaria medicines: a glass half full?

CiteULike malaria tags - 9 February 2016 - 12:38am
Nat Rev Drug Discov, Vol. 14, No. 6. (22 June 2015), pp. 424-442, doi:10.1038/nrd4573

Despite substantial scientific progress over the past two decades, malaria remains a worldwide burden that causes hundreds of thousands of deaths every year. New, affordable and safe drugs are required to overcome increasing resistance against artemisinin-based treatments, treat vulnerable populations, interrupt the parasite life cycle
Timothy Wells, Rob van Huijsduijnen, Wesley Van Voorhis
Categories: malaria news feeds

Unusual antibodies target malaria

CiteULike malaria tags - 7 February 2016 - 7:48pm
Science, Vol. 351, No. 6273. (04 February 2016), pp. 572-573, doi:10.1126/science.351.6273.572-f
KL Mueller
Categories: malaria news feeds

Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites

CiteULike malaria tags - 4 February 2016 - 12:54pm
Malaria Journal, Vol. 15, No. 1. (29 January 2016), doi:10.1186/s12936-016-1097-9
Patrath Ponsuwanna, Theerarat Kochakarn, Duangkamon Bunditvorapoom, Krittikorn Kümpornsin, Thomas Otto, Chase Ridenour, Kesinee Chotivanich, Prapon Wilairat, Nicholas White, Olivo Miotto, Thanat Chookajorn
Categories: malaria news feeds

Association of anemia, pre-eclampsia and eclampsia with seasonality: A realist systematic review

CiteULike malaria tags - 31 January 2016 - 4:23pm
Health & Place, Vol. 31 (January 2015), pp. 180-192, doi:10.1016/j.healthplace.2014.12.003
Tina Hlimi
Categories: malaria news feeds

Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers.

CiteULike malaria tags - 28 January 2016 - 9:16pm
Cell communication and signaling : CCS, Vol. 9 (15 May 2011), 13, doi:10.1186/1478-811x-9-13

This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.
Reza Ehsanian, Carter Van Waes, Stephan Feller
Categories: malaria news feeds

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