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https://www.readbyqxmd.com/read/29670144/chromobacterium-spp-mediate-their-anti-plasmodium-activity-through-secretion-of-the-histone-deacetylase-inhibitor-romidepsin
#1
Raúl G Saraiva, Callie R Huitt-Roehl, Abhai Tripathi, Yi-Qiang Cheng, Jürgen Bosch, Craig A Townsend, George Dimopoulos
The Chromobacterium sp. Panama bacterium has in vivo and in vitro anti-Plasmodium properties. To assess the nature of the Chromobacterium-produced anti-Plasmodium factors, chemical partition was conducted by bioassay-guided fractionation where different fractions were assayed for activity against asexual stages of P. falciparum. The isolated compounds were further partitioned by reversed-phase FPLC followed by size-exclusion chromatography; high resolution UPLC and ESI/MS data were then collected and revealed that the most active fraction contained a cyclic depsipeptide, which was identified as romidepsin...
April 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29649225/insulin-receptor-knockdown-blocks-filarial-parasite-development-and-alters-egg-production-in-the-southern-house-mosquito-culex-quinquefasciatus
#2
Andrew Bradley Nuss, Mark R Brown, Upadhyayula Suryanarayana Murty, Monika Gulia-Nuss
Lymphatic filariasis, commonly known as elephantiasis, is a painful and profoundly disfiguring disease. Wuchreria bancrofti (Wb) is responsible for >90% of infections and the remainder are caused by Brugia spp. Mosquitoes of the genera Culex (in urban and semi-urban areas), Anopheles (in rural areas of Africa and elsewhere), and Aedes (in Pacific islands) are the major vectors of W. bancrofti. A preventive chemotherapy called mass drug administration (MDA), including albendazole with ivermectin or diethylcarbamazine citrate (DEC) is used in endemic areas...
April 12, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29626096/the-mitochondrial-ribosomal-protein-l13-is-critical-for-the-structural-and-functional-integrity-of-the-mitochondrion-in-plasmodium-falciparum
#3
Hangjun Ke, Swati Dass, Joanne M Morrisey, Michael W Mather, Akhil B Vaidya
The phylum Apicomplexa contains a group of protozoan causing diseases in humans and livestock. Plasmodium spp. , the causative agent of malaria, contains a mitochondrion that is very divergent from that of their hosts. The malarial mitochondrion is a clinically validated target for the antimalarial drug atovaquone, which specifically blocks the electron transfer activity of the bc1 complex of the mitochondrial electron transport chain (mtETC). Most mtETC proteins are nuclear-encoded and imported from the cytosol, but three key protein subunits are encoded in the Plasmodium mitochondrial genome: cyt b, COXI, and COXIII...
April 6, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29615050/differential-activity-of-methylene-blue-against-erythrocytic-and-hepatic-stages-of-plasmodium
#4
Henriette Bosson-Vanga, Jean-François Franetich, Valérie Soulard, Daniel Sossau, Maurel Tefit, Bocar Kane, Jean-Christophe Vaillant, Steffen Borrmann, Olaf Müller, Nathalie Dereuddre-Bosquet, Roger Le Grand, Olivier Silvie, Dominique Mazier
BACKGROUND: In the context of malaria elimination/eradication, drugs that are effective against the different developmental stages of the parasite are highly desirable. The oldest synthetic anti-malarial drug, the thiazine dye methylene blue (MB), is known for its activity against Plasmodium blood stages, including gametocytes. The aim of the present study was to investigate a possible effect of MB against malaria parasite liver stages. METHODS: MB activity was investigated using both in vitro and in vivo models...
April 3, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29571157/antimalarial-agents-against-both-sexual-and-asexual-parasites-stages-structure-activity-relationships-and-biological-studies-of-the-malaria-box-compound-1-5-4-bromo-2-chlorophenyl-furan-2-yl-n-piperidin-4-yl-methyl-methanamine-mmv019918-and-analogues
#5
Alessandra Vallone, Sarah D'Alessandro, Simone Brogi, Margherita Brindisi, Giulia Chemi, Gloria Alfano, Stefania Lamponi, Soon Goo Lee, Joseph M Jez, Karin J M Koolen, Koen J Dechering, Simona Saponara, Fabio Fusi, Beatrice Gorelli, Donatella Taramelli, Silvia Parapini, Reto Caldelari, Giuseppe Campiani, Sandra Gemma, Stefania Butini
Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P...
March 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29564256/a-comparative-study-of-epidemiological-investigations-of-malaria-outbreaks-and-related-deaths-in-two-districts-of-jharkhand-during-the-same-prewinter-season-using-shoe-leather-epidemiology
#6
Dewesh Kumar, Shashi Bhushan Singh, Abhishek Kumar, Anupam Kishore, Vivek Kashyap
Background: Following news of deaths in two districts of Jharkhand (West Singhbum and Garhwa) in November 2016, epidemiological investigations were contemplated to investigate any current outbreak of falciparum malaria and deaths attributed to it. Methodology: The epidemiological investigations, verbal autopsy of suspected deaths attributed to malaria and keys interviews were conducted in the 2nd and 4th week of November 2016 in Khuntpani and Dhurki block of West Singhbum and Garhwa districts, respectively, following a strict protocol...
October 2017: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/29559909/qsar-driven-design-and-discovery-of-novel-compounds-with-antiplasmodial-and-transmission-blocking-activities
#7
Marilia N N Lima, Cleber C Melo-Filho, Gustavo C Cassiano, Bruno J Neves, Vinicius M Alves, Rodolpho C Braga, Pedro V L Cravo, Eugene N Muratov, Juliana Calit, Daniel Y Bargieri, Fabio T M Costa, Carolina H Andrade
Malaria is a life-threatening infectious disease caused by parasites of the genus Plasmodium , affecting more than 200 million people worldwide every year and leading to about a half million deaths. Malaria parasites of humans have evolved resistance to all current antimalarial drugs, urging for the discovery of new effective compounds. Given that the inhibition of deoxyuridine triphosphatase of Plasmodium falciparum ( Pf dUTPase) induces wrong insertions in plasmodial DNA and consequently leading the parasite to death, this enzyme is considered an attractive antimalarial drug target...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29558973/the-tripartite-interactions-between-the-mosquito-its-microbiota-and-plasmodium
#8
REVIEW
Ottavia Romoli, Mathilde Gendrin
The microbiota of Anopheles mosquitoes interferes with mosquito infection by Plasmodium and influences mosquito fitness, therefore affecting vectorial capacity. This natural barrier to malaria transmission has been regarded with growing interest in the last 20 years, as it may be a source of new transmission-blocking strategies. The last decade has seen tremendous progress in the functional characterisation of the tripartite interactions between the mosquito, its microbiota and Plasmodium parasites. In this review, we provide insights into the effects of the mosquito microbiota on Plasmodium infection and on mosquito physiology, and on how these aspects together influence vectorial capacity...
March 20, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29548282/prevalence-of-glucose-6-phosphate-dehydrogenase-g6pd-deficiency-among-malaria-patients-in-upper-myanmar
#9
Jinyoung Lee, Tae Im Kim, Jung-Mi Kang, Hojong Jun, Hương Giang Lê, Thị Lam Thái, Woon-Mok Sohn, Moe Kyaw Myint, Khin Lin, Tong-Soo Kim, Byoung-Kuk Na
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) deficiency is one of the most common X-linked recessive hereditary disorders in the world. Primaquine (PQ) has been used for radical cure of P. vivax to prevent relapse. Recently, it is also used to reduce P. falciparum gametocyte carriage to block transmission. However, PQ metabolites oxidize hemoglobin and generate excessive reactive oxygen species which can trigger acute hemolytic anemia in malaria patients with inherited G6PD deficiency...
March 16, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29539423/a-specific-pfemp1-is-expressed-in-p-falciparum-sporozoites-and-plays-a-role-in-hepatocyte-infection
#10
Gigliola Zanghì, Shruthi S Vembar, Sebastian Baumgarten, Shuai Ding, Julien Guizetti, Jessica M Bryant, Denise Mattei, Anja T R Jensen, Laurent Rénia, Yun Shan Goh, Robert Sauerwein, Cornelus C Hermsen, Jean-François Franetich, Mallaury Bordessoulles, Olivier Silvie, Valérie Soulard, Olivier Scatton, Patty Chen, Salah Mecheri, Dominique Mazier, Artur Scherf
Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites...
March 13, 2018: Cell Reports
https://www.readbyqxmd.com/read/29528336/what-goes-around-comes-around-modeling-malaria-transmission-from-humans-back-to-mosquitos
#11
Kazutoyo Miura, Peter D Crompton
Malaria, caused by mosquito-transmitted Plasmodium parasites, continues to take a major toll on global health. The development of drugs and vaccines that reduce malaria transmission from humans back to mosquitos could contribute to the control and eventual eradication of malaria, but research models for the early clinical evaluation of candidate interventions are lacking. In this issue of the JCI, Collins and colleagues report the successful transmission of Plasmodium falciparum parasites from humans to mosquitoes during controlled human malaria infection, thus providing a potential tool to accelerate the development of much needed transmission-blocking drugs and vaccines...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29520067/vector-species-specific-association-between-natural-wolbachia-infections-and-avian-malaria-in-black-fly-populations
#12
Luke Woodford, Giovanni Bianco, Yoana Ivanova, Maeve Dale, Kathryn Elmer, Fiona Rae, Stephen D Larcombe, Barbara Helm, Heather M Ferguson, Francesco Baldini
Artificial infection of mosquitoes with the endosymbiont bacteria Wolbachia can interfere with malaria parasite development. Therefore, the release of Wolbachia-infected mosquitoes has been proposed as a malaria control strategy. However, Wolbachia effects on vector competence are only partly understood, as indicated by inconsistent effects on malaria infection reported under laboratory conditions. Studies of naturally-occurring Wolbachia infections in wild vector populations could be useful to identify the ecological and evolutionary conditions under which these endosymbionts can block malaria transmission...
March 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29518156/crispr-cas9-mediated-gene-knockout-of-anopheles-gambiae-frep1-suppresses-malaria-parasite-infection
#13
Yuemei Dong, Maria L Simões, Eric Marois, George Dimopoulos
Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito's susceptibility to Plasmodium and on mosquito fitness...
March 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29485403/on-a-mission-to-block-transmission
#14
Amanda Ross, Nicolas Mb Brancucci
The controlled infection of volunteers with Plasmodium falciparum parasites could provide a platform to evaluate new drugs and vaccines aimed at blocking malaria transmission.
February 27, 2018: ELife
https://www.readbyqxmd.com/read/29482720/a-randomized-feasibility-trial-comparing-four-antimalarial-drug-regimens-to-induce-plasmodium-falciparum-gametocytemia-in-the-controlled-human-malaria-infection-model
#15
Isaie J Reuling, Lisanne A van de Schans, Luc E Coffeng, Kjerstin Lanke, Lisette Meerstein-Kessel, Wouter Graumans, Geert-Jan van Gemert, Karina Teelen, Rianne Siebelink-Stoter, Marga van de Vegte-Bolmer, Quirijn de Mast, André J van der Ven, Karen Ivinson, Cornelus C Hermsen, Sake de Vlas, John Bradley, Katharine A Collins, Christian F Ockenhouse, James McCarthy, Robert W Sauerwein, Teun Bousema
Background Malaria elimination strategies require a thorough understanding of parasite transmission from human to mosquito. A clinical model to induce gametocytes to understand their dynamics and evaluate transmission-blocking interventions (TBI) is currently unavailable. Here, we explore the use of the well-established Controlled Human Malaria Infection model (CHMI) to induce gametocyte carriage with different antimalarial drug regimens. Methods In a single centre, open-label randomised trial, healthy malaria-naive participants (aged 18-35 years) were infected with Plasmodium falciparum by bites of infected Anopheles mosquitoes (ClinicalTrials...
February 27, 2018: ELife
https://www.readbyqxmd.com/read/29422648/unravelling-the-immune-signature-of-plasmodium-falciparum-transmission-reducing-immunity
#16
Will J R Stone, Joseph J Campo, André Lin Ouédraogo, Lisette Meerstein-Kessel, Isabelle Morlais, Dari Da, Anna Cohuet, Sandrine Nsango, Colin J Sutherland, Marga van de Vegte-Bolmer, Rianne Siebelink-Stoter, Geert-Jan van Gemert, Wouter Graumans, Kjerstin Lanke, Adam D Shandling, Jozelyn V Pablo, Andy A Teng, Sophie Jones, Roos M de Jong, Amanda Fabra-García, John Bradley, Will Roeffen, Edwin Lasonder, Giuliana Gremo, Evelin Schwarzer, Chris J Janse, Susheel K Singh, Michael Theisen, Phil Felgner, Matthias Marti, Chris Drakeley, Robert Sauerwein, Teun Bousema, Matthijs M Jore
Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins...
February 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29422384/efficacy-and-safety-of-primaquine-and-methylene-blue-for-prevention-of-plasmodium-falciparum-transmission-in-mali-a-phase-2-single-blind-randomised-controlled-trial
#17
Alassane Dicko, Michelle E Roh, Halimatou Diawara, Almahamoudou Mahamar, Harouna M Soumare, Kjerstin Lanke, John Bradley, Koualy Sanogo, Daouda T Kone, Kalifa Diarra, Sekouba Keita, Djibrilla Issiaka, Sekou F Traore, Charles McCulloch, Will J R Stone, Jimee Hwang, Olaf Müller, Joelle M Brown, Vinay Srinivasan, Chris Drakeley, Roly Gosling, Ingrid Chen, Teun Bousema
BACKGROUND: Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. METHODS: This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali)...
February 5, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29420756/potent-plasmodium-falciparum-gametocytocidal-compounds-identified-by-exploring-the-kinase-inhibitor-chemical-space-for-dual-active-antimalarials
#18
Mariëtte E van der Watt, Janette Reader, Alisje Churchyard, Sindisiwe H Nondaba, Sonja B Lauterbach, Jandeli Niemand, Sijuade Abayomi, Riëtte A van Biljon, Jessica I Connacher, Roelof D J van Wyk, Claire Le Manach, Tanya Paquet, Diego González Cabrera, Christel Brunschwig, Anjo Theron, Sonia Lozano-Arias, Janneth F I Rodrigues, Esperanza Herreros, Didier Leroy, James Duffy, Leslie J Street, Kelly Chibale, Dalu Mancama, Theresa L Coetzer, Lyn-Marie Birkholtz
Objectives: Novel chemical tools to eliminate malaria should ideally target both the asexual parasites and transmissible gametocytes. Several imidazopyridazines (IMPs) and 2-aminopyridines (2-APs) have been described as potent antimalarial candidates targeting lipid kinases. However, these have not been extensively explored for stage-specific inhibition of gametocytes in Plasmodium falciparum parasites. Here we provide an in-depth evaluation of the gametocytocidal activity of compounds from these chemotypes and identify novel starting points for dual-acting antimalarials...
February 6, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29389671/a-controlled-human-malaria-infection-model-enabling-evaluation-of-transmission-blocking-interventions
#19
Katharine A Collins, Claire Yt Wang, Matthew Adams, Hayley Mitchell, Melanie Rampton, Suzanne Elliott, Isaie J Reuling, Teun Bousema, Robert Sauerwein, Stephan Chalon, Jörg J Möhrle, James S McCarthy
BACKGROUND: Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination. However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Here we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). METHODS: Seventeen healthy malaria-naïve volunteers underwent CHMI by intravenous inoculation of P...
February 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29371619/immunization-with-transgenic-rodent-malaria-parasites-expressing-pfs25-induces-potent-transmission-blocking-activity
#20
K A Sala, F Angrisano, D F Da, I J Taylor, T S Churcher, A M Blagborough
An anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression of P25 with appropriate conformation is problematic and a pre-requisite for achieving functional titers. A potential alternative to recombinant/sub-unit vaccine is immunization with a non-pathogenic, whole-parasite vaccine...
January 25, 2018: Scientific Reports
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