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https://www.readbyqxmd.com/read/28422178/enhancing-protective-immunity-to-malaria-with-a-highly-immunogenic-virus-like-particle-vaccine
#1
Katharine A Collins, Rebecca Snaith, Matthew G Cottingham, Sarah C Gilbert, Adrian V S Hill
The leading malaria vaccine in development is the circumsporozoite protein (CSP)-based particle vaccine, RTS,S, which targets the pre-erythrocytic stage of Plasmodium falciparum infection. It induces modest levels of protective efficacy, thought to be mediated primarily by CSP-specific antibodies. We aimed to enhance vaccine efficacy by generating a more immunogenic CSP-based particle vaccine and therefore developed a next-generation RTS,S-like vaccine, called R21. The major improvement is that in contrast to RTS,S, R21 particles are formed from a single CSP-hepatitis B surface antigen (HBsAg) fusion protein, and this leads to a vaccine composed of a much higher proportion of CSP than in RTS,S...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28417968/rational-development-of-a-protective-p-vivax-vaccine-evaluated-with-transgenic-rodent-parasite-challenge-models
#2
Ahmed M Salman, Eduardo Montoya-Díaz, Heather West, Amar Lall, Erwan Atcheson, Cesar Lopez-Camacho, Jai Ramesar, Karolis Bauza, Katharine A Collins, Florian Brod, Fernando Reis, Leontios Pappas, Lilia González-Cerón, Chris J Janse, Adrian V S Hill, Shahid M Khan, Arturo Reyes-Sandoval
Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28406269/evaluating-the-feasibility-and-uptake-of-a-community-led-hiv-testing-and-multi-disease-health-campaign-in-rural-uganda
#3
REVIEW
(no author information available yet)
INTRODUCTION: Multi-disease community health campaigns can be effective for population-wide HIV testing in a research setting (SEARCH: NCT01864603). We sought to evaluate feasibility and uptake of a community-led health campaign (CLHC) planned and implemented by village leaders and local clinic workers in Uganda. METHODS: Over five months in 2014, locally elected village leaders and Ministry of Health (MoH) clinic staff in a rural parish in Uganda planned a census followed by a CLHC, after training by two SEARCH trial consultants and by leaders from a neighbouring parish that had previously participated in a SEARCH health campaign...
March 29, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28402391/the-relative-effects-of-artemether-lumefantrine-and-non-artemisinin-antimalarials-on-gametocyte-carriage-and-transmission-of-plasmodium-falciparum-a-systematic-review-and-meta-analysis
#4
Matthew M Ippolito, Julia Johnson, Christopher Mullin, Christopher Mallow, Nadia Morgan, Erika Wallender, Tianjing Li, Philip J Rosenthal
Background.: Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption...
April 11, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28399303/efficacy-of-bendiocarb-used-for-indoor-residual-spraying-for-malaria-control-in-madagascar-results-with-local-anopheles-species-diptera-culicidae-from-experimental-hut-trials
#5
Sanjiarizaha Randriamaherijaona, Thiery Nirina Jean Jose Nepomichene, Jade Assoukpa, Yoann Madec, Sébastien Boyer
To control malaria in Madagascar, two primary vector control interventions are being scaled up: insecticide-treated nets and indoor residual spraying of bendiocarb, which was implemented in the Malagasy Central Highlands in 2009. The current efficacy of bendiocarb against Anopheles species was evaluated in a small-scale field trial. An experimental hut trial comparing the effectiveness of bendiocarb sprayed on five substrates (cement, wood, tin, mud, and vegetative materials) was carried out against Anopheles species in two study sites located in the eastern foothills of Madagascar...
March 13, 2017: Journal of Medical Entomology
https://www.readbyqxmd.com/read/28399299/assessment-of-ficam-vc-bendiocarb-residual-activity-on-different-wall-surfaces-for-control-of-anopheles-gambiae-s-s-diptera-culicidae-in-northern-uganda
#6
James Kirunda, Joseph Okello-Onen, Elizabeth A Opiyo, J B Rwakimari, Ranjith de Alwis, Michael Okia, Denis Ambayo, Benard Abola, David F Hoel
Insecticide decay rate on different wall surfaces is of importance to indoor residual spray (IRS) programs used as a malaria control intervention. Past IRS operations showed increasing populations of endophilic malaria vectors resting on indoor surfaces from various sites in Uganda following use of Ficam VC (bendiocarb) insecticide; variability of insecticide life was believed to be primarily due to wall surface type. Bendiocarb longevity was tested in the northern Uganda districts of Amuru, Apac, and Pader to assess its residual efficacy on three commonly encountered wall surfaces...
March 24, 2017: Journal of Medical Entomology
https://www.readbyqxmd.com/read/28395097/artesunate-to-treat-severe-malaria-in-travellers-review-of-efficacy-and-safety-and-practical-implications
#7
Camille Roussel, Eric Caumes, Marc Thellier, Papa Alioune Ndour, Pierre A Buffet, Stéphane Jauréguiberry
Background: Artesunate (AS) is the WHO first-line treatment of severe malaria in endemic countries, in adults and children. However, despite solid evidence that AS is safe and more effective than quinine in endemic areas, its deployment in non-endemic areas has been slow, due in part to the absence of a full good manufacturing practice (GMP) qualification (although prequalification has been granted in 2010). Prospective comparative trials were not conducted in travellers, but several retrospective studies and case reports are providing insights into the efficacy and safety of AS in imported severe malaria...
March 1, 2017: Journal of Travel Medicine
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#8
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen presenting cells (APCs) and tumours sends a negative signal to T cells, which can lead to T-cell exhaustion...
April 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28390397/modelling-the-therapeutic-dose-range-of-single-low-dose-primaquine-to-reduce-malaria-transmission-through-age-based-dosing
#9
Daniel Joseph Hayes, Clifford George Banda, Alexandra Chipasula-Teleka, Dianne Janette Terlouw
BACKGROUND: Low-dose primaquine is a key candidate for use in malaria transmission reduction and elimination campaigns such as mass drug administration (MDA). Uncertainty about the therapeutic dose range (TDR) required for general and paediatric populations challenge the implementation of the World Health Organisation's recommendation to add 0.25 mg/kg to current standard antimalarial treatment in such settings. Modelling work shows that for low-dose primaquine to have an impact, high efficacy and extensive population coverage are needed...
April 8, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28388914/effects-of-community-level-bed-net-coverage-on-malaria-morbidity-in-lilongwe-malawi
#10
Veronica Escamilla, Alisa Alker, Leonard Dandalo, Jonathan J Juliano, William C Miller, Portia Kamthuza, Tapiwa Tembo, Gerald Tegha, Francis Martinson, Michael Emch, Irving F Hoffman
BACKGROUND: The protective effect of insecticide-treated bed nets against individual-level malaria transmission is well known, however community-level effects are less understood. Protective effects from community-level bed net use against malaria transmission have been observed in clinical trials, however, the relationship is less clear outside of a controlled research setting. The objective of this research was to investigate the effect of community-level bed net use against malaria transmission outside of a bed net clinical trial setting in Lilongwe, Malawi following national efforts to scale-up ownership of long-lasting, insecticide-treated bed nets...
April 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28388902/therapeutic-efficacy-and-artemisinin-resistance-in-northern-myanmar-evidence-from-in-vivo-and-molecular-marker-studies
#11
Moe Kyaw Myint, Charlotte Rasmussen, Aung Thi, Dorina Bustos, Pascal Ringwald, Khin Lin
BACKGROUND: In Myanmar, three types of artemisinin-based combination therapy (ACT) are recommended as first-line treatment of uncomplicated falciparum malaria: artemether-lumefantrine (AL), artesunate-mefloquine (AS + MQ), and dihydroartemisinin-piperaquine (DP). Resistance to both artemisinins and ACT partner drugs has been reported from the Greater Mekong Sub-region, and regular efficacy monitoring of the recommended ACT is conducted in Myanmar. This paper reports on results from studies to monitor the efficacy of the three forms of ACT in sentinel sites in northern Myanmar, and investigations of mutations in the Kelch13 (k13) propeller domain...
April 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28376897/a-novel-model-fitted-to-multiple-life-stages-of-malaria-for-assessing-efficacy-of-transmission-blocking-interventions
#12
Ellie Sherrard-Smith, Thomas S Churcher, Leanna M Upton, Katarzyna A Sala, Sara E Zakutansky, Hannah C Slater, Andrew M Blagborough, Michael Betancourt
BACKGROUND: Transmission-blocking interventions (TBIs) aim to eliminate malaria by reducing transmission of the parasite between the host and the invertebrate vector. TBIs include transmission-blocking drugs and vaccines that, when given to humans, are taken up by mosquitoes and inhibit parasitic development within the vector. Accurate methodologies are key to assess TBI efficacy to ensure that only the most potent candidates progress to expensive and time-consuming clinical trials. Measuring intervention efficacy can be problematic because there is substantial variation in the number of parasites in both the host and vector populations, which can impact transmission even in laboratory settings...
April 4, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28376349/genetic-diversity-of-next-generation-antimalarial-targets-a-baseline-for-drug-resistance-surveillance-programmes
#13
Ana Rita Gomes, Matt Ravenhall, Ernest Diez Benavente, Arthur Talman, Colin Sutherland, Cally Roper, Taane G Clark, Susana Campino
Drug resistance is a recurrent problem in the fight against malaria. Genetic and epidemiological surveillance of antimalarial resistant parasite alleles is crucial to guide drug therapies and clinical management. New antimalarial compounds are currently at various stages of clinical trials and regulatory evaluation. Using ∼2000 Plasmodium falciparum genome sequences, we investigated the genetic diversity of eleven gene-targets of promising antimalarial compounds and assessed their potential efficiency across malaria endemic regions...
March 9, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28369746/safety-and-benefits-of-interventions-to-increase-folate-status-in-malaria-endemic-areas
#14
REVIEW
Hans Verhoef, Jacobien Veenemans, Martin N Mwangi, Andrew M Prentice
For decades, folic acid has routinely been given to prevent or treat anaemia in children, pregnant women and people with sickle cell disease. However, there is no conclusive evidence that folate deficiency anaemia constitutes a public health problem in any of these groups. Industrial flour fortification is recommended and implemented in many countries to combat neural tube defects. Dietary folates or folic acid can antagonise the action of antifolate drugs that play a critical role in the prevention and treatment of malaria...
March 29, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28363637/dsm265-for-plasmodium-falciparum-chemoprophylaxis-a-randomised-double-blinded-phase-1-trial-with-controlled-human-malaria-infection
#15
Mihály Sulyok, Thomas Rückle, Alexandra Roth, Raymund E Mürbeth, Stephan Chalon, Nicola Kerr, Sonia Schnieper Samec, Nathalie Gobeau, Carlos Lamsfus Calle, Javier Ibáñez, Zita Sulyok, Jana Held, Tamirat Gebru, Patricia Granados, Sina Brückner, Christian Nguetse, Juliana Mengue, Albert Lalremruata, Kim Lee Sim, Stephen L Hoffman, Jörg J Möhrle, Peter G Kremsner, Benjamin Mordmüller
BACKGROUND: A drug for causal (ie, pre-erythrocytic) prophylaxis of Plasmodium falciparum malaria with prolonged activity would substantially advance malaria control. DSM265 is an experimental antimalarial that selectively inhibits the parasite dihydroorotate dehydrogenase. DSM265 shows in vitro activity against liver and blood stages of P falciparum. We assessed the prophylactic activity of DSM265 against controlled human malaria infection (CHMI). METHODS: At the Institute of Tropical Medicine, Eberhard Karls University (Tübingen, Germany), healthy, malaria-naive adults were allocated to receive 400 mg DSM265 or placebo either 1 day (cohort 1A) or 7 days (cohort 2) before CHMI by direct venous inoculation (DVI) of 3200 aseptic, purified, cryopreserved P falciparum sporozoites (PfSPZ Challenge; Sanaria Inc, Rockville, MD, USA)...
March 28, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28363636/safety-tolerability-pharmacokinetics-and-activity-of-the-novel-long-acting-antimalarial-dsm265-a-two-part-first-in-human-phase-1a-1b-randomised-study
#16
James S McCarthy, Julie Lotharius, Thomas Rückle, Stephan Chalon, Margaret A Phillips, Suzanne Elliott, Silvana Sekuloski, Paul Griffin, Caroline L Ng, David A Fidock, Louise Marquart, Noelle S Williams, Nathalie Gobeau, Lidiya Bebrevska, Maria Rosario, Kennan Marsh, Jörg J Möhrle
BACKGROUND: DSM265 is a novel antimalarial that inhibits plasmodial dihydroorotate dehydrogenase, an enzyme essential for pyrimidine biosynthesis. We investigated the safety, tolerability, and pharmacokinetics of DSM265, and tested its antimalarial activity. METHODS: Healthy participants aged 18-55 years were enrolled in a two-part study: part 1, a single ascending dose (25-1200 mg), double-blind, randomised, placebo-controlled study, and part 2, an open-label, randomised, active-comparator controlled study, in which participants were inoculated with Plasmodium falciparum induced blood-stage malaria (IBSM) and treated with DSM265 (150 mg) or mefloquine (10 mg/kg)...
March 28, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28362936/high-frequency-of-blackwater-fever-among-children-presenting-to-hospital-with-severe-febrile-illnesses-in-eastern-uganda
#17
Peter Olupot-Olupot, Charles Engoru, Sophie Uyoga, Rita Muhindo, Alex Macharia, Sarah Kiguli, Robert O Opoka, Samuel Akech, Carolyne Ndila, Richard Nyeko, George Mtove, Julius Nteziyaremye, Martin Chebet, Elizabeth C George, Abdel G Babiker, Diana M Gibb, Thomas N Williams, Kathryn Maitland
Background: In the Fluid Expansion as a Supportive Treatment (FEAST) trial, an unexpectedly high proportion of participants from eastern Uganda presented with blackwater fever (BWF). Methods: We describe the prevalence and outcome of BWF among trial participants and compare the prevalence of 3 malaria-protective red blood cell polymorphisms in BWF cases vs both trial (non-BWF) and population controls. Results: Of 3170 trial participants, 394 (12...
April 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28356902/is-open-science-the-future-of-drug-development
#18
REVIEW
Daniel L Shaw
Traditional drug development models are widely perceived as opaque and inefficient, with the cost of research and development continuing to rise even as production of new drugs stays constant. Searching for strategies to improve the drug discovery process, the biomedical research field has begun to embrace open strategies. The resulting changes are starting to reshape the industry. Open science-an umbrella term for diverse strategies that seek external input and public engagement-has become an essential tool with researchers, who are increasingly turning to collaboration, crowdsourcing, data sharing, and open sourcing to tackle some of the most pressing problems in medicine...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356302/impact-of-introduction-of-rapid-diagnostic-tests-for-malaria-on-antibiotic-prescribing-analysis-of-observational-and-randomised-studies-in-public-and-private-healthcare-settings
#19
Heidi Hopkins, Katia J Bruxvoort, Matthew E Cairns, Clare I R Chandler, Baptiste Leurent, Evelyn K Ansah, Frank Baiden, Kimberly A Baltzell, Anders Björkman, Helen E D Burchett, Siân E Clarke, Deborah D DiLiberto, Kristina Elfving, Catherine Goodman, Kristian S Hansen, S Patrick Kachur, Sham Lal, David G Lalloo, Toby Leslie, Pascal Magnussen, Lindsay Mangham Jefferies, Andreas Mårtensson, Ismail Mayan, Anthony K Mbonye, Mwinyi I Msellem, Obinna E Onwujekwe, Seth Owusu-Agyei, Hugh Reyburn, Mark W Rowland, Delér Shakely, Lasse S Vestergaard, Jayne Webster, Virginia L Wiseman, Shunmay Yeung, David Schellenberg, Sarah G Staedke, Christopher J M Whitty
Objectives To examine the impact of use of rapid diagnostic tests for malaria on prescribing of antimicrobials, specifically antibiotics, for acute febrile illness in Africa and Asia.Design Analysisof nine preselected linked and codesigned observational and randomised studies (eight cluster or individually randomised trials and one observational study).Setting Public and private healthcare settings, 2007-13, in Afghanistan, Cameroon, Ghana, Nigeria, Tanzania, and Uganda.Participants 522 480 children and adults with acute febrile illness...
March 29, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28341111/generation-characterization-and-immunogenicity-of-a-novel-chimeric-recombinant-protein-based-on-plasmodium-vivax-ama-1-and-msp119
#20
Mariana Vilela Rocha, Kátia Sanches Françoso, Luciana Chagas Lima, Tarsila Mendes Camargo, Ricardo L D Machado, Fabio T M Costa, Laurent Rénia, Francois Nosten, Bruce Russell, Mauricio M Rodrigues, Irene S Soares
Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA166-MSP119)...
March 21, 2017: Vaccine
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