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https://www.readbyqxmd.com/read/28724415/identification-and-characterization-of-the-antiplasmodial-activity-of-hsp90-inhibitors
#1
Claribel Murillo-Solano, Chunmin Dong, Cecilia G Sanchez, Juan C Pizarro
BACKGROUND: The recent reduction in mortality due to malaria is being threatened by the appearance of Plasmodium falciparum parasites that are resistant to artemisinin in Southeast Asia. To limit the impact of resistant parasites and their spread across the world, there is a need to validate anti-malarial drug targets and identify new leads that will serve as foundations for future drug development programmes targeting malaria. Towards that end, the antiplasmodial potential of several Hsp90 inhibitors was characterized...
July 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28722611/phase-2a-open-label-4-escalating-dose-randomized-multicenter-study-evaluating-the-safety-and-activity-of-ferroquine-ssr97193-plus-artesunate-versus-amodiaquine-plus-artesunate-in-african-adult-men-with-uncomplicated-plasmodium-falciparum-malaria
#2
Christian Supan, Ghyslain Mombo-Ngoma, Maryvonne Kombila, Carmen L Ospina Salazar, Jana Held, Bertrand Lell, Cathy Cantalloube, Elhadj Djeriou, Bernhards Ogutu, John Waitumbi, Nekoye Otsula, Duncan Apollo, Mark E Polhemus, Peter G Kremsner, Douglas S Walsh
Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator...
May 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722588/optimizing-direct-membrane-and-direct-skin-feeding-assays-for-plasmodium-falciparum-transmission-blocking-vaccine-trials-in-bancoumana-mali
#3
Mamadou B Coulibaly, Erin E Gabriel, Youssouf Sinaba, Daman Sylla, Adama Sacko, Lakamy Sylla, Boubacar Coulibaly, Jen C C Hume, Ibrahima Baber, Mahamadoun H Assadou, Issaka Sagara, Yimin Wu, Sara A Healy, Ogobara Doumbo, Sekou F Traore, Patrick E Duffy
Malaria transmission-blocking vaccines (TBV) have been evaluated in field trials in Mali, since 2013. However, the assays currently used to measure serum antibody TB activity (TBA) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. Herein, we report a study conducted in Bancoumana village, Mali, where we identify and optimize the parameters that contribute to successful mosquito feeding outcomes in both direct skin feeds (DSFs) and direct membrane feeding assays (DMFA)...
June 26, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28722569/mass-azithromycin-and-malaria-parasitemia-in-niger-results-from-a-community-randomized-trial
#4
Kieran S O'Brien, Sun Y Cotter, Abdou Amza, Boubacar Kadri, Baido Nassirou, Nicole E Stoller, Zhaoxia Zhou, Chris Cotter, Sheila K West, Robin L Bailey, Philip J Rosenthal, Bruce D Gaynor, Travis C Porco, Thomas M Lietman
Studies designed to determine the effects of mass administration of azithromycin on trachoma have suggested that mass azithromycin distributions may also reduce the prevalence of malaria. These studies have typically examined the impact of a small number of treatments over short durations. In this prespecified substudy of a cluster-randomized trial for trachoma, we compared malaria parasitemia prevalence in 24 communities in Niger randomized to receive either annual or biannual mass azithromycin distributions over 3 years...
June 19, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719294/molecular-markers-for-sensitive-detection-of-plasmodium-falciparum-asexual-stage-parasites-and-their-application-in-a-malaria-clinical-trial
#5
Fitsum G Tadesse, Kjerstin Lanke, Issa Nebie, Jodie A Schildkraut, Bronner P Gonçalves, Alfred B Tiono, Robert Sauerwein, Chris Drakeley, Teun Bousema, Sanna R Rijpma
Plasmodium falciparum parasite life stages respond differently to antimalarial drugs. Sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. In this study, we compared the performance of skeleton-binding protein 1 (SBP1), ring-infected erythrocyte surface antigen, Hyp8, ring-exported protein 1 (REX1), and PHISTb mRNA for detecting ring-stage trophozoite-specific transcripts using quantitative reverse transcriptase polymerase chain reaction...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719292/malaria-infection-and-gametocyte-carriage-rates-in-preparation-for-transmission-blocking-vaccine-trials-in-bancoumana-mali
#6
Mahamadoun Hamady Assadou, Issaka Sagara, Sara A Healy, Merepen Agnes Guindo, Mamady Kone, Sintry Sanogo, M'Bouye Doucoure, Sekouba Keita, Ruth D Ellis, Yimin Wu, Freda Omaswa, Patrick E Duffy, Ogobara K Doumbo
The epidemiological characterization of transmission reservoirs is a critical step in preparation for interventional trials for malaria elimination/eradication. Using cluster sampling and households/compounds as units of sampling, we recruited and followed monthly, from June 2011 to June 2012, 250 volunteers 3 months to 50 years of age in Bancoumana, Mali. In July 2012, only participants 5-35 years of age (N = 121) were reenrolled and followed for an additional year. Malaria infection prevalence was highest in October in both 2011 (21...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28716015/illegal-gold-miners-in-french-guiana-a-neglected-population-with-poor-health
#7
Maylis Douine, Emilie Mosnier, Quentin Le Hingrat, Charlotte Charpentier, Florine Corlin, Louise Hureau, Antoine Adenis, Yassamine Lazrek, Florence Niemetsky, Anne-Laure Aucouturier, Magalie Demar, Lise Musset, Mathieu Nacher
BACKGROUND: In French Guiana, a French overseas territory in South America, 6 to 10 thousands undocumented persons work illegally in gold mining sites in the Amazonian forest. Precarious life conditions lead to poor health but few data exist on the health status of illegal gold miners in French Guiana. The objective of this article was to describe the sociodemographic and health status of this vulnerable population. METHOD: A prospective cross-sectional survey was conducted in 2015 on gold mine supply sites at the border between French Guiana and Suriname...
July 17, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28708072/iron-fortified-complementary-foods-containing-a-mixture-of-sodium-iron-edta-with-either-ferrous-fumarate-or-ferric-pyrophosphate-reduce-iron-deficiency-anemia-in-12-to-36-month-old-children-in-a-malaria-endemic-setting-a-secondary-analysis-of-a-cluster-randomized
#8
Dominik Glinz, Rita Wegmüller, Mamadou Ouattara, Victorine G Diakité, Grant J Aaron, Lorenz Hofer, Michael B Zimmermann, Lukas G Adiossan, Jürg Utzinger, Eliézer K N'Goran, Richard F Hurrell
Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire...
July 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28702028/immunization-with-the-malaria-diversity-covering-blood-stage-vaccine-candidate-plasmodium-falciparum-apical-membrane-antigen-1-dico-in-complex-with-its-natural-ligand-pfron2-does-not-improve-the-in-vitro-efficacy
#9
Holger Spiegel, Alexander Boes, Rolf Fendel, Andreas Reimann, Stefan Schillberg, Rainer Fischer
The blood-stage malaria vaccine candidate Plasmodium falciparum apical membrane antigen 1 (PfAMA1) can induce strong parasite growth-inhibitory antibody responses in animals but has not achieved the anticipated efficacy in clinical trials. Possible explanations in humans are the insufficient potency of the elicited antibody responses, as well as the high degree of sequence polymorphisms found in the field. Several strategies have been developed to improve the cross-strain coverage of PfAMA1-based vaccines, whereas innovative concepts to increase the potency of PfAMA1-specific IgG responses have received little attention even though this may be an essential requirement for protective efficacy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28701387/high-iron-stores-in-the-low-malaria-season-increase-malaria-risk-in-the-high-transmission-season-in-a-prospective-cohort-of-rural-zambian-children
#10
Maxwell A Barffour, Kerry J Schulze, Christian L Coles, Justin Chileshe, Ng'andwe Kalungwana, Margia Arguello, Ward Siamusantu, William J Moss, Keith P West, Amanda C Palmer
Background: Higher iron stores, defined by serum ferritin (SF) concentration, may increase malaria risk.Objective: We evaluated the association between SF assessed during low malaria season and the risk of malaria during high malaria season, controlling for inflammation.Methods: Data for this prospective study were collected from children aged 4-8 y (n = 745) participating in a biofortified maize efficacy trial in rural Zambia. All malaria cases were treated at baseline (September 2012). We used baseline SF and malaria status indicated by positive microscopy at endline (March 2013) to define exposure and outcome, respectively...
July 12, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28699823/the-gmz2-malaria-vaccine-from-concept-to-efficacy-in-humans
#11
Michael Theisen, Bright Adu, Benjamin Mordmüller, Subhash Singh
GMZ2 is a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of Plasmodium falciparum, and is designed with the aim of mimicking naturally acquired anti-malarial immunity. The rationale for combining these two antigens is based on a series of immune epidemiological studies from geographically diverse malaria endemic regions; functional in vitro studies; and pre-clinical studies in rodents and New World monkeys. GMZ2 adjuvanted with alhydrogel® (alum) was well tolerated and immunogenic in three phase 1 studies...
July 12, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28687086/ivermectin-susceptibility-and-sporontocidal-effect-in-greater-mekong-subregion-anopheles
#12
Kevin C Kobylinski, Ratawan Ubalee, Alongkot Ponlawat, Chanyapat Nitatsukprasert, Siriporn Phasomkulsolsil, Thanaporn Wattanakul, Joel Tarning, Kesara Na-Bangchang, Patrick W McCardle, Silas A Davidson, Jason H Richardson
BACKGROUND: Novel vector control methods that can directly target outdoor malaria transmission are urgently needed in the Greater Mekong Subregion (GMS) to accelerate malaria elimination and artemisinin resistance containment efforts. Ivermectin mass drug administration (MDA) to humans has been shown to effectively kill wild Anopheles and suppress malaria transmission in West Africa. Preliminary laboratory investigations were performed to determine ivermectin susceptibility and sporontocidal effect in GMS Anopheles malaria vectors coupled with pharmacokinetic models of ivermectin at escalating doses...
July 7, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28685042/comprehensive-review-of-the-evidence-regarding-the-effectiveness-of-community-based-primary-health-care-in-improving-maternal-neonatal-and-child-health-4-child-health-findings
#13
Paul A Freeman, Meike Schleiff, Emma Sacks, Bahie M Rassekh, Sundeep Gupta, Henry B Perry
BACKGROUND: This paper assesses the effectiveness of community-based primary health care (CBPHC) in improving child health beyond the neonatal period. Although there has been an accelerated decline in global under-5 mortality since 2000, mortality rates remain high in much of sub-Saharan Africa and in some south Asian countries where under-5 mortality is also decreasing more slowly. Essential interventions for child health at the community level have been identified. Our review aims to contribute further to this knowledge by examining how strong the evidence is and exploring in greater detail what specific interventions and implementation strategies appear to be effective...
June 2017: Journal of Global Health
https://www.readbyqxmd.com/read/28683750/use-of-malaria-rapid-diagnostic-tests-by-community-health-workers-in-afghanistan-cluster-randomised-trial
#14
Toby Leslie, Mark Rowland, Amy Mikhail, Bonnie Cundill, Barbara Willey, Asif Alokozai, Ismail Mayan, Anwar Hasanzai, Sayed Habibullah Baktash, Nader Mohammed, Molly Wood, Habib-U-Rahman Rahimi, Baptiste Laurent, Cyril Buhler, Christopher J M Whitty
BACKGROUND: The World Health Organisation (WHO) recommends parasitological diagnosis of malaria before treatment, but use of malaria rapid diagnostic tests (mRDTs) by community health workers (CHWs) has not been fully tested within health services in south and central Asia. mRDTs could allow CHWs to diagnose malaria accurately, improving treatment of febrile illness. METHODS: A cluster randomised trial in community health services was undertaken in Afghanistan. The primary outcome was the proportion of suspected malaria cases correctly treated for polymerase chain reaction (PCR)-confirmed malaria and PCR negative cases receiving no antimalarial drugs measured at the level of the patient...
July 7, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28674061/assessment-of-clinical-pharmacokinetic-drug-drug-interaction-of-antimalarial-drugs-%C3%AE-%C3%AE-arteether-and-sulfadoxine-pyrimethamine
#15
Y S Chhonker, V V Bhosale, S K Sonkar, H Chandasana, D Kumar, S Vaish, S C Choudhary, S Bhadhuria, S Sharma, R K Singh, G K Jain, A K Vaish, S P S Gaur, R S Bhatta
The antimalarial drugs combination therapy is now being widely used for treatment of uncomplicated malaria. The objective of the present study was to investigate the effects of co-administration of intramuscular α/β-arteether (AE) and oral sulfadoxine-pyrimethamine (SP) on the pharmacokinetic properties of each drug as a drug-drug interaction study to support developing the fixed-dose combination therapy. Single-dose, open-label, crossover clinical trial was conducted in healthy adult Indian male volunteers (18-45 years, n=13), received single dose of AE, SP and combination dose of AE and SP...
July 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28669839/optimal-antimalarial-dose-regimens-for-chloroquine-in-pregnancy-based-on-population-pharmacokinetic-modelling
#16
Sam Salman, Francesca Baiwog, Madhu Page-Sharp, Kay Kose, Harin A Karunajeewa, Ivo Mueller, Stephen J Rogerson, Peter M Siba, Kenneth F Ilett, Timothy M E Davis
Despite extensive use and accumulated evidence of safety, there have been few pharmacokinetic studies from which appropriate chloroquine (CQ) dose regimens could be developed specifically for pregnant women. Such optimized CQ-based regimens, used as treatment for acute malaria or as intermittent preventive treatment in pregnancy (IPTp), may have a valuable role if parasite CQ sensitivity returns following reduced drug pressure. In this study, population pharmacokinetic-pharmacodynamic modelling was used to simultaneously analyze plasma concentration-time data for CQ and its active metabolite desethylchloroquine (DCQ) in 44 non-pregnant and 45 pregnant Papua New Guinean women treated with CQ and sulfadoxine-pyrimethamine (SP) or azithromycin (AZI)...
June 29, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28668230/global-funding-trends-for-malaria-research-in-sub-saharan-africa-a-systematic-analysis
#17
Michael G Head, Sian Goss, Yann Gelister, Victor Alegana, Rebecca J Brown, Stuart C Clarke, Joseph R A Fitchett, Rifat Atun, J Anthony G Scott, Marie-Louise Newell, Sabu S Padmadas, Andrew J Tatem
BACKGROUND: Total domestic and international funding for malaria is inadequate to achieve WHO global targets in burden reduction by 2030. We describe the trends of investments in malaria-related research in sub-Saharan Africa and compare investment with national disease burden to identify areas of funding strength and potentially neglected populations. We also considered funding for malaria control. METHODS: Research funding data related to malaria for 1997-2013 were sourced from existing datasets, from 13 major public and philanthropic global health funders, and from funding databases...
June 28, 2017: Lancet Global Health
https://www.readbyqxmd.com/read/28646586/vaccine-candidate-discovery-for-the-next-generation-of-malaria-vaccines
#18
REVIEW
James Tuju, Gathoni Kamuyu, Linda M Murungi, Faith H A Osier
Although epidemiological observations, IgG passive transfer studies and experimental infections in humans all support the feasibility of developing highly effective malaria vaccines, the precise antigens that induce protective immunity remain uncertain. Here, we review the methodologies applied to vaccine candidate discovery for Plasmodium falciparum malaria from the pre- to post- genomic era. Probing of genomic and/or cDNA libraries with antibodies of defined specificities or functional activity predominated the former, while reverse vaccinology encompassing high throughput in silico analyses of genomic, transcriptomic or proteomic parasite datasets is the mainstay of the latter...
June 24, 2017: Immunology
https://www.readbyqxmd.com/read/28645255/haemoglobin-changes-and-risk-of-anaemia-following-treatment-for-uncomplicated-falciparum-malaria-in-sub-saharan-africa
#19
Julien Zwang, Umberto D'Alessandro, Jean-Louis Ndiaye, Abdoulaye A Djimdé, Grant Dorsey, Andreas A Mårtensson, Corine Karema, Piero L Olliaro
BACKGROUND: Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. METHODS: Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models...
June 23, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28639487/mrp2-abcc2-c1515y-polymorphism-modulates-exposure-to-lumefantrine-during-artemether-lumefantrine-antimalarial-therapy
#20
Karin Vos, Carlotta Lo Sciuto, Rita Piedade, Michael Ashton, Anders Björkman, Billy Ngasala, Andreas Mårtensson, José Pedro Gil
AIM: To investigate the potential involvement of the hepatic ATP-binding cassette transporters MRP2 and MDR1 in the disposition of lumefantrine (LUM) among patients with uncomplicated Plasmodium falciparum malaria. MATERIALS & METHODS: The tag SNPs MDR1/ABCB1 C3435T and MRP2/ABCC2 C1515Y were determined in two artemether-LUM clinical trials, including a pharmacokinetic/pharmacodynamic study focused on the treatment phase (72 h), and an efficacy trial where day 7 (D7) LUM levels were measured...
July 2017: Pharmacogenomics
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