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https://www.readbyqxmd.com/read/29220497/post-treatment-hrp2-clearance-in-patients-with-uncomplicated-plasmodium-falciparum-malaria
#1
Mateusz M Plucinski, Pedro Rafael Dimbu, Filomeno Fortes, Salim Abdulla, Saumu Ahmed, Julie Gutman, S Patrick Kachur, Aida Badiane, Daouda Ndiaye, Eldin Talundzic, Naomi Lucchi, Michael Aidoo, Venkatachalam Udhayakumar, Eric Halsey, Eric Rogier
Background: Response to antimalarial treatment is assessed using serial microscopy. New techniques for accurate measurement of the Plasmodium falciparum histidine rich protein 2 (HRP2) antigen have made monitoring antigen concentration over time a potential alternative for assessing treatment response. Methods: Post-treatment HRP2 concentration was measured in longitudinal samples from 537 participants with P. falciparum malaria from efficacy trials in Angola, Tanzania, and Senegal...
December 6, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29216395/a-randomized-trial-of-the-prophylactic-activity-of-dsm265-against-pre-erythrocytic-plasmodium-falciparum-controlled-human-malaria-infection-by-mosquito-bites-and-direct-venous-inoculation
#2
Sean C Murphy, Elizabeth R Duke, Kelly J Shipman, Ryan L Jensen, Youyi Fong, Sue Ferguson, Holly E Janes, Kevin Gillespie, Annette M Seilie, Amelia E Hanron, Laurie Rinn, Matthew Fishbaugher, Tracie VonGoedert, Emma Fritzen, Stefan H Kappe, Ming Chang, Jason C Sousa, Sean R Marcsisin, Stephan Chalon, Stephan Duparc, Nicola Kerr, Jörg J Möhrle, Nicole Andenmatten, Thomas Rueckle, James G Kublin
Background: DSM265 is a selective inhibitor of Plasmodium dihydroorotate dehydrogenase that fully protected against controlled human malarial infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites when administered one day pre-challenge and provided partial protection when administered seven days pre-challenge. Methods: A double-blind, randomized, placebo-controlled trial was performed to assess safety, tolerability, pharmacokinetics and efficacy of one oral dose of 400 mg DSM265 pre-CHMI...
December 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29213269/safety-and-immunogenicity-of-malaria-vectored-vaccines-given-with-routine-expanded-program-on-immunization-vaccines-in-gambian-infants-and-neonates-a-randomized-controlled-trial
#3
Victorine A Mensah, Sophie Roetynck, Ebrima K Kanteh, Georgina Bowyer, Amy Ndaw, Francis Oko, Carly M Bliss, Ya Jankey Jagne, Riccardo Cortese, Alfredo Nicosia, Rachel Roberts, Flavia D'Alessio, Odile Leroy, Babacar Faye, Beate Kampmann, Badara Cisse, Kalifa Bojang, Stephen Gerry, Nicola K Viebig, Alison M Lawrie, Ed Clarke, Egeruan B Imoukhuede, Katie J Ewer, Adrian V S Hill, Muhammed O Afolabi
Background: Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29209029/an-in-vitro-assay-to-measure-antibody-mediated-inhibition-of-p-berghei-sporozoite-invasion-against-p-falciparum-antigens
#4
Ana Rodríguez-Galán, Ahmed M Salman, Georgina Bowyer, Katharine A Collins, Rhea J Longley, Florian Brod, Marta Ulaszewska, Katie J Ewer, Chris J Janse, Shahid M Khan, Julius C Hafalla, Adrian V S Hill, Alexandra J Spencer
A large research effort is currently underway to find an effective and affordable malaria vaccine. Tools that enable the rapid evaluation of protective immune responses are essential to vaccine development as they can provide selection criteria to rank order vaccine candidates. In this study we have revisited the Inhibition of Sporozoite Invasion (ISI) assay to assess the ability of antibodies to inhibit sporozoite infection of hepatocytes. By using GFP expressing sporozoites of the rodent parasite P. berghei we are able to robustly quantify parasite infection of hepatocyte cell lines by flow cytometry...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29206727/assessment-of-myocardial-function-and-injury-by-echocardiography-and-cardiac-biomarkers-in-african-children-with-severe-plasmodium-falciparum-malaria
#5
Simon Kotlyar, Peter Olupot-Olupot, Julius Nteziyaremye, Samuel O Akech, Sophie Uyoga, Rita Muhindo, Christopher L Moore, Kathryn Maitland
OBJECTIVES: Perturbed hemodynamic function complicates severe malaria. The Fluid Expansion as Supportive Therapy trial demonstrated that fluid resuscitation, involving children with severe malaria, was associated with increased mortality, primarily due to cardiovascular collapse, suggesting that myocardial dysfunction may have a role. The aim of this study was to characterize cardiac function in children with severe malaria. DESIGN: A prospective observational study with clinical, laboratory, and echocardiographic data collected at presentation (T0) and 24 hours (T1) in children with severe malaria...
December 4, 2017: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/29196702/spatial-statistical-modelling-of-capillary-non-perfusion-in-the-retina
#6
Ian J C MacCormick, Yalin Zheng, Silvester Czanner, Yitian Zhao, Peter J Diggle, Simon P Harding, Gabriela Czanner
Manual grading of lesions in retinal images is relevant to clinical management and clinical trials, but it is time-consuming and expensive. Furthermore, it collects only limited information - such as lesion size or frequency. The spatial distribution of lesions is ignored, even though it may contribute to the overall clinical assessment of disease severity, and correspond to microvascular and physiological topography. Capillary non-perfusion (CNP) lesions are central to the pathogenesis of major causes of vision loss...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190855/efficacy-of-lophira-alata-leaf-extract-and-its-combination-with-artesunate-in-mice-prior-exposed-to-plasmodium-berghei
#7
Mofolusho O Falade, Favour Komoni, Roseangela I Nwuba
Enhanced antimalarial activity of plant extracts used for treatment of malaria in endemic areas is attributed to partial immunity gained by prior infection. This suggests synergy between immunity and extract activity in treatment. Testing this hypothesis, rodent malaria was used to determine efficacy of Lophira alata leaf extracts in treating malaria in prior infected mice. One round of P. berghei infection and Pyrimethamine drug-cure was used to establish partial immunity in mice. Previously Exposed Mice (PEM) and Previously Unexposed Mice (PUM) mice challenged with P...
November 30, 2017: Drug Research
https://www.readbyqxmd.com/read/29179625/the-ethics-of-health-care-delivery-in-a-pediatric-malaria-vaccine-trial-the-perspectives-of-stakeholders-from-ghana-and-tanzania
#8
Claire Leonie Ward, David Shaw, Evelyn Anane-Sarpong, Osman Sankoh, Marcel Tanner, Bernice Elger
This study explores ethical issues raised in providing medical care to participants and communities of low-resource settings involved in a Phase II/III pediatric malaria vaccine trial (PMVT). We conducted 52 key informant interviews with major stakeholders of an international multi-center PMVT (GSK/PATH-MVI RTS,S) (NCT00866619) in Ghana and Tanzania. Based on their stakeholder experiences, the responses fell into three main themes: (a) undue inducement, (b) community disparities, and (c) broad therapeutic misconceptions...
November 1, 2017: Journal of Empirical Research on Human Research Ethics: JERHRE
https://www.readbyqxmd.com/read/29174651/cancer-combination-therapy-of-the-sesquiterpenoid-artesunate-and-the-selective-egfr-tyrosine-kinase-inhibitor-erlotinib
#9
Thomas Efferth
BACKGROUND: The shift from cytotoxic to targeted chemotherapy led to improved treatment outcomes in oncology. Nevertheless, many cancer patients cannot be cured from their disease because of the development of drug resistance and side effects. PURPOSE: There is an ongoing quest for novel compounds, which raised not only the interest in natural products but also in novel combination therapy regimens. STUDY DESIGN: In this review, we report on the inhibition epidermal growth factor receptor (EGFR) by targeted small molecules and their combination with natural products from medicinal plants...
November 10, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29166928/effects-of-long-term-weekly-iron-and-folic-acid-supplementation-on-lower-genital-tract-infection-a-double-blind-randomised-controlled-trial-in-burkina-faso
#10
Loretta Brabin, Stephen A Roberts, Sabine Gies, Andrew Nelson, Salou Diallo, Christopher J Stewart, Adama Kazienga, Julia Birtles, Sayouba Ouedraogo, Yves Claeys, Halidou Tinto, Umberto d'Alessandro, E Brian Faragher, Bernard Brabin
BACKGROUND: Provision of routine iron supplements to prevent anaemia could increase the risk for lower genital tract infections as virulence of some pathogens depends on iron availability. This trial in Burkina Faso assessed whether weekly periconceptional iron supplementation increased the risk of lower genital tract infection in young non-pregnant and pregnant women. METHODS: Genital tract infections were assessed within a double blind, controlled, non-inferiority trial of malaria risk among nulliparous women, randomised to receive either iron and folic acid or folic acid alone, weekly, under direct observation for 18 months...
November 23, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29166911/effective-strategies-for-scaling-up-evidence-based-practices-in-primary-care-a-systematic-review
#11
REVIEW
Ali Ben Charif, Hervé Tchala Vignon Zomahoun, Annie LeBlanc, Léa Langlois, Luke Wolfenden, Sze Lin Yoong, Christopher M Williams, Roxanne Lépine, France Légaré
BACKGROUND: While an extensive array of existing evidence-based practices (EBPs) have the potential to improve patient outcomes, little is known about how to implement EBPs on a larger scale. Therefore, we sought to identify effective strategies for scaling up EBPs in primary care. METHODS: We conducted a systematic review with the following inclusion criteria: (i) study design: randomized and non-randomized controlled trials, before-and-after (with/without control), and interrupted time series; (ii) participants: primary care-related units (e...
November 22, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/29165227/reflections-on-a-community-engagement-strategy-for-mass-antimalarial-drug-administration-in-cambodia
#12
Thomas J Peto, Rupam Tripura, Chan Davoeung, Chea Nguon, Sanann Nou, Chhouen Heng, Pich Kunthea, Bipin Adhikari, Renly Lim, Nicola James, Christopher Pell, Phaik Yeong Cheah
Mass drug administration (MDA) to interrupt malaria transmission requires the participation of entire communities. As part of a clinical trial in western Cambodia, four villages received MDA in 2015-2016. Before approaching study communities, a collaboration was established with the local health authorities, village leaders, and village malaria workers. Formative research guided the development of engagement strategies. In each village, a team of volunteers was formed to explain MDA to their neighbors and provide support during implementation...
November 20, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29162320/controlled-human-infections-a-report-from-the-controlled-human-infection-models-workshop-leiden-university-medical-centre-4-6-may-2016
#13
Meta Roestenberg, Annie Mo, Peter G Kremsner, Maria Yazdanbakhsh
The principle of deliberately infecting humans with infectious agents in a controlled setting, so-called controlled human infections (CHI), is not novel. Many CHI models have a long history and were established decades ago such as the intentional exposure to yellow fever and dengue performed in the 1900's (Reed, 1902) [2]. In these times bioethics and scientific reasoning were in their infancy. Nowadays, clinical trials are highly regulated and CHI are executed worldwide. Controlled human malaria infections and influenza infections are the two most frequently practiced...
November 18, 2017: Vaccine
https://www.readbyqxmd.com/read/29162120/a-village-level-cluster-randomized-entomological-evaluation-of-combination-long-lasting-insecticidal-nets-containing-pyrethroid-plus-pbo-synergist-in-southern-mali
#14
Moussa B M Cisse, Djibril Sangare, Richard M Oxborough, Abdourhamane Dicko, Dereje Dengela, Aboubacar Sadou, Jules Mihigo, Kristen George, Laura Norris, Christen Fornadel
BACKGROUND: There is growing concern that malaria vector resistance to pyrethroid insecticides may reduce the effectiveness of long-lasting insecticidal nets (LLINs). Combination LLINs are designed to control susceptible and pyrethroid-resistant mosquito populations through a mixture of pyrethroid with piperonyl butoxide (PBO) synergist. A cluster randomized trial with entomology outcome measures was conducted in Mali to determine the added benefit over mono-treated pyrethroid predecessors...
November 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29153778/the-frontline-of-controlled-human-malaria-infections-a-report-from-the-controlled-human-infection-models-workshop-in-leiden-university-medical-centre-5-may-2016
#15
Meta Roestenberg, Benjamin Mordmüller, Chris Ockenhouse, Annie Mo, Maria Yazdanbakhsh, Peter G Kremsner
Controlled Human Malaria Infection (CHMI) is the most practiced controlled human infection model nowadays and there is an exponential increase in implementation of the model worldwide. During the Controlled Human Infection Models Workshop in Leiden, one day was dedicated to the discussion of the advances made and gaps in Controlled Human Malaria Infection (CHMI) trials. Factors contributing to this impressive expansion in the number of CHMI trials have been related to the ability to perform CHMI using injectable cryopreserved sporozoites (a product from Sanaria Inc...
November 16, 2017: Vaccine
https://www.readbyqxmd.com/read/29151351/immucillins-in-infectious-diseases
#16
Gary B Evans, Peter C Tyler, Vern L Schramm
Transition state theory proposes that stable chemical mimics of enzymatic transition states will be powerful inhibitors of their cognate enzymes. The Immucillins are chemically stable analogues that mimic the ribocation and leaving-group features of N-ribosyltransferase transition states. Infectious disease agents often rely on ribosyltransferase chemistry in pathways involving precursor synthesis for nucleic acids, salvage of nucleic acid precursors from the host or synthetic pathways with nucleoside intermediates...
November 19, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29144217/mechanisms-of-naturally-acquired-immunity-to-p-falciparum-and-approaches-to-identify-merozoite-antigen-targets
#17
Julie Healer, Chris Y Chiu, Diana S Hansen
Malaria is one the most serious infectious diseases with over 200 million clinical cases annually. Most cases of the severe disease are caused by Plasmodium falciparum. The blood stage of Plasmodium parasite is entirely responsible for malaria-associated pathology. The population most susceptible to severe malaria are children under the age of 5, with low levels of immunity. It is only after many years of repeated exposure that individuals living in endemic areas develop clinical immunity. This form of protection prevents clinical episodes by substantially reducing parasite burden...
November 16, 2017: Parasitology
https://www.readbyqxmd.com/read/29143637/impact-of-malaria-interventions-on-child-mortality-in-endemic-african-settings-comparison-and-alignment-between-list-and-spectrum-malaria-model
#18
Eline Korenromp, Matthew Hamilton, Rachel Sanders, Guy Mahiané, Olivier J T Briët, Thomas Smith, William Winfrey, Neff Walker, John Stover
BACKGROUND: In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. METHODS: The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults...
November 7, 2017: BMC Public Health
https://www.readbyqxmd.com/read/29141763/pilot-study-of-the-addition-of-mass-treatment-for-malaria-to-existing-school-based-programs-to-treat-neglected-tropical-diseases
#19
Lauren M Cohee, Moses Chilombe, Andrew Ngwira, Samuel K Jemu, Don P Mathanga, Miriam K Laufer
Malaria and neglected tropical diseases (NTDs), including schistosomiasis and soil transmitted helminths, threaten the health of school aged in sub-Saharan Africa. Established school-based mass drug administration (MDA) programs are used to control NTDs. Recent clinical trials have shown benefit of mass treatment of malaria in schools. The potential of adding malaria treatment to existing NTD programs has not been thoroughly evaluated. We offered malaria treatment with artemether-lumefantrine during routine NTD MDA and developed peer education programs in two primary schools in southern Malawi...
November 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29141739/advancing-global-health-through-development-and-clinical-trials-partnerships-a-randomized-placebo-controlled-double-blind-assessment-of-safety-tolerability-and-immunogenicity-of-plasmodium-falciparum-sporozoites-vaccine-for-malaria-in-healthy-equatoguinean
#20
Ally Olotu, Vicente Urbano, Ali Hamad, Martin Eka, Mwajuma Chemba, Elizabeth Nyakarungu, Jose Raso, Esther Eburi, Dolores O Mandumbi, Dianna Hergott, Carl D Maas, Mitoha O Ayekaba, Diosdado N Milang, Matilde R Rivas, Tobias Schindler, Oscar M Embon, Adam J Ruben, Elizabeth Saverino, Yonas Abebe, Natasha Kc, Eric R James, Tooba Murshedkar, Anita Manoj, Sumana Chakravarty, Minglin Li, Matthew Adams, Chris Schwabe, Luis Segura, Claudia Daubenberger, Marcel Tanner, Thomas L Richie, Peter F Billingsley, B Kim Lee Sim, Salim Abdulla, Stephen L Hoffman
Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria(®)Plasmodium falciparum sporozoites (PfSPZ) Vaccine is being developed for this purpose. To begin the process of establishing the efficacy of and implementing a PfSPZ Vaccine mass vaccination program in EG, we decided to conduct a series of clinical trials of PfSPZ Vaccine on Bioko Island...
October 30, 2017: American Journal of Tropical Medicine and Hygiene
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