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https://www.readbyqxmd.com/read/28336173/effects-of-artesunate-on-some-biochemical-parameters-in-pregnant-albino-wistar-rats-challenged-with-lethal-strain-plasmodium-berghei-nk65-appreciating-the-activities-of-artemisinin-drugs-on-key-pregnancy-hormone-balance
#1
Chinaka O Nwaehujor, Onyeka V Asuzu, Daniel D Nwibo, Obichukwu C Nwobi, Ihechiluru I Ezeigbo
In humans, malaria in pregnancy can cause serious maternal and foetal morbidity and in extreme untreated cases, foetal mortality occurs. The therapeutic approach to curbing this malaise is the administration of an effective and/or combinations of anti-malaria medicaments. Acute or chronic administration of some of these drugs, however, gives rise to some adverse medical conditions including reproductive dysfunction, especially in pregnancy. Studies aimed at the hormonal interplays following administration of these drugs in pregnancy have been limited due to too few appropriate animal models...
March 20, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28334018/development-of-an-evidence-evaluation-and-synthesis-system-for-drug-drug-interactions-and-its-application-to-a-systematic-review-of-hiv-and-malaria-co-infection
#2
Kay Seden, Sara Gibbons, Catia Marzolini, Jonathan M Schapiro, David M Burger, David J Back, Saye H Khoo
BACKGROUND: In all settings, there are challenges associated with safely treating patients with multimorbidity and polypharmacy. The need to characterise, understand and limit harms resulting from medication use is therefore increasingly important. Drug-drug interactions (DDIs) are prevalent in patients taking antiretrovirals (ARVs) and if unmanaged, may pose considerable risk to treatment outcome. One of the biggest challenges in preventing DDIs is the substantial gap between theory and clinical practice...
2017: PloS One
https://www.readbyqxmd.com/read/28328735/building-workforce-capacity-abroad-while-strengthening-global-health-programs-at-home-participation-of-seven-harvard-affiliated-institutions-in-a-health-professional-training-initiative-in-rwanda
#3
Corrado Cancedda, Robert Riviello, Kim Wilson, Kirstin W Scott, Meenu Tuteja, Jane R Barrow, Bethany Hedt-Gauthier, Gene Bukhman, Jennifer Scott, Danny Milner, Giuseppe Raviola, Barbara Weissman, Stacy Smith, Tej Nuthulaganti, Craig D McClain, Barbara E Bierer, Paul E Farmer, Anne E Becker, Agnes Binagwaho, Joseph Rhatigan, David E Golan
A consortium of 22 U.S. academic institutions is currently participating in the Rwanda Human Resources for Health Program (HRH Program). Led by the Rwandan Ministry of Health and funded by both the U.S. Government and the Global Fund to Fight AIDS, Tuberculosis and Malaria, the primary goal of this seven-year initiative is to help Rwanda train the number of health professionals necessary to reach the country's health workforce targets. Since 2012, the participating U.S. academic institutions have deployed faculty from a variety of health-related disciplines and clinical specialties to Rwanda...
March 21, 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28327271/novel-anti-staphylococcal-and-anti-biofilm-properties-of-two-anti-malarial-compounds-mmv665953-1-3-chloro-4-fluorophenyl-3-3-4-dichlorophenyl-urea-and-mmv665807-5-chloro-2-hydroxy-n-3-trifluoromethyl-phenyl-benzamide
#4
Marta Zapotoczna, Nabila Boksmati, Sinead Donohue, Baizurina Bahtiar, Ahmad Boland, Hamzah Al Somali, Alysia Cox, Hilary Humphreys, James P O'Gara, Marian Brennan, Eoghan O'Neill
PURPOSE: The treatment of device-related infections is challenging and current anti-microbial compounds have poor anti-biofilm activity. We aimed to identify and characterize novel compounds effective in the eradication of Staphylococcus aureus biofilms. METHODOLOGY: Two novel compounds, MMV665953 {1-(3-chloro-4-fluorophenyl)-3-(3,4-dichlorophenyl)urea} and MMV665807{5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide}, effective in killing S. aureus biofilms, were identified by screening of the open access 'malaria box' chemical library...
March 23, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28288639/rhesus-macaque-and-mouse-models-for-down-selecting-circumsporozoite-protein-based-malaria-vaccines-differ-significantly-in-immunogenicity-and-functional-outcomes
#5
Timothy W Phares, Anthony D May, Christopher J Genito, Nathan A Hoyt, Farhat A Khan, Michael D Porter, Margot DeBot, Norman C Waters, Philippe Saudan, Sheetij Dutta
BACKGROUND: Non-human primates, such as the rhesus macaques, are the preferred model for down-selecting human malaria vaccine formulations, but the rhesus model is expensive and does not allow for direct efficacy testing of human malaria vaccines. Transgenic rodent parasites expressing genes of human Plasmodium are now routinely used for efficacy studies of human malaria vaccines. Mice have however rarely predicted success in human malaria trials and there is scepticism whether mouse studies alone are sufficient to move a vaccine candidate into the clinic...
March 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28248238/-omics-informed-drug-and-biomarker-discovery-opportunities-challenges-and-future-perspectives
#6
REVIEW
Holly Matthews, James Hanison, Niroshini Nirmalan
The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose...
September 12, 2016: Proteomes
https://www.readbyqxmd.com/read/28242353/growth-inhibitory-effects-of-standard-pro-and-antioxidants-on-the-human-malaria-parasite-plasmodium-falciparum
#7
Cletus A Wezena, Johannes Krafczyk, Verena Staudacher, Marcel Deponte
The redox metabolism of the malaria parasite Plasmodium falciparum and its human host has been suggested to play a central role for parasite survival and clearance. A common approach to test hypotheses in redox research is to challenge or rescue cells with pro- and antioxidants. However, quantitative data on the susceptibility of infected erythrocytes towards standard redox agents is surprisingly scarce. Here we determined the IC50 values of P. falciparum strains 3D7 and Dd2 for a set of redox agents using a SYBR green-based growth assay...
February 24, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28241112/lysine-deacetylase-inhibitors-in-parasites-past-present-and-future-perspectives
#8
Gebremedhin Solomon Hailu, Dina Robaa, Mariantonietta Forgione, Wolfgang Sippl, Dante Rotili, Antonello Mai
Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their helpfulness is being seriously compromised by the drug resistance problem. Globally, this is pushing discovery research of anti-parasitic drugs towards new agents endowed with new mechanisms of action. By using a "drug repurposing" strategy, histone deacetylase inhibitors (HDACi), which are presently clinically approved for cancer use, are now under investigation for various parasite infections...
February 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28222841/phenotypic-and-functional-characterization-of-peripheral-blood-lymphocytes-from-various-age-and-sex-specific-groups-of-owl-monkeys-aotus-nancymaae
#9
Pramod N Nehete, Bharti P Nehete, Sriram Chitta, Lawrence E Williams, Christian R Abee
Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys...
February 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28213436/host-cell-tropism-and-adaptation-of-blood-stage-malaria-parasites-challenges-for-malaria-elimination
#10
Caeul Lim, Selasi Dankwa, Aditya S Paul, Manoj T Duraisingh
Plasmodium falciparum and Plasmodium vivax account for most of the mortality and morbidity associated with malaria in humans. Research and control efforts have focused on infections caused by P. falciparum and P. vivax, but have neglected other malaria parasite species that infect humans. Additionally, many related malaria parasite species infect nonhuman primates (NHPs), and have the potential for transmission to humans. For malaria elimination, the varied and specific challenges of all of these Plasmodium species will need to be considered...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28199305/sterile-protection-against-human-malaria-by-chemoattenuated-pfspz-vaccine
#11
Benjamin Mordmüller, Güzin Surat, Heimo Lagler, Sumana Chakravarty, Andrew S Ishizuka, Albert Lalremruata, Markus Gmeiner, Joseph J Campo, Meral Esen, Adam J Ruben, Jana Held, Carlos Lamsfus Calle, Juliana B Mengue, Tamirat Gebru, Javier Ibáñez, Mihály Sulyok, Eric R James, Peter F Billingsley, K C Natasha, Anita Manoj, Tooba Murshedkar, Anusha Gunasekera, Abraham G Eappen, Tao Li, Richard E Stafford, Minglin Li, Phil L Felgner, Robert A Seder, Thomas L Richie, B Kim Lee Sim, Stephen L Hoffman, Peter G Kremsner
A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites)...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28193898/systems-analysis-of-protective-immune-responses-to-rts-s-malaria-vaccination-in-humans
#12
Dmitri Kazmin, Helder I Nakaya, Eva K Lee, Matthew J Johnson, Robbert van der Most, Robert A van den Berg, W Ripley Ballou, Erik Jongert, Ulrike Wille-Reece, Christian Ockenhouse, Alan Aderem, Daniel E Zak, Jerald Sadoff, Jenny Hendriks, Jens Wrammert, Rafi Ahmed, Bali Pulendran
RTS,S is an advanced malaria vaccine candidate and confers significant protection against Plasmodium falciparum infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with Plasmodium-infected mosquitoes, 3 wk after the final immunization, resulted in ∼50% protection in both groups of vaccinees...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28187764/new-potential-plasmodium-brasilianum-hosts-tamarin-and-marmoset-monkeys-family-callitrichidae
#13
Denise A M Alvarenga, Anielle Pina-Costa, Cesare Bianco, Silvia B Moreira, Patricia Brasil, Alcides Pissinatti, Claudio T Daniel-Ribeiro, Cristiana F A Brito
BACKGROUND: Non-human primates (NHPs) as a source for Plasmodium infections in humans are a challenge for malaria elimination. In Brazil, two species of Plasmodium have been described infecting NHPs, Plasmodium brasilianum and Plasmodium simium. Both species are infective to man. Plasmodium brasilianum resembles morphologically, genetically and immunologically the human quartan Plasmodium malariae. Plasmodium brasilianum naturally infects species of non-human primates from all New World monkey families from a large geographic area...
February 10, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28182750/chemoprophylaxis-with-sporozoite-immunization-in-p-knowlesi-rhesus-monkeys-confers-protection-and-elicits-sporozoite-specific-memory-t-cells-in-the-liver
#14
Sathit Pichyangkul, Michele D Spring, Kosol Yongvanitchit, Utaiwan Kum-Arb, Amporn Limsalakpetch, Rawiwan Im-Erbsin, Ratawan Ubalee, Pattaraporn Vanachayangkul, Edmond J Remarque, Evelina Angov, Philip L Smith, David L Saunders
Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half...
2017: PloS One
https://www.readbyqxmd.com/read/28179404/a-plasmodium-vivax-plasmid-dna-and-adenovirus-vectored-malaria-vaccine-encoding-blood-stage-antigens-ama1-and-msp142-in-a-prime-boost-heterologous-immunization-regimen-partially-protects-aotus-monkeys-against-blood-stage-challenge
#15
Nicanor Obaldia, Michael G Stockelman, William Otero, Jennifer A Cockrill, Harini Ganeshan, Esteban N Abot, Jianfeng Zhang, Keith Limbach, Yupin Charoenvit, Denise L Doolan, De-Chu C Tang, Thomas L Richie
Malaria is caused by parasites of the genus Plasmodium that are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of P. falciparum it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside of Africa, stressing the importance of developing a vaccine against malaria. In this study we assess the immunogenicity and protective efficacy of two P. vivax antigens, AMA1 and MSP142 in a recombinant DNA plasmid prime/adenoviral vector (Ad) boost regimen in Aotus monkeys...
February 8, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28179403/evaluation-of-pvceltos-as-a-pre-erythrocytic-p-vivax-vaccine
#16
Eduardo Alves, Ahmed M Salman, Fabiana Leoratti, Cesar Lopez-Camacho, Martha Eva Viveros-Sandoval, Amar Lall, Aadil El-Turabi, Martin F Bachmann, Adrian V S Hill, Chris J Janse, Shahid M Khan, Arturo Reyes-Sandoval
Four different vaccine platforms each targeting the human malaria parasite Plasmodium vivax cell-traversal protein for ookinetes and sporozoites (PvCelTOS) were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector ChAd63-PvCelTOS (Ad); a recombinant MVA-PvCelTOS (MVA); a bacteriophage Qβ-PvCelTOS virus-like particle (VLP); and recombinant PvCelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c and outbred CD-1 mice were immunized using the following prime/boost regimens: Ad-MVA, Ad-VLP and Ad-protein...
February 8, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28176636/discovery-of-species-selective-and-resistance-breaking-anticholinesterase-insecticides-for-the-malaria-mosquito
#17
Paul R Carlier, Jeffrey R Bloomquist, Max Totrov, Jianyong Li
Great reductions in malaria mortality have been accomplished in the last 15 years, in part due to the widespread roll-out of insecticide-treated bednets across sub-Saharan Africa. To date, these nets only employ pyrethroids, insecticides that that target the voltage-gated sodium ion channel of the malaria vector, Anopheles gambiae. Due to the growing emergence of An. gambiae strains that are resistant to pyrethroids, there is an urgent need to develop new public health insecticides that engage a different target and possess extremely low mammalian toxicity...
February 6, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28174312/selective-whole-genome-amplification-is-a-robust-method-that-enables-scalable-whole-genome-sequencing-of-plasmodium-vivax-from-unprocessed-clinical-samples
#18
Annie N Cowell, Dorothy E Loy, Sesh A Sundararaman, Hugo Valdivia, Kathleen Fisch, Andres G Lescano, G Christian Baldeviano, Salomon Durand, Vince Gerbasi, Colin J Sutherland, Debbie Nolder, Joseph M Vinetz, Beatrice H Hahn, Elizabeth A Winzeler
Whole-genome sequencing (WGS) of microbial pathogens from clinical samples is a highly sensitive tool used to gain a deeper understanding of the biology, epidemiology, and drug resistance mechanisms of many infections. However, WGS of organisms which exhibit low densities in their hosts is challenging due to high levels of host genomic DNA (gDNA), which leads to very low coverage of the microbial genome. WGS of Plasmodium vivax, the most widely distributed form of malaria, is especially difficult because of low parasite densities and the lack of an ex vivo culture system...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28153778/accelerating-the-clinical-development-of-protein-based-vaccines-for-malaria-by-efficient-purification-using-a-four-amino-acid-c-terminal-c-tag
#19
Jing Jin, Kathryn A Hjerrild, Sarah E Silk, Rebecca E Brown, Geneviève M Labbé, Jennifer M Marshall, Katherine E Wright, Sandra Bezemer, Stine B Clemmensen, Sumi Biswas, Yuanyuan Li, Aadil El-Turabi, Alexander D Douglas, Pim Hermans, Frank J Detmers, Willem A de Jongh, Matthew K Higgins, Rebecca Ashfield, Simon J Draper
Development of bespoke biomanufacturing processes remains a critical bottleneck for translational studies, in particular when modest quantities of a novel product are required for proof-of-concept Phase I/II clinical trials. In these instances the ability to develop a biomanufacturing process quickly and relatively cheaply, without risk to product quality or safety, provides a great advantage by allowing new antigens or concepts in immunogen design to more rapidly enter human testing. These challenges with production and purification are particularly apparent when developing recombinant protein-based vaccines for difficult parasitic diseases, with Plasmodium falciparum malaria being a prime example...
January 30, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28125584/the-real-mccoil-a-method-for-the-concurrent-estimation-of-the-complexity-of-infection-and-snp-allele-frequency-for-malaria-parasites
#20
Hsiao-Han Chang, Colin J Worby, Adoke Yeka, Joaniter Nankabirwa, Moses R Kamya, Sarah G Staedke, Grant Dorsey, Maxwell Murphy, Daniel E Neafsey, Anna E Jeffreys, Christina Hubbart, Kirk A Rockett, Roberto Amato, Dominic P Kwiatkowski, Caroline O Buckee, Bryan Greenhouse
As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available...
January 2017: PLoS Computational Biology
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