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https://www.readbyqxmd.com/read/28813452/plasma-metabolomics-reveals-membrane-lipids-aspartate-asparagine-and-nucleotide-metabolism-pathway-differences-associated-with-chloroquine-resistance-in-plasmodium-vivax-malaria
#1
Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, Dean P Jones
BACKGROUND: Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28811124/two-cap-residues-in-the-s1-subsite-of-a-plasmodium-falciparum-m1-family-aminopeptidase-promote-broad-specificity-and-enhance-catalysis
#2
Matthew Rosati, Seema Dalal, Michael Klemba
The aminopeptidase PfA-M1 is a key contributor to peptide catabolism in the human malaria parasite Plasmodium falciparum. PfA-M1 substrate specificity is shaped by the cylindrical S1 subsite, which accommodates the sidechain of the substrate P1 residue. At the top of the S1 subsite are two "cap" residues, E572 and M1034, that are positioned to influence S1 subsite specificity. In this study, we have mutated the cap residues, individually and together, and have evaluated the effects on PfA-M1 specificity and catalytic efficiency...
August 12, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28810865/cryptic-plasmodium-ovale-concurrent-with-mixed-plasmodium-falciparum-and-plasmodium-malariae-infection-in-two-children-from-central-african-republic
#3
Cynthia Bichara, Philippe Flahaut, Damien Costa, Anne-Lise Bienvenu, Stephane Picot, Gilles Gargala
BACKGROUND: Since several malaria parasite species are usually present in a particular area, co-infections with more than one species of Plasmodium are more likely to occur in humans infected in these areas. In many mixed infections, parasite densities of the cryptic species may be low and often not recognized in clinical practice. CASE PRESENTATION: Two children (3 and 6 years old) adopted recently from Central African Republic were admitted to hospital because of intermittent fever...
August 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28810863/multiple-essential-functions-of-plasmodium-falciparum-actin-1-during-malaria-blood-stage-development
#4
Sujaan Das, Leandro Lemgruber, Chwen L Tay, Jake Baum, Markus Meissner
BACKGROUND: The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins, and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated...
August 15, 2017: BMC Biology
https://www.readbyqxmd.com/read/28810125/cheminformatic-analysis-of-anti-malarial-chemical-space-illuminates-therapeutic-mechanisms-and-offers-strategies-for-therapy-development
#5
Julia Nogueira Varela, María Fernanda Fernanda Lammoglia Cobo, Sandip V Pawar, Vikramaditya G Yadav
The clear and present danger of malaria, which has been amplified in recent years by climate change, and the progressive thinning of our drug arsenal over the past two decades raise uncomfortable questions about the current state and future of anti-malarial drug development. Besides suffering from many of the same technical challenges that affect drug development in other disease areas, the quest for new anti-malarial therapies is also hindered by the complex, dynamic life cycle of the malaria parasite, P. falciparum, in its mosquito and human hosts, and its role thereof in the elicitation of drug resistance...
August 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28808258/hexahydroquinolines-are-antimalarial-candidates-with-potent-blood-stage-and-transmission-blocking-activity
#6
Manu Vanaerschot, Leonardo Lucantoni, Tao Li, Jill M Combrinck, Andrea Ruecker, T R Santha Kumar, Kelly Rubiano, Pedro E Ferreira, Giulia Siciliano, Sonia Gulati, Philipp P Henrich, Caroline L Ng, James M Murithi, Victoria C Corey, Sandra Duffy, Ori J Lieberman, M Isabel Veiga, Robert E Sinden, Pietro Alano, Michael J Delves, Kim Lee Sim, Elizabeth A Winzeler, Timothy J Egan, Stephen L Hoffman, Vicky M Avery, David A Fidock
Antimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes...
August 14, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28808240/micro-epidemiology-and-spatial-heterogeneity-of-p-vivax-parasitaemia-in-riverine-communities-of-the-peruvian-amazon-a-multilevel-analysis
#7
Gabriel Carrasco-Escobar, Dionicia Gamboa, Marcia C Castro, Shrikant I Bangdiwala, Hugo Rodriguez, Juan Contreras-Mancilla, Freddy Alava, Niko Speybroeck, Andres G Lescano, Joseph M Vinetz, Angel Rosas-Aguirre, Alejandro Llanos-Cuentas
Malaria has steadily increased in the Peruvian Amazon over the last five years. This study aimed to determine the parasite prevalence and micro-geographical heterogeneity of Plasmodium vivax parasitaemia in communities of the Peruvian Amazon. Four cross-sectional active case detection surveys were conducted between May and July 2015 in four riverine communities in Mazan district. Analysis of 2785 samples of 820 individuals nested within 154 households for Plasmodium parasitaemia was carried out using light microscopy and qPCR...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808204/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#8
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807026/circulating-micrornas-in-malaria-infection-bench-to-bedside
#9
REVIEW
Supat Chamnanchanunt, Suthat Fucharoen, Tsukuru Umemura
Severe malaria has a poor prognosis with a morbidity rate of 80% in tropical areas. The early parasite detection is one of the effective means to prevent severe malaria of which specific treatment strategies are limited. Many clinical characteristics and laboratory testings have been used for the early diagnosis and prediction of severe disease. However, a few of these factors could be applied to clinical practice. MicroRNAs (miRNAs) were demonstrated as useful biomarkers in many diseases such as malignant diseases and cardiovascular diseases...
August 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28806957/clinical-and-molecular-surveillance-of-artemisinin-resistant-falciparum-malaria-in-myanmar-2009-2013
#10
Myat Htut Nyunt, Myat Thu Soe, Hla Win Myint, Htet Wai Oo, Moe Moe Aye, Soe Soe Han, Ni Ni Zaw, Cho Cho, Phyo Zaw Aung, Khin Thiri Kyaw, Thin Thin Aye, Naychi Aung San, Leonard Ortega, Krongthong Thimasarn, Maria Dorina G Bustos, Sherwin Galit, Mohammad Rafiul Hoque, Pascal Ringwald, Eun-Taek Han, Myat Phone Kyaw
BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10, pffd and pfmdr2. METHODS: A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013...
August 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28804714/reduction-of-mosquito-survival-in-mice-vaccinated-with-anopheles-stephensi-glucose-transporter
#11
J Couto, S Antunes, J Ferrolho, J de la Fuente, A Domingos
Despite the fact that recent efforts to control/eradicate malaria have contributed to a significant decrease in the number of cases and deaths, the disease remains a global health challenge. Vaccines based on mosquito salivary gland antigens are a potential approach for reducing vector populations and malaria parasites. The Anopheles AGAP007752 gene encodes for a glucose transporter that is upregulated during Plasmodium infection, and its knockdown decreases the number of sporozoites in mosquito salivary glands...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28804661/imported-asymptomatic-bancroftian-filariasis-discovered-from-a-plasmodium-vivax-infected-patient-a-case-report-from-singapore
#12
Jean-Marc Chavatte, Roland Jureen
Human lymphatic filariasis is a vector-borne disease mainly caused by the parasitic nematode Wuchereria bancrofti and transmitted worldwide within the tropical and subtropical regions. Singapore was once endemic for bancroftian filariasis but recent reports are scarce and the disease is nearly forgotten. The case report presented here reports the incidental hospital laboratory finding of an asymptomatic microfilaremia in a relapsing Plasmodium vivax imported case during a malaria treatment follow-up appointment...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28804644/a-malaria-vaccine-protects-aotus-monkeys-against-virulent-plasmodium-falciparum-infection
#13
Prakash Srinivasan, G Christian Baldeviano, Kazutoyo Miura, Ababacar Diouf, Julio A Ventocilla, Karina P Leiva, Luis Lugo-Roman, Carmen Lucas, Sachy Orr-Gonzalez, Daming Zhu, Eileen Villasante, Lorraine Soisson, David L Narum, Susan K Pierce, Carole A Long, Carter Diggs, Patrick E Duffy, Andres G Lescano, Louis H Miller
The Plasmodium falciparum protein, apical membrane antigen 1 forms a complex with another parasite protein, rhoptry neck protein 2, to initiate junction formation with the erythrocyte and is essential for merozoite invasion during the blood stage of infection. Consequently, apical membrane antigen 1 has been a target of vaccine development but vaccination with apical membrane antigen 1 alone in controlled human malaria infections failed to protect and showed limited efficacy in field trials. Here we show that vaccination with AMA1-RON2L complex in Freund's adjuvant protects Aotus monkeys against a virulent Plasmodium falciparum infection...
2017: NPJ Vaccines
https://www.readbyqxmd.com/read/28804611/antimalarial-evaluation-of-selected-medicinal-plant-extracts-used-in-iranian-traditional-medicine
#14
Mohammad Hossein Feiz Haddad, Hamidreza Mahbodfar, Zahra Zamani, Ali Ramazani
OBJECTIVES: In an attempt to discover new natural active extracts against malaria parasites, the present study evaluated the antiplasmodial properties of selected plants based on Iranian traditional medicine. MATERIALS AND METHODS: Ten plant species found in Iran were selected and collected based on the available literature about the Iranian traditional medicine. The methanolic extracts of these plants were investigated for in vitro antimalarial properties against chloroquine-sensitive (3D7) and multi-drug resistant (K1) strains of Plasmodium falciparum...
April 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28801627/increased-risk-of-low-birth-weight-in-women-with-placental-malaria-associated-with-p-falciparum-var2csa-clade
#15
Jaymin C Patel, Nicholas J Hathaway, Christian M Parobek, Kyaw L Thwai, Mwayiwawo Madanitsa, Carole Khairallah, Linda Kalilani-Phiri, Victor Mwapasa, Achille Massougbodji, Nadine Fievet, Jeffery A Bailey, Feiko O Ter Kuile, Philippe Deloron, Stephanie M Engel, Steve M Taylor, Jonathan J Juliano, Nicaise Tuikue Ndam, Steven R Meshnick
Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA's ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800735/life-span-of-in-vitro-differentiated-plasmodium-falciparum-gametocytes
#16
Tamirat Gebru, Albert Lalremruata, Peter G Kremsner, Benjamin Mordmüller, Jana Held
BACKGROUND: The sexual stages (gametocytes) of Plasmodium falciparum do not directly contribute to the pathology of malaria but are essential for transmission of the parasite from the human host to the mosquito. Mature gametocytes circulate in infected human blood for several days and their circulation time has been modelled mathematically from data of previous in vivo studies. This is the first time that longevity of gametocytes is studied experimentally in vitro. METHODS: The in vitro longevity of P...
August 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28800732/the-duffy-binding-protein-pkdbp%C3%AE-ii-of-plasmodium-knowlesi-from-peninsular-malaysia-and-malaysian-borneo-show-different-binding-activity-level-to-human-erythrocytes
#17
Khai Lone Lim, Amirah Amir, Yee Ling Lau, Mun Yik Fong
BACKGROUND: The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated...
August 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28800640/knockdown-of-the-plasmodium-falciparum-surfin4-1-antigen-leads-to-an-increase-of-its-cognate-transcript
#18
Tatiane Macedo-Silva, Rosana Beatriz Duque Araujo, Kamila Anna Meissner, Wesley Luzetti Fotoran, Márcia Melo Medeiros, Mauro Ferreira de Azevedo, Gerhard Wunderlich
The genome of the malaria parasite Plasmodium falciparum contains the surf gene family which encodes large transmembrane proteins of unknown function. While some surf alleles appear to be expressed in sexual stages, others occur in asexual blood stage forms and may be associated to virulence-associated processes and undergo transcriptional switching. We accessed the transcription of surf genes along multiple invasions by real time PCR. Based on the observation of persistent expression of gene surf4.1, we created a parasite line which expresses a conditionally destabilized SURFIN4...
2017: PloS One
https://www.readbyqxmd.com/read/28800475/biological-immunological-and-functional-properties-of-two-novel-multi-variant-chimeric-recombinant-proteins-of-csp-antigens-for-vaccine-development-against-plasmodium-vivax-infection
#19
Samaneh H Shabani, Sedigheh Zakeri, Ali H Salmanian, Jafar Amani, Akram A Mehrizi, Georges Snounou, François Nosten, Chiara Andolina, Yousef Mourtazavi, Navid D Djadid
The circumsporozoite protein (CSP) of the malaria parasite Plasmodium vivax is a major pre-erythrocyte vaccine candidate. The protein has a central repeat region that belongs to one of repeat families (VK210, VK247, and the P. vivax-like). In the present study, computer modelling was employed to select chimeric proteins, comprising the conserved regions and different arrangements of the repeat elements (VK210 and VK247), whose structure is similar to that of the native counterparts. DNA encoding the selected chimeras (named CS127 and CS712) were synthetically constructed based on E...
August 8, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28800458/quinoline-hybrids-and-their-antiplasmodial-and-antimalarial-activities
#20
REVIEW
Yuan-Qiang Hu, Chuan Gao, Shu Zhang, Lei Xu, Zhi Xu, Lian-Shun Feng, Xiang Wu, Feng Zhao
Malaria, in particular infection with P. falciparum (the most lethal of the human malaria parasite species, responsible for nearly one million deaths every year), is one of the most devastating and common infectious disease throughout the world. Beginning with quinine, quinoline containing compounds have long been used in clinical treatment of malaria and remained the mainstays of chemotherapy against malaria. The emergence of P. falciparum strains resistant to almost all antimalarials prompted medicinal chemists and biologists to study their effective replacement with an alternative mechanism of action and new molecules...
July 27, 2017: European Journal of Medicinal Chemistry
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