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https://www.readbyqxmd.com/read/29161011/the-design-of-plasmodium-vivax-hypoxanthine-guanine-phosphoribosyltransferase-inhibitors-as-potential-antimalarial-therapeutics
#1
Dianne T Keough, Dominik Rejman, Radek Pohl, Eva Zborníková, Dana Hockova, Tristan Croll, Michael D Edstein, Geoff W Birrell, Marina Chavchich, Lieve M J Naesens, Gregory K Pierens, Ian M Brereton, Luke W Guddat
Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are the foremost causative agents of malaria. Due to the development of resistance to current antimalarial medications, new drugs for this parasitic disease need to be discovered. The activity of hypoxanthine-guanine-[xanthine]-phosphoribosyltransferase, HG[X]PRT, is reported to be essential for the growth of both of these parasites, making it an excellent target for antimalarial drug discovery. Here, we have used rational structure-based methods to design an inhibitor, [3R,4R]-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine, of PvHGPRT and PfHGXPRT which has Ki values of 8 nM and 7 nM, respectively for these two enzymes...
November 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29160791/antimalarial-activity-of-acetylenic-thiophenes-from-echinops-hoehnelii-schweinf
#2
Helen Bitew, Wendimagegn Mammo, Ariaya Hymete, Mariamawit Yonathan Yeshak
Malaria is one of the world's most severe endemic diseases and due to the emergence of resistance to the currently available medicines, the need for new targets and relevant antimalarial drugs remains acute. The crude extract, four solvent fractions and two isolated compounds from the roots of Echinops hoehnelii were tested for their antimalarial activity using the standard four-day suppressive method in Plasmodium berghei-infected mice. The 80% methanol extract exhibited suppression of 4.6%, 27.8%, 68.5% and 78...
November 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29158278/characterization-of-plasmodium-atg3-atg8-interaction-inhibitors-identifies-novel-alternative-mechanisms-of-action-in-toxoplasma-gondii
#3
Joseph M Varberg, Kaice A LaFavers, Gustavo Arrizabalaga, William J Sullivan
Protozoan parasites, including the apicomplexan pathogens Plasmodium falciparum (malaria) and Toxoplasma gondii (toxoplasmosis) infect millions of people world-wide and represent a major human disease burden. Despite their prevalence, therapeutic strategies to treat these infections remain limited and are threatened by the emergence of drug resistance, highlighting the need for the identification of novel drug targets. Recently, homologues of the core autophagy proteins, including Atg8 and Atg3, were identified in many protozoan parasites...
November 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29155671/capacity-development-through-the-us-president-s-malaria-initiative-supported-antimalarial-resistance-monitoring-in-africa-network
#4
Eric S Halsey, Meera Venkatesan, Mateusz M Plucinski, Eldin Talundzic, Naomi W Lucchi, Zhiyong Zhou, Celine I Mandara, Hawela Moonga, Busiku Hamainza, Abdoul Habib Beavogui, Simon Kariuki, Aaron M Samuels, Laura C Steinhardt, Don P Mathanga, Julie Gutman, Yves Eric Denon, Aline Uwimana, Ashenafi Assefa, Jimee Hwang, Ya Ping Shi, Pedro Rafael Dimbu, Ousmane Koita, Deus S Ishengoma, Daouda Ndiaye, Venkatachalam Udhayakumar
Antimalarial drug resistance is an evolving global health security threat to malaria control. Early detection of Plasmodium falciparum resistance through therapeutic efficacy studies and associated genetic analyses may facilitate timely implementation of intervention strategies. The US President's Malaria Initiative-supported Antimalarial Resistance Monitoring in Africa Network has assisted numerous laboratories in partner countries in acquiring the knowledge and capability to independently monitor for molecular markers of antimalarial drug resistance...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#5
Carlos H S Garcia, Delphine Depoix, Rayner M L Queiroz, Jaques M F Souza, Wagner Fontes, Marcelo V de Sousa, Marlon D M Santos, Paulo C Carvalho, Philippe Grellier, Sébastien Charneau
Plasmodium mature sexual cycle occurs in the vector mosquitoes and ensures the transmission to a new host. Gametogenesis takes place within minutes in the vector midgut. Gametocytes have to complete a deep nuclear reorganization, quick differentiation, and in the case of male gametocytes, intracytoplasmic flagellum assembly that results in free-swimming microgametes required for macrogamete fertilization. In efforts to improve our knowledge of molecular mechanisms involved in gamete morphogenesis, we carried out a nanoLC/MSMS based quantitative proteomic analysis throughout the xanthurenic acid-induced gametogenesis of the rodent parasite P...
November 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29152597/identification-of-spiroplasmainsolitum-symbionts-in-anopheles-gambiae
#6
Sharon T Chepkemoi, Enock Mararo, Hellen Butungi, Juan Paredes, Daniel Masiga, Steven P Sinkins, Jeremy K Herren
Background: Insect symbionts have the potential to block the transmission of vector-borne diseases by their hosts. The advancement of a symbiont-based transmission blocking strategy for malaria requires the identification and study of Anopheles symbionts. Methods: High throughput 16S amplicon sequencing was used to profile the bacteria associated with Anopheles gambiae sensu lato and identify potential symbionts. The polymerase chain reaction (PCR) with specific primers were subsequently used to monitor symbiont prevalence in field populations, as well as symbiont transmission patterns...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/29151024/insecticide-resistance-in-anopheles-arabiensis-from-ethiopia-2012-2016-a-nationwide-study-for-insecticide-resistance-monitoring
#7
Louisa A Messenger, Josephat Shililu, Seth R Irish, Gedeon Yohannes Anshebo, Alemayehu Getachew Tesfaye, Yemane Ye-Ebiyo, Sheleme Chibsa, Dereje Dengela, Gunawardena Dissanayake, Estifanos Kebede, Endalew Zemene, Abebe Asale, Mekonnen Yohannes, Hiwot Solomon Taffese, Kristen George, Christen Fornadel, Aklilu Seyoum, Robert A Wirtz, Delenasaw Yewhalaw
BACKGROUND: Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) remain the cornerstones of malaria vector control. However, the development of insecticide resistance and its implications for operational failure of preventative strategies are of concern. The aim of this study was to characterize insecticide resistance among Anopheles arabiensis populations in Ethiopia and describe temporal and spatial patterns of resistance between 2012 and 2016. METHODS: Between 2012 and 2016, resistance status of An...
November 18, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29150282/artesunate-quercetin-luteolin-dual-drug-nanofacilitated-synergistic-treatment-for-malaria-a-plausible-approach-to-overcome-artemisinin-combination-therapy-resistance
#8
Nethravathi Puttappa, Raman Suresh Kumar, Karthik Yamjala
Malaria is one of the major global health challenge with 300 million new cases annually. The best regimen for treating Plasmodium falciparum induced malaria is based on artemisinin and its derivatives which were prescribed as artemisinin combination therapy (ACT). These are highly effective drugs resulting in rapid clearance of parasites even in severe P. falciparum induced malaria patients. However, from the past few years parasites resistant to ACT's have begun to emerge in various parts of the world such as Cambodia and Greater Mekong Subregion...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29141762/efficacy-of-artemether-lumefantrine-for-uncomplicated-plasmodium-falciparum-malaria-in-cruzeiro-do-sul-brazil-2016
#9
Megumi Itoh, Suiane Negreiros do Valle, Sâmela Farias, Thayna Maria Holanda de Souza, Giselle Maria Rachid Viana, Naomi Lucchi, Stella Chenet, Paola Marchesini, Marinete Póvoa, Ana Carolina Faria E Silva Santelli, Alexandre Macedo de Oliveira
We evaluated the therapeutic efficacy of artemether-lumefantrine (AL) fixed-dose combination to treat uncomplicated Plasmodium falciparum malaria in Cruzeiro do Sul, Acre State, in the Amazon region of Brazil. Between December 2015 and May 2016, we enrolled 79 patients, 5-79 years old with fever or history of fever in the previous 48 hours and P. falciparum monoinfection confirmed by microscopy. Attempts were made to provide direct observation or phone reminders for all six doses of AL, and patients were followed-up for 28 days...
November 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29141758/in-vitro-sensitivity-of-pyronaridine-in-thai-isolates-of-plasmodium-falciparum
#10
Kittiya Mahotorn, Peerapan Tan-Ariya, Thunyapit Thita, Toon Ruang-Areerate, Naruemon Sittichot, Nantana Suwandittakul, Mathirut Mungthin
Pyronaridine, a Mannich base antimalarial agent with a high activity against chloroquine-resistant Plasmodium falciparum, has been combined with artesunate as a new artemisinin derivative-based combination therapy (ACT). Pyronaridine-artesunate combination could be one of the choices for the treatment of uncomplicated falciparum malaria in multidrug-resistant areas including Thailand. The aim of this study was to determine in vitro sensitivity and cross-resistance pattern of pyronaridine in Thai isolates of P...
October 23, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29141726/status-of-insecticide-resistance-in-papua-new-guinea-an-update-from-nation-wide-monitoring-of-anopheles-mosquitoes
#11
Gussy Koimbu, Cyrille Czeher, Michelle Katusele, Muker Sakur, Lemen Kilepak, Anthony Tandrapah, Manuel W Hetzel, Justin Pulford, Leanne Robinson, Stephan Karl
Insecticide resistance (IR) monitoring is an important component of vector-borne disease control. The last assessment of IR in Papua New Guinea (PNG) was conducted in 2010. Since then, vector populations have been exposed to higher levels of pyrethroids with the continued nation-wide distribution of insecticide-treated nets. Here, we provide an update on phenotypic IR in four highly malaria-endemic areas of PNG. IR against deltamethrin, lambda-cyhalothrin, and dichlorodiphenyltrichloroethane was assessed using World Health Organization bioassays...
November 6, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29141217/th1-like-plasmodium-specific-memory-cd4-t-cells-support-humoral-immunity
#12
Ryan A Zander, Rahul Vijay, Angela D Pack, Jenna J Guthmiller, Amy C Graham, Scott E Lindner, Ashley M Vaughan, Stefan H I Kappe, Noah S Butler
Effector T cells exhibiting features of either T helper 1 (Th1) or T follicular helper (Tfh) populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140232/country-wide-surveillance-of-molecular-markers-of-antimalarial-drug-resistance-in-senegal-by-use-of-positive-malaria-rapid-diagnostic-tests
#13
Magatte Ndiaye, Doudou Sow, Sidsel Nag, Khadime Sylla, Roger Clement Tine, Jean Louis Ndiaye, Aminata Collé Lo, Oumar Gaye, Babacar Faye, Michael Alifrangis
In Senegal, antimalarial drugs used in treatment and prevention of malaria are one of the main reasons for the current success in controlling malaria. However, the successful control of malaria is highly dependent on continued effectiveness of these drugs which may be compromised by the spread of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles of antimalarial drug resistance markers of Plasmodium falciparum parasites...
November 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29138320/structural-basis-for-antibody-recognition-of-the-nanp-repeats-in-plasmodium-falciparum-circumsporozoite-protein
#14
David Oyen, Jonathan L Torres, Ulrike Wille-Reece, Christian F Ockenhouse, Daniel Emerling, Jacob Glanville, Wayne Volkmuth, Yevel Flores-Garcia, Fidel Zavala, Andrew B Ward, C Richter King, Ian A Wilson
Acquired resistance against antimalarial drugs has further increased the need for an effective malaria vaccine. The current leading candidate, RTS,S, is a recombinant circumsporozoite protein (CSP)-based vaccine against Plasmodium falciparum that contains 19 NANP repeats followed by a thrombospondin repeat domain. Although RTS,S has undergone extensive clinical testing and has progressed through phase III clinical trials, continued efforts are underway to enhance its efficacy and duration of protection. Here, we determined that two monoclonal antibodies (mAbs 311 and 317), isolated from a recent controlled human malaria infection trial exploring a delayed fractional dose, inhibit parasite development in vivo by at least 97%...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29137664/therapeutic-efficacy-of-artemether-lumefantrine-in-the-treatment-of-uncomplicated-plasmodium-falciparum-malaria-in-ethiopia-a-systematic-review-and-meta-analysis
#15
REVIEW
Mohammed Biset Ayalew
BACKGROUND: As Ethiopia is one of the sub-Saharan countries with a great burden of malaria the effectiveness of first line anti-malarial drugs is the major concern. The aim of this study was to synthesize the available evidence on the efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Ethiopia. This was done by performing a meta-analysis of recent studies conducted in the country on this topic. METHODS: Studies published between January 2010 and January 2017 that reported on the efficacy of artemether-lumefantrine in the treatment of P...
November 15, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/29133550/discovery-of-new-inhibitors-of-toxoplasma-gondii-thanks-to-the-pathogen-box
#16
Jérémy Spalenka, Sandie Escotte-Binet, Ali Bakiri, Jane Hubert, Jean-Hugues Renault, Frédéric Velard, Simon Duchateau, Dominique Aubert, Antoine Huguenin, Isabelle Villena
Toxoplasma gondii is a cosmopolitan protozoan parasite which affects approximately 30% of the population worldwide. The drugs currently used against toxoplasmosis are few in number and show several limitations, such as a drug intolerance, poor bioavailability or drug resistance mechanism developed by the parasite. Thus it is important to find new compounds able to inhibit parasite invasion or proliferation. In this study, the 400 compounds of the open access Pathogen Box provided by the Medicines for Malaria Venture (MMV) foundation were screened for their anti-Toxoplasma gondii activity...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29132373/understanding-malaria-treatment-seeking-preferences-within-the-public-sector-amongst-mobile-migrant-workers-in-a-malaria-elimination-scenario-a-mixed-methods-study
#17
Aung Ye Naung Win, Thae Maung Maung, Khin Thet Wai, Tin Oo, Aung Thi, Rungrawee Tipmontree, Ngamphol Soonthornworasiri, Mondha Kengganpanich, Jaranit Kaewkungwal
BACKGROUND: Migration flows and the emerging resistance to artemisinin-based combination therapy in the Greater Mekong Sub-region (GMS) create programmatic challenges to meeting the AD 2030 malaria elimination target in Myanmar. The National Malaria Control Programme (NMCP) targeted migrant workers based mainly on the stability of their worksites (categories 1: permanent work-setting; categories 2 and 3: less stable work-settings). This study aims to assess the migration patterns, malaria treatment-seeking preferences, and challenges encountered by mobile/migrant workers at remote sites in a malaria-elimination setting...
November 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29129935/antimalarial-use-of-malagasy-plants-is-poorly-correlated-with-performance-in-antimalarial-bioassays
#18
Wendy L Applequist, Michel Ratsimbason, Alyse Kuhlman, Stephan Rakotonandrasana, Vincent Rasamison, David G I Kingston
Bioassay screening of plant extracts can identify unique lead compounds for drug development, but the "hit rate" from random screening is very low. Targeted screening of medicinal plants has been repeatedly reported to increase the percentage of samples displaying bioactivity. Contrarily, Maranz (2012) suggested that African antimalarial plants were unsuitable sources of antimalarial drugs because high prevalence of malaria would result in rapid evolution of resistance to active compounds that directly targeted the parasite...
March 2017: Economic Botany
https://www.readbyqxmd.com/read/29129317/the-genetic-legacy-of-the-indian-ocean-slave-trade-recent-admixture-and-post-admixture-selection-in-the-makranis-of-pakistan
#19
Romuald Laso-Jadart, Christine Harmant, Hélène Quach, Nora Zidane, Chris Tyler-Smith, Qasim Mehdi, Qasim Ayub, Lluis Quintana-Murci, Etienne Patin
From the eighth century onward, the Indian Ocean was the scene of extensive trade of sub-Saharan African slaves via sea routes controlled by Muslim Arab and Swahili traders. Several populations in present-day Pakistan and India are thought to be the descendants of such slaves, yet their history of admixture and natural selection remains largely undefined. Here, we studied the genome-wide diversity of the African-descent Makranis, who reside on the Arabian Sea coast of Pakistan, as well that of four neighboring Pakistani populations, to investigate the genetic legacy, population dynamics, and tempo of the Indian Ocean slave trade...
November 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29128848/antimalarial-activity-of-malaria-box-compounds-against-plasmodium-falciparum-clinical-isolates
#20
Jersley D Chirawurah, Felix Ansah, Prince B Nyarko, Samuel Duodu, Yaw Aniweh, Gordon A Awandare
Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box...
October 16, 2017: International Journal for Parasitology, Drugs and Drug Resistance
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