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Kristina R Kesely, Antonella Pantaleo, Francesco M Turrini, Peter Olupot-Olupot, Philip S Low
With half of the world's population at risk for malaria infection and with drug resistance on the rise, the search for mutation-resistant therapies has intensified. We report here a therapy for Plasmodium falciparum malaria that acts by inhibiting the phosphorylation of erythrocyte membrane band 3 by an erythrocyte tyrosine kinase. Because tyrosine phosphorylation of band 3 causes a destabilization of the erythrocyte membrane required for parasite egress, inhibition of the erythrocyte tyrosine kinase leads to parasite entrapment and termination of the infection...
2016: PloS One
Vinicius A Sortica, Juliana D Lindenau, Maristela G Cunha, Maria DO Ohnishi, Ana Maria R Ventura, Ândrea Kc Ribeiro-Dos-Santos, Sidney Eb Santos, Luciano Sp Guimarães, Mara H Hutz
BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients...
October 21, 2016: Pharmacogenomics
Benjamin Roche, Virginie Rougeron, Lluis Quintana-Murci, François Renaud, Jessica Lee Abbate, Franck Prugnolle
Malarial infections have long been recognized as a driver of human evolution, as demonstrated by the influence of Plasmodium falciparum on sickle-cell anemia persistence. Duffy-negativity is another blood disorder thought to have been selected because it confers nearly complete resistance against Plasmodium vivax infection. Recent evidence suggests that the benefits of being Duffy-negative cannot be expected to play a strong selective pressure on humans, whereas its costs cannot be considered as negligible...
October 17, 2016: Trends in Parasitology
Paul C Knox, Ian J C MacCormick, Emme Mbale, Macpherson Malewa, Gabriela Czanner, Simon P Harding
Paediatric cerebral malaria is the most serious complication of Plasmodium falciparum infection. While the majority recover, long-term cognitive impairment has been highlighted as a significant and neglected problem. Persistent or serious deficits in processes such as attention or behavioural inhibition should be manifest in changes to performance on oculomotor tasks. Therefore we investigated the impact of cerebral malaria on the development of reflexive pro-saccades and antisaccades. In a longitudinal study, 47 children previously admitted with retinopathy-confirmed cerebral malaria (mean age at admission 54 months), were compared with 37 local healthy controls (mean ages at first study visit 117 and 110 months respectively)...
2016: PloS One
Inderjeet Kaur, Mohammad Zeeshan, Ekta Saini, Abhinav Kaushik, Asif Mohmmed, Dinesh Gupta, Pawan Malhotra
Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites...
October 20, 2016: Scientific Reports
Myriam Arévalo-Herrera, Juan M Vásquez-Jiménez, Mary Lopez-Perez, Andrés F Vallejo, Andrés B Amado-Garavito, Nora Céspedes, Angélica Castellanos, Karen Molina, Johanna Trejos, José Oñate, Judith E Epstein, Thomas L Richie, Sócrates Herrera
BACKGROUND: Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization. METHODOLOGY/PRINCIPAL FINDINGS: A randomized, single-blinded trial was conducted...
October 2016: PLoS Neglected Tropical Diseases
Aditi A Sidhaye, Kanchan C Bhuran, Sneha Zambare, Munna Abubaker, Niroshini Nirmalan, Kamalinder K Singh
AIM: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. METHODS: Artemether-loaded nanoparticles (AANs) were designed and antimalarial activity evaluated in vitro/in vivo using Plasmodium falciparum/Plasmodium berghei species, respectively...
October 19, 2016: Nanomedicine
Yang Cheng, Feng Lu, Bo Wang, Jian Li, Jin-Hee Han, Daisuke Ito, Deok-Hoon Kong, Lubin Jiang, Jian Wu, Kwon-Soo Ha, Eizo Takashima, Jetsumon Sattabongkot, Jun Cao, Myat Htut Nyunt, Myat Phone Kyaw, Sanjay A Desai, Louis H Miller, Takafumi Tsuboi, Eun-Taek Han
Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has been thought to be unable to infect humans lacking the Duffy (Fy) blood group antigen because this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete the erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA), that bound human erythrocytes regardless of Duffy antigen status...
October 19, 2016: Scientific Reports
Kevin Cheeseman, Gabriela Certad, Jonathan B Weitzman
Over 20 % of cancers have infectious origins, including well-known examples of microbes such as viruses (HPV, EBV) and bacteria (H. pylori). The contribution of intracellular eukaryotic parasites to cancer etiology is largely unexplored. Epidemiological and clinical reports indicate that eukaryotic protozoan, such as intracellular apicomplexan that cause diseases of medical or economic importance, can be linked to various cancers: Theileria and Cryptosporidium induce host cell transformation while Plasmodium was linked epidemiologically to the "African lymphoma belt" over fifty years ago...
October 2016: Médecine Sciences: M/S
Bishnu Joshi, Sarah Hendrickx, Lila Bahadur Magar, Niranjan Parajuli, Pierre Dorny, Louis Maes
BACKGROUND: Nepal is very rich in biodiversity, and no extensive effort has yet been carried out to screen plants that are used by traditional healers against parasitic diseases. The aim of this study was to evaluate the in vitro antileishmanial and antimalarial activity of crude methanolic or ethanolic extracts of 29 plant species that are currently used by local people of Nepal for treating different ailments. METHODS: Crude extracts of leaves, twigs, aerial parts, and/or roots of the selected plants were evaluated for in vitro inhibitory activity against intracellular amastigotes of Leishmania infantum and against erythrocytic stages of Plasmodium falciparum...
September 2016: Journal of Intercultural Ethnopharmacology
Takeshi Akiyama, Tiengkham Pongvongsa, Souraxay Phrommala, Tomoyo Taniguchi, Yuba Inamine, Rie Takeuchi, Tadashi Watanabe, Futoshi Nishimoto, Kazuhiko Moji, Shigeyuki Kano, Hisami Watanabe, Jun Kobayashi
BACKGROUND: Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development...
October 18, 2016: Malaria Journal
Karen Kerkhof, Vincent Sluydts, Somony Heng, Saorin Kim, Myrthe Pareyn, Laura Willen, Lydie Canier, Siv Sovannaroth, Didier Ménard, Tho Sochantha, Marc Coosemans, Lies Durnez
BACKGROUND: Malaria transmission is highly heterogeneous, especially in low endemic countries, such as Cambodia. This results in geographical clusters of residual transmission in the dry, low transmission season, which can fuel the transmission to wider areas or populations during the wet season. A better understanding of spatial clustering of malaria can lead to a more efficient, targeted strategy to reduce malaria transmission. This study aims to evaluate the potential of the use of serological markers to define spatial patterns in malaria exposure...
October 19, 2016: Malaria Journal
Tiengkham Pongvongsa, Daisuke Nonaka, Moritoshi Iwagami, Masami Nakatsu, Panom Phongmany, Futoshi Nishimoto, Jun Kobayashi, Bouasy Hongvanthon, Paul T Brey, Kazuhiko Moji, Toshihiro Mita, Shigeyuki Kano
BACKGROUND: In the Lao PDR, malaria morbidity and mortality have remarkably decreased over the past decade. However, asymptomatic infections in rural villages contribute to the on-going local transmission. The primary objective of this study was to explore the characteristics of infections in a malaria-endemic district of the Lao PDR. The specific objectives were to investigate the prevalence and species of malaria parasites using molecular methods and to assess individual and household parasite levels and the characteristics associated with malaria infection...
October 18, 2016: Malaria Journal
Rosalind E Howes, Sedera Aurélien Mioramalala, Brune Ramiranirina, Thierry Franchard, Andry Joeliarijaona Rakotorahalahy, Donal Bisanzio, Peter W Gething, Peter A Zimmerman, Arsène Ratsimbasoa
BACKGROUND: Malaria remains a major public health problem in Madagascar. Widespread scale-up of intervention coverage has led to substantial reductions in case numbers since 2000. However, political instability since 2009 has disrupted these efforts, and a resurgence of malaria has since followed. This paper re-visits the sub-national stratification of malaria transmission across Madagascar to propose a contemporary update, and evaluates the reported routine case data reported at this sub-national scale...
October 18, 2016: Malaria Journal
Nuredin Abduselam, Ahmed Zeynudin, Nicole Berens-Riha, Dinberu Seyoum, Michael Pritsch, Habtewold Tibebu, Kasahun Eba, Michael Hoelscher, Andreas Wieser, Delenasaw Yewhalaw
BACKGROUND: Around half of the global population is living in areas at risk of malaria infection. Plasmodium vivax malaria has become increasingly prevalent and responsible for a high health and socio-economic burden in Ethiopia. The availability of gametocyte carriers and mosquito species susceptible to P. vivax infection are vital for malaria transmission. Determining the susceptibility of vector species to parasite infection in space and time is important in vector control programs...
October 18, 2016: Parasites & Vectors
Allison T Neal, Max S Ross, Jos J Schall, Anne M Vardo-Zalik
BACKGROUND: The geographic scale and degree of genetic differentiation for arthropod vectors that transmit parasites play an important role in the distribution, prevalence and coevolution of pathogens of human and wildlife significance. We determined the genetic diversity and population structure of the sand fly Lutzomyia vexator over spatial scales from 0.56 to 3.79 km at a study region in northern California. The study was provoked by observations of differentiation at fine spatial scales of a lizard malaria parasite vectored by Lu...
October 18, 2016: Parasites & Vectors
Sindy P Buitrago, Diego Garzón-Ospina, Manuel A Patarroyo
BACKGROUND: Designing a vaccine against Plasmodium vivax has focused on selecting antigens involved in invasion mechanisms that must have domains with low polymorphism for avoiding allele-specific immune responses. The rhoptry neck protein 4 (RON4) forms part of the tight junction, which is essential in the invasion of hepatocytes and/or erythrocytes; however, little is known about this locus' genetic diversity. METHODS: DNA sequences from 73 Colombian clinical isolates from pvron4 gene were analysed for characterizing their genetic diversity; pvron4 haplotype number and distribution, as well as the evolutionary forces determining diversity pattern, were assessed by population genetics and molecular evolutionary approaches...
October 18, 2016: Malaria Journal
Laetitia Piane, Marie-Laure Théron, Marcel Aumann, Catherine Trumel
A 9-year-old, female Maltese dog was referred to the Veterinary School of Toulouse with a 2-day history of anorexia and weakness. On clinical examination, the dog had hyperthermia (39.7°C), abdominal discomfort, and polypnea. Significant laboratory findings included pigmenturia, hyperbilirubinemia, hypercreatininemia, hyperfibrinogenemia, abnormal Snap canine pancreas-specific lipase, and pancytopenia with a nonregenerative anemia. A peripheral blood smear revealed numerous intraerythrocytic large Babesia but no polychromasia...
October 18, 2016: Veterinary Clinical Pathology
Jung Yoon, Seung Gyu Yun, Jeeyong Kim, Yoo Na Jung, Young Eun Koh, Jeong Hun Nam, Eun Taek Han, Chae Seung Lim
We evaluated the diagnostic usefulness of the LH780 Coulter blood cell counter for detection and therapeutic monitoring of malaria including cross-reactivity with nucleated RBC (NRBC) samples. A total of 405 patients (43 patients with Plasmodium vivax malaria and the control group of 120 healthy subjects, 111 patients with fever, and 131 patients with NRBCs) were analyzed with routine CBC using the LH780. We analyzed the CBC results according to three selected parameters: an abnormal peak in the WBC histogram before 35fL, the presence of red dots in the nonwhite cell zone of 2D WBC Diff Dataplot, and platelet-related flags suggesting platelet clumps or giant platelets...
October 14, 2016: Acta Tropica
Kawsar R Talaat, Ruth D Ellis, Janet Hurd, Autumn Hentrich, Erin Gabriel, Noreen A Hynes, Kelly M Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Charles Anderson, David Jones, Joan Aebig, Sarah Brockley, Nicholas J MacDonald, Xiaowei Wang, Michael P Fay, Sara A Healy, Anna P Durbin, David L Narum, Yimin Wu, Patrick E Duffy
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®...
2016: PloS One
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