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Shahriyar Taghavi-Moghadam, Cecil D Kwong, John A Secrist, Shabana I Khan, Alice M Clark
Eupolauridine, an indenonaphthyridine alkaloid, has been previously reported by us to exhibit antifungal activity. This study describes the synthesis of new alkyl and benzyl naphthyridinium/pyridinium analogs of eupolauridine as potential antifungal agents. A majority of the analogs exhibited antifungal activity against opportunistic pathogens such as Candida albicans and Cryptococcus neoformans. Several of them were also effective against bacteria (Staphylococcus aureus, MRS, Pseudomonas and Mycobacterium) and the malaria parasite (Plasmodium falciparum) to variable extents...
February 23, 2016: Bioorganic & Medicinal Chemistry
Christine F Markwalter, Keersten M Ricks, Anna L Bitting, Lwiindi Mudenda, David W Wright
We have developed a rapid magnetic microparticle-based detection strategy for malarial biomarkers Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein II (PfHRPII). In this assay, magnetic particles functionalized with antibodies specific for pLDH and PfHRPII as well as detection antibodies with distinct enzymes for each biomarker are added to parasitized lysed blood samples. Sandwich complexes for pLDH and PfHRPII form on the surface of the magnetic beads, which are washed and sequentially re-suspended in detection enzyme substrate for each antigen...
December 1, 2016: Talanta
Suwanna Chaorattanakawee, Chanthap Lon, Krisada Jongsakul, Jariyanart Gawee, Somethy Sok, Siratchana Sundrakes, Nareth Kong, Chatchadaporn Thamnurak, Soklyda Chann, Sorayut Chattrakarn, Chantida Praditpol, Nillawan Buathong, Nichapat Uthaimongkol, Philip Smith, Narongrid Sirisopana, Rekol Huy, Satharath Prom, Mark M Fukuda, Delia Bethell, Douglas S Walsh, Charlotte Lanteri, David Saunders
BACKGROUND: The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. METHODS: Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ) resistance from sentinel sites on the Thai-Cambodian and Thai-Myanmar borders from 2010 to 2015...
October 21, 2016: Malaria Journal
Alfred Amambua-Ngwa, Bakary Danso, Archibald Worwui, Sukai Ceesay, Nwakanma Davies, David Jeffries, Umberto D'Alessandro, David Conway
BACKGROUND: Previous genome-wide analyses of single nucleotide variation in Plasmodium falciparum identified evidence of an extended haplotype region on chromosome 6 in West Africa, suggesting recent positive selection. Such a pattern is not seen in samples from East Africa or South East Asia, so it could be marking a selective process specific to West Africa. Analyses of the haplotype structure in samples taken at different times could give clues to possible causes of selection. METHODS: This study investigates chromosome 6 extended haplotypes in The Gambia by analysing alleles at multiple microsatellite loci using genome sequence data previously obtained from clinical isolates collected in 2008, followed by genotyping of 13 loci in 439 isolates from 1984, 1991, 2008 and 2014...
October 21, 2016: Malaria Journal
Andrew A Lover, Roly Gosling, Richard Feachem, Jim Tulloch
The emergence in 2009 of Plasmodium falciparum parasites resistant to the primary therapies currently in use (artemisinin-based combination therapy, ACT) in Southeast Asia threatens to set back decades of global progress in malaria control and elimination. Progress to date through multiple sets of initiatives and partners to contain or eliminate these parasites has been hampered due to a wide range of organizational, financial, and health systems-level challenges. In this commentary, a set of seven specific and concrete actions are proposed to directly address these issues and to accelerate P...
October 21, 2016: Malaria Journal
Sittiporn Pattaradilokrat, Vorthon Sawaswong, Phumin Simpalipan, Morakot Kaewthamasorn, Napaporn Siripoon, Pongchai Harnyuttanakorn
BACKGROUND: An effective malaria vaccine is an urgently needed tool to fight against human malaria, the most deadly parasitic disease of humans. One promising candidate is the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum. This antigenic protein, encoded by the merozoite surface protein (msp-3) gene, is polymorphic and classified according to size into the two allelic types of K1 and 3D7. A recent study revealed that both the K1 and 3D7 alleles co-circulated within P. falciparum populations in Thailand, but the extent of the sequence diversity and variation within each allelic type remains largely unknown...
October 21, 2016: Malaria Journal
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
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
Arundhati Barua, Niharika Gill
OBJECTIVE: This comparative cross sectional study was conducted in a teaching hospital in Mumbai during the monsoon of 2014.A significant number of dengue and malaria co-infection cases, along with dengue, malaria and other infective causes of acute febrile illnesses were noted. The objective of the present study was to understand the interplay of both infections. Since the first such reported case in 2005, studies and data on such cases are scarce, hence this study. AIM: To compare the clinical course, laboratory features, severity and outcome of coinfection with monoinfection of malaria and dengue...
August 2016: Journal of the Association of Physicians of India
Rajesh Deshwal
OBJECTIVE: The clinical presentations and laboratory profile of malaria has been changing over the years. Therefore this study was undertaken to study the clinical profile and laboratory parameters of malarial patients. METHODS: This prospective observational study was undertaken in military hospital with high prevalence of malaria. A total of 320 patients were studied. All patients tested positive by peripheral blood smear or rapid diagnostic test were included...
August 2016: Journal of the Association of Physicians of India
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
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
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
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