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Muhammad Ismail, Longbing Ling, Yawei Du, Chen Yao, Xinsong Li
Artemisinin and its derivatives are highly effective drugs in the treatment of P. falciparum malaria. However, their clinical applications face challenges because of short half-life, poor bioavailability and growing drug resistance. In this article, novel dimeric artesunate phospholipid (Di-ART-GPC) based liposomes were developed by combination of dimerization and self-assembly to address these shortcomings. Firstly, Di-ART-GPC conjugate was synthesized by a facile esterification of artesunate (ART) and glycerophosphorylcholine (GPC) and confirmed by MS, 1 H NMR and 13 C NMR...
February 10, 2018: Biomaterials
Rakesh Chopra, Kelly Chibale, Kamaljit Singh
Triazole tethered 7-chloroquinoline-pyrimidine-5-carboxylate hybrids were synthesized and evaluated for antiplasmodial activity against chloroquine sensitive (CQ S ) NF54 strain of Plasmodium falciparum. The most active hybrids of the series were further screened against the chloroquine resistant (CQ R ) Dd2 strain of the parasite and for in vitro cytotoxicity against mammalian Vero cell lines. Further, their physico-chemical properties, binding studies with hemin (monomeric &μ-oxo dimeric) and DNA [pUC-18, calf thymus (CT)] led us to plausible proposed binding mode of the most active member of the present series...
February 9, 2018: European Journal of Medicinal Chemistry
Fukumi Nakamura-Uchiyama, Yuichi Katanami, Tadashi Kikuchi, Saho Takaya, Satoshi Kutsuna, Taiichiro Kobayashi, Yasutaka Mizuno, Tetsuo Hasegawa, Michiko Koga, Yukihiro Yoshimura, Chihiro Hasegawa, Yasuyuki Kato, Mikio Kimura, Haruhiko Maruyama
BACKGROUND: The Research Group on Chemotherapy of Tropical Diseases, Japan, introduced artemether-lumefantrine (AL) in late 2002, mainly for treating uncomplicated Plasmodium falciparum malaria. Because AL was on the market in Japan in March 2017, the effectiveness and safety of AL were analyzed to help medical personnel use AL optimally. METHODS: Case report forms submitted by the attending physicians were analyzed. When necessary, direct contact with the attending physicians was made to obtain detailed information...
February 14, 2018: Travel Medicine and Infectious Disease
Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E Busse, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Elena A Levashina, Peter G Kremsner, Benjamin Mordmüller, Thomas Höfer, Hedda Wardemann
Affinity maturation, the clonal selection and expansion of antigen-activated B cells expressing somatically mutated antibody variants that develop during T cell-dependent germinal center reactions, is considered pivotal for efficient development of protective B cell memory responses to infection and vaccination. Repeated antigen exposure promotes affinity maturation but each time also recruits antigen-reactive naïve B cells into the response. Here, we determined the relative impact of affinity maturation versus antigen-mediated clonal selection of naïve B cells to mount potent B cell memory responses in humans after repeated exposure to a complex pathogen, the malaria parasite Plasmodium falciparum (Pf)...
February 16, 2018: Science Immunology
Solomon Kinde Getawen, Temesgen Ashine, Fekadu Massebo, Daniel Woldeyes, Bernt Lindtjørn
House is the major site for malaria infection where most human-vector contact takes place. Hence, improving housing might reduce the risk of malaria infection by limiting house entry of vectors. This study aimed to explore the impact of screening doors and windows with wire meshes on density and entomological inoculation rate (EIR) of malaria vector, and malaria incidence, and assess the acceptability, durability, and cost of the intervention. The susceptibility status of malaria vector was also assessed. A two-arm randomized trial was done in Arba Minch Town, southwest Ethiopia...
February 13, 2018: Acta Tropica
Vijay Jayaraman, Arpitha Suryavanshi, Pavithra Kalale, Jyothirmai Kunala, Hemalatha Balaram
Plasmodium falciparum (Pf), the causative agent of malaria, has an iron-sulfur cluster-containing class I fumarate hydratase (FH) that catalyzes the interconversion of fumarate to malate, a well-known reaction in the tricarboxylic acid cycle. In humans, the same reaction is catalyzed by class II FH that has no sequence or structural homology with the class I enzyme from Plasmodium. Fumarate is generated in large quantities in the parasite as a byproduct of AMP synthesis and is converted to malate by FH and then used in the generation of the key metabolites oxaloacetate, aspartate, and pyruvate...
February 15, 2018: Journal of Biological Chemistry
Jing Xia, Xibao Huang, Lingcong Sun, Hong Zhu, Wen Lin, Xiaorong Dong, Dongni Wu, Juan Qiu, Li Zheng, Mumin Cao, Si Liu, Huaxun Zhang
BACKGROUND: Hubei Province, China, has been operating a malaria elimination programme. This study aimed at investigating the epidemiologic characteristics of malaria in Hubei Province (2005-2016) to plan resource allocation for malaria elimination. METHODS: Data on all malaria cases from 2005 to 2016 in all counties of Hubei Province were extracted from a web-based reporting system. The numbers of indigenous and imported cases during the disease control (2005-2010) and elimination (2011-2016) stages, as well as their spatiotemporal distribution, were compared...
February 15, 2018: Malaria Journal
Vanka Ravisankar, Gowthamarajan Kuppusamy, Praveen Kumar Simhadri, Uday Krishna Baruah, Veera Venkata Satyanarayana Reddy Karri, Vimal Pandey, Phanithi Prakash Babu
Cerebral malaria (CM) is a fatal neurological complication of Plasmodium falciparum infection that affects children (below five years old) in sub-Saharan Africa and adults in South-East Asia each year having the fatality rate of 10-25%. The survivors of CM also have high risk of long term neurological or cognitive deficits. The objective of the present investigation was to develop optimized nanostructured lipid carriers (NLCs) of artemether (ARM) for enhanced anti-malarial efficacy of ARM.NLCs of ARM were prepared by a combination of high speed homogenization (HSH) and probe sonication techniques...
February 16, 2018: Journal of Microencapsulation
D Mnkandhla, J van Marwijk, H Hoppe, B S Wilhelmi, C G Whiteley
There is increasing requirement for the development of new drug protocols against malaria, a fatal disease caused by the lethal parasite Plasmodium falciparum. Leucine aminopeptidase (Pf LAP) of Plasmodium falciparum, is being pursued as a promising target for the discovery of novel antimalarials. The effects of silver nanoparticles (AgNPs) against P. falciparum leucine amino-peptidase (Pf LAP) and the human homolog (HsLAP) were compared. Pf LAP and HsLAP were expressed in Escherichia coli, and AgNPs (3-10 nm) characterized by ultra-violet spectroscopy and transmission electron microscopy...
February 1, 2018: Journal of Nanoscience and Nanotechnology
Catherine Fagundez, Diver Sellanes, Gloria Lourdes Serra
The results from the synthesis of peptides by Fmoc/SPPS on a 2-CTC resin and then lactamization in solution or solid phase for the preparation of cyclopeptides are presented. Both procedures allow the synthesis of the desired compounds in good to very good yield and with high cyclization efficiency for on-resin macrocyclization. In addition, the activities of the corresponding cyclopeptides against the chloroquine-resistant K1 strain of Plasmodium falciparum were evaluated. Cyclo-Cys(Trt)-Gly-Thr(tBu)-Gly-Cys(Trt)-Gly showed potent in vitro and selective activity against this parasite, EC50 = 28 nM...
February 15, 2018: ACS Combinatorial Science
Mateusz M Plucinski, Baltazar Candrinho, Geraldo Chambe, João Muchanga, Olinda Muguande, Graça Matsinhe, Guidion Mathe, Eric Rogier, Timothy Doyle, Rose Zulliger, James Colborn, Abu Saifodine, Patrick Lammie, Jeffrey W Priest
BACKGROUND: Universal coverage with long-lasting insecticidal nets (LLINs) is a primary control strategy against Plasmodium falciparum malaria. However, its impact on the three other main species of human malaria and lymphatic filariasis (LF), which share the same vectors in many co-endemic areas, is not as well characterized. The recent development of multiplex antibody detection provides the opportunity for simultaneous evaluation of the impact of control measures on the burden of multiple diseases...
February 14, 2018: PLoS Neglected Tropical Diseases
Fumiji Saito, Kouyuki Hirayasu, Takeshi Satoh, Christian W Wang, John Lusingu, Takao Arimori, Kyoko Shida, Nirianne Marie Q Palacpac, Sawako Itagaki, Shiroh Iwanaga, Eizo Takashima, Takafumi Tsuboi, Masako Kohyama, Tadahiro Suenaga, Marco Colonna, Junichi Takagi, Thomas Lavstsen, Toshihiro Horii, Hisashi Arase
This corrects the article DOI: 10.1038/nature24994.
February 14, 2018: Nature
C M Nielsen, J Vekemans, M Lievens, K E Kester, J A Regules, C F Ockenhouse
Although RTS,S remains the most advanced malaria vaccine, the factors influencing differences in vaccine immunogenicity or efficacy between individuals or populations are still poorly characterised. The analyses of genetic determinants of immunogenicity have previously been restricted by relatively small sample sizes from individual trials. Here we combine data from six Phase II RTS,S trials and evaluate the relationship between HLA allele groups and RTS,S-mediated protection in controlled human malaria infections (CHMI), using multivariate logistic or linear regression...
February 10, 2018: Vaccine
Isabelle Zenklusen, Said Jongo, Salim Abdulla, Kamaka Ramadhani, B Kim Lee Sim, Hayley Cardamone, Erika L Flannery, Thao Nguyen, Matthew Fishbaugher, Ryan W J Steel, Will Betz, Nelly Carmago, Sebastian Mikolajczak, Stefan H I Kappe, Stephen L Hoffman, Brandon K Sack, Claudia Daubenberger
The assessment of antibody responses after immunization with radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ) (Sanaria® PfSPZ Vaccine) has focused on IgG isotype antibodies. Here, we aimed to investigate if Pf sporozoite binding and invasion inhibitory IgM antibodies are induced following immunization of malaria pre-exposed volunteers with PfSPZ Vaccine. We found that in addition to anti-PfCSP IgG, Malaria pre-exposed volunteers developed anti-PfCSP IgM antibodies after immunization with PfSPZ Vaccine and that these IgM antibodies inhibited Pf sporozoite-invasion of hepatocytes in vitro...
February 8, 2018: Journal of Infectious Diseases
Shilpy Aggarwal, Deepika Paliwal, Dhirender Kaushik, Girish Kumar Gupta, Ajay Kumar
BACKGROUND: Malaria, one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need of identify new targets for chemotherapy Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P...
February 12, 2018: Combinatorial Chemistry & High Throughput Screening
Hoan Vu, Liliana Pedro, Tin Mak, Brendan McCormick, Jessica Rowley, Miaomiao Liu, Angela Di Capua, Billy Williams-Noonan, Ngoc B Pham, Rebecca H Pouwer, Bao Nguyen, Katherine T Andrews, Tina Skinner-Adams, Jessica Kim, Wim G J Hol, Raymond Hui, Gregory J Crowther, Wesley C Van Voorhis, Ronald J Quinn
Natural products are well known for their biological relevance, high degree of three-dimensionality and access to areas of largely unexplored chemical space. To shape our understanding on the interaction between natural products and protein targets in the post-genomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural product-based fragment library. We reveal here 97 low molecular natural products identified as binding partners of 32 of the putative malarial targets...
February 13, 2018: ACS Infectious Diseases
Justin Y A Doritchamou, Richard A Akuffo, Azizath Moussiliou, Adrian J F Luty, Achille Massougbodji, Philippe Deloron, Nicaise G Tuikue Ndam
BACKGROUND: Among the Plasmodium species that infect humans, adverse effects of P. falciparum and P. vivax have been extensively studied and reported with respect to poor outcomes particularly in first time mothers and in women living in areas with unstable malaria transmission. Although, other non-falciparum malaria infections during pregnancy have sometimes been reported, little is known about the dynamics of these infections during pregnancy. METHODS AND FINDINGS: Using a quantitative PCR approach, blood samples collected from Beninese pregnant women during the first antenatal visit (ANV) and at delivery including placental blood were screened for Plasmodium spp...
February 12, 2018: PLoS Neglected Tropical Diseases
Yanhong Sun, Shuqi Wang, Jianbo Ji, Guangxi Zhai, Jie Xing
Naphthoquine (NQ) is one of important partner drugs of Artemisinin-based combination therapy (ACT), which is recommended for the treatment of uncomplicated Plasmodium falciparum. NQ shows a high cure rate after a single oral administration. It is absorbed quickly (Tmax 2-4 h) and has a long elimination half-life (255 h). However, the metabolism of NQ has not been clarified. In this work, the metabolite profiling of NQ was studied in six liver microsomal incubates (human, cynomolgus monkey, beagle dog, mini pig, rat and CD1 mouse), seven recombinant CYP enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4) and rat (plasma, urine, bile and feces ) using liquid chromatography tandem high-resolution LTQ-Orbitrap mass spectrometry (HRMSn ) in conjunction with online H/D exchange...
February 12, 2018: Biomedical Chromatography: BMC
Giovanni Widmer
Genome sequencing has greatly contributed to our understanding of parasitic protozoa. This is particularly the case for Cryptosporidium species (phylum Apicomplexa) which are difficult to propagate. Because of their polymorphic nature, simple sequence repeats have been used extensively as genotypic markers to differentiate between isolates, but no global analysis of amino acid repeats in Cryptosporidium genomes has been reported. Taking advantage of several newly sequenced Cryptosporidium genomes, a comparative analysis of single-amino-acid repeats (SAARs) in seven species was undertaken...
February 12, 2018: Parasitology
Cho Naing, Maxine A Whittaker
BACKGROUND: Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria. MAIN BODY: A systematic review and meta-analysis of the available literature on thrombocytopaenia in P...
February 9, 2018: Infectious Diseases of Poverty
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