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P. falciparum

M Laura Idda, Valeria Lodde, Grazia Galleri, Jennifer L Martindale, Rachel Munk, Kotb Abdelmohsen, Francesco Cucca, Myriam Gorospe
Nuclear factor 90 (NF90) is a dual DNA- and RNA-binding protein expressed ubiquitously in mammalian cells, including monocytes. Here, to elucidate the function of NF90 in the immune response, we analyzed systematically its influence on gene expression programs in the human monocytic cell line THP-1 expressing normal or reduced NF90 levels. RNA sequencing analysis revealed many mRNAs showing differential abundance in NF90-silenced cells, many of them encoding proteins implicated in the response to immune stimuli and malaria infection...
February 20, 2019: Cell Cycle
Sofía Mira-Martínez, Anastasia K Pickford, Núria Rovira-Graells, Pieter Guetens, Elisabet Tintó-Font, Alfred Cortés, Anna Rosanas-Urgell
During the intraerythrocytic asexual cycle malaria parasites acquire nutrients and other solutes through a broad selectivity channel localized at the membrane of the infected erythrocyte termed Plasmodial Surface Anion Channel (PSAC). The protein product of the Plasmodium falciparum clonally variant clag3.1 and clag3.2 genes determines PSAC activity. Switches in the expression of clag3 genes, which are regulated by epigenetic mechanisms, are associated with changes in PSAC-dependent permeability that can result in resistance to compounds toxic for the parasite such as blasticidin S...
February 19, 2019: Antimicrobial Agents and Chemotherapy
Marie Gladys Robert, Francis Foguim Tsombeng, Mathieu Gendrot, Silman Diawara, Marylin Madamet, Mame Bou Kounta, Khalifa Ababacar Wade, Mansour Fall, Mamadou Wague Gueye, Nicolas Benoit, Aminata Nakoulima, Raymond Bercion, Rémy Amalvict, Bécaye Fall, Boubacar Wade, Bakary Diatta, Bruno Pradines
Dihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6 to 17.1% of P. falciparum isolates collected in Dakar in 2013-2015 showed ex vivo reduced susceptibility to piperaquine. Neither the exonuclease-E415G mutation nor the copy number variation of the Plasmepsin II gene ( Pfpm2 ), associated with piperaquine resistance in Cambodia, was detected in Senegalese parasites.
February 19, 2019: Antimicrobial Agents and Chemotherapy
Ziling Liu, Than Naing Soe, Yan Zhao, Aye Than, Cho Cho, Pyae Linn Aung, Yuling Li, Lin Wang, Huilin Yang, Xiangnan Li, Danni Li, Zhiping Peng, Jiangang Wang, Yan Li, Zhaoqing Yang, Hongning Zhou, Qinghui Wang, Myat Phone Kyaw, Yaming Cao, Liwang Cui
BACKGROUND: The malaria burden of Myanmar still remains high within the Greater Mekong Subregion of Southeast Asia. An important indicator of progress towards malaria elimination is the prevalence of parasite infections in endemic populations. Information about malaria epidemiology is mostly derived from reports of confirmed acute malaria cases through passive case detection, whereas the prevalence of baseline subclinical malaria infections is much less known. METHODS: In this study, cross-sectional surveys were conducted during the rainy season of 2017 in four townships (Bilin, Thabeikkyin, Banmauk and Paletwa) of Myanmar with divergent annual malaria incidences...
February 18, 2019: Parasites & Vectors
Moussa Djimde, Hanen Samouda, Julien Jacobs, Hamidou Niangaly, Mamadou Tekete, Seydou B Sombie, Erick Josephat Mgina, Bakary Fofana, Issaka Sagara, Ogobara K Doumbo, Michel Vaillant, Abdoulaye A Djimde
BACKGROUND: Anti-malarial treatments effectiveness remains a critical challenge for control programmes. However, when drug efficacy is established, the dose is calculated based on a predefined weight according to the patient age. Based on the hypothesis that the standard assumption of weight according to the age when administering the drug could lead to a therapeutic failure potentially due to under-dosing (in the case of overweight) or over-dosing (in case of underweight). In this study, the relationship between weight status and malaria drug efficacy in clearing current Plasmodium falciparum infection and preventing reinfection after treatment was investigated...
February 18, 2019: Malaria Journal
Lola Fagbami, Amy A Deik, Jonathan D Herman, Kritika Singh, Sofia A Santos, Selina Bopp, Amanda K Lukens, Clary B Clish, Dyann F Wirth, Ralph Mazitschek
We have previously identified the cytoplasmic prolyl tRNA synthetase in Plasmodium falciparum as the functional target of the natural product febrifugine and its synthetic analogue halofuginone (HFG), one of the most potent antimalarials discovered to date. However, our studies also discovered that short-term treatment of asexual blood stage P. falciparum with HFG analogues causes a 20-fold increase in intracellular proline, termed Adaptive Proline Response (APR), which renders parasites tolerant to HFG. This novel resistance phenotype lacks an apparent genetic basis but remains stable after drug withdrawal...
February 18, 2019: ACS Infectious Diseases
A Roch, J Prodéo, C Pierart, R N Muller, P Duez
The binding of malaria pigment, hemozoin, by a gradient magnetic field has been investigated in a manual trapping column system. Two types of magnetic filling have been tested to produce field gradients: nickel-plated steel wires, wrapped around a steel core, and superparamagnetic microbeads. The latter system allows an efficient trapping (> 80%) of β-hematin (a synthetic pigment with physical and paramagnetic properties analogous to those of hemozoin). Tests with a Plasmodium falciparum 3D7 culture indicate that hemozoin is similarly trapped...
May 15, 2019: Talanta
Jung Yoon, Jung Ah Kwon, Soo Young Yoon, Woong Sik Jang, Dong June Yang, Jeonghun Nam, Chae Seung Lim
Microscopic examination of blood smears is the standard method for malaria diagnosis but is labor-intensive and requires expert staff. CellaVision DM96 (CellaVision, Lund, Sweden) is a digital hematology analyzer available for advanced morphological analysis of blood films including intracellular parasites. Here, we evaluated the CellaVision DM96 Advanced RBC Application for malaria detection in stained peripheral blood (PB) smears. Two hundred and twenty thin PB smear slides (84 P. vivax, 14 P. falciparum, 122 negative controls) were stained with Wright-Giemsa using automated slidemaker/strainers of Beckman Coulter hematology systems (LH780, Beckman Coulter Inc...
February 12, 2019: Acta Tropica
Lorenz von Seidlein, Thomas J Peto, Jordi Landier, Thuy-Nhien Nguyen, Rupam Tripura, Koukeo Phommasone, Tiengkham Pongvongsa, Khin Maung Lwin, Lilly Keereecharoen, Ladda Kajeechiwa, May Myo Thwin, Daniel M Parker, Jacher Wiladphaingern, Suphak Nosten, Stephane Proux, Vincent Corbel, Nguyen Tuong-Vy, Truong Le Phuc-Nhi, Do Hung Son, Pham Nguyen Huong-Thu, Nguyen Thi Kim Tuyen, Nguyen Thanh Tien, Le Thanh Dong, Dao Van Hue, Huynh Hong Quang, Chea Nguon, Chan Davoeung, Huy Rekol, Bipin Adhikari, Gisela Henriques, Panom Phongmany, Preyanan Suangkanarat, Atthanee Jeeyapant, Benchawan Vihokhern, Rob W van der Pluijm, Yoel Lubell, Lisa J White, Ricardo Aguas, Cholrawee Promnarate, Pasathorn Sirithiranont, Benoit Malleret, Laurent Rénia, Carl Onsjö, Xin Hui Chan, Jeremy Chalk, Olivo Miotto, Krittaya Patumrat, Kesinee Chotivanich, Borimas Hanboonkunupakarn, Podjanee Jittmala, Nils Kaehler, Phaik Yeong Cheah, Christopher Pell, Mehul Dhorda, Mallika Imwong, Georges Snounou, Mavuto Mukaka, Pimnara Peerawaranun, Sue J Lee, Julie A Simpson, Sasithon Pukrittayakamee, Pratap Singhasivanon, Martin P Grobusch, Frank Cobelens, Frank Smithuis, Paul N Newton, Guy E Thwaites, Nicholas P J Day, Mayfong Mayxay, Tran Tinh Hien, Francois H Nosten, Arjen M Dondorp, Nicholas J White
BACKGROUND: The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People's Democratic Republic, where artemisinin resistance is prevalent...
February 2019: PLoS Medicine
Jerald J Nair, Johannes van Staden
Malaria is prevalent in tropical and subtropical regions of the globe. With over 200 million cases reported annually, particularly in sub-Saharan Africa, it is an unnecessary burden to already overworked and ailing healthcare structures. Traditional medicine (TM) remains vibrant in most of these regions wherein plants often serve as the first line of defense against malaria. Given this fact as well as the successes elsewhere of therapies such as Artemisia annua emanating from evidence-based TM, interest in plants as a source of new antimalarial drugs has been rejuvenated...
February 11, 2019: Fitoterapia
R Cimanga Kanyanga, S Nsaka Lumpu, M Tshodi Ehata, B Mbamu Maya, C Kikweta Munduku, F Makila Bool-Miting, Paul Cos, Louis Maes, Arnold J Vlietinck, Vassiliki Exarchou, Emmy Tuenter, Luc Pieters
ETHNOPHARMACOLOGICAL RELEVANCE: An aqueous decoction of root bark of Alstonia congensis Engl. (Apocynaceae) is used in several African countries to treat various ailments including malaria. MATERIALS AND METHODS: Extracts of different polarity and isolated constituents were tested in vitro for their antiplasmodial activity against the chloroquine-resistant strain Plasmodium falciparum K1 and the chloroquine-sensitive strain P. falciparum NF54A19A, as well as for their cytotoxic effects againt MRC-5 cells (human lung fibroblasts)...
February 11, 2019: Journal of Ethnopharmacology
Preeti Yadav, R Ayana, Swati Garg, Ravi Jain, Raj Sah, Nishant Joshi, Soumya Pati, Shailja Singh
Lipid-based palmitoylation is a post-translation modification (PTM) which acts as a biological rheostat in life cycle progression of a deadly human malaria parasite, Plasmodium falciparum . P. falciparum palmitoylation is catalyzed by 12 putative palmitoyl acyl-transferase enzymes containing the conserved DHHC-CRD (DHHC motif within a cysteine-rich domain) which can serve as a druggable target. However, the paucity of high-throughput assays has impeded the design of drugs targeting palmitoylation. We have developed a novel strategy which involves engineering of Escherichia coli , a PTM-null system, to enforce ectopic expression of palmitoyl acyl-transferase in order to study Plasmodium -specific palmitoylation and screening of inhibitors...
February 2019: FEBS Open Bio
T W Yeo, J B Weinberg, D A Lampah, E Kenangalem, P Bush, Y Chen, R N Price, S Young, H Y Zhang, D Millington, D L Granger, N M Anstey
Background: Interactions between the endothelium and infected erythrocytes, microvascular dysfunction and parasite sequestration play major roles in the pathogenesis of severe falciparum malaria. The glycocalyx is a carbohydrate-rich layer lining the endothelium mediating NO production and vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity is not known. Methods: We prospectively enrolled Indonesian inpatients (≥18 years old) with severe (SM) or moderately-severe (MSM) falciparum malaria and healthy controls (HCs)...
February 12, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
John Bradley, Harouna M Soumaré, Almahamoudou Mahamar, Halimatou Diawara, Michelle Roh, Michael Delves, Chris Drakeley, Thomas S Churcher, Alassane Dicko, Roly Gosling, Teun Bousema
Gametocyte density and sex-ratio can predict the proportion of mosquitoes that become infected after feeding on blood of patients receiving non-gametocytocidal drugs. Because primaquine and methylene blue sterilize gametocytes before affecting their density and sex-ratio, mosquito feeding experiments are required to demonstrate their early transmission-blocking effects.
February 12, 2019: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Edwin O Ogola, Edith Chepkorir, Rosemary Sang, David P Tchouassi
BACKGROUND: In Kenya, malaria remains a major public health menace equally affecting the semi-arid to arid ecologies. However, entomologic knowledge of malaria vectors in such areas remains poor. METHODS: Morphologically-identified wild-caught Anopheles funestus (s.l.) specimens trapped outdoors from the semi-arid to arid area of Kacheliba, West Pokot County, Kenya, were analysed by PCR and sequencing for species identification, malaria parasite infection and host blood-meal sources...
February 11, 2019: Parasites & Vectors
Rufin Marie Kouipou Toghueo, Eugénie Aimée Madiesse Kemgne, Pierre Eke, Michelle Ines Mbekou Kanko, Darline Dize, Dinkar Sahal, Fabrice Fekam Boyom
ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata (Annonaceae) is a commonly used medicinal plants in Cameroonian traditional medecines to treat various diseases including malaria. Previous studies have shown that extracts from this plant have antiplasmodial activity. AIM OF THE STUDY: This study aimed to explore the endophyic fungi associated with some parts of this plant for their ability to produce antiplasmodial metabolites. MATERIALS AND METHODS: One hundred and fifty-two endophytic fungi isolated from twelve different organs of A...
February 6, 2019: Journal of Ethnopharmacology
David Nderu, Francis Kimani, Kelvin Thiong'o, Evaline Karanja, Maureen Akinyi, Edwin Too, William Chege, Eva Nambati, Christian G Meyer, Thirumalaisamy P Velavan
Plasmodium falciparum histidine-rich proteins 2 (PfHRP2) based RDTs are advocated in falciparum malaria-endemic regions, particularly when quality microscopy is not available. However, diversity and any deletion in the pfhrp2 and pfhrp3 genes can affect the performance of PfHRP2-based RDTs. A total of 400 samples collected from uncomplicated malaria cases from Kenya were investigated for the amino acid repeat profiles in exon 2 of pfhrp2 and pfhrp3 genes. In addition, PfHRP2 levels were measured in 96 individuals with uncomplicated malaria...
February 8, 2019: Scientific Reports
Enderson Murillo, Carlos Muskus, Luz A Agudelo, Iván D Vélez, Freddy Ruiz-Lopez
Among vector-borne diseases malaria is the leading cause of morbidity in the world, with more than 200 million cases per year and a large number of deaths. The techniques traditionally used for the detection of Plasmodium in humans and Anopheles mosquitoes include microscopy, IRMA, ELISA, antibody or molecular assays, and anopheline dissection. However, these techniques are limited by their requirement of skilled personnel, low sensitivity or long processing times. A PCR-based high-resolution melting (PCR-HRM) analysis was developed for the detection and identification of P...
February 8, 2019: Scientific Reports
Renata M R J da Silva, Marilia O Gandi, Jorge S Mendonça, Alcione S Carvalho, Julia Penna Coutinho, Anna C C Aguiar, Antoniana U Krettli, Nubia Boechat
Malaria remains a major public health problem worldwide, and it is responsible for high rates of morbidity and mortality. Resistance to current antimalarial drugs has been identified, and new drugs are urgently needed. In this study, we designed and synthesized seventeen novel quinolines based on the structures of mefloquine ((2,8-bis(trifluoromethyl)quinolin-4-yl)(piperidin-2-yl)methanol) and amodiaquine (4-((7-chloroquinolin-4-yl)amino)-2-((diethylamino)methyl)phenol) using ring bioisosteric replacement and molecular hybridization of the functional groups...
February 2, 2019: Bioorganic & Medicinal Chemistry
Lynette Isabella Ochola-Oyier, Kevin Wamae, Irene Omedo, Christabel Ogola, Abneel Matharu, Jean Pierre Musabyimana, Francis K Njogu, Kevin Marsh
Erythrocyte surface proteins have been identified as receptors of Plasmodium falciparum merozoite proteins. The ligand-receptor interactions enable the parasite to invade human erythrocytes, initiating the clinical symptoms of malaria. These interactions are likely to have had an evolutionary impact on the genes that encode the ligand and receptor proteins. We used sequence data from Kilifi, Kenya to detect departures from neutrality in a paired analysis of P. falciparum merozoite ligands and their erythrocyte receptor genes from the same population...
February 5, 2019: Infection, Genetics and Evolution
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