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Plasmodium falciparum

Christine F Markwalter, Lauren E Gibson, Lwiindi Mudenda, Danielle W Kimmel, Saidon Mbambara, Philip E Thuma, David W Wright
A rapid, on-bead ELISA for Plasmodium lactate dehydrogenase ( p LDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM ( p LDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify p LDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Nigani Willie, Rajeev K Mehlotra, Rosalind E Howes, Tovonahary A Rakotomanga, Stephanie Ramboarina, Arsène C Ratsimbasoa, Peter A Zimmerman
Plasmodium falciparum histidine-rich protein 2 (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). However, the parasites lacking part or all of the pfhrp2 gene do not express the PfHRP2 protein and are, therefore, not identifiable by PfHRP2-detecting RDTs. We evaluated the performance of the SD Bioline Malaria Ag P.f/Pan RDT together with pfhrp2 variation in Madagascar. Genomic DNA isolated from 260 patient blood samples were polymerase chain reaction (PCR)-amplified for the parasite 18S rRNA and pfhrp2 genes...
March 19, 2018: American Journal of Tropical Medicine and Hygiene
Annemieke Abel, Christiane Steeg, Francis Aminkiah, Otchere Addai-Mensah, Marylyn Addo, Nicola Gagliani, Christian Casar, Denis Dekugmen Yar, Ellis Owusu-Dabo, Thomas Jacobs, Maria Sophia Mackroth
The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4+ T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4+ T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4+ T cells...
March 19, 2018: Scientific Reports
Adelaide S M Dennis, Adele M Lehane, Melanie C Ridgway, John P Holleran, Kiaran Kirk
For an increasing number of antimalarial agents identified in high throughput phenotypic screens there is evidence that they target PfATP4, a putative Na+ efflux transporter on the plasma membrane of the human malaria parasite, Plasmodium falciparum For several such 'PfATP4-associated' compounds it has been noted that their addition to parasitised erythrocytes results in cell swelling. Here we show that six structurally diverse PfATP4-associated compounds, including the clinical candidate KAE609 (cipargamin), induce swelling both of isolated blood-stage parasites and of intact parasitised erythrocytes...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Luciana Pereira de Sousa, Roberto Farina de Almeida, Flávia Lima Ribeiro-Gomes, Leonardo José de Moura Carvalho, Tadeu Mello E Souza, Diogo Onofre Gomes de Souza, Cláudio Tadeu Daniel-Ribeiro
BACKGROUND: Cerebral malaria, the main complication of Plasmodium falciparum infection in humans, is associated with persistent neurocognitive sequels both in human disease and the murine experimental model. In recent years, cognitive deficits related to uncomplicated (non-cerebral) malaria have also been reported in chronically exposed residents of endemic areas, but not in some murine experimental models of non-cerebral malaria. This study aimed at evaluating the influence of uncomplicated malaria on different behavioural paradigms associated with memory and anxiety-like parameters in a murine model that has the ability to develop cerebral malaria...
March 20, 2018: Parasites & Vectors
Melanie Bannister-Tyrrell, Nguyen Xuan Xa, Johanna Helena Kattenberg, Nguyen Van Van, Vu Khac Anh Dung, Truong Minh Hieu, Nguyen Van Hong, Eduard Rovira-Vallbona, Nguyen Thanh Thao, Tran Thanh Duong, Anna Rosanas-Urgell, Koen Peeters Grietens, Annette Erhart
BACKGROUND: In Vietnam, malaria persists in remote forested regions where infections are spatially heterogeneous, mostly asymptomatic and with low parasite density. Previous studies in Vietnam have investigated broad behavioural concepts such as 'engaging in forest activities' as risk factors for malaria infection, which may not explain heterogeneity in malaria risk, especially in malaria elimination settings. METHODS: A mixed methods study combining ethnographic research and a cross-sectional survey was embedded in a 1-year malariometric cohort study in three ethnic minority villages in South Tra My district, Quang Nam Province in Central Vietnam...
March 19, 2018: Malaria Journal
Yair Fastman, Shany Assaraf, Miriam Rose, Elad Milrot, Katherine Basore, B Sivanandam Arasu, Sanjay A Desai, Michael Elbaum, Ron Dzikowski
Plasmodium falciparum, the causative agent of the deadliest form of human malaria, alternates expression of variable antigens, encoded by members of a multi-copy gene family named var. In var2csa, the var gene implicated in pregnancy-associated malaria, translational repression is regulated by a unique upstream open reading frame (uORF) found only in its 5' UTR. Here, we report that this translated uORF significantly alters both transcription and posttranslational protein trafficking. The parasite can alter a protein's destination without any modifications to the protein itself, but instead by an element within the 5' UTR of the transcript...
March 15, 2018: Nucleic Acids Research
Seda Yerlikaya, Ana Campillo, Iveth J Gonzalez
Despite the increased use and worldwide distribution of malaria rapid diagnostic tests (RDTs) which distinguish between Plasmodium falciparum and non-falciparum species, little is known about their performance for detecting Plasmodium knowlesi (Pk), Plasmodium malariae (Pm), and Plasmodium ovale (Po). The objective of this review is to analyze results of published studies evaluating the diagnostic accuracy of malaria RDTs in detecting Pk, Pm and Po mono-infections.MEDLINE, EMBASE, Web of Science and CENTRAL databases were systematically searched to identify studies which reported on the performance of RDTs in detecting Pk, Pm,Po mono-infections...
March 15, 2018: Journal of Infectious Diseases
Joshua Tan, Brandon K Sack, David Oyen, Isabelle Zenklusen, Luca Piccoli, Sonia Barbieri, Mathilde Foglierini, Chiara Silacci Fregni, Jessica Marcandalli, Said Jongo, Salim Abdulla, Laurent Perez, Giampietro Corradin, Luca Varani, Federica Sallusto, Betty Kim Lee Sim, Stephen L Hoffman, Stefan H I Kappe, Claudia Daubenberger, Ian A Wilson, Antonio Lanzavecchia
Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P...
March 19, 2018: Nature Medicine
Neville K Kisalu, Azza H Idris, Connor Weidle, Yevel Flores-Garcia, Barbara J Flynn, Brandon K Sack, Sean Murphy, Arne Scho N, Ernesto Freire, Joseph R Francica, Alex B Miller, Jason Gregory, Sandra March, Hua-Xin Liao, Barton F Haynes, Kevin Wiehe, Ashley M Trama, Kevin O Saunders, Morgan A Gladden, Anthony Monroe, Mattia Bonsignori, Masaru Kanekiyo, Adam K Wheatley, Adrian B McDermott, S Katie Farney, Gwo-Yu Chuang, Baoshan Zhang, Natasha Kc, Sumana Chakravarty, Peter D Kwong, Photini Sinnis, Sangeeta N Bhatia, Stefan H I Kappe, B Kim Lee Sim, Stephen L Hoffman, Fidel Zavala, Marie Pancera, Robert A Seder
Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection...
March 19, 2018: Nature Medicine
María Andrea Hernández-Castañeda, Smart Mbagwu, Kehinde Adebayo Babatunde, Michael Walch, Luis Filgueira, Pierre-Yves Mantel
Malaria is a life-threatening disease caused by Plasmodium parasites, with P. falciparum being the most prevalent on the African continent and responsible for most malaria-related deaths globally. Several factors including parasite sequestration in tissues, vascular dysfunction, and inflammatory responses influence the evolution of the disease in malaria-infected people. P. falciparum-infected red blood cells (iRBCs) release small extracellular vesicles (EVs) containing different kinds of cargo molecules that mediate pathogenesis and cellular communication between parasites and host...
February 14, 2018: Journal of Visualized Experiments: JoVE
Mie Ikeda, Megumi Kaneko, Shin-Ichiro Tachibana, Betty Balikagala, Miki Sakurai-Yatsushiro, Shouki Yatsushiro, Nobuyuki Takahashi, Masato Yamauchi, Makoto Sekihara, Muneaki Hashimoto, Osbert T Katuro, Alex Olia, Paul S Obwoya, Mary A Auma, Denis A Anywar, Emmanuel I Odongo-Aginya, Joseph Okello-Onen, Makoto Hirai, Jun Ohashi, Nirianne M Q Palacpac, Masatoshi Kataoka, Takafumi Tsuboi, Eisaku Kimura, Toshihiro Horii, Toshihiro Mita
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates...
April 2018: Emerging Infectious Diseases
Wandayi Emmanuel Amlabu, Ishaya Haruna Nock, Naveen Kumar Kaushik, Dinesh Mohanakrishnan, Jyoti Tiwary, Patrick Ahmadu Audu, Musbahu S Abubakar, Dinkar Sahal
The plant kingdom continues to hold great promise for the eradication of Malaria infection following the challenges of insecticide resistance by the vector mosquito, drug resistance by the parasite, and the development of a vaccine still being a mirage. Acalypha wilkesiana Muller Argoviensis, 1866 (family: Euphorbiaceae) leaves have the ethnopharmacological reputation for use as a remedy against dermal microbial infections in Nigeria. Here, we have studied the antiplasmodial potential of the extract of the leaves of this ornamental plant...
March 17, 2018: Parasitology Research
Karteek Kadimisetty, Jinzhao Song, Aoife M Doto, Young Hwang, Jing Peng, Michael G Mauk, Frederic D Bushman, Robert Gross, Joseph N Jarvis, Changchun Liu
Molecular diagnostics that involve nucleic acid amplification tests (NAATs) are crucial for prevention and treatment of infectious diseases. In this study, we developed a simple, inexpensive, disposable, fully 3D printed microfluidic reactor array that is capable of carrying out extraction, concentration and isothermal amplification of nucleic acids in variety of body fluids. The method allows rapid molecular diagnostic tests for infectious diseases at point of care. A simple leak-proof polymerization strategy was developed to integrate flow-through nucleic acid isolation membranes into microfluidic devices, yielding a multifunctional diagnostic platform...
March 10, 2018: Biosensors & Bioelectronics
Sylvie Daunes, Claudius D'Silva
N-Benzyloxycarbony-S-(2,4-dinitrophenyl)glutathione diesters have been investigated for antimalarial activity against chloroquinine sensitive (NF54) and resistant (K1) strains of P. falciparum. Both strains appear equally susceptible to inhibition by compounds 1-4, with an IC50  ∼ 4.92-6.97 μM, consistent with the target of these compounds being the PfMRP transporter. Against the NF54 strain, diester derivatives containing ethyl side chains showed lower in vitro activity than those with methyl side chains 1-4, IC50  ∼ 5...
March 7, 2018: Bioorganic Chemistry
Kelle Velasques, Tamara Ramos Maciel, Ana Helena de Castro Dal Forno, Flávia Elizabete Guerra Teixeira, Amanda Luisa da Fonseca, Fernando de Pilla Varotti, André Ricardo Fajardo, Daiana Silva de Ávila, Sandra Elisa Haas
Drugs used for the treatment and prevention of malaria have resistance-related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second-line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti-plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co-encapsulated QN + CR-loaded polysorbate-coated polymeric nanocapsules (NC-QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans...
March 14, 2018: European Journal of Pharmaceutical Sciences
Smita Das, Roger B Peck, Rebecca Barney, Ihn Kyung Jang, Maria Kahn, Meilin Zhu, Gonzalo J Domingo
BACKGROUND: As malaria endemic countries shift from control to elimination, the proportion of low density Plasmodium falciparum infections increases. Current field diagnostic tools, such as microscopy and rapid diagnostic tests (RDT), with detection limits of approximately 100-200 parasites/µL (p/µL) and 800-1000 pg/mL histidine-rich protein 2 (HRP2), respectively, are unable to detect these infections. A novel ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT) was evaluated in laboratory conditions to define the test's performance against recombinant HRP2 and native cultured parasites...
March 17, 2018: Malaria Journal
Kostantinos Kiakos, Bernhard Englinger, Stephanie K Yanow, Debora Wernitznig, Michael A Jakupec, Walter Berger, Bernhard K Keppler, John A Hartley, Moses Lee, Pravin C Patil
HxTfA 4 is a fluorescent analog of a potent cytotoxic and antimalarial agent, TfA 3, which is currently being investigated for the development of an antimalarial vaccine, PlasProtect®. HxTfA contains a p-anisylbenzimidazole or Hx moiety, which is endowed with a blue emission upon excitation at 318 nm; thus enabling it to be used as a surrogate for probing the cellular fate of TfA using confocal microscopy, and addressing the question of nuclear localization. HxTfA exhibits similar selectivity to TfA for A-tract sequences of DNA, alkylating adenine-N3, albeit at 10-fold higher concentrations...
March 5, 2018: Bioorganic & Medicinal Chemistry Letters
Muzamil Mahdi Abdel Hamid, Kamala Thriemer, Maha E Elobied, Nouh S Mahgoub, Salah A Boshara, Hassan M H Elsafi, Suhaib A Gumaa, Tassneem Hamid, Hanadi Abdelbagi, Hamid M Basheir, Jutta Marfurt, Ingrid Chen, Roly Gosling, Ric N Price, Benedikt Ley
BACKGROUND: First-line schizontocidal treatment for uncomplicated malaria in the Republic of the Sudan is artesunate (total dose 12 mg/kg) plus Sulphadoxine/pyrimethamine (25/1.25 mg/kg) (AS/SP). Patients with Plasmodium vivax are also treated with 14 days primaquine (total dose 3.5 mg/kg) (PQ). The aim of this study was to assess the efficacy of the national policy. METHODS: Patients above 1 year, with microscopy-confirmed, Plasmodium falciparum and/or P. vivax malaria were treated with AS/SP...
March 16, 2018: Malaria Journal
Beatriz Galatas, Helena Martí-Soler, Lidia Nhamussua, Pau Cisteró, Pedro Aide, Francisco Saute, Clara Menéndez, N Regina Rabinovich, Pedro L Alonso, Quique Bassat, Alfredo Mayor
Background: Afebrile Plasmodium falciparum infections usually remain undetected and untreated in the community and could potentially contribute to sustaining local malaria transmission in areas aiming for malaria elimination. Methods: Thirty-two men with afebrile P. falciparum infections detected with rapid diagnostic test (RDTs) were followed for 28 days. Kaplan-Meier estimates were computed to estimate probability of parasite positivity and of reducing parasitaemia by half of its initial level by day 28...
March 13, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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