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Malaria biomarker

Surendra K Sharma, Anunay Gupta, Ashutosh Biswas, Abhishek Sharma, Atul Malhotra, K T Prasad, Sreenivas Vishnubhatla, Sajal Ajmani, Hridesh Mishra, Manish Soneja, Shobha Broor
BACKGROUND & OBJECTIVES: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. METHODS: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study...
June 2016: Indian Journal of Medical Research
Andrea L Conroy, Michael Hawkes, Chloe R McDonald, Hani Kim, Sarah J Higgins, Kevin R Barker, Sophie Namasopo, Robert O Opoka, Chandy C John, W Conrad Liles, Kevin C Kain
Background.  Host responses to infection are critical determinants of disease severity and clinical outcome. The development of tools to risk stratify children with malaria is needed to identify children most likely to benefit from targeted interventions. Methods.  This study investigated the kinetics of candidate biomarkers of mortality associated with endothelial activation and dysfunction (angiopoietin-2 [Ang-2], soluble FMS-like tyrosine kinase-1 [sFlt-1], and soluble intercellular adhesion molecule-1 [sICAM-1]) and inflammation (10 kDa interferon γ-induced protein [CXCL10/IP-10] and soluble triggering receptor expressed on myeloid cells-1 [sTREM-1]) in the context of a randomized, double-blind, placebo-controlled, parallel-arm trial evaluating inhaled nitric oxide versus placebo as adjunctive therapy to parenteral artesunate for severe malaria...
September 2016: Open Forum Infectious Diseases
Babina Chakma, Priyamvada Jain, Naveen K Singh, Pranab Goswami
A novel label free spectrophotometric detection of malarial biomarker HRP-II following an indicator displacement assay has been developed. The assay is based on competitive displacement of murexide dye from its complex with Ni(2+) by HRP-II present in serum samples. The binding constant (Kd) discerned for the dye and HRP-II to Ni(2+) were 1.4 × 10(-6) M(-1) and 6.8 × 10(-9) M(-1), respectively. The progress of the reaction could be monitored from the change of color from orange (∼λ482 nm) to pink (∼λ515 nm) with the concomitant increase in HRP-II concentration in the mixture...
October 18, 2016: Analytical Chemistry
Fikregabrail Aberra Kassa, Kristin Van Den Ham, Anthony Rainone, Sylvie Fournier, Eric Boilard, Martin Olivier
Cerebral malaria claims the life of millions of people each year, particularly those of children, and is a major global public health problem. Thus, the identification of novel malaria biomarkers that could be utilized as diagnostic or therapeutic targets is becoming increasingly important. Using a proteomic approach, we previously identified unique biomarkers in the sera of malaria-infected individuals, including apolipoprotein E (ApoE). ApoE is the dominant apolipoprotein in the brain and has been implicated in several neurological disorders; therefore, we were interested in the potential role of ApoE in cerebral malaria...
2016: Scientific Reports
Matthew Sievers Alkaitis, Hans C Ackerman
Tetrahydrobiopterin (BH4) is an essential cofactor for both phenylalanine hydroxylase and nitric oxide synthase. Patients with severe malaria have low urinary BH4, elevated plasma phenylalanine, and impaired endothelium-dependent vasodilation, suggesting that BH4 depletion may limit phenylalanine metabolism and nitric oxide synthesis. We infected C57BL/6 mice with Plasmodium berghei ANKA to characterize BH4 availability and to investigate the effects of BH4 supplementation. P. berghei ANKA infection lowered BH4 in plasma, erythrocytes and brain tissue, but raised it in aorta and liver tissue...
September 19, 2016: ACS Infectious Diseases
Aiko Kume, Dang Trinh Minh Anh, Mototada Shichiri, Noriko Ishida, Hiroshi Suzuki
BACKGROUND: Artemisinin-based combination therapy (ACT) has been adopted as national policy for the first-line treatment in large number of malaria-endemic regions. However, artemisinin-resistant parasites have emerged and are spreading, with slow-cleaning parasites being reported in patients treated with ACT. It means that more parasites are exposed to the partner drug alone and the risk of developing resistant parasites against the partner drug is increasing. Therefore, the development of a new method to enhance the effect of artemisinin is required...
2016: Malaria Journal
Gurjeet Singh, Raksha Singh, Anant Dattatraya Urhehar
INTRODUCTION: Malaria is a human disease of which causes high morbidity and mortality. In Plasmodium falciparum malaria, the resistance to antimalarial drugs, especially chloroquine (CQ) is one of the paramount factors contributing to the global increase in morbidity and mortality, due to malaria. Hence, there is a need for detection of chloroquine drug resistance genes i.e., pfcrt-o (Plasmodium falciparum chloroquine resistance transporter-o) and pfmdr-1 (Plasmodium falciparum multidrug resistance-1) of P...
July 2016: Journal of Clinical and Diagnostic Research: JCDR
Marlies E van Wolfswinkel, Liese C Koopmans, Dennis A Hesselink, Ewout J Hoorn, Rob Koelewijn, Jaap J van Hellemond, Perry J J van Genderen
BACKGROUND: Acute kidney injury (AKI) is a frequently encountered complication of imported Plasmodium falciparum infection. Markers of structural kidney damage have been found to detect AKI earlier than serum creatinine-based prediction models but have not yet been evaluated in imported malaria. This pilot study aims to explore the predictive performance of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for AKI in travellers with imported P. falciparum infection...
2016: Malaria Journal
Niteen D Karnik, Anish V Gupta
Acute respiratory distress syndrome (ARDS) is a fulminant clinical disorder of varied etiology, characterized by diffuse lung injury and severe hypoxemia. It is a leading cause of ICU admission and the associated high mortality has sparked a lot of research on etiology, outcome, scoring systems, mortality predictors, biomarkers including inflammatory cytokines and even genomics in ARDS. The previously used AECC (American European Consensus Conference) definition (1994) of ARDS was replaced by the recent Berlin definition (2012) so as to improve its validity and reliability...
November 2015: Journal of the Association of Physicians of India
Rupert Weaver, Linda Reiling, Gaoqian Feng, Damien R Drew, Ivo Mueller, Peter M Siba, Takafumi Tsuboi, Jack S Richards, Freya J I Fowkes, James G Beeson
Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children...
September 8, 2016: Scientific Reports
Parmila Verma, Rajan K Pandey, Priyanka Prajapati, Vijay K Prajapati
MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNA with size ranging from 19 to 24 nucleotides. They endogenously regulate the gene expression at the post transcriptional level either through translation repression or mRNA degradation. MiRNAs have shown the potential to be used as a biomarker for the diagnosis, prognosis, and therapy of infectious diseases. Many miRNAs have shown significantly altered expression during infection. The altered expression of miRNA level in an infected human can be identified by the use of advanced diagnostic tools...
2016: Frontiers in Microbiology
Babacar Mbengue, Mouhamadou Mansour Fall, Maguette Sylla Niang, Birahim Niang, Marie Louise Varela, Antoine Marie Diatta, Moustapha Mbow, Kantome Ndiaye, Rokhaya Ndiaye Diallo, Alioune Dieye, Ronald Perraut
Background. Management of clinical malaria requires the development of reliable diagnostic methods and efficient biomarkers for follow-up of patients. Protection is partly based on IgG responses to parasite antigens exposed at the surface of infected erythrocytes (iRBCs). These IgG responses appeared low during clinical infection, particularly in severe disease. Methods. We analyzed the IgG binding capacity to the surface of live erythrocytes infected by knob positive FCR3 strain. Sera from 69 cerebral malaria (CM) and 72 mild malaria (MM) cases were analyzed by ELISA for IgG responses to five antigens from iRBC and by flow cytometry for IgG binding as expressed in labeling index ratio (LIR)...
2016: BioMed Research International
Uri S Markakpo, Kwabena M Bosompem, Mawuli Dzodzomenyo, Anthony Danso-Appiah, Edward E Essuman, William K Anyan, Mitsuko Suzuki, Judith K Stephens, Isaac Anim-Baidoo, Richard H Asmah, Michael F Ofori, Parnor Madjitey, Jonas B Danquah, Naa Adjeley Frempong, Kofi D Kwofie, Michael Amoa-Bosompem, David Sullivan, Julius N Fobil, Isabella A Quakyi
OBJECTIVE: To generate monoclonal antibodies (MAbs) for developing a rapid malaria diagnostic urine-based assay (RUBDA), using Plasmodium-infected human urinary antigens. METHODS: Plasmodium-infected human urinary (PAgHU) and cultured parasite (CPfAg) antigens were used to generate mouse MAbs. The reactivity and accuracy of the MAbs produced were then evaluated using microplate ELISA, SDS-PAGE, Western blotting assay, microscopy and immunochromatographic tests. RESULTS: Ninety-six MAb clones were generated, of which 68...
October 2016: Tropical Medicine & International Health: TM & IH
Brian T Grimberg, Kerry O Grimberg
Malaria remains widespread throughout the tropics and is a burden to the estimated 3.5 billion people who are exposed annually. The lack of a fast and accurate diagnostic method contributes to preventable malaria deaths and its continued transmission. In many areas diagnosis is made solely based on clinical presentation. Current methods for malaria diagnosis take more than 20 minutes from the time blood is drawn and are frequently inaccurate. The introduction of an accurate malaria diagnostic that can provide a result in less than 1 minute would allow for widespread screening and treatment of endemic populations, and enable regions that have gained a foothold against malaria to prevent its return...
October 2016: Expert Review of Anti-infective Therapy
Keersten M Ricks, Nicholas M Adams, Thomas F Scherr, Frederick R Haselton, David W Wright
BACKGROUND: The characteristic ease of use, rapid time to result, and low cost of malaria rapid diagnostic tests (RDTs) promote their widespread use at the point-of-care for malaria detection and surveillance. However, in many settings, the success of malaria elimination campaigns depends on point-of-care diagnostics with greater sensitivity than currently available RDTs. To address this need, a sample preparation method was developed to deliver more biomarkers onto a malaria RDT by concentrating the biomarker from blood sample volumes that are too large to be directly applied to a lateral flow strip...
2016: Malaria Journal
Nagasundaram N, George Priya Doss C, Chiranjib Chakraborty, Karthick V, Thirumal Kumar D, Balaji V, Siva R, Aiping Lu, Zhang Ge, Hailong Zhu
Artemisinin resistance in Plasmodium falciparum threatens global efforts in the elimination or eradication of malaria. Several studies have associated mutations in the PfATP6 gene in conjunction with artemisinin resistance, but the underlying molecular mechanism of the resistance remains unexplored. Associated mutations act as a biomarker to measure the artemisinin efficacy. In the proposed work, we have analyzed the binding affinity and efficacy between PfATP6 and artemisinin in the presence of L263D, L263E and L263K mutations...
2016: Scientific Reports
Ann M Guggisberg, Sesh A Sundararaman, Miguel Lanaspa, Cinta Moraleda, Raquel González, Alfredo Mayor, Pau Cisteró, David Hutchinson, Peter G Kremsner, Beatrice H Hahn, Quique Bassat, Audrey R Odom
Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days after combination treatment with fosmidomycin-clindamycin. However, 28-day cure rates were low (45.9%), owing to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we used a selective whole-genome amplification method to amplify parasite genomes from blood spot DNA samples...
October 1, 2016: Journal of Infectious Diseases
Samuel Tassi Yunga, Audrey Davidson Thévenon, Rose Gana Fomban Leke, Diane Wallace Taylor
Background.  During pregnancy, the placenta is inaccessible for diagnosis of placental malaria (PM), but soluble tumor necrosis factor-α receptors (sTNFR) are elevated in the plasma of women with PM. Methods.  In this study, sTNFR-1 and sTNFR-2 were quantified in urine of pregnant and nonpregnant Cameroonian women who were positive or negative for malaria by blood-smear microscopy. Results.  We found that levels of both sTNFR in urine were higher in pregnant compared with nonpregnant women, but malaria-positive pregnant women excreted substantially more sTNFR-1 (P = ...
April 2016: Open Forum Infectious Diseases
Thomas J Peto, Rupam Tripura, Sue J Lee, Thomas Althaus, Susanna Dunachie, Chea Nguon, Mehul Dhorda, Cholrawee Promnarate, Jeremy Chalk, Mallika Imwong, Lorenz von Seidlein, Nicholas P Day, Arjen M Dondorp, Nicholas J White, Yoel Lubell
BACKGROUND: Subclinical infections in endemic areas of Southeast Asia sustain malaria transmission. These asymptomatic infections might sustain immunity against clinical malaria and have been considered benign for the host, but if they are associated with chronic low-grade inflammation this could be harmful. We conducted a case-control study to explore the association between subclinical malaria and C-reactive protein (CRP), an established biomarker of inflammation. METHODS: Blood samples from asymptomatic villagers in Pailin, Western Cambodia were tested for malaria by high-volume ultra-sensitive polymerase chain reaction (uPCR) to determine the Plasmodium species...
2016: PloS One
Cheong-Meng Chong, Wenhua Zheng
The pathological increase in the levels of reactive oxygen species (ROS) in the retinal pigment epithelium (RPE), is implicated in the development of age-related macular degeneration (AMD). The discovery of drug candidates to effectively protect RPE cells from oxidative damage is required to resolve the pathological aspects and modify the process of AMD. In this study, a FDA-approved anti-malaria drug, Artemisinin was found to suppress hydrogen peroxide (H2O2)-induced cell death in human RPE cell-D407 cells...
June 20, 2016: Redox Biology
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