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https://www.readbyqxmd.com/read/28333921/bioenergetics-based-modeling-of-plasmodium-falciparum-metabolism-reveals-its-essential-genes-nutritional-requirements-and-thermodynamic-bottlenecks
#1
Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28329368/intermittent-preventive-treatment-with-dihydroartemisinin-piperaquine-for-the-prevention-of-malaria-among-hiv-infected-pregnant-women
#2
Paul Natureeba, Abel Kakuru, Mary Muhindo, Eric Littmann, Teddy Ochieng, John Ategeka, Catherine A Koss, Albert Plenty, Edwin D Charlebois, Tamara D Clark, Bridget Nzarubara, Miriam Nakalembe, Deborah Cohan, Gabrielle Rizzuto, Atis Muehlenbachs, Theodore Ruel, Prasanna Jagannathan, Diane V Havlir, Moses R Kamya, Grant Dorsey
Background.: Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide treated nets (ITNs) remain the main interventions for prevention of malaria in HIV-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these intervention and new ones are needed. Methods.: We conducted a double-blind randomized placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide (IRS) had recently been implemented...
February 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329141/frequent-spread-of-plasmodium-vivax-malaria-maintains-high-genetic-diversity-at-the-myanmar-china-border-without-distance-and-landscape-barriers
#3
Eugenia Lo, Nancy Lam, Elizabeth Hemming-Schroeder, Jennifer Nguyen, Guofa Zhou, Ming-Chieh Lee, Zhaoqing Yang, Liwang Cui, Guiyun Yan
Background.: In Myanmar, civil unrest and the establishment of internally displaced persons (IDP) settlements along the Myanmar-China border have impacted malaria transmission. Methods.: Microsatellite markers were used to examine source-sink dynamics for Plasmodium vivax between IDP and surrounding villages in the border region. Genotypic structure and diversity were compared across the three years following the establishment of IDP in order to infer demographic history...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28329034/use-of-pfhrp2-only-rdts-rapidly-select-for-pfhrp2-negative-parasites-with-serious-implications-for-malaria-case-management-and-control
#4
Michelle L Gatton, Jessica Dunn, Alisha Chaudhry, Sadmir Ciketic, Jane Cunningham, Qin Cheng
Background: Rapid diagnostic tests (RDTs) are an important tool for malaria diagnosis, with most utilising antibodies against histidine-rich protein 2 (PfHRP2). Reports of Plasmodium falciparum lacking this protein are increasing, creating a problem for diagnosis of falciparum malaria in locations without quality microscopy. Methods: An agent-based stochastic simulation model of P.falciparum transmission was used to investigate the selective pressure exerted on parasite populations by use of RDTs for diagnosis of symptomatic cases...
March 8, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28327802/in-vitro-and-in-vivo-antileishmanial-activity-of-artemisia-annua-l-leaf-powder-and-its-potential-usefulness-in-the-treatment-of-uncomplicated-cutaneous-leishmaniasis-in-humans
#5
Luz Estella Mesa, Daniel Vasquez, Pierre Lutgen, Iván Darío Vélez, Adriana María Restrepo, Isabel Ortiz, Sara María Robledo
INTRODUCTION: Cutaneous leishmaniasis (CL) is a tropical disease that affects millions of individuals worldwide. The current drugs for CL may be effective but have serious side effects; hence, alternatives are urgently needed. Although plant-derived materials are used for the treatment of various diseases in 80% of the global population, the validation of these products is essential. Gelatin capsules containing dried Artemisia annua leaf powder were recently developed as a new herbal formulation (totum) for the oral treatment of malaria and other parasitic diseases...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28327793/insights-into-cytochrome-bc1-complex-binding-mode-of-antimalarial-2-hydroxy-1-4-naphthoquinones-through-molecular-modelling
#6
Ana Carolina Rennó Sodero, Bárbara Abrahim-Vieira, Pedro Henrique Monteiro Torres, Pedro Geraldo Pascutti, Célia Rs Garcia, Vitor Francisco Ferreira, David Rodrigues da Rocha, Sabrina Baptista Ferreira, Floriano Paes Silva
BACKGROUND: Malaria persists as a major public health problem. Atovaquone is a drug that inhibits the respiratory chain of Plasmodium falciparum, but with serious limitations like known resistance, low bioavailability and high plasma protein binding. OBJECTIVES: The aim of this work was to perform molecular modelling studies of 2-hydroxy-1,4-naphthoquinones analogues of atovaquone on the Qo site of P. falciparum cytochrome bc1 complex (Pfbc1) to suggest structural modifications that could improve their antimalarial activity...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28327148/drug-resistance-mediating-plasmodium-falciparum-polymorphisms-and-clinical-presentations-of-parasitaemic-children-in-uganda
#7
Stephen Tukwasibwe, Patrick Tumwebaze, Melissa Conrad, Emmanuel Arinaitwe, Moses R Kamya, Grant Dorsey, Samuel L Nsobya, Bryan Greenhouse, Philip J Rosenthal
BACKGROUND: Plasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles...
March 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28327145/diagnostic-challenges-and-case-management-of-the-first-imported-case-of-plasmodium-knowlesi-in-sri-lanka
#8
A Dewanee Ranaweera, Manjula N Danansuriya, Kusumawathie Pahalagedera, W M Kumudunayana T de A W Gunasekera, Priyani Dharmawardena, Keng Wai Mak, Pei-Sze Jeslyn Wong, Mei-Zhi Irene Li, Cheong Huat Tan, Hapuarachchige C Hapuarachchi, Hema D B Herath, Deepika Fernando
BACKGROUND: Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed. CASE PRESENTATION: An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider...
March 21, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28325370/targeting-the-parasite-to-suppress-malaria-transmission
#9
R E Sinden
This article attempts to draw together current knowledge on the biology of Plasmodium and experience gained from past control campaigns to interpret and guide current efforts to discover and develop exciting new strategies targeting the parasite with the objective of interrupting transmission. Particular note is made of the advantages of targeting often unappreciated small, yet vital, bottleneck populations to enhance both the impact and the useful lifetime of hard-won interventions. A case is made for the standardization of methods to measure transmission blockade to permit the rational comparison of how diverse interventions (drugs, vaccines, insecticides, Genetically Modified technologies) targeting disparate aspects of parasite biology may impact upon the commonly used parameter of parasite prevalence in the human population...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28323050/antiplasmodial-activity-of-mezoneuron-benthamianum-leaves-and-identification-of-its-active-constituents
#10
Olivia Jansen, Alembert T Tchinda, Jean Loua, Virginie Esters, Ewa Cieckiewicz, Allison Ledoux, Paul D Toukam, Luc Angenot, Monique Tits, Aliou M Balde, Michel Frédérich
ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of the leaves of M. benthamianum Baill. are used by traditional healers in Guinea to treat malaria and this use was validated by a preliminary clinical assay. AIM OF THE STUDY: To evaluate the in vitro antiplasmodial activity and to identify active compounds from extracts of M. benthamianum leaves. MATERIAL AND METHODS: Antiplasmodial activity of extracts, fractions and pure compounds was evaluated in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity...
March 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28322872/plasmodium-hsp40-and-human-hsp70-a-potential-cochaperone-chaperone-complex
#11
Payal Jha, Shyamasree Laskar, Swati Dubey, Mrinal K Bhattacharyya, Sunanda Bhattacharyya
Out of the total forty four members of Plasmodium falciparum Hsp40 protein family, nineteen of them possess a PEXEL motif, and are predicted to be exported into the cytosol of an infected RBC. It is speculated that the human Hsp70 (hHsp70), which resides into the cytosol of the host erythrocyte, along with the exported PfHsp40s assists in the folding of parasitic proteins, thus playing a crucial role in the establishment of virulence. However, till date no experimental evidence supports this hypothesis. Our work establishes that the PEXEL motifs containing Type II PfDNAJ proteins specifically interact with hHsp70 (HSPA1A)...
March 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28322705/three-divergent-subpopulations-of-the-malaria-parasite-plasmodium-knowlesi
#12
Paul C S Divis, Lee C Lin, Jeffrine J Rovie-Ryan, Khamisah A Kadir, Fread Anderios, Shamilah Hisam, Reuben S K Sharma, Balbir Singh, David J Conway
Multilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P...
April 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28321277/clinical-outcomes-among-febrile-children-aged-2-to-59-months-with-negative-malaria-rapid-diagnostic-test-results-in-mchinji-district-malawi
#13
Dyson Mwandama, Chawanangwa Mwale, Andrew Bauleni, Themba Phiri, Joseph Chisaka, Humphreys Nsona, Don P Mathanga
BACKGROUND: Malawi malaria treatment guidelines recommend a definitive diagnosis, using a malaria rapid diagnostic test (mRDT), for all patients with fever or history of fever. Improving the management and outcomes of febrile children with negative mRDT results should be a priority. METHODS: Through a prospective cohort study designed to investigate clinical outcomes of children treated at the community level, we followed, for 7 days, children aged 2 to 59 months, who had negative mRDT results and were treated with antipyretic medication...
December 2016: Malawi Medical Journal: the Journal of Medical Association of Malawi
https://www.readbyqxmd.com/read/28320838/early-immune-regulatory-changes-in-a-primary-controlled-human-plasmodium-vivax-infection-cd1c-mdc-maturation-arrest-induction-of-the-kynurenine-pathway-and-regulatory-t-cell-activation
#14
Tonia Woodberry, Jessica R Loughland, Gabriela Minigo, Julie G Burel, Fiona H Amante, Kim A Piera, Yvette McNeil, Tsin W Yeo, Michael F Good, Denise L Doolan, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to this species are not clear. Dendritic cells (DC) are essential for immune cell priming, but also perform immune-regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterised plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4(+)CD25(+)CD127(lo) Treg activation and IDO activity...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28320828/malaria-epigenetics
#15
Alfred Cortés, Kirk W Deitsch
Organisms with identical genome sequences can show substantial differences in their phenotypes owing to epigenetic changes that result in different use of their genes. Epigenetic regulation of gene expression plays a key role in the control of several fundamental processes in the biology of malaria parasites, including antigenic variation and sexual differentiation. Some of the histone modifications and chromatin-modifying enzymes that control the epigenetic states of malaria genes have been characterized, and their functions are beginning to be unraveled...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28320404/tryptophan-rich-domains-of-plasmodium-falciparum-surfin4-2-and-plasmodium-vivax-pvstp2-interact-with-membrane-skeleton-of-red-blood-cell
#16
Xiaotong Zhu, Yang He, Yifan Liang, Osamu Kaneko, Liwang Cui, Yaming Cao
BACKGROUND: Plasmodium falciparum dramatically alters the morphology and properties of the infected red blood cells (iRBCs). A large group of exported proteins participate in these parasite-host interactions occurring at the iRBC membrane skeleton. SURFIN4.2 is one of iRBC surface protein that belongs to surface-associated interspersed protein (SURFIN) family. Although the intracellular tryptophan-rich domain (WRD) was proposed to be important for the translocation of SURFINs from Maurer's clefts to iRBC surface, the molecular basis of this observation has yet to be defined...
March 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28320390/false-negative-malaria-rapid-diagnostic-tests-in-rwanda-impact-of-plasmodium-falciparum-isolates-lacking-hrp2-and-declining-malaria-transmission
#17
Christina T Kozycki, Noella Umulisa, Stephen Rulisa, Emil I Mwikarago, Jean Pierre Musabyimana, Jean Pierre Habimana, Corine Karema, Donald J Krogstad
BACKGROUND: Rapid diagnostic tests (RDTs) for histidine rich protein 2 (HRP2) are often used to determine whether persons with fever should be treated with anti-malarials. However, Plasmodium falciparum parasites with a deletion of the hrp2 gene yield false-negative RDTs and there are concerns the sensitivity of HRP2-based RDTs may fall when the intensity of transmission decreases. METHODS: This observational study enrolled 9226 patients at three health centres in Rwanda from April 2014 to April 2015...
March 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28320389/age-and-geographic-patterns-of-plasmodium-falciparum-malaria-infection-in-a-representative-sample-of-children-living-in-burkitt-lymphoma-endemic-areas-of-northern-uganda
#18
Marlena Maziarz, Tobias Kinyera, Isaac Otim, Paul Kagwa, Hadijah Nabalende, Ismail D Legason, Martin D Ogwang, Samuel Kirimunda, Benjamin Emmanuel, Steven J Reynolds, Patrick Kerchan, Moses M Joloba, Andrew W Bergen, Kishor Bhatia, Ambrose O Talisuna, Robert J Biggar, James J Goedert, Ruth M Pfeiffer, Sam M Mbulaiteye
BACKGROUND: Falciparum malaria is an important risk factor for African Burkitt lymphoma (BL), but few studies have evaluated malaria patterns in healthy BL-age children in populations where both diseases are endemic. To obtain accurate current data, patterns of asymptomatic malaria were investigated in northern Uganda, where BL is endemic. METHODS: Between 2011 and 2015, 1150 apparently healthy children under 15 years old were sampled from 100 villages in northern Uganda using a stratified, multi-stage, cluster survey design...
March 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28320254/antimalarial-and-antiplasmodial-activity-of-husk-extract-and-fractions-of-zea-mays
#19
Jude E Okokon, Bassey S Antia, Dinesh Mohanakrishnan, Dinkar Sahal
CONTEXT: Zea mays L. (Poacae) husk decoctions are traditionally used in the treatment of malaria by various tribes in Nigeria. OBJECTIVE: To assess the antimalarial and antiplasmodial potentials of the husk extract and fractions on malaria parasites using in vivo and in vitro models. MATERIALS AND METHODS: The ethanol husk extract and fractions (187-748 mg/kg, p.o.) of Zea mays were investigated for antimalarial activity against Plasmodium berghei using rodent (mice) malaria models and in vitro activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using the SRBR green assay method...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28319831/structure-based-prediction-of-host-pathogen-protein-interactions
#20
REVIEW
Rachelle Mariano, Stefan Wuchty
The discovery, validation, and characterization of protein-based interactions from different species are crucial for translational research regarding a variety of pathogens, ranging from the malaria parasite Plasmodium falciparum to HIV-1. Here, we review recent advances in the prediction of host-pathogen protein interfaces using structural information. In particular, we observe that current methods chiefly perform machine learning on sequence and domain information to produce large sets of candidate interactions that are further assessed and pruned to generate final, highly probable sets...
March 16, 2017: Current Opinion in Structural Biology
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