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https://www.readbyqxmd.com/read/28445677/overexpression-of-the-cytokine-baff-and-autoimmunity-risk
#1
Maristella Steri, Valeria Orrù, M Laura Idda, Maristella Pitzalis, Mauro Pala, Ilenia Zara, Carlo Sidore, Valeria Faà, Matteo Floris, Manila Deiana, Isadora Asunis, Eleonora Porcu, Antonella Mulas, Maria G Piras, Monia Lobina, Sandra Lai, Mara Marongiu, Valentina Serra, Michele Marongiu, Gabriella Sole, Fabio Busonero, Andrea Maschio, Roberto Cusano, Gianmauro Cuccuru, Francesca Deidda, Fausto Poddie, Gabriele Farina, Mariano Dei, Francesca Virdis, Stefania Olla, Maria A Satta, Mario Pani, Alessandro Delitala, Eleonora Cocco, Jessica Frau, Giancarlo Coghe, Lorena Lorefice, Giuseppe Fenu, Paola Ferrigno, Maria Ban, Nadia Barizzone, Maurizio Leone, Franca R Guerini, Matteo Piga, Davide Firinu, Ingrid Kockum, Izaura Lima Bomfim, Tomas Olsson, Lars Alfredsson, Ana Suarez, Patricia E Carreira, Maria J Castillo-Palma, Joseph H Marcus, Mauro Congia, Andrea Angius, Maurizio Melis, Antonio Gonzalez, Marta E Alarcón Riquelme, Berta M da Silva, Maurizio Marchini, Maria G Danieli, Stefano Del Giacco, Alessandro Mathieu, Antonello Pani, Stephen B Montgomery, Giulio Rosati, Jan Hillert, Stephen Sawcer, Sandra D'Alfonso, John A Todd, John Novembre, Gonçalo R Abecasis, Michael B Whalen, Maria G Marrosu, Alessandra Meloni, Serena Sanna, Myriam Gorospe, David Schlessinger, Edoardo Fiorillo, Magdalena Zoledziewska, Francesco Cucca
Background Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Methods Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE)...
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28445672/a-baffling-association-between-malaria-resistance-and-the-risk-of-multiple-sclerosis
#2
EDITORIAL
Thomas Korn, Mohamed Oukka
No abstract text is available yet for this article.
April 27, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28445503/therapeutic-efficacy-of-artemether-lumefantrine-against-uncomplicated-plasmodium-falciparum-malaria-in-a-high-transmission-area-in-northwest-ethiopia
#3
Michael Teklemariam, Ashenafi Assefa, Moges Kassa, Hussien Mohammed, Hassen Mamo
Malaria, particularly due to Plasmodium falciparum, remains a major public health threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line antimalarial drug against uncomplicated P. falciparum malaria in the country since 2004. Regular monitoring of antimalarial drugs is recommended by the World Health Organization (WHO) to help early detection of drug resistant strains of the parasite and contain their rapid spread. The objective of this study was to assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia...
2017: PloS One
https://www.readbyqxmd.com/read/28438929/molecular-profile-of-malaria-drug-resistance-markers-of-plasmodium-falciparum-in-suriname
#4
Stella M Chenet, Sheila Akinyi Okoth, Julia Kelley, Naomi Lucchi, Curtis S Huber, Stephen Vreden, Alexandre Macedo de Oliveira, John W Barnwell, Venkatachalam Udhayakumar, Malti R Adhin
In Suriname, an artesunate monotherapy therapeutic efficacy trial was recently conducted to evaluate partial artemisinin resistance emerging in Plasmodium falciparum We genotyped the PfK13 propeller domain of P. falciparum in forty samples as well as other mutations proposed to be associated with artemisinin resistant mutants. We did not find any mutations previously associated with artemisinin resistance in Southeast Asia but we found fixed resistance mutations for chloroquine and sulfadoxine-pyrimethamine...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438194/malaria-profiles-and-challenges-in-artemisinin-resistance-containment-in-myanmar
#5
Thet Wai Nwe, Tin Oo, Khin Thet Wai, Shuisen Zhou, Johan van Griensven, Palanivel Chinnakali, Safieh Shah, Aung Thi
BACKGROUND: This study examined evolving malaria profiles from January, 2010 to December, 2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in Myanmar. METHODS: Using National Malaria Control Programme (NMCP) data, a cross-sectional descriptive study of 52 townships in artemisinin-resistant containment areas in Myanmar was conducted. Annual program data were analysed, and trends over time are graphically presented...
April 25, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28438145/insights-into-the-availability-and-distribution-of-oral-artemisinin-monotherapy-in-myanmar-evidence-from-a-nationally-representative-outlet-survey
#6
Si Thu Thein, Hnin Su Su Khin, Aung Thi
BACKGROUND: The containment of artemisinin resistance in Myanmar, historically an important probable origin and route of anti-malarial resistance to the India sub-continent and beyond, is crucial to global malaria control and elimination. This paper describes what is currently known about the sale and distribution of oral artemisinin monotherapy (AMT) across Myanmar, where this medicine is commonly found. METHODS: A nationally representative 2015 outlet survey was conducted in the private sector, and among community health workers across four geographical domains...
April 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28437449/insecticide-resistance-status-of-malaria-vectors-in-lao-pdr
#7
Sébastien Marcombe, Julie Bobichon, Boutsady Somphong, Nothasin Phommavan, Santi Maithaviphet, Simone Nambanya, Vincent Corbel, Paul T Brey
Knowledge on insecticide resistance in Anopheles species is a basic requirement to guide malaria vector control programs. In Lao PDR, vector control relies on insecticide residual spraying (IRS) and impregnated bed-nets (ITNs) with the use of pyrethroids. Here, the susceptibility of Anopheles species, including several malaria vectors (An. maculatus and An. minimus), to various insecticides was investigated in ten provinces of Lao PDR through a north-south transect. Bioassays were performed on field caught female mosquitoes using the standard WHO susceptibility tests with DDT (4%), deltamethrin (0...
2017: PloS One
https://www.readbyqxmd.com/read/28435886/discovery-of-a-novel-antifungal-agent-in-the-pathogen-box
#8
François L Mayer, James W Kronstad
Human fungal pathogens cause over 2 million infections per year and are major drivers of morbidity and mortality. Cryptococcus neoformans and Candida albicans are two of the most common fungal pathogens of humans, together accounting for a staggering 1.4 million infections annually, with very high mortality rates. Patients with dysfunctional immune systems, such as individuals with HIV/AIDS, are particularly susceptible to fungal infections. Unfortunately, relatively few antifungal drugs are currently available and fungi frequently develop resistance, further complicating treatment approaches...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435533/discovery-of-antimalarial-azetidine-2-carbonitriles-that-inhibit-p-falciparum-dihydroorotate-dehydrogenase
#9
Micah Maetani, Nobutaka Kato, Valquiria A P Jabor, Felipe A Calil, Maria Cristina Nonato, Christina A Scherer, Stuart L Schreiber
Dihydroorotate dehydrogenase (DHODH) is an enzyme necessary for pyrimidine biosynthesis in protozoan parasites of the genus Plasmodium, the causative agents of malaria. We recently reported the identification of novel compounds derived from diversity-oriented synthesis with activity in multiple stages of the malaria parasite life cycle. Here, we report the optimization of a potent series of antimalarial inhibitors consisting of azetidine-2-carbonitriles, which we had previously shown to target P. falciparum DHODH in a biochemical assay...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28428243/genome-wide-transcription-and-functional-analyses-reveal-heterogeneous-molecular-mechanisms-driving-pyrethroids-resistance-in-the-major-malaria-vector-anopheles-funestus-across-africa
#10
Jacob M Riveron, Sulaiman S Ibrahim, Charles Mulamba, Rousseau Djouaka, Helen Irving, Murielle J Wondji, Intan H Ishak, Charles S Wondji
Pyrethroid resistance in malaria vector, An. Funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions including long lasting insecticidal Nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from Southern (Malawi), East (Uganda) and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions...
April 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28427450/presence-of-susceptible-wild-strains-of-anopheles-gambiae-in-a-large-industrial-palm-farm-located-in-aboisso-south-eastern-of-c%C3%A3-te-d-ivoire
#11
Cécile M A Sadia-Kacou, Ludovic P Ahoua Alou, Ako V C Edi, Celine M Yobo, Maurice A Adja, Allassane F Ouattara, David Malone, Alphonsine A Koffi, Yao Tano, Benjamin G Koudou
BACKGROUND: The effectiveness of malaria control programmes through implementation of vector control activities is challenged by the emergence of insecticide resistance. In the South-Eastern region of Côte d'Ivoire, where palm oil plantations remain the predominant agricultural crop, the susceptibility of wild Anopheles gambiae sensu lato species is still unknown and thus requires a particular attention. The current study was carried out to address the gap by in-depth characterization of susceptibility level of An...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28427447/benchmarking-insecticide-resistance-intensity-bioassays-for-anopheles-malaria-vector-species-against-resistance-phenotypes-of-known-epidemiological-significance
#12
Nelius Venter, Shȕné V Oliver, Mbanga Muleba, Craig Davies, Richard H Hunt, Lizette L Koekemoer, Maureen Coetzee, Basil D Brooke
BACKGROUND: Insecticide use via indoor residual spraying (IRS) or treated nets is the primary method for controlling malaria vector populations. The incidence of insecticide resistance in vector populations is burgeoning globally making resistance management key to the design of effective malaria control and elimination strategies. Vector populations can be assessed for insecticide resistance using a binary (susceptible or resistant) classification based on the use of the standard WHO insecticide susceptibility assay for adult anopheline mosquitoes...
April 20, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28427418/immunity-as-a-predictor-of-anti-malarial-treatment-failure-a-systematic-review
#13
Katherine O'Flaherty, Julia Maguire, Julie A Simpson, Freya J I Fowkes
BACKGROUND: Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure. METHODS: Four databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28427415/insecticide-resistance-patterns-in-uganda-and-the-effect-of-indoor-residual-spraying-with-bendiocarb-on-kdr-l1014s-frequencies-in-anopheles-gambiae-s-s
#14
Tarekegn A Abeku, Michelle E H Helinski, Matthew J Kirby, James Ssekitooleko, Chris Bass, Irene Kyomuhangi, Michael Okia, Godfrey Magumba, Sylvia R Meek
BACKGROUND: Resistance of malaria vectors to pyrethroid insecticides has been attributed to selection pressure from long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS), and the use of chemicals in agriculture. The use of different classes of insecticides in combination or by rotation has been recommended for resistance management. The aim of this study was to understand the role of IRS with a carbamate insecticide in management of pyrethroid resistance. METHODS: Anopheles mosquitoes were collected from multiple sites in nine districts of Uganda (up to five sites per district)...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28427409/efficacies-of-dha-ppq-and-as-sp-in-patients-with-uncomplicated-plasmodium-falciparum-malaria-in-an-area-of-an-unstable-seasonal-transmission-in-sudan
#15
Abdelrahim O Mohamed, Muzamil M Abdel Hamid, Omer S Mohamed, Nuha S Elkando, Abdelmaroof Suliman, Mariam A Adam, Fahad Awad Ali Elnour, Elfatih M Malik
BACKGROUND: Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable...
April 20, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28420446/immune-resistance-and-tolerance-strategies-in-malaria-vector-and-non-vector-mosquitoes
#16
Tibebu Habtewold, Zoe Groom, George K Christophides
BACKGROUND: The Anopheles gambiae complex consists of species that vary greatly in their capacity to transmit malaria. The mosquito immune system has been identified as a key factor that can influence whether Plasmodium infection establishes within the mosquito vector. This study was designed to investigate the immune responses of An. coluzzii, An. arabiensis and An. quadriannulatus mosquitoes. The first two mosquito species are major vectors of malaria in sub-Saharan Africa, while the third is thought to be a non-vector...
April 18, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28420422/high-resolution-melting-a-useful-field-deployable-method-to-measure-dhfr-and-dhps-drug-resistance-in-both-highly-and-lowly-endemic-plasmodium-populations
#17
Yaye Dié Ndiaye, Cyrille K Diédhiou, Amy K Bei, Baba Dieye, Aminata Mbaye, Nasserdine Papa Mze, Rachel F Daniels, Ibrahima M Ndiaye, Awa B Déme, Amy Gaye, Mouhamad Sy, Tolla Ndiaye, Aida S Badiane, Mouhamadou Ndiaye, Zul Premji, Dyann F Wirth, Souleymane Mboup, Donald Krogstad, Sarah K Volkman, Ambroise D Ahouidi, Daouda Ndiaye
BACKGROUND: Emergence and spread of drug resistance to every anti-malarial used to date, creates an urgent need for development of sensitive, specific and field-deployable molecular tools for detection and surveillance of validated drug resistance markers. Such tools would allow early detection of mutations in resistance loci. The aim of this study was to compare common population signatures and drug resistance marker frequencies between two populations with different levels of malaria endemicity and history of anti-malarial drug use: Tanzania and Sénégal...
April 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28420403/molecular-surveillance-of-plasmodium-falciparum-drug-resistance-in-the-republic-of-congo-four-and-nine-years-after-the-introduction-of-artemisinin-based-combination-therapy
#18
Felix Koukouikila-Koussounda, Sankarganesh Jeyaraj, Christian N Nguetse, Charles Nchotebah Nkonganyi, Kossiwa Clarisse Kokou, Mandingha K Etoka-Beka, Francine Ntoumi, Thirumalaisamy P Velavan
BACKGROUND: Resistance to anti-malarial drugs hinders efforts on malaria elimination and eradication. Following the global spread of chloroquine-resistant parasites, the Republic of Congo adopted artemisinin-based combination therapy (ACT) in 2006 as a first-line treatment for uncomplicated malaria. To assess the impacts after implementation of ACT, a molecular surveillance for anti-malarial drug resistance was conducted in Congo 4 and 9 years after the introduction of ACT. METHODS: Blood samples of 431 febrile children aged 1-10 years were utilized from two previous studies conducted in 2010 (N = 311) and 2015 (N = 120)...
April 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28420389/assessment-of-copy-number-variation-in-genes-related-to-drug-resistance-in-plasmodium-vivax-and-plasmodium-falciparum-isolates-from-the-brazilian-amazon-and-a-systematic-review-of-the-literature
#19
Gabriel Luíz Costa, Lara Cotta Amaral, Cor Jesus Fernandes Fontes, Luzia Helena Carvalho, Cristiana Ferreira Alves de Brito, Taís Nóbrega de Sousa
BACKGROUND: Parasite resistance to anti-malarials represents a great obstacle for malaria elimination. The majority of studies have investigated the association between single-nucleotide polymorphisms (SNPs) and drug resistance; however, it is becoming clear that the copy number variation (CNV) is also associated with this parasite phenotype. To provide a baseline for molecular surveillance of anti-malarial drug resistance in the Brazilian Amazon, the present study characterized the genetic profile of both markers in the most common genes associated with drug resistance in Plasmodium falciparum and Plasmodium vivax isolates...
April 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28419927/synthesis-and-evaluation-of-anti-plasmodial-and-cytotoxic-activities-of-epoxyazadiradione-derivatives
#20
P Ashok Yadav, Ch Pavan Kumar, Bandi Siva, K Suresh Babu, Aparna Devi Allanki, Puran Singh Sijwali, Nishant Jain, A Veerabhadra Rao
Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti-plasmodial activity against CQ-resistant and CQ-sensitive strains of the most virulent human malaria parasite P. falciparum. A series of analogues were synthesized by modification of the key structural moieties of this high yield natural product. Out of the library of all compounds tested, compounds 3c and 3g have showed modest anti-plasmodial activity against CQ-sensitive (IC50 2.8 ± 0.29 μM and 1.5 ± 0.01 μM) and CQ-resistant strains (IC50 1...
April 13, 2017: European Journal of Medicinal Chemistry
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