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https://www.readbyqxmd.com/read/29579263/the-etiology-of-placental-plasmodium-falciparum-malaria-in-african-women
#1
Michael F Ofori, Helena Lamptey, Emmanuel K Dickson, Eric Kyei-Baafour, Lars Hviid
Plasmodium falciparum parasites causing placental malaria (PM) express the VAR2CSA type of the clonally variant antigen family PfEMP1. This enables evasion of pre-existing immunity and results in placental accumulation of infected erythrocytes (IEs). We present data on seasonal variation in levels of VAR2CSA-specific IgG and IgG specific for a PM-unrelated PfEMP1 protein among Ghanaian women at first antenatal visit. Our results indicate that PM does not require recent exposure to infected mosquitoes, in contrast to malaria in general...
March 22, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29554358/an-upstream-open-reading-frame-uorf-signals-for-cellular-localization-of-the-virulence-factor-implicated-in-pregnancy-associated-malaria
#2
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
https://www.readbyqxmd.com/read/29523137/antibody-levels-to-recombinant-var2csa-domains-vary-with-plasmodium-falciparum-parasitaemia-gestational-age-and-gravidity-but-do-not-predict-pregnancy-outcomes
#3
Michal Fried, Jonathan D Kurtis, Bruce Swihart, Robert Morrison, Sunthorn Pond-Tor, Amadou Barry, Youssoufa Sidibe, Sekouba Keita, Almahamoudou Mahamar, Naissem Andemel, Oumar Attaher, Adama B Dembele, Kadidia B Cisse, Bacary S Diarra, Moussa B Kanoute, David L Narum, Alassane Dicko, Patrick E Duffy
BACKGROUND: Maternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodies to the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibody levels and thereby confound analyses of immune protection, gravidity-dependent changes in antibody levels during and after infection, and the effect of VAR2CSA antibodies on pregnancy outcomes were evaluated...
March 9, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29396010/burden-pathology-and-costs-of-malaria-in-pregnancy-new-developments-for-an-old-problem
#4
REVIEW
Stephen J Rogerson, Meghna Desai, Alfredo Mayor, Elisa Sicuri, Steve M Taylor, Anna M van Eijk
Over the past 10 years, knowledge of the burden, economic costs, and consequences of malaria in pregnancy has improved, and the prevalence of malaria caused by Plasmodium falciparum has declined substantially in some geographical areas. In particular, studies outside of Africa have increased the evidence base of Plasmodium vivax in pregnancy. Rapid diagnostic tests have been poor at detecting malaria in pregnant women, while PCR has shown a high prevalence of low density infection, the clinical importance of which is unknown...
January 30, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29378797/clinical-outcomes-of-submicroscopic-infections-and-correlates-of-protection-of-var2csa-antibodies-in-a-longitudinal-study-of-pregnant-women-in-colombia
#5
Kenneth Gavina, Sedami Gnidehou, Eliana Arango, Chloe Hamel-Martineau, Catherine Mitran, Olga Agudelo, Carolina Lopez, Aisha Karidio, Shanna Banman, Jaime Carmona-Fonseca, Ali Salanti, Nicaise Ndam, Michael Hawkes, Amanda Maestre, Stephanie K Yanow
BACKGROUND: Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium (P.) falciparum and P. vivax co-circulate. METHODS: A cohort of 187 pregnant women living in Puerto Libertador in Northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, RT-qPCR, and placental histopathology...
January 29, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29378634/evaluating-antibody-functional-activity-and-strain-specificity-of-vaccine-candidates-for-malaria-in-pregnancy-using-in-vitro-phagocytosis-assays
#6
Mirja Hommel, Jo-Anne Chan, Alexandra J Umbers, Christine Langer, Stephen J Rogerson, Joseph D Smith, James G Beeson
BACKGROUND: Malaria in pregnancy is a major cause of poor maternal and infant health, and is associated with the sequestration of P. falciparum-infected erythrocytes (IE) in the placenta. The leading vaccine candidate for pregnancy malaria, VAR2CSA, has been shown to induce antibodies that inhibit IE adhesion to the placental receptor chondroitin sulfate A (CSA), potentially preventing placental infection. However, the ability of vaccination-induced antibodies to promote opsonic phagocytosis is not well defined, but likely to be an important component of protective immunity...
January 29, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29361940/plasmodium-falciparum-genetic-variation-of-var2csa-in-the-democratic-republic-of-the-congo
#7
Robert Verity, Nicholas J Hathaway, Andreea Waltmann, Stephanie M Doctor, Oliver J Watson, Jaymin C Patel, Kashamuka Mwandagalirwa, Antoinette K Tshefu, Jeffrey A Bailey, Azra C Ghani, Jonathan J Juliano, Steven R Meshnick
BACKGROUND: The Democratic Republic of the Congo (DRC) bears a high burden of malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a crucial role in pregnancy-associated malaria (PAM), and hence quantifying diversity at the var2csa locus in the DRC is important in understanding the basic epidemiology of PAM, and in developing a robust vaccine against PAM. METHODS: Samples were taken from the 2013-14 Demographic and Health Survey conducted in the DRC, focusing on children under 5 years of age...
January 24, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29342401/matched-placental-and-circulating-plasmodium-falciparum-parasites-are-genetically-homologous-at-the-var2csa-id1-dbl2x-locus-by-deep-sequencing
#8
Andreea Waltmann, Jaymin C Patel, Kyaw L Thwai, Nicholas J Hathaway, Christian M Parobek, Achille Massougbodji, Nadine Fievet, Jeffery A Bailey, Philippe Deloron, Jonathan J Juliano, Nicaise Tuikue Ndam, Steven R Meshnick
In pregnancy-associated malaria, infected erythrocytes accumulate in the placenta. It is unclear if in polyclonal infections this results in distinct peripheral and placental parasite populations. We used long amplicon deep sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral and placental samples collected at delivery from a high transmission area to determine genetic homology. Despite substantial sequence variation and detecting 23 haplotypes, the matched pairs mostly contained the same genetic variants, with 11 pairs sharing 100% of their variants, whereas others showed some heterogeneity...
January 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29150483/correction-for-de-moraes-et-al-murine-model-for-preclinical-studies-of-var2csa-mediated-pathology-associated-with-malaria-in-pregnancy
#9
Luciana V de Moraes, Sebastien Dechavanne, Patrícia M Sousa, André Barateiro, Sónia F Cunha, Sofia Nunes-Silva, Flávia A Lima, Oscar Murillo, Claudio R F Marinho, Stephane Gangnard, Anand Srivastava, Joanna A Braks, Chris J Janse, Benoit Gamain, Blandine Franke-Fayard, Carlos Penha-Gonçalves
No abstract text is available yet for this article.
December 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29121643/pfi1785w-a-highly-conserved-protein-associated-with-pregnancy-associated-malaria
#10
Claire Kamaliddin, Virginie Salnot, Marjorie Leduc, Sem Ezinmegnon, Cédric Broussard, Nadine Fievet, Philippe Deloron, François Guillonneau, Gwladys I Bertin
Pregnancy-associated malaria (PAM) is one of the severe forms of Plasmodium falciparum infection. The main antigen VAR2CSA is the target of vaccine development. However, the large size of VAR2CSA protein and its high degree of variability limit to the efficiency of the vaccination. Using quantitative mass spectrometry method, we detected and quantified proteotypic peptides from 5 predicted PAM associated proteins. Our results confirmed that PFI1785w is over-expressed in PAM samples. Then, we investigated PFI1785w variability among a set of parasite samples from various endemic areas...
2017: PloS One
https://www.readbyqxmd.com/read/29089635/a-versatile-high-through-put-bead-based-phagocytosis-assay-for-plasmodium-falciparum
#11
Yukie M Lloyd, Elise P Ngati, Ali Salanti, Rose G F Leke, Diane W Taylor
Antibody-mediated phagocytosis is an important immune effector mechanism against Plasmodium falciparum-infected erythrocytes (IE); however, current phagocytosis assays use IE collected from infected individuals or from in vitro cultures of P. falciparum, making them prone to high variation. A simple, high-throughput flow cytometric assay was developed that uses THP-1 cells and fluorescent beads covalently-coupled with the malarial antigen VAR2CSA. The assay is highly repeatable, provides both the overall percent phagocytosis and semi-quantitates the number of antigen-coupled beads internalized...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29062332/a-var2csa-csp-conjugate-capable-of-inducing-dual-specificity-antibody-responses
#12
Matondo Sungwa, Thrane Susan, Janitzek Christoph Mikkel, Kavishe Reginald Adolph, Mwakalinga Steven Boniface, Theander Thor Grundtvig, Salanti Ali, Nielsen Morten Agertoug, Sander Adam Frederik
BACKGROUND: Vaccine antigens targeting specific P. falciparum parasite stages are under pre-clinical and clinical development. It seems plausible that vaccine with multiple specificities will offer higher protection. With this hypothesis, we exploited the Spy-Tag/SpyCatcher conjugation system to make a, post expression, dual antigen conjugate vaccine, comprising two clinically tested antigen candidates (CSP and VAR2CSA). METHODS: The DBL1x-DBL2x-ID2a region of VAR2CSA was genetically fused with SpyTag at N-terminus...
June 2017: African Health Sciences
https://www.readbyqxmd.com/read/29038124/plasmodium-falciparum-pfemp1-modulates-monocyte-macrophage-transcription-factor-activation-and-cytokine-and-chemokine-responses
#13
Natália Guimarães Sampaio, Emily Marie Eriksson, Louis Schofield
Immunity to Plasmodium falciparum malaria is slow to develop, and it is often asserted that malaria suppresses host immunity, although this is poorly understood and the molecular basis for such activity remains unknown. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a virulence factor that plays a key role in parasite-host interactions. We investigated the immunosuppressive effect of PfEMP1 on monocytes/macrophages, which are central to the antiparasitic innate response. RAW macrophages and human primary monocytes were stimulated with wild-type 3D7 or CS2 parasites or transgenic PfEMP1-null parasites...
January 2018: Infection and Immunity
https://www.readbyqxmd.com/read/28962616/statistical-prediction-of-immunity-to-placental-malaria-based-on-multi-assay-antibody-data-for-malarial-antigens
#14
Chathura Siriwardhana, Rui Fang, Ali Salanti, Rose G F Leke, Naveen Bobbili, Diane Wallace Taylor, John J Chen
BACKGROUND: Plasmodium falciparum infections are especially severe in pregnant women because infected erythrocytes (IE) express VAR2CSA, a ligand that binds to placental trophoblasts, causing IE to accumulate in the placenta. Resulting inflammation and pathology increases a woman's risk of anemia, miscarriage, premature deliveries, and having low birthweight (LBW) babies. Antibodies (Ab) to VAR2CSA reduce placental parasitaemia and improve pregnancy outcomes. Currently, no single assay is able to predict if a woman has adequate immunity to prevent placental malaria (PM)...
September 29, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28893687/genetic-analysis-of-id1-dbl2x-predicts-its-validity-as-a-vaccine-candidate-in-colombia-and-supports-at-least-two-independently-introduced-plasmodium-falciparum-populations-in-the-region
#15
J Rajwani, C M Klinger, E Arango, M I Arroyo, A Sabbagh, A Maestre, J B Dacks, S Gnidehou, S K Yanow
Pregnancy-associated malaria (PAM) poses a threat to both the mother and fetus, increasing the risk of severe maternal anemia, fetal growth restriction and low birth weight infants. Two vaccines are currently in development to protect women from Plasmodium falciparum in pregnancy. Both vaccine constructs target the ID1-DBL2X domain of VAR2CSA, a protein expressed on the surface of infected erythrocytes (IEs) that mediates parasite sequestration in the placenta. Although development of an effective vaccine may be hampered by ID1-DBL2X polymorphisms expressed by field isolates, a recent study showed that genetic variation of this domain in South American parasite populations is much lower than in other geographical locations...
September 8, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28818101/a-new-method-for-sequencing-the-hypervariable-plasmodium-falciparum-gene-var2csa-from-clinical-samples
#16
Antoine Dara, Mark A Travassos, Matthew Adams, Sarah Schaffer DeRoo, Elliott F Drábek, Sonia Agrawal, Miriam K Laufer, Christopher V Plowe, Joana C Silva
BACKGROUND: VAR2CSA, a member of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, mediates the binding of P. falciparum-infected erythrocytes to chondroitin sulfate A, a surface-associated molecule expressed in placental cells, and plays a central role in the pathogenesis of placental malaria. VAR2CSA is a target of naturally acquired immunity and, as such, is a leading vaccine candidate against placental malaria. This protein is very polymorphic and technically challenging to sequence...
August 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28801627/increased-risk-of-low-birth-weight-in-women-with-placental-malaria-associated-with-p-falciparum-var2csa-clade
#17
Jaymin C Patel, Nicholas J Hathaway, Christian M Parobek, Kyaw L Thwai, Mwayiwawo Madanitsa, Carole Khairallah, Linda Kalilani-Phiri, Victor Mwapasa, Achille Massougbodji, Nadine Fievet, Jeffery A Bailey, Feiko O Ter Kuile, Philippe Deloron, Stephanie M Engel, Steve M Taylor, Jonathan J Juliano, Nicaise Tuikue Ndam, Steven R Meshnick
Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA's ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716094/an-analytical-approach-to-reduce-between-plate-variation-in-multiplex-assays-that-measure-antibodies-to-plasmodium-falciparum-antigens
#18
Rui Fang, Andrew Wey, Naveen K Bobbili, Rose F G Leke, Diane Wallace Taylor, John J Chen
BACKGROUND: Antibodies play an important role in immunity to malaria. Recent studies show that antibodies to multiple antigens, as well as, the overall breadth of the response are associated with protection from malaria. Yet, the variability and reliability of antibody measurements against a combination of malarial antigens using multiplex assays have not been well characterized. METHODS: A normalization procedure for reducing between-plate variation using replicates of pooled positive and negative controls was investigated...
July 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28715465/multiplexing-detection-of-igg-against-plasmodium-falciparum-pregnancy-specific-antigens
#19
Ana Maria Fonseca, Llorenç Quinto, Alfons Jiménez, Raquel González, Azucena Bardají, Sonia Maculuve, Carlota Dobaño, Maria Rupérez, Anifa Vala, John J Aponte, Esperanza Sevene, Eusebio Macete, Clara Menéndez, Alfredo Mayor
BACKGROUND: Pregnant women exposed to Plasmodium falciparum generate antibodies against VAR2CSA, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. There is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. Here we aimed at developing a multiplex-immunoassay to detect antibodies against VAR2CSA antigens. METHODS AND FINDINGS: We constructed two multiplex-bead arrays, one composed of 3 VAR2CSA recombinant-domains (DBL3X, DBL5Ɛ and DBL6Ɛ) and another composed of 46 new peptides covering VAR2CSA conserved and semi-conserved regions...
2017: PloS One
https://www.readbyqxmd.com/read/28698275/crispr-cas9-genome-editing-reveals-that-the-intron-is-not-essential-for-var2csa-gene-activation-or-silencing-in-plasmodium-falciparum
#20
Jessica M Bryant, Clément Regnault, Christine Scheidig-Benatar, Sebastian Baumgarten, Julien Guizetti, Artur Scherf
Plasmodium falciparum relies on monoallelic expression of 1 of 60 var virulence genes for antigenic variation and host immune evasion. Each var gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the var promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs...
July 11, 2017: MBio
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