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Immunological factors in malaria

Estela Shabani, Robert O Opoka, Paul Bangirana, Gregory S Park, Gregory M Vercellotti, Weihua Guan, James S Hodges, Thomas Lavstsen, Chandy C John
The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC)...
2016: Scientific Reports
Laura N Cruz, Yang Wu, Henning Ulrich, Alister G Craig, Célia R S Garcia
BACKGROUND: Plasmodium has a complex biology including the ability to interact with host signals modulating their function through cellular machinery. Tumor necrosis factor (TNF) elicits diverse cellular responses including effects in malarial pathology and increased infected erythrocyte cytoadherence. As TNF levels are raised during Plasmodium falciparum infection we have investigated whether it has an effect on the parasite asexual stage. METHODS: Flow cytometry, spectrofluorimetric determinations, confocal microscopy and PCR real time quantifications were employed for characterizing TNF induced effects and membrane integrity verified by wheat germ agglutinin staining...
July 2016: Biochimica et Biophysica Acta
Jannike Blank, Lars Eggers, Jochen Behrends, Thomas Jacobs, Bianca E Schneider
Malaria and tuberculosis (Tb) are two of the main causes of death from infectious diseases globally. The pathogenic agents, Plasmodium parasites and Mycobacterium tuberculosis, are co-endemic in many regions in the world, however, compared to other co-infections like HIV/Tb or helminth/Tb, malaria/Tb has been given less attention both in clinical and immunological studies. Due to the lack of sufficient human data, the impact of malaria on Tb and vice versa is difficult to estimate but co-infections are likely to occur very frequently...
2016: Frontiers in Microbiology
Rhea J Longley, Jetsumon Sattabongkot, Ivo Mueller
Plasmodium vivax is the most geographically widespread of the malaria parasites causing human disease, yet it is comparatively understudied compared with Plasmodium falciparum. In this article we review what is known about naturally acquired immunity to P. vivax, and importantly, how this differs to that acquired against P. falciparum. Immunity to clinical P. vivax infection is acquired more quickly than to P. falciparum, and evidence suggests humans in endemic areas also have a greater capacity to mount a successful immunological memory response to this pathogen...
February 2016: Parasitology
Katrien Deroost, Thao-Thy Pham, Ghislain Opdenakker, Philippe E Van den Steen
Coevolution of humans and malaria parasites has generated an intricate balance between the immune system of the host and virulence factors of the parasite, equilibrating maximal parasite transmission with limited host damage. Focusing on the blood stage of the disease, we discuss how the balance between anti-parasite immunity versus immunomodulatory and evasion mechanisms of the parasite may result in parasite clearance or chronic infection without major symptoms, whereas imbalances characterized by excessive parasite growth, exaggerated immune reactions or a combination of both cause severe pathology and death, which is detrimental for both parasite and host...
March 2016: FEMS Microbiology Reviews
L Manning, J Cutts, D I Stanisic, M Laman, A Carmagnac, S Allen, A O'Donnell, H Karunajeewa, A Rosanas-Urgell, P Siba, T M E Davis, P Michon, L Schofield, K Rockett, D Kwiatkowski, I Mueller
Genetic factors are likely to contribute to low severe malaria case fatality rates in Melanesian populations, but association studies can be underpowered and may not provide plausible mechanistic explanations if significant associations are detected. In preparation for a genome-wide association study, 29 candidate single-nucleotide polymorphisms (SNPs) with minor allele frequencies >5% were examined in a case-control study of 504 Papua New Guinean children with severe malaria. In parallel, an immunological substudy was performed on convalescent peripheral blood mononuclear cells (PBMCs) from cases and controls...
January 2016: Genes and Immunity
M Barasa, Z W Ng'ang'a, G A Sowayi, J M Okoth, M B O Barasa, F B M Namulanda, E A Kagasi, M M Gicheru, S H Ozwara
Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages...
2012: Open veterinary journal
G G Simon
The neglected tropical diseases (NTDs) are the most common infections of humans in Sub-Saharan Africa. Virtually all of the population living below the World Bank poverty figure is affected by one or more NTDs. New evidence indicates a high degree of geographic overlap between the highest-prevalence NTDs (soil-transmitted helminths, schistosomiasis, onchocerciasis, lymphatic filariasis, and trachoma) and malaria and HIV, exhibiting a high degree of co-infection. Recent research suggests that NTDs can affect HIV and AIDS, tuberculosis (TB), and malaria disease progression...
January 2016: International Journal of Infectious Diseases: IJID
Peter Pemberton-Ross, Thomas A Smith, Eva Maria Hodel, Katherine Kay, Melissa A Penny
Effective population-level interventions against Plasmodium falciparum malaria lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality whenever they are deployed in ways that do not permanently interrupt transmission. When long-term intervention programmes target specific age-groups of human hosts, the age-specific morbidity rates ultimately adjust to new steady-states, but it is very difficult to study these rates and the temporal dynamics leading up to them empirically because the changes occur over very long time periods...
2015: Malaria Journal
Cyril Badaut, Léa Guyonnet, Jacqueline Milet, Emmanuelle Renard, Rémy Durand, Firmine Viwami, Gratien Sagbo, Francis Layla, Philippe Deloron, Serge Bonnefoy, Florence Migot-Nabias
BACKGROUND: The three members of the ring-infected erythrocyte surface antigen (RESA) proteins family share high sequence homologies, which impair the detection and assignment to one or another protein of some pathogenic processes inherent to Plasmodium falciparum malaria. The present study was intended to determine if the antibody and inflammatory responses of children living in a malaria-endemic area varied depending on the RESA-1, RESA-2 or RESA-3 proteins and the severity of the disease, two groups of severe and uncomplicated malaria cases being considered...
2015: Malaria Journal
Tsige Ketema, Ketema Bacha, Esayas Alemayehu, Argaw Ambelu
Although more emphasis has been given to the genetic and environmental factors that determine host vulnerability to malaria, other factors that might have a crucial role in burdening the disease have not been evaluated yet. Therefore, this study was designed to assess the effect of khat chewing on the incidence of severe malaria syndromes and immune responses during malaria infection in an area where the two problems co-exist. Clinical, physical, demographic, hematological, biochemical and immunological data were collected from Plasmodium falciparum mono-infected malaria patients (age ≥ 10 years) seeking medication in Halaba Kulito and Jimma Health Centers...
2015: PloS One
Liz Stevenson, Erik Laursen, Graeme J Cowan, Betty Bandoh, Lea Barfod, David R Cavanagh, Gregers R Andersen, Lars Hviid
Rosetting, the adhesion of Plasmodium falciparum-infected erythrocytes to uninfected erythrocytes, involves clonal variants of the parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP1) and soluble serum factors. While rosetting is a well-known phenotypic marker of parasites associated with severe malaria, the reason for this association remains unclear, as do the molecular details of the interaction between the infected erythrocyte (IE) and the adhering erythrocytes. Here, we identify for the first time a single serum factor, the abundant serum protease inhibitor α2-macroglobulin (α2M), which is both required and sufficient for rosetting mediated by the PfEMP1 protein HB3VAR06 and some other rosette-mediating PfEMP1 proteins...
July 2015: PLoS Pathogens
Peter C Dumoulin, Stefanie A Trop, Jinxia Ma, Hao Zhang, Matthew A Sherman, Jelena Levitskaya
Malaria, the disease caused by Plasmodium parasites, remains a major global health burden. The liver stage of Plasmodium falciparum infection is a leading target for immunological and pharmacological interventions. Therefore, novel approaches providing specific detection and isolation of live P. falciparum exoerythrocytic forms (EEFs) are warranted. Utilizing a recently generated parasite strain expressing green fluorescent protein (GFP) we established a method which, allows for detection and isolation of developing live P...
2015: PloS One
Abigail J Perrin, S Josefin Bartholdson, Gavin J Wright
BACKGROUND: Plasmodium parasites typically elicit a non-sterile but protective immune response in human host populations, suggesting that the parasites actively modulate normal immunological mechanisms. P-selectin is a cell surface receptor expressed in mammals, that is a known component of the inflammatory response against pathogens and has been previously identified as a host factor that influences malaria-associated pathology both in human patients and rodent infection models. METHODS: To better understand the molecular mechanisms underlying the involvement of P-selectin in the pathogenesis of malaria, a systematic extracellular protein interaction screen was used to identify Plasmodium falciparum merozoite surface protein 7 (MSP7) as a binding partner of human P-selectin...
2015: Malaria Journal
Pilar Requena, Diana Barrios, Leanne J Robinson, Paula Samol, Alexandra J Umbers, Regina Wangnapi, Maria Ome-Kaius, Anna Rosanas-Urgell, Alfredo Mayor, Marta López, Elisa de Lazzari, Myriam Arévalo-Herrera, Carmen Fernández-Becerra, Hernando del Portillo, Chetan E Chitnis, Peter M Siba, Stephen Rogerson, Ivo Mueller, Azucena Bardají, Clara Menéndez, Carlota Dobaño
Pregnancy triggers immunological changes aimed to tolerate the fetus. However, it has not been properly addressed whether similar changes occur in tropical areas with high infection pressure and whether these changes render women more susceptible to infectious diseases. We compared the frequencies of T cell subsets, including regulatory T cells, in pregnant and nonpregnant women from Papua New Guinea, a high malaria transmission area, and from Spain, a malaria-free country. We also assessed the relationship among these cellular subsets, malaria infection, and delivery outcomes...
April 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Lars Hviid, Lea Barfod, Freya J I Fowkes
In areas with stable transmission of Plasmodium falciparum parasites, even partially-protective immunity to malaria is acquired only after years of exposure and several infections. It has long been speculated that malaria parasites are directly able to undermine the establishment and maintenance of immunological memory, and that the often transient antibody responses to this parasite are evidence of such a dysfunction. We propose that long-lived antibody responses may not always be a prerequisite for protection, and that antibody longevity varies in an exposure- and age-dependent manner...
March 2015: Trends in Parasitology
Peter Liehl, Patrícia Meireles, Inês S Albuquerque, Mykola Pinkevych, Fernanda Baptista, Maria M Mota, Miles P Davenport, Miguel Prudêncio
Following transmission through a mosquito bite to the mammalian host, Plasmodium parasites first invade and replicate inside hepatocytes before infecting erythrocytes and causing malaria. The mechanisms limiting Plasmodium reinfections in humans living in regions of malaria endemicity have mainly been explored by studying the resistance induced by the blood stage of infection. However, epidemiologic studies have suggested that in high-transmission areas, preerythrocytic stages also activate host resistance to reinfection...
March 2015: Infection and Immunity
Sue D Xiang, Ying Y Kong, Jennifer Hanley, Martina Fuchsberger, Blessing Crimeen-Irwin, Magdalena Plebanski
BACKGROUND: Many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. We propose that their particulate nature contributes to non-specific effects. Herein, we demonstrate polystyrene nanoparticles modulate dendritic cell (DC) homeostasis, thereby promoting a persistent enhanced state of immune readiness to a subsequent infectious challenge. METHODS: Particles (approximately 40 nm and 500 nm carboxylated polystyrene nanoparticles; PSNPs) alone or conjugated to a model antigen were injected in mice, and DCs in draining lymph nodes (dLNs) and bone-marrow (BM) quantified by flow cytometry...
January 2015: Transactions of the Royal Society of Tropical Medicine and Hygiene
Severin Zinöcker, Christine E Schindler, Jeff Skinner, Tobias Rogosch, Michael Waisberg, Jean-Nicolas Schickel, Eric Meffre, Kassoum Kayentao, Aïssata Ongoïba, Boubacar Traoré, Susan K Pierce
Immunity to Plasmodium falciparum malaria is naturally acquired in individuals living in malaria-endemic areas of Africa. Abs play a key role in mediating this immunity; however, the acquisition of the components of Ab immunity, long-lived plasma cells and memory B cells (MBCs), is remarkably inefficient, requiring years of malaria exposure. Although long-lived classical MBCs (CD19(+)/CD20(+)/CD21(+)/CD27(+)/CD10(-)) are gradually acquired in response to natural infection, exposure to P. falciparum also results in a large expansion of what we have termed atypical MBCs (CD19(+)/CD20(+)/CD21(-)/CD27(-)/CD10(-))...
February 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Frances C Recuenco, Ryo Takano, Shiori Chiba, Tatsuki Sugi, Hitoshi Takemae, Fumi Murakoshi, Akiko Ishiwa, Atsuko Inomata, Taisuke Horimoto, Yoshiyasu Kobayashi, Noriyuki Horiuchi, Kentaro Kato
BACKGROUND: There is an urgent need to develop and test novel compounds against malaria infection. Carrageenans, sulphated polysaccharides derived from seaweeds, have been previously shown to inhibit Plasmodium falciparum in vitro. However, they are inflammatory and alter the permeability of the blood-brain barrier, raising concerns that their use as a treatment for malaria could lead to cerebral malaria (CM), a severe complication of the disease. In this work, the authors look into the effects of the administration of λ-carrageenan to the development and severity of CM in BALB/c mice, a relatively non-susceptible model, during infection with the ANKA strain of Plasmodium berghei...
2014: Malaria Journal
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