High burden of asymptomatic malaria and anaemia despite high adherence to malaria control measures: a cross-sectional study among pregnant women across two seasons in a malaria-endemic setting in Ghana.

Purpose: Anaemia remains a serious concern among pregnant women, and thus, it is closely monitored from the onset of pregnancy through to delivery to help prevent adverse maternal and neonatal outcomes. In malaria-endemic settings, continuous low-level carriage of P. falciparum parasites is common and its contribution to maternal anaemia should not be underestimated.

Anti-phosphatidylserine antibody levels are low in multigravid pregnant women in a malaria-endemic area in Nigeria, and do not correlate with anti-VAR2CSA antibodies.

Anemia is a common malaria-associated complication in pregnant women in endemic regions. Phosphatidylserine (PS) is exposed to the immune system during the massive destruction of red blood cells (RBCs) that accompany malaria, and antibodies against PS have been linked to anemia through destruction of uninfected RBCs. We determined levels of anti-PS IgG antibodies in pregnant women in Ibadan, Nigeria and correlated them to parameters of importance in development of anemia and immunity.

The Rapid and Spontaneous Postpartum Clearance of Plasmodium falciparum Is Related to Expulsion of the Placenta.

Parasitemia among pregnant women with protective immunity to Plasmodium falciparum malaria is often dominated by VAR2CSA-positive infected erythrocytes (IEs). VAR2CSA mediates sequestration of IEs in the placenta. We hypothesized that the previously observed spontaneous postpartum clearance of parasitemia in such women is related to the expulsion of the placenta, which removes the sequestration focus of VAR2CSA-positive IEs.

Cryo-EM reveals the conformational epitope of human monoclonal antibody PAM1.4 broadly reacting with polymorphic malarial protein VAR2CSA.

Malaria during pregnancy is a major global health problem caused by infection with Plasmodium falciparum parasites. Severe effects arise from the accumulation of infected erythrocytes in the placenta. Here, erythrocytes infected by late blood-stage parasites adhere to placental chondroitin sulphate A (CS) via VAR2CSA-type P.

Measuring Rosetting Inhibition in Plasmodium falciparum Parasites Using a Flow Cytometry-Based Assay.

Rosetting is the ability of Plasmodium falciparum-infected erythrocytes (IEs) to bind to host receptors on the surface of uninfected erythrocytes (uE) leading to the formation of a cluster of cells with a central IE surrounded by uE. It is a hallmark event during the pathogenesis of P. falciparum malaria, the most severe species causing malaria, which affects mostly young children in Africa.

Expression of Single-Domain Soluble and Disulfide-Folded PfEMP1 Antigens in the Escherichia coli SHuffle Expression System.

The genome of Plasmodium falciparum has an A/T content of around 81%. This, together with a high cysteine content and the high molecular weight of several proteins, make the expression of recombinant parasite proteins in heterologous systems challenging. P.

Analysis of allelic cross-reactivity of monoclonal IgG antibodies by a multiplexed reverse FluoroSpot assay.

The issue of antibody cross-reactivity is of central importance in immunology, and not least in protective immunity to malaria, where key antigens show substantial allelic variation (polymorphism). However, serological analysis often does not allow the distinction between true cross-reactivity (one antibody recognizing multiple antigen variants) and apparent cross-reactivity (presence of multiple variant-specific antibodies), as it requires analysis at the single B-cell/monoclonal antibody level. ELISpot is an assay that enables that, and a recently developed multiplexed variant of ELISpot (FluoroSpot) facilitates simultaneous assessment of B-cell/antibody reactivity to several different antigens.

mSphere of Influence: Structural Insights into the Molecular Mechanism Underlying Placental Malaria.

Maria del Pilar Quintana works on immunology and pathogenesis of severe malaria. In this mSphere of Influence article, she reflects on how the papers "Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA" (R. Ma, T.

Measuring Naturally Acquired Phagocytosis-Inducing Antibodies to Plasmodium falciparum Parasites by a Flow Cytometry-Based Assay.

The protocol describes how to set up and run a flow cytometry-based phagocytosis assay of Plasmodium falciparum-infected erythrocytes (IEs) opsonized by naturally acquired IgG antibodies specific for VAR2CSA. VAR2CSA is the parasite antigen that mediates the selective sequestration of IEs in the placenta that can cause a severe form of malaria in pregnant women, called placental malaria (PM). Protection from PM is mediated by VAR2CSA-specific antibodies that are believed to function by inhibiting placental sequestration and/or by opsonizing IEs for phagocytosis.

Endemic Burkitt lymphoma - an aggressive childhood cancer linked to Plasmodium falciparum exposure, but not to exposure to other malaria parasites.

Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma. The prevalence of BL is ten-fold higher in areas with stable transmission of Plasmodium falciparum malaria, where it is the most common childhood cancer, and is referred to as endemic BL (eBL). In addition to its association with exposure to P.

Comprehensive analysis of Fc-mediated IgM binding to the Plasmodium falciparum erythrocyte membrane protein 1 family in three parasite clones.

PfEMP1 is a family of adhesive proteins expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs), where they mediate adhesion of IEs to a range of host receptors. Efficient PfEMP1-dependent IE sequestration often depends on soluble serum proteins, including IgM. Here, we report a comprehensive investigation of which of the about 60 var gene-encoded PfEMP1 variants per parasite genome can bind IgM via the Fc part of the antibody molecule, and which of the constituent domains of those PfEMP1 are involved.

Evasion of Classical Complement Pathway Activation on -Infected Erythrocytes Opsonized by PfEMP1-Specific IgG.

Members of the PfEMP1 protein family are expressed on the surface of -infected erythrocytes (IEs), where they contribute to the pathogenesis of malaria and are important targets of acquired immunity. Although the PfEMP1-specific antibody response is dominated by the opsonizing and complement-fixing subclasses IgG1 and IgG3, activation of the classical complement pathway by antibody-opsonized IEs does not appear to be a major immune effector mechanism. To study the molecular background for this, we used ELISA and flow cytometry to assess activation of the classical component pathway by recombinant and native PfEMP1 antigen opsonized by polyclonal and monoclonal PfEMP1-specific human IgG.

SURGE complex of Plasmodium falciparum in the rhoptry-neck (SURFIN4.2-RON4-GLURP) contributes to merozoite invasion.

Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process engaging proteins on the merozoite surface and those contained and sequentially released from the apical organelles (micronemes and rhoptries). Fundamental to invasion is the formation of a moving junction (MJ), a region of close apposition of the merozoite and the RBC plasma membranes, through which the merozoite draws itself before settling into a newly formed parasitophorous vacuole (PV). SURFIN4.

Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface.

Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer the course of a malaria infection by reducing sequestration and stimulating phagocytosis of pRBC. Here we have studied a selection of proteins representing three different parasite gene families employing a well-characterized parasite with a severe malaria phenotype (FCR3S1.2).

Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor.

Pregnancy-associated malaria commonly involves the binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate A (CSA) through the PfEMP1-VAR2CSA protein. VAR2CSA is translationally repressed by an upstream open reading frame. In this study, we report that the P.

Epitopes of anti-RIFIN antibodies and characterization of rif-expressing Plasmodium falciparum parasites by RNA sequencing.

Variable surface antigens of Plasmodium falciparum have been a major research focus since they facilitate parasite sequestration and give rise to deadly malaria complications. Coupled with its potential use as a vaccine candidate, the recent suggestion that the repetitive interspersed families of polypeptides (RIFINs) mediate blood group A rosetting and influence blood group distribution has raised the research profile of these adhesins. Nevertheless, detailed investigations into the functions of this highly diverse multigene family remain hampered by the limited number of validated reagents.

Phagocytosis-inducing antibodies to Plasmodium falciparum upon immunization with a recombinant PfEMP1 NTS-DBL1α domain.

Background: Individuals living in endemic areas gradually acquire natural immunity to clinical malaria, largely dependent on antibodies against parasite antigens. There are many studies indicating that the variant antigen PfEMP1 at the surface of the parasitized red blood cell (pRBC) is one of the major targets of the immune response. It is believed that antibodies against PfEMP1 confer protection by blocking sequestration (rosetting and cytoadherence), inducing antibody-dependent cellular-inhibitory effect and opsonizing pRBCs for phagocytosis.

Rosette-Disrupting Effect of an Anti-Plasmodial Compound for the Potential Treatment of Plasmodium falciparum Malaria Complications.

The spread of artemisinin-resistant parasites could lead to higher incidence of patients with malaria complications. However, there are no current treatments that directly dislodge sequestered parasites from the microvasculature. We show that four common antiplasmodial drugs do not disperse rosettes (erythrocyte clusters formed by malaria parasites) and therefore develop a cell-based high-throughput assay to identify potential rosette-disrupting compounds.

A sequence in subdomain 2 of DBL1α of Plasmodium falciparum erythrocyte membrane protein 1 induces strain transcending antibodies.

Immunity to severe malaria is the first level of immunity acquired to Plasmodium falciparum. Antibodies to the variant antigen PfEMP1 (P. falciparum erythrocyte membrane protein 1) present at the surface of the parasitized red blood cell (pRBC) confer protection by blocking microvascular sequestration.

Plasmodium falciparum rosetting epitopes converge in the SD3-loop of PfEMP1-DBL1α.

The ability of Plasmodium falciparum parasitized RBC (pRBC) to form rosettes with normal RBC is linked to the virulence of the parasite and RBC polymorphisms that weaken rosetting confer protection against severe malaria. The adhesin PfEMP1 mediates the binding and specific antibodies prevent sequestration in the micro-vasculature, as seen in animal models. Here we demonstrate that epitopes targeted by rosette disrupting antibodies converge in the loop of subdomain 3 (SD3) which connects the h6 and h7 α-helices of PfEMP1-DBL1α.