Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria.

Protective immunity to malaria depends on acquisition of parasite-specific antibodies, with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) being one of the most important target antigens. The effector functions of PfEMP1-specific IgG include inhibition of infected erythrocyte (IE) sequestration and opsonization of IEs for cell-mediated destruction. IgG glycosylation modulates antibody functionality, with increased affinity to FcγRIIIa for IgG lacking fucose in the Fc region (Fc-afucosylation).

Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria.

Background: Acquired immunity to Plasmodium falciparum malaria is mainly mediated by immunoglobulin G (IgG) targeting erythrocyte membrane protein 1 (PfEMP1). These adhesins mediate infected erythrocyte (IE) sequestration, protecting IEs from splenic destruction. PfEMP1-specific IgG is therefore thought to protect mainly by inhibiting IE sequestration.

Placental malaria and circumsporozoite protein-specific immunity.

Circumsporozoite protein-specific active and passive immunization can protect significantly against Plasmodium falciparum malaria and are being considered as tools to prevent placental malaria. Despite recent encouraging findings, a closer view of the underlying biology indicates significant challenges to preventing placental malaria.

Biomarker of Anopheles exposure in Ghanaian children with haemoglobin S and C.

Heterozygous carriers of haemoglobin S and C (HbAS and HbAC) have a reduced risk of severe malaria but are not protected from Plasmodium falciparum infection, suggesting that the protection involves acquired immunity. During a blood meal, female Anopheles mosquitoes inject saliva that can elicit a host antibody response, which can serve as a proxy for exposure to Plasmodium infection. Previous studies have shown that the peptide gSG6-P1 of An.

Correction: A conformational epitope in placental malaria vaccine antigen VAR2CSA: What does it teach us?

[This corrects the article DOI: 10.1371/journal.ppat.

Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria.

Introduction: Limited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM).

Methods: A prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra.

Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.

Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria.

infection and naturally acquired immunity to malaria antigens among Ghanaian children in northern Ghana.

Background: The surge in malaria cases and deaths in recent years, particularly in Africa, despite the widespread implementation of malaria-control measures could be due to inefficiencies in malaria control and prevention measures in malaria-endemic communities. In this context, this study provides the malaria situation report among children in three Municipalities in Northern Ghana, where Seasonal Malaria Chemotherapy (SMC) is implemented by Ghana Health Service (GHS).

Methods: A cross-sectional household survey was carried out to assess the malaria knowledge, attitudes, and practices (KAP) and malaria prevalence in 394 households in 13 rural communities in the Kumbugu, Nanton and Tolon Municipalities, Northern Region, Ghana.

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.

A conformational epitope in placental malaria vaccine antigen VAR2CSA: What does it teach us?

VAR2CSA is the Plasmodium falciparum variant surface antigen that mediates binding of infected erythrocytes to chondroitin sulfate A (CSA) and their sequestration in intervillous spaces of the placenta, leading to placental malaria (PM). Relatively high polymorphism in VAR2CSA sequences has hindered development of a vaccine that induces broadly neutralizing immunity. Recent research has highlighted that a broadly reactive human monoclonal antibody, called PAM1.

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.

ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children.

Members of the highly polymorphic Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on the surface of infected erythrocytes (IEs) are important virulence factors, which mediate vascular adhesion of IEs via endothelial host receptors and are targets of naturally acquired immunity. The PfEMP1 family can be divided into clinically relevant subgroups, of which some bind intercellular adhesion molecule 1 (ICAM-1). While the acquisition of IgG specific for ICAM-1-binding DBLβ domains is known to differ between PfEMP1 groups, its ability to induce antibody-dependent cellular phagocytosis (ADCP) is unclear.

Enzyme-Linked Immunosorbent Assay for Activation of the Classical Complement Pathway by Plasmodium falciparum-Infected Erythrocyte Surface Antigen-Specific Antibodies.

Enzyme-linked immunosorbent assays (ELISA) have a wide range of applications, ranging from specific antibody titer determination to quantification of any biological or non-biological substance with a specific binding partner (usually an antibody). The activity of biological cascades, such as the complement cascade of the innate immune system, can also be assessed by ELISA. We present here an assay optimized for the detection of the activation of the classical complement pathway by polyclonal and monoclonal antibodies (mAbs) specific for Plasmodium falciparum-infected erythrocyte surface antigens.

Analysis by Flow Cytometry of α-Macroglobulin and Nonimmune IgM-Binding to Plasmodium falciparum-Infected Erythrocytes.

Several members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family can bind human serum proteins such as IgM and α-macroglobulin (αM). This binding seems to play a role in pathogenesis and immune evasion by improving the avidity of PfEMP1-mediated binding to erythrocyte receptors and/or by masking antibody epitopes in PfEMP1. In this protocol, we describe a flow cytometry-based protocol to evaluate IgM- and αM-binding to intact and unfixed mature-stage IEs.

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.

Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil.

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin.

Influence of α-Macroglobulin, Anti-Parasite IgM and ABO Blood Group on Rosetting in Clinical Isolates and Their Associations with Disease Severity in a Ghanaian Population.

Purpose: The severity of infections is associated with the ability of the infected red blood cells to cytoadhere to host vascular endothelial surfaces and to uninfected RBCs. Host blood group antigens and two serum proteins α-macroglobulin (αM) and IgM have been implicated in rosette formation in laboratory-adapted . However, there is only limited information about these phenotypes in clinical isolates.

No sweet deal: the antibody-mediated immune response to malaria.

IgG antibodies are key effector molecules in acquired immunity to Plasmodium falciparum malaria, and the PfEMP1 adhesins expressed on the surface of the infected erythrocytes are crucial immunological targets. The antigen specificity of these antibodies has therefore been a major research focus. However, we recently reported that the Fc domain of naturally induced PfEMP1-specific IgG1 is selectively modified by post-translational omission of fucose from the conserved Fc glycan.

PfEMP1-Specific Immunoglobulin G Reactivity Among Beninese Pregnant Women With Sickle Cell Trait.

Background: Sickle cell trait (HbAS) protects against severe malaria but not against placental malaria (PM). In this study, erythrocyte membrane protein (PfEMP1)-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants.

Methods: Plasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure immunoglobulin (Ig)G levels to 6 recombinant PfEMP1 proteins and 3 corresponding native proteins expressed on the infected erythrocyte (IE) surface.

Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients With Uncomplicated Malaria.

Studies have proposed that malaria may lead to electrocardiographic (ECG) changes and pericardial inflammation. We aimed to investigate the frequency of ECG alterations, determined by ECG and Holter monitoring, and pericardial effusion in patients with malaria infection. We performed a prospective observational study of adult patients with uncomplicated malaria in Amazonas, Brazil.