A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults.

BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45.

Prospective multicentre study of host response signatures in neonatal sepsis in Sub Saharan Africa.

Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. While the role of host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating new biomarkers targeting host response in regions where sepsis burden is high and medico-economic resources are scarce. The objective of the study is to evaluate diagnostic and prognostic accuracy of biomarkers of neonatal sepsis in Sub Saharan Africa.

SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region.

Introduction: Neonatal sepsis outreaches all causes of neonatal mortality worldwide and remains a major societal burden in low and middle income countries. In addition to limited resources, endemic morbidities, such as malaria and prematurity, predispose neonates and infants to invasive infection by altering neonatal immune response to pathogens. Nevertheless, thoughtful epidemiological, diagnostic and immunological evaluation of neonatal sepsis and the impact of gestational malaria have never been performed.

Changes in monocyte subsets are associated with clinical outcomes in severe malarial anaemia and cerebral malaria.

Monocytes are plastic heterogeneous immune cells involved in host-parasite interactions critical for malaria pathogenesis. Human monocytes have been subdivided into three populations based on surface expression of CD14 and CD16. We hypothesised that proportions and phenotypes of circulating monocyte subsets can be markers of severity or fatality in children with malaria.

Maternal malaria but not schistosomiasis is associated with a higher risk of febrile infection in infant during the first 3 months of life: A mother-child cohort in Benin.

Background: Malaria and schistosomiasis represent two of the most prevalent and disabling parasitic infections in developing countries. Few studies have evaluated the effect of maternal schistosomiasis and malaria in the peri-conceptional period on infant's risk of infection.

Methods: In Benin, women were followed from the preconception period until delivery.

Poor maternal anthropometric status before conception is associated with a deleterious infant growth during the first year of life: a longitudinal preconceptional cohort.

Background: According to the Developmental Origins of Health and Diseases concept, exposures in the preconception period may be critical. For the first time, we evaluated the effect of preconception poor anthropometric status on infant's growth in sub-Saharan Africa.

Methods: A mother-child cohort was followed prospectively from preconception to 1 year old in Benin.

From genomic to LC-MS/MS evidence: Analysis of PfEMP1 in Benin malaria cases.

Background: PfEMP1 is the major protein from parasitic origin involved in the pathophysiology of severe malaria, and PfEMP1 domain subtypes are associated with the infection outcome. In addition, PfEMP1 variability is endless and current publicly available protein repositories do not reflect the high diversity of the sequences of PfEMP1 proteins. The identification of PfEMP1 protein sequences expressed with samples remains challenging.

PFI1785w: A highly conserved protein associated with pregnancy associated malaria.

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.

Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae.

Background: The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond.

Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria.

Plasmodium falciparum is responsible of severe malaria, including cerebral malaria (CM). During its intra-erythrocytic maturation, parasite-derived proteins are expressed, exported and presented at the infected erythrocyte membrane. To identify new CM-specific parasite membrane proteins, we conducted a mass spectrometry-based proteomic study and compared the protein expression profiles between 9 CM and 10 uncomplicated malaria (UM) samples.

Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum.

Maternal parasitoses modulate fetal immune development, manifesting as altered cellular immunological activity in cord blood that may be linked to enhanced susceptibility to infections in early life. Plasmodium falciparum typifies such infections, with distinct placental infection-related changes in cord blood exemplified by expanded populations of parasite antigen-specific regulatory T cells. Here we addressed whether such early-onset cellular immunological alterations persist through infancy.

Nrf2-driven CD36 and HO-1 gene expression in circulating monocytes correlates with favourable clinical outcome in pregnancy-associated malaria.

Background: Pregnancy-associated malaria (PAM) constitutes one of the most severe forms of malaria infection leading to fetal growth restriction and high risk of infant death. The severity of the pathology is largely attributed to the recruitment of monocytes and macrophages in the placenta which is evidenced by dysregulated inflammation found in placental blood. Importantly, CD36(+) monocytes/macrophages are also thought to participate in the tight control of the pro- and anti-inflammatory responses following Plasmodium detection through elimination of apoptotic cells and malaria-infected erythrocytes, internalization and recycling of oxidized forms of low-density lipoprotein and collaboration with TLR2 in pro-inflammatory response.

Insights Into Circulating Cytokine Dynamics During Pregnancy in HIV-Infected Beninese Exposed to Plasmodium falciparum Malaria.

We investigated the circulating plasma levels of Th1- (Interleukin-2 [IL-2], tumor necrosis factor-α [TNF-α], interferon-gamma [IFN-γ]) and Th2-type (IL-4, IL-5, IL-10) cytokines in human immunodeficiency virus (HIV)-infected pregnant women living in a malaria-endemic area. We analyzed samples from 200 pregnant women included in the prevention of pregnancy-associated malaria in HIV-infected women: cotrimoxazole prophylaxis versus mefloquine (PACOME) clinical trial who were followed until delivery. Cytokine concentrations were measured by flow cytometry-based multiplex bead array.

Plasmodium falciparum Polymorphisms associated with ex vivo drug susceptibility and clinical effectiveness of artemisinin-based combination therapies in Benin.

Artemisinin-based combination therapies (ACTs) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. We assessed the association of Plasmodium falciparum polymorphisms and ex vivo drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine (n = 96), fixed-dose artesunate-amodiaquine (n = 96), and sulfadoxine-pyrimethamine (n = 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed.

Differential adhesion-inhibitory patterns of antibodies raised against two major variants of the NTS-DBL2X region of VAR2CSA.

Background: VAR2CSA is a large polymorphic Plasmodium falciparum protein expressed on infected erythrocytes (IE) that allows their binding in the placenta, thus precipitating placental malaria (PM). The N-terminal part of VAR2CSA that contains the binding site to placental chondroitin sulfate A (CSA) is currently recognized as the most attractive region for vaccine development. An ultimate challenge is to define epitopes in this region that induce a broad cross-reactive adhesion inhibitory antibody response.

Differential protein expression profiles between Plasmodium falciparum parasites isolated from subjects presenting with pregnancy-associated malaria and uncomplicated malaria in Benin.

Background: Plasmodium falciparum is responsible for severe malaria, including pregnancy-associated malaria (PAM). During intra-erythrocytic maturation, the infected erythrocyte (iE) membrane is modified by insertion of parasite-derived proteins, primarily consisting of variant surface antigens such as P. falciparum erythrocyte membrane protein-1.

Malaria modifies neonatal and early-life toll-like receptor cytokine responses.

Protection from infections in early life relies extensively on innate immunity, but it is unknown whether and how maternal infections modulate infants' innate immune responses, thereby altering susceptibility to infections. Plasmodium falciparum causes pregnancy-associated malaria (PAM), and epidemiological studies have shown that PAM enhances infants' susceptibility to infection with P. falciparum.

Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy.

Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ∼1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery.

First-trimester Plasmodium falciparum infections display a typical "placental" phenotype.

Background: Plasmodium falciparum-infected erythrocytes (IEs) adhere to host cell receptors, allowing parasites to sequester into deep vascular beds of various organs. This defining phenomenon of malaria pathogenesis is key to the severe clinical complications associated with cerebral and placental malaria. The principal ligand associated with the binding to chondroitin sulfate A (CSA) that allows placental sequestration of IEs is a P.