Type I Interferon Receptor Variants in Gene Regulatory Regions are Associated with Susceptibility to Cerebral Malaria in Malawi.

Cerebral malaria (CM) remains an important cause of morbidity and mortality. Risk for developing CM partially depends on host genetic factors, including variants encoded in the type I interferon (IFN) receptor 1 (IFNAR1). Type I IFNs bind to IFNAR1 resulting in increased expression of IFN responsive genes, which modulate innate and adaptive immune responses.

Extensive alterations of blood metabolites in pediatric cerebral malaria.

Cerebral malaria (CM) presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood.

STING-Licensed Macrophages Prime Type I IFN Production by Plasmacytoid Dendritic Cells in the Bone Marrow during Severe Plasmodium yoelii Malaria.

Malaria remains a global health burden causing significant morbidity, yet the mechanisms underlying disease outcomes and protection are poorly understood. Herein, we analyzed the peripheral blood of a unique cohort of Malawian children with severe malaria, and performed a comprehensive overview of blood leukocytes and inflammatory mediators present in these patients. We reveal robust immune cell activation, notably of CD14+ inflammatory monocytes, NK cells and plasmacytoid dendritic cells (pDCs) that is associated with very high inflammation.

Activated Neutrophils Are Associated with Pediatric Cerebral Malaria Vasculopathy in Malawian Children.

Unlabelled: Most patients with cerebral malaria (CM) sustain cerebral microvascular sequestration of Plasmodium falciparum-infected red blood cells (iRBCs). Although many young children are infected with P. falciparum, CM remains a rare outcome; thus, we hypothesized that specific host conditions facilitate iRBC cerebral sequestration.

Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria.

Background: Cerebral malaria (CM) remains a significant cause of morbidity and mortality in children in sub-Saharan Africa. CM mortality has been associated with increased brain volume, seen on neuroimaging studies.

Methods: To examine the potential role of blood metabolites and inflammatory mediators in increased brain volume in Malawian children with CM, an association study was performed between plasma metabolites, cytokine levels and phospholipase A2 (PLA2) activity with brain volume.

HIV Malaria Co-Infection Is Associated with Atypical Memory B Cell Expansion and a Reduced Antibody Response to a Broad Array of Plasmodium falciparum Antigens in Rwandan Adults.

HIV infected individuals in malaria endemic areas experience more frequent and severe malaria episodes compared to non HIV infected. This clinical observation has been linked to a deficiency in antibody responses to Plasmodium falciparum antigens; however, prior studies have only focused on the antibody response to <0.5% of P.

The T-Cell Inhibitory Molecule Butyrophilin-Like 2 Is Up-regulated in Mild Plasmodium falciparum Infection and Is Protective During Experimental Cerebral Malaria.

Plasmodium falciparum infection can result in severe disease that is associated with elevated inflammation and vital organ dysfunction; however, malaria-endemic residents gain protection from lethal outcomes and manifest only mild symptoms during infection. To characterize host responses associated with this more effective antimalarial response, we characterized whole-blood transcriptional profiles in Rwandan adults during a mild malaria episode and compared them with findings from a convalescence sample. We observed transcriptional up-regulation in many pathways, including type I interferon, interferon γ, complement activation, and nitric oxide during malaria infection, which provide benchmarks of mild disease physiology.

Antibodies against Mycobacterial proteins as biomarkers for HIV-associated smear-negative tuberculosis.

Serology data are limited for patients with sputum smear-negative HIV-associated active tuberculosis (TB). We evaluated the serum antibody responses against the mycobacterial proteins MPT51, MS, and echA1 and the 38-kDa protein via enzyme-linked immunosorbent assay (ELISA) in South African (S.A.

Mild Plasmodium falciparum malaria following an episode of severe malaria is associated with induction of the interferon pathway in Malawian children.

Infection with Plasmodium falciparum can lead to a range of severe to minimal symptoms, occasionally resulting in death in young children or nonimmune adults. In areas of high transmission, older children and adults generally suffer only mild or asymptomatic malaria infections and rarely develop severe disease. The immune features underlying this apparent immunity to severe disease remain elusive.