11 research outputs found
Acute Brain MRI Findings in 120 Malawian Children with Cerebral Malaria: New Insights into an Ancient Disease
Comparative proteomic analysis of two Entamoeba histolytica strains with different virulence phenotypes identifies peroxiredoxin as an important component of amoebic virulence
Brain MRI of children with retinopathy-negative cerebral malaria
Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with retinopathy-negative cerebral malaria (CM) and investigate whether any findings on acute MRI were associated with adverse outcomes. We performed MRI scans on children admitted to the hospital in Blantyre, Malawi with clinically defined CM. Two hundred and seventeen children were imaged during the study period; 44 patients were malarial retinopathy-negative; and 173 patients were retinopathy-positive. We compared MRI findings in children with retinopathy-negative and retinopathy-positive CM. In children who were retinopathy-negative, we identified MRI variables that were associated with death and adverse neurologic outcomes. On multivariate analysis, cortical diffusion weighted imaging (DWI) abnormality and increased brain volume were strongly associated with neurologic morbidity in survivors. Investigations to explore the underlying pathophysiologic processes responsible for these MRI changes are warranted
Brain MRI of children with retinopathy-negative cerebral malaria
Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with retinopathy-negative cerebral malaria (CM) and investigate whether any findings on acute MRI were associated with adverse outcomes. We performed MRI scans on children admitted to the hospital in Blantyre, Malawi with clinically defined CM. Two hundred and seventeen children were imaged during the study period; 44 patients were malarial retinopathy-negative; and 173 patients were retinopathy-positive. We compared MRI findings in children with retinopathy-negative and retinopathy-positive CM. In children who were retinopathy-negative, we identified MRI variables that were associated with death and adverse neurologic outcomes. On multivariate analysis, cortical diffusion weighted imaging (DWI) abnormality and increased brain volume were strongly associated with neurologic morbidity in survivors. Investigations to explore the underlying pathophysiologic processes responsible for these MRI changes are warranted
Diffusion-Weighted MR Imaging in a Prospective Cohort of Children with Cerebral Malaria Offers Insights into Pathophysiology and Prognosis
A mixed-methods evaluation of neurorehabilitation resources for pediatric cerebral malaria survivors in Blantyre, Malawi
Breaking the species barrier: use of SCID mouse-human chimeras for the study of human infectious diseases
Mouse–human chimeras have become a novel way to model the interactions between microbial pathogens and human cells, tissues or organs. Diseases studied with human xenografts in severe combined immunodeficient (SCID) mice include Pseudomonas aeruginosa infection in cystic fibrosis, group A streptococci and impetigo, bacillary and amoebic dysentery, and AIDS. In many cases, disease in the human xenograft appears to accurately reproduce the disease in humans, providing a powerful model for identifying virulence factors, host responses to infection and the effects of specific interventions on disease. In this review, we summarize recent studies that have used mouse–human chimeras to understand the pathophysiology of specific bacterial and protozoan infections
Adipose tissue parasite sequestration drives leptin production in mice and correlates with human cerebral malaria.
Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice infected with parasite strains that fail to sequester in WAT displayed reduced leptin production and protection from ECM. WAT sequestration and leptin induction were lost in CD36KO mice; however, ECM susceptibility revealed sexual dimorphism. Adipocyte leptin was regulated by the mechanistic target of rapamycin complex 1 (mTORC1) and blocked by rapamycin. In humans, although Plasmodium falciparum infection did not increase circulating leptin levels, iRBC sequestration, tissue leptin production, and mTORC1 activity were positively correlated with CM in pediatric postmortem WAT. These data identify WAT sequestration as a trigger for leptin production with potential implications for pathogenesis of malaria infection, prognosis, and treatment