Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria.

Cerebral malaria (CM) can be classified as retinopathy-positive or retinopathy-negative, based on the presence or absence of characteristic retinal features. While malaria parasites are considered central to the pathogenesis of retinopathy-positive CM, their contribution to retinopathy-negative CM is largely unknown. One theory is that malaria parasites are innocent bystanders in retinopathy-negative CM and the etiology of the coma is entirely non-malarial.

Automated Detection of Malarial Retinopathy in Digital Fundus Images for Improved Diagnosis in Malawian Children with Clinically Defined Cerebral Malaria.

Cerebral malaria (CM), a complication of malaria infection, is the cause of the majority of malaria-associated deaths in African children. The standard clinical case definition for CM misclassifies ~25% of patients, but when malarial retinopathy (MR) is added to the clinical case definition, the specificity improves from 61% to 95%. Ocular fundoscopy requires expensive equipment and technical expertise not often available in malaria endemic settings, so we developed an automated software system to analyze retinal color images for MR lesions: retinal whitening, vessel discoloration, and white-centered hemorrhages.

Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria.

Background:  Plasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion.

Methods:  We used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene.

Safety of lumbar puncture in comatose children with clinical features of cerebral malaria.

Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM).

Methods: This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness.

Longitudinal Visuomotor Development in a Malaria Endemic Area: Cerebral Malaria and Beyond.

Paediatric cerebral malaria is the most serious complication of Plasmodium falciparum infection. While the majority recover, long-term cognitive impairment has been highlighted as a significant and neglected problem. Persistent or serious deficits in processes such as attention or behavioural inhibition should be manifest in changes to performance on oculomotor tasks.

Comparison of the effectiveness of three retinal camera technologies for malarial retinopathy detection in Malawi.

The purpose of this study was to test the suitability of three available camera technologies (desktop, portable, and i-phone based) for imaging comatose children who presented with clinical symptoms of malaria. Ultimately, the results of the project would form the basis for a design of a future camera to screen for malaria retinopathy (MR) in a resource challenged environment. The desktop, portable, and i-phone based cameras were represented by the Topcon, Pictor Plus, and Peek cameras, respectively.

Grading fluorescein angiograms in malarial retinopathy.

Background: Malarial retinopathy is an important finding in Plasmodium falciparum cerebral malaria, since it strengthens diagnostic accuracy, predicts clinical outcome and appears to parallel cerebral disease processes. Several angiographic features of malarial retinopathy have been described, but observations in different populations can only be reliably compared if consistent methodology is used to capture and grade retinal images. Currently no grading scheme exists for fluorescein angiographic features of malarial retinopathy.

Developing retinal biomarkers of neurological disease: an analytical perspective.

The inaccessibility of the brain poses a problem for neuroscience. Scientists have traditionally responded by developing biomarkers for brain physiology and disease. The retina is an attractive source of biomarkers since it shares many features with the brain.

Automated Detection of Vessel Abnormalities on Fluorescein Angiogram in Malarial Retinopathy.

The detection and assessment of intravascular filling defects is important, because they may represent a process central to cerebral malaria pathogenesis: neurovascular sequestration. We have developed and validated a framework that can automatically detect intravascular filling defects in fluorescein angiogram images. It first employs a state-of-the-art segmentation approach to extract the vessels from images and then divide them into individual segments by geometrical analysis.

Automated detection of leakage in fluorescein angiography images with application to malarial retinopathy.

The detection and assessment of leakage in retinal fluorescein angiogram images is important for the management of a wide range of retinal diseases. We have developed a framework that can automatically detect three types of leakage (large focal, punctate focal, and vessel segment leakage) and validated it on images from patients with malarial retinopathy. This framework comprises three steps: vessel segmentation, saliency feature generation and leakage detection.

Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of malawian children with fatal cerebral malaria.

Background: Malarial retinopathy (MR) has diagnostic and prognostic value in children with Plasmodium falciparum cerebral malaria (CM). A clinicopathological correlation between observed retinal changes during life and the degree of sequestration of parasitized red blood cells was investigated in ocular and cerebral vessels at autopsy.

Methods: In 18 Malawian children who died from clinically defined CM, we studied the intensity of sequestration and the maturity of sequestered parasites in the retina, in nonretinal ocular tissues, and in the brain.

A comprehensive texture segmentation framework for segmentation of capillary non-perfusion regions in fundus fluorescein angiograms.

Capillary non-perfusion (CNP) in the retina is a characteristic feature used in the management of a wide range of retinal diseases. There is no well-established computation tool for assessing the extent of CNP. We propose a novel texture segmentation framework to address this problem.

Cerebral malaria in children: using the retina to study the brain.

Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria.

Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting.

What happens to intraocular pressure at high altitude?

Purpose: To investigate changes of intraocular pressure on ascent to high altitude.

Methods: The Apex 2 medical research expedition provided the opportunity to measure intraocular pressure (IOP) and central corneal thickness (CCT) in 76 healthy lowlanders. They all arrived in La Paz, Bolivia (altitude, 3700 m), where they spent 4 days before being driven more than 2 hours to the Cosmic Physics Laboratory at Chacaltaya (5200 m) where they stayed for 7 days.