Search

Background: In patients with cerebral malaria (CM), retinal angiography allows the study of infected central nervous system microvasculature in vivo. We aimed to examine retinal perfusion in children with CM by use of fluorescein angiography to investigate the pathophysiology of CM., Methods: We performed fluorescein angiography on children with CM admitted to Queen Elizabeth Central Hospital, Malawi. We related angiograms to funduscopic findings., Results: Fluorescein angiography was performed for 34 patients with CM, and impaired perfusion was identified in 28 (82%). Areas of capillary nonperfusion (CNP) were seen in 26 patients (76%). Multiple, scattered areas of CNP were typical and topographically matched to retinal whitening. Larger retinal vessels were occluded in 9 patients (26%) who had associated ischemia. These vessels appeared white on ophthalmoscopy. Intravascular abnormalities were seen in 9 patients (26%), including filling defects and mottling of the blood column. Limited fluorescein leakage occurred in 15 patients (44%) and was not related to angiographic intravascular abnormalities or visible vessel discoloration., Conclusions: Impaired perfusion occurs in the retinal microvasculature of most children with CM. This is evidence for hypoxia and ischemia as important components in the pathogenesis of CM. Vessel occlusion and filling defects are likely to be due to sequestration of infected erythrocytes. Interventions which improve perfusion or limit hypoxic injury may be beneficial in CM.

The mechanisms leading to death in cerebral malaria (CM) remain unclear. We compared clinical and laboratory data among children with CM, categorized by ocular fundus findings, to elucidate differences that suggest different underlying pathological processes. From 1999-2005, standard examinations, treatment and record keeping were used for children with a clinical diagnosis of CM. Children were divided into ocular subgroups: normal fundus (N), malarial retinopathy (R), or papilloedema alone (P) and appropriate statistical tests were used to compare clinical and laboratory findings among groups. Eight hundred and eighty children who had eye examinations within 6 h of admission were included in the analysis. The groups differed significantly in case-fatality rates: Group P, 44.4% (95% CI 25.3-63.2), Group R, 18.0% (95% CI 15.6-22.3) and Group N, 7.0% (95% CI 4.2-9.8). There were also significant differences among the groups in blood pressure, prevalence of deep breathing, haematocrit, parasite density, platelet concentration and, among survivors, hours taken to recover from coma. Differences among groups suggest that different underlying pathophysiological processes are operating in children with CM defined by existing criteria. Our proposed classification, by improving the specificity of diagnosis, would enhance consistency among different study sites and prove useful in future research studies.

Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. The detection of malarial retinopathy is a candidate diagnostic test for cerebral malaria. Malarial retinopathy consists of a set of retinal abnormalities that is unique to severe malaria and common in children with cerebral malaria. Its presence and severity are related to risk of death and length of coma in survivors. A large, prospective autopsy study of children dying with cerebral malaria in Malawi found that malarial retinopathy was better than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. However, visualization has to date relied on specialist examination techniques. Further studies are planned to evaluate the usefulness of funduscopy by general clinicians in a variety of settings across Africa. Studies of the retina and retinal blood vessels provide an unparalleled opportunity to visualize an infected microvasculature and its effect on neural tissue in vivo. This report reviews current knowledge of malarial retinopathy, including its use as a diagnostic test in the comatose child, and its value as a tool for research into the pathophysiology of cerebral malaria.

Objectives: To relate retinal findings in children treated for severe malaria to disease outcome and to determine the course of changes in the fundus., Methods: A prospective study of children with cerebral malaria (CM) and severe malarial anemia admitted to the Malaria Research Project, Blantyre, Malawi, during 2 malaria seasons. Indirect and direct ophthalmoscopy were performed on admission and daily, subject to the patient's cooperation., Results: Three hundred twenty-six patients (91%) with complicated malaria were recruited. Two hundred seventy-eight patients had CM and of these 170 (61%) had some degree of retinopathy; 25 (53%) of 47 with severe malarial anemia had retinopathy. In CM, retinopathy was associated with subsequent death (relative risk, 3.7; 95% confidence interval, 1.6-8.5) and papilledema conferred the highest risk (relative risk, 4.5; 95% confidence interval, 2.7-7.6). Increasing severity of retinal signs was related to increasing risk of a fatal outcome (P<.05), independent of papilledema. In survivors, retinal signs were associated with prolonged time to recover consciousness (P<.001). Patients with severe malarial anemia had better outcomes and less severe retinopathy than those with CM. In 116 patients with CM, fundi were followed up longitudinally during admission and in 27 patients after hospital discharge. A large increase in retinal hemorrhages was associated with death (P =.02). Retinal signs resolved over 1 to 4 weeks without retinal sequelae., Conclusions: In childhood CM, severity of retinopathy is related to prolonged coma and death. Our results support the hypothesis that retinal signs in CM are related to cerebral pathophysiology.

Objective: To investigate retinal lesions in children with severe falciparum malaria., Methods: Color photography and fluorescein angiography were performed in consecutive children admitted to a pediatric high-dependency unit in Kenya during 1 malaria season. The presence and category of retinal lesion was compared with disease severity, clinical outcome, anemia, lactic acidosis, and parasite count., Results: Twenty-six patients with cerebral malaria and 14 patients who were prostrate were studied. Thirty-one of the patients had clinical features of ocular disease, including round, flame-shaped, and white-centered hemorrhages; peripheral and foveal retinal opacification; peripheral vascular occlusion; venous dilation; disc edema with hyperemia; and arterial pulsatility. Of 8 patients with retinal opacification, only 2 showed small, infrequent zones of capillary nonperfusion on fluorescein angiography; the leakage of dye at sites of opacification was not seen. Retinal opacification was significantly associated with a higher parasite count (P < .02). White-centered hemorrhages were significantly associated with a higher parasite count (P < .05), severe disease (p < .05), and severe anemia (P < .02)., Conclusions: The blood-retina barrier and retinal vascular flow remain substantially normal despite widespread pathological features. Retinal features in children with severe malaria are consistent with cellular hypoxia, nutritional deficiency, or both rather than with vascular occlusion; they support the concept of metabolic steal by parasites.