Identification of Malaria Retinopathy Improves the Specificity of the Clinical Diagnosis of Cerebral Malaria: Findings from a Prospective Cohort Study

International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan, USA.
The American journal of tropical medicine and hygiene (Impact Factor: 2.7). 02/2010; 82(2):231-4. DOI: 10.4269/ajtmh.2010.09-0532
Source: PubMed


The diagnosis of cerebral malaria (CM) is difficult to confirm in endemic regions with limited neurodiagnostics. Accurate diagnoses are critical for trials and outcomes studies. Findings from an autopsy-based study suggest that identifying malaria retinopathy in children satisfying the standard clinical case definition of CM improves our ability to accurately diagnose CM in vivo. In a post hoc analysis of a prospective exposure-control study to evaluate CM as a risk factor for epilepsy, we stratified children meeting the standard case definition by their retinopathy status (presence versus absence) and compared these groups for pre-existing risk factors for epilepsy. We also compared them to the concurrently enrolled, non-comatose controls. Children meeting the standard case definition of CM who lacked malaria retinopathy had a higher prevalence of pre-existing developmental problems and family history of epilepsy. This subset of patients may represent children with a pre-existing propensity to adverse neurologic symptoms and outcomes.

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Available from: Peter W Kaplan
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    • "Poor language skills are associated with difficulties in emotional regulation and problem behaviors (Qi & Kaiser, 2004; Vallotton & Ayoub, 2011), which may impair social functioning and schooling ability later in the child's life. Studies in African children show that behavioral problems appear much later after CM (Birbeck, Molyneux, et al., 2010; Idro, Kakooza-Mwesige, et al., 2010). It is not fully understood how poor language skills, which appear much earlier, are associated with these behavioral problems that appear much later. "
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    ABSTRACT: This study assessed the effects of cerebral malaria (CM) and severe malarial anemia (SMA) on individual neurocognitive domains. Eighty children with CM, 86 with SMA, and 61 community children (CC) were assessed for gross motor skills, fine motor skills, visual reception, receptive language, and expressive language a week after discharge (CM or SMA) or at enrolment (CC), and 6 and 12 months later. At 12-months follow-up, children with CM had significantly lower scores than CC for all outcomes. Children with SMA had significantly lower scores than CC for visual reception, receptive language, and expressive language, and scores that were lower but did not reach significance for gross and fine motor skills. Children with CM had significantly lower scores than children with SMA for fine motor skills. Children with SMA and CM have long-term impairment in multiple neurocognitive domains. Fine motor skills may be affected more profoundly in CM than SMA.
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    • "wholemounts. The retina parallels the pathological changes in the brain in both human and experimental cerebral malaria (Chan- Ling et al., 1992; White et al., 2009), and retinal changes have considerable diagnostic and pathophysiological significance in the human condition (Beare et al., 2004; White et al., 2009; Birbeck et al., 2010). Astrogliosis in murine malaria is seen in cerebral malaria but not in severe anemia (Medana et al., 1996; Ampawong et al., 2014). "
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    ABSTRACT: There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma (IFN-γ). In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by IFN-γ in the pathogenesis of this often fatal and debilitating condition.
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    • "Recently, endothelial activation markers such as ang-2, soluble Tie-2 receptor, vWF have been shown to be associated with severe malaria [22,25]. Furthermore ang-2 is associated with retinopathy [25], a feature identified as a surrogate marker for cerebral sequestration [5,26] and a recent study found fibrin deposition in the brain to be associated with sequestration of IE [27]. If there is a connection between parasite var expression patterns and disease severity, through mechanisms involving sequestration and endothelial activation we would expect to observe a relationship between the expression of the var subset associated with severe malaria and markers of endothelial activation. "
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