Browsing by Author "Villaverde, Chandler"

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    Clinical Comparison of Retinopathy-Positive and Retinopathy-Negative Cerebral Malaria
    (American Society of Tropical Medicine and Hygiene, 2017-05) Villaverde, Chandler; Namazzi, Ruth; Shabani, Estela; Opoka, Robert O.; John, Chandy C.; Pediatrics, School of Medicine
    AbstractCerebral malaria (CM) is a severe and often lethal complication of falciparum malaria. A classic malaria retinopathy is seen in some (retinopathy-positive [RP]) children but not others (retinopathy-negative [RN]), and is associated with increased parasite sequestration. It is unclear whether RN CM is a severe nonmalarial illness with incidental parasitemia or a less severe form of the same malarial illness as RP CM. Understanding the clinical differences between RP and RN CM may help shed light on the pathophysiology of malarial retinopathy. We compared clinical history, physical examination, laboratory findings, and outcomes of RP (N = 167) and RN (N = 87) children admitted to Mulago Hospital, Kampala, Uganda. Compared with RN children, RP children presented with a longer history of illness, as well as physical examination and laboratory findings indicative of more severe disease and organ damage. The hospital course of RP children was complicated by longer coma duration and a greater transfusion burden than RN children. Mortality did not differ significantly between RP and RN children (14.4% versus 8.0%, P = 0.14). Further, severity of retinal hemorrhage correlated with the majority of variables that differed between RP and RN children. The data suggest that RP and RN CM may reflect the spectrum of illness in CM, and that RN CM could be an earlier, less severe form of disease.
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    Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria
    (Oxford University Press, 2020-11-10) Villaverde, Chandler; Namazzi, Ruth; Shabani, Estela; Park, Gregory S.; Datta, Dibyadyuti; Hanisch, Benjamin; Opoka, Robert O.; John, Chandy C.; Pediatrics, School of Medicine
    Background: Our prior study findings suggest that Plasmodium falciparum is the cause of disease in both malaria retinopathy-positive (RP) and most retinopathy-negative (RN) cerebral malaria (CM), and that absence of retinopathy and decreased disease severity in RN CM may be due to shorter duration of illness, lower parasite biomass, and decreased var gene expression in RN compared to RP CM. In the present study, we assessed the pathophysiology of RP and RN CM. Methods: We compared markers of systemic and central nervous system inflammation, oxidative stress, neuronal injury, systemic endothelial activation, angiogenesis, and platelet activation in Ugandan children with RP (n = 167) or RN (n = 87) CM. Results: RP children had higher plasma C-reactive protein (P = .013), ferritin and erythropoietin (both P < .001) levels, an elevated cerebrospinal fluid (CSF):plasma albumin ratio (P < .001), and higher CSF tau protein levels (P = .049) than RN children. Levels of plasma and CSF proinflammatory and anti-inflammatory cytokines and oxidative stress markers did not differ between RP and RN children. RN children had higher plasma levels of endothelin 1 (P = .003), platelet-derived growth factor (P = .012), and platelet factor 4 (P = .034). Conclusions: RP and RN CM may represent different phases of CM. RN CM may be driven by early vasospasm and platelet activation, whereas the more advanced RP CM is associated with greater inflammation, increased erythropoietic drive, blood-brain barrier breakdown, and neuronal injury, each of which may contribute to greater disease severity.