Retinopathy and microcirculation in adult severe malaria

Maude, Richard J.; Sayeed, Abdullah Abu; Beare, Nicholas A. V.; Charunwatthana, Prakaykaew; Faiz, Abul; Hossain, Amir; Yunus, Emran Bin; Hoque, Gofranul; Hasan, Mohammad Rashedul; White, Nicholas J.; Day, Nicholas P. J.; Dondorp, Arjen M.

doi:10.1186/1475-2875-9-s2-i7

Cited by 2 publications

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“…Thin and thick blood smears [3] Rapid diagnostic test (RDT) [3] Polymerase chain reaction (PCR) [3] Malaria retinopathy [174,175,176] Lumbar puncture [177] Fundoscopy (direct and indirect retinoscopy) [142,174] Electroencephalogram (EEG) [314] Cerebral fluid sample (CFS) [315] Cerebral imaging (MRI) [316] in the brain parenchyma. [25,142,156,157] This results in increase fluid leakage, vasogenic edema, and herniation of the brain.…”

Section: Diagnostic Methods Referencesmentioning

confidence: 99%

“…Currently, an efficient and safe way to evaluate CM blood obstruction is through assessment for malarial retinopathy by retinal observation. [174][175][176] The presence of malarial retinopathy is an important clinical feature that distinguishes CM subjects from those with alternative pathologies, such as meningitis. To further confirm CM diagnosis in most patients, lumbar puncture is highly recommended in other to exclude other bacterial infections.…”

Section: Diagnosis Of Cerebral Malariamentioning

confidence: 99%

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Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models

2022

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Reorganization of host red blood cells by the malaria parasite Plasmodium falciparum enables their sequestration via attachment to the microvasculature. This artificially increases the dwelling time of the infected red blood cells within inner organs such as the brain, which can lead to cerebral malaria. Cerebral malaria is the deadliest complication patients infected with P. falciparum can experience and still remains a major public health concern despite effective antimalarial therapies. Here, the current understanding of the effect of P. falciparum cytoadherence and their secreted proteins on structural features of the human blood-brain barrier and their involvement in the pathogenesis of cerebral malaria are highlighted. Advanced 2D and 3D in vitro models are further assessed to study this devastating interaction between parasite and host. A better understanding of the molecular mechanisms leading to neuronal and cognitive deficits in cerebral malaria will be pivotal in devising new strategies to treat and prevent blood-brain barrier dysfunction and subsequent neurological damage in patients with cerebral malaria. MalariaMalaria is an ancient mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. According to the latest World Malaria Report published by the World Health

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Section: Diagnostic Methods Referencesmentioning

confidence: 99%

Section: Diagnosis Of Cerebral Malariamentioning

confidence: 99%

Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models

2022

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“…As the retina and brain share anatomically similar structures with the retinal vasculature considered a direct extension of cerebral vasculature, visualization of retinal changes in CM can provide insights into cerebral pathology (Maude et al, 2009). Among 164 children with retinal findings assessed, the most frequent abnormalities noted were retinal hemorrhages in 56.1% (92/164), macular whitening in 37.2% (61/164), vessel color changes in 25.0% (41/164), and peripheral whitening in 24.4% (40/164).…”

Section: Retinopathy the Kidney And Brain Injurymentioning

confidence: 99%

“…The pathogenesis of cerebral malaria in children includes radiologic evidence of cerebral edema (Newton et al, 1994;Seydel et al, 2015;Sahu et al, 2021), focal blood-brain-barrier (BBB) disruption (Brown et al, 1999(Brown et al, , 2001Medana and Turner, 2006;Greiner et al, 2015), pronounced metabolic changes that include altered amino acid metabolism (Enwonwu et al, 1999;Lopansri et al, 2006;Gupta et al, 2017;Leopold et al, 2019;Conroy et al, 2022), acidosis (Taylor et al, 1993;Krishna et al, 1994;von Seidlein et al, 2012), and an accumulation of neuroactive metabolites (Erhardt et al, 2001;Medana et al, 2003;Holmberg et al, 2017). Pediatric CM is also characterized by a series of retinal changes that mirror findings in the brain at autopsy (Maude et al, 2009;Barrera et al, 2015), including hemorrhages, retinal whitening suggestive of tissue ischemia (Beare et al, 2009b), vessel color changes detected on indirect ophthalmoscopy, and papilledema (reviewed in Beare et al, 2004Beare et al, , 2009aMaude et al, 2009;Barrera et al, 2015). Finally, there is emerging evidence that acute kidney injury (AKI) is an important mediator of disease severity and an independent risk factor for neurocognitive deficits and behavioral problems in survivors (Conroy et al, 2016(Conroy et al, , 2019Namazzi et al, 2022a,b).…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis

Conroy

Datta

Opoka

et al. 2023

Front. Hum. Neurosci.

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IntroductionCerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria.MethodsWe evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum.ResultsThe mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain.ConclusionIn children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.

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Retinopathy and microcirculation in adult severe malaria

Cited by 2 publications

References 0 publications

Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models

Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis

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