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

Barrera V, Hiscott PS, Craig AG, White VA, Milner DA, Beare NA, MacCormick IJ, Kamiza S, Taylor TE, Molyneux ME, Harding SP - J. Infect. Dis. (2014)

Bottom Line: MR severity correlated with percentage of microvessels parasitized in the retina, brain, and nonretinal tissues with some neuroectodermal components (all P < .01).In moderate/severe MR cases (n = 8), vascular congestion was more intense (ρ = 0.841; P < .001), sequestered parasites were more mature, and the quantity of extraerythrocytic hemozoin was higher, compared with mild MR cases (n = 5).In addition to being a valuable tool for clinical diagnosis, retinal observations give important information about neurovascular pathophysiology in pediatric CM.

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Affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool.

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Maturation stage of parasitized red blood cells (pRBCs) in retinal microvasculature. A, Representative image of retinal venules containing unpigmented (immature form, with parasite nucleus stained blue inside the infected RBC) stage pRBCs detected in patient 5. B and C, Box plots showing the relative number of unpigmented (white boxes) and pigmented (gray boxes) pRBCs sequestered in 100 retinal capillaries (B) and venules (C) across classification groups. There were 5 specimens in the group with no malaria retinopathy (MR), 5 in the mild MR group, and 8 in the moderate/severe (m/s) MR group. D, Representative image of retinal microvessel with extraerythrocytic hemozoin (HZ) from patient 2, who had m/s MR (E). Bar graphs showing the percentage of retinal capillaries and venules containing extraerythrocytic HZ across classification groups. Results are reported as means ± SD for each individual MR group. F, Box plots showing the percentage of parasitized retinal capillaries in the same patients as in panel E, but clustered by CM classification. CM1, sequestration of pRBCs in cerebral capillaries; CM2, sequestration of pRBCs in cerebral capillaries plus intravascular and perivascular pathology (Supplementary Table 1); CM3, sequestration of <21% of cerebral capillaries. Boxes denote medians and 25th and 75th percentiles. Data were analyzed by the Kruskal–Wallis test within classification groups. *P ≤ .05 and **P ≤ .01. Scale bars: 50 μm (A); 20 μm (D).
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JIU592F6: Maturation stage of parasitized red blood cells (pRBCs) in retinal microvasculature. A, Representative image of retinal venules containing unpigmented (immature form, with parasite nucleus stained blue inside the infected RBC) stage pRBCs detected in patient 5. B and C, Box plots showing the relative number of unpigmented (white boxes) and pigmented (gray boxes) pRBCs sequestered in 100 retinal capillaries (B) and venules (C) across classification groups. There were 5 specimens in the group with no malaria retinopathy (MR), 5 in the mild MR group, and 8 in the moderate/severe (m/s) MR group. D, Representative image of retinal microvessel with extraerythrocytic hemozoin (HZ) from patient 2, who had m/s MR (E). Bar graphs showing the percentage of retinal capillaries and venules containing extraerythrocytic HZ across classification groups. Results are reported as means ± SD for each individual MR group. F, Box plots showing the percentage of parasitized retinal capillaries in the same patients as in panel E, but clustered by CM classification. CM1, sequestration of pRBCs in cerebral capillaries; CM2, sequestration of pRBCs in cerebral capillaries plus intravascular and perivascular pathology (Supplementary Table 1); CM3, sequestration of <21% of cerebral capillaries. Boxes denote medians and 25th and 75th percentiles. Data were analyzed by the Kruskal–Wallis test within classification groups. *P ≤ .05 and **P ≤ .01. Scale bars: 50 μm (A); 20 μm (D).

Mentions: In moderate/severe MR cases, pigmented pRBCs were the most predominant forms, with unpigmented pRBCs composing <10% of the total amount of pRBCs sequestered, except patient 5 (Figure 6A). Unpigmented pRBCs were more commonly observed in retinopathy-negative and mild MR cases (Figure 6B and 6C). We used hemozoin as an additional marker of parasite maturation across classification groups (Figure 6D–E). In patients with no MR and those with mild MR, extraerythrocytic hemozoin was seen in <2% of retinal capillaries and <15% of retinal venules. Mean percentages (±SD) of retinal capillaries and venules containing extraerythrocytic hemozoin were high in the moderate/severe MR group (43% ± 24% and 59% ± 28%, respectively). The percentage of retinal capillaries with extraerythrocytic hemozoin was significantly greater in patients with cerebral sequestration plus additional vascular pathology in the brain (CM2) than in patients with cerebral sequestration alone (CM1; P < .05; Figure 6F), confirming previously published evidence for hemozoin in cerebral capillaries [2].Figure 6.


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

Barrera V, Hiscott PS, Craig AG, White VA, Milner DA, Beare NA, MacCormick IJ, Kamiza S, Taylor TE, Molyneux ME, Harding SP - J. Infect. Dis. (2014)

Maturation stage of parasitized red blood cells (pRBCs) in retinal microvasculature. A, Representative image of retinal venules containing unpigmented (immature form, with parasite nucleus stained blue inside the infected RBC) stage pRBCs detected in patient 5. B and C, Box plots showing the relative number of unpigmented (white boxes) and pigmented (gray boxes) pRBCs sequestered in 100 retinal capillaries (B) and venules (C) across classification groups. There were 5 specimens in the group with no malaria retinopathy (MR), 5 in the mild MR group, and 8 in the moderate/severe (m/s) MR group. D, Representative image of retinal microvessel with extraerythrocytic hemozoin (HZ) from patient 2, who had m/s MR (E). Bar graphs showing the percentage of retinal capillaries and venules containing extraerythrocytic HZ across classification groups. Results are reported as means ± SD for each individual MR group. F, Box plots showing the percentage of parasitized retinal capillaries in the same patients as in panel E, but clustered by CM classification. CM1, sequestration of pRBCs in cerebral capillaries; CM2, sequestration of pRBCs in cerebral capillaries plus intravascular and perivascular pathology (Supplementary Table 1); CM3, sequestration of <21% of cerebral capillaries. Boxes denote medians and 25th and 75th percentiles. Data were analyzed by the Kruskal–Wallis test within classification groups. *P ≤ .05 and **P ≤ .01. Scale bars: 50 μm (A); 20 μm (D).
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Related In: Results  -  Collection

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JIU592F6: Maturation stage of parasitized red blood cells (pRBCs) in retinal microvasculature. A, Representative image of retinal venules containing unpigmented (immature form, with parasite nucleus stained blue inside the infected RBC) stage pRBCs detected in patient 5. B and C, Box plots showing the relative number of unpigmented (white boxes) and pigmented (gray boxes) pRBCs sequestered in 100 retinal capillaries (B) and venules (C) across classification groups. There were 5 specimens in the group with no malaria retinopathy (MR), 5 in the mild MR group, and 8 in the moderate/severe (m/s) MR group. D, Representative image of retinal microvessel with extraerythrocytic hemozoin (HZ) from patient 2, who had m/s MR (E). Bar graphs showing the percentage of retinal capillaries and venules containing extraerythrocytic HZ across classification groups. Results are reported as means ± SD for each individual MR group. F, Box plots showing the percentage of parasitized retinal capillaries in the same patients as in panel E, but clustered by CM classification. CM1, sequestration of pRBCs in cerebral capillaries; CM2, sequestration of pRBCs in cerebral capillaries plus intravascular and perivascular pathology (Supplementary Table 1); CM3, sequestration of <21% of cerebral capillaries. Boxes denote medians and 25th and 75th percentiles. Data were analyzed by the Kruskal–Wallis test within classification groups. *P ≤ .05 and **P ≤ .01. Scale bars: 50 μm (A); 20 μm (D).
Mentions: In moderate/severe MR cases, pigmented pRBCs were the most predominant forms, with unpigmented pRBCs composing <10% of the total amount of pRBCs sequestered, except patient 5 (Figure 6A). Unpigmented pRBCs were more commonly observed in retinopathy-negative and mild MR cases (Figure 6B and 6C). We used hemozoin as an additional marker of parasite maturation across classification groups (Figure 6D–E). In patients with no MR and those with mild MR, extraerythrocytic hemozoin was seen in <2% of retinal capillaries and <15% of retinal venules. Mean percentages (±SD) of retinal capillaries and venules containing extraerythrocytic hemozoin were high in the moderate/severe MR group (43% ± 24% and 59% ± 28%, respectively). The percentage of retinal capillaries with extraerythrocytic hemozoin was significantly greater in patients with cerebral sequestration plus additional vascular pathology in the brain (CM2) than in patients with cerebral sequestration alone (CM1; P < .05; Figure 6F), confirming previously published evidence for hemozoin in cerebral capillaries [2].Figure 6.

Bottom Line: MR severity correlated with percentage of microvessels parasitized in the retina, brain, and nonretinal tissues with some neuroectodermal components (all P < .01).In moderate/severe MR cases (n = 8), vascular congestion was more intense (ρ = 0.841; P < .001), sequestered parasites were more mature, and the quantity of extraerythrocytic hemozoin was higher, compared with mild MR cases (n = 5).In addition to being a valuable tool for clinical diagnosis, retinal observations give important information about neurovascular pathophysiology in pediatric CM.

View Article: PubMed Central - PubMed

Affiliation: Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool.

Show MeSH
Related in: MedlinePlus