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1.
World Health Organization, 2015. World Malaria Report 2015. Geneva, Switzerland: World Health Organization.
-
2.
Newton CR, Hien TT, White N, 2000. Cerebral malaria. J Neurol Neurosurg Psychiatry 69: 433–441.
-
3.
John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ, 2008. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122: e92–e99.
-
4.
Ponsford MJ, Medana IM, Parapansilp P, Hien TT, Lee SJ, Dondorp AM, Esiri MM, Day NP, White NJ, Turner GD, 2012. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis 205: 663–671.
-
5.
MacCormick IJ, Beare NA, Taylor TE, Barrera V, White VA, Hiscott P, Molyneux ME, Dhillon B, Harding SP, 2014. Cerebral malaria in children: using the retina to study the brain. Brain 137: 2119–2142.
-
6.
Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME, 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10: 143–145.
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Beare NA, Southern C, Chalira C, Taylor TE, Molyneux ME, Harding SP, 2004. Prognostic significance and course of retinopathy in children with severe malaria. Arch Ophthalmol 122: 1141–1147.
-
8.
White VA, Lewallen S, Beare NA, Kayira K, Carr RA, Taylor TE, 2001. Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans R Soc Trop Med Hyg 95: 618–621.
-
9.
Lewallen S, White VA, Whitten RO, Gardiner J, Hoar B, Lindley J, Lochhead J, McCormick A, Wade K, Tembo M, Mwenechanyana J, Molyneux ME, Taylor TE, 2000. Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria. Arch Ophthalmol 118: 924–928.
-
10.
Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME, 2009. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 199: 263–271.
-
11.
Barrera V, Hiscott PS, Craig AG, White VA, Milner DA, Beare NA, MacCormick IJ, Kamiza S, Taylor TE, Molyneux ME, Harding SP, 2015. Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of Malawian children with fatal cerebral malaria. J Infect Dis 211: 1977–1986.
-
12.
Lewallen S, Bronzan RN, Beare NA, Harding SP, Molyneux ME, Taylor TE, 2008. Using malarial retinopathy to improve the classification of children with cerebral malaria. Trans R Soc Trop Med Hyg 102: 1089–1094.
-
13.
Postels DG, Birbeck GL, 2011. Children with retinopathy-negative cerebral malaria: a pathophysiological puzzle. Pediatr Infect Dis J 30: 953–956.
-
14.
Essuman VA, Ntim-Amponsah CT, Astrup BS, Adjei GO, Kurtzhals JA, Ndanu TA, Goka B, 2010. Retinopathy in severe malaria in Ghanaian children: overlap between fundus changes in cerebral and non-cerebral malaria. Malar J 9: 232.
-
15.
Brand NR, Opoka RO, Hamre KES, John CC, 2016. Differing causes of lactic acidosis in cerebral malaria and severe malarial anemia may explain differences in acidosis-related mortality. PLOS One 11: e0163728.
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16.
Trang TT, Phu NH, Vinh H, Hien TT, Cuong BM, Chau TT, Mai NT, Waller DJ, White NJ, 1992. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis 15: 874–880.
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17.
von Seidlein L, Olaosebikan R, Hendriksen IC, Lee SJ, Adedoyin OT, Agbenyega T, Nguah SB, Bojang K, Deen JL, Evans J, Fanello CI, Gomes E, Pedro AJ, Kahabuka C, Karema C, Kivaya E, Maitland K, Mokuolu OA, Mtove G, Mwanga-Amumpaire J, Nadjm B, Nansumba M, Ngum WP, Onyamboko MA, Reyburn H, Sakulthaew T, Silamut K, Tshefu AK, Umulisa N, Gesase S, Day NP, White NJ, Dondorp AM, 2012. Predicting the clinical outcome of severe falciparum malaria in African children: findings from a large randomized trial. Clin Infect Dis 54: 1080–1090.
-
18.
Seydel KB, Fox LL, Glover SJ, Reeves MJ, Pensulo P, Muiruri A, Mpakiza A, Molyneux ME, Taylor TE, 2012. Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children. J Infect Dis 206: 309–318.
-
19.
Yeo TW, Lampah DA, Tjitra E, Gitawati R, Kenangalem E, Piera K, Granger DL, Lopansri BK, Weinberg JB, Price RN, Duffull SB, Celermajer DS, Anstey NM, 2009. Relationship of cell-free hemoglobin to imparied endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria. J Infect Dis 200: 1522–1529.
-
20.
Yeo TW, Lampah DA, Kenangalem E, Tjitra E, Weinberg JB, Granger DL, Price RN, Anstey NM, 2014. Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria. J Infect Dis 210: 1627–1632.
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21.
Polder TW, Jerusalem CR, Eling WM, 1991. Morphological characteristics of intracerebral arterioles in clinical (Plasmodium falciparum) and experimental (Plasmodium berghei) cerebral malaria. J Neurol Sci 101: 35–46.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 380 | 312 | 21 |
| Full Text Views | 345 | 12 | 2 |
| PDF Downloads | 133 | 17 | 2 |
Clinical Comparison of Retinopathy-Positive and Retinopathy-Negative Cerebral Malaria
Chandler Villaverde
Chandler Villaverde
The Warren Alpert Medical School, Brown University, Providence, Rhode Island.
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Ruth Namazzi
Ruth Namazzi
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
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Estela Shabani
Estela Shabani
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Department of Pediatrics, Indiana University, Indianapolis, Indiana.
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Department of Pediatrics, Indiana University, Indianapolis, Indiana.
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Robert O. Opoka
Robert O. Opoka
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
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Chandy C. John
Chandy C. John
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Department of Pediatrics, Indiana University, Indianapolis, Indiana.
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Department of Pediatrics, Indiana University, Indianapolis, Indiana.
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Cerebral 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.
Author Notes
Financial support: This work was supported by the U.S. National Institutes of Health National Institute of Neurological Disorders and Stroke and the Fogarty International Center (R01 NS055349 and D43 NS078280) and the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at the University of Minnesota. Chandler Villaverde is a Doris Duke International Clinical Research Fellow.
Authors' addresses: Chandler Villaverde, The Warren Alpert Medical School, Brown University, Providence, RI, E-mail: chandler_villaverde@brown.edu. Ruth Namazzi and Robert O. Opoka, Makerere University College of Health Sciences, Kampala, Uganda, E-mails: namazzi101@gmail.com and opokabob@yahoo.com. Estela Shabani, Department of Pediatrics, Indiana University, Indianapolis, IN, E-mail: shaba026@umn.edu. Chandy C. John, Ryan White Center for Pediatric Infectious Disease and Global Health, Indianapolis, IN, E-mail: chjohn@iu.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2015. World Malaria Report 2015. Geneva, Switzerland: World Health Organization.
-
2.
Newton CR, Hien TT, White N, 2000. Cerebral malaria. J Neurol Neurosurg Psychiatry 69: 433–441.
-
3.
John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, Wu B, Boivin MJ, 2008. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics 122: e92–e99.
-
4.
Ponsford MJ, Medana IM, Parapansilp P, Hien TT, Lee SJ, Dondorp AM, Esiri MM, Day NP, White NJ, Turner GD, 2012. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis 205: 663–671.
-
5.
MacCormick IJ, Beare NA, Taylor TE, Barrera V, White VA, Hiscott P, Molyneux ME, Dhillon B, Harding SP, 2014. Cerebral malaria in children: using the retina to study the brain. Brain 137: 2119–2142.
-
6.
Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME, 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10: 143–145.
-
7.
Beare NA, Southern C, Chalira C, Taylor TE, Molyneux ME, Harding SP, 2004. Prognostic significance and course of retinopathy in children with severe malaria. Arch Ophthalmol 122: 1141–1147.
-
8.
White VA, Lewallen S, Beare NA, Kayira K, Carr RA, Taylor TE, 2001. Correlation of retinal haemorrhages with brain haemorrhages in children dying of cerebral malaria in Malawi. Trans R Soc Trop Med Hyg 95: 618–621.
-
9.
Lewallen S, White VA, Whitten RO, Gardiner J, Hoar B, Lindley J, Lochhead J, McCormick A, Wade K, Tembo M, Mwenechanyana J, Molyneux ME, Taylor TE, 2000. Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria. Arch Ophthalmol 118: 924–928.
-
10.
Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME, 2009. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 199: 263–271.
-
11.
Barrera V, Hiscott PS, Craig AG, White VA, Milner DA, Beare NA, MacCormick IJ, Kamiza S, Taylor TE, Molyneux ME, Harding SP, 2015. Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of Malawian children with fatal cerebral malaria. J Infect Dis 211: 1977–1986.
-
12.
Lewallen S, Bronzan RN, Beare NA, Harding SP, Molyneux ME, Taylor TE, 2008. Using malarial retinopathy to improve the classification of children with cerebral malaria. Trans R Soc Trop Med Hyg 102: 1089–1094.
-
13.
Postels DG, Birbeck GL, 2011. Children with retinopathy-negative cerebral malaria: a pathophysiological puzzle. Pediatr Infect Dis J 30: 953–956.
-
14.
Essuman VA, Ntim-Amponsah CT, Astrup BS, Adjei GO, Kurtzhals JA, Ndanu TA, Goka B, 2010. Retinopathy in severe malaria in Ghanaian children: overlap between fundus changes in cerebral and non-cerebral malaria. Malar J 9: 232.
-
15.
Brand NR, Opoka RO, Hamre KES, John CC, 2016. Differing causes of lactic acidosis in cerebral malaria and severe malarial anemia may explain differences in acidosis-related mortality. PLOS One 11: e0163728.
-
16.
Trang TT, Phu NH, Vinh H, Hien TT, Cuong BM, Chau TT, Mai NT, Waller DJ, White NJ, 1992. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis 15: 874–880.
-
17.
von Seidlein L, Olaosebikan R, Hendriksen IC, Lee SJ, Adedoyin OT, Agbenyega T, Nguah SB, Bojang K, Deen JL, Evans J, Fanello CI, Gomes E, Pedro AJ, Kahabuka C, Karema C, Kivaya E, Maitland K, Mokuolu OA, Mtove G, Mwanga-Amumpaire J, Nadjm B, Nansumba M, Ngum WP, Onyamboko MA, Reyburn H, Sakulthaew T, Silamut K, Tshefu AK, Umulisa N, Gesase S, Day NP, White NJ, Dondorp AM, 2012. Predicting the clinical outcome of severe falciparum malaria in African children: findings from a large randomized trial. Clin Infect Dis 54: 1080–1090.
-
18.
Seydel KB, Fox LL, Glover SJ, Reeves MJ, Pensulo P, Muiruri A, Mpakiza A, Molyneux ME, Taylor TE, 2012. Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children. J Infect Dis 206: 309–318.
-
19.
Yeo TW, Lampah DA, Tjitra E, Gitawati R, Kenangalem E, Piera K, Granger DL, Lopansri BK, Weinberg JB, Price RN, Duffull SB, Celermajer DS, Anstey NM, 2009. Relationship of cell-free hemoglobin to imparied endothelial nitric oxide bioavailability and perfusion in severe falciparum malaria. J Infect Dis 200: 1522–1529.
-
20.
Yeo TW, Lampah DA, Kenangalem E, Tjitra E, Weinberg JB, Granger DL, Price RN, Anstey NM, 2014. Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria. J Infect Dis 210: 1627–1632.
-
21.
Polder TW, Jerusalem CR, Eling WM, 1991. Morphological characteristics of intracerebral arterioles in clinical (Plasmodium falciparum) and experimental (Plasmodium berghei) cerebral malaria. J Neurol Sci 101: 35–46.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 380 | 312 | 21 |
| Full Text Views | 345 | 12 | 2 |
| PDF Downloads | 133 | 17 | 2 |