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BMC Medicine
Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Plasmodium Falciparum | Correspondence

What causes severe malaria and its complications in children? Lessons learned over the past 15 years

Authors: Andrea L. Conroy, Dibyadyuti Datta, Chandy C. John

Published in: BMC Medicine | Issue 1/2019

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Abstract

Over the past 15 years, malaria mortality has reduced by approximately 50%. However, malaria still causes more than 400,000 deaths annually, most of which occur in African children under 5 years of age. Significant advances in understanding the pathogenesis of the disease provide a basis for future work to prevent severe malaria and its complications. Herein, we provide an overview of advances in our understanding of severe malaria in African children over the past 15 years, highlighting key complications and identifying priorities to further reduce malaria-associated mortality.
Literature
1.
2.
Sypniewska P, Duda JF, Locatelli I, Althaus CR, Althaus F, Genton B. Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis. BMC Med. 2017;15:147.CrossRef
3.
von Seidlein L, Olaosebikan R, Hendriksen IC, Lee SJ, Adedoyin OT, Agbenyega T, Nguah SB, Bojang K, Deen JL, Evans J, et al. Predicting the clinical outcome of severe falciparum malaria in african children: findings from a large randomized trial. Clin Infect Dis. 2012;54(8):1080–90.CrossRef
4.
Bernabeu M, Smith JD. EPCR and malaria severity: the center of a perfect storm. Trends Parasitol. 2017;33(4):295–308.CrossRef
5.
Turner GD, Ly VC, Nguyen TH, Tran TH, Nguyen HP, Bethell D, Wyllie S, Louwrier K, Fox SB, Gatter KC, et al. Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol. 1998;152(6):1477–87.PubMedPubMedCentral
6.
Conroy AL, Glover SJ, Hawkes M, Erdman LK, Seydel KB, Taylor TE, Molyneux ME, Kain KC. Angiopoietin-2 levels are associated with retinopathy and predict mortality in Malawian children with cerebral malaria: a retrospective case-control study*. Crit Care Med. 2012;40(3):952–9.CrossRef
7.
Higgins SJ, Purcell LA, Silver KL, Tran V, Crowley V, Hawkes M, Conroy AL, Opoka RO, Hay JG, Quaggin SE, et al. Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria. Sci Transl Med. 2016;8(358):358ra128.CrossRef
8.
Barrera V, Hiscott PS, Craig AG, White VA, Milner DA, Beare NAV, MacCormick IJC, Kamiza S, Taylor TE, Molyneux ME, et al. Severity of retinopathy parallels the degree of parasite sequestration in the eyes and brains of Malawian children with fatal cerebral malaria. J Infect Dis. 2015;211(12):1977–86.CrossRef
9.
Seydel KB, Kampondeni SD, Valim C, Potchen MJ, Milner DA, Muwalo FW, Birbeck GL, Bradley WG, Fox LL, Glover SJ, et al. Brain swelling and death in children with cerebral malaria. N Engl J Med. 2015;372(12):1126–37.CrossRef
10.
Kessler A, Dankwa S, Bernabeu M, Harawa V, Danziger SA, Duffy F, Kampondeni SD, Potchen MJ, Dambrauskas N, Vigdorovich V, et al. Linking EPCR-binding PfEMP1 to brain swelling in pediatric cerebral malaria. Cell Host Microbe. 2017;22(5):601–14.e605.CrossRef
11.
Brand NR, Opoka RO, Hamre KES, John CC. Differing causes of lactic acidosis and deep breathing in cerebral malaria and severe malarial anemia may explain differences in acidosis-related mortality. PLoS One. 2016;11(9):e0163728.CrossRef
12.
Sriboonvorakul N, Ghose A, Hassan MMU, Hossain MA, Faiz MA, Pukrittayakamee S, Chotivanich K, Sukthana Y, Leopold SJ, Plewes K, et al. Acidosis and acute kidney injury in severe malaria. Malaria J. 2018;17:128.CrossRef
13.
Elphinstone RE, Conroy AL, Hawkes M, Hermann L, Namasopo S, Warren HS, John CC, Liles WC, Kain KC. Alterations in systemic extracellular heme and hemopexin are associated with adverse clinical outcomes in Ugandan children with severe malaria. J Infect Dis. 2016;214(8):1268–75.CrossRef
14.
KDIGO. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;2(Suppl):1–138.
15.
Conroy AL, Hawkes M, Elphinstone RE, Morgan C, Hermann L, Barker KR, Namasopo S, Opoka RO, John CC, Liles WC, et al. Acute kidney injury is common in pediatric severe malaria and is associated with increased mortality. Open Forum Infect Dis. 2016;3(2):ofw046.CrossRef
16.
17.
Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, Romero RA, Shapiro E, John CC. Severe malarial anemia is associated with long-term neurocognitive impairment. Clin Infect Dis. 2014;59(3):336–44.CrossRef
18.
John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics. 2008;122(1):e92–9.CrossRef
19.
Idro R, Marsh K, John CC, Newton CRJ. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr Res. 2010;68(4):267–74.CrossRef
20.
Shabani E, Ouma BJ, Idro R, Bangirana P, Opoka RO, Park GS, Conroy AL, John CC. Elevated cerebrospinal fluid tumor necrosis factor is associated with acute and long-term neurocognitive impairment in cerebral malaria. Parasite Immunol. 2017;39(7):e12438.CrossRef
21.
Holmberg D, Franzén-Röhl E, Idro R, Opoka RO, Bangirana P, Sellgren CM, Wickström R, Färnert A, Schwieler L, Engberg G, et al. Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria. Malaria J. 2017;16:303.CrossRef
Metadata
Title
What causes severe malaria and its complications in children? Lessons learned over the past 15 years
Authors
Andrea L. Conroy
Dibyadyuti Datta
Chandy C. John
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1291-z

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