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Malar J. 2018 Mar 23;17(1):125. doi: 10.1186/s12936-018-2272-y.

Cerebrospinal fluid Plasmodium falciparum histidine-rich protein-2 in pediatric cerebral malaria.

Author information

1
Division of Critical Care and Hospitalist Neurology, Department of Neurology, Columbia University Medical Center, 177 Fort Washington Avenue, Milstein Hospital, 8GS-300, New York, NY, 10032, USA. ktt2115@cumc.columbia.edu.
2
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. jimmyvareta@gmail.com.
3
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
4
Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi.
5
Neuroradiology Division, Department of Imaging Sciences, University of Rochester, Rochester, NY, USA.
6
Queen Elizabeth Central Hospital, Blantyre, Malawi.
7
Epilepsy Division, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
8
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
9
Department of Eye and Vision Science, University of Liverpool, Liverpool, UK.
10
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
11
Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
12
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Abstract

BACKGROUND:

Cerebral malaria (CM) causes a rapidly developing coma, and remains a major contributor to morbidity and mortality in malaria-endemic regions. This study sought to determine the relationship between cerebrospinal fluid (CSF) Plasmodium falciparum histidine rich protein-2 (PfHRP-2) and clinical, laboratory and radiographic features in a cohort of children with retinopathy-positive CM.

METHODS:

Patients included in the study were admitted (2009-2013) to the Pediatric Research Ward (Queen Elizabeth Central Hospital, Blantyre, Malawi) meeting World Health Organization criteria for CM with findings of malarial retinopathy. Enzyme-linked immunosorbent assay was used to determine plasma and CSF PfHRP-2 levels. Wilcoxon rank-sum tests and multivariable logistic regression analysis assessed the association of clinical and radiographic characteristics with the primary outcome of death during hospitalization.

RESULTS:

In this cohort of 94 patients, median age was 44 (interquartile range 29-62) months, 53 (56.4%) patients were male, 6 (7%) were HIV-infected, and 10 (11%) died during hospitalization. Elevated concentrations of plasma lactate (p = 0.005) and CSF PfHRP-2 (p = 0.04) were significantly associated with death. On multivariable analysis, higher PfHRP-2 in the CSF was associated with death (odds ratio 9.00, 95% confidence interval 1.44-56.42) while plasma PfHRP-2 was not (odds ratio 2.05, 95% confidence interval 0.45-9.35).

CONCLUSIONS:

Elevation of CSF, but not plasma PfHRP-2, is associated with death in this paediatric CM cohort. PfHRP-2 egress into the CSF may represent alteration of blood brain barrier permeability related to the sequestration of parasitized erythrocytes in the cerebral microvasculature.

KEYWORDS:

Cerebrospinal fluid; Coma; Parasitic infections

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