Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria
Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a w...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-01-01
|
Series: | Malaria Journal |
Subjects: | |
Online Access: | https://doi.org/10.1186/s12936-020-03545-6 |
id |
doaj-336cc6a2e397413ea27600dfafdda385 |
---|---|
record_format |
Article |
spelling |
doaj-336cc6a2e397413ea27600dfafdda3852021-01-10T12:57:51ZengBMCMalaria Journal1475-28752021-01-0120111010.1186/s12936-020-03545-6Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malariaBenson J. Ouma0Paul Bangirana1John M. Ssenkusu2Dibyadyuti Datta3Robert O. Opoka4Richard Idro5Kevin C. Kain6Chandy C. John7Andrea L. Conroy8Department of Medical Microbiology, College of Health Sciences, Makerere UniversityDepartment of Psychiatry, College of Health Sciences, Makerere UniversityDepartment of Epidemiology and Biostatistics, College of Health Sciences, Makerere UniversityRyan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of MedicineDepartment of Paediatrics and Child Health, Makerere University College of Health SciencesDepartment of Paediatrics and Child Health, Makerere University College of Health SciencesDepartment of Medicine, University of Toronto and University Health NetworkRyan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of MedicineRyan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of MedicineAbstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.https://doi.org/10.1186/s12936-020-03545-6Angiopoietin-2Severe malariaCognitionChildren |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Benson J. Ouma Paul Bangirana John M. Ssenkusu Dibyadyuti Datta Robert O. Opoka Richard Idro Kevin C. Kain Chandy C. John Andrea L. Conroy |
spellingShingle |
Benson J. Ouma Paul Bangirana John M. Ssenkusu Dibyadyuti Datta Robert O. Opoka Richard Idro Kevin C. Kain Chandy C. John Andrea L. Conroy Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria Malaria Journal Angiopoietin-2 Severe malaria Cognition Children |
author_facet |
Benson J. Ouma Paul Bangirana John M. Ssenkusu Dibyadyuti Datta Robert O. Opoka Richard Idro Kevin C. Kain Chandy C. John Andrea L. Conroy |
author_sort |
Benson J. Ouma |
title |
Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria |
title_short |
Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria |
title_full |
Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria |
title_fullStr |
Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria |
title_full_unstemmed |
Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria |
title_sort |
plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in ugandan children following severe malaria |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2021-01-01 |
description |
Abstract Background Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated. Methods Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini–Hochberg Procedure of False Discovery Rate. Results Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. Conclusion Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years. |
topic |
Angiopoietin-2 Severe malaria Cognition Children |
url |
https://doi.org/10.1186/s12936-020-03545-6 |
work_keys_str_mv |
AT bensonjouma plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT paulbangirana plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT johnmssenkusu plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT dibyadyutidatta plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT robertoopoka plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT richardidro plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT kevinckain plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT chandycjohn plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria AT andrealconroy plasmaangiopoietin2isassociatedwithagerelateddeficitsincognitivesubscalesinugandanchildrenfollowingseveremalaria |
_version_ |
1724341958614188032 |