Michael J Boivin1,2,3, Alla Sikorskii1,4, Noeline Nakasujja5, Horacio Ruiseñor-Escudero6, Itziar Familiar-Lopez6, Robert O Opoka7, Bruno Giordani8,9,10,11. 1. From the Departments of Psychiatry. 2. Neurology and Ophthalmology, Michigan State University, East Lansing, Michigan. 3. Department of Psychiatry, University of Michigan, Ann Arbor, Michigan. 4. Department of Statistics and Probability, Michigan State University, East Lansing, Michigan. 5. Department of Psychiatry, Makerere University, Kampala, Uganda. 6. Department of Psychiatry, Michigan State University, East Lansing, Michigan. 7. Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda, Departments of. 8. Psychiatry. 9. Psychology. 10. Neurology. 11. Nursing, University of Michigan, Ann Arbor, Michigan.
Abstract
BACKGROUND: We explored 3 immunopathogenic biomarkers collected during acute malaria illness as potential moderators of gains from a computerized cognitive rehabilitation training (CCRT) intervention. METHOD:Von Willebrand Factor (vWF), tumor necrosis factor (TNF) and Regulated on Activation, Normal T Expressed and Secreted (RANTES) were assayed from plasma and cerebral spinal fluid (CSF) of children during acute severe malaria anemia or cerebral malaria. Two years after acute malaria illness, 150 surviving children and 150 nonmalaria community controls (CCs) from their households 6-12 years old entered a 3-arm randomized controlled trial of titrating and nontitrating CCRT against no CCRT. Tests of cognition [Kaufman Assessment Battery for Children (KABC)], Tests of Variables of Attention and Achenbach Child Behavior Checklist (CBCL) were administered before and after 24 CCRT sessions over a 3-month period, and at 1-year follow-up. Differences in outcomes by trial arms and biomarker levels were evaluated using linear mixed effects models. RESULTS:Severe malaria survivors with lower levels of vWF, lower CSF levels of TNF and higher levels of plasma and CSF RANTES had better KABC cognitive performance after both titrating and nontitrating CCRT compared with no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and nontitrating CCRT, whereas high TNF plasma was predictive of the benefit for both interventions. These biomarker moderating effects were not evident for CC children. CONCLUSIONS:Severe malaria immunopathogenic biomarkers may be related to poorer long-term brain/behavior function as evidenced by diminished benefit from a computerized cognitive rehabilitation intervention.
RCT Entities:
BACKGROUND: We explored 3 immunopathogenic biomarkers collected during acute malaria illness as potential moderators of gains from a computerized cognitive rehabilitation training (CCRT) intervention. METHOD:Von Willebrand Factor (vWF), tumor necrosis factor (TNF) and Regulated on Activation, Normal T Expressed and Secreted (RANTES) were assayed from plasma and cerebral spinal fluid (CSF) of children during acute severe malaria anemia or cerebral malaria. Two years after acute malaria illness, 150 surviving children and 150 nonmalaria community controls (CCs) from their households 6-12 years old entered a 3-arm randomized controlled trial of titrating and nontitrating CCRT against no CCRT. Tests of cognition [Kaufman Assessment Battery for Children (KABC)], Tests of Variables of Attention and AchenbachChild Behavior Checklist (CBCL) were administered before and after 24 CCRT sessions over a 3-month period, and at 1-year follow-up. Differences in outcomes by trial arms and biomarker levels were evaluated using linear mixed effects models. RESULTS:Severe malaria survivors with lower levels of vWF, lower CSF levels of TNF and higher levels of plasma and CSF RANTES had better KABC cognitive performance after both titrating and nontitrating CCRT compared with no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and nontitrating CCRT, whereas high TNF plasma was predictive of the benefit for both interventions. These biomarker moderating effects were not evident for CC children. CONCLUSIONS: Severe malaria immunopathogenic biomarkers may be related to poorer long-term brain/behavior function as evidenced by diminished benefit from a computerized cognitive rehabilitation intervention.
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