Browsing by Author "Boivin, Michael J."
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Item The Association between Cognition and Academic Performance in Ugandan Children Surviving Malaria with Neurological Involvement(PLoS One, 2013) Bangirana, Paul; Menk, Jeremiah; John, Chandy C.; Boivin, Michael J.; Hodges, James S.The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This study's objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement.62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention) and academic performance (reading, spelling, arithmetic) three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA) and structural equation models (SEM) were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance.In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, p<0.01) and Spelling (0.46, 0.13 to 0.78, p<0.01), Visual Spatial Skills was associated with Arithmetic (0.15, 0.03 to 0.26, p<0.05), and Learning was associated with Reading (0.06, 0.00 to 0.11, p<0.05). One latent cognitive factor was identified using EFA. The SEM found a strong association between this latent cognitive ability and each academic performance measure (P<0.0001). Working memory, visual spatial ability and learning were the best predictors of academic performance.Academic performance is strongly associated with the latent variable labelled “cognitive ability” which captures most of the variation in the individual specific cognitive outcome measures. Working memory, visual spatial skills, and learning together stood out as the best combination to predict academic performance.Item Cerebral Malaria in Children Is Associated With Long-term Cognitive Impairment(Pediatrics, 2008) John, Chandy C.; Bangirana, Paul; Byarugaba, Justus; Opoka, Robert O.; Idro, Richard; Jurek, Anne M.; Wu, Baolin; Boivin, Michael J.Cerebral malaria affects >785000 African children every year. We previously documented an increased frequency of cognitive impairment in children with cerebral malaria 6 months after their initial malaria episode. This study was conducted to determine the long-term effects of cerebral malaria on the cognitive function of these children.Children who were 5 to 12 years of age and presented to Mulago Hospital, Kampala, Uganda, with cerebral malaria (n = 44) or uncomplicated malaria (n = 54), along with healthy, asymptomatic community children (n = 89), were enrolled in a prospective cohort study of cognition. Cognitive testing was performed at enrollment and 2 years later. The primary outcome was presence of a deficit in ≥1 of 3 cognitive areas tested.At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in ≥1 area, as compared with 7.6% of community children. Deficits in children with cerebral malaria were primarily in the area of attention (cerebral malaria, 18.4%, vs community children, 2.5%). After adjustment for age, gender, nutrition, home environment, and school level, children with cerebral malaria had a 3.67-fold increased risk for a cognitive deficit compared with community children. Cognitive impairment at 2-year follow-up was associated with hyporeflexia on admission and neurologic deficits 3 months after discharge.Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors. Future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation.Item Cognition, Behaviour And Academic Skills After Cognitive Rehabilitation In Ugandan Children Surviving Severe Malaria: A Randomised Trial(BMC neurology, 2011) Bangirana, Paul; Allebeck, Peter; Boivin, Michael J.; John, Chandy C.; Page, Connie; Ehnvall, Anna; Musisi, SegganeInfection with severe malaria in African children is associated with not only a high mortality but also a high risk of cognitive deficits. There is evidence that interventions done a few years after the illness are effective but nothing is known about those done immediately after the illness. We designed a study in which children who had suffered from severe malaria three months earlier were enrolled into a cognitive intervention program and assessed for the immediate benefit in cognitive, academic and behavioral outcomes.This parallel group randomised study was carried out in Kampala City, Uganda between February 2008 and October 2010. Sixty-one Ugandan children aged 5 to 12 years with severe malaria were assessed for cognition (using the Kaufman Assessment Battery for Children, second edition and the Test of Variables of Attention), academic skills (Wide Range Achievement Test, third edition) and psychopathologic behaviour (Child Behaviour Checklist) three months after an episode of severe malaria. Twenty-eight were randomised to sixteen sessions of computerised cognitive rehabilitation training lasting eight weeks and 33 to a non-treatment group. Post-intervention assessments were done a month after conclusion of the intervention. Analysis of covariance was used to detect any differences between the two groups after post-intervention assessment, adjusting for age, sex, weight for age z score, quality of the home environment, time between admission and post-intervention testing and pre-intervention score. The primary outcome was improvement in attention scores for the intervention group. This trial is registered with Current Controlled Trials, number ISRCTN53183087.Significant intervention effects were observed in the intervention group for learning mean score (SE), [93.89 (4.00) vs 106.38 (4.32), P = 0.04] but for working memory the intervention group performed poorly [27.42 (0.66) vs 25.34 (0.73), P = 0.04]. No effect was observed in the other cognitive outcomes or in any of the academic or behavioural measures.In this pilot study, our computerised cognitive training program three months after severe malaria had an immediate effect on cognitive outcomes but did not affect academic skills or behaviour. Larger trials with follow-up after a few years are needed to investigate whether the observed benefits are sustained.Item Cognitive Impairment After Cerebral Malaria In Children: A Prospective Study(Pediatrics, 2007) Boivin, Michael J.; Bangirana, Paul; Byarugaba, Justus; Opoka, Robert O.; Idro, Richard; Jurek, Anne M.; John, Chandy C.This study was conducted to assess prospectively the frequency of cognitive deficits in children with cerebral malaria.Cognitive testing in the areas of working memory, attention, and learning was performed for Ugandan children 5 to 12 years of age with cerebral malaria (n = 44), children with uncomplicated malaria (n = 54), and healthy community children (n = 89) at admission and 3 and 6 months later.Six months after discharge, 21.4% of children with cerebral malaria had cognitive deficits, compared with 5.8% of community children. Deficits were seen in the areas of working memory (11.9% vs 2.3%) and attention (16.7% vs 2.3%). Children with cerebral malaria had a 3.7-fold increased risk of a cognitive deficit, compared with community children, after adjustment for age, gender, nutritional status, school level, and home environment. Among children with cerebral malaria, those with a cognitive deficit had more seizures before admission (mean: 4.1 vs 2.2) and a longer duration of coma (43.6 vs 30.5 hours), compared with those without a deficit. Children with uncomplicated malaria did not have an increased frequency of cognitive deficits.Cerebral malaria may be a major cause of cognitive impairment in children in sub-Saharan Africa. Cognitive deficits in children with cerebral malaria are more likely for those who have multiple seizures before effective treatment for cerebral malaria.Item Computerized Cognitive Rehabilitation Training for Ugandan Seniors Living with HIV: A Validation Study(Journal of Clinical Medicine, 2020) Ezeamama, Amara E.; Sikorskii, Alla; Sankar, Parvathy R.; Nakasujja, Noeline; Ssonko, Michael; Kaminski, Norbert E.; Guwatudde, David; Boivin, Michael J.; Giordani, BrunoThe feasibility, acceptability and preliminary efficacy of computerized cognitive rehabilitation therapy (CCRT) for mitigating neurocognitive decline was evaluated in African adults 50 years old. Eighty-one Ugandans with (n = 40) and without (n = 41) chronic human immunodeficiency viruses (HIV) were allocated CCRT—i.e., 20–45-min cognitive training sessions with culturally adapted video games delivered via Captain’s Log Software, or standard of care (SOC). Pre and post (i.e., 8-weeks later) intervention performance based neurocognitive tests, quality of life (QOL) and frailty related phenotype (FRP) were determined in all respondents. Multivariable linear regression estimated CCRT- vs. SOC-related di erences ( ) in neurocognitive batteries, QOL and FRP. E ect sizes (ES) for estimated were calculated. CCRT protocol was completed by 92.8% of persons allocated to it. Regardless of HIV status, CCRT was associated with higher performance in learning tests than SOC—interference list ( = 1.00, 95%CI: (0.02, 1.98); ES = 0.43) and delayed recall ( = 1.04, 95%CI: (0.06, 2.02); ES = 0.47). CCRT e ect on verbal fluency was clinically important (ES = 0.38), but statistical significance was not reached ( = 1.25, 95%CI: (0.09, 2.58)). Among HIV-positive adults, clinically important post-CCRT improvements were noted for immediate recall (ES = 0.69), working memory (ES = 0.51), verbal fluency (ES = 0.51), and timed gait (ES = 0.44) tasks. Among HIV-negative adults, CCRT resulted in moderate post-intervention improvement in learning tests (ES = 0.45) and large decline in FRP (ES = 0.71), without a positive e ect on simple attention and visuomotor coordination tasks. CCRT intervention is feasible among older Ugandan adults with potential benefit for learning and verbal fluency tests regardless of HIV status and lowering FRP in HIV-negative older adults.Item High Plasma Soluble CD163 During Infancy Is a Marker for Neurocognitive Outcomes in Early-Treated HIV-Infected Children(Journal of acquired immune deficiency syndromes, 2019) Benki-Nugent, Sarah F.; Martopullo, Ira; Laboso, Tony; Tamasha, Nancy; Wamalwa, Dalton C.; Tapia, Kenneth; Langat, Agnes; Obimbo, Elizabeth Maleche; Marra, Christina M.; Bangirana, Paul; Boivin, Michael J.; Stewart, Grace C. JohnMonocyte activation may contribute to neuronal injury in aviremic HIV-infected adults; data are lacking in children. We examined the relation between monocyte activation markers and early and long-term neurodevelopmental outcomes in early-treated HIV-infected children.Prospective study of infant and child neurodevelopmental outcomes nested within a randomized clinical trial () and extended cohort study in Kenya.HIV-infected infants (N=67) initiated ART at age <5 months. Plasma soluble (s) CD163 (sCD163), sCD14 and neopterin were measured pre-ART (entry) and 6 months later. Milestone attainment was ascertained monthly during 24 months and neuropsychological tests (NPTs) were performed at 5.8–8.2 years post-initiation of ART (N=27). The relationship between neurodevelopment and sCD163, sCD14 and neopterin at entry and 6 months post-ART was assessed using Cox proportional hazards models and linear regression.Infants with high entry sCD163 had unexpected earlier attainment of supported sitting (5 vs 6 mo.; P=0.006) and supported walking (10 vs 12 mo.; P =0.02) with trends in adjusted analysis. Infants with high 6-month post-ART sCD163 attained speech later (17 vs 15 mo.; P=0.006; aHR, 0.47; P=0.02), threw toys later (18 vs 17 mo.; P =0.01; aHR, 0.53; P =0.04), and at median 6.8 years post-ART, had worse NPT scores (adj. mean z-score differences, cognition, −0.42; P =0.07; short-term memory, −0.52; P =0.08; nonverbal test performance, −0.39, P =0.05).Prior to ART, monocyte activation may reflect transient neuroprotective mechanisms in infants. Following ART and viral suppression, monocyte activation may predict worse short- and long-term neurodevelopment outcomes.Item Immediate Neuropsychological And Behavioral Benefits Of Computerized Cognitive Rehabilitation In Ugandan Pediatric Cerebral Malaria Survivors(Journal of developmental and behavioral pediatrics, 2009) Bangirana, Paul; Giordani, Bruno; John, Chandy C.; Page, Connie; Opoka, Robert O.; Boivin, Michael J.Our earlier studies on Ugandan children surviving cerebral malaria showed cognitive deficits mainly in attention and memory. We now present the first study in sub-Saharan Africa to investigate the feasibility and potential benefits of computerized cognitive rehabilitation training on neuropsychological and behavioural functioning of children surviving cerebral malaria.A randomized trial in which 65 children admitted 45 months earlier with cerebral malaria were recruited at Mulago Hospital, Kampala, Uganda. For eight weeks, 32 of the children received weekly training sessions using Captain’s Log cognitive training software and the other 33 were assigned to a non treatment condition. Pre- and post-intervention assessments were completed using CogState, a computerized neuropsychological battery, measuring Visuomotor Processing Speed, Working Memory, Learning, Attention and Psychomotor Speed and the Child Behavior Checklist measuring Internalising Problems, Externalising Problems and Total Problems.Pre-intervention scores were similar between both groups. Treatment effects were observed on Visual Spatial Processing Speed (group effect (standard error) 0.14 (0.03); p< 0.001); on a Working Memory and Learning task (0.08 (0.02); p< 0.001), Psychomotor Speed (0.14 (0.07); p= 0.04) and on Internalising Problems (−3.80 (1.56); p= 0.02) after controlling for age, sex, school grade, quality of the home environment and weight for age z scores. Similar treatment effects were observed when no adjustments for the above covariates were made.Computerized cognitive training long after the cerebral malaria episode has immediate benefit on some neuropsychological and behavioral functions in African children. The long-term benefit of this intervention needs to be investigated.Item Implementing an early childhood school-based mental health promotion intervention in low-resource Ugandan schools: study protocol for a cluster randomized controlled trial(Trials, 2014) Huang, Keng-Yen; Nakigudde, Janet; Calzada, Esther; Boivin, Michael J.; Ogedegbe, Gbenga; Brotman, Laurie MillerChildren in Sub-Saharan Africa (SSA) are burdened by significant unmet mental health needs, but this region has limited access to mental health workers and resources to address these needs. Despite the successes of numerous school-based interventions for promoting child mental health, most evidence-based interventions are not available in SSA. This study will investigate the transportability of an evidence-based program from a developed country (United States) to a SSA country (Uganda). The approach includes task-shifting to early childhood teachers and consists of professional development (five days) to introduce strategies for effective behavior management and positive teacher-student interactions, and group-based consultation (14 sessions) to support adoption of effective practices and tailoring to meet the needs of individual students. Methods/Design: The design of this study is guided by two implementation frameworks, the Consolidated Framework for Implementation Research and the Teacher Training Implementation Model, that consider multidimensional aspects of intervention fidelity and contextual predictors that may influence implementation and teacher outcomes. Using a cluster randomized design, 10 schools in Uganda will be randomized to either the intervention group (five schools) or the waitlist control group (five schools). A total of 80 to 100 early childhood teachers will be enrolled in the study. Teacher utilization of evidence-based strategies and practices will be assessed at baseline, immediate post-intervention (six months after baseline), and at seven months post-intervention (during a new academic year). Fidelity measures will be assessed throughout the program implementation period (during professional development and consultation sessions). Individual teacher and contextual factors will be assessed at baseline. Data will be collected from multiple sources. Linear mixed-effect modeling, adjusting for school nesting, will be applied to address study questions. Discussion: The study will produce important information regarding the value of an evidence-based early intervention, and a theory-guided implementation process and tools designed for use in implementing early childhood evidence-based programs in SSA countries or resource-constrained community settings.Item Malaria With Neurological Involvement In Ugandan Children: Effect On Cognitive Ability, Academic Achievement And Behaviour(Malaria journal, 2011) Bangirana, Paul; Musisi, Seggane; Boivin, Michael J.; Ehnvall, Anna; John, Chandy C.; Bergemann, Tracy L.; Allebeck, PeterMalaria is a leading cause of ill health and neuro-disability in children in sub-Saharan Africa. Impaired cognition is a common outcome of malaria with neurological involvement. There is also a possibility that academic achievement may be affected by malaria with neurological involvement given the association between cognitive ability and academic achievement. This study investigated the effect of malaria with neurological involvement on cognitive ability, behaviour and academic achievement.This prospective case-control study was carried out in Kampala City, Uganda between February 2008 and October 2010. Sixty-two children with a history of malaria with neurological involvement were followed up and given assessments for cognitive ability (working memory, reasoning, learning, visual spatial skills and attention), behaviour (internalizing and externalizing problems) and academic achievement (arithmetic, spelling and reading) three months after the illness. Sixty-one community controls recruited from the homes or neighbouring families of the cases were also given the same assessments. Tests scores of the two groups were compared using analysis of covariance with age, sex, level of education, nutritional status and quality of the home environment as covariates. This study was approved by the relevant ethical bodies and informed consent sought from the caregivers.Children in the malaria group had more behavioural problems than the community controls for internalizing problems (estimated mean difference = -3.71, 95% confidence interval (CI), = -6.34 to -1.08, p = 0.007). There was marginal evidence of lower attention scores (0.40, CI = -0.05 to 0.86, p = 0.09). However, excluding one child from the analyses who was unable to perform the tests affected the attention scores to borderline significance (0.32, CI, = 0.01 to 0.62, p = 0.05). No significant differences were observed in other cognitive abilities or in academic achievement scores.Malaria with neurological involvement affects behaviour, with a minimal effect on attention but no detectable effect on academic achievement at three months post discharge. This study provides evidence that development of cognitive deficits after malaria with neurological involvement could be gradual with less effect observed in the short term compared to the long term.Item Neurocognitive and Motor Deficits in HIV-Infected Ugandan Children With High CD4 Cell Counts(Clinical Infectious Diseases, 2012) Ruel,Theodore D.; Boivin, Michael J.; Boal, Hannah E.; Bangirana, Paul; Charlebois,Edwin; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey,Grant; Achan, Jane; Akello, Carolyne; Kamya, Moses R.; Wong, Joseph K.Background. Human immunodeficiency virus (HIV) infection causes neurocognitive or motor function deficits in children with advanced disease, but it is unclear whether children with CD4 cell measures above the World health Organization (WHO) thresholds for antiretroviral therapy (ART) initiation suffer significant impairmentItem Psychosocial Adjustment in Ugandan Children: Coping With Human Immunodeficiency Virus Exposure, Lifetime Adversity, and Importance of Social Support(New Directions for Child and Adolescent Development, 2020) Tuke, Robert; Sikorskii, Alla; Zalwango, Sarah K.; Webster, Kyle D.; Ismail, Alexander; Pobee, Ruth A.; Barkin, Jennifer L.; Boivin, Michael J.; Giordani, Bruno; Ezeamama, Amara E.Cumulative lifetime adversity and social support were investigated as determinants of psychosocial adjustment (esteem, distress, hopefulness, positive outlook/ future aspirations, and sense of purpose) over 12months in 6–10-years-old HIV-infected, HIV-exposed uninfected and HIV-unexposed uninfected children from Uganda. Each determinant and psychosocial adjustment indicator was self-reported using standardized questionnaires administered at baseline, 6, and 12 months. Linear mixed effects models were used to relate time-varying lifetime adversity and social support to psychosocial adjustment over 12 months. Regardless of HIV status, higher adversity predicted lower esteem (coefficient b = −2.98, 95% confidence interval (CI): [−4.62, −1.35]) and increased distress (b =3.96, 95% CI: [1.29, 6.62]) but was not associated with hopefulness, positive outlook or sense of purpose. Low social support predicted higher distress (b =9.05, 95% CI: [7.36, 10.73]), lower positive outlookItem Rehabilitation for cognitive impairments after cerebral malaria in African children: strategies and limitations(Tropical Medicine & International Health, 2006) Bangirana, Paul; Idro, Richard; John, Chandy C.; Boivin, Michael J.Cerebral malaria results in short- to long-term cognitive impairments in many of its child survivors. Although some of the risk factors for impairments have been identified, no attempts have been made to address the plight of those who develop cognitive impairments. This paper discusses the burden of cognitive impairment caused by cerebral malaria and suggests some rehabilitation strategies based on brain injury and cognitive rehabilitation studies. Potential cognitive rehabilitation solutions such as cognitive exercises, environmental enrichment, nutritional supplementation, physical therapy and speech therapy are highlighted. The limitations of implementing these interventions and solutions are discussed in light of the limited human resources and infrastructure of the developing countries that are malaria endemic.Item Reliability of the Luganda version of the Child Behaviour Checklist in measuring behavioural problems after cerebral malaria(Child and adolescent psychiatry and mental health, 2009) Bangirana, Paul; Nakasujja, Noeline; Giordani, Bruno; Opoka, Robert O.; John, Chandy C.; Boivin, Michael J.No measure of childhood behaviour has been validated in Uganda despite the documented risks to behaviour. Cerebral malaria in children poses a great risk to their behaviour, however behavioural outcomes after cerebral malaria have not been described in children. This study examined the reliability of the Luganda version of the Child Behaviour Checklist (CBCL) and described the behavioural outcomes of cerebral malaria in Ugandan children.The CBCL was administered to parents of 64 children aged 7 to 16 years participating in a trial to improve cognitive functioning after cerebral malaria. These children were assigned to the treatment or control group. The CBCL parent ratings were completed for the children at baseline and nine weeks later. The CBCL was translated into Luganda, a local language, prior to its use. Baseline scores were used to calculate internal consistency using Cronbach Alpha. Correlations between the first and second scores of the control group were used to determine test-retest reliability. Multicultural norms for the CBCL were used to identify children with behavioural problems of clinical significance.The test-retest reliability and internal consistency of the Internalising scales were 0.64 and 0.66 respectively; 0.74 and 0.78 for the Externalising scale and 0.67 and 0.83 for Total Problems. Withdrawn/Depressed (15.6%), Thought Problems (12.5%), Aggressive Behaviour (9.4%) and Oppositional Defiant Behaviour (9.4%) were the commonly reported problems.The Luganda version of the CBCL is a fairly reliable measure of behavioural problems in Ugandan children. Depressive and thought problems are likely behavioural outcomes of cerebral malaria in children. Further work in children with psychiatric diagnoses is required to test its validity in a clinical setting.Item Seizure Activity And Neurological Sequelae In Ugandan Children Who Have Survived An Episode Of Cerebral Malaria(African health sciences, 2009) Opoka, Robert O.; Bangirana, Paul; Boivin, Michael J.; John, Chandy C.; Justus Byarugaba, JustusSeizures are a common presenting feature in children with cerebral malaria (CM) and neurologic deficits have been described in survivors of CM. However few prospective studies have described the frequency of seizure activity and neurologic deficits in survivors of CM over time.Eighty-two children aged 3 to 12 years who survived an episode of CM were followed up and monitored for seizure activity and neurologic deficits at discharge, 3, 6 and 24 months. Seventy six children with uncomplicated malaria (UM) and 105 healthy community controls (CC) age 3 to 12 years were recruited as comparison groups and the frequency of seizures in the 6 to 24 month follow-up period was compared in the 3 groups.Cumulative incidence of seizures increased over time in children with CM, with a total of 2 of 76 children (2.6%) reporting seizures at 3 months, 3 of 74 children (4.1%) at 6 months and 11 of 68 children (16.2%) at 24 months (Chi square for trend = 9.36, P=0.002). In contrast, neurologic deficits almost completely resolved over time, occurring in 19 of 76 children with CM (25%) at discharge, 2 of 74 children (2.7%) at 6 months, and 1 of 68 (1.5%) children at 24 months.During the 24 months following a CM episode, neurologic deficits resolve but the cumulative incidence of seizures increases in children with CM. Neurologic impairment after an episode of CM may not be limited to the neurologic deficits seen at discharge.Item Serum n-6 Fatty Acids are Positively Associated with Growth in 6-to-10-Year Old Ugandan Children Regardless of HIV Status—A Cross-Sectional Study(Nutrients, 2019) Jain, Raghav; Ezeamama, Amara E.; Sikorskii, Alla; Yakah, William; Zalwango, Sarah; Musoke, Philippa; Boivin, Michael J.; Fenton, Jenifer I.Fatty acids (FAs) are crucial in child growth and development. In Uganda, antiretroviral therapy (ART) has drastically reduced perinatal human immunodeficiency virus (HIV) infection of infants, however, the interplay of FAs, ART, and HIV in relation to child growth is not well understood. To investigate this, serum was collected from 240 children between 6–10 years old in Uganda and analyzed for FAs using gas-chromatography mass-spectrometry. HIV status and anthropometric measurements were taken, and relationships with FAs were assessed. No significant differences in growth parameters or serum FAs were found between HIV uninfected children with and without exposure to ART. HIV positive children had significantly lower height-for-age-z-scores (HAZ) than uninfected children (p < 0.001). HIV-positive children had higher arachidonic acid than uninfected children (p = 0.003). Total omega-6 FAs were significantly associated with HAZ regardless of HIV status (p = 0.035). Mean total omega-3 FAs (2.90%) were low in this population compared to other cohorts in Africa. These results provide reference serum FA values for 6–10-year-old children in Uganda and may be used to inform lipid supplementation programs to promote child growth. Future studies should investigate the relationships between child growth trajectories in relation to HIV status and serum FAs. View Full-TextItem Serum Vitamin D is Di erentially Associated with Socioemotional Adjustment in Early School-Aged Ugandan Children According to Perinatal HIV Status and In Utero/Peripartum Antiretroviral Exposure History(Nutrients, 2019) Yakah, William; Fenton, Jenifer I.; Sikorskii, Alla; Zalwango, Sarah K.; Tuke, Robert; Musoke, Philippa; Boivin, Michael J.; Giordani, Bruno; Ezeamama, Amara E.An impact of vitamin D in neurocognitive function has been theorized but it remains unknown whether vitamin-D insufficiency (VDI) is associated with worse socio-emotional adjustment (SEA) in vulnerable early school-aged children. This study examines the thesis that deficits in SEA are related to VDI using longitudinal data from 254 children that are perinatally HIV-infected (PHIV), exposed-uninfected (HEU), or unexposed-uninfected (HUU). In utero/peripartum antiretroviral (IPA) exposure was established per medical record documentation of biological mother’s ART regimen in pregnancy. Four caregiver-reported age- and sex-standardized measures of SEA were obtained at months 0, 6, and 12 for dependent children aged 6–10 years: externalizing problems (EPC), internalizing problems (IPC), behavioral symptoms index (BSI), and adaptive skills index (ASI). VDI was highly prevalent (74%, n = 188), and its association with change in SEA measures over 12 months varied by HIV-status (VDI*HIV, all p-values < 0.03). There was further variation in relationship of vitamin-D to SEA by IPA among PHIV (for ASI, BSI, and EPC, vitamin-D*IPA, p-value ≤ 0.01) and HEU (for BSI and EPC, vitamin-D*IPA, p-value ≤ 0.04). Among HUU, BSI (β = −0.32, 95% CI: −0.50, −0.13), IPC (β = −0.28, 95% CI: −0.47, −0.09), and EPC (β = −0.20, 95% CI: −0.37, −0.02) all declined moderately per quartile increment in VD. Among PHIV, on the one hand higher vitamin D predicted ASI gains (moderate vs. low VD, β = 0.52, p = 0.002), but this protective association was absent for BSI, EPC, and IPC (β = 0.36–0.77, p < 0.05). In absence of IPA-exposure, increasing vitamin-D predicted declines in BSI and EPC (moderate vs. low Vitamin D, β = −0.56 to −0.71, p ≤ 0.02) among HEU. However, given IPA exposure among HEU, higher VDI predicted moderate elevation in BSI (β = 0.39, 95% CI: 0.00, 0.78) and IPC (β = 0.48, 95% CI: 0.05, 0.92). Interaction between VD and IPA exposure for SEA outcomes among HEU and PHIV children warrants further investigation. The vitamin-D associated SEA improvement among HUU and HEU without IPA exposure suggests vitamin-D supplementation may remediate behavioral and adaptive deficits in this groups. View Full-TextItem Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions(PloS one, 2009) Bangirana, Paul; John, Chandy C.; Idro, Richard; Opoka, Robert O.; Byarugaba, Justus; Jurek, Anne M.; Boivin, Michael J.Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions.A cohort of 89 healthy children (45 females) aged 5 to 12 years old were followed over 24 months and had cognitive tests measuring visual spatial processing, memory, attention and spatial learning administered at baseline, 6 months and 24 months. Nutritional status, child's educational level, maternal education, socioeconomic status and quality of the home environment were also measured at baseline. A multivariate, longitudinal model was then used to identify predictors of cognition over the 24 months.A higher child's education level was associated with better memory (p = 0.03), attention (p = 0.005) and spatial learning scores over the 24 months (p = 0.05); higher nutrition scores predicted better visual spatial processing (p = 0.002) and spatial learning scores (p = 0.008); and a higher home environment score predicted a better memory score (p = 0.03).Cognition in Ugandan children is predicted by child's education, nutritional status and the home environment. Community interventions to improve cognition may be effective if they target multiple socioeconomic variablesItem Validity of Neuropsychological Testing in Young African Children Affected by HIV(Journal of pediatric infectious diseases, 2018) Chernoff, Miriam C.; Laughton, Barbara; Kamthunzi, Portia; Kabugho, Enid; Joyce, Celeste; Jean-Philippe, Patrick; Boivin, Michael J.Western-constructed neuropsychological tests have been used in low- and middle-income countries to assess the impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and other chronic illnesses. We explore using such instruments cross-culturally in a sub-Saharan African setting. IMPAACT P1104S was a 2-year observational study performed at six clinical sites (South Africa—three sites, Malawi, Uganda, and Zimbabwe) to assess and compare neuropsychological outcomes in three cohorts of children between the ages of 5 and 11 years: HIV-infected (HIV), HIV-exposed but uninfected (HEU), and HIV unexposed and uninfected (HU). Descriptive statistics compared sociodemographic characteristics among children at sites. Instruments included the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) cognitive ability, Test of Variables of Attention (TOVA) attention/impulsivity, Bruininks–Oseretsky Test of Motor Proficiency, 2nd edition (BOT-2) motor proficiency tests, and Behavior Rating Inventory for Executive Function (BRIEF) executive function problems. Test characteristics were assessed using intraclass and Spearman's nonparametric correlations, linear regression, and principal factor analyses. Of the 611 participants, 50% were males and mean age ranged from 6.6 to 8 years. In Malawi, Uganda, and Zimbabwe, substantial proportions of families lived in rural settings in contrast to the South African sites. Intraclass correlation coefficients between weeks 0 and 48 were highest for the KABC scores, ranging between 0.42 and 0.71. Correlations among similar test domains were low to moderate but significant, with positive correlation between KABC sequential and TOVA scores and negative correlation between BRIEF and KABC scores. TOVA response time scores correlated negatively with the BOT-2 total points score. Strong and significant associations between individual measures of growth, disability, and development with all test scores were observed. Performance-based measures were markedly lower for HIV compared with HEU and HU participants, even after controlling for age, sex, and site. Factor analyses confirmed the underlying theoretical structure of the KABC scaled item scores. The KABC, TOVA, BRIEF, and BOT-2 were valid and reliable tools for assessing the neuropsychological impact of HIV in four sub-Saharan African countries.Item A Year-Long Caregiver Training Program to Improve Neurocognition in Preschool Ugandan HIV-Exposed Children(Journal of developmental and behavioral pediatrics, 2013) Boivin, Michael J.; Bangirana, Paul; Nakasujja, Noeline; Page, Connie F.; Shohet, Cilly; Givon, Deborah; Bass, Judith K.; Opoka, Robert O.; Klein, Pnina S.Mediational intervention for sensitizing caregivers (MISC) is a structured program enabling caregivers to enhance their child’s cognitive and emotional development through daily interactions. The principal aim was to evaluate if a year-long MISC caregiver training program produced greater improvement in child cognitive and emotional development compared with a control program. 119 uninfected HIV-exposed preschool children and their caregivers were randomly assigned to one of two treatment arms: biweekly MISC training alternating between home and clinic for one year or a health and nutrition curriculum. All children were evaluated at baseline, 6 months, and 1 year with the Mullen Early Learning Scales, Color-Object Association Test (COAT) for memory, and Achenbach Child Behavior Checklist (CBCL) for psychiatric symptoms. Caregivers were evaluated on the same schedule with the Hopkins Symptoms Checklist (HSCL-25) for depression and anxiety.The treatment arms were compared using repeated-measures ANCOVA with child age, gender, weight, SES, caregiving quality, caregiver anxiety, and caregiver education as covariates. The MISC children had significantly greater gains compared to controls on the Mullen Receptive and Expressive Language development, and on the Mullen composite score of cognitive ability. COAT total memory for MISC children was marginally better than controls. No CBCL differences between the groups were noted. Caldwell HOME scores and observed mediational interaction scores from videotapes measuring caregiving quality also improved significantly more for the MISC group.MISC enhanced cognitive performance, especially in language development. These benefits were possibly mediated by improved caregiving and positive emotional benefit to the caregiver.