Browsing by Author "Bangirana, Paul"
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Item Acute Kidney Injury In Ugandan Children With Severe Malaria Is Associated With Long-Term Behavioral Problems(PloS one, 2019) Hickson, Meredith R.; Conroy, Andrea L.; Bangirana, Paul; Opoka, Robert O.; Idro, Richard; Ssenkusu, John M.; John, Chandy C.Acute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown.We conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity.AKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age.AKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.Item Acute Kidney Injury Is Associated With Impaired Cognition And Chronic Kidney Disease In A Prospective Cohort Of Children With Severe Malaria(BMC medicine, 2019) Conroy, Andrea L.; Opoka, Robert O.; Bangirana, Paul; Idro, Richard; Ssenkusu, John M.; Datta, Dibyadyuti; Hodges, James S.; Morgan, Catherine; John, Chandy C.Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown. Ugandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age.The prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption.AKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.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 Association of COVID-19-related perceptions and experiences with depression and anxiety in Ugandan caregivers of young children with malaria and iron deficiency: A cross-sectional study(Public Library of Science, 2024-12-10) Park, Saeun; Bangirana, Paul; Mupere, Ezekiel; Baluku, Reagan I; Helgeson, Erika S; Cusick, Sarah ECaregivers of young children may have been particularly vulnerable to mental health challenges during the COVID-19 pandemic due to its negative impacts on their housing, finances, and childcare demands. This study explored the associations between COVID-19-related experiences and symptoms of depression and anxiety among Ugandan caregivers. This cross-sectional study included 100 Ugandan caregivers of young children aged 6-59 months with uncomplicated malaria and iron deficiency (N = 85) and without malaria or anemia (N = 15) who were enrolled in the Optimizing Iron Status in Malaria-Endemic Areas (OptiM) study. Sociodemographic data and COVID-19 experiences were collected using an internally developed survey and symptoms of depression and anxiety were measured using the Hopkins Symptom Checklist (HSCL-25) and the Center for Epidemiologic Studies Depression (CESD-20) scale. Multiple linear regression models were used to assess the associations between COVID-19 survey scores with HSCL-25 or CESD-20 scores. Nearly half of caregivers reported clinically meaningful symptoms of depression (46%) and/or anxiety (49%). Caregivers had more severe symptoms of depression and/or anxiety if they experienced greater changes in living situations or decreases in physical activity (CESD-20: [beta] = 3.35, 95% CI [1.00, 5.70], p = .01), food insecurity (HSCL-25: [beta] = 3.25, 95% CI [0.41, 6.10], p = .03, CESD-25: [beta] = 3.09, 95% CI [0.79, 5.39], p = .01), and domestic violence (HSCL-25: [beta] = 3.82, 95% CI [0.94, 6.70], p = .01) during COVID-19. These associations did not vary depending on whether the caregivers had children with malaria. Negative COVID-19 experiences were significantly associated with more severe depression and anxiety in Ugandan caregivers, regardless of their children's malaria status. Urgent attention and action are needed to support the mental well-being of this vulnerable population. Further prospective studies should investigate the long-term impact of COVID-19 on caregivers and their children.Item Caregivers’ Depressive Symptoms And Parent-Report Of Child Executive Function Among Young Children In Uganda(Learning and individual differences, 2016) Familiar, Itziar; Nakasujja, Noeline; Bass, Judith; Sikorskii, Alla; Murray, Sarah; Escudero, Horacio Ruisenor; Bangirana, Paul; Opoka, Robert; Boivina, Michael J.Maternal mental health (particularly depression) may influence how child behavior report. Few research has focused on sub-Saharan countries where pediatric HIV concentrates and impacts child neuropsychological development and caregiver mental health. We investigated the associations between caregivers' depressive symptoms and neuropsychological outcomes in HIV-infected (n=118) and HIV-exposed (n=164) Ugandan children aged 2–5years. We compared performance-based tests of development (Mullen Scales of Early Learning, Color Object Association Test), to a caregiver report of executive function (Behavior Rating Inventory of Executive Function, BRIEF). Caregivers were assessed with Hopkins Symptom Checklist-25 depression subscale. The associations between all BRIEF indices and caregiver's depression symptoms were differential according to child's HIV status. Caregivers with greater depressive symptoms reported their HIV-infected children as having more behavioral problems related to executive functioning. The assessment of behavior of HIV-infected children should incorporate a variety of sources of information and screening of caregiver mental health.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 Community based sociotherapy for depressive symptomatology of Congolese refugees in Rwanda and Uganda (CoSTAR): a protocol for a cluster randomised controlled trial(Informa UK Limited, 2023-01-20) Kagabo, Daniel M.; Bangirana, Paul; Burnside, Girvan; Chiumento, Anna; Duarte, Rui; Gishoma, Darius; Girvan, Michelle; Jansen, Angela; Jansen, Stefan; Kasujja, Rosco; Lubunga, Rachel; Nevitt, Sarah; Nzaramba, Lucie; Sarabwe, Emmanuel; Jackson, Clare; Rahman, Atif; Richters, Annemiek; Robinson, Jude; Rutayisire, Theoneste; Ventevogel, Peter; White, Ross G.Background: Conflict in the Democratic Republic of Congo has led to large numbers of refugees fleeing to Uganda and Rwanda. Refugees experience elevated levels of adverse events and daily stressors, which are associated with common mental health difficulties such as depression. The current cluster randomised controlled trial aims to investigate whether an adapted form of Community-based Sociotherapy (aCBS) is effective and cost-effective in reducing depressive symptomatology experienced by Congolese refugees in Uganda and Rwanda. Methods: A two-arm, single-blind cluster randomised controlled trial (cRCT) will be conducted in Kyangwali settlement, Uganda and Gihembe camp, Rwanda. Sixty-four clusters will be recruited and randomly assigned to either aCBS or Enhanced Care As Usual (ECAU). aCBS, a 15-session group-based intervention, will be facilitated by two people drawn from the refugee communities. The primary outcome measure will be self-reported levels of depressive symptomatology (PHQ-9) at 18-weeks post-randomisation. Secondary outcomes will include levels of mental health difficulties, subjective wellbeing, post-displacement stress, perceived social support, social capital, quality of life, and PTSD symptoms at 18-week and 32-week post-randomisation. Cost effectiveness of aCBS will be measured in terms of health care costs (cost per Disability Adjusted Life Year, DALY) compared to ECAU. A process evaluation will be undertaken to investigate the implementation of aCBS. Conclusion: This cRCT will be the first investigating aCBS for mental health difficulties experienced by refugees and will contribute to knowledge about the use of psychosocial interventions for refugees at a time when levels of forced migration are at a record high.Item Delayed Iron Does Not Alter Cognition Or Behavior Among Children With Severe Malaria And Iron Deficiency(Pediatric research, 2020) Ssemata, Andrew S.; Hickson, Meredith; Ssenkusu, John M.; Cusick, Sarah E.; Nakasujja, Noeline; Opoka, Robert O.; Kroupina, Maria; Georgieff, Michael K.; Bangirana, Paul; John, Chandy C.Malaria and iron deficiency (ID) in childhood are both associated with cognitive and behavioral dysfunction. The current standard of care for children with malaria and ID is concurrent antimalarial and iron therapy. Delaying iron therapy until inflammation subsides could increase iron absorption but also impair cognition.In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment.All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 μmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from −0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06).Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up.Item Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria(Critical care medicine, 2020) Ouma, Benson J.; Ssenkusu, John M.; Shabani, Estela; Datta, Dibyadyuti; Opoka, Robert O.; Idro, Richard; Bangirana, Paul; Park, Gregory; Joloba, Moses L.; Kain, Kevin C.; John, Chandy C.; Conroy, Andrea L.Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors.Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. Mulago National Referral Hospital in Kampala, Uganda.Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months.Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β −0.42, 95% CI, −0.69 to −0.15, p = 0.002; children ≥ 5, β −0.39, 95% CI, −0.67 to −0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau).These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.Item Epilepsy in Onchocerca volvulus Sero-Positive Patients From Northern Uganda—Clinical, EEG and Brain Imaging Features(Frontiers in Neurology, 2021) Ogwang, Rodney; Ningwa, Albert; Akun, Pamela; Bangirana, Paul; Anguzu, Ronald; Mazumder, Rajarshi; Abbo, Catherine; Mwaka, Amos Deogratius; Idro, RichardGlobally, epilepsy is the most common chronic neurological disorder. The incidence in sub-Saharan Africa is 2-3 times higher than that in high income countries. Infection by Onchocerca volvulus may be an underlying risk factor for the high burden and based upon epidemiological associations, has been proposed to cause a group of disorders—Onchocerca associated epilepsies (OAE) like nodding syndrome (NS). To improve our understanding of the disease spectrum, we described the clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) features of children with epilepsy and sero-positive for Onchocerca volvulus (possible OAEs other than nodding syndrome). Twenty-nine children and adolescents with non-nodding syndrome OAE in northern Uganda were enrolled. A diagnosis of OAE was made in patients with epilepsy and seizure onset after age 3 years, no reported exposure to perinatal severe febrile illness or traumatic brain injury, no syndromic epilepsy diagnosis and a positive Ov-16 ELISA test. Detailed clinical evaluation including psychiatric, diagnostic EEG, a diagnostic brain MRI (in 10 patients) and laboratory testing were performed. Twenty participants (69%) were male. The mean age was 15.9 (standard deviation [SD] 1.9) years while the mean age at seizure onset was 9.8 (SD 2.9) years. All reported normal early childhood development. The most common clinical presentation was a tonic-clonic seizure. The median number of seizures was 2 (IQR 1–4) in the previous month. No specific musculoskeletal changes, or cranial nerve palsies were reported, neither were any vision, hearing and speech difficulties observed. The interictal EEG was abnormal in the majority with slow wave background activity in 52% (15/29) while 41% (12/29) had focal epileptiform activity. The brain MRI showed mild to moderate cerebellar atrophy and varying degrees of atrophy of the frontal, parietal and occipital lobes. The clinical spectrum of epilepsies associated with Onchocerca may be broader than previously described. In addition, focal onset tonic-clonic seizures, cortical and cerebellar atrophy may be important brain imaging and clinical features.Item Exploring The Mental Health And Psychosocial Problems Of Congolese Refugees Living In Refugee Settings In Rwanda And Uganda: A Rapid Qualitative Study(Conflict and Health, 2020) Chiumento, Anna; Rutayisire, Theoneste; Sarabwe, Emmanuel; Hasan, Tasdik; Kasujja, Rosco; Nabirinde, Rachel; Mugarura, Joseph; Kagabo, Daniel M.; Bangirana, Paul; Jansen, Stefan; Ventevogel, Peter; Robinson, Jude; White, Ross G.Refugees fleeing conflict often experience poor mental health due to experiences in their country of origin, during displacement, and in new host environments. Conditions in refugee camps and settlements, and the wider socio-political and economic context of refugees’ lives, create structural conditions that compound the effects of previous adversity. Mental health and psychosocial support services must address the daily stressors and adversities refugees face by being grounded in the lived reality of refugee’s lives and addressing issues relevant to them.We undertook a rapid qualitative study between March and May 2019 to understand the local prioritisation of problems facing Congolese refugees living in two refugee settings in Uganda and Rwanda. Thirty free list interviews were conducted in each setting, followed by 11 key informant interviews in Uganda and 12 in Rwanda.Results from all interviews were thematically analysed following a deductive process by the in-country research teams. Free list interview findings highlight priority problems of basic needs such as food, shelter, and healthcare access; alongside contextual social problems including discrimination/inequity and a lack of gender equality. Priority problems relating to mental and psychosocial health explored in key informant interviews include discrimination and inequity; alcohol and substance abuse; and violence and gender-based violence.Our findings strongly resonate with models of mental health and psychosocial wellbeing that emphasise their socially determined and contextually embedded nature. Specifically, findings foreground the structural conditions of refugees’ lives such as the physical organisation of camp spaces or refugee policies that are stigmatising through restricting the right to work or pursue education. This structural environment can lead to disruptions in social relationships at the familial and community levels, giving rise to discrimination/inequity and gender-based violence. Therefore, our findings foreground that one consequence of living in situations of pervasive adversity caused by experiences of discrimination, inequity, and violence is poor mental health and psychosocial wellbeing. This understanding reinforces the relevance of feasible and acceptable intervention approaches that aim to strengthening familial and community-level social relationships, building upon existing community resources to promote positive mental health and psychosocial wellbeing among Congolese refugees in these settings.Item High Plasma Erythropoietin Levels are Associated With Prolonged Coma Duration and Increased Mortality in Children With Cerebral Malaria(Clinical Infectious Diseases, 2015) Shabani, Estela; Opoka, Robert O.; Idro, Richard; Schmidt, Robert; Park, Gregory S.; Bangirana, Paul; Vercellotti, Gregory M.; Hodges, James S.; Widness, John A.; John, Chandy C.Elevated endogenous plasma erythropoietin (EPO) levels have been associated with protection from acute neurologic deficits in Kenyan children with cerebral malaria (CM). Based on these findings and animal studies, clinical trials of recombinant human EPO (rHuEPO) have been started in children with CM. Recent clinical trials in adults with acute ischemic stroke have demonstrated increased mortality with rHuEPO treatment. We conducted a study in children with CM to assess the relationship of endogenous plasma and cerebrospinal fluid (CSF) EPO levels with mortality and acute and long-term neurologic outcomes.A total of 210 children between 18 months and 12 years of age with a diagnosis of CM, were enrolled at Mulago Hospital, Kampala, Uganda. Plasma (n = 204) and CSF (n = 147) EPO levels at admission were measured by radioimmunoassay and compared with mortality and neurologic outcomes. After adjustment for age and hemoglobin level, a 1-natural-log increase in plasma EPO level was associated with a 1.74-fold increase in mortality (95% confidence interval, 1.09–2.77, P = .02). Plasma and CSF EPO levels also correlated positively with coma duration (P = .05 and P = .02, respectively). Plasma and CSF EPO levels did not differ in children with vs those without acute or long-term neurologic deficits. Plasma EPO levels correlated positively with markers of endothelial and platelet activation and histidine-rich protein-2 levels, but remained associated with mortality after adjustment for these factors.High endogenous plasma EPO levels are associated with prolonged coma duration and increased mortality in children >18 months of age with CM.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 Inpatient Mortality in Children With Clinically Diagnosed Malaria As Compared With Microscopically Confirmed Malaria(The Pediatric infectious disease journal, 2008) Opoka, Robert O.; Xia, Zongqi; Bangirana, Paul; John, Chandy C.Inpatient treatment for malaria without microscopic confirmation of the diagnosis occurs commonly in sub-Saharan Africa. Differences in mortality in children who are tested by microscopy for Plasmodium falciparum infection as compared with those not tested are not well characterized.A retrospective chart review was conducted of all children up to 15 years of age admitted to Mulago Hospital, Kampala, Uganda from January 2002 to July 2005, with a diagnosis of malaria and analyzed according to microscopy testing for P. falciparum.A total of 23,32 children were treated for malaria during the study period, 991 (4.2%) of whom died. Severe malarial anemia in 7827 (33.5%) and cerebral malaria in 1912 (8.2%) were the 2 common causes of malaria-related admissions. Children who did not receive microscopy testing had a higher case fatality rate than those with a positive blood smear (7.5% versus 3.2%, P < 0.001). After adjustment for age, malaria complications, and comorbid conditions, children who did not have microscopy performed or had a negative blood smear had a higher risk of death than those with a positive blood smear [odds ratio (OR): 3.49, 95% confidence interval (CI): 2.88–4.22, P < 0.001; and OR: 1.59, 95% CI: 1.29–1.96, P < 0.001, respectively].Diagnosis of malaria in the absence of microscopic confirmation is associated with significantly increased mortality in hospitalized Ugandan children. Inpatient diagnosis of malaria should be supported by microscopic or rapid diagnostic test confirmation.Item Long-term Behavioral Problems in Children With Severe Malaria(Pediatrics, 2016) Ssenkusu, John Mbaziira; Hodges, James Steven; Opoka, Robert Opika; Idro, Richard; Shapiro, Elsa; John, Chandy Chiramukhathu; Bangirana, PaulSevere malaria in children is associated with long-term neurocognitive impairment, but it is unclear whether it is associated with long-term behavioral problems.Children <5 years old with cerebral malaria (CM) or severe malarial anemia (SMA) treated at Mulago Hospital, Kampala, Uganda were assessed for behavioral outcomes at 0, 6, 12, and 24 months using the Child Behavior Checklist. Sample sizes at 0, 12, and 24 months were 122, 100, and 80 in the CM group, 130, 98, and 81 in the SMA group, and 149, 123, and 90 in healthy community control (CC) children, respectively. Age adjusted z-scores for behavioral outcomes were computed using scores for the CC group. Study groups were compared using regression models adjusted for age, nutritional status, preschool education, and socioeconomic status.At 12 months, children with SMA had higher z-scores than CC children for internalizing (mean difference, 0.49; SE, 0.14; P = .001), externalizing (mean difference, 0.49; SE, 0.15; P = .001), and total problems (mean difference, 0.51; SE, 0.15; P < .001). Children with CM had higher adjusted z-scores than CC children for externalizing problems (mean difference, 0.39; SE, 0.15; P = .009) but not internalizing or total problems. At 24 months, children with CM or SMA both had increased internalizing and externalizing behavioral problems compared with CC children (P ≤ .05 for all).CM and SMA are associated with long-term internalizing and externalizing behavioral problems in children. They may contribute substantially to mental health morbidity in children <5 years old in malaria endemic areas.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 impairment