Paul Bangirana

• PhD
• Associate Professor at Makerere University

Introduction Academic proficiency is crucial for advancing learning goals, school advancement, and future economic security. Children with sickle cell anemia (SCA) in sub‐Saharan Africa (SSA) may be at risk of disease‐associated learning difficulties. Limited data exist on this topic among school‐age children in the region. We aimed to assess acade...

Children with sickle cell anemia (SCA) frequently develop progressive neurocognitive impairment. We aimed to determine effects of hydroxyurea therapy on neurocognitive function in Ugandan children with SCA by comparing levels at enrollment to a planned 18-month interim assessment. Ugandan children (N=264) ages 3-9 years were enrolled from a SCA cli...

Background Virus co-infection or reactivation may modify the host response during cerebral malaria. Cytomegalovirus (CMV) DNAemia has been associated with increased morbidity and mortality in adults with sepsis; however, the impact of CMV DNAemia on adverse outcomes in children with cerebral malaria is unknown. Methods Clinical, physiological, and...

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl⁻¹) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were...

Background: Parenting children with physical disabilities is associated with unique challenges for the caregivers putting them at risk of developing psychological distress. In Uganda where 3.5% of children have a physical disability, parents experience strain and significant levels of stress but it is not known how this relates to psychological dis...

Background Caregivers 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 caregiver...

Background Few studies have described post-discharge morbidity of children with specific manifestations of severe malaria (SM) beyond severe malarial anaemia or cerebral malaria. Methods Children 6 months to 4 years of age admitted at Jinja and Mulago hospitals in Uganda, with one or more of the five most common forms of SM, cerebral malaria (n =...

Interpersonal violence is a significant public health and human rights concern. People living with severe mental illness are especially vulnerable. The Sustainable Development Goals 2030 Agenda aims to end violence. To this end, we gathered information on the prevalence and factors associated with interpersonal violence among one of the most impact...

Introduction: Children with sickle cell anemia (SCA) are at risk of neurocognitive impairment. The primary outcome of our open label hydroxyurea (HU) trial for children with SCA in Uganda, “BRAIN SAFE II,” was neurocognitive function at month 30 trial completion compared to enrolment. We previously reported significantly improved function at the mo...

Background In low-and-middle-income countries (LMICs), children are exposed to multiple risks that may compromise their neurodevelopment, especially during the early years. Early childhood developmental trajectories are crucial, especially in such at-risk populations as they help predict future neurocognitive potential. In LMICs where numerous fact...

Introduction: Few studies have described post-discharge morbidity of children with specific manifestations of severe malaria (SM) beyond severe malarial anemia or cerebral malaria. Methods: Children 6 months to 4 years of age admitted at Jinja and Mulago hospitals in Uganda, with one or more of the five most common manifestations of SM, cerebral ma...

Objective: Academic achievement in school-age children is crucial for advancing learning goals. Children with sickle cell anaemia (SCA) in Sub-Saharan Africa may be at risk of disease-associated school difficulties. Limited data exist on the academic achievement of children with SCA in the region. This study aimed to assess academic achievement of...

Introduction The neurocognitive functions in Ugandan children aged 1–12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment. Methods This cross-sectional study of the neurocognitive functions in children with SCA ( N = 242) and non-SCA siblings ( N = 127) used age-...

Introduction Children with sickle cell anemia (SCA) experience severe illness and risk of malnutrition in sub-Saharan Africa. Treatment with hydroxyurea (HU) decreases SCA complications. In high-income regions, hydroxyurea also improves pediatric growth and overall quality of life. We assessed the effects of hydroxyurea on growth and body compositi...

Introduction: Cerebrovascular injury can lead to neurocognitive impairment in children with sickle cell anemia (SCA). The prospective impact of hydroxyurea therapy on neurocognitive function has not been previously reported in a large sample of children with SCA in sub-Saharan Africa. We assessed the impact of hydroxyurea therapy at the trial's18-m...

Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders. In paediatric...

Background: The relationship of apolipoprotein-E4 (APOE4) to mortality and cognition after severe malaria in children is unknown. Methods: APOE genotyping was performed in children with cerebral malaria (CM, n = 261), severe malarial anemia (SMA, n = 224) and community children (CC, n = 213). Cognition was assessed over 2-year follow-up. Result...

Introduction: Infection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV sub-type D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether sub-type-specific differences are also observed among children receiving ART. Materials and Methods: Children w...

Objectives: To compare neurocognitive function between children with sickle cell anemia (SCA) and their non-SCA siblings and determine risk factors for poor neurocognition in Uganda. Study Design: This cross-sectional study assessed children with SCA and their non-SCA siblings for neurocognitive and executive function at a childrens SCA clinic in K...

Background There is little research on alcohol and other drugs (AOD) use by school-age children in low-resource settings like Uganda. Including the voices of children in research can inform prevention and early intervention efforts for those at risk of AOD use. The aim of this study was to understand the perspectives of children aged 6 to 13 years...

Background: Undertaking child-focused evaluations using a participatory approach has received recognition in recent years. Such an approach is critical not only to build capacity amongst children and youth but also to increase the rigour, validity and usefulness of evaluation findings. Objectives: The current paper builds on the methods used in a...

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI‐MRA) in sub‐Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood‐based brain biomarkers of cerebral infarcts have been identified in non‐SCA adults. Using plasma sa...

Background For children with cerebral malaria, mortality is high, and, in survivors, long-term neurologic and cognitive dysfunction are common. While specific clinical factors are associated with death or long-term neurocognitive morbidity in cerebral malaria, the association of EEG features with these outcomes, particularly neurocognitive outcomes...

Background: Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been pu...

Introduction Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by eval...

Background: Cerebral malaria (CM) and severe malarial anemia (SMA) are associated with neurocognitive impairment in childhood but their effects on long-term academic achievement are not known. Methods: Ugandan children 5 to 12 years old who participated in a previous study evaluating cognitive outcomes after CM (n = 73) or SMA (n = 56), along wi...

Background: Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear. Setting: Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya. Methods: Cognitive, behavioral and motor outcomes were assessed in children with HIV (...

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 whe...

Background Malaria in pregnancy has been associated with worse cognitive outcomes in children, but its association with behavioral outcomes and the effectiveness of malaria chemoprevention on child neurodevelopment are not well characterized. Methods To determine if more effective malaria chemoprevention in mothers and their children results in be...

Background: Global changes in amino acid levels have been described in severe malaria (SM) but the relationship between amino acids and long-term outcomes in SM have not been evaluated. Methods: We measured enrollment plasma concentrations of twenty amino acids using high-performance liquid chromatography in 500 Ugandan children aged 18 months t...

Background: Murine experimental cerebral malaria studies suggest both protective and deleterious central nervous system effects from alterations in the interleukin-33 (IL-33)/ST2 pathway. Methods: We assessed whether soluble ST2 (sST2) was associated with neuronal injury or cognitive impairment in a cohort of Ugandan children with cerebral malar...

Introduction: Children and adolescents living with HIV (C/ALHIV) are at a risk for significant neurocognitive deficits. There is limited literature that addresses the role of socioeconomic factors in neurocognitive deficits among CALHIV in Sub Saharan Africa (SSA), as it is very difficult to establish this causal relationship. Our systematic revie...

Background Forcibly displaced people are at elevated risk of experiencing circumstances that can adversely impact on mental health. Culturally and contextually relevant tools to assess their mental health and psychosocial needs are essential to inform the development of appropriate interventions and investigate the effectiveness of such interventio...

Abstarct Objective Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments. Methods A sub-sa...

Background Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. Methods Between 2014 and 2017, 600 children aged 6...

Background Globally, 85% of acute kidney injury (AKI) cases occur in low-and-middle-income countries. There is limited information on persistent kidney disease (acute kidney disease [AKD]) following severe malaria-associated AKI. Methods Between March 28, 2014, and April 18, 2017, 598 children with severe malaria and 118 community children were en...

Importance Cerebral malaria (CM) and severe malarial anemia (SMA) are associated with persistent neurocognitive impairment (NCI) among children in Africa. Identifying blood biomarkers of acute brain injury that are associated with future NCI could allow early interventions to prevent or reduce NCI in survivors of severe malaria. Objective To inves...

Background:Severe malaria (SM) remains a major global health problem causing ~275,000 pediatric deaths annually, worldwide. Continuous, non-invasive monitoring of peripheral perfusion can help detect abnormalities in systemic circulation, a common problem in critically ill patients, and can improve outcomes in children hospitalized with SM. Perfusi...

Background: Perinatal HIV and antiretroviral therapy (ART) exposure may influence neurocognitive outcomes, though evidence is mixed and most studies are limited to outcomes in the first 24 months. We compared neurocognitive outcomes in school-aged children who were HIV-exposed uninfected (CHEU) and HIV-unexposed uninfected (CHUU). Setting: Childre...

Background The frequency of recovery from undernutrition after an episode of severe malaria, and the relationship between undernutrition during severe malaria and clinical and cognitive outcomes are not well characterized. Methods We evaluated undernutrition and cognition in children in Kampala, Uganda 18 months to 5 years of age with cerebral mal...

Background: In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM. Methods: From 2008 to 2013, 5...

Background Depression is a major cause of the global disease burden and globally affects 350–400 million persons making it the largest contributor to years lived with disability. Among of patients with chronic physical illnesses like tuberculosis, depression affects up to 25–33% of individuals. There are limited studies on the comorbidity of depres...

Background: Suicidal behavior and HIV/AIDS are vital public health challenges especially in low and middle-income countries. As suicide in adults is perturbing for those closest to them, this sentiment is much more intense and generalized in the case of a child or adolescent. Knowledge of factors associated with suicidal ideation in HIV infected ch...

Abstract Background Severe malaria is associated with long-term mental health problems in Ugandan children. This study investigated the effect of a behavioural intervention for caregivers of children admitted with severe malaria, on the children’s mental health outcomes 6 months after discharge. Methods This randomized controlled trial was conducte...

Globally, 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...

Abstract Background HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to b...

Purpose : To determine the prevalence of behavioural problems and the associated factors in children with epilepsy (CWE). Methods : This was a cross-sectional study conducted at Mulago National Referral Hospital, Kampala, Uganda, from December 2019 to May 2020. A total of 300 CWE aged 6 to 17 years were consecutively enrolled and assessed for beha...

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and...

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 m...

Background: Severe malaria manifests as various conditions with severe malarial anemia being the most common and cerebral malaria being the most severe and affecting over 200,000 children annually. A 2010 review highlighted blood brain barrier degradation and decreased cerebral perfusion as contributors to the long-term behavioral, cognitive, and n...

Background Severe anaemia is a global public health challenge commonly associated with morbidity and mortality among children < 5 years of age in Sub-Saharan Africa. However, less is known about the behavioural performance of children < 5 years surviving severe anaemia in low resource settings. We investigated social-emotional and adaptive behaviou...

Background: 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 prev...

Background Severe anaemia is a common clinical problem among young children in sub-Saharan Africa. However, the effect of severe anaemia on neurodevelopment of these children is not well described. Therefore, we assessed the neurodevelopmental performance of preschool children diagnosed with severe anaemia in Northern Uganda. Methods We conducted...

Background: Given the limited integration of mental health services into pediatric HIV care in sub-Saharan Africa, there is limited information on the nature of mental health service use sought by caregivers of children and adolescents living with HIV/AIDS. Methods: We analyzed data from a sample of 135 children and adolescents living with HIV/A...

Background: Severe malaria is associated with long-term mental health problems in Ugandan children. This study investigated the effect of a behavioral intervention for caregivers of children admitted with severe malaria, on the children’s mental health outcomes six months after discharge. Methods: This randomized controlled trial was conducted at N...

Background: Malaria is one of the major contributing risk factors for poor development of children living in low- and middle-income countries (LMICs). However, little is known about the specific domains of cognition and behavior that are impacted by malaria, the extent of these deficits, and the different types of the malaria spectrum that are ass...

Objectives: Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors. Design: Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children. Setting: Mulago National Referral Hospital in Kampala, Uganda. Subjects:...

Background: Severe anaemia is a global public health challenge commonly associated with morbidity and mortality among children <5 years of age in Sub-Saharan Africa. However, less is known about the behavioural performance of preschool children surviving severe anaemia in low resource settings. We investigated social-emotional and adaptive behaviou...

Background: Severe anaemia is a global public health challenge commonly associated with morbidity and mortality among children <5 years of age in Sub-Saharan Africa. However, less is known about the behavioural performance of children < 5 years surviving severe anaemia in low resource settings. We investigated social-emotional and adaptive behaviou...

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 chi...

Background: Malaria is one of the major contributing risk factor for poor development of children living in low- and middle- income countries (LMICs). However, little is known about the specific domains of cognition and behavior that are impacted by malaria, the extent of these deficits, and the severity of malaria infection that is associated with...

Background: Malaria is one of the major contributing risk factors for poor development of children living in low- and middle- income countries (LMICs). However, little is known about the specific domains of cognition and behaviour that are impacted by malaria, the extent of these deficits, and the different types of the malaria spectrum that are as...

Background: Malaria is one of the major contributing risk factors for poor development of children living in low- and middle- income countries (LMICs). However, little is known about the specific domains of cognition and behaviour that are impacted by malaria, the extent of these deficits, and the different types of the malaria spectrum that are as...

Introduction Hospital based studies for psychotic disorders are scarce in low and middle income countries. This may impact on development of intervention programs. Objective We aimed to determine the burden of psychotic disorders among first treatment contact patients at the national psychiatric referral hospital in Uganda. Methods A retrospectiv...

Background 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. Methods 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...

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke, impaired neurocognitive function and other manifestations of pediatric cerebral vasculopathy. Detailed multifaceted evaluations of children with SCA in sub-Saharan Africa are limited, including neurocognitive testing. Methods: We aimed to establish the prevalence a...

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Inflammation is a risk factor for acute stroke. In a cross-sectional study of Ugandan children, we asked whether inflammatory markers correlated with findings on neurological and neurocognitive testing and...

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations of children with SCA in sub-Saharan Africa are limited, especially magnetic resonance imaging and angiography (MRI/MRA). In a sample of Ugandan children receiving care at the Mulago Ho...

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited. Methods: We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Ugan...

Autoantibodies targeting host antigens contribute to autoimmune disorders, frequently occur during and after infections and have been proposed to contribute to malaria-induced anemia. We measured anti-phosphatidylserine (PS) and anti-DNA antibody levels in 382 Ugandan children prospectively recruited in a study of severe malaria (SM). High antibody...

Background: Deaf children face many challenges in dealing with educational opportunities and ensuring attainment of academic skills. A parent's involvement in the child's education has the potential to enhance academic performance. We sought to study the association between parental involvement and academic achievement among deaf children in Ugand...

Introduction: Hospital based studies for psychotic disorders are scarce in low and middle income countries. This may impact on development of intervention programs. Objective: We aimed to determine the burden of psychotic disorders among first treatment contact patients at the national psychiatric referral hospital in Uganda. Methods: A retrospecti...

Abstract Background Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown. Methods 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 c...

Background: Elevated concentrations of cerebrospinal fluid (CSF) tau, a marker of axonal injury, have been associated with coma in severe malaria (cerebral malaria). However, it is unknown whether axonal injury is related to long-term neurologic deficits and cognitive impairment in children with cerebral malaria (CM). Methods: Admission CSF tau...

Background Traumatic brain injuries in Uganda are on the increase, however little is known about the neuropsychological outcomes in survivors. This study characterized patients with traumatic brain injury (TBI) and the associated six-month neuropsychological outcomes in a Ugandan tertiary hospital. Methods Patients admitted at Mulago Hospital with...

Background: Monocyte 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. Setting: Prospective study of infant and child neurodevelopmental...

Maternal infection during pregnancy can have lasting effects on neurodevelopment, but the impact of malaria in pregnancy on child neurodevelopment is unknown. We present a case of a 24-year-old gravida three woman enrolled at 14 weeks 6 days of gestation in a clinical trial evaluating malaria prevention strategies in pregnancy. She had two blood sa...

Introduction: Despite high prevalence of Sickle Cell Anemia (SCA) in sub-Saharan Africa, systematic evaluation of structural and functional impact of pediatric sickle cerebrovasculopathy has been limited. In a cross-sectional study of children with HbSS, ages 1-12 years, receiving care at the Mulago Hospital SCD clinic in Kampala, we hypothesized t...

Sickle Cell Anemia (SCA) is a leading cause of childhood stroke in sub-Saharan Africa and sickle cell brain vasculopathy manifests either as overt stroke or clinically "silent infarcts". This study aimed to describe brain abnormalities seen on magnetic resonance imaging in Ugandan SCA children. Our hypothesis was that multi-model abnormalities woul...

Background: Severe malaria in children is often associated with long-term behavioural and cognitive problems. A sizeable minority of children go on to experience repeated malaria due to the high transmission and infection rates in the region. The purpose of this study was to explore caregivers' experiences of parenting a child with a history of se...

Background Iron therapy started concurrently with antimalarial treatment in children with severe malaria and iron deficiency may not be well absorbed due to inflammation‐induced impairment of iron absorption and trapping of iron in reticuloendothelial stores under the influence of the hepatic protein hepcidin. Malaria‐induced increases in hepcidin...

Background The beneficial effects from exclusive breastfeeding (EBF) have been widely acknowledged. We assessed the effect of exclusive breastfeeding promotion by peer counsellors in Uganda and Burkina Faso, on cognitive abilities, social emotional development, school performance and linear growth among 5–8 years old children. Methods Children in...

Post hoc power assessment. (DOCX)

Baseline characteristics of the children studied in PROMISE Saving Brains and those not re-enrolled. Continuous variables. (DOCX)

CONSORT checklist: USE_CONSORT Checklist_August_2017.doc. (DOC)

Baseline characteristics of the children studied in PROMISE Saving Brains and those not re-enrolled. Categorical variables. (DOCX)

Protocol for the Saving Brains study in Burkina Faso and Uganda: USE_PROTOCOL_Saving Brain_BFA_UGA.doc. (DOC)

Children and adolescents are affected in different ways by HIV/AIDS. Neurocognitive deficits are one of the most significant long term effects on HIV infected children and adolescents. Several factors are thought to influence cognitive outcomes and this include immune status, Highly Active Antiretroviral Therapy (HAART), education and social suppor...

Background Severe malaria is a leading cause of acquired neurodisability in Africa and is associated with reduced nitric oxide (NO) bioavailability. A neuroprotective role for inhaled NO has been reported in animal studies, and administration of inhaled NO in preterm neonates with respiratory distress syndrome is associated with a 47% reduced risk...