BackgroundChildren 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.MethodsWe aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1–12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second).ResultsMean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5–12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23–1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ −2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01–1.86, p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95–24.3, p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30, p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected.ConclusionsThe high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.

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 conducted at Naguru Hospital in Kampala, Uganda from January 2018 to July 2019. Caregiver and child dyads were randomly assigned to either a psycho-educational arm providing information about hospital procedures during admission (control group), or to a behavioural arm providing information about the child’s possible emotions and behaviour during and after admission, and providing age appropriate games for the caregiver and child (intervention group). Pre- and post-intervention assessments for caregiver anxiety and depression (Hopkins Symptom Checklist) and child mental health problems (Strength and Difficulties Questionnaire and the Child Behaviour Checklist) were done during admission and 6 months after discharge, respectively. T-tests, analysis of covariance, Chi-Square, and generalized estimating equations were used to compare outcomes between the two treatment arms. Results There were 120 caregiver-child dyads recruited at baseline with children aged 1.45 to 4.89 years (mean age 2.85 years, SD = 1.01). The intervention and control groups had similar sociodemographic, clinical and behavioural characteristics at baseline. Caregiver depression at baseline, mother’s education and female child were associated with behavioural problems in the child at baseline (p < 0.05). At 6 months follow-up, there was no difference in the frequency of behavioural problems between the groups (6.8% vs. 10% in intervention vs control groups, respectively, p = 0.72). Caregiver depression and anxiety scores between the treatment arms did not differ at 6 months follow-up. Conclusion This behavioural intervention for caregivers and their children admitted with severe malaria had no effect on the child’s mental health outcomes at 6 months. Further studies need to develop interventions for mental health problems after severe malaria in children with longer follow-up time. Trail registration ClinicalTrials.gov Identifier: NCT03432039

BACKGROUND AND OBJECTIVES: Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness. METHODS: Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid–upper arm circumference for age z-score. Neurodevelopment was assessed with the Malawi Developmental Assessment Tool (MDAT development-for-age z-score [DAZ]) at hospital discharge and after 6 months. RESULTS: We included 645 children at hospital discharge (mean age 12.3 months ± 5.5; 55% male); 262 (41%) with severe wasting, 134 (21%) with moderate wasting, and 249 (39%) without wasting. Four recovery trajectories were identified: high–stable, n = 112; wasted–improved, n = 404; severely wasted–greatly improved, n = 48; and severely wasted–not improved, n = 28. The children in the severely wasted–greatly improved group demonstrated a steep positive MDAT-DAZ recovery slope. This effect was most evident in children with both wasting and stunting (interaction wasted–improved × time × stunting: P &lt; .001). After 6 months, the MDAT DAZ in children with wasting recovery did not differ from community children. In children who never recovered from wasting, there remained a significant delay in MDAT DAZ scores. CONCLUSIONS: Neurodevelopment recovery occurred in parallel with wasting recovery in children convalescing from acute illness and was influenced by stunting.

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 and types of neurocognitive dysfunction in a cross-sectional study in a randomly selected sample of patients with HbSS ages 1-12 years at a large SCD clinic in Kampala, Uganda. Neurocognitive function was assessed by Mullen Scales of Early Learning (ages 1-4) and Kaufman Assessment Battery for Children, 2nd edition (ages 5-12) using linguistically validated local translations (John CC, Pediatrics 2008; Bangirana P., Clin Infect Dis. 2014). The Behavioral Rating Inventory for Executive Function was used to assess executive function. Children also underwent standardized stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) for measuring stroke risk by arterial velocities in pediatric SCD. Results: Experienced testers performed neurocognitive assessment in 242 participants: 100 (41%) ages of 1-4 years and 142 ages 5-12 years (58.7%). Mean age was 5.44 ±2.9 years; 51.6% were male. Mean hemoglobin was 7.3 ±1.02 g/dl; 76.5% had hemoglobin <8.0 g/dl. Using established international standards, 16% were malnourished. In the older age group, more children were female, malnourished, and had a clinical evidence of a stroke. In all, 27 (11.2%) had neurocognitive dysfunction, and 63 (25.8%) with impaired executive function. In the 1-4 age group, 5 (5%) had an abnormal neurocognitive exam, with a lower average standardized Global Executive Functioning score (mean -1.70 (SD 0.78)) than in the overall neurocognitive testing. Dysfunction was more common in the group ages 5-12. Among the 5-12 age group, 22 children (15.4%) had overall neurocognitive dysfunction, with the lowest group average z-score being the standardized neurocognitive Global Executive functioning z-score (Mean -0.71, SD 0.84). In the overall sample, factors associated with neurocognitive dysfunction included age (OR 1.43, 95%CI 1.23-1.98), abnormal stroke examination (OR 6.60, 95%CI 2.14-20.4), and non-normal TCD (OR 2.90, 95%CI 1.09-7.74) (Table 1; bold font denotes significance at p<0.05). These results were consistent within the age subgroups. Adjusting for sex, hemoglobin, malnutrition and stroke, age (aOR 1.50, 95%CI 1.25-1.79) and stroke (aOR 6.96, 95%CI 2.01-24.1) remained significant predictors of neurocognitive dysfunction in the entire sample. Conclusion: In children with SCA, executive function was the most common impairment. Overall, only 11% of the SCA children had impaired neurocognitive function. The major predictors of impairment were age, prior stroke and elevated TCD arterial velocity. These abnormalities were highly prevalent in the sample, and identifies significant disease-associated morbidity. Disease-modifying therapy should be assessed for improved neuropsychological function in these children. Disclosures No relevant conflicts of interest to declare.