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.

Aims. Nodding syndrome is a poorly understood acquired disorder affecting children in sub‐Saharan Africa. The aetiology and pathogenesis are unknown, and no specific treatment is available. Affected children have a distinctive feature (repeated clusters of head nodding) and progressively develop many other features. In an earlier pilot study, we proposed a five‐level clinical staging system. The present study aimed to describe the early features and natural history of nodding syndrome and refine the proposed clinical stages. Methods. This was a retrospective study of the progressive development of symptoms and complications of nodding syndrome. Participants were a cohort of patients who had been identified by community health workers and were referred for treatment. A detailed history was obtained to document the chronological development of symptoms before and after onset of head nodding and a physical examination and disability assessment performed by a team of clinicians and therapists. Results. A total of 210 children were recruited. The mean age at the onset of head nodding was 7.5 (SD: 3.0) years. Five overlapping clinical stages were recognised: prodromal, head nodding, convulsive seizures, multiple impairments, and severe disability stages. Clinical features before the onset of head nodding (prodromal features) included periods of staring blankly or being inattentive, complaints of dizziness, excessive sleepiness, lethargy, and general body weakness, all occurring two weeks to 24 months before nodding developed. After the onset of head nodding, patients progressively developed convulsive seizures, cognitive and psychiatric dysfunction, physical deformities, growth arrest, and eventually, in some patients, severe disability. Conclusions. The description of the natural history of nodding syndrome and especially the prodromal features has the potential of providing a means for the early identification of at‐risk patients and the prompt initiation of interventions before extensive brain injury develops. The wide spectrum of symptoms and complications emphasises the need for multi‐disciplinary investigations and care.

ObjectivePlasmodium falciparum is epileptogenic and in malaria endemic areas, is a leading cause of acute seizures. In these areas, asymptomatic infections are common but considered benign and so, are not treated. The effects of such infections on seizures in patients with epilepsy is unknown. This study examined the relationship between P. falciparum infection and seizure control in children with a unique epilepsy type, the nodding syndrome.DesignThis cross-sectional study was nested in an ongoing trial ‘Doxycycline for the treatment of nodding syndrome (NCT02850913)’. We hypothesised that, in patients with epilepsy, infection by P. falciparum, including asymptomatic infections, increases the risk of seizures and impairs seizure control.Setting and participantsParticipants were Ugandan children with nodding syndrome, age ≥8 years, receiving sodium valproate. All had standardised testing including documentation of the number of seizures in the past month, a rapid malaria test and if positive, the peripheral blood parasite density.OutcomesThe primary outcome was the number of seizures in the past month (30 days).ResultsA total of 164/240 (68%) had malaria. Asymptomatic infections (without fever) were seen in 160/240 (67%) and symptomatic infections in 4/240 (2.7%). In participants without malaria, the median (IQR) number of seizures in the past month was 2.0 (1.0–4.0) and it was 4.0 (2.0–7.5) in participants with malaria, p=0.017. The number of seizures in asymptomatic persons was 3.0 (IQR 2.0–7.3) and 6.0 (IQR 4.0–10.0) in symptomatic individuals, p=0.024. Additionally, in asymptomatic patients, a positive correlation was observed between the parasite density and number of seizures, r=0.33, p=0.002.ConclusionIn patients with nodding syndrome, both asymptomatic and symptomatic malaria are associated with an increased risk of seizures and poorer seizure control. Similar effects should be examined in other epilepsy disorders. Malaria prevention should be strengthened for these patients and chemotreatment and prevention studies considered to improve seizure control.

Background: Following initiation of MDR-TB treatment, patients have a choice to receive follow up DOT supervision at either the central initiating facility or at a peripheral facility. Objectives: We describe the adherence patterns of MDR-TB patients undergoing DOT supervision at the two health facility categories during intensive phase of treatment. Methods: We used a retrospective cohort of patients initiated on MDR TB treatment at Mulago National Referral Hospital between 2014 and 2016. We extracted data from the National Tuberculosis and Leprosy Program records and analysed these using STATA V14. Results: Majority (84.01%) of the patients received their DOT supervision from the peripheral facilities. Males made up 62.1% of patients, and 91.2% had had their household contacts screened for MDR-TB. 26.5% of the patients on peripheral DOT supervision had good adherence to treatment protocol compared to 0% among patients on central initiating health fa- cility DOT supervision. Among the patients with good adherence, 24.1% had contacts screened for MDR-TB as compared to 3.6% with poor adherence. Conclusion: More patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settings. Keywords: MDR-TB; adherence; central initiating; peripheral health facility; DOTS; SORT IT.

Background Rapid reviews have emerged as an approach to provide contextualized evidence in a timely and efficient manner. Three rapid review centers were established in Ethiopia, Lebanon, and South Africa through the Alliance for Health Policy and Systems Research, World Health Organization, to stimulate demand, engage policymakers, and produce rapid reviews to support health policy and systems decision-making. This study aimed to assess the experiences of researchers and policymakers engaged in producing and using rapid reviews for health systems strengthening and decisions towards universal health coverage (UHC). Methods Using a case study approach with qualitative research methods, experienced researchers conducted semi-structured interviews with respondents from each center (n = 16). The topics covered included the process and experience of establishing the centers, stimulating demand for rapid reviews, collaborating between researchers and policymakers, and disseminating and using rapid reviews for health policies and interventions and the potential for sustaining and institutionalizing the services. Data were analyzed using thematic analysis. Results Major themes interacted and contributed to shape the experiences of stakeholders of the rapid review centers, including the following: organizational structural arrangements of the centers, management of their processes as input factors, and the rapid reviews as the immediate policy-relevant outputs. The engagement process and the rapid review products contributed to a final theme of impact of the rapid review centers in relation to the uptake of evidence for policy and systems decision-making. Conclusions The experiences of policymakers and researchers of the rapid review centers determined the uptake of evidence. The findings of this study can inform policymakers, health system managers, and researchers on best practices for demanding, developing and using rapid reviews to support decision- and policymaking, and implementing the universal healthcare coverage agenda.

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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 would be associated with cerebrovasculopathy found on MRI/MRA. Methods As part of a larger study to determine the burden and spectrum of neurological and cognitive impairments in SCA children in Uganda, we selected 81 children ages 1-12 years with HbSS, a sample enriched for possible brain pathology from Mulago hospital SCA clinic out of a random sample of 265 stable children. None was receiving hydroxyurea. All had detailed clinical history, and physical, neurological and cognitive testing, trans-cranial Doppler (TCD) cerebral blood flow velocity determination and non-contrasted brain MRI/MRA using a 1.5 Tesla scanner. Cognitive testing was performed using age-specific tools validated for Ugandan children. Results Of the 81 participants imaged, 61 had one or more of history of stroke, an abnormal neurological exam, cognitive impairment or abnormal TCD, while 20 had normal test results. MR abnormalities were seen in 35/61 (63.9%) participants with probable brain pathology and in 4/20 (20.0%) without any probable brain pathology. They included different structural abnormalities seen in all brain regions ranging from only T2 weighted hyper-intensities, white matter lacuna infarction to bilateral ischemic and multi-focal cerebral infarcts with associated compensatory hydrocephalus. MRA abnormalities ranged from cerebral microangiopathy to multiple stenosis and occlusions of major arteries, including moya-moya in 4 subjects. Severe vessel obstructions were also seen in multiple young children <36 months. Conclusions Brain injury in Uganda children with SCA begins early in childhood and becomes a common finding during later childhood. Early screening for stroke and intervention therapy is warranted to prevent sickle brain vasculopathy initiated early after diagnosis. The risk factors for such early brain injury should be investigated. Disclosures No relevant conflicts of interest to declare.

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 there would be high prevalence of multi-modal brain injury and stroke risk, as defined by 4 different adverse outcomes. Here we present our completed study results. Methods: Patients were randomly selected from the electronic clinic roster. None was taking hydroxyurea. Exclusion criteria: acute illness, Hb <6.0gm/dl, transfusion within the prior 3 months or participation in an unrelated clinical study. Adverse outcome was defined as abnormalities in ≥1 of 4 modalities examined. Stroke examination: were performed by pediatric NIH Stroke Scale (NIHSS). Psychometric testing: Age-appropriate Mullen Scales of Early Learning or Kaufman Assessment Battery, 2nd edition for Children-II, for ages 1-4 or 5-12, respectively, performed by skilled testers using validated versions in English or a predominant local language. Abnormal results defined as >2 Z scores below age-specific established community norms. Transcranial doppler ultrasounds (TCDs): Non-imaging TCDs (SonaraTek) were performed by two study trained staff (excellent inter-operator reliability >0.85); read by a U.S.-certified co-investigator. Brain magnetic resonance imaging (MRI), including arterial imaging (MRA): Subset of 81 (30.1%) of subjects (n=81), enriched for 1 or more testing abnormality, underwent non-contrast MRI/MRA imaging by a single 1.5T scanner. Two radiologists performed clinical reads. Statistical methods: ANOVA, multivariate, chi square, logistic regression. Results: Of 287 patients screened, all 265 eligible subjects were enrolled. Mean age was 5.5 SD 2.9 years, 52.3% male (Table 1). Mean Hb was 7.3 SD1.0 gm/dl. Each outcome was normally distributed.Stroke exam: Results: see below. Neurocognitive results: Overall results: see below. Poor testing: 2 of 100 ages 1-4 (2.0%) and 25 of 144 ages 5-12 (17.4%). TCDs: 13 of 251 (5.2%) were unread due to inadequate bone windows (12), poorly cooperative subject (1). Overall results: see below. MRI/MRAs: Overall results: see below. Abnormalities ranged from multiple small infarcts to multiple, bilateral infarcts and multi-vessel arterial stenoses. Among those with abnormal MRI/MRA, 13 (29.5%) also had a non-normal TCD. Summary data: In all, 58 (21.9%) subjects had ³1 abnormal outcomes. Among the 81 subjects with MR imaging, 28 (34.6%) had ³2 abnormal outcomes: 18 had 2; 9 had 3; 1 had all 4. Analyses: Abnormal neurocognitive results were highly dependent (6.8-fold) on age (<0.001) (Table 2). Abnormal MR imaging was associated had a 3-fold with abnormal neurocognitive results (0.034), but not significant when adjusted for age. Conclusions: These data demonstrate early, frequent neurovascular pathology for each outcome tested. Abnormal neurocognitive test results significantly increased with age or non-normal TCD. Our findings provide a baseline for longitudinal assessment and incentive for intervention. Enhanced research capacity was gained for junior faculty, trainees and staff, in areas of the conduct of brain research and focus on pediatric SCD, TCD performance and neuro-epidemiology. Funding: 1R21HD089791 (PIs: Idro, Green) Disclosures No relevant conflicts of interest to declare.