Use of tobacco and other illicit drugs among adolescent boys and young men in Kampala, Uganda: A result of low parental attention?

INTRODUCTION: Although the use of illicit drugs is common among young people, limited data exists on the use of illicit drugs among adolescent boys and young men (ABYM). We assessed the use of tobacco, marijuana and khat among ABYM to inform the design of harm-reduction interventions. METHODS: This secondary analysis uses data from a formative study conducted among 2,500 ABYM across the five divisions of Kampala between July and August 2020. Survey questions were adopted from the Global Youth Tobacco Survey and Global School-based Student Health Survey. We computed proportions of ABYM that had ever used any form of tobacco or marijuana or khat in the past year and the proportion that had used any of these products in the past 30 days (i.e. 'current users'). In a sub-group analysis, we assessed if any patterns existed between ABYM's use of illicit drugs and selected parental attention attributes. RESULTS: Of 2,500 ABYM, 47.3% (n = 1,182) were aged 15-19 years. Overall, 16.4% (n = 410) reported past-year use of tobacco products while 11.6% (n = 289) and 10.5% (n = 263) reported past-year use of marijuana and khat, respectively. Current use of any illicit drugs was higher among past-year khat (46%, n = 133) and marijuana users (36.9%, n = 97) than past-year tobacco users (4%, n = 17). Current use of any illicit drugs was higher among out-of-school than in-school ABYM and increased with increasing age and education levels. However, parental attention was lower among out-of-school than in-school ABYM and decreased with increasing age and education levels. CONCLUSION: Use of illicit drugs is common among ABYM and increased with age and education levels but parental attention among current illicit drug users decreased with increasing age and education levels. These findings suggest that interventions intended to improve parental attention among illicit drug users may help to reduce the prevalence of illicit drug use among ABYM.

How interventions to maintain services during the COVID-19 pandemic strengthened systems for delivery of maternal and child health services: a case-study of Wakiso District, Uganda.

BACKGROUND: Health systems are resilient if they absorb, adapt, and transform in response to shocks. Although absorptive and adaptive capacities have been demonstrated during the COVID-19 response, little has been documented about their transformability and strengthened service delivery systems. We aimed to describe improvements in maternal and child health service delivery as a result of investments during the COVID-19 response. METHODS: This was a descriptive case study conducted in Wakiso District in central Uganda. It included 21 nurses and midwives as key informants and 32 mothers in three focus group discussions. Data were collected using an interview guide following the Systems Engineering Initiative for Patient Safety theoretical framework for service delivery. RESULTS: Maternal and child health service delivery during the pandemic involved service provision without changes, service delivery with temporary changes and outcomes, and service delivery that resulted into sustained changes and outcomes. Temporary changes included patient schedule adjustments, community service delivery and negative outcomes such as increased workload and stigma against health workers. Sustained changes that strengthened service delivery included new infrastructure and supplies such as ambulances and equipment, new roles involving infection prevention and control, increased role of community health workers and outcomes such as improved workplace safety and teamwork. CONCLUSIONS: In spite of the negative impact the COVID-19 pandemic had on health systems, it created the impetus to invest in system improvements. Investments such as new facility infrastructure and emergency medical services were leveraged to improve maternal and child health services delivery. The inter-departmental collaboration during the response to the COVID-19 pandemic resulted into an improved intra-hospital environment for other service delivery. However, there is a need to evaluate lessons beyond health facilities and whether these learnings are deliberately integrated into service delivery. Future responses should also address the psychological and physical impacts suffered by health workers to maintain service delivery.

Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.

Background: Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may prevent or decrease SCVI for reduced incident stroke, stroke risk and potentially cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesize that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA. Methods: The BRAIN SAFE II study is an open-label, single-arm trial of daily hydroxyurea for 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and clinically followed per local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages ≥5 years, along with biomarkers of anemia, inflammation and malnutrition (secondary outcomes). At trial midpoint (18 months) and completion (36 months), primary outcomes will be compared to participants' baseline to determine hydroxyurea impact and relationships to secondary outcomes. Conclusion: This open-label, single-arm trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide important insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.

Complete sources of cluster variation on the risk of under-five malaria in Uganda: a multilevel-weighted mixed effects logistic regression model approach.

BACKGROUND: Malaria, a major cause of mortality worldwide is linked to a web of determinants ranging from individual to contextual factors. This calls for examining the magnitude of the effect of clustering within malaria data. Regrettably, researchers usually ignore cluster variation on the risk of malaria and also apply final survey weights in multilevel modelling instead of multilevel weights. This most likely produces biased estimates, misleads inference and lowers study power. The objective of this study was to determine the complete sources of cluster variation on the risk of under-five malaria and risk factors associated with under-five malaria in Uganda. METHODS: This study applied a multilevel-weighted mixed effects logistic regression model to account for both individual and contextual factors. RESULTS: Every additional year in a child's age was positively associated with malaria infection (AOR = 1.42; 95% CI 1.33-1.52). Children whose mothers had at least a secondary school education were less likely to suffer from malaria infection (AOR = 0.53; 95% CI 0.30-0.95) as well as those who dwelled in households in the two highest wealth quintiles (AOR = 0.42; 95% CI 0.27-0.64). An increase in altitude by 1 m was negatively associated with malaria infection (AOR = 0.98; 95% CI 0.97-0.99). About 77% of the total variation in the positive testing for malaria was attributable to differences between enumeration areas (ICC = 0.77; p < 0.001). CONCLUSIONS: Interventions towards reducing the burden of under-five malaria should be prioritized to improve individual-level characteristics compared to household-level features. Enumeration area (EA) specific interventions may be more effective compared to household specific interventions.

Xanthine oxidase levels and immune dysregulation are independently associated with anemia in Plasmodium falciparum malaria.

Severe anemia is an important contributor to mortality in children with severe malaria. Anemia in malaria is a multi-factorial complication, since dyserythropoiesis, hemolysis and phagocytic clearance of uninfected red blood cells (RBCs) can contribute to this syndrome. High levels of oxidative stress and immune dysregulation have been proposed to contribute to severe malarial anemia, facilitating the clearance of uninfected RBCs. In a cohort of 552 Ugandan children with severe malaria, we measured the levels of xanthine oxidase (XO), an oxidative enzyme that is elevated in the plasma of malaria patients. The levels of XO in children with severe anemia were significantly higher compared to children with severe malaria not suffering from severe anemia. Levels of XO were inversely associated with RBC hemoglobin (ρ = - 0.25, p < 0.0001), indicating a relation between this enzyme and severe anemia. When compared with the levels of immune complexes and of autoimmune antibodies to phosphatidylserine, factors previously associated with severe anemia in malaria patients, we observed that XO is not associated with them, suggesting that XO is associated with severe anemia through an independent mechanism. XO was associated with prostration, acidosis, jaundice, respiratory distress, and kidney injury, which may reflect a broader relation of this enzyme with severe malaria pathology. Since inhibitors of XO are inexpensive and well-tolerated drugs already approved for use in humans, the validation of XO as a contributor to severe malarial anemia and other malaria complications may open new possibilities for much needed adjunctive therapy in malaria.

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women.

Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labor and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24 weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33 weeks gestation had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24 weeks of gestation.

Dihydroartemisinin-piperaquine or sulphadoxine-pyrimethamine for the chemoprevention of malaria in children with sickle cell anaemia in eastern and southern Africa (CHEMCHA): a protocol for a multi-centre, two-arm, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: An estimated 300,000 babies are born with sickle cell anaemia (SCA) annually. Affected children have chronic ill health and suffer premature death. Febrile illnesses such as malaria commonly precipitate acute crises in children with SCA. Thus, chemoprophylaxis for malaria is an important preventive strategy, but current regimes are either sub-optimally effective (e.g. monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g. daily proguanil). We propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa. METHODS: This will be a randomised, double-blind, parallel-group superiority trial of weekly single-day courses of DP compared to monthly single-day courses of SP in children with SCA. The study will be conducted in eastern (Uganda) and southern (Malawi) Africa using randomisation stratified by body weight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. We will investigate the efficacy, safety, acceptability and uptake and cost-effectiveness of malaria chemoprevention with weekly courses of DP vs monthly SP in 548 to 824 children with SCA followed up for 12-18 months. We will also assess toxicity from cumulative DP dosing and the development of resistance. Participant recruitment commenced on 30 April 2021; follow-up is ongoing. DISCUSSION: At the end of this study, findings will be used to inform regional health policy. This manuscript is prepared from protocol version 2.1 dated 1 January 2022. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov, NCT04844099 . Registered on 08 April 2021.

Severe Malaria and Academic Achievement.

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 with community children (CC, n = 100) from the same household or neighborhood, were on average enrolled 67.1 months (range, 19-101 months) after the severe malaria episode or previous study enrollment. Academic achievement in word reading, sentence comprehension, spelling, and math computation was evaluated using the Wide Range Achievement Test, Fourth Edition. Age-adjusted z-scores for academic achievement outcomes were calculated from CC scores. RESULTS: After adjustment for age and time from enrollment, reading scores were lower (mean difference from CC [95% confidence interval]) in children with CM (-0.15 [-0.27 to -0.03], P = .02) or SMA (-0.15 [-0.28 to -0.02], P = .02) than CC. Postdischarge malaria episodes were associated with worse spelling and reading scores in CM and worse spelling scores only in SMA. Pathway analysis showed that incidence of postdischarge uncomplicated malaria contributed significantly to the association of CM or SMA with poorer reading scores. CONCLUSION: Children with CM or SMA have poorer long-term reading skills. Postdischarge malaria episodes contribute significantly to this association. Postdischarge malaria chemoprevention should be assessed as an intervention to improve long-term academic achievement in children with severe malaria.

Interventions for Maintenance of Essential Health Service Delivery during the COVID-19 Response in Uganda, between March 2020 and April 2021.

INTRODUCTION: The COVID-19 pandemic overwhelmed health systems globally and affected the delivery of health services. We conducted a study in Uganda to describe the interventions adopted to maintain the delivery of other health services. METHODS: We reviewed documents and interviewed 21 key informants. Thematic analysis was conducted to identify themes using the World Health Organization health system building blocks as a guiding framework. RESULTS: Governance strategies included the establishment of coordination committees and the development and dissemination of guidelines. Infrastructure and commodity strategies included the review of drug supply plans and allowing emergency orders. Workforce strategies included the provision of infection prevention and control equipment, recruitment and provision of incentives. Service delivery modifications included the designation of facilities for COVID-19 management, patient self-management, dispensing drugs for longer periods and the leveraging community patient networks to distribute medicines. However, multi-month drug dispensing led to drug stock-outs while community drug distribution was associated with stigma. CONCLUSIONS: Health service maintenance during emergencies requires coordination to harness existing health system investments. The essential services continuity committee coordinated efforts to maintain services and should remain a critical element of emergency response. Self-management and leveraging patient networks should address stigma to support service continuity in similar settings and strengthen service delivery beyond the pandemic.

Plasma Amino Acid Concentrations in Children With Severe Malaria Are Associated With Mortality and Worse Long-term Kidney and Cognitive Outcomes.

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 has not been evaluated. METHODS: We measured enrollment plasma concentrations of 20 amino acids using high-performance liquid chromatography in 500 Ugandan children aged 18 months to 12 years, including 122 community children and 378 children with SM. The Kidney Disease: Improving Global Outcomes criteria were used to define acute kidney injury (AKI) at enrollment and chronic kidney disease (CKD) at 1-year follow-up. Cognition was assessed over 2 years of follow-up. RESULTS: Compared to laboratory-defined, age-specific reference ranges, there were deficiencies in sulfur-containing amino acids (methionine, cysteine) in both community children and children with SM. Among children with SM, global changes in amino acid concentrations were observed in the context of metabolic complications including acidosis and AKI. Increases in threonine, leucine, and valine were associated with in-hospital mortality, while increases in methionine, tyrosine, lysine, and phenylalanine were associated with postdischarge mortality and CKD. Increases in glycine and asparagine were associated with worse attention in children <5 years of age. CONCLUSIONS: Among children with SM, unique amino acid profiles are associated with mortality, CKD, and worse attention.

Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury that has been adapted to a urine dipstick test. However, there is limited data on its use in low-and-middle-income countries where diagnosis of acute kidney injury remains a challenge. To study this, we prospectively enrolled 250 children with sickle cell anemia aged two to 18 years encompassing 185 children hospitalized with a vaso-occlusive pain crisis and a reference group of 65 children attending the sickle cell clinic for routine care follow up. Kidney injury was defined using serial creatinine measures and a modified-Kidney Disease Improving Global Outcome definition for sickle cell anemia. Urine NGAL was measured using the NGAL dipstick and a laboratory reference. The mean age of children enrolled was 8.9 years and 42.8% were female. Among hospitalized children, 36.2% had kidney injury and 3.2% died. Measured urine NGAL levels by the dipstick were strongly correlated with the standard enzyme-linked immunosorbent assay for urine NGAL (hospitalized children, 0.71; routine care reference, 0.88). NGAL levels were elevated in kidney injury and significantly increased across injury stages. Hospitalized children with a high-risk dipstick test (300ng/mL and more) had a 2.47-fold relative risk of kidney injury (95% confidence interval 1.68 to 3.61) and 7.28 increased risk of death (95% confidence interval 1.10 to 26.81) adjusting for age and sex. Thus, urine NGAL levels were found to be significantly elevated in children with sickle cell anemia and acute kidney injury and may predict mortality.

Acute kidney injury in hospitalized children with sickle cell anemia.

BACKGROUND: Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC. METHODS: We prospectively enrolled 185 children from 2 - 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital in Uganda. Kidney function was assessed on admission, 24-48 h of hospitalization, and day 7 or discharge. Creatinine was measured enzymatically using an isotype-dilution mass spectrometry traceable method. AKI was defined using the original-KDIGO definition as ≥ 1.5-fold change in creatinine within seven days or an absolute change of ≥ 0.3 mg/dl within 48 h. The SCA modified-KDIGO (sKDIGO) definition excluded children with a 1.5-fold change in creatinine from 0.2 mg/dL to 0.3 mg/dL. RESULTS: Using KDIGO, 90/185 (48.7%) children had AKI with 61/185 (33.0%) AKI cases present on admission, and 29/124 (23.4%) cases of incident AKI. Overall, 23 children with AKI had a 1.5-fold increase in creatinine from 0.2 mg/dL to 0.3 m/dL. Using the sKDIGO-definition, 67/185 (36.2%) children had AKI with 43/185 (23.2%) cases on admission, and 24/142 (16.9%) cases of incident AKI. The sKDIGO definition, but not the original-KDIGO definition, was associated with increased mortality (0.9% vs. 7.5%, p = 0.024). Using logistic regression, AKI risk factors included age (aOR, 1.10, 95% CI 1.10, 1.20), hypovolemia (aOR, 2.98, 95% CI 1.08, 8.23), tender hepatomegaly (aOR, 2.46, 95% CI 1.05, 5.81), and infection (aOR, 2.63, 95% CI 1.19, 5.81) (p < 0.05). CONCLUSION: These results demonstrate that AKI is a common complication in children with SCA admitted with VOC. The sKDIGO definition of AKI in children with SCA was a better predictor of clinical outcomes in children. There is need for promotion of targeted interventions to ensure early identification and treatment of AKI in children with SCA.

Acute kidney injury, persistent kidney disease, and post-discharge morbidity and mortality in severe malaria in children: A prospective cohort study.

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 enrolled in a two-site prospective cohort study in Uganda and followed up for 12 months. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define AKI (primary exposure) and AKD at 1-month follow-up (primary outcome). Plasma neutrophil gelatinase-associated lipocalin (NGAL) was assessed as a structural biomarker of AKI. FINDINGS: The prevalence of AKI was 45·3% with 21·5% of children having unresolved AKI at 24 h. AKI was more common in Eastern Uganda. In-hospital mortality increased across AKI stages from 1·8% in children without AKI to 26·5% with Stage 3 AKI (p < 0·0001). Children with a high-risk plasma NGAL test were more likely to have unresolved AKI (OR, 7·00 95% CI 4·16 to 11·76) and die in hospital (OR, 6·02 95% CI 2·83 to 12·81). AKD prevalence was 15·6% at 1-month follow-up with most AKD occurring in Eastern Uganda. Risk factors for AKD included severe/unresolved AKI, blackwater fever, and a high-risk NGAL test (adjusted p < 0·05). Paracetamol use during hospitalization was associated with reduced AKD (p < 0·0001). Survivors with AKD post-AKI had higher post-discharge mortality (17·5%) compared with children without AKD (3·7%). INTERPRETATION: Children with severe malaria-associated AKI are at risk of AKD and post-discharge mortality. FUNDING: This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS055349 to CCJ) and the Fogarty International Center (D43 TW010928 to CCJ), and a Ralph W. and Grace M. Showalter Young Investigator Award to ALC.

Effect of four or more antenatal care visits on facility delivery and early postnatal care services utilization in Uganda: a propensity score matched analysis.

INTRODUCTION: Maternal mortality remains a global public health issue, more predominantly in developing countries, and is associated with poor maternal health services utilization. Antenatal care (ANC) visits are positively associated with facility delivery and postnatal care (PNC) utilization. However, ANC in itself may not lead to such association but due to differences that exist among users (women). The purpose of this study, therefore, is to examine the effect of four or more ANC visits on facility delivery and early PNC and also the effect of facility-based delivery on early PNC using Propensity Score Matched Analysis (PSMA). METHODS: The present study utilized the 2016 Uganda Demographic and Health Survey (UDHS) dataset. Women aged 15 - 49 years who had given birth three years preceding the survey were considered for this study. Propensity score-matched analysis was used to analyze the effect of four or more ANC visits on facility delivery and early PNC and also the effect of facility-based delivery on early PNC. RESULTS: The results revealed a significant and positive effect of four or more ANC visits on facility delivery [ATT (Average Treatment Effect of the Treated) = 0.118, 95% CI: 0.063 - 0.173] and early PNC [ATT = 0.099, 95% CI: 0.076 - 0.121]. It also found a positive and significant effect of facility-based delivery on early PNC [ATT = 0.518, 95% CI: 0.489 - 0.547]. CONCLUSION: Policies geared towards the provision of four or more ANC visits are an effective intervention towards improved facility-based delivery and early PNC utilisation in Uganda.

Falling through the net: An adaptive assessment of the 'Three Delays' encountered by patients seeking emergency maternal and neonatal care within a remote health system on Lake Victoria, Kenya.

In rural sub-Saharan Africa, preventable delays in accessing emergency care remain a dominant factor in maternal and neonatal deaths. The MOMENTUM study is a pragmatic cohort investigation designed to measure the "Three Delays", i.e. delays in recognizing need for care (Type 1), reaching care (Type 2), and receiving care (Type 3) within a remote island health system on Lake Victoria, Kenya. The study utilizes an adaptive methodology to provide actionable data for a locally-directed "Health Navigation" intervention. We present analysis of 56 maternal and neonatal emergency cases occurring between January 2019 and February 2020. The mean Total Delay Interval (Type 1-3) reported was 39.3 ± 32.3hours. Notably, 18 cases in this cohort resulted in a neonatal (n = 16) or maternal death (n = 2). Sub-analysis indicates significant delay interval reductions associated with involvement of a "Health Navigator" in emergency care coordination for Type 2 Delay Intervals (0.5 ± 0.3 vs. 1.2 ± 1.1 hrs., p = 0.002) and Type 3 Delay Intervals (17.9 ± 14.1 vs. 32.9 ± 33.7 hrs., p = 0.030). Prolonged delays, complex barriers, and high mortality highlight the fraught nature of maternal emergencies in this remote setting. We discuss practical considerations for application of the Three Delays model, and avenues for further investigation.

Evaluating kidney function using a point-of-care creatinine test in Ugandan children with severe malaria: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) disproportionately affects individuals in low-and middle-income countries (LMIC). However, LMIC-particularly countries in sub-Saharan Africa- are under-represented in global AKI research. A critical barrier in diagnosing AKI is access to reliable serum creatinine results. We evaluated the utility of a point-of-care test to measure creatinine and diagnose AKI in Ugandan children with malaria. METHODS: Paired admission creatinine was assessed in 539 Ugandan children 6 months to 4 years of age hospitalized with severe malaria based on blood smear or rapid diagnostic test. Creatinine levels were measured using isotope dilution mass spectrometry (IDMS)-traceable methods. The reference creatinine was measured using the modified Jaffe method by a certified laboratory and the point-of-care testing was conducted using an i-STAT blood analyzer (i-STAT1, with and without adjustment for the partial pressure of carbon dioxide). AKI was defined and staged using the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The mean age of children was 2.1 years, and 21.6% of children were stunted. Mortality was 7.6% in-hospital. Over the entire range of measured creatinine values (<0.20mg/dL-8.4mg/dL), the correlation between the reference creatinine and adjusted and unadjusted point-of-care creatinine was high with R2 values of 0.95 and 0.93 respectively; however, the correlation was significantly lower in children with creatinine values <1mg/dL (R2 of 0.44 between the reference and adjusted and unadjusted i-STAT creatinine). The prevalence of AKI was 45.5% using the reference creatinine, and 27.1 and 32.3% using the unadjusted and adjusted point-of-care creatinine values, respectively. There was a step-wise increase in mortality across AKI stages, and all methods were strongly associated with mortality (p<0.0001 for all). AKI defined using the reference creatinine measure was the most sensitive to predict mortality with a sensitivity of 85.4% compared to 70.7 and 63.4% with the adjusted and unadjusted point-of-care creatinine values, respectively. CONCLUSIONS: Point-of-care assessment of creatinine in lean Ugandan children <4 years of age underestimated creatinine and AKI compared to the clinical reference. Additional studies are needed to evaluate other biomarkers of AKI in LMIC to ensure equitable access to AKI diagnostics globally.

Parenteral artemisinins are associated with reduced mortality and neurologic deficits and improved long-term behavioral outcomes in children with severe malaria.

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, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up. RESULTS: 346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07-0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine. CONCLUSIONS: Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.

Use of the creating opportunities for parent empowerment programme to decrease mental health problems in Ugandan children surviving severe malaria: a randomized controlled trial.

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.

Alcohol use and associated factors among adolescent boys and young men in Kampala, Uganda.

BACKGROUND: Alcohol use leads to about 3 million deaths globally. The alcohol industry employs marketing strategies to establish their brands in the lives of young people at a time when addictive behaviors are initiated and reinforced. We conducted a survey among adolescent boys and young men (ABYM) to estimate the prevalence of alcohol use and associated factors using the Health Belief Model as the guiding framework. METHODS: The study was conducted among ABYM in- or out-of-school aged 10-24 years in Kampala, Uganda. We used questions adopted from the Global School-based Student Health Survey and the WHO STEPwise approach to Surveillance questionnaire to collect data. The outcome of interest was alcohol use within 30 days before the interview. We also asked about characteristics such as alcohol use by siblings, parents/ guardians, school status among others. We used odds ratios obtained via a logistic regression model as the measure of association. RESULTS: A total of 2500 ABYM participated, of which 262 (10.5 %, 95 %CI 9.3-11.7) had consumed alcohol within 30 days before the interview. Out-of-school ABYM had higher odds of consuming alcohol compared with their in-school counterparts AOR 1.55 (95 %CI 1.09-2.20). Compared with ABYM whose parents/ guardians did not drink alcohol, ABYM whose both parents consumed alcohol had higher odds of consuming alcohol AOR 2.24 (95 %CI 1.38-3.64) as were those with only a mother or female guardian who consumed alcohol AOR 1.95 (95 %CI 1.11-3.41). ABYM with siblings that drink alcohol had higher odds of consuming alcohol AOR 2.25 (95 %CI 1.80-3.52). ABYM who possessed items with an alcohol brand logo had higher odds of consuming alcohol AOR 2.00 (95 %CI 1.33-3.01). CONCLUSIONS: There are significant levels of alcohol consumption among ABYM which calls for evidence-based measures targeting this age group to reduce consumption and recognizing the role of the family, school and community in prevention and promotion of use. There is need to regulate alcohol marketing and ensuring availability of alcohol dependence treatment services that build confidence among youth.

Neurocognitive function among HIV-infected children on protease inhibitor -based versus non-protease inhibitor based antiretroviral therapy in Uganda: a pilot study.

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 better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children's neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART. METHODS: We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5-12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel's method was used to adjust for multiple testing. RESULTS: We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03). CONCLUSIONS: We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.