RESUMO
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.
Assuntos
Malária , Criança , Feminino , Humanos , Modelos Logísticos , Uganda/epidemiologia , Malária/epidemiologia , Fatores de Risco , Características da FamíliaRESUMO
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.
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Injúria Renal Aguda , Malária , Insuficiência Renal Crônica , Criança , Humanos , Pré-Escolar , Assistência ao Convalescente , Alta do Paciente , Aminoácidos/metabolismo , Rim/metabolismo , Malária/complicações , Metionina , Insuficiência Renal Crônica/complicações , CogniçãoRESUMO
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.
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Injúria Renal Aguda , Anemia Falciforme , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Proteínas de Fase Aguda/urina , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Biomarcadores/urina , Criança , Creatinina , Feminino , Humanos , Lipocalina-2 , Lipocalinas , Masculino , Proteínas Proto-OncogênicasRESUMO
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.
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Parto Obstétrico/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cuidado Pós-Natal , Cuidado Pré-Natal , Adolescente , Adulto , Demografia , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Pontuação de Propensão , Uganda , Adulto JovemRESUMO
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.
Assuntos
Antimaláricos , Artemisininas , Malária Cerebral , Malária Falciparum , Assistência ao Convalescente , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Criança , Humanos , Malária Cerebral/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Alta do Paciente , Quinina/uso terapêuticoRESUMO
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.
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Terapia Comportamental/instrumentação , Cuidadores/psicologia , Saúde da Criança/estatística & dados numéricos , Empoderamento , Saúde Mental/estatística & dados numéricos , Pais/psicologia , Pré-Escolar , Humanos , Lactente , UgandaRESUMO
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 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini-Hochberg Procedure of False Discovery Rate. RESULTS: Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode. CONCLUSION: Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.
Assuntos
Angiopoietina-2/sangue , Cognição , Malária Falciparum/parasitologia , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Plasma/química , UgandaRESUMO
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.
Assuntos
Injúria Renal Aguda/diagnóstico , Creatinina/sangue , Malária/complicações , Testes Imediatos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Biomarcadores/sangue , Pré-Escolar , Humanos , Lactente , Estudos Prospectivos , Uganda/epidemiologiaRESUMO
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.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Infecções por HIV/tratamento farmacológico , Humanos , Projetos Piloto , Estudos Prospectivos , Inibidores de Proteases/uso terapêutico , Qualidade de Vida , Uganda , Carga ViralRESUMO
BACKGROUND: Elevated concentrations of cerebrospinal fluid (CSF) tau, a marker of axonal injury, have been associated with coma in severe malaria (cerebral malaria [CM]). However, it is unknown whether axonal injury is related to long-term neurologic deficits and cognitive impairment in children with CM. METHODS: Admission CSF tau concentrations were measured in 145 Ugandan children with CM and compared to clinical and laboratory factors and acute and chronic neurologic and cognitive outcomes. RESULTS: Elevated CSF tau concentrations were associated with younger age, increased disease severity (lower glucose and hemoglobin concentrations, malaria retinopathy, acute kidney injury, and prolonged coma duration, all P < .05), and an increased CSF:plasma albumin ratio, a marker of blood-brain barrier breakdown (P < .001). Admission CSF tau concentrations were associated with the presence of neurologic deficits at hospital discharge, and at 6, 12, and 24 months postdischarge (all P ≤ .02). After adjustment for potential confounding factors, elevated log10-transformed CSF tau concentrations correlated with worse cognitive outcome z scores over 2-year follow-up for associative memory (ß coefficient, -0.31 [95% confidence interval [CI], -.53 to -.10]) in children <5 years of age, and for overall cognition (-0.69 [95% CI, -1.19 to -.21]), attention (-0.78 [95% CI, -1.34 to -.23]), and working memory (-1.0 [95% CI, -1.68 to -.31]) in children ≥5 years of age (all P < .006). CONCLUSIONS: Acute axonal injury in children with CM is associated with long-term neurologic deficits and cognitive impairment. CSF tau concentrations at the time of the CM episode may identify children at high risk of long-term neurocognitive impairment.
Assuntos
Disfunção Cognitiva , Malária Cerebral , Assistência ao Convalescente , Biomarcadores , Criança , Humanos , Malária Cerebral/complicações , Alta do Paciente , Uganda/epidemiologia , Proteínas tauRESUMO
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: Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, ß -0.42, 95% CI, -0.69 to -0.15, p = 0.002; children ≥ 5, ß -0.39, 95% CI, -0.67 to -0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau). CONCLUSIONS: These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.
Assuntos
Injúria Renal Aguda/etiologia , Angiopoietina-2/biossíntese , Disfunção Cognitiva/etiologia , Endotélio/metabolismo , Malária Cerebral/complicações , Injúria Renal Aguda/fisiopatologia , Fatores Etários , Anemia Falciforme/epidemiologia , Criança , Pré-Escolar , Disfunção Cognitiva/fisiopatologia , Comorbidade , Feminino , Hemólise/fisiologia , Humanos , Imunoensaio , Lactente , Mediadores da Inflamação/metabolismo , Malária Cerebral/epidemiologia , Malária Cerebral/fisiopatologia , Masculino , Fatores de Risco , Índice de Gravidade de Doença , Fatores Socioeconômicos , Sobreviventes , Uganda/epidemiologiaRESUMO
BACKGROUND: 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. METHODS: In this study, Ugandan children 18 months to 5 years old with cerebral malaria (CM, n = 79), severe malarial anemia (SMA, n = 77), or community children (CC, n = 83) were enrolled and tested for ID. Children with ID were randomized to immediate vs. 28-day delayed iron therapy. Cognitive and neurobehavioral outcomes were assessed at baseline and 6 and 12 months (primary endpoint) after enrollment. RESULTS: All children with CM or SMA and 35 CC had ID (zinc protoporphyrin concentration ≥80 µmol/mol heme). No significant differences were seen at 12-month follow-up in overall cognitive ability, attention, associative memory, or behavioral outcomes between immediate and delayed iron treatment (mean difference (standard error of mean) ranged from -0.2 (0.39) to 0.98 (0.5), all P ≥ 0.06). CONCLUSIONS: Children with CM or SMA and ID who received immediate vs. delayed iron therapy had similar cognitive and neurobehavioral outcomes at 12-month follow-up. IMPACT: The optimal time to provide iron therapy in children with severe malaria is not known. The present study shows that delay of iron treatment to 28 days after the malaria episode, does not lead to worse cognitive or behavioral outcomes at 12-month follow-up. The study contributes new data to the ongoing discussion of how best to treat ID in children with severe malaria.
Assuntos
Anemia Ferropriva/fisiopatologia , Transtornos do Comportamento Infantil/fisiopatologia , Heme/análise , Deficiências de Ferro , Ferro/uso terapêutico , Malária Cerebral/fisiopatologia , Anemia Ferropriva/complicações , Atenção , Comportamento , Pré-Escolar , Cognição , Esquema de Medicação , Emoções , Feminino , Seguimentos , Humanos , Lactente , Malária Cerebral/complicações , Masculino , Memória , Protoporfirinas/sangue , Uganda/epidemiologiaRESUMO
BACKGROUND: Acute kidney injury (AKI) is increasingly recognized as a consequential clinical complication in children with severe malaria. However, approaches to estimate baseline creatinine (bSCr) are not standardized in this unique patient population. Prior to wide-spread utilization, bSCr estimation methods need to be evaluated in many populations, particularly in children from low-income countries. METHODS: We evaluated six methods to estimate bSCr in Ugandan children aged 6 months to 12 years of age in two cohorts of children with severe malaria (n = 1078) and healthy community children (n = 289). Using isotope dilution mass spectrometry (IDMS)-traceable creatinine measures from community children, we evaluated the bias, accuracy and precision of estimating bSCr using height-dependent and height-independent estimated glomerular filtration (eGFR) equations to back-calculate bSCr or estimating bSCr directly using published or population-specific norms. RESULTS: We compared methods to estimate bSCr in healthy community children against the IDMS-traceable SCr measure. The Pottel-age based equation, assuming a normal GFR of 120 mL/min per 1.73m2, was the more accurate method with minimal bias when compared to the Schwartz height-based equation. Using the different bSCr estimates, we demonstrated the prevalence of KDIGO-defined AKI in children with severe malaria ranged from 15.6-43.4%. The lowest estimate was derived using population upper levels of normal and the highest estimate was derived using the mean GFR of the community children (137 mL/min per 1.73m2) to back-calculate the bSCr. Irrespective of approach, AKI was strongly associated with mortality with a step-wise increase in mortality across AKI stages (p < 0.0001 for all). AKI defined using the Pottel-age based equation to estimate bSCr showed the strongest relationship with mortality with a risk ratio of 5.13 (95% CI 3.03-8.68) adjusting for child age and sex. CONCLUSIONS: We recommend using height-independent age-based approaches to estimate bSCr in hospitalized children in sub-Saharan Africa due to challenges in accurate height measurements and undernutrition which may impact bSCr estimates. In this population the Pottel-age based GFR estimating equation obtained comparable bSCr estimates to population-based estimates in healthy children.
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Injúria Renal Aguda/sangue , Análise Química do Sangue/métodos , Creatinina/sangue , Taxa de Filtração Glomerular , Malária/complicações , Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Análise de Variância , Biomarcadores/sangue , Peso Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Malária/sangue , Malária/mortalidade , Masculino , Modelos Estatísticos , Prevalência , Estudos Prospectivos , Magreza , Uganda/epidemiologiaRESUMO
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 cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age. RESULTS: The prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption. CONCLUSIONS: AKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.
Assuntos
Injúria Renal Aguda/epidemiologia , Transtornos Cognitivos/epidemiologia , Malária/complicações , Malária/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Injúria Renal Aguda/complicações , Injúria Renal Aguda/psicologia , Criança , Pré-Escolar , Transtornos Cognitivos/etiologia , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Humanos , Lactente , Malária/patologia , Malária/psicologia , Malária Cerebral/complicações , Malária Cerebral/epidemiologia , Masculino , Prevalência , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/psicologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Uganda/epidemiologiaRESUMO
OBJECTIVES: Few studies have been conducted in Africa to assess prevalence of sexually transmitted infections (STIs) and risk factors among men who have sex with men (MSM). We report findings from the first behavioural survey to include STI testing among MSM in Kampala, Uganda. METHODS: Respondent-driven sampling (RDS) was used to recruit MSM for a biobehavioural survey. Eligible participants were men who reported anal sex with another man in the previous 3â months, were 18â years or older, and resided in Kampala. Information was collected on demographics, sexual behaviour, alcohol and drug use, and STI symptoms. Blood, urine and rectal specimens were tested for syphilis, HIV, rectal and urethral gonorrhoea, and chlamydia. Analyses weighted for RDS were conducted to assess associations with STI diagnosis. RESULTS: A total of 295 MSM participated in the survey. Almost half (weighted percentage: 47.3%) reported STI symptoms in the last 6â months and 12.9% tested HIV-positive. Prevalence of non-HIV STI was 13.5%; syphilis prevalence was 9.0%. Adjusting for age and education, STI was associated with HIV (adjusted OR (AOR)=3.46, 95% CI 1.03 to 11.64), alcohol use before sex (AOR=4.99, 95% CI 1.86 to 13.38) and having sold sex in the last 3â months (AOR=3.17, 95% CI 1.25 to 8.07), and inversely associated with having anonymous sex partners (AOR=0.20, 95% CI 0.07 to 0.61). CONCLUSIONS: We observed high levels of self-reported STI symptoms and STI prevalence associated with alcohol use and HIV among MSM in Kampala. Public health interventions supporting MSM are needed to address STI risk and facilitate access to diagnosis and treatment services.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Infecções por HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Fatores Etários , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/etiologia , Estudos Transversais , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Gonorreia/etiologia , Infecções por HIV/complicações , Humanos , Masculino , Prevalência , Fatores de Risco , Parceiros Sexuais/classificação , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/etiologia , Inquéritos e Questionários , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/etiologia , Uganda/epidemiologia , Adulto JovemRESUMO
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.
Assuntos
COVID-19 , Serviços de Saúde da Criança , Criança , Humanos , COVID-19/epidemiologia , Pandemias/prevenção & controle , Uganda/epidemiologia , Agentes Comunitários de SaúdeRESUMO
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.
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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 children with SCA in Uganda compared to siblings without SCA. Design and setting: A cross-sectional study conducted at Mulago Hospital SCA Clinic in Uganda. Participants: School-going children (6-12 years) with SCA and age-matched sibling controls without SCA. Outcome measures: Academic achievement was tested using the Wide Range Achievement Test, Fourth Edition (WRAT4). Outcome measures were spelling, mathematical computation, word reading, and sentence comprehension by age-normalized Z-scores on the WRAT4 test. Results: Among 68 SCA and 69 control, the mean age (standard deviation) was 9.44 (2.04) and 9.42 (2.02) years and males were 55.9% and 46.4% respectively. Mean haemoglobin was 7.9 (SD 0.89)g/dL in the SCA group versus 12.8 (SD 0.89)g/dL in the controls, (p<0.001). Children with SCA scored lower in spelling, (mean difference [95% confidence interval] - 0.36 [-0.02 to -0.69], p=0.04) and mathematical computation, (mean difference [95% confidence interval] -0.51 [-0.17 to -0.85], p=0.003) than the controls. In the SCA group, lower scores in spelling correlated with age, while males performed better than females in mathematical computation. Conclusion: School-aged children with SCA are at risk of poor performance in spelling and mathematical computation. Our findings support the need for educational evaluation and possible support, especially in these two areas.
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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.
Assuntos
Sucesso Acadêmico , Anemia , Malária Cerebral , Criança , Humanos , Pré-Escolar , Assistência ao Convalescente , Alta do Paciente , Malária Cerebral/epidemiologia , Anemia/complicaçõesRESUMO
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.