Sophie Namasopo - Academia.edu (original) (raw)

Papers by Sophie Namasopo

The Journal of Infectious Diseases

Background Severe malaria is associated with multiple organ dysfunction syndrome (MODS), which ma... more Background Severe malaria is associated with multiple organ dysfunction syndrome (MODS), which may involve the gastrointestinal tract. Methods In a prospective cohort study in Uganda, we measured markers of intestinal injury (intestinal fatty-acid binding protein [I-FABP] and zonula occludens-1 [ZO-1]) and microbial translocation (lipopolysaccharide binding protein [LBP] and soluble complement of differentiation 14 [sCD14]) among children admitted with malaria. We examined their association with biomarkers of inflammation, endothelial activation, clinical signs of hypoperfusion, organ injury, and mortality. Results We enrolled 523 children (median age 1.5 years, 46% female, 7.5% mortality). Intestinal FABP was above the normal range (≥400 pg/mL) in 415 of 523 patients (79%). Intestinal FABP correlated with ZO-1 (ρ = 0.11, P = .014), sCD14 (ρ = 0.12, P = .0046) as well as markers of inflammation and endothelial activation. Higher I-FABP levels were associated with lower systolic bloo...

PLOS Medicine

Background Despite the global burden of pneumonia, reliable triage tools to identify children in ... more Background Despite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death. Methods and findings We conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia. Circulating plasma markers of immune (IL-6, IL-8, CXCL-10/IP-10, CHI3L1, sTNFR1, and sTREM-1) and endothelial (sVCAM-1, sICAM-1, Angpt-1, Angpt-2, and sFlt-1) activation measured at hospital presentation were compared to lactate, respiratory ra...

Evaluation of missing data used in analysis in survivors and non-survivors. Table S2. Unadjusted ... more Evaluation of missing data used in analysis in survivors and non-survivors. Table S2. Unadjusted odds ratios for fatal outcome based on clinical severity scores and individual variables.

Additional file 1. Longitudinal dataset. This dataset was used for analysis of change in VWF anti... more Additional file 1. Longitudinal dataset. This dataset was used for analysis of change in VWF antigen over time. The file is available as an excel spreadsheet.

from Canada in collaboration with the Ministry of Health of Uganda. We plan to enroll a total of ... more from Canada in collaboration with the Ministry of Health of Uganda. We plan to enroll a total of 2400 children in the study across 20 hospitals in Uganda. All children in the study will in addition receive the standard treatment in hospital for their disease. B. Background and rationale for the study: Previously, we determined that a new way of delivering oxygen, using solar power, is as effective for giving oxygen to patients as standard oxygen tanks. We are now expanding solar oxygen across Uganda, and we are tracking patients to measure the benefit of bringing solar oxygen to the hospital in terms of lives saved.

Cytokine, 2022

Pneumonia is the leading infectious cause of death in children, with especially high mortality in... more Pneumonia is the leading infectious cause of death in children, with especially high mortality in low- and middle-income countries. Interleukin-18 binding protein (IL-18BP) is a natural antagonist of the pro-inflammatory cytokine interleukin-18 and is elevated in numerous autoimmune conditions and infectious diseases. We conducted a prospective cohort study to determine the association between admission IL-18BP levels and clinical severity among children admitted to two hospitals in Uganda for hypoxemic pneumonia. A total of 42 children (median age of 1.2 years) were included. IL-18BP levels were higher in patients with respiratory distress, including chest indrawing (median 15 ng/mL (IQR 9.8-18) versus 4.5 ng/mL (IQR 3.8-11) without chest indrawing, P = 0.0064) and nasal flaring (median 15 ng/mL (IQR 9.7-19) versus 11 ng/mL (IQR 5.4-14) without nasal flaring, P = 0.034). IL-18BP levels were positively correlated with the composite clinical severity score, Pediatric Early Death Index for Africa (PEDIA-e, ρ = 0.46, P = 0.0020). Patients with IL-18BP > 14 ng/mL also had slower recovery times, including time to sit (median 0.69 days (IQR 0.25-1) versus 0.15 days (IQR 0.076-0.36) with IL-18BP < 14 ng/mL, P = 0.036) and time to fever resolution (median 0.63 days (IQR 0.16-2) versus 0.13 days (IQR 0-0.42), P = 0.016). In summary, higher IL-18BP levels were associated with increased disease severity and prolonged recovery times in Ugandan children with pneumonia.

JAMA Network Open, 2021

IMPORTANCE Pneumonia is the leading cause of childhood mortality worldwide. Severe pneumonia asso... more IMPORTANCE Pneumonia is the leading cause of childhood mortality worldwide. Severe pneumonia associated with hypoxemia requires oxygen therapy; however, access remains unreliable in low-and middle-income countries. Solar-powered oxygen delivery (solar-powered O 2) has been shown to be a safe and effective technology for delivering medical oxygen. Examining the costeffectiveness of this innovation is critical for guiding implementation in low-resource settings. OBJECTIVE To determine the cost-effectiveness of solar-powered O 2 for treating children in low-resource settings with severe pneumonia who require oxygen therapy. DESIGN, SETTING, AND PARTICIPANTS An economic evaluation study of solar-powered O 2 was conducted from January 12, 2020, to February 27, 2021, in compliance with the World Health Organization Choosing Interventions That Are Cost-Effective (WHO-CHOICE) guidelines. Using existing literature, plausible ranges for component costs of solar-powered O 2 were determined in order to calculate the expected total cost of implementation. The costs of implementing solarpowered O 2 at a single health facility in low-and middle-income countries was analyzed for pediatric patients younger than 5 years who required supplemental oxygen. EXPOSURES Treatment with solar-powered O 2. MAIN OUTCOMES AND MEASURES The incremental cost-effectiveness ratio (ICER) of solarpowered O 2 was calculated as the additional cost per disability-adjusted life-year (DALY) saved. Sensitivity of the ICER to uncertainties of input parameters was assessed through univariate and probabilistic sensitivity analyses. RESULTS The ICER of solar-powered O 2 was estimated to be 20(USdollars)perDALYsaved(9520 (US dollars) per DALY saved (95% CI, 20(USdollars)perDALYsaved(952.83-$206) relative to the null case (no oxygen). Costs of solar-powered O 2 were alternatively quantified as 26perpatienttreatedand26 per patient treated and 26perpatienttreatedand542 per life saved. Univariate sensitivity analysis found that the ICER was most sensitive to the volume of pediatric pneumonia admissions and the case fatality rate. The ICER was insensitive to component costs of solar-powered O 2 systems. In secondary analyses, solar-powered O 2 was cost-effective relative to grid-powered concentrators (ICER 140perDALYsaved)andcost−savingrelativetofuelgenerator−poweredconcentrators(costsavingof140 per DALY saved) and cost-saving relative to fuel generator-powered concentrators (cost saving of 140perDALYsaved)andcost−savingrelativetofuelgenerator−poweredconcentrators(costsavingof7120). CONCLUSIONS AND RELEVANCE The results of this economic evaluation suggest that solarpowered O 2 is a cost-effective solution for treating hypoxemia in young children in low-and middleincome countries, relative to no oxygen. Future implementation should prioritize sites with high rates (continued) Key Points Question Is solar-powered oxygen delivery (solar-powered O 2) a costeffective intervention for use in children younger than 5 years with hypoxemia in low-resource settings? Findings This economic evaluation compared the costs and health outcomes of solar-powered O 2 with (1) null case with no oxygen, (2) gridpowered oxygen concentrators, and (3) fuel generator-powered concentrators. Use of solar-powered O 2 was costeffective relative to the null case and grid-powered concentrators and was cost-saving relative to fuel generatorpowered concentrators. Meaning The results of this economic evaluation suggest that solar-powered O 2 is a cost-effective intervention for pediatric patients with hypoxemia in low-resource settings.

Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but... more Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children at risk of sepsis due to all causes. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843-0.944) and 0.901 in external validation (95% CI 0.856-0.947). sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of d...

Pediatric Hematology and Oncology, 2019

Parenteral artesunate for the treatment of severe malaria in nonimmune travelers is associated wi... more Parenteral artesunate for the treatment of severe malaria in nonimmune travelers is associated with late-onset hemolysis. In children in sub-Saharan Africa, the hematologic effects of malaria and artesunate are less well documented. Here we report a prospective case series of 91 children with severe malaria treated with parenteral artesunate, managed at a resource-poor hospital in Africa, with longitudinal data on hemoglobin (Hb), lactate dehydrogenase (LDH), haptoglobin, and erythrocyte morphology. The median (range) age was 2 (1-8) years and 43 (47%) were female. The median (IQR) admission Hb level was 69 (55-78) g/L and 20 patients (22%) had severe malarial anemia (Hb < 50 g/L). During hospitalization, 69 patients (76%) received one or more blood transfusions. Fatal outcome in 8 patients was associated with severe anemia in 6/8 cases. Follow-up Hb measurement was performed on 35 patients (38%) at day 14 after initial hospital admission; the remaining patients had no clinical evidence of anemia at the follow-up visit. The convalescent Hb was median (range) 90 (60-138) g/L, which was significantly higher than the paired admission levels (median increase þ28 g/L, p < .001). Evidence of hemolysis (elevated LDH and low haptoglobin) was common at admission and improved by day 14. No patient met the standardized definition of post-artemisinin delayed hemolysis (PADH). In this cohort of young children with severe malaria treated with artesunate, anemia was common at admission, required one or more transfusions in a majority of patients, and markers of hemolysis had normalized by day 14.

Trials, 2019

Background Child mortality due to pneumonia is a major global health problem and is associated wi... more Background Child mortality due to pneumonia is a major global health problem and is associated with hypoxemia. Access to safe and continuous oxygen therapy can reduce mortality; however, low-income countries may lack the necessary resources for oxygen delivery. We have previously demonstrated proof-of-concept that solar-powered oxygen (SPO2) delivery can reliably provide medical oxygen remote settings with minimal access to electricity. This study aims to demonstrate the efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness across Uganda. Methods Objectives: Demonstrate efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness. Study design: Multi-center, stepped-wedge cluster-randomized trial. Setting: Twenty health facilities across Uganda, a low-income, high-burden country for pediatric pneumonia. Site selection: Facilities with pediatric inpatient services lacking consistent O2 supply on pediatric wards. Participants: Childre...

Paediatrics and International Child Health, 2019

The American Journal of Tropical Medicine and Hygiene, 2018

Globally, pneumonia is the leading cause of death among children younger than 5 years old, with m... more Globally, pneumonia is the leading cause of death among children younger than 5 years old, with most deaths occurring in low-income countries. Rapid bedside tools to assist practitioners to accurately triage and risk-stratify these patients may improve clinical care and patient outcomes. We conducted a prospective cohort study of children with pneumonia admitted to two Ugandan hospitals to examine the predictive value of a single point-of-care lactate measurement using a commercially available handheld device, the Lactate Scout Analyzer. One hundred and fifty-five children were included, 90 (58%) male, with a median (interquartile range [IQR]) age of 11 (1.4-20) months. One hundred and twenty-five (81%) patients had chest indrawing, 133 (86%) were hypoxemic, and 75 (68%) had a chest x-ray abnormality. In-hospital mortality was 22/155 (14%). Median (IQR) admission lactate level was 2.4 (1.8-3.6) mmol/L among children who survived versus 7.2 (2.6-9.7) mmol/L among those who died (P < 0.001). Lactate was a better prognostic marker of mortality (area under receiver operator characteristic 0.76, 95% confidence interval: 0.69-0.87, P £ 0.001), than any single clinical sign or composite clinical risk score. Lactate level at admission of < 2.0, 2.0-4.0, and > 4.0 mmol/L accurately riskstratified children, with 5-day mortality of 2%, 11% and 26%, respectively (P < 0.001). Slow lactate clearance also predicted subsequent mortality in children with repeated lactate measurements. Hand-held lactate measurement is a clinically informative and convenient tool in low-resource settings for triage and risk stratification of pediatric pneumonia.

Malaria journal, Jan 15, 2018

Chitinase-3-like 1 (CHI3L1) is a glycoprotein elevated in paediatric severe malaria, and an emerg... more Chitinase-3-like 1 (CHI3L1) is a glycoprotein elevated in paediatric severe malaria, and an emerging urinary biomarker of acute kidney injury (AKI). Based on the hypothesis that elevated CHI3L1 levels in malaria are associated with disease severity, the relationship between plasma CHI3L1 levels, AKI and mortality was investigated in Ugandan children enrolled in a clinical trial evaluating inhaled nitric oxide (iNO) as an adjunctive therapy for severe malaria. Plasma CHI3L1 levels were measured daily for 4 days in children admitted to hospital with severe malaria and at day 14 follow up. AKI was defined using the Kidney Disease: Improving Global Outcomes consensus criteria. This is a secondary analysis of a randomized double-blind placebo-controlled trial of iNO versus placebo as an adjunctive therapy for severe malaria. Inclusion criteria were: age 1-10 years, and selected criteria for severe malaria. Exclusion criteria included suspected bacterial meningitis, known chronic illness ...

PloS one, 2018

Severe malaria is a leading cause of acquired neurodisability in Africa and is associated with re... more Severe malaria is a leading cause of acquired neurodisability in Africa and is associated with reduced nitric oxide (NO) bioavailability. A neuroprotective role for inhaled NO has been reported in animal studies, and administration of inhaled NO in preterm neonates with respiratory distress syndrome is associated with a 47% reduced risk of cognitive impairment at two years of age. A randomized double-blind placebo-controlled trial of inhaled NO versus placebo as an adjunctive therapy for severe malaria was conducted in Uganda between 2011 and 2013. Children received study gas for a maximum 72 hours (inhaled NO, 80 parts per million; room air placebo). Neurocognitive testing was performed on children<5 years at 6 month follow-up. The neurocognitive outcomes assessed were overall cognition (a composite of fine motor, visual reception, receptive language, and expressive language), attention, associative memory, and the global executive composite. Main outcomes were attention, associ...

The International Journal of Tuberculosis and Lung Disease, 2016

SETTING A resource-limited paediatric hospital in Uganda. OBJECTIVE Pneumonia is a leading cause ... more SETTING A resource-limited paediatric hospital in Uganda. OBJECTIVE Pneumonia is a leading cause of child mortality worldwide. Access to life-saving oxygen therapy is limited in many areas. We designed and implemented a solar-powered oxygen delivery system for the treatment of paediatric pneumonia. DESIGN Proof-of-concept pilot study. A solar-powered oxygen delivery system was designed and piloted in a cohort of children with hypoxaemic illness. RESULTS The system consisted of 25 × 80 W photovoltaic solar panels (daily output 7.5 kWh [range 3.8-9.7kWh]), 8 × 220 Ah batteries and a 300 W oxygen concentrator (output up to 5 l/min oxygen at 88% [±2%] purity). A series of 28 patients with hypoxaemia were treated with solar-powered oxygen. Immediate improvement in peripheral blood oxygen saturation was documented (median change +12% [range 5-15%], P < 0.0001). Tachypnoea, tachycardia and composite illness severity score improved over the first 24 h of hospitalisation (P < 0.01 for all comparisons). The case fatality rate was 6/28 (21%). The median recovery times to sit, eat, wean oxygen and hospital discharge were respectively 7.5 h, 9.8 h, 44 h and 4 days. CONCLUSION Solar energy can be used to concentrate oxygen from ambient air and oxygenate children with respiratory distress and hypoxaemia in a resource-limited setting.

Journal of tropical pediatrics, Jan 8, 2017

Oxygen is essential, life-saving, supportive treatment for children with hypoxaemia but is not av... more Oxygen is essential, life-saving, supportive treatment for children with hypoxaemia but is not available in many resource-constrained health facilities. We conducted a cross-sectional survey of oxygen availability and nurses' skills for oxygen administration at the paediatric wards of 11 district hospitals in eastern Uganda. Functional oxygen delivery was available at the paediatric wards of only 2 of 11 (18%) hospitals. Of the six concentrators found, two did not function at all and two produced a stream of O2 <80% pure. Most nurses (76%) had adequate knowledge on how to use a concentrator, but the majority did not know how to use a pulse oximeter or administer cylinder oxygen. All nurses felt the need for further training on O2 administration and equipment. Given the large number of childhood pneumonia deaths occurring in resource-limited settings, improving availability of oxygen and nursing skills to administer oxygen could lead to substantial gains in global child survival.

BMC pediatrics, Nov 4, 2016

Exposure of red blood cells to oxidants increases production of methemoglobin (MHb) resulting in ... more Exposure of red blood cells to oxidants increases production of methemoglobin (MHb) resulting in impaired oxygen delivery to tissues. There are no reliable estimates of methemoglobinemia in low resource clinical settings. Our objectives were to: i) evaluate risk factors for methemoglobinemia in Ugandan children hospitalized with fever (study 1); and ii) investigate MHb responses in critically ill Ugandan children with severe malaria treated with inhaled nitric oxide (iNO), an oxidant that induces MHb in a dose-dependent manner (study 2). Two prospective studies were conducted at Jinja Regional Referral Hospital in Uganda between 2011 and 2013. Study 1, a prospective cohort study of children admitted to hospital with fever (fever cohort, n = 2089 children 2 months to 5 years). Study 2, a randomized double-blind placebo-controlled parallel arm trial of room air placebo vs. 80 ppm iNO as an adjunctive therapy for children with severe malaria (RCT, n = 180 children 1-10 years receiving ...

Open Forum Infectious Diseases, 2016

Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adu... more Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm deve...

Malaria Journal, 2015

Background: Severe malaria remains a major cause of childhood mortality globally. Decreased endot... more Background: Severe malaria remains a major cause of childhood mortality globally. Decreased endothelial nitric oxide is associated with severe and fatal malaria. The hypothesis was that adjunctive inhaled nitric oxide (iNO) would improve outcomes in African children with severe malaria. Methods: A randomized, blinded, placebo-controlled trial of iNO at 80 ppm by non-rebreather mask versus room air placebo as adjunctive treatment to artesunate in children with severe malaria was conducted. The primary outcome was the longitudinal course of angiopoietin-2 (Ang-2), an endothelial biomarker of malaria severity and clinical outcome. Results: One hundred and eighty children were enrolled; 88 were assigned to iNO and 92 to placebo (all received IV artesunate). Ang-2 levels measured over the first 72 h of hospitalization were not significantly different between groups. The mortality at 48 h was similar between groups [6/87 (6.9 %) in the iNO group vs 8/92 (8.7 %) in the placebo group; OR 0.78, 95 % CI 0.26-2.3; p = 0.65]. Clinical recovery times and parasite clearance kinetics were similar (p > 0.05). Methaemoglobinaemia >7 % occurred in 25 % of patients receiving iNO and resolved without sequelae. The incidence of neurologic deficits (<14 days), acute kidney injury, hypoglycaemia, anaemia, and haemoglobinuria was similar between groups (p > 0.05). Conclusions: iNO at 80 ppm administered by non-rebreather mask was safe but did not affect circulating levels of Ang-2. Alternative methods of enhancing endothelial NO bioavailability may be necessary to achieve a biological effect and improve clinical outcome.

Trials, 2015

Background: Pneumonia is a leading cause of childhood mortality globally. Oxygen therapy improves... more Background: Pneumonia is a leading cause of childhood mortality globally. Oxygen therapy improves survival in children with pneumonia, yet its availability remains limited in many resource-constrained settings where most deaths occur. Solar-powered oxygen delivery could be a sustainable method to improve oxygen delivery in remote areas with restricted access to a supply chain of compressed oxygen cylinders and reliable electrical power. Methods/Design: This study is a randomized controlled trial (RCT). Solar-powered oxygen delivery systems will be compared to a conventional method (oxygen from cylinders) in patients with hypoxemic respiratory illness. Enrollment will occur at two sites in Uganda: Jinja Regional Referral Hospital and Kambuga District Hospital. The primary outcome will be the length of hospital stay. Secondary study endpoints will be mortality, duration of supplemental oxygen therapy (time to wean oxygen), proportion of patients successfully oxygenated, delivery system failure, cost, system maintenance and convenience. Discussion: The RCT will provide useful data on the feasibility and noninferiority of solar-powered oxygen delivery. This technological innovation uses freely available inputs, the sun and the air, to oxygenate children with pneumonia, and can be applied "off the grid" in remote and/or resource-constrained settings where most pneumonia deaths occur. If proven successful, solar-powered oxygen delivery systems could be scaled up and widely implemented for impact on global child mortality. Trial registration: Clinicaltrials.gov registration number NCT0210086 (date of registration: