Publications by authors named "Opoka R"
We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts.
View Article and Find Full Text PDFBackground: In many sub-Saharan African countries, it is recommended that children with sickle cell anaemia receive malaria chemoprevention with monthly sulfadoxine-pyrimethamine or daily proguanil as the standard of care. However, the efficacy of these interventions is compromised by high-grade antifolate resistance of Plasmodium falciparum and poor adherence. We aimed to compare the efficacy of weekly dihydroartemisinin-piperaquine and monthly sulfadoxine-pyrimethamine for the prevention of clinical malaria in children with sickle cell anaemia in areas with high-grade sulfadoxine-pyrimethamine resistance of P falciparum in Uganda and Malawi.
View Article and Find Full Text PDFBackground: 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 reduce SCVI resulting in potential impact on reducing stroke and cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA.
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- A study conducted in Uganda followed children aged 6 months to 4 years who were discharged from the hospital after being treated for specific severe malaria manifestations, comparing their post-discharge health to asymptomatic community children.
- Over 12 months, 56.6% of children with severe malaria experienced one or more hospitalizations, significantly higher than the 30.8% of community children, with a majority of the hospitalizations being malaria-related.
- The findings indicate a pressing need for research into post-discharge malaria prevention treatments to help reduce the healthcare burden on children who have suffered from severe malaria.
Introduction: Few studies have described post-discharge morbidity of children with specific manifestations of severe malaria (SM) beyond severe malarial anemia or cerebral malaria.
Methods: Children 6 months to 4 years of age admitted at Jinja and Mulago hospitals in Uganda, with one or more of the five most common manifestations of SM, cerebral malaria (n=53), respiratory distress syndrome (n=108), malaria with complicated seizures (n=160), severe malarial anemia (n=155) or prostration (n=75), were followed for 12 months after discharge, along with community children (CC) (n=120) recruited from the household or neighborhood of the children with SM. Incidence and risk of post-discharge readmission, death or outpatient clinic visits were compared between children with SM and CC.
Article Synopsis
- Children with severe malarial anemia (SMA) have low in-hospital mortality but face high risks of readmission or death after discharge, potentially due to factors impacting blood production and vascular health.
- A study of 145 children in Kampala, Uganda, showed that higher plasma levels of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) upon admission were linked to a significantly lower risk of readmission or death within 12 months.
- The findings suggest that these angiogenesis-promoting factors may help reduce the likelihood of severe malaria recurrences in these children.
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- Co-infection with intestinal helminths and malaria is common in certain communities, but the relationship between these infections and malaria severity remains unclear.
- A study analyzed stool samples from children with severe malaria and asymptomatic children in Uganda, finding a very low prevalence of intestinal helminth infections in both groups.
- The results indicated that helminth infections were not linked to increased risk of severe malaria, which may be attributed to the success of Uganda's national deworming program introduced in 2003.
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- Pneumonia is a major cause of death in children under 5, particularly among those with poor nutrition, making it important to identify body composition measures that can predict survival rates in these patients.* -
- This study analyzed 369 children aged 6-59 months with severe pneumonia in Uganda and Kenya, comparing indices of fat and muscle mass to see which was a better predictor of 6-month survival.* -
- Results showed that while Arm-Fat-Area had a comparable predictive ability for survival as Arm-Muscle-Area and Arm-Muscle-Circumference, none of these were significantly better than the measurement of Mid-Upper Arm Circumference (MUAC).*
Article Synopsis
- The study aimed to evaluate the relationship between the perfusion index (PI), a noninvasive tool, and clinical markers of perfusion in critically ill children hospitalized with severe malaria, investigating its potential to identify those at higher risk of mortality.
- Conducted in two hospitals in Uganda, the research analyzed data from 600 children under five with severe malaria and found that lower admission PI correlated with clinical signs of poor perfusion and complications, as well as higher mortality odds.
- The results indicated that consecutive low PI measures (< 1%) were predictive of mortality, suggesting that PI could serve as an important indicator for managing severe malaria in pediatric patients.
Article Synopsis
- - Unexplained increases in blackwater fever (BWF) in Eastern Uganda prompted a study examining how immune complexes and glucose-6-phosphate dehydrogenase (G6PD) deficiency relate to severe malaria (SM) in children.
- - The study, involving 557 children with SM and 101 community children, found that those with SM had significantly higher levels of circulating immune complexes (cIC), which were linked to complications like severe anemia and jaundice, along with predicting readmissions.
- - G6PD deficiency, particularly in males, was shown to elevate cIC levels, and the analysis indicated that this deficiency contributes to recurring severe anemia and BWF due to the presence of these immune complexes.
Background: Sub-Saharan Africa bears the highest burden of sickle cell disease (SCD) globally with Nigeria, Democratic Republic of Congo, Tanzania, Uganda being the most affected countries. Uganda reports approximately 20,000 SCD births annually, constituting 6.67% of reported global SCD births.
View Article and Find Full Text PDFObjective: 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.
View Article and Find Full Text PDFBackground: Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis.
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- - The study compared neurocognitive functions in Ugandan children aged 1-12 years with sickle cell anemia (SCA) to their non-SCA siblings, finding that SCA children had significantly lower cognitive scores, particularly in older age groups.
- - Methods included standardized tests for cognition, executive function, and attention, along with stroke risk assessments, revealing that younger SCA children did not differ significantly from their siblings in cognitive abilities.
- - Results showed that disease status, age, and prior stroke were key predictors of neurocognitive outcomes in SCA children, highlighting the need for further research on interventions that could improve their cognitive functioning.
Article Synopsis
- People with sickle cell anemia often need blood transfusions, and hydroxyurea can help reduce this need, but access and dosage challenges hinder its use in Africa.
- The ADAPT trial will investigate how hydroxyurea affects transfusion rates and whether personalized dosing through pharmacokinetics can improve treatment in children with SCA in Uganda.
- Success in reducing transfusion reliance and optimizing hydroxyurea dosing could enhance access to this life-saving treatment for sickle cell anemia across sub-Saharan Africa.
Background: Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes.
Methods: COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)).
Background: Supplemental O is not always available at health facilities in low-income and middle-income countries (LMICs). Solar-powered O delivery can overcome gaps in O access, generating O independent of grid electricity. We hypothesized that installation of solar-powered O systems on the paediatrics ward of rural Ugandan hospitals would lead to a reduction in mortality among hypoxaemic children.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFAfter starting hydroxyurea treatment, Ugandan children with sickle cell anemia had 60% fewer severe or invasive infections, including malaria, bacteremia, respiratory tract infections, and gastroenteritis, than before starting hydroxyurea treatment (incidence rate ratio, 0.40 [95% confidence interval, 0.29-0.
View Article and Find Full Text PDFBackground: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia.
View Article and Find Full Text PDFBackground: Malaria is an important cause of mortality in African children. Identification of biomarkers to identify children at risk of mortality has the potential to improve outcomes.
Methods: We evaluated 11 biomarkers of host response in 592 children with severe malaria.
Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders. In paediatric severe malaria, elevated tau is associated with mortality and neurocognitive complications.
View Article and Find Full Text PDFIntroduction: Neurocognitive function in Ugandan children aged 1-12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment.
Methods: This cross-sectional neurocognitive function study of children with SCA (N=242) and non-SCA siblings (N=127) used age- and linguistically-appropriate standardized tests of cognition, executive function and attention for children ages 1-4 and 5-12 years. Test scores were converted to locally derived age-normalized z-scores.
Background: The relationship of apolipoprotein-E4 (APOE4) to mortality and cognition after severe malaria in children is unknown.
Methods: APOE genotyping was performed in children with cerebral malaria (CM, n = 261), severe malarial anemia (SMA, n = 224) and community children (CC, n = 213). Cognition was assessed over 2-year follow-up.