Robert O Opoka

Robert O Opoka
Makerere University · Department of Paediatrics and Child Health

MBCH MMED MPH

About

263
Publications
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Publications

Publications (263)
Article
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Severe malaria (SM) increases the risk of invasive bacterial infection, and there is evidence to suggest increased gastrointestinal permeability. Studies have shown sequestration of infected erythrocytes in intestinal microvasculature, and in vivo studies of rectal mucosa have demonstrated disruption of microvascular blood flow. However, the extent...
Article
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 (lipopolysacchari...
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Severe malaria caused by Plasmodium falciparum is difficult to diagnose accurately in children in high-transmission settings. Using data from 2649 pediatric and adult patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic markers: the platel...
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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 m...
Article
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Background: Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood. Methods: A prospective observational cohort study was conducted to evaluate the association between BWF and AKI...
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Background: Sickle cell anaemia (SCA) has historically been associated with high levels of childhood mortality in Africa. Although malaria has a major contribution to this mortality, to date, the clinical pathology of malaria among children with SCA has been poorly described. We aimed to explore the relationship between SCA and Plasmodium falcipar...
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Background: Murine experimental cerebral malaria studies suggest both protective and deleterious central nervous system effects from alterations in the interleukin-33 (IL-33)/ST2 pathway. Methods: We assessed whether soluble ST2 (sST2) was associated with neuronal injury or cognitive impairment in a cohort of Ugandan children with cerebral malar...
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Background: Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk...
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Background: We hypothesized that oxidative stress in Ugandan children with severe malaria is associated with mortality. Methods: We evaluated biomarkers of oxidative stress in children with cerebral malaria (CM, n=77) or severe malarial anemia (SMA, n=79), who were enrolled in a randomized clinical trial of immediate vs. delayed iron therapy, comp...
Article
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...
Article
Access to therapeutic oxygen in low-resource settings remains a significant global problem. Solar powered oxygen (SPO2) delivery is a reliable and cost-effective solution. We followed implementation research methodology to gather data on engineering parameters (remote monitoring), nurse training (before and after knowledge questionnaire), patients...
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Sickle cell anemia (SCA) is common in sub‐Saharan Africa where approximately 1% of births are affected. Severe anemia is a common cause for hospital admission within the region yet few studies have investigated the contribution made by SCA. The TRACT trial (ISRCTN84086586) investigated various treatment strategies in 3,983 children admitted with se...
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Acute kidney injury (AKI) is a life-threatening complication. Malaria and sepsis are leading causes of AKI in low-and-middle-income countries, but its etiology and pathogenesis are poorly understood. A prospective observational cohort study was conducted to evaluate pathways of immune and endothelial activation in children hospitalized with an acut...
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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 t...
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In a prospective cohort study of 77 children with severe pneumonia from two hospitals in Uganda, we assessed soluble T cell immunoglobulin and mucin-domain containing protein 3 (sTIM-3) levels at hospital admission and their association with pneumonia severity and subsequent mortality. sTIM-3 levels were positively correlated with the Respiratory I...
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Background The TRACT trial established the timing of transfusion in children with uncomplicated anaemia (haemoglobin 4–6 g/dL) and the optimal volume (20 vs 30 mL/kg whole blood or 10 vs 15 mL/kg red cell concentrates) for transfusion in children admitted to hospital with severe anaemia (haemoglobin <6 g/dL) on day 28 mortality (primary endpoint)....
Article
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 coh...
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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 en...
Preprint
Background Children discharged from hospital after recovery from severe malarial anaemia (SMA) are at high risk of readmission and death in subsequent months. Clinical trial results show that three months of post-discharge malaria chemoprevention (PMC) with dihydroartemisinin-piperaquine reduces this risk. Methods We developed a compartmental math...
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Cerebral malaria (CM), coma caused by Plasmodium falciparum-infected red blood cells (iRBCs), is the deadliest complication of malaria. The mechanisms that lead to CM development are incompletely understood. Here we report on the identification of activation and inhibition pathways leading to mouse CM with supporting evidence from the analysis of h...
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Importance Cerebral malaria (CM) and severe malarial anemia (SMA) are associated with persistent neurocognitive impairment (NCI) among children in Africa. Identifying blood biomarkers of acute brain injury that are associated with future NCI could allow early interventions to prevent or reduce NCI in survivors of severe malaria. Objective To inves...
Article
Background:Severe malaria (SM) remains a major global health problem causing ~275,000 pediatric deaths annually, worldwide. Continuous, non-invasive monitoring of peripheral perfusion can help detect abnormalities in systemic circulation, a common problem in critically ill patients, and can improve outcomes in children hospitalized with SM. Perfusi...
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Background Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. Methods Secondary analyses of the trial examined 3894 c...
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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 with sepsis at risk of all-cause mortality. In a prospective cohort study of 2,502 children...
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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...
Article
Hydroxyurea is efficacious against sickle cell anaemia (SCA)-related complications in African children. Prior studies demonstrated conflicting results on the effect of hydroxyurea on risk of infection, the most common cause of morbidity and mortality in African children with SCA. We evaluated the incidence of infections before and after starting hy...
Preprint
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Background Severe falciparum malaria is difficult to diagnose accurately in children in high transmission settings. Platelet counts and plasma concentrations of P. falciparum histidine-rich protein-2 (PfHRP2) are potential biomarkers to increase diagnostic accuracy. Methods We fitted Bayesian latent class models to platelet counts and PfHRP2 concen...
Article
Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the ‘Treat’ element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been...
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Background The frequency of recovery from undernutrition after an episode of severe malaria, and the relationship between undernutrition during severe malaria and clinical and cognitive outcomes are not well characterized. Methods We evaluated undernutrition and cognition in children in Kampala, Uganda 18 months to 5 years of age with cerebral mal...
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Background The provision of post-discharge malaria chemoprevention (PMC) in children recently admitted with severe anemia reduces the risk of death and re-admissions in malaria endemic countries. The main objective of this trial was to identify the most effective method of delivering dihydroartemesinin-piperaquine to children recovering from severe...
Article
Background: To prevent poor long-term outcomes (deaths and readmissions) the integrated global action plan for pneumonia and diarrhoea recommends under the ‘Treat’ element of Protect, Prevent and Treat interventions the importance of continued feeding but gives no specific recommendations for nutritional support. Early nutritional support has been...
Preprint
Full-text available
Background Practice based learning is crucial in forming appropriate strategies for improving learning among the medical students that support the country’s understaffed health sector. Unsatisfactory learning consequently results into poor performance of students and poor quality of health care workforce in the long run. Exploring the perceptions a...
Article
Plasmodium falciparum malaria causes morbidity and mortality in African children with sickle cell anemia (SCA), but comparisons of host responses to P. falciparum between children with SCA (HbSS) and HbAA are limited. We assessed parasite biomass and plasma markers of inflammation and endothelial activation in children with HbAA (n=208) or HbSS (n=...
Article
BACKGROUND: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. METHODS: Secondary analyses of the trial examined 3894...
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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, 5...
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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 O2) has been shown to be a safe and effective technology for delivering medical oxygen. E...
Article
Background: HIV-exposed but uninfected (HEU) infants are at increased risk of impaired early linear growth and cognitive development. We examined associations between prenatal and postnatal growth and subsequent neurodevelopment in Ugandan HEU infants, hypothesizing that early insults may explain alterations in both somatic growth and brain develo...
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Purpose: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. Methods: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2 < 80%) to high-flow nasal therapy (HFNT) or low-flow ox...
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The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40–60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mo...
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Gut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown whether gut microbiota provide signals that dynamically regulate distal immune responses following an extra-gastroin...
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Circulating levels of the adipokine leptin are linked to neuropathology in experimental cerebral malaria (ECM), but its source and regulation mechanism remain unknown. Here, we show that sequestration of infected red blood cells (iRBCs) in white adipose tissue (WAT) microvasculature increased local vascular permeability and leptin production. Mice...
Preprint
Full-text available
Gut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown if gut microbiota provide signals that dynamically regulate distal immune responses following an extra-gastrointesti...
Article
Full-text available
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 month...
Article
Background: In 2018, malaria produced an estimated 272,000 deaths in children <5 years of age, accounting for 67% of all malaria deaths worldwide, with a majority in the WHO African Region. Malnutrition is an important risk factor for malaria. Wasting, Stunting and Underweight are crucial indicators of malnutrition. Annually, 14 million children <5...
Article
Background Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. Methods We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals...
Article
COVID-19 and its prevention has put considerable strain on health care systems in low and middle-income countries (LMIC). In Uganda, a national lockdown was declared on March 18, 2020, in response to COVID-19 pandemic and concern of spread of cases without aggressive measures to prevent spread. The lockdown consisted of closure of all offices excep...
Article
Introduction: Hydroxyurea is a potent therapeutic agent for sickle cell anemia (SCA), and treatment at maximum tolerated dose (MTD) is becoming the standard of care. Hydroxyurea exerts its disease-modifying effects primarily through induction of fetal hemoglobin (HbF), although the cellular and molecular mechanisms by which hydroxyurea increases Hb...
Article
Introduction: Elevated levels of fetal hemoglobin (HbF) are known to ameliorate both the morbidity and mortality of sickle cell anemia (SCA). Sustained post-natal HbF expression is heritable and regulated by multiple quantitative trait loci. Previous genomic studies have identified three major gene loci (BCL11A, HBS1L-MYB, and HBG2) that account fo...
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Background Severe anaemia is a common clinical problem among young children in sub-Saharan Africa. However, the effect of severe anaemia on neurodevelopment of these children is not well described. Therefore, we assessed the neurodevelopmental performance of preschool children diagnosed with severe anaemia in Northern Uganda. Methods We conducted...
Article
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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 populati...
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The role of inflammation in severe anemia (SA) in African children has not been well characterized. We conducted a study to evaluate risk factors for SA in young children admitted at a tertiary unit in Uganda. Clinical, infectious, and micronutrient risk factors for anemia, along with markers of inflammation, were evaluated in children aged < 5 yea...
Article
Objective Pneumonia is the leading cause of death in children under 5, with the highest burden in resource-limited countries. Endothelial activation occurs in pneumonia and can be assessed using quantitative levels of biomarkers angiopoietin (Ang)-1 and Ang-2. We examined admission levels of Ang-1 and Ang-2 in pediatric pneumonia and their associat...
Preprint
Full-text available
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 Ugan...
Article
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:...
Article
Background Hydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that out...
Preprint
Full-text available
Background: Severe anaemia is a global public health challenge commonly associated with morbidity and mortality among children <5 years of age in Sub-Saharan Africa. However, less is known about the behavioural performance of preschool children surviving severe anaemia in low resource settings. We investigated social-emotional and adaptive behaviou...
Preprint
Full-text available
Background: Severe anaemia is a global public health challenge commonly associated with morbidity and mortality among children <5 years of age in Sub-Saharan Africa. However, less is known about the behavioural performance of children < 5 years surviving severe anaemia in low resource settings. We investigated social-emotional and adaptive behaviou...
Article
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. In this study, Ugandan chi...
Article
We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38...
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Background: Prematurity is the leading cause of mortality in children under 5 years of age globally and is also frequently associated with postnatal growth failure (PGF). Although most preterm births occur in low resource settings, little is known about their postnatal growth outcomes especially in rural areas. We evaluated the incidence and facto...
Article
Background: WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. Objectives: We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would i...