Browsing by Author "Opoka, Robert"
Now showing 1 - 10 of 12
Results Per Page
Sort Options
Item Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria(Oxford University Press, 2022) Namazzi, Ruth; Opoka, Robert; Datta, Dibyadyuti; Bangirana, Paul; Batte, Anthony; Berrens, Zachary; Goings, Michael J.; Schwaderer, Andrew L.; Conroy, Andrea L.; John, Chandy C.; Pediatrics, School of MedicineBackground: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. Methods: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria. Results: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59). Conclusions: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria.Item Admission EEG findings in diverse paediatric cerebral malaria populations predict outcomes(BMC, 2018-05-22) Postels, Douglas G.; Wu, Xiaoting; Li, Chenxi; Kaplan, Peter W.; Seydel, Karl B.; Taylor, Terrie E.; Kousa, Youssef A.; Idro, Richard; Opoka, Robert; John, Chandy C.; Birbeck, Gretchen L.; Medicine, School of MedicineElectroencephalography at hospital presentation may offer important insights regarding prognosis that can inform understanding of cerebral malaria (CM) pathophysiology and potentially guide patient selection and risk stratification for future clinical trials. Electroencephalogram (EEG) findings in children with CM in Uganda and Malawi were compared and associations between admission EEG findings and outcome across this diverse population were assessed. Demographic, clinical and admission EEG data from Ugandan and Malawian children admitted from 2009 to 2012 with CM were gathered, and survivors assessed for neurological abnormalities at discharge. RESULTS: 281 children were enrolled (Uganda n = 122, Malawi n = 159). The Malawian population was comprised only of retinopathy positive children (versus 72.5% retinopathy positive in Uganda) and were older (4.2 versus 3.7 years; p = 0.046), had a higher HIV prevalence (9.0 versus 2.8%; p = 0.042), and worse hyperlactataemia (7.4 versus 5.2 mmol/L; p < 0.001) on admission compared to the Ugandan children. EEG findings differed between the two groups in terms of average voltage and frequencies, reactivity, asymmetry, and the presence/absence of sleep architecture. In univariate analyses pooling EEG and outcomes data for both sites, higher average and maximum voltages, faster dominant frequencies, and retained reactivity were associated with survival (all p < 0.05). Focal slowing was associated with death (OR 2.93; 95% CI 1.77-7.30) and a lower average voltage was associated with neurological morbidity in survivors (p = 0.0032). CONCLUSIONS: Despite substantial demographic and clinical heterogeneity between subjects in Malawi and Uganda as well as different EEG readers at each site, EEG findings on admission predicted mortality and morbidity. For CM clinical trials aimed at decreasing mortality or morbidity, EEG may be valuable for risk stratification and/or subject selection.Item Caregivers and community perceptions of blood transfusion for children with severe anaemia in Uganda(Wiley, 2019-02) Dhabangi, Aggrey; Idro, Richard; John, Chandy C.; Dzik, Walter H.; Opoka, Robert; Siu, Godfrey E.; Ayebare, Florence; van Hensbroek, Michael B.; Pediatrics, School of MedicineObjective To describe local perceptions of blood transfusion for children with severe anaemia in Uganda. Background Blood transfusion is a common emergency treatment for children with severe anaemia and saves millions of lives of African children. However, the perceptions of transfusion recipients have not been well studied. A better understanding of the perceived risk may improve transfusion care. Methods A qualitative study based on 16 in‐depth interviews of caregivers of transfused children, and six focus group discussions with community members was conducted in three regions of Uganda between October and November 2017. Results Caregivers of children and community members held blood transfusion in high regard and valued it as life‐saving. However, there were widespread perceived transfusion risks, including: Human immunodeficiency virus (HIV) transmission, too rapid blood infusion and blood incompatibility. Other concerns were: fatality, changes in behaviour, donor blood being ‘too strong’ and use of animal blood. In contrast, recent transfusion, older age, knowledge of HIV screening of blood for transfusion, faith in God and having a critically ill child were associated with less fear about transfusion. Respondents also emphasised challenges to transfusion services access including distance to hospitals, scarcity of blood and health workers' attitudes. Conclusion Perceptions of the community and caregivers of transfused children in Uganda about blood transfusion were complex: transfusion is considered life‐saving but there were strong perceived transfusion risks of HIV transmission and blood incompatibility. Addressing community perceptions and facilitating access to blood transfusion represent important strategies to improve paediatric transfusion care.Item Economic evaluation of postdischarge malaria chemoprevention in preschool children treated for severe anaemia in Malawi, Kenya, and Uganda: A cost-effectiveness analysis(Elsevier, 2022-10-01) Kühl, Melf-Jakob; Gondwe, Thandile; Dhabangi, Aggrey; Kwambai, Titus K.; Mori, Amani T.; Opoka, Robert; John, C. Chandy; Idro, Richard; ter Kuile, Feiko O.; Phiri, Kamija S.; Robberstad, Bjarne; Pediatrics, School of MedicineBackground: Children hospitalised with severe anaemia in malaria-endemic areas are at a high risk of dying or being readmitted within six months of discharge. A trial in Kenya and Uganda showed that three months of postdischarge malaria chemoprevention (PDMC) with monthly dihydroartemisinin-piperaquine (DP) substantially reduced this risk. The World Health Organization recently included PDMC in its malaria chemoprevention guidelines. We conducted a cost-effectiveness analysis of community-based PDMC delivery (supplying all three PDMC-DP courses to caregivers at discharge to administer at home), facility-based PDMC delivery (monthly dispensing of PDMC-DP at the hospital), and the standard of care (no PDMC). Methods: We combined data from two recently completed trials; one placebo-controlled trial in Kenya and Uganda collecting efficacy data (May 6, 2016 until November 15, 2018; n=1049), and one delivery mechanism trial from Malawi collecting adherence data (March 24, 2016 until October 3, 2018; n=375). Cost data were collected alongside both trials. Three Markov decision models, one each for Malawi, Kenya, and Uganda, were used to compute incremental cost-effectiveness ratios expressed as costs per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty. Findings: Both PDMC strategies were cost-saving in each country, meaning less costly and more effective in increasing health-adjusted life expectancy than the standard of care. The estimated incremental cost savings for community-based PDMC compared to the standard of care were US$ 22·10 (Malawi), 38·52 (Kenya), and 26·23 (Uganda) per child treated. The incremental effectiveness gain using either PDMC strategy varied between 0·3 and 0·4 QALYs. Community-based PDMC was less costly and more effective than facility-based PDMC. These results remained robust in sensitivity analyses. Interpretation: PDMC under implementation conditions is cost-saving. Caregivers receiving PDMC at discharge is a cost-effective delivery strategy for implementation in malaria-endemic southeastern African settings.Item Hydroxyurea reduces infections in children with sickle cell anemia in Uganda(American Society of Hematology, 2024) Namazzi, Ruth; Bond, Caitlin; Conroy, Andrea L.; Datta, Dibyadyuti; Tagoola, Abner; Goings, Michael J.; Jang, Jeong Hoon; Ware, Russell E.; Opoka, Robert; John, Chandy C.; Pediatrics, School of MedicineAfter 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, 0.29-0.54 ]; P < .001 ).Item Investigating Differences in Nutritional Parameters in Ugandan Children with Plasmodium falciparum Severe Malaria(2020-07) Brown, Lucy; Co, Katrina; Bond, Caitlin; Opoka, Robert; Datta, Dibya; John, ChandyBackground: The past two decades have witnessed a 60% decline in global malaria mortality. However, two thirds of all malaria deaths continue to occur among children <5 years, 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, and are associated with increased mortality in children <5. Annually, 14 million children <5 are classified as wasted and 59 million children are classified as stunted. Objective: The objective of this study is to look at nutritional parameters, weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ), and how they differ over time in children <5 with severe malaria (SM) from the Ugandan cities Mulago and Jinja and the outcomes of mortality and nutritional parameters, underweight, stunting, and wasting. Methods: We defined underweight, stunting, and wasting as 2SD below the WAZ, HAZ, and WHZ means. We evaluated Z-scores and mortality status from children <5 years enrolled in a prospective cohort study (NDI, Neurodevelopmental Impairment in Children with Severe Malaria) at enrollment and 12-month follow-up between two sites. Results: WAZ, HAZ and WHZ at baseline were significantly lower among SM groups than in CC (p<0.01), and the SM group maintained significantly lower WHZ (p<0.01) and HAZ (p<0.001) at 12-month follow-up. Among the children who died, there were no significant differences of nutritional markers in Mulago, but in Jinja there was found to be a significant association between mortality and low WAZ (p<0.05) and underweight (p<0.05). Of children classified as underweight in Jinja, 37.5% of them died compared to 15.9% who survived; additionally, the odds ratio for decreased WAZ and mortality was 0.58 (p<0.05). Conclusion: Underweight, stunting, and wasting may be risk factors for SM, and underweight may exacerbate poor mortality outcomes in rural areas like Jinja. While underweight is worsened among children with SM at 1 month and normalizes by 12 months, stunting remains persistently low at 12 months. Nutritional interventions must be aimed at maintaining linear growth throughout the first year of SM in children <5 to reduce the risk factor of underweight on poor mortality outcomes.Item Malaria Chemoprevention in the Postdischarge Management of Severe Anemia(Massachusetts Medical Society, 2020-12-03) Kwambai, Titus K.; Dhabangi, Aggrey; Idro, Richard; Opoka, Robert; Watson, Victoria; Kariuki, Simon; Onyango, Eric D.; Otieno, Kephas; Samuels, Aaron M.; Desai, Meghna R.; Boele van Hensbroek, Michael; Wang, Duolao; John, Chandy C.; Robberstad, Bjarne; Phiri, Kamija S.; Ter Kuile, Feiko O.; Pediatrics, School of MedicineBACKGROUND: 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 in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach. RESULTS: From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine. CONCLUSIONS: In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT02671175.).Item Malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: study protocol for a multi-centre, two-arm, randomised, placebo-controlled, superiority trial(BMC, 2018-11-06) Kwambai, Titus K.; Dhabangi, Aggrey; Idro, Richard; Opoka, Robert; Kariuki, Simon; Samuels, Aaron M.; Desai, Meghna; van Hensbroek, Michael Boele; John, Chandy C.; Robberstad, Bjarne; Wang, Duolao; Phiri, Kamija; Ter Kuile, Feiko O.; Pediatrics, School of MedicineBACKGROUND: Children hospitalised with severe anaemia in malaria endemic areas in Africa are at high risk of readmission or death within 6 months post-discharge. Currently, no strategy specifically addresses this period. In Malawi, 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment courses of artemether-lumefantrine given at discharge and at 1 and 2 months prevented 30% of all-cause readmissions by 6 months post-discharge. Another efficacy trial is needed before a policy of malaria chemoprevention can be considered for the post-discharge management of severe anaemia in children under 5 years of age living in malaria endemic areas. OBJECTIVE: We aim to determine if 3 months of PMC with monthly 3-day treatment courses of dihydroartemisinin-piperaquine is safe and superior to a single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths (composite primary endpoint) by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia of any or undetermined cause. METHODS/DESIGN: This is a multi-centre, two-arm, placebo-controlled, individually randomised trial in children under 5 years of age recently discharged following management for severe anaemia. Children in both arms will receive standard in-hospital care for severe anaemia and a 3-day course of artemether-lumefantrine at discharge. At 2 weeks after discharge, surviving children will be randomised to receive either 3-day courses of dihydroartemisinin-piperaquine at 2, 6 and 10 weeks or an identical placebo and followed for 26 weeks through passive case detection. The trial will be conducted in hospitals in malaria endemic areas in Kenya and Uganda. The study is designed to detect a 25% reduction in the incidence of all-cause readmissions or death (composite primary outcome) from 1152 to 864 per 1000 child years (power 80%, α = 0.05) and requires 520 children per arm (1040 total children). RESULTS: Participant recruitment started in May 2016 and is ongoing.Item Post-discharge malaria chemoprevention in children admitted with severe anaemia in malaria-endemic settings in Africa: a systematic review and individual patient data meta-analysis of randomised controlled trials(Elsevier, 2024) Phiri, Kamija S.; Khairallah, Carole; Kwambai, Titus K.; Bojang, Kalifa; Dhabangi, Aggrey; Opoka, Robert; Idro, Richard; Stepniewska, Kasia; van Hensbroek, Michael Boele; John, Chandy C.; Robberstad, Bjarne; Greenwood, Brian; Ter Kuile, Feiko O.; Pediatrics, School of MedicineBackground: 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. Methods: This analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged <15 years) admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. The investigators from all eligible trials shared pseudonymised datasets, which were standardised and merged for analysis. The primary outcome was all-cause mortality during the intervention period. Analyses were performed in the modified intention-to-treat population, including all randomly assigned participants who contributed to the endpoint. Fixed-effects two-stage meta-analysis of risk ratios (RRs) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data (readmissions or clinic visits) were analysed using one-stage mixed-effects Prentice-Williams-Peterson total-time models to obtain hazard ratios (HRs). This study is registered with PROSPERO, CRD42022308791. Findings: Our search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child [range 1-6]; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 [95% CI 0·08-0·70], p=0·0094, I2=0%) and a 55% reduction in all-cause readmissions (HR 0·45 [95% CI 0·36-0·56], p<0·0001) compared with placebo. The protective effect was restricted to the intervention period and was not sustained after the direct pharmacodynamic effect of the drugs had waned. The small number of trials limited our ability to assess heterogeneity, its sources, and publication bias. Interpretation: In malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity.Item Risk factors for recurrent severe anemia among previously transfused children in Uganda: an age-matched case-control study(Biomed Central, 2019-01-18) Dhabangi, Aggrey; Idro, Richard; John, Chandy C.; Dzik, Walter H.; Opoka, Robert; Ssenyonga, Ronald; van Hensbroek, Michael Boele; Pediatrics, School of MedicineBACKGROUND: In resource-poor settings, transfused children often experience recurrence of severe anemia (SA) following discharge from hospital. This study determined the factors associated with recurrent severe anemia (RSA) among previously transfused Ugandan children aged less than 5 years. METHODS: A case-control study was conducted in five hospitals in Uganda from March 2017 to September 2018. We prospectively enrolled 196 hospitalised children who had been transfused for severe anemia 2 weeks to 6 months prior to enrollment. Of these, 101 children (cases) were re-admitted with a hemoglobin [Hb] level of ≤6 g/dL and required transfusion; and 95 children (age-matched controls) were admitted for other clinical illness with a Hb > 6 g/dL. Children known to have sickle cell anemia, cancer, or bleeding disorders were excluded. Clinical and laboratory evaluation were done. Conditional logistic regression adjusted for age, was used to determine factors associated with RSA. RESULTS: The median time (IQR) between the earlier transfusion and enrollment was 3.5 (1.9-5.7) months for cases, and was 5.0 (2.9-6.0) months for controls (p-value = 0.015). Risk factors (adjusted odds ratio, 95% confidence interval, and significance) for development of RSA were: hemoglobinuria (36.33, 2.19-600.66, p = 0.012); sickle cell anemia - newly diagnosed (20.26, 2.33-176.37, p = 0.006); history of earlier previous transfusions (6.95, 1.36-35.61, p = 0.020) and malaria infection (6.47, 1.17-35.70, p = 0.032). CONCLUSION: Malaria chemoprevention, follow up visit for Hb check after discharge from hospital and sickle cell screening among previously transfused children represent practical strategies to prevent and identify children at risk for recurrent severe anemia. The cause of hemoglobinuria in children merits further investigations.