Browsing by Author "Uyoga, Sophie"

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    Co-Trimoxazole Or Multivitamin Multimineral Supplement For Post-Discharge Outcomes After Severe Anaemia In African Children: A Randomised Controlled Trial
    (The Lancet Global Health, 2019) Maitland, Kathryn; Olupot, Peter Olupot; Kiguli, Sarah; Chagaluka, George; Alaroker, Florence; Opoka, Robert O.; Mpoya, Ayub; Walsh, Kevin; Engoru, Charles; Nteziyaremye, Julius; Mallewa, Machpherson; Nakuya, Margaret; Kennedy, Neil; Namayanja, Cate; Kayaga, Julianne; Nabawanuka, Eva; Sennyondo, Tonny; Aromut, Denis; Kumwenda, Felistas; Musika, Cynthia Williams; Thomason, Margaret J.; Bates, Imelda; Hensbroek, Michael Boele von; Evans, Jennifer A .; Uyoga, Sophie; Williams, Thomas N.; Frost, Gary; George, Elizabeth C.; Gibb, Diana M.; Walker, A. Sarah; the TRACT trial group
    Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomes remain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-discharge interventions that might improve outcomes.Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 months to 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three in Uganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second non-sequentially numbered set of allocations stratified by centre and severity, to enhanced nutritional supplementation with iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatment doses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally and were given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusion management. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population; follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN84086586, and follow-up is complete.From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followed up for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement, 1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day 180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron and folate group had died (hazard ratio [HR] 0·97, 95% CI 0·79–1·21; p=0·81) and 172 (9%) who received co-trimoxazole versus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86–1·32; p=0·56). We found no evidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180, 489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folate group (HR 0·95, 95% CI 0·84–1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) children in the no co-trimoxazole group (1·01, 0·89–1·15; p=0·85) had had one or more serious adverse events. Most serious adverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions).Neither enhanced supplementation with multivitamin multimineral supplement versus iron and folate treatment or co-trimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretched health services in Africa.
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    Pharmacokinetics And Pharmacodynamics Of Azithromycin In Severe Malaria Bacterial Co-Infection In African Children (TABS-PKPD): A Protocol For A Phase II Randomised Controlled Trial
    (Wellcome Open Research, 2021) Olupot, Peter Olupot; Okiror, William; Mnjalla, Hellen; Muhindo, Rita; Uyoga, Sophie; Mpoya, Ayub; Williams, Thomas N.; terHeine, Rob; Burger, David M.; Urban, Britta; Connon, Roisin; George, Elizabeth C.; Gibb, Diana M.; Walker, A. Sarah; Maitland, Kathryn
    African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection.
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    Whole blood versus red cell concentrates for children with severe anaemia: a secondary analysis of the Transfusion and Treatment of African Children (TRACT) trial
    (The Lancet Global Health, 2022) George, Elizabeth C.; Uyoga, Sophie; M’baya, Bridon; Kyeyune Byabazair, Dorothy; Kiguli, Sarah; Olupot-Olupot, Peter; Opoka, Robert O.; Chagaluka, George; Alaroker, Florence; Williams, Thomas N.; Bates, Imelda; Mbanya, Dora; Gibb, Diana M.; Walker, A. Sarah; Maitland, Kathryn
    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). Because data on the safety of blood components are scarce, we conducted a secondary analysis to examine the safety and efficacy of different pack types (whole blood vs red cell concentrates) on clinical outcomes. Methods This study is a secondary analysis of the TRACT trial data restricted to those who received an immediate transfusion (using whole blood or red cell concentrates). TRACT was an open-label, multicentre, factorial, randomised trial conducted in three hospitals in Uganda (Soroti, Mbale, and Mulago) and one hospital in Malawi (Blantyre). The trial enrolled children aged between 2 months and 12 years admitted to hospital with severe anaemia (haemoglobin <6 g/dL). The pack type used (supplied by blood banks) was based only on availability at the time. The outcomes were haemoglobin recovery at 8 h and 180 days, requirement for retransfusion, length of hospital stay, changes in heart and respiratory rates until day 180, and the main clinical endpoints (mortality until day 28 and day 180, and readmission until day 180), measured using multivariate regression models. Findings Between Sept 17, 2014, and May 15, 2017, 3199 children with severe anaemia were enrolled into the TRACT trial. 3188 children were considered in our secondary analysis. The median age was 37 months (IQR 18–64). Whole blood was the first pack provided for 1632 (41%) of 3992 transfusions. Haemoglobin recovery at 8 h was significantly lower in those who received packed cells or settled cells than those who received whole blood, with a mean of 1·4 g/dL (95% CI –1·6 to –1·1) in children who received 30 mL/kg and –1·3 g/dL (–1·5 to –1·0) in those who received 20 mL/kg packed cells versus whole blood, and –1·5 g/dL (–1·7 to –1·3) in those who received 30 mL/kg and –1·0 g/dL (–1·2 to –0·9) in those who received 20 mL/kg settled cells versus whole blood (overall p<0·0001). Compared to whole blood, children who received blood as packed or settled cells in their first transfusion had higher odds of receiving a second transfusion (odds ratio 2·32 [95% CI 1·30 to 4·12] for packed cells and 2·97 [2·18 to 4·05] for settled cells; p<0·001) and longer hospital stays (hazard ratio 0·94 [95% CI 0·81 to 1·10] for packed cells and 0·86 [0·79 to 0·94] for settled cells; p=0·0024). There was no association between the type of blood supplied for the first transfusion and mortality at 28 days or 180 days, or readmission to hospital for any cause. 823 (26%) of 3188 children presented with severe tachycardia and 2077 (65%) with tachypnoea, but these complications resolved over time. No child developed features of confirmed cardiopulmonary overload. Interpretation Our study suggests that the use of packed or settled cells rather than whole blood leads to additional transfusions, increasing the use of a scarce resource in most of sub-Saharan Africa. These findings have substantial cost implications for blood transfusion and health services. Nevertheless, a clinical trial comparing whole blood transfusion with red cell concentrates might be needed to inform policy makers.