Browsing by Author "Uyoga, Sophie"

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    Comparing HemoCue® and Quantitative Buffy Coat® and Coulter Counter‑measured haemoglobin concentrations in African children with acute uncomplicated malaria: a Bland–Altman analysis
    (BMC, 2025) Ayuen, S. Dhol; Olupot‑Olupot, Peter; Muhindo, Rita; Onyamboko, A. Marie; Ajayi, Seun; Chimjinda, Natenapa; Taya, Chiraporn; Uyoga, Sophie; Williams, N. Thomas; Maitland, Kathryn; Fanello, Caterina; Day, P. J. Nicholas; Taylor, R. Walter; Mukaka, Mavuto
    Background: Anaemia is a deleterious consequence of malaria, and its accurate diagnosis is crucial for effective management. However, laboratory methods for measuring haemoglobin (Hb) concentration, like the Coulter Counter and the Quantitative Buffy Coat® (QBC®), are costly and not widely accessible in resource-limited settings. The pointof-care HemoCue® test is a cheaper alternative and suitable in rural areas. The study aimed to determine the level of agreement between Coulter Counter/QBC® vs. HemoCue®-measured Hb concentrations by Bland–Altman analysis. Methods: As part of a randomized, placebo-controlled trial of single low-dose primaquine in Ugandan and Congolese children with acute uncomplicated Plasmodium falciparum malaria, Hb concentrations were measured on days 0, 3, 7, and 28 using Coulter Counter (Uganda, n=1880 paired values), QBC® (DR Congo, n=1984 paired values) and HemoCue® Hb-301™. The predefined clinically acceptable limits were set at±0.5 g/dL. Results: The Bland–Altman analysis showed that the HemoCue® minus Coulter Counter mean Hb difference was − 0.15 g/dL with lower and upper limits of agreement of − 3.68 g/dL and 3.39 g/dL, respectively. Corresponding HemoCue® minus QBC® values were − 0.23 g/dL, − 1.66 g/dL and 1.22 g/dL. Linear regression of Hb concentration differences vs. mean Hb concentrations showed negative correlations: r=− 0.43 and r=− 0.34 for HemoCue® vs. Coulter Counter and HemoCue® vs. QBC®, respectively. Conclusions: Compared to Coulter and QBC®, mean HemoCue® measured Hb concentrations were lower and, compared to the Coulter or QBC® methods, had an overall tendency to measure lower Hb concentrations with increasing Hb concentrations. Upper and lower limits of agreement were wider than the predefined clinically acceptable limits of±0.5 g/dL. HemoCue® should be used with caution in settings where decisions about blood transfusions are made. Keywords Bland–Altman analysis, Haemoglobin, Anaemia, Malaria, HemoCue, Coulter Counter, QBC®
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    Hydroxyurea - Pragmatic Reduction in Mortality and Economic burden (H-PRIME): A 2x2x2 factorial randomized open-label trial investigating practical approaches to the treatment of sickle cell disease at four sites in Eastern Uganda.
    (Wellcome Open Research, 2025) Olupot-Olupot, Peter; Amorut, Denis; Ongodia, Paul; Okalebo, B. Charles; Abeso, Julian; Aloroker, Florence; Asio, Sarah; Odiit, Amos; Kiyaga, Charles; Muhindo, Rita; Uyoga, Sophie; Mochamah, George; Muyinda, Asad; Abongo, Grace; Nyutu, Gideon; Mogaka, Christabel; Maitland, Kathryn; Walker, Sarah Ann; Gibb, Diana; Connon, Roisin; George, Elizabeth; Ware, E Russell; Williams, N. Thomas
    Background Sickle cell disease is the most common and severe genetic disease in humans worldwide. The majority of those affected are born in subSaharan Africa, where resources to diagnose and manage them are often limited. Fresh approaches to the pragmatic management of children with sickle cell disease in Africa that improve both morbidity and mortality are urgently needed. Methods Hydroxyurea - Pragmatic Reduction in Mortality and Economic burden (H-PRIME) is a 2 × 2 × 2 factorial randomized open-label trial that is investigating three separate interventions. Eighteen hundred children aged 1-10 years attending sickle cell clinics at one of four sites in Eastern Uganda are being randomized to: (1) hydroxyurea administered at a low dose (10 mg/kg/day) versus high dose (25mg/kg/day), prescribed pragmatically through a weight-band-based approach and with clinically, rather than laboratory-guided monitoring; (2) enhanced malaria prophylaxis with weekly doses of dihydroartemisinin-piperaquine versus monthly doses of sulfadoxinepyrimethamine (standard of care); and (3) enhanced antibacterial prophylaxis with daily cotrimoxazole throughout life versus twice daily penicillin until the age of 5 years (standard of care). All children will be followed up for 48 months after the date on which the first child was randomized. The primary endpoint for the hydroxyurea randomization will be mortality, for the antimalarial random will be malaria-associated hospital admission, and for the antimicrobial randomization will be all-cause hospital admission. Secondary outcomes will include the incidence of sickle-specific complications, receipt of blood transfusions, hemoglobin and fetal hemoglobin concentrations, and economic costs and benefits of the three interventions. Conclusions The first participant was recruited for the trial on January 16, 2024. In total, 1487 of the 1800 target children were recruited by February 17, 2025. H-PRIME will efficiently answer three important pragmatic questions regarding the management of children with sickle cell disease in Africa. Keywords sickle cell disease, hydroxyurea, malaria, bacterial infections, Uganda
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    Plasma folate dynamics in Plasmodium falciparum-infected African children treated with artemisinin combination therapy and single low-dose primaquine or placebo
    (BMC, 2025) Ajayi, Seun; Onyamboko, A. Marie; Olupot-Olupot, Peter; Ayuen, S Dhol; Chimjinda, Natenapa; Taya, Chiraporn; Williams, N Thomas; Uyoga, Sophie; Maitland, Kathryn; Fanello, Caterina; Day, P J Nicholas; Mukaka, Mavuto; Taylor, R J Walter
    Background: Adding single low-dose (0.25 mg/kg) primaquine (SLDPQ) to block Plasmodium falciparum transmission is now a WHO recommendation. Whether SLDPQ increases haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) patients, leading to increased folate demand and impaired haemoglobin (Hb) recovery is unknown. This study sought to answer this question. Methods: This randomized, placebo-controlled trial measured serial plasma folate concentrations [Day (D) 0, 3, 7 and 28] in falciparum-infected Ugandan and Congolese children (6 months to 11 years), treated with age-dosed SLDPQ/placebo and artemether-lumefantrine/dihydroartemisinin-piperaquine. Genotyping defined G6PD (G6PD c.202T allele) status. Multiple linear and non-linear, mixed effects, cubic spline regression were fitted to identify factors significantly associated with plasma folate at baseline and over time, respectively. Results: 408 children (3 had missing D0 values) had ≥ 1 plasma folate value. Of these, 66 (16.2%) were G6PD-deficient, 51 (12.5%) heterozygous females, 283 normal and 8 unknown. Mean baseline folate concentrations were 10.83 [standard deviation (SD) 3.58, SLDPQ] vs 10.92 (SD 4.54, placebo) ng/ml, associated independently with baseline Hb [estimate: 0.52 ng/ml (95% CI: 0.26 to 0.79, p = 0.0001)] and baseline parasitaemia [estimate: - 0.18 ng/ml (- 0.32 to - 0.05, p = 0.007)]. For all patients, mean plasma folate concentration paralleled mean haemoglobin concentration with an initial mean fall of 1.65 ng/ml (p < 0.0001 vs. baseline), followed by a sustained rise achieving a mean D28 concentration of 11.04 (SD 4.45) ng/ml. Over time, only age (p = 0.0001), male sex (p = 0.017) and baseline parasitaemia (p = 0.029) were significantly associated with a reduced plasma folate. Conclusion: SLDPQ and G6PD status did not compromise posttreatment plasma folate concentrations in young children with acute uncomplicated falciparum malaria, providing additional evidence of SLDPQ safety and supporting its use without G6PD testing. Trial registration: The trial is registered, reference number ISRCTN11594437. Keywords: Folate; Glucose-6-phosphate dehydrogenase; Malaria; Single low-dose primaquine