Browsing by Author "Okiror, William"

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    A phase I/II randomized controlled clinical trial to assess the feasibility, safety, and preliminary effectiveness of paracetamol in resolving acute kidney injury in children with severe malaria.
    (Springer Nature, 2026) Paasi, George; Namayanja, Cate; Ongodia, Paul; Okalebo, Charles; Okiror, William; Abongo, Grace; Masifa, George; Amorut, Denis; Muhindo, Rita; Olupot-Olupot, Peter
    Background: Acute kidney injury (AKI) is prevalent among children with severe malaria, contributing to considerable morbidity and mortality. Oxidative stress has been implicated in the pathophysiology of malaria-induced AKI, and paracetamol, with its antioxidant properties, has been proposed as a solution. This phase I/II randomized trial evaluated paracetamol as a potential renoprotective adjunct in children with severe malaria and acute kidney injury. Methods: We conducted a phase I/II open label parallel randomised controlled trial of 40 hospitalised children aged >6month to <12 years with malaria-induced AKI in eastern Uganda. Participants were randomized by a sealed envelope 1:1 to receive either oral paracetamol 20mg/kg 6-hourly for 48 hours or tepid sponging every 30 minutes until fever subsided. Only the assessors of the primary outcome were masked to the intervention. The primary outcome was renal recovery at 48 hours assessed using restricted mean survival time (RMST) in intention to treat population of children according to their randomisation groups. Results: Between 19 September 2021 and 25 August 2023, 250 children with haemoglobinuric severe malaria were screened and the 40 enrolled were randomly assigned paracetamol (n=20) or tepid sponging (n=20). The mean age was 6.54 (2.61) years. The mean time to renal recovery in the paracetamol group was 0.491 hours (95% CI: -9.265 to 10.248; p=0.921) longer than the control group within 48 hours, but this difference was not statistically significant even after adjusting for age and weight: 1.04 hours (95% CI: -8.61-10.70; p=0.832). The safety assessment indicated no significant differences in adverse events and hepatoxicity in either group. Conclusions: Although Paracetamol was safe, it did not significantly improve renal recovery in children with malaria-induced AKI. Further larger studies are needed to explore this role of paracetamol. The trial registration: ISRCTN84974248. Keywords: Acute kidney injury, Paracetamol, Children, Severe malaria, Blackwater fever, Restricted mean survival time, Randomised controlled trial
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    Comprehensive analysis of molecular markers linked to antimalarial drug resistance in Plasmodium falciparum in Northern, Northeastern and Eastern Uganda
    (Springer Nature, 2025) Olupot‑Olupot, Peter; Paasi, George; Katairo, Thomas; Alunyo, Patrick Jimmy; Nakiyemba, Alice; Ocen, Gilibrays Gilbert; Pande, Stephen; Alaroker, Florance; Okiror, William; Ocen, Emmaluel; Oula, Alex; Okalebo, Benard Charles; Ongodia, Paul; Amorut, Denis; Tukwasibwe, Stephen; Ndidde, Nabadda Susan; Sewanyana, Isaac; Nsobya, L. Samuel
    Background in Uganda, antimalarial resistance in Plasmodium falciparum poses serious public health and treatment challenges. Globally, recent data have highlighted the roles of following genes in malaria resistance: Plasmodium falciparum dihydrofolate reductase (Pfdhfr), Plasmodium falciparum dihydropteroate synthetase (Pfdhps), Plasmodium falciparum chloroquine resistance transporter (Pfcrt), Plasmodium falciparum multidrug resistance gene 1 (Pfmdr1), and Plasmodium falciparum K13 propeller domain (Pfk13). This study investigated the prevalence and characteristics of P. falciparum molecular markers linked to antimalarial resistance in Northern, Northeastern, and Eastern Uganda. Methods This cross-sectional study collected 200 dried blood samples from children (2 months to 12 years) in Northern, Eastern, and Northeastern Uganda. Samples were from malaria-positive cases confirmed by rapid diagnostic tests and microscopy. Genomic DNA was extracted from these samples and analysed using Molecular Inversion Probes to detect Plasmodium falciparum genetic mutations. The sequencing was performed on the Illumina MiSeq platform, and raw data was organized and analysed with MIPTools software. Results: The study sequenced over 50% of the samples at each site as follows: Apac 87.7% (43/49), Moroto 68.0% (34/50), Soroti 65.0% (13/20) and Mbale 53.1% (43/81). The Pfk13 A675V and C469Y mutations varied from 0 to 23.3% and 8.3–14.3%, in four sites, with consistently low prevalence in Apac. The Pfdhfr N51I and S108N mutations were fixed in all districts, while C59R was fixed in Moroto and nearing fixation (92–97%) in other regions. The emerging I164L mutation ranged from 1 to 10% in all sites. The Pfdhps A437G and K540E mutations were fixed in Soroti, with 3–5% wild-type prevalence in other sites. The A581G mutation showed 2.3% mixed genotypes in Mbale only. The Pfcrt K76T was predominantly wild type, except for 5% mutants in Mbale and Moroto. The pfmdr1 N86Y were wild type across all districts, except for 15% mixed genotypes in Soroti. Conclusion: This study reveal rising partial artemisinin resistance and widespread antifolate resistance surpassing WHO thresholds in Northern, Northeastern, and Eastern Uganda. Emerging super-resistant parasites pose a serious threat to malaria control, necessitating urgent enhanced surveillance and alternative treatment strategies. Keywords Antimalarial resistance, Uganda, Pfk13, Pfdhfr, Pfdhps Pfmdr1, Pfcrt
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    Early weaning from oxygen therapy in African children with severe pneumonia.
    (BMC Medicine, 2025) Maitland, Kathryn; Giallongo, Elisa; Hamaluba, Mainga; Alaroker, Florence; Opoka, O. Robert; Tagoola, Abner; Nalwanga, Damalie; Nabawanuka, Eva; Okiror, William; Nakuya, Margaret; Aromut, Denis; Williams, N. Thomas; Thomas, Karen; Harrison, A. David; Mouncey, Paul; Bush, Andrew; Fraser, F. J.; Rowan, Kathy; Olupot‑Olupot, Peter; Kiguli, Sarah
    Background: In Africa, severe pneumonia remains the major cause of paediatric hospitalisation, resulting in high requirements for oxygen therapy. Adequate supplies of oxygen are key challenges for many low-resource hospitals. The World Health Organization manual for oxygen therapy advises 2–3 days of oxygen therapy for pneumonia and recommends against early weaning, even in the absence of hypoxaemia. Few data support this recommendation. We describe the oxygen use and timing of weaning in the COAST trial of oxygen therapy (ISRCTN15622505). Methods: Children aged 28 days to 12 years presenting to 6 hospitals in Uganda and Kenya with severe pneumonia and hypoxaemia (saturations<92% on pulse oximetry (SpO2) were eligible for the trial. Children in two strata (a) severe hypoxaemia (SpO2<80%) and (b) moderate hypoxaemia (SpO2 80–91%) were allocated to receive high flow nasal therapy (HFNT), low flow oxygen delivery (LFO) or control (no immediate oxygen (moderate hypoxaemia stratum only)). Children were closely monitored over 48 h by pulse oximetry and weaned off oxygen once ­SpO2>92%. We describe the oxygen use and proportion requiring respiratory support over time by intervention strategy. Results: Of the 1842 children enroled the majority, 1454 (79%) had moderate hypoxaemia. In this stratum, by 2 and 8 h, 148 (41%) and 200/360 (55.6%) in the LFO arm had been weaned; in the HFNT arm, 213/362 (59%) were receiving respiratory support at 2 h in room alone, and by 8 h, 164/362 (45%) had been weaned. At 48 h, in the respective strata, 77–80% and 53–63% still had respiratory distress but without hypoxaemia and were thus not receiving oxygen. Median oxygen use at 48 h in the moderate hypoxaemia group was highest in LFO am 480L (IQR 236.2, 2132.2) compared to 113.4 L (IQR 0.0, 1453.9) in the HFNT and 0 L (IQR 0.0) in the control arms. Children requiring oxygen beyond 48 h, 17/33 (51.1%) and 9/46 (19.5%) in the respective strata, had additional cardiac conditions. Conclusions: Closely monitoring SpO2 resulted in early weaning and reduced the use of and exposure to oxygen. Where oxygen supplies are at a premium, this approach may improve equitable access for children with severe pneumonia. Keywords Severe pneumonia, African children, Oxygen therapy, High flow nasal therapy
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    Epidemiology, clinical spectrum, and outcomes of severe malaria in Eastern Uganda : a prospective study.
    (BMC, 2025) Namayanja, Cate; Paasi, George; Alunyo, Patrick Jimmy; Amorut, Denis; Okalebo, Benard Charles; Okiror, William; Ongodia, Paul; Abongo, Grace; Muhindo, Rita; Lubaale, A. M. Yovani; Olupot‑Olupot, Peter
    Background: In sub-Saharan Africa, malaria remains a public health problem despite some reports of declining incidence in the period 2000–2018. Since 2019, there have been some reports of disease epidemics and resurgences in areas that had registered steep declines and unusual clinical presentations. This study aimed to describe the epidemiology, clinical spectrum, and outcomes of severe malaria in children among malaria-endemic Eastern Uganda, a region that has recently experienced disease epidemics. Methods: This prospective study was conducted at Mbale Regional Referral Hospital, Uganda, from 08th May 2019 to August 15, 2023, as part of the Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda (EDCTP–TMA2016SF-1514-MEPIE Study). Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical World Health Organization criteria for surveillance of severe malaria were enrolled into the study following appropriate informed consent. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, lactate, glucose, blood gases, electrolytes, metabolites, and coagulation markers. In addition, urinalysis using dipsticks was done. Data were analysed using STATA V15. The study had ethical and regulatory approval before data collection commenced. Results: A total of 1,379 participants were recruited. The median age was 4 years (2 months–12 years). Most children 757/1379 (54.9%) were under 5 years, and 825/1379 (59.8%) were males. The common symptoms were fever 1368 (99.2%), poor appetite 1095 (79.5%), inability to sit upright 1051 (76.2%), vomiting 944 (68.4%) and yellow eyes 833 (60.4%). The common signs included prostration, haemoglobinuria and jaundice. Prolonged hospitalization was found in 284/1339 (21.2%) and was associated with impaired consciousness 116/166 (30.1%), P=0.003; haemoglobinuria 514/705 (27.1%), P<0.001 and jaundice 505/690 (26.8%) P<0.001. The overall mortality was 40/1347 (3.0%). Children who had>1 severity feature were at a higher risk of mortality. Conclusion: In this prospective study of children with severe malaria in Eastern Uganda, the overall mortality was 3.0% and the more the disease clinical syndromes the higher the risk of death. Keywords: Clinical spectrum, Severe malaria, Child, Prolonged hospitalisation, Mortality
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    The association between malaria parasite geometrical mean and clinical spectrum of severe disease in a high-transmission setting in eastern Uganda : a cross-sectional study.
    (Wiley, 2025) Egiru, Isaiah Eregu Emma; Namayanja, Cate; Paasi, George; Okiror, William; Ongodia, Paul; Okalebo, Benard Charles; Muhindo, Rita; Abongo, Grace; Oguttu, Faith; Okibure, Ambrose; Okello, Francis; Tegu, Crispus; Mukunya, David; Chebet, Martin; Olupot-Olupot, Peter
    Background: Malaria burden remains significant, especially in high-transmission settings. While some data show an association between severe malaria and high-malaria parasite geometrical mean (GM), few data describe this phenomenon in malaria hightransmission settings. We described the malaria parasite GM and clinical spectrum of severe malaria in Eastern Uganda to advance understanding of its implications on disease severity and patient outcomes. Methods: We conducted a cross-sectional study in Mbale Regional Referral Hospital (MRRH), Eastern Uganda. Children admitted with severe malaria confirmed by microscopy with ages between 2 months and 12 years were enrolled in the study from September 21, 2021, to September 21, 2022. Data were collected on patient sociodemographics, clinical symptoms and signs, laboratory parameters, treatment details, and outcomes. From the blood samples collected at the bedside, blood films/smears were made. The malaria parasite count was obtained from the patients’ smears by counting the malaria parasites against 200 white blood cells (WBCs). The GMs of malaria were obtained after the logarithmic transformation of the parasite counts. Data were analyzed using Stata 15, and significant associations were reported at p values of 0.05 at 95% confidence intervals. Results: A total of 376 children with a mean age of 4.65 years were recruited, of whom 57.71% (217/376) were male. Children under 5 years constituted 61.7% (232/376). The common clinical manifestations were prostration 76.9% (289/376), jaundice 55.6% (209/376), severe anemia 48.4% (182/377), and hemoglobinuria 46.5% (175/376). The overall malaria parasite GM was 12,238.42 parasites/microliter (95% CI: 9166.72–16,339.43). The highest GM of 197,000 parasites/microliter (95% CI:40,817.64–946,368) and the lowest of 8938.185 parasites/microliter (95% CI: 5932.8–13,466.01) were observed in shock and severe anemia, respectively. Inpatient mortality was 3.4%. Conclusion: In malaria high-transmission settings of Eastern Uganda, patients with severe malaria had low parasite GMs similar to those in uncomplicated malaria. Thus, malaria parasite GM should not be relied upon to determine disease severity in these settings.