Browsing by Author "Ongodia, Paul"

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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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    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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    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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    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.
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    The resurgence of blackwater fever among children in sub-Saharan Africa : a scoping review.
    (Research Square, 2025) Paasi, George; Namazi, Ruth; Malaika, Nancy; Namayanja, Cate; Ongodia, Paul; Okalebo, Benard Charles; Amorut, Denis; Asiimwe, Glorias; Okello, Francis; Mukunya, David; Munabi, Guyton Ian; Kiguli, Sarah; Idro, Richard; Olupot-Olupot, Peter
    Background: Blackwater fever (BWF), a life-threatening complication of Plasmodium falciparum malaria, has reemerged as a significant health concern among children in sub-Saharan Africa (SSA). Characterized by acute intravascular hemolysis, hemoglobinuria, and severe anemia, BWF necessitates urgent medical intervention. Despite its clinical severity, data on its burden, risk factors, and management remain fragmented. Therefore, this scoping review aimed to systematically map the existing literature on BWF in SSA, focusing on its epidemiology, clinical presentation, risk factors, management strategies, and outcomes among children in SSA. Methods: Following the Arksey and O’Malley framework, a comprehensive search was conducted across six databases (PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, web of science) and grey literature sources including preprint servers, conference proceedings, theses, dissertations, WHO reports and clinical trials registries (PACTR, clinicaltrials.gov). Studies published from inception to December 2024 were included. Data were extracted and synthesized narratively, with findings categorized thematically by epidemiology, clinical features, risk factors, management, and outcomes. Results: BWF was geographical clustered in East and Central Africa, particularly Uganda (53.8%) and the DRC (26.9%). Prevalence ranged from 4.4% to 52.7%, with higher incidence during rainy seasons. MBL2 AA polymorphisms, elevated IgG1 and quinine exposure (aOR 50.19-57.33) were significant contributors while G6PD deficiency (G6PDd) had conflicting associations. Clinical hallmarks were dark urine (100% of cases), jaundice (22.7-100%), and severe anemia (23.7-77%) aligning with the “hemolytic triad” reported in BWF. Acute kidney injury (AKI) (16.2-90.6% of cases) and recurrent episodes (50-68% readmission rates) exacerbated morbidity. Diagnosis relied on clinical criteria, with limited laboratory confirmation, while management emphasized artemisinin-based therapies and supportive care. Delays in blood transfusions and renal replacement therapy contributed to poor outcomes. Conclusion: BWF resurgence in SSA highlights critical gaps in diagnostics, equitable care, and adherence to artemisinin-based treatments. Targeted surveillance during malaria peaks, standardized diagnostic protocols, and improved access to supportive therapies are urgently needed to mitigate BWF-associated mortality and morbidity in high-burden regions.