Browsing by Author "Paasi, George"
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Item 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, PeterBackground: 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 trialItem Capacity building in field epidemiology in Sub Saharan Africa : findings from Infectious Disease Field Epidemiology and Biostatistics in Africa (IDEA) Fellowship Program(Taylor & Francis Group, 2025) Alunyo, Patrick Jimmy; Paasi, George; Ario, Riolexus Alex; Olupot-Olupot, PeterBackground: Emerging and re-emerging infectious diseases (EREIDs) remain a major public health threat globally, particularly in sub-Saharan Africa (SSA), where fragile health systems, inadequate infrastructure, and limited workforce training exacerbate vulnerabilities. Uganda, a recognised hotspot for outbreaks, faces increasing risk due to anthropogenic and environmental drivers. To address critical capacity gaps, the Infectious Disease Epidemiology and Biostatistics in Africa (IDEA) Fellowship was launched as Uganda’s first master’s-level programme in infectious disease field epidemiology. Led by Busitema University, in collaboration with national and international partners, the programme was funded through EDCTP-II (CSA2020E). Methods: The IDEA Fellowship combined theoretical instruction with fieldwork and research tailored to national health priorities. Activities included outbreak investigations, disease modelling, and surveillance, supported by Africa CDC, Uganda’s Ministry of Health, and UK institutions. A REDCap-based survey was administered to 202 public health professionals across SSA to assess training needs, skill gaps, and barriers. Data were analysed using descriptive statistics and thematic analysis. Results: The programme trained 15 master‘s-level fellows, strengthening Uganda’s capacity in surveillance, early detection, and outbreak response. Survey results showed that 55.4% of professionals required further training, with skill gaps in zoonotic disease management (64.4%), outbreak preparedness (64.9%), and data management (59.4%). Key barriers included limited diagnostic capacity (73.8%) and weak collaboration (49.5%). Qualitative findings highlighted inconsistent mentorship, restricted data access, and limited funding for fieldwork. Respondents advocated for structured mentorship, longer training durations (≥3–6 months), and hybrid delivery models (42.3%). Conclusion: The IDEA Fellowship demonstrates a scalable model for infectious disease capacity building in SSA. Training African scientists in local contexts promotes relevance, retention, and cost-effectiveness. Regional expansion, cross-sector collaboration, and systemic investment are essential for sustainable epidemic preparedness and global health security. Keywords: field epidemiology, capacity building, infectious disease training, Sub-Saharan AfricaItem Catastrophic expenditure associated with childhood hospitalisation for acute illness in Kenya and Uganda : a cross-sectional study.(BMJ Group, 2025) Jemutai, Julie; Njuguna, Gathoni Rebecca; Laurence, V Yoko; Murunga, Sheila; Ogwang, Caroline; Mwaringa, Shalton; Mwalekwa, Laura; Timbwa, Molline; Paasi, George; Olupot-Olupot, Peter; Juma, Mwanajuma; Thitiri, Johnstone; Ngao, Narshion; Singa, Benson; Mukisa, John; Mupere, Ezekiel; Lancioni, Christina; Sukhtankar, Priya; Tickell, D Kirkby; Uddin, Fakhar Md; Molyneux, Sassy; Walson, L Judd; Vassall, Anna; Berkley, JamesIntroduction: Childhood illness and hospitalization result in both direct and indirect costs to families before, during and after admission. We aimed to estimate the catastrophic expenditure during hospitalisation for children with acute illness. Methods: This was a prespecified cross-sectional substudy nested within two prospective studies. Participants were recruited and interviewed from three rural and three urban hospitals in Kenya and Uganda. A costing questionnaire was administered to the caregivers of 731 children hospitalised for acute illness to evaluate direct and indirect costs incurred by caregivers and families. Costs incurred were compared for families with children both with and without complicated severe malnutrition (CSM). Catastrophic out-of-pocket expenditure exceeding 10% and 25% of monthly income was assessed. Results: The median (IQR) total cost during hospitalization per child was US$47 (US$24–US$84), with higher costs for children with CSM, especially during hospitalisation (US$56 (US$26–US$99) vs US$36 (US$20–US$65); p<0.001). During hospitalisation, bed charges followed by food were the main cost drivers. Caregivers reported losing a median of 7 (4–11) days of productive time during a child’s hospitalisation with a mean loss of income of US$10 (SD US$25.6, median US$0 (US$0–US$10)). 92% and 74% of households experienced catastrophic expenditure at thresholds of 10% and 25% of monthly income, respectively. Caregivers reported borrowing, selling property and withdrawing other children from school to cope with costs. Conclusions: Despite intentions of free healthcare services for under 5, families of acutely ill children very commonly faced catastrophic expenditure, especially for children with CSM. Interventions aimed at supporting financial protection, reducing additional healthcare costs, and lowering health service charges may help prevent catastrophic expendituresItem Changes in haematological indices among children with sickle cell disease on hydroxyurea treatment for at least 1 year : a cohort study.(PLOS One, 2025) Emuli, Stephen; Tegu, Crispus; Oguttu, Faith; Nantale, Ritah; Ochieng, Paul; Paasi, George; Abeso, Julian; Wamulugwa, Joan; Musaba, Milton W.; Namazi, Ruth; Kiguli, Sarah; Mukunya, DavidBackground Sickle cell disease is the 12th cause of under-five mortality in Africa, with over 81,000 deaths attributed to sickle cell disease annually. Hydroxyurea is one of the few disease-modifying therapies available for the management of sickle cell disease. This study aimed to assess changes in haematological indices among children who had been initiated on hydroxyurea for at least one year in a non-trial setting at a regional referral hospital in Eastern Uganda. Methods We conducted a cohort study, which included children who attended the sickle cell clinic from 21/Aug/2024 to 30/Oct/2024. Data were analyzed using Stata version 18.0. We conducted a paired sample t-test comparing the haematological indices of children with sickle cell disease at baseline and at least one year later. Results We included 324 children. Nearly half 155/324 (47.8%) of the participants had good monthly adherence to hydroxyurea. The mean haemoglobin level at follow-up increased by 0.77g/dl (p <0.001) from 7.07g/dl (SD 0.10) at baseline to 7.84g/dl (SD 0.09). There was an increase in the mean corpuscular volume [0.97fl (p=0.645)] and mean corpuscular haemoglobin [0.58pg (p=0.120)]. The white blood cell count decreased by 6.17x103/µl (p<0.001) from 20.77x103/µl (SD ± 0.806) at baseline to 14.60x103/µl (SD ± 0.613) at follow-up. The differential white cell counts of neutrophils, lymphocytes, monocytes, and basophils also decreased. Conclusion Hydroxyurea resulted in an increase in mean haemoglobin level and a decrease in absolute and differential white blood cell count. The benefit was more pronounced among children with good adherence to hydroxyurea. We add our voice to calls for continued advocacy for the availability of hydroxyurea for use by children with sickle cell disease in low-resource settings. We also recommend a routine complete blood count to monitor response to treatment and also guide patient management among children with sickle cell disease initiated on hydroxyurea.Item 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. SamuelBackground 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, PfcrtItem Cross-border transmission corridors and diffusion velocities of Ebola-virus in in the Great-lakes basin : a 1976-2025 multilayered phylogeographic analysis.(Research Square, 2025) Paasi, George; Okware, Samuel; Olupot-Olupot, PeterBackground Ebola disease (EBOD) outbreaks are recurrent and highly lethal in the Great-Lakes basin, yet regional scale evolutionary reconstructions are lacking. Objectives To locate the long-term reservoir, quantify cross-border transmission corridors and measure diffusion velocities of EBOD outbreaks across central Africa during 1976–2025. Methods We curated 110 complete Ebola virus genomes from GenBank and BV-BRC, aligned them with MAFFT, and inferred a time-scaled phylogeny in BEAST v1.10.5. A dual-layer Bayesian framework coupled (i) a discrete Bayesian stochastic-search variable-selection (BSSVS) model for country-to-country migration with (ii) a continuous Cauchy relaxed random walk (RRW) for kilometre-scale movement. Posterior trees (300 million states; ESS > 200) were visualised in EvoLaps 2.42; Markov-jump counts, Bayes factors (BF) and branch velocities were extracted. Results Our dual-layer reconstruction shows that Ebola circulation is firmly rooted in north-eastern DRC: 80% of the root posterior density clusters within a 150 km radius of the Yambuku-Ituri-Likati forests axis, identifying this block of lowland rainforest as a persistent enzootic cradle. From that focus, diffusion unfolded in three distinct temporal phases initially as short-range local spread (1976–1987), then as a westward, Congo/Kasai river-mediated wave (1994–2007), and, since 2007, as an east-south-east advance toward Lakes Albert and Edward that underpins recent Ugandan outbreaks. Cross-border movement is dominated by the Lake-Albert corridor: Bayes factors of 32.1 for DRC to Uganda and 26.4 for Uganda to DRC, together with a median 13.4 Markov-jump events, account for three-quarters of all international transitions in the posterior; by contrast, only a single westward leap reaches the Gabon/Cameroon littoral (BF = 6.4). Continuous-model vectors yield a mean radial expansion of 7.9 km year⁻¹ (95% HPD: 5.4–10.6 km year⁻¹), yet the distribution’s heavy tail reveals rare founder events that cover more than 150 km in a single transmission chain. Conclusions A single Yambuku-Ituri-Likati forest axis hearth has seeded all documented EBOD outbreaks, with transmission funnelling chiefly through informal Lake-Albert crossings. Sentinel surveillance in this area, corridor-focused border health teams, and pre-emptive vaccine positioning along the Ituri-Lakes corridor could blunt future outbreaks. Keywords: Ebola virus, Zaire ebolavirus, phylodynamics, phylogeography, Bayesian stochastic search variable selection, continuous diffusion, cross-border transmission, Great Lakes region, Democratic Republic of the Congo (DRC), UgandaItem 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, PeterBackground: 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, MortalityItem High-resolution ecological niche maps identify population-density hot-spots for Ebola disease spillover in Uganda.(Research Square, 2025) Paasi, George; Okware, Samuel; Olupot-Olupot, PeterBackground Uganda experiences recurrent Ebola disease (EBOD) outbreaks, but the only available risk maps pool virus species and resolve five-kilometre grids insufficient for district-level preparedness. Therefore, this study aimed to generate one-kilometre, species-resolved MaxEnt risk surfaces for Uganda (2000–2024) and quantify the population living in predicted spill-over hotspots. Methods We compiled 71 laboratory-confirmed spill-over localities for Sudan, Bundibugyo and imported Zaire ebolaviruses and paired them with eleven minimally collinear environmental and anthropogenic predictors. Species-specific MaxEnt models were tuned with ENMeval (feature classes = L, Q, H; β = 0.5- 3.0) and evaluated by four-fold spatial block cross-validation. A 10% training-presence threshold converted continuous suitability to binary maps; the union surface was stratified into four risk tiers. WorldPop 2023 provided population counts. Results Models showed excellent discrimination: the pooled model achieved a spatially validated AUC of 0.927, while species-specific AUCs ranged from 0.961 to 0.999. Human population density dominated permutation importance (median 77%), followed by precipitation seasonality (7%) and bat-roost probability (8%). Tier 1 pixels (highrisk, cloglog ≥ 0.65) occupied only 58 % of Uganda’s land but contained 13.7 million residents (9 % of the national population), clustering along the Kampala-Hoima corridor and the Albertine Rift escarpment. All 15 historical outbreak epicentres fell within 8 km of Tier 1 or Tier 2 pixels. An alternative checkerboard partition raised mean AUC by Δ = +0.006 and preserved identical tier rankings, confirming robustness. Conclusions One-kilometre, species-resolved MaxEnt maps pinpoint compact geographic targets where intensified One-Health surveillance, GeneXpert diagnostics and future vaccine rings could most effectively curb EBOD emergence in Uganda.Item Hydroxyurea pharmacokinetics in children with sickle cell anemia across different global populations(PubMed Central, 2025) Power-Hays, Alexandra; McElhinney, E. Kathryn; Williams, N. Thomas; Mochamah, George; Olupot-Olupot, Peter; Paasi, George; Reid, E. Marvin; Rankine-Mullings, E. Angela; Opoka, O. Robert; John, C. Chandy; McGann, T. Patrick; Quinn, T. Charles; Punt, C. Nieko; Smart, R. Luke; Latham, S. Teresa; Vinks, A. Alexander; Ware, E. RussellHydroxyurea provides effective disease-modifying treatment for people with sickle cell anemia (SCA), especially when escalated to maximum tolerated dose (MTD), which has wide interpatient dosing variability due to pharmacokinetic (PK) differences. Whether hydroxyurea PK parameters differ among children with SCA in different global regions is unknown. We compared hydroxyurea PK parameters among children with SCA from 5 clinical trials: HUSTLE (United States), TREAT (United States), NOHARM (Uganda), REACH (Uganda and Kenya), and EXTEND (Jamaica). Key hydroxyurea PK parameters were determined using HdxSim, a validated hydroxyurea PK software program. The results were compared across regions by analysis of variance. PK profiles from 451 children with SCA (146 from the United States, 265 from Africa, and 40 from the Caribbean) were included. Children from Africa had slightly lower volumes of distribution, but absorption rate and clearance were similar across regions. The PK-recommended doses to achieve MTD were statistically different but clinically similar across the United States (26.6 ± 5.9 mg/kg per day), Africa (27.6 ± 6.5 mg/kg per day), and the Caribbean (25.2 ± 4.7 mg/kg per day) (P = .04). In multivariable regression, younger age and increased reticulocyte counts were associated with higher PK-recommended doses. Hydroxyurea PK parameters in children with SCA differ minimally across global populations, predicting clinically similar doses to achieve MTD. Individualized hydroxyurea dosing based on a PKpopulation model derived from US children with SCA can be used broadly to maximize the benefits of this critical medication in other global populations. These trials were registered at www.ClinicalTrials.gov as #NCT00305175 (HUSTLE), #NCT02286154 (TREAT), #NCT01976416 (NOHARM), #NCT01966731 (REACH), and #NCT02556099 (EXTEND).Item 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, PeterBackground: 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.Item The Impact of Diagnostic Delays and Timeliness of Response on Ebola Disease outbreak-level case-fatality Ratios in Uganda (2000–2023) : a Rapid Systematic Review and meta-analysis(Springer, 2025) Paasi, George; Okware, Sam; Olupot-Olupot, PeterBackground: Uganda has experienced seven laboratory-confirmed Ebola virus disease (EBOD) outbreaks from 2000 to 2022, with reported case‐fatality ratios (CFRs) varying widely. The influence of diagnostic and response delays on outbreak‐level mortality has not been systematically assessed. We conducted a rapid systematic review and meta-analysis to quantify the effect of diagnostic and response delays on outbreak-level mortality. Methods: We registered the review on OSF and adhered to PRISMA-2020 guidelines. We searched PubMed, Embase, Scopus, Web of Science, WHO Global Index Medicus, and grey literature through 30 April 2025. Eligible reports described laboratory-confirmed human EBOD in Uganda (2000–2022) and reported case counts, deaths, or quantitative timeliness metrics. Outbreak-level CFRs were meta-analyzed using random-effects models with Freeman–Tukey transformation (metafor package in R). Mixed-effects meta-regression assessed the association between continuous delay metrics and transformed CFR. Results: Fifteen reports met inclusion criteria, spanning 741 confirmed cases and 358 deaths. The pooled CFR was 45.4% (95% CI: 26.2%–65.2%; I² = 87.8%) across seven outbreaks. By species, Sudan ebolavirus outbreaks (n = 5) had a CFR of 44.6% (95% CI: 33.7%–55.6%), Bundibugyo ebolavirus (n = 1) 24.8% (95% CI: 18.2%–32.1%), and Zaire ebolavirus (n = 1) 100% (95% CI: 61.2%–100.0%). In meta-regression, each additional day from first case report to specimen collection was associated with a significant increase in CFR (β = 0.142 on the transformed scale; p = 0.025; R² = 62%), translating to an approximate absolute increase of 3.8% points in CFR per day at a baseline risk of 45%. Conversely, longer delays from symptom onset in the index case to national outbreak declaration were linked to a slight decrease in CFR (β = − 0.00765; p = 0.047). Conclusions Uganda’s EBOD outbreaks exhibit high and variable mortality, with diagnostic delays substantially amplifying case-fatality. Rapid specimen collection and prompt public health responses are critical to reducing EBOD mortality. Strengthening laboratory networks and accelerating declaration protocols should be central to future outbreak preparedness in Uganda and similar contexts. Keywords: Ebola virus disease • Case-fatality ratio • Uganda • Diagnostic timeliness • Outbreak response • Sudan ebolavirus (SUDV) • Bundibugyo ebolavirus (BDBV) • Zaire ebolavirus (EBOV) • Systematic review and meta‐analysis.Item 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, PeterBackground: 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.