Browsing by Author "Muhindo, Rita"

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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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    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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    Congenital cytomegalovirus in eastern Uganda : prevalence and outcomes.
    (BMC Pediatrics, 2025) Okalany, Regina Akwi Noela; Engebretsen, Marie S. Ingunn; Mukunya, David; Chebet, Martin; Okello, Francis; Weeks, D. Andrew; Mwanda, Edrin; Muhindo, Rita; Bisso, Fred; Tylleskär, Thorkild; Olupot-Olupot, Peter; Burgoine, Kathy
    Background: Cytomegalovirus (CMV) infection poses risks to both maternal and neonatal health, however there are limited comprehensive data on congenital CMV in low-resource settings where the virus is widespread, particularly among women of reproductive age. Our research in eastern Uganda aimed to assess the prevalence of congenital CMV and outcomes among infants to inform public health policies and interventions in similar settings, addressing a significant gap in current knowledge. Methods: We conducted a descriptive study, nested within the BabyGel Trial, across Mbale and Budaka districts in eastern Uganda, between May 2023 and January 2024. Infants underwent saliva sampling within the first week of life, which was validated through urine polymerase chain reaction testing within the first 21 days of life. At three months of age, a cranial ultrasound examination, neurological examination, developmental evaluation, and audiological assessment were conducted for all infants diagnosed with congenital CMV infection. Statistical analyses were performed using Stata 17.0. Results: Congenital CMV infection was found in 5 out of 1,265 newborns tested, indicating a prevalence of 0.4% (95% CI: 0.16 to 0.96). Of these 5 infected infants, two experienced febrile illness at birth and required hospitalisation within the first week of life, and three had findings on ultrasound examination consistent with congenital cytomegalovirus during the neonatal period. Audiologic follow-up until three months of age revealed that three infants had failed unilateral and bilateral hearing screening. Neurodevelopment assessments using the Malawi Development Assessment Tool fell within optimal ranges for all 5 infants; however, when evaluated using the Hammersmith Infant Neurological Examination, four infants scored below optimal levels. Conclusion: Our community-based study revealed a low prevalence of congenital CMV infection. Further longitudinal multi-site research is needed to assess the generalisability of these findings. Also, long-term follow-up of children is crucial to understanding the outcomes and sequelae of infected infants to inform prevention strategies, targeted interventions and scalable screening frameworks in resource-limited settings. Keywords: Cytomegalovirus, Congenital, Prevalence, Neurodevelopment, Hearing, Low-resource setting, Uganda
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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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    Nasopharyngeal Microbiome Composition and its Clinical Correlates in Children Hospitalized with Severe Pneumonia in East Africa
    (Oxford University Press, 2026) Makori, O. Timothy; Gicheru, T. Elijah; Mburu, W. Maureen; Sada, S. Mercy; Nyawa, Omar; Mutunga, Martin; Lewa, Clement; Cheruiyot, Robinson; Kiguli, Sarah; Olupot-Olupot, Peter; Muhindo, Rita; Mogaka, Christabel; Williams, N. Thomas; Agoti, N. Charles; Maitland, Kathryn; Sande, J. Charles
    Background: Pneumonia remains the leading cause of infectious mortality in children under 5, with the highest burden in sub-Saharan Africa. Dysbiosis in nasopharyngeal (NP) microbiota may influence pneumonia susceptibility and progression, but little is known about its composition or clinical relevance in low- and middle-income countries. We characterized the NP microbiota of children hospitalized with severe pneumonia in East Africa and investigated associations with clinical outcomes. Methods: We performed 16S rRNA partial gene sequencing of NP swabs collected at hospital admission from 876 children enrolled in the COAST trial across 5 sites in Kenya and Uganda. Clinical, demographic, and virological data were prospectively collected. Microbial profiles were analyzed using hierarchical clustering, nonmetric multidimensional scaling, and multivariable regression to assess associations with respiratory viral infections, sepsis, cyanosis, bacteremia, coma, HIV status, malnutrition, sickle cell disease, malaria, and mortality. Results: The NP microbiome was structured in 6 distinct clusters, each dominated by different genera, including Staphylococcus, Streptococcus, Haemophilus, Dolosigranulum, Corynebacterium, and Moraxella. Multivariable models adjusting for study site and age showed a positive association between Corynebacterium and early mortality. Temporal analysis showed elevated Corynebacterium abundance in children who died within 48 hours of admission, then declined over longer 56 survival intervals, approaching levels observed in survivors. However, time-continuous models did not support this persistent association, suggesting a subgroup effect. Conclusions: We provide one of the largest high-resolution surveys of the pediatric upper airway microbiome in Africa, identifying microbial patterns associated with viral infection, HIV status, early death, and bacteremia. Keywords: 16 seconds rRNA sequencing; nasopharyngeal microbiome; pediatric pneumonia.
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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.