Mbarara University of Science and Technology Institutional Repository (MUST-IR)

MUST-IR preserves research output from the MUST Community

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Recent Submissions

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    Targeting mucosal immunity in malaria control: the underexplored role of IgA
    (Frontiers in malaria, 2025-06-25) Haruna Muwonge; Isaac Ssewanyana; Adoke Yeka; Pauline Byakika-Kibwika
    Malaria remains a global health crisis, causing an estimated 263 million cases and 597,000 deaths in 2023. Current measures—including insecticide-treated nets, ACTs, and the RTS,S vaccine—have stalled in reducing mortality, highlighting the need for novel strategies. While studies IgG and IgM have dominated malaria immunology research, recent data reveal a broader role for Immunoglobulin A (IgA). Evidence suggests that IgA can block parasite entry, activate complement, and modulate inflammation, although its protective efficacy has yet to be established. This review synthesizes the emerging literature on sporozoite- and merozoite-specific IgA responses, examines how IgA arises in a “non-mucosal” infection like malaria, and explores vaccine platforms-oral, nasal, or primeboost-that might harness IgA alongside IgG. We also identify critical gaps in correlating IgA levels with clinical immunity, emphasizing the need for specialized animal models and longitudinal human cohorts. Ultimately, leveraging IgA-driven mucosal immunity could significantly reinforce existing malaria interventions by preventing parasite establishment at mucosal or skin interfaces. By uniting mucosal and systemic immunity, research on IgA-based vaccines promises a next-generation approach to reducing malaria transmission, thereby creating a path towards global eradication.
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    Bioethics training needs assessment for HIV research in vulnerable populations: a survey of trainees at college of health sciences, Makerere university
    (BMC Medical Ethics, 2025) Josephine Nayiga; Stephen Okoboi; Grace Banturaki; Pauline Byakika-Kibwika; Barbara Castelnuovo
    Background Research involving vulnerable populations of people living with HIV (PLWH), such as children, adolescents, older adults, pregnant and lactating women, hospitalized patients, and key populations, presents complex bioethical challenges. We assessed bioethics training needs for trainees engaged in HIV research from the School of Medicine (SoM) of Makerere University and the Infectious Disease Institute (IDI) to inform the development of a comprehensive bioethics training program for trainees. Methods: A cross-sectional quantitative study was conducted from March to May 2024 using an online structured questionnaire distributed via Google Forms. Participants included former and current trainees who have conducted research with PLWH within the past five years. Data collected included self-rated bioethics knowledge, frequency of encountering bioethical challenges, confidence in addressing challenges across vulnerable populations, and preferred training topics and delivery formats. Descriptive data analysis was performed using STATA Version 17. Results: We attained a response rate of 67.5% (108/160). While 75.9% reported formal bioethics training, 58.3% rated their knowledge moderate. Frequently encountered challenges included maintaining confidentiality and privacy (61.1%), conducting informed consent processes (56.1%), applying bioethical principles, engaging with communities (54.6%), and selecting appropriate research participants (51.4%). Confidence in addressing bioethical challenges was notably lower for vulnerable populations than for general HIV research. Confidence of the trainees was higher in research involving older PLWH and pregnant/lactating women, moderate with children/adolescents and hospitalized individuals, and very low with key populations. Trainees expressed limited confidence in addressing cultural sensitivity, stigma, coercion, community engagement, harm monitoring, and compensation for research-related harm across all the populations. Top training priorities included ethical issues with research involving vulnerable populations (97.2%), reporting ethical concerns (94.4%), community engagement (93.6%), research on stored samples/data (94.5%), and stigma/discrimination Conclusion Trainees faced diverse bioethical challenges and exhibited varying confidence levels in addressing these issues across different vulnerable populations. These findings underscore the need for targeted, context-specific bioethics training tailored to conducting research with vulnerable PLWH. This study has informed the development of a comprehensive training program to improve the ethical conduct of HIV research in Uganda.
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    Clinical utility of the FilmArray® meningitis/ encephalitis panel in children with suspected central nervous system infection in a low-resource setting – a prospective study in Southwestern Uganda
    (BMC Infectious Diseases, 2025) Reza Rast; Elias Kumbakumba; Deborah Nanjebe; Phuthumani Mlotshwa; Milly Nassejje; John Mzee; Stephen Businge; Gilbert Akankwasa; Dan Nyehangane; Jesper Gantelius; Yap Boum II; Andreas Mårtensson; Juliet Mwanga-Amumpaire; Tobias Alfvén; Giulia Gaudenzi
    Background: In low-resource settings, limited laboratory capacity adds to the burden of central nervous system (CNS) infections in children and spurs overuse of antibiotics. The commercially available BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) with its capability to simultaneously detect 14 pathogens in cerebrospinal fluid (CSF), could potentially narrow such a diagnostic gap. Methods: In Mbarara, Uganda, we compared clinical utility (clinical turnaround time [cTAT], microbial yield, and influence on patient outcome and antibiotic exposure) of FA-ME with bacterial culture, in children 0–12 years with suspected CNS infection. Results: Of 212 enrolled children, CSF was sampled from 194. All samples underwent bacterial culture, of which 193 also underwent FA-ME analyses. FA-ME analyses prospectively influenced care for 169 of the 193 patients, and they constituted an ‘Index group’. The remaining 43/212 patients constituted a ‘Reference group’. Of all 194 CSF-sampled patients, 87% (168) had received antibiotics before lumbar puncture. Median cTAT for FA-ME was 4.2 h, vs. two days for culture. Bacterial yield was 12% (24/193) and 1.5% (3/194) for FA-ME and culture, respectively. FA-ME viral yield was 12% (23/193). Fatality rate was 14% in the Index group vs. 19% in the Reference group (P=0.20). From clinician receival of FA-ME results, median antibiotic exposure was 6 days for bacteria-negative vs. 13 days for bacteria-positive patients (P=0.03). Median hospitalization duration was 7 vs. 12 days for FA-ME negative and positive patients, respectively (P<0.01). Conclusions: In this setting, clinical FA-ME utility was found in a higher and faster microbial yield and shortened hospitalization and antibiotic exposure of patients without CSF pathology. More epidemiologically customized pathogen panels may increase FA-ME utility locally, although its use in similar settings would require major cost reductions.
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    Characterizing stroke presenting to a regional referral hospital before and during the COVID-19 pandemic in Uganda: a retrospective analysis
    (International Journal of Emergency Medicine, 2025) Josephine Nambi Najjuma; Timothy Mwanje Kintu; Jane Nakibuuka; Mark Kaddumukasa; Scovia N. Mbalinda; Martin Kaddumukasa; Christopher Burant; Shirley Moore; Martha Sajatovic; Edwin Nuwagira
    Introduction: Stroke, a leading cause of global morbidity and mortality, disproportionately impacts low and middle income countries, particularly in sub-Saharan Africa (SSA) which reports the highest stroke burden. The COVID-19 pandemic further complicated this situation, emerging as a significant stroke risk factor. The pandemic also disrupted healthcare systems worldwide, affecting stroke management and care accessibility, and leading to deteriorated conditions in stroke patients upon hospital admission. In this pre/during COVID-19 pandemic analysis of acute stroke cases presenting to a Ugandan hospital, we investigated the relationship between stroke admissions, management and treatment outcomes. Methods: This was a retrospective medical record review in which we analyzed medical charts of stroke patients admitted to Mbarara Regional Referral Hospital in 2019 (pre-COVID-19) and 2020 (during COVID-19). Sociodemographic data, stroke subtypes, medical history, and physical examination findings were extracted from the hospital records. Data analysis was performed using R-Studio, employing descriptive statistics and inferential analyses to compare stroke characteristics and outcomes across the two periods. Results: Data from 175 stroke patients was analyzed, with higher admission numbers in 2020 (69.7%), but a slightly higher mortality rate in 2019 as compared to 2020 (22.6% versus 18.9%, p=0.711). A significant increase in acute ischemic stroke cases was observed in 2020, with no significant differences in stroke severity or functional ability between the two years. Clinical parameters such as admission oxygen saturation, blood sugar, temperature, and Glasgow Coma Scale (GCS) score, along with complications like aspiration pneumonia and infections, correlated with mortality. There was no significant difference in survival probability between pre- and during-pandemic periods. Admission GCS, pulse rate, and aspiration pneumonia were significant predictors of 14-day in-hospital mortality. Conclusions: The surge in acute ischemic stroke cases during the pandemic highlights the need for robust stroke care systems, especially in high-burden regions like SSA. Some key predictors of mortality are potentially modifiable, suggesting that early intervention and vigilant monitoring of risk parameters could improve survival rates. Findings also highlight the need for tailored care strategies and health system improvements especially during public health emergencies to enhance patient outcomes.
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    A narrative review of the pathophysiology of sepsis in sub-Saharan Africa: Exploring the potential for corticosteroid therapy
    (PLOS Glob Public Health, 2025-04-09) Phoebe Gruccio; William S. Girard; Amelia D. Badipour; Reagan Kakande; Victor Adejayan; Muhammad Zulfiqar; Michael Ndyomugabe; Philemon Ojuman; Philemon Ojuman; Megan Nul; Jeffrey Sturek; ,Tania Thomas; Stellah Mpagama; Conrad Muzoora; Eva Otoupalova; Edwin Nuwagira; Christopher C. Moore
    Sepsis remains a significant global health threat with a disproportionate burden in low-income countries including those in sub-Saharan Africa where case fatality rates are as high as 30% to 50%. Defined as a severe systemic response to infection, sepsis leads to widespread immune dysregulation and organ dysfunction, including adrenal insufficiency. Critical illness-related corticosteroid insufficiency (CIRCI) arises from dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids, all of which can occur during sepsis. Clinical trials of corticosteroids for the treatment of patients with sepsis and septic shock have shown improvements in shock reversal, and in some studies, patient survival; however, their role in the treatment of sepsis in sub-Saharan Africa is unknown. The incidence of sepsis in sub-Saharan Africa is compounded by high rates of human immunodeficiency virus (HIV) and co-infections, including tuberculosis (TB), which is the leading cause of sepsis. Both HIV and TB can cause immune dysregulation and adrenal insufficiency, which may exacerbate CIRCI and prolong shock. Existing sepsis research has been predominantly conducted in high-income countries and has largely excluded people living with HIV or TB. Therefore, there is a need to better understand sepsis and CIRCI pathophysiology in the context of specific regional host and pathogen characteristics. In this narrative review, we explored the pathophysiology of sepsis in sub-Saharan Africa including the existing literature on the immune response to sepsis and the prevalence of adrenal insufficiency in patients with HIV and TB, with a focus on the implications for corticosteroid management. We found a compelling need to further evaluate corticosteroids for the treatment of sepsis in Africa.