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ItemThe role of oxidative stress response in modulating fluconazole resistance in cryptococcus clinical isolates(Makerere University, 2025)Introduction Fluconazole-resistant Cryptococcus neoformans has emerged as a significant public health concern, complicating the management and treatment of cryptococcal infections. Resistance to fluconazole is associated with increased rates of treatment failure, relapse, and mortality. Resistant strains have been reported globally, with varying prevalence rates. Objectives This study aimed to asses the role of oxidative stress resistance in modulating fluconazole resistance using cryptococcal isolates. Methods A laboratory-based experimental study was conducted at the Makerere University Microbiology Laboratory. Twenty Cryptococcus species isolates were analysed for tolerance to hydrogen peroxide (H2O2) and fluconazole resistance. Minimum inhibitory concentrations (MICs) were determined before and after oxidative stress exposure. Data were analyzed using STATA to calculate the proportion of H2O2- and fluconazole-resistant isolates. Fluconazole resistant Cryptococcus neoformans has emerged as a significant public health concern, posing challenges in the management and treatment of Cryptococcal infections. This abstract provides a comprehensive overview of the epidemiology, mechanism of resistance, clinical implications and therapeutic strategies associated with fluconazole resistant Cryptococcus neoformans. fluconazole resistant Cryptococcus neoformans strains have been reported worldwide, with varying prevalence rates. The clinical implications of fluconazole resistance include increased rates of treatment failure, relapse and mortality. To address the challenges due to fluconazole resistance, alternative treatment approaches have been explored. combination therapy, employing multiple antifungal agents with different mechanisms of action. This study determined the resistance pattern of Cryptococcus isolates with and without external oxidative stress. In a laboratory-based experiment study, we analysed 20 Cryptococcus species isolates at the Makerere University Microbiology laboratory. We determined their tolerance levels to hydrogen peroxide and assessed for their resistance partners before and after exposure to hydrogen peroxide. Data was analysed to determine the proportion of H2O2 and fluconazole resistant isolates were calculated using STATA. At lower doses of H2O2, most isolates-maintained growth although there was a heterogeneity response at higher concentrations. The MIC values for C. gattii were higher in stressed compared with non-stressed conditions. While in C. neoformans, there was a heterogenous response to Fluconazole post-oxidative stress exposure. We observed that oxidative stress sensitizes cryptococcus isolates to fluconazole though there were a number of isolates that remined resistant after exposure. This study demonstrates that the resistance patterns of Cryptococcus isolates are oxidative stress dependant and heterogenous in nature. The results highlight the heterogenous resistance nature of Cryptococcus isolates underpinning the need for cases to case analysis of resistance profiles. Results • At lower H2O2 concentrations, most isolates-maintained growth, though responses varied at higher doses. C. gattii showed increased MICs under oxidative stress compared to non-stressed conditions. C. neoformans exhibited a heterogeneous response to fluconazole following H2O2 exposure. Oxidative stress sensitized some isolates to fluconazole, although several remained resistant. At lower H2O2 concentrations, most isolates-maintained growth, though responses varied at higher doses. • C. gattii showed increased MICs under oxidative stress compared to non-stressed conditions. • C. neoformans exhibited a heterogeneous response to fluconazole following H2O2 exposure. • Oxidative stress sensitized some isolates to fluconazole, although several remained resistant. Recommendations Routine resistance profiling should be incorporated into clinical management of cryptococcal infections. Combination antifungal therapy using agents with diverse mechanisms of action should be considered for resistant cases. Further research is needed to understand the molecular basis of oxidative stress-induced sensitivity and resistance. Conclusion Resistance patterns in Cryptococcus isolates are influenced by oxidative stress and are highly heterogeneous. These findings highlight the complexity of antifungal resistance and the need for individualized resistance profiling.
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ItemMachine learning based-prediction of Hepatitis B Virus co-infection among HIV infected individuals in Uganda(Makerere University, 2025)Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection was reported to be a major clinical challenge in sub-Saharan Africa, particularly in Uganda, where both infections were highly prevalent. Evidence indicated that co-infected individuals faced an elevated risk of rapid liver disease progression, morbidity, and mortality. Early detection of HBV among people living with HIV was noted to be limited due to resource constraints, absence of routine screening, and the asymptomatic nature of early-stage HBV. Objectives: The study aimed to develop and evaluate a machine learning-based model for predicting HBV co-infection among HIV-infected individuals in Uganda. Study design: A retrospective study design was applied. Methods: Data was obtained from the Joint Clinical Research Centre (JCRC) electronic medical records (EMR) system including socio-demographic, clinical, and laboratory variables. Multiple supervised machine learning models were trained and evaluated using standard performance metrics, with cross-validation applied to assess model robustness. Results: The feature importance and interpretability analysis showed that Age, ALB, BILT and CD4 and ART duration were significant predictors of HBV co-infection. The best-performing model achieved accuracy of 92%, sensitivity of 80%, and specificity of 100%. Conclusion: It was concluded that a machine learning-based approach could accurately predict HBV co-infection in HIV-infected individuals, offering a cost-effective and scalable screening aid in resource-limited settings. Way forward: The integration of such predictive models into routine HIV care was recommended to improve early HBV detection and guide timely interventions, with further validation in larger and more diverse cohort.
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ItemResearch protocol amendments at Makerere University College of Health Sciences Research Ethics Committees during the COVID-19 pandemic : a retrospective documentary analysis(Makerere University, 2025)Background: It is an ethical and regulatory requirement globally, that protocol amendments are approved by the Research Ethics Committee before they are implemented to eliminate an apparent risk to the participants and to ensure smooth implementation of research. The COVID-19 pandemic led to disruption of several activities including research processes. However, it is not known to what extent the pandemic prompted protocol amendments. Objective: The study aimed to understand the reasons, frequency, nature, and responses of the Research Ethics Committees to applications for protocol amendments at Makerere University College of Health Sciences one year before and a year after Uganda introduced COVID-19, prevention and management restrictions. Methods: A desk review was used to retrospectively abstract data from protocol amendment requests submitted to Research Ethics Committees one year before and one year after COVID-19 restrictions were put in place by the Government of Uganda. A data abstraction template was used to code data for analysis using STATA version 15. Results: There were 259 protocol reviews and 345 amendments in the 2-year study period. During the one-year prior to COVID-19 pandemic, there were 140/259 (54%) reviews for a two-year total and contributed 201/345 (58%) amendments registered in the study period. One year after the introduction of COVID-19 prevention and management restrictions there were 46% reviews (119/259) and contributed 42% (144/345) amendments. During the two-year study period, there was a steady increase in uncommon reasons for which researchers sought amendments. The most prevalent reasons included informed consent (24%), the need to modify study tools at (11%), change of study sites at (10%), and the need to revise compensation at post the implementation of the COVID-19 mitigation measures. Other reasons included the need to collect more data/information, change of guidelines/regulations/laws and organizations, the need to adjust study budgets, sample storage plans of specimen, data safety and protection plans. When Uganda introduced the countrywide COVID-19, prevention and management restrictions, the RECs implemented new mandatory prevention requirements for conducting research during the pandemic. This was accompanied by a remarkable shift from regular Research Ethics Committee review meetings to expeditious individual member assigned amendment reviews as an approval mechanism. Conclusion: During the COVID-19 pandemic, there was a drop in the number of protocol reviews but researchers had a great need to implement project amendments. During this challenging context, the Research Ethics Committees’ attempt to cope with the heightened burden, may have led to the observed increase in irregular ethical research practices.
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ItemAssessing clinicians’ awareness and perceptions of patients’ rights in Mulago National Referral Hospital(Makerere University, 2025)Background: Patient rights encompass essential rules for interactions between patients and healthcare providers, including but not limited to: access to care, respect, communication, dignity, confidentiality, Privacy, refusal of treatment, medical records, and consent. These rights are upheld best when clinicians are aware of them. Although many studies focus on patients and the general public, there is a lack of research on clinicians' perceptions and awareness of patient rights in Uganda. This study aims to address this gap. Objective: To assess clinicians’ awareness and perception of patients’ rights in clinical care at Mulago National Referral Hospital. Methods: The study employed a qualitative cross-sectional approach, conducting 18 in-depth interviews with clinicians (9 medical doctors and 9 nurses) from Mulago National Referral Hospital. Data collection involved audio-recorded interviews, and the analysis was carried out using inductive thematic analysis with NVivo version 12 software. Participants were selected purposely to ensure diversity in age, gender, education, profession, and experience. Results: Fifteen of eighteen (15/18) participants demonstrated a good understanding of human and patient rights in particular. They could accurately define and provide examples of patient rights, such as the right to information, respect, non-discrimination, access to care, privacy, autonomy, and the right to refuse treatment. These rights were linked to professional codes, patient charters, the Hippocratic Oath, and ethical principles like autonomy, justice, beneficence, and non-maleficence. A few participants showed limited awareness, often due to a lack of refresher training. Participants agreed that all patient rights are equally important and none should be prioritized over the other. While respecting these rights generally promotes quality care and adherence, it can sometimes delay decision-making, as seen with the right to refuse treatment. Participants were divided on the use of deception, but agreed that accurate information should be provided at the right time. Regarding the feasibility of implementing patient rights in Uganda, some clinicians believed all rights are feasible, but most acknowledged challenges. Difficulties include ward congestion, insufficient resources, cultural and religious beliefs, and gaps in knowledge. These challenges were categorized into infrastructure, resource-related issues, cultural beliefs, and knowledge gaps. Conclusions and Recommendations: It was found that clinicians are aware of patient rights and generally support their importance in promoting quality care. Challenges like limited space, underfunding, cultural beliefs, and knowledge gaps hinder the implementation of these rights. Recommendations include enhanced training for both clinicians and the public, increasing the health budget, improving staffing levels, developing insurance policies, and strengthening reporting and monitoring mechanisms to better uphold patient rights in Uganda.
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ItemContamination and susceptibility patterns of Enterobacteriaceae in uncooked chicken and beef from supermarkets in Kampala Central Division(Makerere University, 2025)Background: Enterobacteriaceae contaminants such as Escherichia, Salmonella, Shigella, and Klebsiella, are some of the causative agents of gastrointestinal infections. The extent of Enterobacteriaceae contamination of raw chicken and beef in supermarkets of Kampala’s central division and its antibiotic susceptibility pattern still remains largely unknown. Objectives: The study aimed at determining the prevalence of Enterobacteriaceae contamination and its antibiotic susceptibility pattern in raw chicken and beef in Kampala city central division supermarkets. Methods: A cross-sectional study was conducted with a total of 48 samples from Six random supermarkets. Samples were tested for contamination status and reported as Colony forming units per gram (CFU/g). A panel of ten antibiotics was used for susceptibility testing of the isolated contaminants. Results: The general prevalence of Enterobacteriaceae was shown to be 83.33% (40/48) with Escherichia coli at 38% (35/92), klebsiella at 32% (30/92) and Citrobacter at 34% (32/92) being the predominant Enterobacteriaceae. Chicken (100%) was found to be more contaminated as compared to beef (66.67%) with a statistically significant difference among them (p value 0.002). There was no significant difference in the contamination of these foods across supermarkets and parishes (p value 0.549 and 0.441 respectively). The antibiotic susceptibility of Enterobacteriaceae from beef and chicken was generally good with all the organisms being susceptible to most antibiotics used except Ampicillin and ceftriaxone. Escherichia coli showed a 60% and 57.1% resistance to Ampicillin and ceftriaxone respectively while klebsiella showed a 56.7 % resistance to Ampicillin. No statistically significant difference was observed in the antibiotic susceptibility patterns of organisms isolated among chicken and beef (p value 0.00575). Conclusion: This study reveals a high prevalence of Enterobacteriaceae contamination in chicken especially as compared to beef and a low resistance burden to the antibiotics tested with the exception of Ampicillin and Ceftriaxone.