School of Bio-Medical Sciences (Bio-Medical) Collections

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    Bacteria aetiologies and antibiotic resistance profiles in pediatric urinary tract infections associated with congenital abnormalities of the kidney and urinary tract at Entebbe Children's Surgical Hospital
    (Makerere University, 2025) Apio, Priscilla
    Background: Urinary Tract Infections (UTIs) are among the most common bacterial infections in childhood. Malformation of the urinary tract often leads to recurrent infections. The increased risk of UTIs in children with these malformations often leads to a higher need for antibiotic treatment which can result in antimicrobial resistance. This study aimed to investigate the bacterial etiologies and antibiotic resistance profiles in urinary tract infections among pediatric patients with anatomical urological abnormalities at the Children's Surgical Hospital Entebbe (CSHE). Methods: A quantitative cross-sectional study was, conducted at the CSHE, from January 2024 to May 2025. Pediatric patients below 18 years with CAKUT except bladder exstrophy and urine analysis suggestive of UTI were sampled purposively. A structured questionnaire was used to collect data and midstream urine, neonatal bagged urine, in and out foley, or suprapubic urine was collected aseptically for urinalysis and isolated organisms antibiotic resistance profiles tested. Descriptive statistics and logistic regression in Stata 18 were used to analyze the data. Results: Of 101 participants 35.6% were aged 1-3 years and 90.1% male. The prevalence of UTI was 18.8%. Bacteria isolates were predominantly gram-negative with Escherichia coli (42.1%) and Pseudomonas aeruginosa (26.3%) being the commonly isolated bacteria. E.coli had high sensitivity to amikacin, gentamicin, meropenem, and chloramphenicol (100%), but exhibited complete resistance to amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole. P.aeruginosa was completely sensitive to ciprofloxacin (100%) but had decreased sensitivity (60%) for amikacin, gentamicin, and meropenem. Enterococcus faecium was completely resistant to ampicillin, ciprofloxacin, and gentamicin synergy but sensitive to vancomycin. Male sex (AOR = 0.03; 95% CI = 0.00–0.52, p = 0.017) and recent hospitalization (AOR = 12.43; 95% CI = 1.08–141.88, p = 0.042) were statistically significant independent predictors of UTI. Conclusion: UTIs among children with CAKUT were primarily caused by drug-resistant Gram-negative organisms. Male sex was protective against UTI, while recent hospitalization significantly increased UTI risk. The findings emphasize the importance of routine culture and sensitivity testing to guide appropriate antibiotic use.
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    Roll-out and scale-up of who-endorsed technologies for tuberculosis diagnosis in Africa: Opportunities, strengths, and challenges
    (Makerere University, 2025) Iragena, Jean de Dieu
    Introduction: Tuberculosis (TB) remains a major public health challenge in the WHO African Region, with high morbidity and mortality, particularly among people living with HIV and those affected by multidrug-resistant TB (MDR-TB). In response, the World Health Organization (WHO) has endorsed several diagnostic technologies to improve TB detection. However, the pace of roll-out and scale-up of these technologies across Africa has been uneven. This thesis aims to assess the implementation status of WHO-endorsed TB diagnostics, identify factors influencing their uptake, and propose a practical guide for integration of TB laboratory services into broader health system responses. Methods: A mixed-methods approach was employed. First, a literature review was conducted to assess the uptake of WHO-endorsed TB diagnostics between 2007 and 2017 and implemented up to 2021 across 47 WHO African Region (WHO/AFR) countries. Second, a structured survey was distributed to National TB Programme (NTP) and National TB Reference Laboratory (NTRL) managers, as well as technical partners, to identify predisposing, enabling, and need (PEN) factors influencing uptake. Finally, lessons learned from TB diagnostic services during recent pandemics were synthesized to develop a practical guide to increase the uptake and rollout in the scope of integrated disease diagnosis. Results: Objective 1: The literature review revealed that uptake of technologies such as Xpert MTB/RIF, Line Probe Assay (LPA), and Mycobacteria Growth Indicator Tube (MGIT) was slow, with median adoption times ranging from 2.5 to 6-9 years respectively. Objective 2: Survey responses from 47 of countries highlighted that laboratory preparedness, staff competence, and policy reform were key predisposing factors; funding availability was the main enabling factor; and the emergence of MDR-TB was the primary need factor. Objective 3: Good governance and political commitment emerged as critical factors. As a key output, the proposed Guide for the Rapid Uptake and Rollout of Tuberculosis Diagnostics in Africa consolidates good practices and lessons learned from the objective 1 and 2, including insights from fieldwork during the COVID-19 pandemic and other emergency disease outbreaks. This guide is designed to support member states in leveraging TB diagnostics to strengthen broader laboratory systems. It also promotes collaboration with the Supranational Reference laboratory Network and other regionally driven laboratory initiatives to catalyze in-country TB laboratory networks, moving towards integrated diagnosis of multiple diseases. Conclusion: Despite WHO endorsement, the roll-out and scale-up of TB diagnostic technologies in Africa have been delayed by systemic and contextual barriers. Addressing PEN factors and leveraging existing TB laboratory networks can accelerate implementation. The proposed guide offers a strategic direction for integrating TB diagnostics into broader disease surveillance and response systems, enhancing preparedness for future health emergencies.
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    Correlation of fluconazole minimum inhibitory concentrations with clinical outcomes of patients with HIV/AIDS having cryptococcal meningitis at the infectious diseases institute Kampala Uganda.
    (Makerere University, 2025) Obeny, Abel
    Introduction: Cryptococcal Meningitis (CM) is a severe fungal infection with varying clinical outcomes predominantly affecting people living with HIV/AIDS, especially in sub-Saharan Africa. Understanding the correlation between fluconazole minimum inhibitory concentrations (MICs) and clinical outcomes is crucial for optimizing treatment strategies. Methods: A cross-sectional study was conducted from April 2024 to July 2024 at the Infectious Diseases Institute. We included 51 HIV-positive patients diagnosed with CM. Data on demographic and clinical characteristics, fluconazole MICs, and clinical outcomes were collected. Fluconazole MICs were determined using VITEX machine and classified as R (Resistant), SDD (Susceptible dose-dependent) and S (Susceptible), and outcomes were categorized as cure or therapeutic failure. Statistical analysis was performed using R studio R.4.4.2. Results: The study population had a mean age of 36 years (Standard deviation 9.03), with 55% (28/51) being male. Of the 51 patients; the clinical outcomes were as follows: Fluconazole minimum inhibitory concentrations (MICs) indicated resistance in 70.6% of the post storage C. neoformans isolates, susceptible dose dependent susceptibility (SDD) in 21.6%, and susceptibility in 7.8% . Despite the high resistance rates, 92.2% (47/51) of patients were cured, while 7.8% (4/51) experienced therapeutic failure. Therapeutic failure encompassed the presence of persistent symptoms, death due to Cryptococcal meningitis and positive cultures for C. neoformans beyond the 10-week treatment duration. Those with therapeutic failure exhibited lower mean cerebrospinal fluid (CSF) lactate (2.94 mmol/L), CSF glucose (2.73 mmol/L), and peripheral CD4 count (28cells/μL) compared to those who were cured. Patients were categorized as cured if they exhibited absence of symptoms and yielded negative CSF cultures for C.neoformans after completing a 10-week fluconazole treatment regimen. However, there was no significant correlation between fluconazole MIC and patient outcomes (p = 1.000), suggesting that the distribution of MIC categories (SDD, Resistant, Susceptible) does not significantly differ between cured and therapeutic failure groups. Conclusion: Fluconazole MICs, particularly SDD, appear to be a significant prognostic indicator for patient outcomes in CM. Although high resistance was observed, the majority of patients achieved clinical cure. These findings suggest the need for routine MIC testing to guide treatment strategies for CM in patients with HIV/AIDS.
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    Analysis of population specific transcriptomic variations among patients with acute lymphoblastic leukemia
    (Makerere University, 2025) Nalukwago, Mercy Kamya
    Acute Lymphoblastic Leukemia (ALL) is the most common childhood cancer globally, accounting for 25% of cancer diagnoses in children under 15 years of age and 72% of all cases of childhood leukemia. It is also a clinically and biologically heterogeneous malignancy with striking variation in incidence, progression, and outcome based upon racial/ethnic groups.While this research has made progress, current studies are constrained to a large degree by the lack of representation of minority populations in genomic and transcriptomic datasets, which impairs the reliable discovery of race-related gene expression signatures. In addition, the functional impact of these transcriptomic differences on upstream biological pathways (e.g., cell cycle regulation, immune signaling, drug metabolism) is poorly defined, and hence, the merging of transcriptomics with genetic ancestry and clinical covariates to distinguish genetic from social determinants of health is limited.This study provides a comprehensive transcriptomic analysis of acute lymphoblastic leukemia (ALL) patient cohorts, emphasizing population-specific patterns of molecular subtype distribution, differential gene expression, and druggable target profiles. Using gene set-based clustering and nearest neighbor scores, the research delineates molecular groupings aligned with progenitor cell origin and highlights critical associations between transcriptomic signatures and clinical variables such as relapse, age, and race. I employed bioinformatic methods to analyze patterns of differential gene expression and molecular pathway enrichment to detect unique molecular signatures associated with different racial ancestries. Special focus was given to genes that play a role in leukemogenesis, immunological regulation, and medication metabolism because they may be responsible for racial differences. Notably, unique subtypes and druggable targets were identified among African patients, such as the CEBP subtype and mitochondrial gene signatures, suggesting therapeutic vulnerabilities and protective mechanisms exclusive to this population. Druggability assessments further reveal distinct landscapes across racial groups, with implications for targeted therapies and precision medicine strategies. The study contextualizes these findings within persistent racial disparities in ALL outcomes, advocating for inclusive molecular profiling and tailored therapeutic approaches to improve health equity and treatment efficacy. Limitations include sample size and reliance on ivexisting drug databases, with recommendations for future functional studies and expanded cohorts to validate the impact of population-specific transcriptomic features on ALL prognosis and management. This work underscores the necessity of integrating genomics, clinical annotation, and population diversity for optimizing precision oncology in ALL.
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    Effects of selected methanolic and ethereal medicinal plant extracts on efflux pumps of klebsiella pneumoniae and escherichia coli strains isolated from patients at mulago national referral hospital
    (Makerere University, 2025) Walungama, Andrew Kiyingi
    Background: Antimicrobial resistance (AMR) is a significant global health issue, with multidrug-resistant (MDR) Enterobacterales increasingly prevalent in Ugandan healthcare. Efflux pumps contribute to AMR, enabling resistance to antibiotics like Tetracycline. Data exists on tetraccyline’s performance against MDR Enterobacterales in Uganda. Medicinal plant extracts show promise as alternative/adjunctive therapies due to their potent biological activity. This study investigated selected plant extracts' role in reversing efflux pump-mediated resistance in MDR Escherichia coli and Klebsiella pneumonia in Uganda, using tetracycline as the test antibiotic. Objective: To assess the effect of selected methanolic and ethereal medicinal plant extracts on efflux pump activity among MDR Escherichia coli and Klebsiella pneumoniae isolates at Mulago National Referral Hospital, Kampala, Uganda. Materials and Methods: The study analyzed clinical isolates of E. coli and K. pneumonia from patients in an urban hospital. A total of 70 clinical isolates resistant to atleast three antibiotic classes including Tetracycline were selected from a pool of 385 strains at the Department of Medical Microbiology, Makerere University. Efflux pump activity of the strains was assessed by determining the effect of Omeprazole, a known proton pump inhibitor, on the MICS of tetracycline using the agar dilution method. Medicinal plant extracts underwent standard extraction procedures and antimicrobial testing via the agar well diffusion method. MIC values were assessed in the presence and absence of sub-inhibitory antibiotic concentrations to evaluate the extracts’ potentiation effects on Tetracycline. Results: Omeprazole significantly reduced tetracycline MICs to a value less than 2mcg./mL(p< 0.001) in 70 MDR E. coli and K. pneumonia isolates, confirming robust efflux pump inhibition. For plant extracts’inherent activity, Mango ether extract had highest MIC of 31.25 mcg/mL, followed by garlic and eucalyptus extracts that had moderate activity.Tetracycline potentiation with plant extracts was untested due to insufficient volumes. It is recommended to exploreOmeprazole’s mechanism, securie resources for mango, garlic, and ginger potentiation with tetracycline, and extending MIC tests to more antibiotics for enhanced MDR management