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

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    Characterization of transcriptome diversity of invasive ductal carcinoma tissue from individuals of different ethnicities and ages
    (Makerere University, 2023) Ssegawa, Abdulkarim
    Breast cancer is a heterogeneous disease, and its incidence and prognosis are influenced by various factors including age and ethnicity. Consequently, tumors from individuals of different age groups and ethnicities may exhibit unique molecular fingerprints including transcriptomic profiles. However, while much work has been done to characterize tumors and describe their heterogeneity across epidemiological states, our understanding of their molecular features remains limited. This knowledge is critical and a prerequisite in the quest to fully understand the etiology of the disease and biology of tumors for the prevention, early diagnosis, and improved treatment of cancer. RNA sequencing (RNA-Seq) has emerged as a powerful tool for transcriptome analysis, providing a comprehensive view of gene expression and regulation. Therefore, in this study, we aimed to use RNA-Seq to investigate transcriptome diversity in breast cancer tissue from individuals of different ethnicities and ages. This study aimed to obtain RNA-Sequence sample data of breast cancer tissue from various ethnicities and age groups and perform RNA-Seq to analyze the gene expression profiles. The objectives of this study are to identify differentially expressed genes and pathways associated with breast cancer progression and prognosis and to characterize the transcriptome diversity between breast cancer tissues from individuals of different ethnicities and ages. Additionally, we will explore the potential clinical implications of our findings by investigating the relationship between transcriptome diversity, treatment responses, and survival outcomes. Ultimately, our study aims to provide important insights into the molecular basis of ethnic and age-related differences in breast cancer biology and to identify potential targets for personalized breast cancer management.
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    Treatment outcomes of isoniazid mono-resistant mycobacterium tuberculosis patients in Uganda: a retrospective cross-sectional study from 2017 to 2022
    (Makerere University, 2024-10) Kabugo, Joel
    Globally, isoniazid-resistant, rifampicin-susceptible TB is estimated to occur in 13.1% (95% confidence interval [CI]: 9.9–16.9%) of new cases and 17.4% (95% CI: 0.5–54.0%) of previously treated cases. Current WHO guidelines recommend treatment with Rifampicin (RFP), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (LFX, Q) for 6 months in patients with isoniazid mono-resistant TB (Hr-TB) but the effectiveness and use of other regimens in managing Hr-TB has not been established. There is a need to pay increased attention to the timely identification of Hr-TB patients in order to improve treatment success along with reduction of the risk for further drug resistance development Methodology: Selected isolates were tested for mutations associated with isoniazid resistance. Patient demographic data was obtained from the National TB Reference Laboratory (NTRL) electronic data system and request forms with additional data, such as treatment regimen, adverse effects, and treatment start dates obtained from treatment registers. The main outcome was dichotomized as unsuccessful treatment outcome (failed, died, lost to follow-up and not evaluated) vs successful treatment outcome (cured or completed). The independent variables available (age, sex, regimen used, M. tuberculosis mutation genes for isoniazid specifically InhA and KatG, history of TB, HIV status, and reporting year) were assessed as possible factors in the relationship between Hr-TB and treatment success. Results: A total of 85 isolates from different patients were analyzed in this study. Most of the participants 36(42.4%) turned culture negative at month one upon initiation of treatment. The findings from this study show that the most dominant Mycobacterium tuberculosis mutation occurred in the KatG MUT1 region with a nucleotide change of S315T1 and with inhA MUT2, MUT3A, and 3B region being registered with no mutations in this study. However, the study found that the majority of deaths were among people aged above 36 years 71.4% (5/7 participants). Conclusion: This study revealed delayed culture conversation of beyond 2 months as a significant factor associated with unsuccessful treatment of isoniazid mono-resistant TB and this can be used as a predictor in routine patient management. The study found a higher proportion of mutations known to confer high-level isoniazid drug resistance among patients with isoniazid drug resistance but the treatment outcome across the different mutations never varied. Hr-TB was commonest among the male and also mainly among participants who previously had TB and had been initiated on anti-TB treatment. In this study Majority of the patients had successful treatment outcome.
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    Occurrence of quinolone resistance genes qep, QnrA, QnrB and QnrS in uropathogenic E. coli from female clinical samples at Makerere University College of Health Sciences
    (Makerere University, 2022) Tusabe, Godwin Wenka
    Drug resistant Escherichia coli (E Coli) is the leading cause of community and hospital acquired urinary tract infections affecting approximate 150 million people each year worldwide. Uropathogenic Escherichia coli (UPEC) strains accounts for the main causative agents, this increase in prevalence is attributed to the indiscriminate use of antibiotics. Objectives The purpose of this study is to evaluate the prevalence of quinolone resistant genes qep, qnrA, qnrB and qnrS among Escherichia coli isolates obtained from female patients at the microbiology laboratory Makerere University college of Health Sciences. Two mechanisms of quinolone resistance have been established: 1) alterations in the targets of quinolones and decreasing drug accumulation inside cells through membrane impermeability or an over expression of efflux pump. 2) Mutations in specific domains of qep, qnrS, qnrA and qnrB causing variations in single amino acid of either gyrase or topoisomerase IV leading to resistance to quinolones. Methods and materials The study was a cross sectional study carried out using female samples stored in Makerere university microbiology laboratory and known to have quinolone resistance. From the archived samples, DNA extraction was done, polymerase chain reaction and agarose gel electrophoresis. Outcomes In total, 21 isolates resistant to ciprofloxacin and nalidixic acid. The highest rates of antibiotic resistance were obtained for nalidixic acid (100%), ciprofloxacin (80%). Of the 21 quinoloneresistant strains, 01 (7.1%) isolates harbored qep genes. None of the isolates harboured the qnrA gene, qnrB and qnrS. Conclusion These findings suggest a possible resistance to fluoroquinolone is of high interest for better management of patients and control of antimicrobial resistance in Uganda.
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    The informed consent process for emergency surgery at public and private hospital surgical emergency units in the urban Ugandan setting
    (Makerere University, 2024) Kituuka, Olivia
    Introduction: Informed consent is a process that can have challenges when required for emergency surgery, because the patient might not have the capacity to consent, and consent may be obtained from the next of kin, or surrogate decision-makers. The key stakeholders in the informed consent process for patients undergoing emergency surgery are the patient, the next of kin or surrogate decision–makers, and the emergency staff. This study hoped to contribute to a better and more nuanced understanding of how patients and their next of kin engage with the informed consent process in cases where emergency surgery is required. The study was conducted in the emergency units of one urban public, and one urban private not-for-profit hospital, to assess the knowledge and perspectives of the patients, their next of kin, and the emergency staff, towards the informed consent process for emergency surgery. Methods: We used a descriptive cross-sectional study design, combining quantitative and qualitative methods. We conducted a quantitative survey of 380 patients and their next of kin (210 from the public hospital, and 170 from the private hospital). Qualitatively, we conducted 39 in-depth interviews of patients, and the next of kin of patients who had undergone emergency surgery, 17 key informant interviews of emergency staff involved in the informed consent process, and direct observation of emergency staff during the informed consent process at these 2 units. Results: From the survey, 79.7% of patients did not have the risks of the surgery communicated to them, 87.6% were not given alternative options, and 57.4% had no opportunity to ask questions. There were 7 themes from the in-depth interviews of the patients, and the next of kin. These were attitudes and experiences regarding the informed consent process, decision-making in the informed consent process, disclosure, knowledge, and communication of the informed consent process, emergency staff role in the informed consent process, resources affecting the consent process, challenges encountered during the consent process, and recommendations to improve the informed consent process. Six themes studied for the key informant interviews of emergency staff were; knowledge and perspectives on informed consent; processes, procedures, and practices regarding informed consent; communication strategies for informed consent; ethical considerations; benefits of informed consent; and challenges of emergency informed consent. Direct observation of emergency staff showed that consent was conducted in a noisy environment, greeting of patients, disclosure of risks, and assessment of understanding were poorly done at both institutions. Conclusions: Risks and benefits should be disclosed to the patient in simple language, and patients should be given an opportunity to ask questions, to improve understanding and decision-making during the consent process. A communitarian approach, combined with shared decision-making between the doctor and the patient and NOK, should be used during the consent process. Emergency staff at both institutions need procedure-specific consent documents, which capture the information that is given to the patient and institutional guidelines and policies on consent for incapacitated patients, who have no surrogates.
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    Accuracy of the M-kit absolute concentration method for detection of drug-resistant mycobacterium tuberculosis in Uganda
    (Makerere University, 2024) Orena, Beatrice
    With an increasing incidence of multidrug-resistant tuberculosis (MDR-TB), accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis to first-line and second-line plus new individualized anti-TB drugs has become crucial for proper patient management. Diagnosis of DR-TB is mainly performed using Lowenstein Jensen (LJ) and BACTEC MGIT 960 phenotypic DST methods at the Uganda National TB Reference Laboratory (NTRL). These methods have high skills demand and some require 4-6 weeks to report results with high contamination rates. Although WHO recently recommended molecular DST assays like GeneXpert and Hein MDRplus and MDRsl Line Probe Assay, these methods also present performance challenges with low coverage for drug-resistance-conferring mutations and few anti-TB agents tested. This study evaluated the diagnostic accuracy of the Multiplexing Kit (M-Kit) absolute concentration method in the detection of Drug-Resistant Mycobacterium Tuberculosis in Uganda, against the conventional LJ proportion phenotypic DST methods. A total of 212 freshly grown MTB Isolates from Tuberculosis patients referred to NTRL, were tested for drug resistance for Isoniazid, Rifampicin, Ethambutol, Moxifloxacin, Levofloxacin, Amikacin and P-Nitro Benzoic acid, on M-Kit and LJ proportion DST assay. Data obtained was entered in Microsoft Excel-2010 and statistical data analyzed using SPSS version 27 software; whereas inferential statistics, sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) and Kappa value for M-Kit with respect to the gold standard method(s) were calculated using the MedCalc software. The sensitivity and specificity findings of the M-Kit assay for different studied drugs was; Isoniazid 98.3%, 97.9%, Rifampicin 94.8%, 96.9%, Ethambutol 68.6%, 96.7%, Moxifloxacin 100%, 99.6%, Levofloxacin 100%, 99.0% respectively, and Amikacin with specificity of 100%. The accuracy for various drugs studied ranged between 87.9 % to 99.9%, with an excellent concordance between the two methods showed by kappa values ranging from 0.806 to 0.962. The M-kit absolute concentration method was found to be highly accurate in susceptibility testing of M. tuberculosis against various first and second line drugs; Isoniazid, Rifampicin, Moxifloxacin, Levofloxacin, and Amikacin, with suboptimal performance for Ethambutol, when compared with the LJ proportion method in Uganda.