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ItemMalaria circumsporozoite protein-specific antibody titres among HIV-infected and non HIV-infected children under 5 years of age, resident in areas of high malaria transmission in Uganda(Makerere University, 2025)Background: Malaria and HIV co-endemicity presents a major public health burden in sub-Saharan Africa, with young children bearing the greatest morbidity and mortality. The Plasmodium falciparum circumsporozoite protein (CSP) is the antigenic target of leading malaria vaccines such as, RTS,S/AS01, where CSP-specific IgG antibodies are critical mediators of protection. HIV infection may dysregulate humoral immunity through germinal center attrition, impaired isotype switching, and depletion of long-lived plasma cells, potentially diminishing anti-CSP responses and heightening malaria vulnerability. Furthermore, HIV-exposed uninfected (HEU) children—those born to HIV-positive mothers but uninfected themselves—may exhibit altered immune function due to in utero and perinatal exposures. Understanding the landscape of malaria-specific immunity, as measured by CSP-IgG titres, among HIV-infected (HIV+), HEU, and HIV-unexposed uninfected (HUU) children under five years in Uganda’s high-transmission zones is essential yet remains inadequately characterized. This study investigated the impact of HIV status and sero-exposure on CSP-IgG titres to inform targeted prevention and vaccination strategies in co-endemic settings. Methods: We conducted a hospital-based cross-sectional study from February 2025 to June 2025 among 206 children aged less than 5 years residing in five high malaria transmission districts of Eastern Uganda (Sironko, Budaka, Kibuku, Mbale, Pallisa). Participants were stratified into three groups: HIV+ (n=69), HEU (n=69), and HUU (n=68). Standardized questionnaires captured demographic (age, sex, district, setting, household income), clinical (HIV status, ART adherence, cotrimoxazole prophylaxis [CTX] and adherence, malaria history within past year), and environmental factors (insecticide-treated net [ITN] use frequency/condition, indoor residual spraying [IRS] in past year, presence of stagnant water). CSP-specific IgG titres (ng/L) were quantified using standardized enzyme-linked immunosorbent assay (ELISA). Log-transformed titres were analyzed using multivariable linear regression, adjusting for age, malaria episode history, ITN use, household income, setting, and crucially, CTX use. Models accounted for district-level clustering using mixed-effects approaches. Sensitivity analyses assessed robustness to outliers and missing data. Results: HIV+ children (all on CTX prophylaxis) exhibited significantly lower geometric mean CSP-IgG titres (351.7 ng/L; median: 218 ng/L, IQR: 126-714) compared to HEU (412.4 ng/L; median: 330 ng/L, IQR: 196-600) and HUU children (536.9 ng/L; median: 506 ng/L, IQR: 298-968; Kruskal-Wallis p<0.001). Strikingly, among HEU children, those receiving CTX (n=25) had markedly lower CSP IgG titres (mean: 294.2 ng/L; median: 248 ng/L) than HEU children not on CTX (n=44; mean: 622.7 ng/L; median: 580 ng/L; Mann-Whitney U (p<0.001). Adjusted regression confirmed HIV+ status was associated with a 42% reduction in log-transformed titres (β = -0.42, 95% CI: -0.65, -0.19; p<0.001) relative to HUU children. Increasing age (β = 0.02 per month, p<0.01) and number of prior malaria episodes (β = 0.15 per episode, p<0.001) were independently associated with higher titres. Suboptimal vector control was evident since IRS coverage was minimal (4.9%), and ITN use, while widespread, was often inconsistent ("sometimes"). Conclusion: HIV infection is independently associated with substantially impaired acquisition of malaria CSP-specific antibodies in young Ugandan children, potentially increasing their biological susceptibility in high-transmission settings. The profound suppression of titres among both HIV+ and CTX-using HEU children likely reflects the combined effect of HIV-related immune dysregulation and the confounding prophylactic effect of CTX in reducing antigenic exposure. While consistent ART adherence may attenuate HIV-associated immunosuppression, its specific role in immune response to the CSP antigen warrants further study. Critically low IRS coverage and inconsistent ITN use underscore persistent environmental risks. Our findings advocate for integrated HIV-malaria control that includes optimizing ART and CTX adherence, while simultaneously scaling up effective vector interventions (ITN distribution campaigns, expanded IRS) for HIV-affected children. These findings advocate for integrated HIV-malaria care that prioritizes consistent vector control and considers tailored malaria vaccination strategies for HIV-affected children to mitigate their increased biological susceptibility..
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ItemDiagnostic accuracy of stool xpert MTB/RIF ultra assay for pulmonary tuberculosis among PLHIV in Kampala, Uganda(Makerere University, 2025)Tuberculosis (TB) continues to be the leading cause of health complications and fatal outcomes among PLHIV. Current WHO-recommended strategies for diagnosing pulmonary tuberculosis among PLHIV faces challenges of poor or absolute lack of sputum in this population, hence, low sensitivity. Alternative samples are therefore being sought. We aimed to evaluate how accurately the stool Xpert MTB/RIF Ultra assay detects Mycobacterium tuberculosis in adult individuals living with HIV. Methods: This was a cross-sectional diagnostic accuracy study among 139 individuals with presumptive PTB, aged ≥18 years, male and female PLHIV, attending Mengo Hospital and Kiswa Health Centre III, Kampala Uganda. One stool sample and one routine spot sputum sample were collected from each participant, processed on the GeneXpert PCR System, brand name (Ultra; Cepheid, Sunnyvale,CA,USA). Between August 15, 2025, and October 15, 2025, 139 participants were enrolled (78 [55.7%] female and 62 [44.3%] men). PTB was confirmed using the molecular assay in 7 participants (5%). The sputum and stool Ultra tests demonstrated similar sensitivity and specificity. A higher positivity rate (57.1%) was observed in males aged 24–44 years relative to females in the corresponding age group. These results point to the potential role of stool Ultra as an additional diagnostic approach for tuberculosis in people with HIV. Although early morning sputum samples typically contain higher bacillary loads than spot samples, our study utilized spot sputum specimens as they were more practical for routine same-day collection at the study sites. Additionally, total CD4 count and HIV viral load measurements were not obtained due to financial and time constraints. These unmeasured variables may have influenced the diagnostic performance (sensitivity and specificity) of the stool Xpert MTB/RIF Ultra assay, representing an important limitation of our study. Future research should include early morning sputum samples and incorporate CD4 and viral load measurements to improve diagnostic accuracy and control for host-related confounders.
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ItemHealth worker's practices and perspectives on the allocation of solid organs based on Govind Persad et al. criteria: a case of Mulago Hospital(Makerere university, 2026)Allocation of solid human organs is complex due to global scarcity amidst high demand necessitating transparent, equitable and efficient allocation policies. In Uganda, the absence of a formal organ distribution framework raises concerns about fairness and consistency in decision-making. This study explored the practices and perspectives of health workers in Uganda regarding organ allocation, guided by Govind Persad’s ethical criteria. A qualitative cross-sectional study was conducted with 15 health workers involved in organ transplant services at Mulago National Referral Hospital, Kampala. Key-informant interviews were audio-recorded, transcribed verbatim, and analyzed by two independent coders. Analysis was primarily deductive, guided by Ajzen’s Theory of Planned Behaviour and Persad et al.’s multi-principle framework, complemented by inductive analysis to capture emergent themes. NVIVO 14 software supported data management and organization. Four themes emerged: practices for organ transplant scheduling, attitudes towards organ allocation based on Persad’s ethical principles, perceived control and ethical dilemmas encountered. Current practices at Mulago Hospital are largely influenced by an institutional culture that prioritizes first-degree relatives identified by patients. Compatibility screening and psychosocial support are provided and standard operating procedures emphasize voluntarism, informed consent, and respect for religious values. Health workers expressed positive attitudes toward adopting global organ allocation models but emphasized the need for contextual adaptation. Perceived control over transplant scheduling was limited due to systemic constraints, including resource scarcity and infrastructure limitations, which negatively affect equity. Ethical dilemmas commonly arose from challenges in identifying familial coercion and managing emotional distress linked to transplant disqualifications or delays. Formal organ allocation frameworks are essential for promoting equity and transparency in transplant scheduling. Adjusting global allocation models to align with the resource, cultural, and systemic constraints represents a pragmatic approach to strengthening organ allocation practices at Mulago National Referral Hospital and similar resource-limited settings.
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ItemUnderstanding stakeholder perspectives, preferences and experiences on the return of individual pharmacogenomic research results(Makerere University, 2025)Globally, the return of results from genomic analyses including pharmacogenomics research has been approached with several debates in the past decades. Despite research participants’ high demand for individual genomic and pharmacogenomic research results, there is little consensus on whether results should be returned at all in research setting and if so, what kinds of results, how they should be returned, and under what circumstances should results be returned. This study aimed to analyse stakeholder perspectives, experiences, and preferences to develop an institutional procedural guidance for the return of individual pharmacogenomic research results to people living with HIV. We carried out three sub studies at Makerere University College of Health Sciences and affiliated HIV research institutions located on Mulago Hill. In sub-study I, a convergent parallel mixed methods study was conducted where 225 participants were enrolled in a survey and 30 of them participated in deliberative focus group discussions (dFGDs). Qualitative data were analysed using thematic analysis method. Quantitative data were analysed using a Poisson model and a multinomial logistic regression model to determine the factors influencing the primary outcome (preferences for either all results, partial results or none of the results) and secondary outcome (preference for either the active role, collaborative role or passive role) respectively. In Sub-study II, an exploratory descriptive qualitative study was conducted with 12 REC members, 12 researchers and 30 CAB members to analyse the stakeholder perspectives and ethical considerations on how individual results should be safely returned to people living with HIV. The data were analysed using thematic analysis. In sub-study III, a modified ADAPTE process methodology was employed to develop an institutional procedural guidance for the return of individual pharmacogenomic research results in three phases. These included the set-up phase, adaptation phase, and finalization phase. We utilized the findings from sub-study I and II in the adaptation phase to develop the first draft of the procedural guidance. We also utilized the feedback from the panelists and potential end-users to develop the second and final draft of the procedural guidance. Sub-study I: For the primary outcome; the majority (98%) participants wanted to receive individual primary pharmacogenomics research results. Factors that significantly influenced preference for all results were antiretroviral experience for than five years (PR: 1.69, p=0.001), attending the IDI clinic from more than five years (PR: 1.19, p=0.045), and religion (PR: 0.76, p=0.036). Reasons for the desire to receive results were reciprocity for valuable time and effort, preparing for future eventualities, and the right to health information. For the secondary outcome; most participants 55.2% (122/221) preferred the collaborative role, 30.3% (67/221) preferred the active role, and 14.5% (32/221) preferred the passive role. Factors that significantly influenced preference for an active role compared with a collaborative role were marital status (OR: 0.282, p=0.013), research experience (OR: 4.37, p=0.028), and religion (OR: 2.346, p=0.041). The reasons proffered for the active role included prior experience with antiretroviral treatment and increased exposure to research activities. Sub-study II: The prominent themes from the interviews and deliberative focus group discussions included stakeholder’s attitudes, ethical and social implications, perceived challenges and recommendations to the process of returning individual results. Additionally, five themes emerged regarding the key considerations for a safe return of individual results. These included, (i) defining the nature of research results to return to participants; (ii) obtaining informed consent and preparing research participants to receive their individual results; (iii) opinion on how to communicate results to participants, (iv) community engagement strategies for promoting understanding of pharmacogenomic results; (v) perceived roles of stakeholders in promoting participants’ understanding and utilization of pharmacogenomic research results. Sub-study III: The institutional procedural guidance comprised of three main phases, which include pre-study phase (protocol development phase), the feedback of individual results phase, and the post-feedback of individual results phase. In each phase, several key considerations have been described to guide researchers on how individual results can be safely returned to participants. This study provides insights into stakeholder perspectives, preferences, and experiences on whether and how individual pharmacogenomic research results should be returned to PLHIV safely. These insights contribute to the national and international debates on whether and how genomic and genetic results should be returned to participants. Of interest, all stakeholders agree that individual results provide an opportunity to improve participants’ quality of life and uphold the principle of autonomy. However, there is a need for caution when returning such results, especially the incidental findings whose implications do not only affect an individual but might extend to their families and communities. We recommend further research to explore the feasibility of using various culturally appropriate strategies to enhance participants’ understanding of pharmacogenomic research information and the implications of these results.
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ItemEEG charateristics in patients with CT or MRI localized intra-axial brain tumors at a tertiary hospital in Uganda.(Makerere University, 2022)Introduction: EEG findings in brain tumors vary. The various types of electroencephalographic alterations, when they occur, may include delta slowing, spikes and spike-wave elements & “typical interictal epileptiform discharges” among others. These observations promise a useful insight into the pathophysiology of epilepsy. Objectives: we described EEG findings in 31patient with intra-axial brain tumors with the primary aim of delineating the neuroanatomical structures involved in modulating the observed EEG findings. Methods: This was a cross-sectional study in 31 patients with intra-axial brain tumors. Size and intra-axial positions of the brain tumours was determined and confirmed using CT or MRI scans then surface EEG was done and its characteristics described and documented by a blinded reader in the corresponding cases. Results: For both infratentorial and supratentorial loci we find that the tumor size is not linearly related to the EEG characteristics. The clear cut EEG findings were three (i.e. Normal, polymorphic slowing and interictal epileptiform spikes and sharp waves). The total number of normal EEG was 11 (35.5%) in patients with tumors of both infratentorial and supratentorial locations. Polymorphic slowing was 12 in total (38.7%) mainly in patients with tumors located in the superficial cerebral white matter and at the cerebral white-grey matter boundary. Total interictal epileptiform discharges were 9, of which 4 were overlapping with polymorphic slowing. The interictal epileptiform spikes were mainly in tumors of the cerebral grey matter. Significance: The lack of linearity of the EEG characteristics to the tumor size and the distribution of normal EEGs throughout the brain in our study indicate that certain neuroanatomical pathways must first be compromised before any EEG change can be realized. Reduction of the cholinergic tone in neuromodulation has in previous studies been associated with delta and polymorphic EEG. We now propose and implicate the destruction of cholinergic fibres in the production of polymorphic EEG changes which we observed in the current series. The observation of interictal spikes (some sleep potentiated) on polymorphic slow background EEG activities of 4 patients with white matter tumors implicate polymorphic slowing as a precursor to interictal epileptiform spikes and focal cortical hyper- excitability in cases of white matter & subcortical tumors. We therefore propose that the aforementioned destruction of cholinergic fibres set the stage for this focal cortical hyper excitability by abetting an abnormal form of frequency dependent synaptic plasticity that has previously been described as augmenting response. In cases of purely grey matter tumors where interictal epileptiform discharges were observed without polymorphic background slowing of the EEG the mode of epileptogenesis suggested above therefore may not apply.