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    Perceived treatment failure of artemisinin combination therapy among healthcare providers in Kampala District and associated factors
    (Makerere University, 2021) Nabirye, Leah.
    The integrity of artemisinin-based combination therapies (ACTs) is critical in successfully combating malaria in endemic countries. However, ACT use has been linked to treatment failure which can be heightened by overuse, non-compliance by patients to treatment and dosage regimes and proliferation of substandard and falsified medicines among others. This results in high rates of re-infection and changes in artemisinin sensitivity patterns. Perceived ACT treatment failure among healthcare providers may influence their decision-making during health service delivery, and also provide clues on what happens to the health system when there is a failing drug. Objective: To determine the healthcare provider-perceived ACT treatment failure and associated factors in Kampala district. Methods: A cross-sectional study among 297 eligible healthcare providers in Kampala, recruited using a multistage sampling. Data was collected using self-administered questionnaires and then entered into EPIDATA 3.1 and analyzed using STATA V 13 with logistic regression analysis. Responses to the open-ended questions were coded and analyzed. Results: Between June 2018 and July 2018, 297 healthcare providers were recruited. Of these, 165(56) were males and 132(44) were females with ages ranging between 21 and 51 years. Those that reported having ever encountered treatment failure were 62%. The factors that were associated with health worker perceived ACT treatment failure include Age (P<0.001). Professional experience (P<0.001), color of ACT tablets (P=0.001) and previous patient complaints about ACTs (P<0.001). Six in every ten healthcare providers had ever perceived ACT treatment failure of healthcare providers during treatment of uncomplicated malaria. This was high when compared to a similar study done among nurses in Nigeria, where about four in every ten nurses had ever perceived ACT treatment failure. The perception of most of the healthcare providers interviewed in this study was that risk of ACT failure has been associated with overuse. In addition, factors which could lead to perceived treatment failure identified included poor patient adherence. Healthcare providers reported patient concerns on color, size, and number of tablets prescribed. Since healthcare providers, during patient care, always interact with medicines, their perceptions about ACTs will influence their decision-making during service delivery. It is important for the MOH to empower healthcare providers with information to make more informed decisions at the point of care.
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    Nsambi. R. (2025), Comparative Evaluation of Real-Time PCR and Kato-Katz Microscopy for the Detection and Quantification of Giardia intestinalis in Lakeshore Communities of Buikwe and Buvuma Districts. (Unpublished Master's Dissertation) Makerere University, Kampala, Uganda.
    (Makerere University., 2025-10-13) Nsambi, Robert.
    Background: Giardia intestinalis is a significant cause of waterborne diarrheal disease globally, particularly in communities with poor sanitation and limited access to clean water. Accurate diagnosis is crucial for effective control, yet the widely used Kato-Katz microscopy method has limited sensitivity, especially for low-intensity and asymptomatic infections. This study aimed to develop and validate a Real-Time Polymerase Chain Reaction (Real-Time PCR) assay for the sensitive detection and quantification of G. intestinalis and to compare its performance with the conventional Kato-Katz technique in lakeshore communities of Buikwe and Buvuma districts, Uganda. Methods: A cross-sectional study was conducted involving 162 participants from health centres in Buikwe and Buvuma districts. Stool samples were collected and analyzed in parallel using Kato-Katz microscopy and a newly developed quantitative Real-Time PCR assay. The PCR assay targeted the small-subunit ribosomal RNA (ssrRNA) gene. Diagnostic performance parameters, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa agreement, were calculated.Results: Real-Time PCR detected a significantly higher number of G. intestinalis infections (15/162, 9.3%) compared to Kato-Katz microscopy (5/162, 3.1%). All microscopy-positive samples were also positive by PCR. Using a composite reference standard, Real-Time PCR demonstrated a sensitivity of 75% and a specificity of 100%. The positive and negative predictive values were 100% and 93.6%, respectively. The agreement between the two methods was moderate (kappa = 0.47). The assay showed a high detection limit, capable of identifying as little as 0.1 pg of Giardia DNA. Stool consistency was significantly associated with parasite detection, with watery stools yielding more positives. Conclusion: This study confirms that Real-Time PCR is a substantially more sensitive and reliable tool for diagnosing Giardia intestinalis than Kato-Katz microscopy, particularly in detecting low-level and asymptomatic infections. The findings advocate for the integration of molecular diagnostics into public health strategies in endemic regions to improve disease surveillance, ensure accurate burden estimation, and guide effective control interventions against giardiasis.Keywords: Giardia intestinalis, Giardiasis, Real-Time PCR, Kato-Katz, Diagnostic performance, Buikwe, Buvuma.
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    Malaria 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) Ssemwanga, Moses
    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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    Diagnostic accuracy of stool xpert MTB/RIF ultra assay for pulmonary tuberculosis among PLHIV in Kampala, Uganda
    (Makerere University, 2025) Mugalu, Isaac
    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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    Health 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) Mwebaza, Betty Deborah.
    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.